Pediatrics Bradley 2020 PDF

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Pediatrics
SEVENTH EDITION
SEVENTH EDITION
Bradley S. Marino, MD, MPP, MSCE

Professor of Pediatrics and Medical Social Sciences
Departments of Pediatrics and Medical Social Sciences
Northwestern University Feinberg School of Medicine
Heart Center Co-Director, Research and Academic Affairs
Divisions of Cardiology and Critical Care Medicine
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois
Pediatric Inpatient Specialist

Hemby Children 's Hospital
Presbyterian Medica l Center
Novant Health
Charlotte, North Carolina
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Library of Congress Cataloging-in-Publication Data

Names: Marino, Bradley S., author. I Fine, Katie S. (Katie Snead), author.
Title: Blueprints pediatrics I Bradley S. Marino, Katie S. Fine.
Other titles: Blueprints.
Description: Seventh edition. I Philadelphia : Wolters Kluwer Health, [2020] I
Series: Blueprints I Includes index.
Identifiers: LCCN 2018039789 I ISBN 9781496396464 (paperback)
Subjects: I MESH: Pediatrics I Examination Questions
08Silification: LCC RJ48.3I NLM WS 18.21 DDC 618.92/00076-dc23 LC record available at https://lccn.loc.gov/2018039789
This work is no substitute for individual patient assessment based upon healthcare professionals' examination of each pa-
tient and consideration of, among other things, age, weight, gender, current or prior medical conditions, medication history,
laboratory data and other factors unique to the patient The publisher does not provide medical advice or guidance and this
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Contents
CollbtbiiiDrs • ••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••• 'VII

Pre'face •••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••• :xii
Acknowledgments•••••••••••••••••••••••••••••••••••••••••••••••••••••••• XIII
,Abbreviations. • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • .x.iv
"I General Pediatrics 1
2 Neonatal Medicine 20
a Adolescent Medicine 51
.... Nutrition 65
5 Fluid, Electrolyte, and pH Management 72
a Pulmonology fiT
7 Infectious Diaeasa 112
a Immunology, Allergy, and Rheumatology 143
a Neurology 165
10 Dennatoloay 197
11 cardiology 210
"12 Hematology 247
"13 Oncology 7li1
14 Gastroenterology 305
115 Endocrinology 328
"18 Orthopedics 348
y
•
vi • Contributors
"17 Nephrology 383
"18 Urology 382
"'a Genetic Disonlers 390
2 Emergency Medicine: Tbe Acutely IU and InJured ChUd 403
QUesriiDIIS • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • 434
Answers ................................•....•.•....•....•. .• ...•....•.. 44!1
Appertdix: Additional Images I I I I I I I I I I I I I I I • I I I I • I I I I I I • I I I I • I I I I I I • I I I I • I I 485
Index ••••••• • •••••••••••••••••••••••••••••••••••••••••••••• • •••••••••• • 473
Contributors
Rudy Allen, MD Jeffrey B. Brown, MD

Instructor Associate Professor
Department of Pediatrics Department of Pediatrics
Northwestern University Feinberg School of Northwestern University Feinberg School of
Medicine Medicine
Attending Physician Attending Physician
Division of Hematology, Oncology, and Stem Cell Division of Gastroenterology, Hepatology, and
Transplantation Nutrition
Ann & Robert H. Lurie Children's Hoapital ofOUcago Ann & Robert H. Lurie Children's Hospital of
Chicago, Illinois Chicago
Chicago, illinois
Elizabeth R. Alpern, MD, MSCE
Professor Michael R. Carr, MD
Assistant Professor
Department of Pediatrics
Northwestern University Feinberg School of Department of Pediatrics
Northwestern University Feinberg School of
Medicine
Medicine
Division Chief
Attending Physician
Division of Emergency Medicine
Division of Cardiology
Ann & Robert H. Lurie Children's Hospital of
Chicago
Chicago
Chicago, Illinois
Chicago, illinois
Shertf M. Badawy, MD, MS, MBBCh Eart Y. Cheng, MD
Assistant Professor Professor
DepartmentofPediatrks Department of Urology
Medicine Medicine
Attending Physician Division Chief
DiviJi.on of Hematology, Oncology, and Stem Cell Division of Pediatric Urology
Transplantation Ann & Robert H. Lurie Children's Hospital of
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago Chicago, illinois
Chicago, Illinois
David 1-Wang Chu, MD, MSCE
Christina M. Barriteau, MD Assistant Professor
Pediatric Hematology/Oncology Fellow Department of Urology
DiviJi.on of Hematology, Oncology and Stem Cell Northwestern University Feinberg School of
Transplantation Medicine
Northwestern University Feinberg School of Attending Urologist
Medicine Division of Pediatrk Urology
Ann & Robert H. Lurie Children's Hospital of Ann & Robert H. Lurie Children's Hospital of
Chicago Chicago
Chicago, Illinois Chicago, Illinois
Yll
viii • Contributors
Megan L. Curran, MD Northwestern University Feinberg School of

Assistant Professor Medicine
Department of Pediatrics Division Chief
Northwestern University Feinberg School of Division of Critical Care
Medicine Department of Pediatrics
Attending Physician Ann & Robert H. Lurie Children's Hospital of
Division of Rheumatology Chicago
Ann & Robert H. Lurie's Children's Hospital of Chicago, Illinois
Chicago
Chicago, lllinois Priya G. Jain, MD
Assistant Profeuor
Matthew M. Davis, MD, MAPP Department of Pediatrics
Professor Northwestern University Feinberg School of
Departments of Pediatrics, Medicine, Medical Medicine
Social Sciences, and Preventive Medicine Attending Physician
Northwestern University Feinberg School of Division of Emergency Medicine
Medicine Department of Pediatrics
Division Chief Ann & Robert H. Lurie Children's Hospital of
Division of Academic General Pediatrics and Chicago
Primary Care Chicago, Illinois
Chicago Rachel B. Kadakia, MD
Chicago, illinois Instructor
Leon G. Epstein, MD Northwestern University Feinberg School of
Proressor Medicine
Departments of Pediatrics and Neurology Attending Physician
Division OUef Division of Endocrinology
Division of Neurology Department of Pediatrics
Chicago Chicago
Chicago, illinois Chicago, Illinois
Katie S. Fine, MD Aroop Kar, MD

Pediatric Inpatient Specialist Health System Clinician
Hemby Children's Hospital Division of Hematology, Oncology, and Stem Cell
Presbyterian Medical Center Transplantation
Novant Health Northwestern University Feinberg School of
Charlotte, North Carolina Medicine
Paula Goldenberg, MD, MSW, MSCE Chicago
Assistant Professor Chicago, Illinois
Harvard Medical School Lacey L. Kruse, MD
Medical Geneticist Assistant Professor
Division ofGenetics Departments of Pediatrics and Dermatology
Massachusetts General Hospital Northwestern University Feinberg School of
Boston, Massachusetts Medicine
Attending Physician
Z. Leah Harris, MD Division of Dermatology
Posy and John Krehbiel Professor in Critical Care Ann & Robert H. Lurie Children's Hospital of
Professor of Pediatrics Chicago
Department of Pediatrics Chicago, Illinois
Contributors • lx
Tomitra Latimer, MD Praati Patel Matkins, MD, F.AAP, FSAHM

Assistant Professor Executive Director
Department of Pediatrics Veritas Collaborative
Northwestern University Feinberg School of Professor of Pediatrics
Medicine Carolinas Medical Center
Attending Physician 0\arlotte, North Carolina
Academic General Pediatrics and Primary Care Associate Clinical Professor of Pediatrics
Attending Physician University of North Carolina School of
Division of Dermatology Medicine
Ann & Robert H. Lurie Children's Hospital of Chapel Hill, North Carolina
Chicago
Chicago, Dlinois Susanna A. McColley, MD
Professor
Trisha Lewin, MS, RD, LDN Department of Pediatrics and Pulmonology
Clinical Dietician Northwestern University Feinberg School of
Nutrition Services Medicine
Ann & Robert H. Lurie Children's Hospital of Associate Chief Research Officer for
Chicago Clinical Trials
Chicago, Dlinois Stanley Manne Children's Research
Institute
Anne W. Lucky, MD Attending Physician
Adjunct Professor Division of Pulmonology
Departments of Dermatology and Pediatrics Ann & Robert H. Lurie Children's Hospital of
University of Cincinnati College ofMedicine Chicago
Adjunct Professor Chicago, Illinois
Divisions of General and Community Pediatrics
and Dermatology Leena B. Mithal, MD, MSCI
Cincinnati Children's Hospital AMistant Professor
Cincinnati, Ohio Department of Pediatrics
Kerri Z. Machut, MD Medicine
Assistant Professor Attending Physician
Department of Pediatrics Pediatric Infectious Diseases
Northwestern University Feinberg School of Ann & Robert H. Lurie Children's Hospital of
Medicine Chicago
Attending Neonatologist Chicago, Illinois
Ann & Robert H. Lurie Children's Hospital of Saeed Mohammad, MD, MS
Chicago Assistant Professor
Chicago, Dlinois Department of Pediatrics
Bradley S. Marino, MD, MPP, MSCE Medicine
Professor of Pediatrics and Medical Social Sciences Attending Physician
Departments of Pediatrics and Medical Social Division of Gastroenterology, Hepatology, and
Sciences Nutrition
Northwestern University Feinberg School of Ann & Robert H. Lurie Children's Hospital of
Medicine Chicago
Heart Center Co~Directot Research and Chicago, Illinois
Academic A.ffain
Dlvisi.ons of Cardiology and Critical Care Medicine
Chicago
Chicago, Illinois
x • Contributors
Joshua Daniel Prozialeck, MD, MSA Suzanne M. Schmidt, MD

Assistant Professor Assistant Professor
Deparbnent of Pediatrics Department of Pediatrics
Medicine Medicine
Division of Gastroenterology, Hepatology, and Division of .Emergency Medicine
Nutrition Department of Pediatrics
Chicago Chicago
Chicago, Dlinois Chicago, lllinols
Maheen Quadri, MD, MS Vineeta Swaroop, MD

Assistant Professor Assistant Professor
Deparbnent of Pediatrics Department of Orthopaedic Surgery
Medicine Medicine
Academic General Pediatrics and Primary Care Division of Orthopedic Surgery
Chicago Chicago
Chicago, Dlinois Chicago, lllinois
Jane A. Rivas, MD Maria V. Talamo-Guevara, MD

Pediatric Resident Physician Attending Physician
Department of Pediatrics Pediatric Pulmonary Medicine
Ann & Robert H. Lurie Children's Hospital of Cook Children's
Chicago Fort Worth, Texas
Chicago, DlinoJs
Philip T. Thrush, MD
v.
Natalie Roebuck. MD Assistant Professor
Pediatric Critical Care Medicine Fellow Department of Pediatrics
Division of Critical Care Medlcln.e Northwestern University Feinberg School of
Northwestern University Feinberg School of Medicine
Medicine Attending Physician
Ann & Robert H. Lurie Children's Hospital of Division of Cardiology
Chicago Ann & Robert H. Lurie Children's Hospital of
Chicago, Dlinois Chicago
Chicago, lllinois
John F. Sarwark, MD
Professor Ren6 G. VanDeVoorde Ill, MD
Department of Orthopedic Surgery Assistant Professor of Pediatrics
Northwestern University Feinberg School of Department of Pediatrics
Medicine University of Cincinnati College of
Division OUef Medicine
Division of Sports Medicine Division of Nephrology and
Orthopaedic Surgery Hypertenaion
Ann & Robert H. Lurie Children's Hospital of Cincinnati Children's Hospital
Chicago Medical Center
Chicago, Dlinois Cincinnati, Ohio
Contributors • xl
R. Gregory Webster, MD, MPH Barry K. Wershil, MD

Assistant Professor Professor
Department of Pediatrics Department of Pediatrics
Medicine Medicine
Attending Physician Division Chief
Division of Cardiology Division of Gastroenterology, Hepatology and
Ann & Robert H. Lurie Children's Hospital of Nutrition
Chicago Ann & Robert H. Lurie Children's Hospital of
Chicago, Dlinob Chicago
Chicago, illinois
Aaron J. Weiss, MD
Neonatology Fellow
Division of Neonatology
Medicine
Chicago
Chicago, Dlinois
Preface
lueprints Pediatrics was first published almost Each chapter in the book comists of a single
B 20 years ago as part ofa .series of books designed
to help medical students prepare for USMLE Steps
subject for review. Most can be read in less than
an hour. The topics contained in each chapter are
2 and 3. Just as pro&ssional board evaluatioru; have grouped in an orderly fashion, with an end-of-chapter
developed over time, and medical training continues "Key Poinbi• section that permits instant review and
to advance, so too has hdiatric Blueprints evolved highlights the concepts most frequently tested. This
to assist practitioners and students across multiple edition includes 100 questions and answers written
evaluation settings. Examination preparation remains in the "Clinical V'Igne~ style used on USMLE and
a core component of the series; to that end, the au- Pediatric Board examinations. Thus, readers not
thors review the subject parameters posted by the only can evaluate their grasp of the material but
testing board before each edition. The authors and also begin to acclimate themselves to the expected
editors work together to organize the most important testing environment.
and factually current material into a complete yet We are proud to offer this seventh edition of
concise review guide. Our ultimate goal remains Blueprints hdiatria. It incorporates suggestiol18
integrating tkpth offactual knowledge with breadth we have received from medical students, faculty,
of practice information in order to optimize both providers, and even program directors with regard to
understanding and retention. We have been pleased content and organization. Vlrtually all of the chapters
to hear from our readen that the book is utilized by are coauthored by at least one pediatric expert in
many medical students during their pediatric clinical the respective content area. Utilizing authors with
rotatiom, as well as in preparation for shelf and board dual backgrounds in academic medicine and private
examinatioru;. Residenbi in emergency medicine and practice permits incorporation of the most recent
family practice as well as nurse practitionen and information and practice parameters available and
physicians' a..Watants have found Blueprints helpful accepted at publication.
during the pediatric portion of their training. We We hope you find Blueprints Pediatrics to be a
believe the book's applications have broadened with beneficial investment, regardless of how you use it.
each edition due to the quality of our guest authors
and their dedication to highlighting and clarifying Bradley S. Marino
a targeted range of basic yet important topics that
must be mastered in order to treat children. Katie S. F'me
xll
Acknowledgments
his book is a tribute to our patients and their We would like to dedicate this edition ofBlueprints
T families. Each day we are reminded haw truly
precious children are and what an honor it is to
Pediatrics to our spouses and children. without whose
support, forbearance, and encouragement none of
care for them. We are grateful to our colleagues, this would have been possible.
including residents, fellows, attenclings, providers,
nurses, and support staff; we continue to learn from Bradley S. Marino
your knowledge of patient care and compassion for
the human condition. Your enthusium and positive Katie S. Pine
energy remind ua both that we really do have •the
best job in the world~
XIII
Abbreviations
ABG arterial blood gas fVC forced vital capacity

AC11I adrenocorticotropic hormone G6PD glucose-6-phosphate dehydrogenase
AIDS acquired immunodeficiency syndrome Gl gastrointestinal
All acute lymphocytic leukemia Hgb hemoglobin
ALT alanine transaminase Hlb Haemophllus lnjluenuu type b
AMP adenosine monophosphate HIV human immunodeficiency virus
ANA antinuclear antibody HLA human leukocyte antigen
AP anteroposterior IFA immunofluorescent antibody
ARDS adult respiratory distress syndrome lg immunoglobulin
ASD atrial septal defect IM intramuscular
ASO antistreptolysin INH isoniazid
AST aspartate t:rarua.minase IV intravenous
All' zidovudine IVC inferior vena cava
BUN blood urea nitrogen MG intravenous immunoglobulin
CA.VV common atrioventricular valve .ItA Juvenile rheumatoid arthritis
esc complete blood count JVP Jugular venous pressure
CDC Centers for Disease Control and KUB ld.dneys/ureterlhladder
Prevention LDH lactate dehydrogenase
CF cystic fibrosis LFTs liver function tests
CHF congestive heart failure LP lumbar puncture
CK creatine kinase us lecithin-to-sphingomyelin (ratio)
CNS central nervous system LV left ventricle
CSF cerebrospinal fluid LVH left ventricular hypertrophy
CT computed tomography MMR measles-mumps-rubella
DIC cli.saeminated intravucular MRI magnetic resonance imaging
coagulation NG nasogastric
DMD Duchenne-type muscular dystrophy NPO nil per os (nothing by mouth)
D1P diphtheria/tetanus/pertussis NSAID nonsteroidal anti-inflammatory drug
D1Rs deep bmdon reflexes PCR polymerase chain reaction
DVT deep venous thrombosis PDA patent ductus arteriosus
EBV Epstein-Barr virus PFTs pulmonary function tests
ECG electrocardiography PMI point of maxhnal intensity
ECMO extracorporeal membrane oxygenation PPD purltled protein derivative
EEG electroencephalography PT prothrombin time
BJSA. enzyme-linked immunosorbent assay m partial thromboplastin time
EMS electromyography RBC red blood cell
ESR erythrocyte sedimentation rate RF rheumatoid factor
FEV forced expiratory volume RPR rapid plasma reagin (test)
FTA-ABS fluorescent treponemal antibody RSV respiratory syncytial virus
absorption RV right ventricle
xlv
Abbreviations • x.v
RVH right ventricular hypertrophy liD upper respiratory infection

SIDS sudden infant death syndrome us ultrasoWld
lip status post VMA vanillylmandelic acid
T3RU triiodothyronine resin uptake VSD ventricular Jeptal defect
Tc thyroxine vWF von Willebrand factor
1SH thyroid~stimulating hormone wac white blood cell
UA urinalysis
General Pediatrics
Tomitra Latimer, Maheen Quadri, Katie S. Fine, and
Matthew M. Davis
INTRODUCTION OBSERVING THE PARENT(S) AND CHILD

In most pediatric practices in developed nations, At every visit, it is important to closely observe the
infants and children are routinely examined several parent-child interaction. (Of note, the word "parent"
times in the first 2 months of life, every 2 to 3 months is used in this chapter to signify a child's primary
until18 months, every 6 months through age 3 years, caregiver and may include a grandparent, foster
and generally yearly thereafter. The frequency of parent, or other adult.) Are parental expectations for
routine exams is often higher if children have chronic the child's behavior in line with the developmental
medical conditions or high-risk social situations. age? For instance, is the parent communicating in
In addition to routine exams, infants and children ways an infant or young child may understand? Does
(especially 1 to 5 years old) are susceptible to acute the child seek the attention of the parent before em-
illnesses that often prompt visits to their general barking on a new behavior? If the parent feels that
pediatricians aside from their routine care. Of note, the child is behaving inappropriately, how does the
in this chapter the term "general pediatrician" is used parent react? Does the parent of an older child give
to indicate a primary care- focused pediatrician; the her or him enough freedom and time to respond to
clinical routines and expectations apply in situations questions that you ask directly of the child?
when the clinician involved is another physician (e.g.,
family physician), or an advanced practice provider
PARTNERING WITH FAMILIES IN A
(e.g., advanced practice nurse, physician's assistant)
PATIENT-CENTERED MEDICAL HOME
with whom pediatricians and family physicians often
share clinical practice. To optimize health promotion and illness prevention,
Table 1-1 encompasses a List of items (categorized clinicians must establish effective family-centered
by age group) that should be considered in pediatric partnerships that encourage open and supportive
health supervision visits from ages 1 month through communication with children and families. The
10 years. Other age visits are considered elsewhere general pediatric practice should affirm the strengths
in this book (Chapters 2 and 3). This list is by no of individual family members. A health supervision
means exhaustive, but should provide a starting partnership should be established between the child,
point and direction for further study. The steps of family, community, and health care team. The pe-
a pediatric visit are not always completed in a set diatrician should provide the family and child with
order. For example, the sequence may change on the evidence-based information to assist them in making
basis of the age of the patient; older children may medical decisions.
be embarrassed in a medical gown and are able to In most cases, the primary care pediatrician should
listen and respond more comfortably when they lead and coordinate the care of children with significant
are fully dressed. A complete physical examination medical problems and special needs, establishing a
is needed at each health supervision visit, with key medical home for patients and families. This respon-
highlights noted in the table. sibility extends beyond the time of a scheduled patient
1
•
I ll)
TABLE 1·1. Healttl Supervision in Infancy and Childhood
llnalopmaiitll Ker eo....-nen~s or Unlnrsal
AI• lutrtllon Slnllllluae Pllplcal Exami..Uon Anllcl........, Guldlla Scrllnln!f
lmo Encourage exclusive Calms when upset Growth trajectory Back to sleep, tummy time when awake Postpartum
breastfeeding Follows parents with and percentiles Rear-facing car seat in back depression
Correct formula eyes Rashes, bruising Scald prevention: home water heater at 12o•p, no hot Review newborn
preparation Recognizes caregiver Fontanelles beverage while holding infant screening results
Vitamin D adequacy voice Eye mobility, red Fall prevention Thberculosis (TB)
Iron supplement if Starts to smile reflexes Passive smoking risk risk assessment
premature Lifts head when prone Murmurs, pulses Dealing with crying baby Developmental
No water or solids Back surveillance
Hip stability
Tone, strength
2mo Encourage exclusive Social smile Growth trajectory Back to sleep, tummy time when awake Postpartum
breastfeeding Self-comforts and percentiles Encourage self-comforting to sleep depression
Correct formula Holds head up Rashes, bruising Rear-facing car seat in back Review newborn
preparation Symmetric movements Fontanelles Scald prevention screening results, if
Vitamin D adequacy Begins to push up when Eye mobility, red Fall prevention not already done
No water or solids prone reflexes Passive smoking risk Developmental
Murmurs, pulses Dealing with crying baby surveillance
Hip stability
Tone, strength
4mo Encourage exclusive Expressive babbling Growth trajectory Encourage self-comforting to sleep Postpartum
breastfeeding Pushes chest to elbows and percentiles Stop night feedings depression
Correct formula when prone Rashes, bruising Rear-facing car seat in back Developmental
preparation Begins to roll over and Fontanelles Scald prevention surveillance
Vitamin D and iron reach Skull shape Fall prevention
adequacy Eye mobility, red Passive smoking risk
Can start single item reflexes, corneal light Keep small objects, plastic bags, poisons away from baby
solids at 4-6 mo, cereal reflexes
only with spoon (not in Murmurs, pulses
bottle) Hip symmetry
No honey under 12 mo Tone, strength
6mo Encourage exclusive Recognizes faces Growth trajectory Assess fluoride source, clean teeth, avoid bottle propping Postpartum
breastfeeding Babbles, vocal turn and percentiles and grazing depression
Correct formula taking Rashes, bruising Read picture books to baby Oral health
preparation Responds to name Fontanelles Rear-facing car seat in back TB risk assessment
Vitamin D adequacy Visual and oral Skull shape Scald prevention Developmental
Introduction of cereal, exploration Eye mobility, red Fall prevention surveillance
vegetables, fruits, meats Hand to mouth reflexes, corneal light Passive smoking risk
Cereal only with spoon Rolls over, sits with reflexes Keep small objects, plastic bags, poisons from baby
(not in bottle/cup) support, stands Murmurs, pulses Home safety check: gates, barriers, storage of dangerous
Can start water, no juice supported and bounces Hip symmetry items, no infant walkers
::;12mo Tone, strength Bath supervision
Introduce use of cup Poison Controll-800-222-1222
No honey under 12 mo
9mo Encourage self-feeding Stranger anxiety Growth trajectory Keep consistent daily routines Oral health
Regular mealtime Points to objects and percentiles Read picture books aloud; avoid TV, other screens Developmental
routines Plays peek-a-boo Rashes, bruising Rear-facing car seat in back screening
Vitamin D adequacy Says "dada/mama~ Fontanelles Scald prevention
Table food introduction nonspecifically Skull shape Fall prevention
Cup drinking; plan to Sits with no support, Eye mobility, red Passive smoking risk
stop bottle use by 12 mo pulls to stand, cruising, reflexes Keep small objects, plastic bags, poisons from baby
No juice ::;12 mo may crawl Murmurs, pulses Home safety check: gates, barriers, storage of dangerous
Continue breastfeeding if Immature pincer grasp Hip symmetry items, no infant walkers
desirable Tone, strength Bath supervision
No honey under 12 mo Poison Control1-800-222-1222
Smoking-free home
1y Three meals, 2 snacks Waves bye-bye Growth trajectory Apply fluoride varnish; dental referral Oral health
Whole milk 16-24 oz One to two words, and percentiles Childproof home Anemia, lead
per day, cup only; use "dada/marnaw specific, Eye mobility, cover/ Rear-facing car seat in back (high-prevalence
reduced-fat milk if family imitates sounds uncover, red reflexes Scald prevention areas, high-risk
history of cardiovascular Stands alone, taking Dental caries, Bath supervision housing, Medicaid)
disease steps/walking plaques Read picture books aloud; avoid TV, other screens TB risk assessment
Limit juice to ::;4 oz daily Bangs 2 cubes Pulses Store guns unloaded and locked, with ammunition locked Developmental
Iron-rich foods Mature pincer grasp Hip symmetry separately surveillance
Fruits/vegetables Testes descended Poison Controll-800-222-1222
Avoid choking hazards Bruising Smoking-free home
(continued)
... TABLE 1-1. Health Supervision in Infancy and Childhood (continued)
...
15
lutrlllon
Three meals, 2 snacks
.................
Slnellllance
Imitates activities
Key eo....-nents or
Pliplcal Exlmi..Uon
Growth trajectory
Anllcl......., .......
Discipline, praise good behavior
Un.._.
Screenlnlf
Oral Health
mo Whole milk 16-24 Two to three words, fol- and percentiles (How are you managing your child's behavior? Do you and Developmental
oz daily, cup only (re- lows one-step command Eye mobility, cover/ other caregivers agree on how to do it?) surveillance
duced-fat milk if family Walks well uncover, red reflexes Apply fluoride varnish; dental referral
history of cardiovascular Scribbles Dental caries, Read picture books aloud; avoid TV, other screens
disease) plaques Rear-facing car seat in back
Limit juice to ~4 oz daily Pulses Store guns unloaded and locked, with ammunition locked
Iron-rich foods Bruising separately
Fruits/vegetables Wmdow guards above ground level
Avoid choking hazards Smoke detector; fire plan
Poison Control1-800-222-1222
Smoking-free home
18 Three meals, 2 snacks Points to 1 body part Growth trajectory Discipline, praise good behavior Oral Health
mo Whole milk 16-24 Six to 10 words and percentiles Read picture books aloud; avoid TV, other screens Developmental
oz daily, cup only (re- Walks up steps, runs Eye cover/uncover, Apply fluoride varnish; dental referral screening
duced-fat milk if family Stacks 2-3 blocks red reflexes Discuss toilet-training readiness Autism (M-CHAT)
history of cardiovascular Uses spoon Dental caries, Rear-facing car seat in back
disease) plaques Store guns unloaded and locked, with ammunition locked
Limit juice to ~4 oz daily Observe gait separately
Iron-rich foods Bruising Wmdow guards above ground level
Fruits/vegetables Smoke detector; fire plan
Avoid choking hazards Poison Control1-800-222-1222
Smoking-free home
2y Three meals, 2 snacks At least 50 words, Growth trajectory Discipline, praise good behavior Oral Health
Reduced-fat or fat-free two-word phrases, and percentiles, in- Read picture books aloud; limit TV, other screens to 1-2 h TB risk assessment
milk 16-24 oz daily, cup follows two-step com- cluding body mass daily and assess quality Developmental
only mands, 50'.16 of speech index (BMl) Encourage play with other children surveillance
Limit juice to :54 oz daily understandable Eye cover/uncover, (How does your child act around other kids?) Autism (M-CHAT)
Iron-rich foods Throws ball overhand red reflexes Discuss toilet training, personal hygiene Lead (if high risk/
Fruits/vegetables Jumps up Dental caries, Encourage physical activity Medicaid)
Avoid choking hazards Stacks 5-6 blocks plaques Apply fluoride varnish; dental referral Anemia (ifhigh.
Observe run- Car seat placed in back risk or patient ane-
ning, scribbling, Bike helmet mic at age 12 mo)
socialization Supervise child outside
Wmdow guards above ground level
Smoke detector; fire plan
Store guns unloaded and locked, with ammunition locked
separately
Smoking-free home
30m Three meals, 2 snacks Points to 6 body parts Growth trajectory Read picture books aloud; limit TV, other screens to 1-2 h Developmental
Reduced-fat/fat-free milk Three- to four-word and percentiles, in- daily and assess quality screening
16-24 oz daily phrases, ;;:: 50% of cludingBMI Encourage family physical activity
Limit juice to :54 oz daily speech understandable Eye cover/uncover, (Tell me what you do together as a family)
Iron-rich foods (Is your child starting to red reflexes Encourage independence by offering choices
Fruits/vegetables speak in sentences?) Observe coordina- Discuss toilet training, personal hygiene
Avoid choking hazards Dresses with help tion, language clarity, Apply fluoride varnish; dental referral
Copies vertical line socialization Car seat placed in back
Bike helmet
Supervise child outside
Wmdow guards above ground level
Smoke detector; fire plan
Water safety, swimming lessons
separately
Smoking-free home
(continued)
l CD
TABLE 1-1. Health Supervision in Infancy and Childhood (continued)
...
3y
lutrlllon
Three meals, 2 snacks
.................
Slnelllluce
Gender identity
Key eo....-nents or
Pliplcal Exlmi..Uon
Blood pressure,
Anllcl......., .......
Read books aloud, limit TV, other screens
Un.._.
Screanlnlf
VIsual acuity
Reduced-fat/fat-free milk 2-3-word sentences growth trajectory and Encourage interactive games, taking turns TB risk assessment
16-24 oz daily Speech 75% percentiles, including Family time and exercise Developmental
Limit juice to :S4 oz daily understandable BMI Dental referral surveillance
Iron-rich foods Tower of 6-8 blocks Fundoscopic exam Car seat placed in back
Fruits/vegetables Alternates feet up stairs Dental caries, Bike helmet
Feeds, dresses self plaques, gingivitis Supervise child outside
Copies circle Speech clarity Wmdow guards above ground level
Adult-child Smoke detector; fire plan
interaction Store guns unloaded and locked, with ammunition locked
separately
Smoking-free home
4y Three meals, 2 snacks Fantasy play Blood pressure, Opportunities for play with other kids VISual acuity,
Reduced-fat/fat-free milk Says full name growth trajectories Read aloud and talk together with child hearing
24ozdaily 100% of speech and percentiles, in- Regular bedtime rituals, meals without TV TB risk assessment
Limit juice to 4-6 oz daily understandable cludingBMI Limit TV and total screen time to 1-2 h daily, no TV or Development
Fruits/vegetables Knows what to do if Fundoscopic exam screens in bedroom surveillance
cold/tired/hungry (2 Fine/gross motor Family physical activities
outof3) skills Use anatomic body tenns
Knows 4 colors Speech fluency/ Rules to be safe with adults:
Hops on 1 foot clarity • No secrets from parents
Copies cross or square Thought content/ • No adult should be interested in child's private parts
Draws person, 3-4 body abstraction • No adult should ask child for help with his or her private
parts parts
Dresses self • Car seat in back until maximum manufacturer limit, then
belt-positioning booster seat
• Bike helmet
• Supervise child outside
• Wmdow guards above ground level
• Smoke detector; fire plan
• Store guns unloaded and locked, with ammunition
locked separately
Smoking-free home
5-6 y Reduced-fat/fat-free milk Displays school-readi- Blood pressure, School readiness VISion, hearing
24ozdaily ness skills growth trajectories (To child: Do you feel happy/safe at your school? TB risk assessment
Limit juice to 4-6 oz Good articulation/lan- and percentiles, in- To parent: What concerns do you have about your child's
daily guage skills cludingBMI school work?)
Fruits/vegetables Counts to 10 Fundoscopic exam Mental health
(To child: What are your Balances on one foot, Dental caries, gingi- (To parent: Doell yourfamily have chores/routinet~?
favorite foods? hops, skips vitis, malocclusion How do you discipline your child? Is it effective?
7b parent: Doell your Able to tie knot Fine/gross motor How does your child resolve conflict?)
child eatfrom allfood Mature pencil grasp skills
groups? Draws person, 6 body Speech fluency/
How much milk/juice/ parts clarity
soda per day?) Can copy triangle Thought content/
abstraction
(continue same age How much exercise does your child average per day?
group) How much screen time does your child have on a typical day
(TV. video games, computer, mobile device)?
Dental care
(Brushes how many timet~ a day?
Flosses daily?
Vuiu dentist twice a year?)
Safety
(Booster/seat belt/rear seat of car?
Stranger danger?
Are there smokers in the home? Smoke alarms?
Water safety/sunscreen?)
separately.
Rules to be safe with adults (see earlier row)
Smoking-free home
(continued)
... .
l CD
TABLE 1-1. Health Supervision in Infancy and Childhood (continued)
................. Key eo....-~~~~~~s or
Anllcl......., Gu...._
Un.._.
AI• lutrlllon Slnelllluce Pliplcel Exlmi..Uon Screanlnlf
7-8 y Reduced-fat/fat-free milk (To child: How do you Blood pressure, Discuss rules and consequences TB risk assessment
24ozdaily like school? growth parameters, (What types ofdiscipline do you use?)
Limit juice to 8 oz daily Any problems with bul- including BMI Be aware of pubertal changes
Fruits/vegetables X 5 lying at your school? Hip, knee, ankle (What have you told your child about how to carefor her or
servings daily To parent: How is your function his changing body?)
(To child: What are your child doing in school? Dental caries, gingi- 1 h of physical activity daily
favorite foods? How does your child vitis, malocclusion Eat meals as family
To parent: Does your get along with family Limit screen time to 2 hr daily
child eatfrom allfood members/friends?) Dental care
groups? Rules to be safe with adults (see earlier row)
How much sweet drinks (To child: What would you do ifyou felt unsafe at a friend's
per day? house?)
What do you think of
your child's growth over
the past year?)
(continuing same age Has anyone ever touched you in a way that made you feel
group) uncomfortable?)
Booster per state law, and until shoulder belt fits over chest
and shoulder when seated in regular seat
Safety equipment (helmet, pads, mouth guard)
Smoke-free home
Monitor Internet use
Rules to be safe with adults (see earlier row)
separately
Smoking-free home
9-10 Reduced-fat/fat-free milk (To child: What things Blood pressure, Promote independence, assign chores VISion and hearing
y 24ozdaily are you good at in growth parameters, Be positive role model for respect, anger management (at 10 y)
Limit juice to 8 oz daily school? including BMI Know child's friends Lipid screening
Fruits/vegetables X 5 Any difficult things? Dental caries, gingi- Discuss puberty, sexuality. substance use (once between 9
servings daily To parent: How does vitis, malocclusion (To child: What questions do you have about the way your andll y)
your child get along Observe for signs of body is developing? TB risk assessment
with family members/ abuse or self-inflicted How do you feel about how you look?)
friends?) injuries, signs of Rules to be safe with adults (see earlier row)
puberty 1 hr physical activity daily
Back exam (scoliosis) Dentist twice a year
Safety equipment (hehnet, pads, mouth guard)
Smoke-free home
Monitor Internet use
separately
Smoking-free home
I CO
10 • BWEPRINTS Pediatrics
visit and may involve the usistance of other office the examination (e.g., while examining the mouth,
staff. Ongoing communication with subspecialists, "How many times a day does your chlld brush her
home care providers, child care or school ~ and or his teeth? Does she or he see a dentist every 6
parents is essential in the management of care for months for routine evaluation?"). Many practices
ch1ldren with complex health conditions. make use of written materials and ancillary staff to
provide this preventive health information.
In infancy, a leading cause of death is 1adden
infant death IIJildrome. Infants should be placed
to .sleep on their backs but should spend some time
Some effective behaviors by the clinician include prone (in discussion with parents: •tummy time")
Introducing oneself, greeting each family member. when awake and supervised to prevent positional
and sitting at the same level as the parent or older brachycephaly and encourage st:rength.ening of the
child. Patients and parents want to be listened to upper extremities and posterior neck muscles.
without interruption. Summarize the symptoms or Another preventable cause of death in infancy,
questions of the patient or parent to make it clear and extending through the remainder ofchlldhood,
you understand them correctly. It is useful to encour~ is traumatic injuries. The predominant causes of
age questions and provide full answers in ordinary these injuries change with age, and this knowledge
language, free of medical jargon. Drawings may be has influenced the prioritization ofissues to discuss
helpful to illustrate your responses. For younger at health supervision visits.
children, bringing a book or toy into the exam room • Motor vehicle injar:io are major causes of mar~
can be a diatraction technique as well as provide bidity and mortality for all chlldren and are the
useful information about the child's behavior and leading cause of injury death starting from age 3.
development. If languase barriers are evident at Car safety seats have been found tn prevent deaths in
the beginning of the visit, make arrangements for 71CJii ofinfants (birth to 1 year) and 54IJCi oftoddlers
appropriate translation before proceeding further. (1 to 4 years). Child car safety recommendations
are undergoing modification; the most updated
information may be found at http://www.aap.org. In
GOAL SETTING DURING ntE HEALTH addition. child pedestrian deaths may be prevented
SUPERVISION VISIT by careful supervision of children near traffic.
To make the most efficient use of time, it is helpful • Each year, thousands ofchildren and adolescents
at the start of the visit to decide with the patient and are injured whlle ridiDc bic:ydd; many of these
parent on a mutual agenda. Ask the parent and/or injuries were preventable if helmetl were used
patient what they would like to get out of the visit. universaUy by children when riding.
Beyond the regular "checkup; do they have any • .Falb are the leading cause of nonfatal injuries
concerns they would like addressed? Summarize In children. Many of these may be prevented
their concerns and ape to address those that are by installing stairway gates, installing window
realistic to cover at that visit, and make a plan to guards on upper floors, avoiding infant walkers,
cover all concerns either at the current visit or in employing safe playground design, and supervising
another setting. children closely.
• Homlclcle and saldcle are leading causes of
death throughout childhood and adolescence,
ANTICIPATORY GUIDANCE and nonfatal firearm-related mjuries are also very
Primary care pediatrics focuses on health promotion common. Half ofU.S. households have guns, and
and prevention ofdisease and injury, and an import~ in about half of these households, the firearms
ant tool for this effort is anticipatory guidance, the are stored loaded. Homes with guns have three
advice that clinicians give to parents and children. times the risk of homicide and five times the risk
Parents may have limited ability to retain long lists ofsuicide as those without firearms. Recommen-
of recommendations, and so it is useful to limit the dations to store guns locked and unloaded, and to
number ofitems discussed at each visit and to prior- store ammunition separately, may prevent many
itize items to highlight that focus on the sources of ofthese injuries and deaths.
greatest health risks for each child on the basis ofage. • Drowning is another frequent injury-related cause
Some physicians integrate anticipatory guidance with ofdeath in childhood. Many drowning deaths are
Chapter 1 I General Pediatrics • 11
due to lack ofsupervision in the bathtub, unpro- • Dental cari.e1 (tooth decay) is the most common
tected access to a pool, or lack ofswimming skills. chronic disease among U.S. children. Untreated
Toddlers and young children must be supervised caries causes inkction and pain, which in turn
at all times while in the bathtub or around pools or can affect speech, dietary intake, and learning.
other bodies ofwater. Residential and commercial Proper dental care can prevent dental caries. A
swimming pools should be fenced in (with on- first dental checkup is recommended within 6
scalable fences) and have locked gates. Isolation months ofinitial tooth eruption or at 12 months
fencing (fencing limited to the immediate pool of age, whichever cornea first. Many pediatric
area) is more effective at preventing accidental offices also apply fluoride topically to developing
drowning than perimeter property fencing. Car- dentition in young children.
diopulmonary resuscitation training is available to
parents through the American Heart Association
SCREENING
and many area hospitals. Learning to swim is an
important preventive measure but does not take Many pediatric health supervision visits are asso-
the place of close supervision. ciated with recommended screening tests. These
• Fires and biU'DI are another source ofpreventable tests are meant to identify treatable conditions
Injury mortality for children. Forty percent offire that may benefit from early detection. In deciding
deaths occur In homes without smoke alarms. which screening tests to recommenct there should
Most victims die from smoke or toxic gases rather be evidence that the screened condition is more
than bums, and children are among the leading treatable when detected early, that the treatment is
victims. Working smoke alarms, with batteries available to the patient. and that the benefits of the
replaced annually, and home fire escape plans treatment outweigh the risks of both the treatment
are helpful to reduce these hazards. Importantly, and the screening program.
smoking cessation decreases the likelihood that Due to the rarity of many conditions screened in
matches or lighters will be left where children can pediatrics, the majority of positive tests are actually
experiment with them. Scald burllll also cause false positives associated with no disease. A known
significant morbidity and may be prevented by risk and challenge in pediatrics is the negative psy-
close supervision of young children near stoves chological impact oflabellna children with conditions
and hot water faucets, as well as turning down they do not have (the so~called '\rulnerable child
home water heaters to 12o-F. syndromej, and false positive screening tests add
• CholdnJ also causes injuries and death in chil- to this burden. When conveying positive screening
dren. Choking risk starts when infants begin to test results to parents, it is particularly important to
grab small items and move them toward their be aware of this issue.
mouths, around 6 months of age, and remains The American Academy of Pediatrics (AAP) rec-
high through age 3 years. Many children do not ommends universal screening for anemia at 1 year
have fully erupted second molars until age 30 of age. Patients with hemoglobin levels <11.0 mt,1
months; inappropriate food choices include nuts, dL require additional evaluation for iron deficiency
popcorn, hot dogs, hard vegetables, meat with (Chapter 11). Patients with low hemoglobin levels
bones, and seeds. Fooct coins, small toys, and at 12 months of age and those at higher risk for
small items that look like toys (e.g., disc batteries) iron~deficiency anemia are tested again at age 2.
constitute commonly aspirated objects. Adequate This Includes children with exposure to lead, chU~
supervision of infants and toddlers reduces the dren with iron-poor diets and/or who conswne
risk of choking. more than 24 oz/day of cow's milk, those with poor
• Poiloning is a major source of morbidity growth or inadequate nutrition associated with
in childhood. Risk begins with the onset of specific health problems, and children in families
band-to~mouth behavior in infancyand increases of low socioeconomic status.
as the chlld becomes mobile. Medications, Recommendations for screening for lead poisoning
cleaners, cosmetics, and plants are the leading were revised by the American Academy of Pediatrics
poisons. Parents should keep these items out of in 2016 (Table 1-2).
reach of young children and have the National Screening for tuberculosis (TB) via the purified
Poison Control hotline number accessible at all protein derivative test is recommended in certain
times (1~800-222·1222). populations at health maintenance visits. This
TABLE 1-2. Recommandations for Lead Scraaning as Primary Pravention

! VIrtually all chlldren in the Unitl:d States are at risk for lead exposure and should be screened for lead In early
j childhood. Blood lead levels typically increase up through age 18 mo, and the fastest rate of rise for blood lead
!i levels is between
Asymptomatic 6 and 12
children mo ofbe
ahould age.
tested according to federal, local, and state requirements (conmlt loc:al and :',_!
' ,,
i state pub!Jc health authorities for guld.ance).

l 'Thrgeted saeening mould be oonducted with a peripheral (venous blood) lead level at 12 and 24 mo ofage fur '
l children who: 1
' • Liw in communities with ~259' ofhousing built before 1960 !
!• Liw in communities with a prevalence ~5'16 of children's blood lead c:oncentratiora ~5 microgranu/d.L I
~ • Liw in or visit a home or child care facility with an identified lead hazard or a home built before 1960 that is in ~
l poor repair or was renovated in the put 6 months l
i Inunigrant, migrant, and refugee children should be tested upon their arrival in the United State5 because of their i
l increased risk oflead exposure in their countries of origin. l
1Adapted from Ame~can Aoadttmy of Pedlalr1cs Council on Environmental Health. PI'8V8ntlon at Childhood Lead Toxicity. Pfldittrlr:8.
i:................................................................................................................................................................................................................................................................................................
2016;88{1):820161493. http://pedlatrlcs.aappubllcatlons.orglcontenV138f1/e20161493. !:
includes children emigrating from countries where not receive the influenza vaccine. Contraindic::ati.ons
TB is endemic, children who visit such countries are vaccine specific, and discussion of this topic is
or have frequent visitors from those countries, and beyond the scope of this source.
children with mv. Especially since the publication of fraudulent,
and later retracted, data in 1998 purporting to link
autism with childhood vaccination (against measles
VACCINATIONS in particular), and despite ample scientific evidence
Vaccines are one of the keystones to primary care and that va<lcines are not associated with autism, general
successful primary prevention in pediatrics. Vaccines pediatricians encountersome parental vaccine hesi-
contain all or part of a killed or weakened form of tancy and outright vaccine refusal. Concurrently, there
the infectious organism. Vaccination stimulates the has been a resurgence of diseases such as measles
recipient's immune system to devdop a protecti~ and pertussis in the United States. The American
respoMe that mimics that of natural infection but Academy ofPediatrics encourages clinicians to talk
that usually presents little or no risk to the recipient. with families about these issues and be prepared in
The 2018 consensus vaccination schedule (calendar) a nonconfrontational manner to counter myths or
was recommended by the Centers for Disease Con- misinformation with a discussion about the benefits
trol and Prevention (CDC) Advisory Committee of vaccines and written infonnation from trustworthy
on Immunization (ACIP), American Academy of websites (e.g., cdc.gov, immunize.org, aap.org). De-
Pediatrics, American Academy ofFam.Uy Physicians, spite such efforts, pediatricians recognize that some
and American College of Obstetricians and Gyne- parents seem entrenched in their vaccine beliefs.
cologists for children ages birth through 18 years Whereas some pediatricians discharge families from
in the United States. Full explanatory footnotes are their practices ifthey do not vaccinate their children
available for the schedule at https://www.cdc.gov/ as recommended, most pediatricians continue to try
vaccines/schedules/hcp/im%/child-adolescent.html to persuade vaccine-hesitant parents as a regular
The CDC also makes available a vaccine schedules focus of each well child visit.
app that is free and available for download to mobile Some parent information sources sugest spacing
devices (https://www.cdc.gov/vaccines/schedules/ out vaccine doses over lonser periods of time and
hcp/schedule-app.html). not administering vacdnes together as recommended
Despite their long history ofsafe use and favorable in the consensus vaccination schedule. However,
coat-to-benefit ratio, there are some contraindic:ations given that infanbl and young children are typically
to use of certain vaccinations. A hmory of anaphy- more at risk than older individuals for the target
lactic reaction to a component of a vaccine is an diseases against which vaccines have been developed.
absolute contraindication; for instance, people who delaying vaccines can place infants and children at
have anaphylaxis to egg or chicken protein should unnecessary risk.
Autism spectrum disorder (ASD) is a de-

DEVELOPMENTAL MILESTONES
velopmental disorder characterized by impaired
Developmental milestones are skills that infants social interaction. communication difficulties, and
and children follow and perform at certain ages restrictive and repetitive behaviors, interests, or
before progressing to the next stage. There are four activities. ASD affects 1 out of 68 children; boys
developmental milestom domains offocns: fine and are five times more likely to be diagnosed than are
groas motor, social, language/speech, and cognitive. girls, and Caucasian children are more likely to be
Early identification of developmental delay is vital diagnosed than are African American and Hupanic/
to begin intervention services and can improve Latino children. There can be a wide range of
function. Therefore, developmental surveillance symptoms and severity. No matter the severity, all
should occur at every well child visit. It is important children with ASD can benefit from interventions
to remember that milestone checldists should serve such as speech and occupational therapy; the earlier
only as a guide for growth and development. noting the intervention. often the better the outcome and
that skills develop within a predictable age range; function, It is essential to recognize that parents
some infants and children may achieve skills a little of children with autism, as with all developmental
earlier and some chJldren a little later. The AAP also delays, also need support to address feelings of
recommends using more formal screening tools at grief, frustration. and isolation in raising a child
routine well child visits,like Ages and Stages (ASQ), with special needs.
Denver Developmental Screening Test, or the Child
Development Inventory. LANGUAGE DELAY
All children at 9, 18, 24, and 30 months should
be screened for developmental delay with formal Language is a strong indicator offuture intellectual
testing in the pediatrician's office, even if there potential, and language delay is the most commonly
are no symptoms or concerns, These tests are diagnosed form ofdevelopmental delay in preschool
validated but can be time consuming and rely children. Speech disorders involve difficulty producing
heavily on parental report; importantly, the tests the sounds and rhythms ofspeech. Phonetic disorders
are for screening and cannot be used to make a are problems with articulation. Speech and phonetic
diagnosis. Equally as important as formal testing difficulties together are e.xp~ive disorders, while
is querying the parents' concerns about develop- language disorders often affect both expressive and
ment and directly observing the child during the receptive language skills.
well child visit. Bringing in age-appropriate toys, Dyafluency produces interruptions in the flow
crayons, and other props to directly observe how ofspeech. Developmental dysfluency is observed in
the infant or child plays with toys and interacts many preschoolers, resolves by age 4 years, and is
with the caregiver is an outstanding way to assess not pathologic. True dysfluency (stuttering} is char-
for age-specific developmental delays. acterized by signs of muscular tension and struggle
If a potential developmental problem is iden- when speaking, and/or complete speech blockage,
tified, then further developmental evaluation is accompanied by frustration in the child. Stuttering
indicated by a trained provider. Parents or pe- can significantly impede the ability of an affected
diatricians can refer children 0 to 3 years old to child to communicate orally. Speech therapy is often
community-based early intervention programs quite effective for children who stutter.
for evaluation. If found to have at least moderate Since young children may be uncomfortable
developmental delay, the infant or child can qualify speaking freely in front of strangers, a detailed
for speech, occupational, physical, and develop- history is often necessary to characterize the
mental therapy, depending on the circunutances. quantity and quality of a child's speech. Parental
Early intervention programs are free for families concern about a child's language development
that qualify, and therapy can conveniently occur is a good predictor of the need for further eval-
in the home or daycare. uation, which should always begin with a full
Developmental delays occur when an in&nt or audiologic (hearing) assessment. Referral to a
child is slower to reach milestones compared with speech pathologist for evaluation and treatment
others the same age. This delay can be focal or just (if indicated) should follow. The most frequent
occur in one domain (e.g., expressive language delay) cause of mild-to-moderate hearing loss in young
or be global (affect all four domains). children is otitis media with effusion.
Delayed dentition, defined as no teeth by 16

DENTAL DEVELOPMENT AND CARE months of age, warrants an evaluation. Consider
Assessment oforal health is an important responsibility hypothyroidism; in addition, delayed eruption of the
of primary care pediatricians, especially when there teeth can be found in certain syndromes like Down
can be poor access to dental care for Medicaid-covered syndrome or Apert syndrome (a genetic disorder
children and very young children. Poor access to with craniosynostosis and syndactyly).
dental care can exacerbate early childhood caries, a Primary teeth begin to exfoliate (fall out) about
major public health problem especially for social1y 6 to 7 years of age, beginning with the lateral and
disadvantaged populations. Early childhood caries central incisors. The 20 primary teeth are eventually
(ECC), defined as the presence ofdecayed. missing, replaced with 32 permanent teeth. usually by the
or filled teeth in children ss years, is very prevent- third decade oflife.
able yet it is the most common chronic disease Early dental care is vital to the prevention of
among children. Education to promore oral health ECC. The American Academy of Pediatric Dentistry
as soon as the first tooth erupts can help decrease (AAPD) recommends (since 2014) that parents
the prevalence ofECC. begin brushing their children's teeth with a small
At birth. children usually have 20 primary teeth smear of toothpaste with fluoride at the first tooth
(10 upper, 10 lower) which start to erupt around 6 eruption. This is a change from previous years, when
months ofage. From there primary teeth erupt in a nonfl.uoridated toothpaste was recommended to use
.stepwise fashion. The lower central incisors erupt for patients younger than 2 years. Fluoride not only
first (6 tolO months), followed by the upper central prevents dental decay but also cures early cavities.
incisors (8 to 12 months), then the upper lateral The AAPD advises scheduling a dental visit at the
incisors (9 to 13 months), then the lower lateral in- first tooth eruption or by the child's first birthday.
cisors (10-16 months), followed by the canines and The AAPD recommends weaning infants from using
the molars. The full set of 20 primary teeth would a bottle by 12 months of age and limiting sugary
have usually erupted by between 2 and 3 years ofage. beverages and solids throughout childhood.
KEY POINTS
• The leading causa of death through 4 months • Unti12 years of age, a child's chronological age
of age Is sudden infant death syndrome. should be adjusted for gestational age at birth
• After 4 months of age, the leading cause of when al8888ing developmental milestones.
childhood death is trauma. • The Denver, ASQ, and M-CHAT are develop-
• Motor vehicle injuries cause most traumatic mental screening tests used at several visits
deaths after age 3. in early childhood to identify potential devel·
opmental delays.
• Drowning is the second leading cause of injury
death In childhood. • All chlldr.n should be screened for autism
spectrum disorders at 18 and 24 months.
• Fi'ee and burns are the third leading cause of
injury death in children. • Language Is the best indicator of Intellectual
poblntial.
• Most fires occur in homes without working
smoke alarms. • Any child with suspected speech or language
disorder should be referred for a full audiology
• Scald burns can be prevented by turning water evaluation.
heater temperature down to 120•F.
• The full set of 20 primary teeth should erupt
• Risk for choking and poisoning Is highest be-
by age 33 months.
tween ages 9 months and 3 years.
• Although too much fluoride may cause Irreversible
• Falla are the leading cause of nonfatal injuries staining of permanent teeth, pediatric dentists
In children. recently began recommending brushing teeth
• Dental caries is the leading chronic l lness in with a small amount of fluoridated toothpaste
childhood. upon eruption.
CLINICAL VIGNETTES
VIGNETTE1 2. The parent asks you if fluoride drops should be

A frmonth-old infant is seen fer a well visit, and his given to 1he infant. Which of the following is the
parents have lots of questions. most appropriate response?
L Fluoride drops should be given to all infants
1. The parents ask you how to prevent scald burns. after tooth eruption.
You recommend: b. Fluoride drops should only be given to infants
a. Be in the next room when t he infant is in who do not receive adequate amounts from
the bath. fluoridated water.
b. Turn the water heater temperature to 120°F. c. Most U.S. communities do not supply fluori-
c. Hold the baby in your opposite arm when you dated tap water.
drink a hot beverage. d. Most bottle water contains adequate fluortde.
d. Turn the water heater temperature to 130°F. a. Too much fluoride does not cause significant
e. Not an important issue for this age. problems.
2. The parents ask about the infant's diet. Appro- 3. The parents ask you when their child's full set
priate nutritional recommendations at this age of primary teeth should come in. Which of the
include all except following Is correct?
L Breastfed babies require vitamin Dsupplementation. L 12 to 17 months
b. Solid foods should be introduced and should b. 18 to 24 months
only be given by spoon. c. 25 to 33 months
c. Water should be added to the diet. d. 3yeara
d. Appropriate fluoride intake should be assured. e. 4yeara
e. Honey may be added to the diet.
3. They note that the baby is putting everything in VIGNETTE3
his mouth. You use this as an opportunity to make A neighbor of yours has three children.
which correct statement: 1. The first child speaks In two-word phrases, can
L Poisoning does not become an important risk stack fiVe blocks, jumps up, and throws a ball
until later, when children walk and climb. overhand. This child's developmental age is ci08EJSt
b. The best thing to do if they think their child to which of the following?
has swallowed a poisonous substance Is to L 15 months
call the pediatric office. b. 18 months
c. Alcoholic beverages are the leading polson c. 2years
In children. d. 3years
d. All small objects, cosmetics, cleaners, med- e. 4years
ications, toxic plants, and other poisonous
substances should be kept out of reach. 2. The second child speaks two sentences at a time
e. Parents should always try to induce vomiting and is mainly understandable, feeds and dresses
immediately if their child is suspected of swal- independently, stacks seven blocks, alternates feet
lowing a poison. going upstairs, and copies a circle. This child's d~
velopmental age is closest to which of the following?
VIGNETTE2 L 15 months
At a 9-month health supervision visit, you notice that b. 18 months
the infant's first teeth have erupted. c. 2 years
d. 3years
1. You use this as an opportunity to discuss which e. 4 years
of the following with the parent(s)?
a. There is no need to clean baby teeth. 3. The third child can say her full name, knows five
b. Oral fluoride is dangerous fer children below different colors, hops on one foot, and dresses
1 year of age. herself. This child's developmental age is closest
c. An adequate fluoride source should be to which of the following?
documented. L 2years
d. Formal care by a dentist is not necessary until b. 3years
4 years of age. c. 4years
e. Primary teeth continue to erupt until 5 years d. 5years
of age. e. 6years
VIGNB'TE4 c. All families should have working smoke alarms

An 18-month-old child's parent iS concerned because and home tire escape plans.
she says no words other than •mama" and •dada." d. Fires are the leading cause of InJury deaths
In children.
1. You should do all o1 the foUowing except e. Children are not the main victims of fire deaths
a. Refer for audiology evaluation. because they are typically reecued early.
11. Administer an M-CHAT screening test.
c. Administer a developmental screening test, 3. Other important safety advice for a 9-year-old
suchasASQ. includes au of 1he folloWing except:
d. Refer to a speech pathologist for evaluation. L Wear a helmet when rtdlng a bicycle.
e. Do no further evaluation now, reassure the II. Learn to swim.
parent that 1he child is likely to catch up, and c. Replace smoke alarm battertes every 2 years.
arrange for a follow-up visit at age 2. d. Wear appropriate protective padding when
using skateboards, scooters, or roller skates.
2. This child's audiology report shows a bilateral e. Apply sunscreen before going outside for more
conductive hearing loss. Which of the following than 1 0 minutes.
Is 1he most likely cause of this?
a. Otitis media with effusion VIGNETTE&
11. Congenital infection The parents of a full-term newborn have questions
c. A genetic condition about establishing a healthy diet for their infant.
d. Earwax
e. Excessive noise exposure 1. All of the following statements about juice are
correct except.
3. Which of the following Is the most appropriate a. Juice should be introduced at 6 months of age.
interpl9tation of a PQ6itive score on the M-CHAT b. Juice consumption is associated with risk for
teet in this 18-month-old child? overweight and obesity.
a. It ia definitive proof of an autism spectrum c. If juice is part of a child's diet, 100% fruit juice
disorder. is preferT8d.
II. It is not a significant indicator of abnormal d. Juice should be limited to s4 ounces until 4
behavior at this age. years of age.
c. The parent should be reassured and the test e. Juice consumptions Is more likely to cause
repeated at 24 months. dental cartes If offered between meals Instead
d. The child is at risk for a developmental disorder of with meals.
primarily affecting his or her motor development.
e. The child is at risk tor an autism spectrum 2. The parents report they have a strong family
disorder and should be referred for further history of heart disease and obesity. When can
evaluation. the parents switch from giving their infant whole
milk to reduced-fat milk?
L 2years
VIGNmES
11. 18 months
A parent of a 9-year-old asks about injury prevention. The
c. They can switch from breast milk/formula to
parent reveals 1hat there are firearms present in the home.
reduced-fat milk at 9 months.
1. Which of the following represents appropriate d. They can switch from breast milk/formula to
advice to prevent firearm injuries and deaths? reduced-fat milk at 12 months.
a. Store guns locked and unloaded, with ammu- e. They should only switch to reduced-fat milk if
nition stored in a separate location. the infant becomes overweight.
b. Store loaded guns out of reach of children.
3. An Iron supplement should be given to:
c. Umit young children to violent TV programs
L An exclusively bnilastfed newborn
and video games only on weekends.
b. A newborn who was born prematurely
d. Do not be concerned when children have play
c. A newborn who ia being fed soy formula
dates in other homes, since very few other
d. A 4-month-old infant who is being fed cow's
homes have loaded guns.
milk formula
e. Let your child take your gun to school for
show-and-tell to promote gun safety.
e. An 18-month-old child with a broad diet who
drinks cow's milk three servings each day
2. The parent also asks you about preventing injuries
from fires. Which of the following is true? VI6NET1E7
a. Most child deaths In fires are due to burns. The parent of a 2-month-old brings her to your
11. Smoke alarms are present in most house fires. office for a routine checkup. She has questions
and concerns for you about the vaccines you an~ VIGNETTES
recommending. A parent brings her 12-month-old son for a routine
1. Correct statements about vaccines and the risk of checkup. They live in a rented unit in a building con-
autism in children include all of the foUowing except structed in 1948, which has been undergoing renovation.
L The most well-known study of vaccines and They live in a neighborhood where the city says that
autism published in 1998 was fraudulent and 7% of children have blood lead levels ~ ~g!dl. You
ultimately nttractad. plan to check the child's blood lead level as part of
b. Multiple scientific studies of thousands of routine screening.
children have found no association between 1. All of the following are risk factors for lead exposure
vaccines and autism. in this child except:
c. Publication of fraudulent data about vaccines ._Age
and autism has prompted parents to be hesitant b. Housing
about vaccinating their children. c. Male sex
d. Spacing out vaccinee for children will reduce d. Local prevalence of elevated blood lead levels
the risk of autism. among children
2. At the 2-month visit, which af the following vac- 2. Lead exposure should be checked in this child
cines will you recommend In accordance with using:
consensus recommendations? L Venous blood
L DTaP, rotavirus, hepatitis B b. Stool sample
b. Tdap, pneumococcal polysaccharide c. Fingerstick
c. Pneumococcal conjugate, human papillomavirus d. Urine sample
d. Rotavirus, Tdap, meningococcal conjugate
3. Under what circumstances would you have wanted
a Which of the following represents an absolute to check this child's blood lead level when he
contraindication to giving vaccines to this was younger?
2-month-old child? L Status as an immigrant, migrant, or refugee
a. Redness at the site of her newborn hepatitis b. Uving in an apartment constructed in 2010
B injection c. Exclusive breastfeeding t hrough 6 months
b. Mother's feeling of malaise after she received of age
the Tdap vaccine during pregnancy d. Taking multivitamins as an infant
c. Anaphylaxis to the newborn hepatitis B injection
d. Low-grade fever during the visit today
ANSWERS
VIGNETTE 1 Qul81ion 1 VIGNETTE 1 Question 3

1.Answer B: 3.Answar D:
Scald burns are an important source of injury at this Poisoning and choking become Important sources of
age. Parents and caregivers should be at "touch injury starting when infants develop hand-to-mouth
distance" when bathing infants and toddlers. Hot behavior at around 4 to 6 months, with a marked
beverages should not be held near Infants. Water increase at age 9 months. If a poisonous ingestion
heaters should be turned down to 120°F to prevent Is suspected, parents should call the Polson Control
significant scalding. hotllne Immediately and should not Induce vomiting.
Cosmetics, cleaners, medications, and plants are the
VIGNETTE 1 Question 2 leading poisons in children. Prevention includes keep-
2.Answer E: ing dangerous substances and objects out of reach.
Breast milk does not contain adequate vitamin 0;
infants require 400 IU of vitamin D daily f rom the VIGNETIE 2 Qu..tlon 1
first few days of life. Solids should be started by 6 1•.AnawarC:
months and only fed by spoon. Free water should also Baby teeth should be cleaned twice daily from the time
be introduced at this age. Fluoride may be supplied of eruption. Fluoride is effective in preventing dental
by fluoridated water or supplemental drops. Honey caries. Dentist referral is recommended starting at 1
should not be given under 12 months because of year. The 20 primary teeth should erupt by 25 to 33
risk of botulism. months of age.
VIGNETTE 2 Question 2 common cause of conductive hearing loss in children

2.AnswerB: after the neonatal period Ia otnls media wnh effusion.
Fluoride will help prevent caries and should be provided
to aU infants after tooth eruption. Approximately 60% VIGNETlE 4 Quaatlan 3
of U.S. communities are supplied with fluoridated 3.Answer E:
water. Most bottled water does not have adequate The M..CHAT is a ecreening teat for ASD, which primarily
fluoride, except for some brands designed for infants. affect social interaction and communication. It should
Supplemental fluoride drops should only be provided if be administered at 18 and 24 months, and a positive
there is inadequate intake from water. Excess fluoride result should trigger referral for further evaluation
ingestion may cause fluorosis, a permanent staining because it indicates increased risk for ASD.
of dental enamel.
VIGNETlE 5 Question 1
VIGNETTE 2 Question 3 1.AnswerA:
3.AnswerC: Guns should be stored locked, unloaded, and in a
The first teeth usually erupt from 6 to 12 months of separate location from ammunition. All TV and other
age. The full set of 20 primary teeltl erupts by 25to screen time should be limned to none before age 2
33 months and begins to exfoliate at 6 to 7 years. years, and maximum 2 hours dally thereafter. Content
should be appropriate for age, and there should be no
VIGNETTE 3 Questlon1 TV In the child's bedroom. Gun safety should be Inquired
1.Answer C: about in all homes the child visits because half of U.S.
A 2-year-old child who is developmentally normal should homes have guns and half oftheae are stored loaded.
be able to speak at least 60 words, use two-word
phrases, stack five to six blocks, throw a ball overhand, VIGNETlE 5 Que&tlon 2
and jump up in the air. 2.AnawerC:
Fire is the third leading cause of injury death in children.
VIGNETTE 3 Question 2 Most deaths are due to smoke and toxic gas inhala-
2.Answer 0: tion, not to bums. Only 40% of homes in fires have
A developmentally normal 3-year-old should be able working smoke alarms. Children and the elder1y are
to feed and dress Independently, speak two to three the main victims of fire deaths. Anticipatory guidance
sentences with speech at least 75% understandable, for having functional smoke alarms and a 11re escape
know his or her gender, stack a tower of six to eight plan Is recommended as part of health surveillance.
blocks, alternate feet going up stairs, and copy a circle.
VIGNETTE 3 Q..Uon 3 3.AnswerC:
3.Anawerc: Helmets should always be wom while riding bicycle to
A developmentally normal4-year-old child should be prevent serious head injuries. Learning to swim will help
able to hop on one foot, know four colors, say her prevent drowning. Smoke alarm batteries should be
full name, dress herself, copy a cross, and respond replaced annually. Protective padding will help prevent
correctly to the majority of questions such as, ''What injuries on various mobile devices. Sunscreen should
do you do when you are coldltiredlhungry?" always be applied before sun exposure to prevent
damage due to ultraviolet rays, which increases the
VIGNETTE 4 Quesllon1 risk of skin cancer later in life.
1.Answer E:
Language delay Is the most common type of devel- VIGNETlE 6 Question 1
opmental delay in early childhood. All 18-month-old 1.AnswerA:
children should be screened for developmental delay It is now recommended to wait until1 year of age
and autism spectrum d isorders. All children w ith to introduce juice. Juice consumption is associated
concerns about language delay should be referred with risk for overweight and obesity, as well as den-
for audiology and speech evaluations. tal caries; because the length of t ime of exposure
to sugar-sweetened substances is a factor in cavity
VIGNETTE 4 a-tion 2 development, juice is even more likely to cause caries
2.AnswerA: if offered between meals instead of only with meals.
Congenital infections and genetic conditions are im- Juice should be limited to s 4 ounces per day until
portant causes of sensonneuflll hearing loss, which may 4 years of age, and fruit juice Is preferable to juice
be detected by newbom hear1ng scrMnlng. The most cocktails or drinks because It contains more fiber.
VIGNETIE 6 Quesllan 2 VIGNETIE 7 Question 3

2.AnswerD: 3.AnswerC:
In 2011 , the National Heart, Lung, and Blood Institute Anaphylaxis is an absolute contraindication to giving
recommended that infants at risk for future cardio- the hepatitis B vaccine again to this child. Other vac-
vascular disease can switch directly from formula cines should be administered with appropriate caution
to reduced-fat milk at 12 months. instead of waiting in the office setting because the benefits outweigh
to switch from whole milk to reduced-fat milk at 24 risks of vaccination and there is no indication that
months, which had been the previous recommendation. there is cross-reactivity to other antigens contained
The majority of U.S. toddlers get sufficient fat for brain in the other vaccines. Redness at the site of a prior
development from the rest of their diet. Cow's milk vaccine injection and the mother's feeling of malaise
or other milk substitutes should not replace formula when she received a prior vaccine during pregnancy
or breast milk until at least 12 monttls of age, in part are somewhat common and do not represent con-
because of the rtsk for developing anemia. tralndlcatlons. llle presence of low-grade fever
durtng the visit today Is a precaution Q.a., parents
VIGNETIE 6 Question 3 should monitor fever carefully after the vaccinations
3.Answer B: and call with any change In symptoms) but Is not a
Breast milk and fonnula have enough iron for healthy contraindication.
full-term newborn Infanta. Newborns who were born
prematurely do need an Iron supplement because infant VIGNE'llE 8 QuiKtlon 1
iron stores are established later in pregnancy. For all 1.AnswerC:
infants, these stores start to get depleted around 4 Children's blood lead levels typically rise fastest
months of age, and at this time exclusively breastfed between 6 and 12 months, and peak by age 18
infants need an iron supplement. Standard U.S. for- months. Housing built before 1960, and/or that is
mulas, Including soy, have adequate amounts of iron. in poor repair or undergoing renovations in the past
Once full-term Infants start eating iron-fortified ceraals 6 months, places a child at risk for lead exposure.
and iron-rich foods like meats around 6 months of age, Evidence of locally more frequent elevated blood
most will no longer need extra iron supplementation. lead levels among c hildren (above 5" o1 those
tested) Indicates that this child may also be exposed
VIGNETIE 7 Question 1 to environmental sources of lead outside his home
1.Answer D: (e.g., In a daycare sattlng or via the water supply).
Spacing out vaccines, or otherwise deviating from the Thera are no known differences in lead exposure for
recommended childhood immunization schedule, has males versus females.
not been shown to reduce the risk of autism. The original
study of measles vaccination and autism published in VIGNE'llE 8 QuiKtlon 2
1998 was found to be fraudulent and was ultimately 2.AnswerA:
retracted, while multiple subsequent studies of large The most accurate measure of blood lead level in a
cohorts of children have found no elevated risk of autism child is through a venous sample. Although fingerstick
for vaccinated children versus unvaccinated children. samples are sometimes used in practice settings, they
However, the publication of the 1998 study (by Wakefield can be contaminated by surface lead on the skin and
et al. In l..anaJt) has prompted parents' vaccine hesitancy. lead to artificially elevated 1'88Uits. Stool and urine are
not appropr1ate for measurtng lead levels.
VIGNETIE 7 Quesllan 2
2. Answer A:. VIGNETIE 8 Question 3
At the 2-month-old visit, prtmary vaccination Is recom- 3. Answer A:.
mended against diphtheria, tetanus, pertussis, polio, Children who are immigrants, migrants, or refugees
Haemophilus influenzae type b, hepatitis B, rotavirus, are considered to be at elevated riak for lead exposure
and pneumococcus using the pneumococcal conjugate in 1heir countries of origin, and therefore, testing is
vaccine. Only answer (a) includes a subset of these recommended at the time of their entry to the United
vaccines and no incorrect answers. Answers (b), (c), States, even if 1hey are younger than 12 months.
and (d) each contain one or more vaccines that are Uving in housing constructed after 1960, exclusively
part of 1he adolescent immunization schedule (Tdap, breastfeeding, and taking multivitamins during infancy
human papillomavirus, and meningococcal conjugate). are not related to blood lead levels.
Neonatal Medicine
Aaron J. Weiss, Katie S. Fine, and Kerri Z. Machut
With few exceptions, the information presented length, and head circumference assist in determining
herein is limited largely to conditions encountered appropriateness for gestational age. The three
in term or near-term infants. Infants are considered data points are plotted and compared with expected
term when delivered at or after 37 weeks' gestation. ranges of values for that particular gestational age.
More specialized topics regarding neonatal intensive In particular, the term "appropriate for gestational
care can be found elsewhere. age" (AGA) typically refers primarily to an infant's
weight, although all three measurements are equally
important in assessing potential problems. Fetal,
PHYSICAL EXAMINATION OF
maternal, and placental factors all influence fetal
THE INFANT
growth (see Table 2-1). Chromosomal anomalies,
The physical examination of the term newborn, congenital malformations, and inborn errors of me-
as presented here, is organized from head to toe. tabolism are discussed in their respective chapters.
Many practitioners choose to examine the infant Newborns with weights less than the lOth percentile
in a different order: starting with the heart, lungs, for gestational age are termed small for gestational
and abdomen and ending with the back, hips, and age (SGA). In some cases, growth parameters may
oropharynx. This method permits auscultation of be less than expected because the baby is actually
the aforementioned systems while the patient is premature (i.e., the true gestational age is less than
(hopefully) quiet, delaying maneuvers that are more the estimated gestational age). Findings consistent
likely to elicit crying until the end. Regardless of with prematurity include paucity of sole creases, ab-
the approach, it is important that one develops a sent or smaller-than-expected breast nodules, fuzzy
standardized routine to ensure that all systems are scalp hair, prominent veins, absence of ear cartilage,
checked and nothing is overlooked. and undescended testes in boys. Some SGA infants
are constitutionally small, follow a stable growth
GROWTH PARAMETERS curve throughout fetal development, and are simply
Weight, height, and head circumference are typically in the lower percentiles. Others suffered abnormal
recorded in stable term newborns shortly after birth. growth restriction at some point in the pregnancy.
Most nurseries also routinely assess newborns with Regardless of the etiology, SGA status predisposes
both neuromuscular and physical maturity rating infants to certain problems, including hypoglyce-
scales (i.e., Dubowitz or Ballard scoring). The scales mia (because of decreased glycogen reserves) and
are particularly helpful when the mother has not re- hypothermia (because of decreased subcutaneous
ceived prenatal care, does not know when she became fat and increased surface-to-volume ratio). Fetal
pregnant, or when the scores diverge significantly demise, fetal distress, and neonatal death rates are
from expected. The growth measurements and higher in SGA babies as a group than in the general
maturity scores are compared with those expected birth population.
based on the newborn's recorded gestational age Intrauterine growth retardation (IUGR) is
(an estimate via maternal date of last menstrual divided into two categories based on gestational
period and/or sonography). In cases of in vitro age at onset. In cases of early-onset IUGR, the in-
fertilization, the gestational age is precise. Weight, sult resulting in growth restriction begins prior to
20
Chapter 2 I Neonatal Medicine • 21
TAil.E 2-1. Factors Conbibuting to lntrautBrine hypoglycemia (because of hyperinsulinism), are

Growth Retardation more common in LGA patients than in the general
neonatal population.
~ FtJtM FM:IIJtl
IChrom01omal anomalies (triaomy 13) VITALS AND GENERAL APPEARANCE
ICongenital malfurmations (Potter syndrome)
I
The initial assessment is your first impression of the
i Conpnital mctiow (cytomeplovfrua) patient and includes appraisals of (1) overall appear-
IInborn errors ofmetaboli&m (plactolelllJa) ance C'well" VB. "toxic"), (2) general body habitus,
(3) comfort or level ofdistress, and (4) color. Is the
l, , .Fat:IDrs infant active? 0~ if sleepins. easily arousable and
!Reduced or restricted uteroplacerrtal t1ow appropriately responsive? When provoked. is the cry
I(preeciamplla, maternal hypertenlion) strong or weak? Overall, is the infant the size, heft,
IMaternal malnutrition and level ofdevelopment that you would expect for
IMultiple pregnancies the gestational age ofthe baby? Is the infant breath-
ing easily~ or is the respiratory rate increased and
i Maternal smoldng
accompanied by signs of increased effort? The skin
IMaternal alcohol abuse should be warm and may be ruddy but should not
i Maternal drug use be pale or cyanotic. Parts of this initial evaluation
! Pftlctlntal FM:tots become more intuitive over many years of practice,
lPlacental inJJafficiency but the elements do not change.
!Anomalies ofthe placenta or cord (two-veuel cord) SKIN
!..~.!~.~~~~:... . . . . . . . . . . . . . . . . . . . ... . . . . . . . . . . . . . . . . .. Following initial maternal-Infant bonding, the well
term baby is unwrapped and placed under a warmer
28 weeks' gestation, typically causing •symmetric• to permit full examination and prophylactic interven-
restriction, involving the infant's weight, length, and tions. The warmer reduces the amount ofenergy the
head circumference. This term means all metrics infant needs to expend in order to maintain normal
will be smalL Fetal etiologies, such as chromosomal temperature when unwrapped. as evaporative and
anomalies, often result in symmetric IUGR. Infan.t:s convective heat loss through the thin skin of the
with late-onsetHJGR have sparing of the (relatively newborn is comparably quite high.
normal) head circumference, but length and espe- Common birthmarks include salmon patches
dally weight are below expected values, causing and Mongolian spots. The salmon patch (nevus
•asymmetr:~c• restriction. These infants often appear simplex), commonly termed a stork bite, is a su-
long and thin, even emaciated. In these cases, there perficial nonblanching hemangiotic lesion most
is more often a maternal or placentlll etiology that commonly located on the eyelids and posterior neck
causes fetlll growth to decrease later in pregnancy. at the hairline. The lesions become more prominent
Congenital infections can cause either early-onset with bathing or crying but often fade greatly over
or late-onset IUGR depending on the timing. time. Moqolian spots (congenital dermal melano-
Newborns with weights greater than the 90th cytosi.s) are flat. dark blue-black pigmented macules
percentile for gestational age are termed larJe for usually seen over the lower back and buttocks, most
pftatioualage (LGA). Again, some of these infants commonlyin African-American {90%), As1an (80%),
are simply healthy babies with weights in the higher and Hispanic (7096) infants. The hyperpigmented
percentiles. Others are larger than expected because areas fade as the chlld ages; they present no known
they are postterm. (gestational age > 42 weeks) or long-tenn problems but may occasionally be mistaken
maternal dates are incorrect. Postt:erm infants will for abusive trauma, as the appearance is somewhat
have cracked, leathery, and wrinkled skin, which is similar to that of a bruise. In such cases, providers
typically peeling. Some have underlying conditions should attempt to correlate findings with more spe-
that contn'bute to their increased size. This is true for cific JruU'kers ofabusive trauma, such as ear bruises,
infants ofdiabetic mothers and neonates with Beck- cheek bruises, bruises at different stages of healing,
with-Wredemann syndrome. Birth trauma. such and pathognomonic fractures. Port-wine stains,
as shoulder dystocia and clavicle fractures, polycy- cafe au lait spots, and hypopigmented lesions are
themia (because of increased oxygen demand), and leas common skin findings that may be associated
with underlying neurologic conditioru; these are molding from true pathology. Molding is the slight
discussed more fully in Chapter 10. cephalad-to-caudal elongation of the head because
A few commonly acquired rashes often noted in of pressure from the pelvic bones and narrow vaginal
the first month of life are milia, erythema toxicum. canal as the head •presents:' Caput •ucx:edaneum.
neonatorum, seborrheic dermatitis, and neonatal which is generally benign, is a more marked pre-
acne. MJlJa is characterized by pearly white or pale sentation with a slmilar etiology. It is characterized
yellow papules caused by retEntion of keratin and by generalized boggy scalp edema that crosses the
sebaceous material within hair follicles. They are midline and/or suture lines. It is firm but mobile and
commonly found on the nose, chin, and forehead •pits'" to gentle pressure. Bruising may or may not be
and exfoliate/ disappear within the first few weeks present, and the swelling typically resolves without
oflife. No treatment is necessary. intervention. A cephalohematoma involves bleeding
The extremely common rash of erythema tox- into the subperiosteal space. Thus, the swelling is
icum consists of evanescent papules, vesicles, and limited by suture lines and therefore does not cross
pustules, each on an erythematous base, that usually the midline. This swelling is more firm than caput
occur initially on the trunk and spread outward to succedaneum. The majority of cephalohematomas
the extremities. The rash typically appears 24 to resolve spontaneously over several weeks without
72 hours after birth but may be seen earlier. Of note, intervention.
the lesions •move around" over time; that is, they are Subpleal hemorrhqes, which are rare but
visible in a particular spot for several hours only but potentially life threatening, develop when blood
may persist in a region for longer. The rash resolves accumulates in the space between the periosteum
over 3 to 5 days without therapy, and the condition of the skull and the aponeurosis, as a result of
is of no clinicalligni.fican.ce. sheared and severed emissary veins. They are of-
Infantile aeborrhea appears between 3 weeks and ten associated with scalp traction during delivery,
12 months and is commonly called "cradle cap" when typically secondary to vacuum extractions. This
it appears on the scalp. It may also involve the face area is a large potential space and can hold up to
and, less commonly, other areas rich in sebaceous 40CJII of an infant's blood volume. Therefore, these
glands (e.g., perineum. postauricular. and intertrig- infants typically present in hypovolemic shock with
inous areas). It is characterized by erythematous, coagulopathy and require volume resuscitation
dry, scaling, crusty lesions. Affected areas are often as the Initial treatment. The initial appearance of
sharply demarcated from uninvolved skin. Most the bleed mirrors that of caput succedaneum and
cases require no treatment. However, with severe crosses the midline. However, over time, the swelling
cradle cap, baby oil can be applied to the scalp for 15 moves inferiorly down the neck and displaces the
minutes, followed by washing with an antidandruff ears anteriorly.
shampoo. Occasionally, 0.5% to 196 hydrocortisone The fetal skull bones are not fused at birth,
cream may be indicated. If candida! superinfection which permits the brain and head to grow nor-
occurs, nystatin ointment is recommended. mally. Both an anterior and a posterior fontanelle
Neonatal ac:o.e typically develops on the cheeks are present. The suture lines may be slightly apart
and nose around age 3 to 4 weeks and persists or mildly overlapping. Gaping sutures lines can be
for up to 3 months. The rash, which mirrors the associated with systemic processes, such as hypo-
appearance and pattern of adolescent acne, con- thyroidism or Down syndrome. When seen with a
sists of small inflammatory pustules and papules. bulging (usually anterior) fontanelle, this suggests
Although the appearance is similar, comedones are increased intracranial pressure from hydrocephalus
not present in neonatal acne. Like neonatal breast or meningitis. Overlapping is common following
budding and vaginal bleeding, neonatal acne results vaginal deliveries but should normalize within a
from secondary maternal hormone stimulation and few weeks.
resolves gradually as these hormones are degraded
In the infant. No treatment is required. FACE
The face, too, can be asymmetric and may be
HEAD bruised depending on the length and difficulty of
Asymmetry of the newborn head is very common the delivery. Syndromic features (i.e., hypertelori.sm.
in the product of a vaginal birth. However, it is up-/downslanting palpebral fi.uures, epicanthal folds,
important to differentiate appropriate transitional low-set ears) are often appreciated.
EYES in 50~ to 60~ ofinfants with choanal atresia. This

Opening a newborn's eyes is difficult because of finding may be part ofa syndrome or constellation
edema ofthe lids secondary to birth. Often the baby of associated defects, such as Treacher Collins
will open the eyes when the lights are dimmed and syndrome, CHARGE syndrome, and VACTERL
when the baby is held upright. In that few seconds, association.
assess the symmetry of eye opening and pupils, if
poiW'ble. Dyscon,jugate gaze is a normal finding in
MOliTlt/THROAT
infanu prior to age 4 to 6 months. Lip and mouth movement should be aymmetric when
Ifprophylactic antibiotic drops have recently been the baby is crying. Perioral cyanosis, a blue-graydis-
instilled in the newborn's eyes, it may be difficult to see coloration to the area around the lips, is normalin the
bilateral clear red reflexes via fundoscopy. However. immediate moments after birth. This process, which
this finding is critical to assess and document because also affects the palms and soles, is called acrocyiiiWSis
it indicates that nothing is blocking the pathway from and refers to benign vasomotor changes that result
lens to retina. Congenital cataracts, glaucoma, and in peripheral vasoconstriction. However, perioral
tumors (retinoblastoma) will cloud the red reflex; cyanosis should resolve with normal transition and
often these must be removed or treated very early become pink by 5 minutes ofage. Persistent perioral
in life for the development of normal vision. cyanosis beyond this period Indicates central cyanosis
because of arterial hypoxemia and warrants imme-
EARS diate evaluation. The tongue should fit within the
Ears should be examined for normal shape, placement. closed mouth, with the inferior frenulum long enough
size, and rotation. Abnormalities in any of these are to permit easy movement of the tip of the tongue.
associated with numerous genetic and congenital Tongue tie, also known as ankyloglouia, warrants
conditions. The helix. antihelix, tragus, antitragus, surgical repair when it interferes with feeding in the
and lobe should appear typical and symmetric newborn period or articulation later in childhood.
between sides. Ear tags and ear pits are not uncom- A cleft lip is obvious. On examination, both hard
mon. Preaw'icular pits may be associated with other and soft palates should be palpated to the posterior
branchial arch abnormalities, renal anomalies, and oropharynx to evaluate for a cleft palate. A bifid
hearing loss. Infants with preauricular pits warrant uvula with or without an abnormal examination
formal audiologic evaluation. Otoscopy is extremely may suggest a submucous cleft palate, which can
difficult in newborns because of the narrowness of negatively affect feeding and, later, speech. Cleft lip
the ear canal; it is not typically performed. and palate are discussed in more detail later in the
chapter (see Congenital Anomalies section).
NOSE
Neonates are "obligate nose breathers;" This means NECK
that they primarily breathe through the nose unless The newborn neck moves freely and is rather short.
crying or distressed. Choana! atresia, a congenital Restriction of head 1l1ming to either side may indicate
condition, is the blockage of the posterior nasal tortic:olli1, a unilateral congenital fibrotic shorten-
airway by a membranous or bony obstruction. The ing of the sternocleidomastoid muscle. First-line
obstruction may be partial/unilateral or complete. treatments include central positioning and passive
In cases ofcomplete obstruction, respiratory failure stretching. Surgery is often not necessary. Girls with
can develop acutely after birth. Infanb with choanal Turner syndrome may have neck webbing with a
atresia develop respiratory distress with cyanosis low posterior hairline. Check the neck for masses
and may become apneic when the mouth is either or cysts. Thyroglossal duct cysts are located at the
occluded during feeding or simply closed while the midline and branchial cleft cysts are more lateral.
infant is calm or resting. Infants who are cyanotic Both are prone to periodic fluctuations in size and
when calm or feeding but have improved color recurrent infections.
with crying should have a small catheter passed
through each side of the nose. Failure of passage CARDIAC/PULSES
strongly suggests choana! atresia. In the short term, The heart exmrlnation in the infant is similar to
placement ofan oral airway or even intubation may that in any other patient. The heart sounds should
be indicated. Surgery restores patency of the nua.l be evaluated across the precordium as well as on the
passages. Other congenital anomalies are present right (to diagnose situs inversus, if present) and in
the back. Both heart sounds should be present and with congenital infections and in some patients with
normal in character. It is often difficult to distinguish congenital heart disease.
the s2 split in infants because of rates that may If the baby is newly born. the cord should be
range from 100 to 200 beats per minute or greater. checked for the presence ofa vein and two arteries.
Evaluate for extra heart sounds and murmurs. A Two-vessel cords increase the ll1cellhood ofgastro-
murmur may be appreciated ln the first few days intestinal (Gl), genitourinary, and renal anomalies. If
of lite as the ductus arteriosus closes, most often noted prior to delivery, a comprehensive sonographic
a continuous •machine-like• murmur over the assessment of the fetus and genetic screening are
second left intercostal space heard throughout the reasonable first-line approaches. The cord •dries"
cardiac cycle. It is important to palpate the brachial within days and typically falls off within 3 to 4
and femoral pulses for symmetry; both should be weeks. Persistence of the cord beyond 8 weeks is
strong but not bounding. Coarctation of the aorta abnormal and may sisnify a neutrophil disorder,
is associated with weak and/or delayed femoral such as leukocyte adhesion deficiency. The inherent
pulses as compared with the right brachial pulse. relative weakness of the abdominal wall around the
When assessing oxygen saturations, it is important cord insertion may result in intermittent protrusion
to place the pulse oximeter on the right hand. This of abdominal contents (covered by a membranous
location receives preductal blood glow, which has sac) through the space. These umbi.lical. hernias
the same oxygen content as blood traveling to the are conunon, generally benign, and resolve in the
brain and heart. See Chapter 11 for details regarding majority ofcases over time. They appear larger when
the presentationa, differentiation, and management the infant is crying or straining to stool Those that
of congenital heart diseases. are particularly large or persist beyond 5 years of
age are repaired surgically.
LUNGS/CHEST
Rhonchi (transmitted upper airway sounds) are very GENITALIA
common in the hours after delivery because ofresid- Female
ual amniotic fluid. True cracldes and wheezing are Although the labia majora typically cover the labia
pathologic. Signs of respiratory distress. ifpresent, are minora in newborn females, this is not always the
usually noted early ln the examination of the infant. case. Maternal estrogen stimulates growth of the
Increased respiratory rate, retractions, grunting, and labia minora, which may appear more prominent
nasal flaring are signs of neonatal distress, which than expected in older children. For the same
may or may not be primarily respiratory in origin; hormonal reason, mucoid vaginal secretions and
neonatal sepsis and some congenital heart disorders occasionally blood may be noted in the introitus.
present in an indistinguishable manner. These will resolve over time. The clitoris is also
The character of the cry should be noted. A weak relatively larger at this age than in older children
cry, high-pitched shrill cry, and/or unexplained and adolescents. A clitoris that appears overly large
hoarseness warrant further investigation. and virilized may represent ambiguous genitalia
(most commonly because of congenital adrenal
ABDOMEN hyperplasia in a genetic female). Both vagina and
anus (in both females and males) should be patent
In an infant, the abdomen appears full because of and normally placed, and skin tags may be present
as-yet-underdeveloped abdominal musculature. If in either region.
present, abdominal distention suggests a congeni-
tal obstruction (functional VII. anatomic); scaphoid Male
abdomen is more characteristic of diaphragmatic In term neonates, the penis averages 3 to 4 em
hernia (see Congenital Anomalies section). Typical long when stretched, and the testes are about 1 em
bowel sounds are generally present within the first across. The uncircumcised penis has a foreskin that
few hours of life, and stool is passed within the is minimally retractable; full retraction should never
first 24 hours in 95" of term babies (and warrants be attempted. The ventral surface of the penis should
further evaluation if delayed). In neonates and be inspected for any evidence ofan (abnormal) ure-
older infants, the liver is often palpable up to a few thral opening called hypo1padiu. Chordae is the
centimeters below the anterior costal margin. The fixed fibrotic ventral bowing of the penis; it is often
spleen tip should be only barely palpable, if at all associated with hypospadias. Urethral openings
Hepatosplenomegaly is a common finding in babies along the penile shaft should prompt a radiographic
workup of the genitourinary system to identify other detected at birth. Diagnosis is made by radiograph,
associated anomalies, which are not uncommon. which differentiates clavicle fracture from brachial
Chordae and hypospadias require urosurgical inter- plexus inJury, humeral shaft fracture, or shoulder
vention, and the repair may need to be completed dislocation.
in stages. Children with either of these conditions Movement at the arms and shoulders should be
should not be drcumclsed in the newborn nursery, symmetric and. generally free, exrepting normal
as is routinely undertaken ifthe parents request, but minor flexion contracture& at the elbows, knees, and
instead managed by a surgical specialist. hips. Birth trauma can also result in brachial plexus
Both testes are generally palpable in the scrotal injuries from stretching of the nerve roots. Erb palsy
saa, but this may not be the case. Ifa testis is •miss- involves damage to C5- C6 nerve roots, and Klumpke
ing," begin palpating for a testis--sized mass in the paralysis involves damage to C7, C8, and Tl nerve
lower abdomen and proceed along the inguinal canal roots. The former is much more common. The infant
Retractile teltel are those that, when located, can with Erb pally holds the affected arm close to the
be gently massaged into the associated scrotum. If body, extended at the elbow, internally rotated, with
no testis is found, or the mass is fixed, the testicle the forearm fixed in pronation but hand movement
is termed undescended, a condition referred to as preserved. The classical algn is called "'waiter's tip•
c:rypton:bkU.IDI, Ifthe testis has not descended into deformity because it appears the infant's hand is
the scrotal sac by age 1 year, it is surgically relocated outstretched at its side, requesting a tip. In Klumpke
there. Complications from untreated cryptorchidism paralym, the upper arm is unaffected, but the hand
include inguinal hernia, testicular torsion. testicular muscles are weak, and the grasp reflex may not be
trauma, subfertility, and testicular cancer. Moving present. Both conditions often resolve over the first
the testis does not decrease the associated risks of 48 hours of life. In those that do not, improvement
malignancy and sterility, but it does make the testis can be expected up to age 6 months. Thereafter,
easier to examine and monitor. A mass that bulges residual deficits may gradually improve for up to
from the groin area (possibly extending into the 18 months with intensive physical therapy. Surgery
scrotal sac) and that increases in size with crying may be indicated for static cases.
and straining may represent an iDguinal hemiL Inspect the palmar creases. A single transverse
The scrotal sacs should also be palpated for crease is often noted in patients with Down syndrome,
other masses, most notably hydroceles, which are but most patients with this finding are typical, healthy
fluid-filled remnants of the processus vaginalis. Hy- infants. Examine and count fingers and fingernails.
drocele& transilluminate, which helps differentiate
them clinically from other ma511e5. The great majority LOWER EXlREMmES
resolve by 1 year of age. Anterior and posterlor medial thigh creases and
gluteal folds should be symmetric. If the "lines"
UPPER EXTREMITIES do not match up, consider whether hip df-plalia
Palpate the entirety ofthe clavicles for bony step-offs may be a cause. Ortolani and Barlow maneuvers
or crepitus, indicating a clavicle fracture, present in are discussed in detail in Chapter 16 and should be
up to 2% ofdeliveries. Clavicular fractures are more performed in all newborns and at all early infancy
common in large infants and deliveries complicated health maintenance visits. Of note, breech presenta-
by shoulder dystocia or other trauma. The timing tion of the fetus increases the risk of developing hip
of presentation and diagnosis are dependent on dysplasia, and outpatient ultrasound ia recommended
whether the fracture is displaced or nondisplaced. for all of these babies at 6 weeks. The feet should be
Displaced (complete) fractures are often associated examined for metatanua adductuJ (medial curving
with abnormal examination findings, such as crepitus, of the forefoot), talipes equinol'U'US ("clubfoot"),
edema, lack of movement ofthe affected extremity, and other anomalies. The diagnoses and treatments
asymmetric bone contour, asymmetric Moro reflex. of these conditions are discussed in Chapter 16.
or crying with passive motion. Incomplete (nondis-
placed) fractures are usually missed at birth. with BACK
the diagnosis becoming evident when a reactive Palpate the entire length of the bony spine. Look
callus is noted in the area 2 to 4 weeks later. Com- for dimples, hair tufts, or hemangiomas overlying
plete fractures should be immobilized. No speclflc the spine. They may be associated with underlying
treatment is necessary for simple clavicle fractures neurologic anomalies (see Chapter 9). Small, shallow,
solitary sacral dimples located within 2.5 em of the impaired fetal swallowing, which may occur in the
anal verge are common and benign. If concerning setting of congeni1al Gl obstruction or malfonna-
signs are present, or there are associated neurologic tion, conditions that interfere with neural function,
functional deficits, radiographic imaging with MRI and certain other congenital conditions (trisomies.
should be undertaken to assess for underlying ana- Beclcwith.-Wledemann. achondroplasia). Other eti-
tomic abnonnalities in the spine an.d/or neural tissue. ologies to consider include elOOessive production of
fetal (multiple fetuses, hydrops CetaliJ) or maternal
NBJROLOGIC (REFlEXES AND TONE) origin (gestational diabetes).
The neonate should exhibit good tone, be arousable Too little flukt or oUgobydramnioa, restricts
from sleep, and readily be calmed with feeding or fetal movement, lung distention and growth, and
sucking. A few beats of ankle clonus are found in (if severe) placental blood flow. The most common
many typical healthy newborns. Age-specific reflexes cause is fetal renal or urologic disease, particularly
that should disappear over time include the rooting bilateral renal agenesis, widespread multicystic
and mcking reflexes, the reflex grasp, and the Moro disease, or severe obstruction of the urinary tract.
reflex, among others. These appropriately disap- Severe oligohydramnios over time results in Potter
pear by 4 to 6 months. When one cheek is lightly syndrome, characterized by compression deforr
brushed from the corner of the mouth toward the mities of the face and limbs (clubbed feet and hip
ear, the neonate turns the head toward that side dislocation), and pulmonary hypoplasia. Pulmonary
(rooting). The infant should have a strong suck from hypoplasia causes respiratory insufficiency and can
birth. When the examiner's finger is placed in the lead to death in the neonatal period.
center of the open palm or on the plantar aspect
of the foot, the baby's fingers/toes reflexively curl CONGENITAUPERINATAL INFECTIONS
around it in a grip. To elicit the Moro reflex, lift Congenital typically describes events that take place
the supine infant's chest and shoulders up slightly in utero, whereasperinatal encompasses the period
from a flat surface with your hands and forearms. just before, during, and after birth. However, the two
Gendy but suddenly allow your hands and arms to terms are often used interchangeably when referring
move back toward the bed. Both the infant's arms to maternally derived infections. A perinatal infec-
should abduct suddenly away from the midline with tion results when a neonate becomes infected with
the finsers extended. If the response is asymmetric, a pathogenic organism transmitted via the placenta
there may be weakness on one side or abnormally (to the embryo or fetus) or via exposure in the birth
increased tone on the other. Repeated asymmetric canal during labor. Table 2-3 lists numerous key
trials should prompt more thorough neurologic aspects regarding the identification and treatment
evaluation. Brachial plexus injuries and upper of perinatal infections.
extremity fractures are common etiologies for an
asymmetric Moro. CONGENITAL EXPOSURE TO TERATOGENIC
SUBSTANCES
Exposure to alcohol, prescription drugs, and illegal
BEFORE THE DELIVERY: PRENATAL substances can lead to characteristic clinical presen-
CONDITIONS tations, syndromes, and/or birth defects. Table 2-4
A wealth of important information can be gleaned overviews the most commonly used nonprescribed
from the prenatal and delivery records In a matter substances that are known to have effects on the
of minutes (Table 2·2). Knowledge of these factors fetus. Table 2-5 provides a list ofseveral prescription
can assist the pediatrician in uncovering subde ex- agents that are associated with lcnown birth defects.
amination findings and suggest targeted laboratory
and radiographic studies. IN THE DELIVERY ROOM
ABNORMALITIES IN AMNIGnC FWID VOWME APGAR SCORES
Amniotic fluid balance iJ maintained through nor- In the delivery room, Apgar scores are assessed at 1
mal production of fluid and permeability across and 5 minutes based on defined physiologic responses
fetal (lung and skin) membranes and, later, release to the birth process (see Table 2-6). The !-minute
of adequate volumes of fetal urine. The most com- score is generally considered to be reflective of the
mon cause of polyhydramnios (excess of fluid) is newborn's intrauterine environment and immediate
Chapter 2 I Neonatal Medicine • 2:1
TOLl 2·2. Review of the Prenatal and Delivery Reamls

!Pnmltal
IAp ol. the mother (advanced matemal age. young mother)
!MecUcalldstory ofthe mother (dJabetes, hypertension. mental illness, etc.)
i ~ clmiD& the prepaDCy (particularlythose II.JliOCiated with birth c:lefect3)
l Famlly hliiDl'y (bleeding disorders, heritable metabollc disorders and chromosomal anomallel, stillbirths, etc.)
i Social hbtoa-y (ctprette smoking, alcohol use, drug use, domestic violence)
IIDitiatioll of prenatal care {adequate, sporadic:, late, frequent missed appointments, none)
INamber ofpnpwac:iel aut lift cbll.clNn
I Maternal preuatallaboratory resulta
i Blood type (including Rh factor)
Rapid plasma reagin (screelliJ18 test for syphilis)
[gs::_
~~==)
j Mantoux acreening teat (PPD) (if indicated)
l=..::.::::.::::....w_-........,utrloomy13,18,ond21)
! Dlapoatlc pnetlc teltiq resulD (a variety of condition& can be detected from chorionic villus wnpling or
: amniocentaia)
!Jle•ulb ofpreaatal altruomul (lize, dates, estimated fetal wei8ht. multiple fetules, fetal movement, adequacy
: of amniotic tluid wlume, and c:ongenital anomalles of the palate, gastrointestinal, renal, skeletal, and urologic
Isylteml)
IDetmry
i DuratiOll ofraptan ofmembranes (prolonged if 2:18 h)
ICharacterization ofamniotic fluid (clear, meconium stained, purulent, foul smelling)
i Medl.,tioDII adminlltefed duriq delivery (particularly opioi.d& or antibiotia)
IFetal heart ram mcmltoring and Ule ofKalp electrodes
I Ro'* ofcleliftl'Y (vaginal or cesarean delivery)
I Ifceaan!BD: elective, repeat. &!tal distraa, failure to progreu, breech presentation
I Ifwsina): spontaneous, forceps, or vacuum extraction
i Complkatiou (twin gestation, nuchal cord. chorioamnionit:is, etc.)
! APGAJliClOftS
j Jlesusdtatioa, ifneceuary (stimulation. oxyzen. bagging, compreMiona, intubation)
l GNtwioul ap (via dates) at deliwry
I Birth weipt (SGA. AGA. LGA)
!AbbAMalions: N3A. appropriate for gestational age; LGA, large for gestational age; PPD, purified protein derivative; SGA, small for
!..~~~~~-~--~:............................................................................................................................................................................................................................................................!
TABLE 2-3. Transmission, Presentation, Identification, and Treatment of Perinatal Infections

Cytameg1lovlrus (t:M1
~ 'I'ruwnillion urytime during the pregnancy or through e:xpoaun! to mab!mal fluida clwinglafter
birth (includins breast milk). Transmission rate significantly higher ifthe mother initially acquires the infedion
during pregnanq. Tranlmiaion possible even when the primary maternal infection O<lCUll'ed yean before the
prepancy.
Prust,.,.,. (amgmit.al): Asymptomatic (90'.16) or combination of any of the fullowing: preterm birth.
intrauterine growth retardation (IUGR), microcephaly, poor feeding, lethargy, petechiae/purpura. "blueberry
muffin• spots, jaundice, hepatoaplenomegaly, elevated liver tranaaminues, anemia, thrombocytopenia,
intracranial (pvticularly periventricular) calcifications, seizures, chorioretinit:is. Acquked infectiow generally
asymptomatic.
Dicpt»U: CMV detected in the urine (or aaliva or blood) within the flnt 2 wk. oflife Ia corW.It:ent with cottge11ltal
infection.
~t: Ganclclovir and supportive care.
LoiJI-ID'm ~ Co,.,Utal CMV;., the most common ctUUe ofnonhereditary wuorlniUl'fll hellring losl.
Seventy-Jive percent ofinfants with symptomatic congenital CMV will clevelop hearing lou. Hearing is often
normal at birth. with progressive impairment over the first year. Other possible Ions-term complications include
developmental delay, mental retardation, cerebral palsy (motor spasticity}, and dental defects (abnormal enamel
production). Acquired lnlectl.olll are generally free of sequelae.
Sown.in6t)rfl'atlo-.: Antibody testing before or early in pregnancy to document prior infection.
Herpes Simplex VIrus (HSV)
~Perinatal infection acquired through expomre to organism in maternal pnital tract during
cleliym-y. Traiwnia8ion ram aignificantly hisher ifthe mother contracts primary infection during pregnancy (up to
~ vs. <~ foe infants born to mothers with recurrent infections). 11urt being said, mtJ$f ln/lutU with MOiflltlll
HSV.,. born tu "'*" who 1uwe Mver ~ qmpt1mrs tWldo Mt bow tlrM they.,. infoctzd. In&nts may
also become infected postoat:allr through c:ootact with ~ breast lesions while feeding or from secretions
from ao iDfected caretaker.
Prust,.,.,.: Neonatal HSV presents in the first 4 wk oflife with any of the following three distinct clinical
picturea:
1. Isolated mucocutaneou. lesions (skin, eye. and/or mouth), including keratoconjunctivitia
2. EncepJuzUtis
3. Disseminated disease involving multiple organs (lung&, liver, often central nervousl}'lltem [CNS])
Infants with eru:ephalitia and/or dJueminated HSV disease may not manifest the characte.rist:i vesl.cular skin
lesions, leading to a delay in cllagnosil.
DltlpoN: Viral culture and direct fluorescent antibody testing of veGcu1ar scraplnp. Surface cultures of
n.uopharynx. conjunctl.vae, and rectum. Blood and cerebrospinal fluid polymerase chain reactl.on (PCR) testing.
EEG shows periodic epJleptlform cUacharges.
Trutmat: Intravenous acyclovir. Acyclovir should be started for any neonate with vesicular lesions or other
clinical suspicion of HSV, pending laboratory confirmation.
Lo,-.,.,. ~
LoC4l dlmue: Recurrent mucocut:aneoUJiesions.
Encephalitis: c.taractslblinclnea; microcephaly; developmental delay!learnins disabilities.
~ dlwue: Severe neurologic Impairment, death(>~).
~~ Matemalsuppressive antmral therapy beginning at 36 wit' gestation.~ infants by

C-section ifgenitallelions are present at the start of labor. Jfmatemallesionl found after delivery, culture infant
and treat with acydovir if culture-positive or symptoms develop.
Pltvorirutl
n..mtiultNU Congenital infection with vertical transmiJsion.
TAILII-3. Transmission, Presentation, Identification, and Treatment of Per1natallnfectlons (continued)

Pruatlltlotl: Hydrops fetal1s (risk increased ifmother becomes infected during the ftrst trl.melrer).
~ Ma~ immUDO&lobulin (Ig)M. IsG levels.
~&:Intrauterine blood tran&fiWons; supportive care.
~..,.,.,.. None, if &:tua IW'ViveB pregnancy and perinatallnterveatlona.
Sawai1rQp'l'fl!RtiOIJ: None routine.

Human lmmunodlrficiencyVirua (HIV)
Thu.IJntuio~~:
Cowgenttal: TransmUiion may occur at any time during the pregnancy. Ukellhood ofvertical triU1&ltUaslon
increues with increasing maternal viral load
Acquired: Transmiuion through exposure to the organism Jn maternal genital tract or breut milk.
PreMctiJIUnu Most Infected Infants are asymptomatic. Clinical manifestations that may develop over time
include lymphadenopathy/hepatosplenomegaly, f:ai1ure to thrive, developmental delay, encephalopathy, frequent
bacterial infections, opportunistic infection (PMIIItiOCJstis jirovea'), and lymphoid Interstitial pneumonitis.
Diapui&: H1V cultureJ PCR.
~tl Antlretroviral therapy.
Lo~~.K-W7n ~All of the above listed under "Presentation•; death.

ScrrJailwiJ11WVt111tloll: Antibody tl!llting early in pregnancy to document infection. Ant:iretroviral therapy
adminiaWed to the infected mother throughout pregnancy and during delivery. and to the infant tOr the first
6 wk of life. This protocol decreuea the rate oftransmission from 25" to <2". Breut:feedl.ng il contraindicated.
Yarlcelll Zostlr VIrus
~
ColflMltal: Transmillion may occur at any time during the pregnancy. Rash developing within the first 10 d of
life Ia due to In utero infection.
Neon~~tlll ~Infants with mothers who develop varicella lesions anytime from 5 d before delivery to 2 d
after delivery are at high. rilk for aevere disease.
Acquired: Transmission through exposure to the organism in vesicular fluid, mucosa, or infected respiratory
secretions.
Pruatlltlotl:
Congenital: Congenital varicella syndrome includes any combination of the following: nJGR, cutaneous •zigzag"
scarring, llmb atrophy, ocular abnormalities (cataracts, chorl.oretlnitis).
Neon~~tlll acqutred: Widespread cutaneous lesions, pneumonia, hepatitis; death in up to a third of affected infants. I
Acquired: Mild clJnical difleaae. I
Dillpod6: Generally c1inlcal; PCR or lmmWlOfluorescent antibody testlDg of vealcular ICrap1np is confirmatory. j
~t: Intravenous acyclovir for infants at risk for severe disease.
Lo,..,_., ~.A. earlier and CNS abnormalities (atrophy, aeizurel, mmUl retardation) In congenital
varlalla. otherwile m.ln.lmal.
Sawltllw/ll'l'fl!Rtioa: Vaccination prior to pregnancy; acyclovir for the mother ifshe develops primary disease
during the pregnancy. Varlcella zoster l.mmune globulin for infants exposed to mothers with llgns of varlceUa
around the time ofdelivery.
Rullella
~ Congenitallnfec:tlon may occur at any time during pregnancy; clln1.callywone ifcontracted
during the f1nt 20 wk.
Preanflltloru Fetal demise, premature delivery. and!or congenital rubella syndro~ a constellation of any ofthe l
following: cataracts, llellSOrineural hearing lou (the most common Impairment auoclated with congenital rubella !
syndrome), congenital cardiac defects, developmental delay (may be accompanied by nJGR, hepatosplenomegaly. 1
thrombocytopenic purpura). !
(continued)
TilLE 24. Transmission, Presentation, Identification, and Treatment of PerinatallnfBctions (continUBd)

!Du.pa.ll: Maternal antibody titers during pregnancy; after birth, the infant may be tested mr the virus, rubella-
j spedfi<: lgM, or penistently elevmd rubella-specific IgG.
1 ~t: No &peclfk treatment.
!~~Hearing lmpalrment. glaucoma, mental retardation.
1 Sowailr6fl'~lia..: All women of child-bearing age should have documented evidence ofappropriate
! vaccination or immunity. Immunity should be confirmed with serology in all women who are considering
! becoming pregnant.
j Syphilis
~ 'l'NaiJIWIM: Transplacental transmission ofspirochetes and may occur at any time during the pregnancy, with
Ihighest transmission ntes in ftnUsecond trimesters.
~ ~t.tMm: Fetal demiae) premature delivery; infants may be asymptomatic at birth but develop typical skin
!lesions, anemia, thrombocytopenia, jaundice, "'muffles; hepatosplenomegaly, elevated liver enzymes, and skeletal !
l abnormalities, such as osteochondritis (inflammation of the cartilage and bone around a joint) and periostitis. j
!DUip06U: Quantitative nontreponemal testing should be carried out ln all aymptomatic infantJ u well u !
!asymptomatic .lnfant& of mothers with potltive screens whose treatment occurred within 1 mo of delivery, wu !
!inadequate or undocwnented, or did not result in a reduction in nontreponemal titer&. !
! 7'twltmat: PenicWln G. All infantJ should be presumed to have neurosyphilis and be treated with aqueous !
! crystalline pen1d11ln G (IV) or procaine peniclll.ln (IM) Cor 10 d. !
ILo111-1D711 ~Neurosyphilis (ifuntreated), deafness. i
!Saft'llbtgpl'f!VMtiOIU Routine maternal nontreponemal testing confirmed by a treponemal teat; treatment of !
! maternal ctiaease during pregnancy. l
!ToJDplamOils I
i ~ 1'ranlm1llion may ocxur at any time during the pregnancy. Fetal inkctioo rata are lowest in tbe !
l fint t:rilt-':er and JUsheat in the third; CXIIlVel'llely, diJeue -nty ia highest in the tint trimester and lowest in ~
: the third. ~
iPraafMiort: Intracranial calclft.cationa and chorioretinitis; anemia, jaundice, hepam.plenomegaly, I
! lymphadenopathy; Infant& may be a&ymptomati.c at birth. ~
IDUip06U: Toxoplaama-specific antibody testing in the infant. I
I~t: Multidrug therapy of the infant. I
lLo111-,.,.,. ~ Blin.dneu, clevelopmental deJay. I
ISaull.iiiQp,..,.,.tiotu Keep cats indoors and change litter frequently; avoid eating undercooked. meats; limit I
j exposure to contaminated soil. i
i Adapted wfth permission from Ana KS. Pedt8t11c Bo8rr:J Recettmcatlon, 1st ed. Philadelphia, PA: Upplnoott Wllllama l Wilkins;
! 2008:61~, Table 5-8. l
:•••••••••••••••••••••••••••••••••••••••••••• ••••••• ••••" '"'''' '''''' ''''''' ''''''' '''''''''''' ' ''''"''''''hoooonooooo<ooooooOoooooOoooooo•••••••••o•oo•••••o•••••••••••••••••••••••••••••••••••••••••••••••••••••• ••OOOOo••••••••••••• •••••••••••••••••nooooooOOooooo ooooooOooooooOoooooO,.:;
response to delivery. The 5-minute score indicates will have significant hypoxic .injury and long-term
the infant's adjustment to the extrauterine environ- neurologic dallla8e.
ment. If the S·minute Apgar score is low, or there
are ongoing resuscitation attempts, a 10-minute MECONIUM-STAINED AMNIOTIC FLUID
Apgar may be recorded. Apgar scoret are helpful Meconium is present in the fetal intestine by the
in suggesting which infants are transitioning well; second trimester. However, intrauterine passage of
howeve~ they are not an accurate prognostic tool meconium is unusual before 37 weeks' gestation
to predict neonatal morbidity and mortality. The because ofdelayed IDl.OOth muscle and neural plexus
decision to institute resuscitation measures should maturation. Meconium-stained amniotic fluid at
be based on the patient's condition, rather than delivery is common (12% to 15% of all deliveries),
Apgar scores. Infants with sustained low scores are with a higher incidence in African-American and
virtually always acidemic, and the longer the Ap- postterm infants. Often, intrauterine passage of
gar score remains :S3, the more likely the patient meconium is associated with fetal stress, especially
TilLE 2-4. Maternal Substance Use: AssociatBd Fetal AbnonnalitiesiNeonatal Wrthdrawal Syndromes
Alcobol (Oillel: • Gtowth retardation•

llallll lllkaf: ........................
Newboml with fetal aklohol Mental retardation.
6-12 h after birth) • Mkrocephaly syndrome are irritable and Impaired linear pwth i
• Short palpebral &.urea'" tremuioua. reganllea ofwhether Sensorineural hearing lou ~
Micl&ce hypopluia they were exposed after the Strabimms 1
Smooth pbiltnun• first trimester. H the moth« Developmental~ i
Thin, smooth upper is intoxicated at delivery, the (motor, speech) :
vermillion border" infant may be lethargic and Learning disorder.. :
• Joint aoomaliel hypoglycemic. Withdrawal is Behavior problems !
• Altered palmar creases uncommon but may indude (attention-deficit j
• Small distal phalanges sweatiog, irritability, jitterinels, hyperactivity disorde!;. i
• Hypoplastic nails tachypnea, tremon, hypertonia,
• Fifth finler clinodactyly and seizures.
• Hirsutism
• Congenital (septal)
heart defects
leowne • Preterm birth Irritability; otherwise none
recognized
Increased incidence
of sudden infant death
• Intrauterine growth
restriction syndrome; subde 1
• Intracranial hemorrhage
• Seizures concentration
I • Umb reduction defects

• Int8tinal atrelia
1 ~-
• Gl.lltrollchiais
• Urinary tract
abnonnalities
No known organ Uncommon and mllclo One Under inve.tlption; 1
teratogeniclty tremorJ, ampliftecl Mom re6ex poalbly meuurable effects 1
onlQ l
1 Opioids: No known organ Hyperirritability, gutrointe5tinal Developmental delay !
! short-acting teratogenJclty dysfunction. feeding difftcultles, Behavioral problems j
i narcotics6 (onaet • Impaired fetal growth respiratory dlstrea, vague
! ofwithdrawal autonomic symptoms (yawning,
! syndrome within sneezing, mottling, fever),
! l-4d) tremulousness, Jltterinea, high-
pitched cry, increaaed mUlde
lop-
1methadone•
1(o01etof
No known organ
teratogenicity
• Impaired fetal growth
tone, irritability, loose stools
Any combination of the above Developmental delay
Behavioral problems
!withdrawal
! syndrome within
13wk)
! Tobooa>
No known organ
teratogenicity
Fine tremors, hypertonia Sudden infant death
syndrome
Intrauterine growth Developmental delay
restriction A.thma
Low birth weight Otitis media
I! Pretenn labor
Late fetal demise
-chiii'BCter1s11o 11ndlngs of fetal alcohol syndrome.
! "Requires medical interwntion with paregoric, phenobartlital, or methadone and assistance wllh feeding.
! Adapted wltn permlslllon from Fine KS. PediBtrfc Bo8rc:J Recetttllcatlon. 1st ed. Philadelphia, PA: Upplnoott Wiliams & Wilkins;
!..~~:~.~:. :.~~. ~-~:...... ..... . . . . .... . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ... . . .... . ............... . .. . . ..... . . . . . . ..... . . . . :
TABLE M. Prescription Medications Associated with TABLE Z-8. Apgar Scoring

Birth Defects [PIIJslll:al ........ • ~ .. 1 ...........
!'lll. .llllc
!•••;.... EIIWcll
I I Paint 1 Mit I Mill
1 Heart rate Abient < lOObpm :2l00bpm
iWbamazepine ~~~~~ l Respiratory Absent Irregula!o Vigoroua cry
ILithium ::n
anomaly of the triCUJpid
leffort
iColor Pale,
weak cry
Cyanotic
cyanotic extremitiea
~':, Phenytoin ~~=~~;;:road IMuscle Absent Weak.
slightly
microcephaly, mental retardation) ltme flexed
~.!:', Retinoic acid Severe otic anomalies; thymic l Reflex Absent Grimace
aplasia; anomalies of the heart
and/or aorta; central nervous i irritability
Y.~E.~.~.~ ;;~~~~.~~~~··················'
i. ~~.~~.~.~:. ~.~.~.:. ~~-~!...~!~~!:.........................................................1
I. .............
when pre~ent in preterm pregnancies. ~ a group, neonatal conjunctivitis, in particular infections

infants born through meconium-stained amniotic because of Neisseria gonorrhoeae and Chlamydia
fluid have lower serum pH results and are more Ukely trachomatls, still a leac:Uns cause of blindness in the
to have nonreusuring fetal heart tracings. developing world. Vitamin K prevents the develop-
Fetal exposure to meconium-stained amniotic ment ofvitamin K- deficlent bleeding, also known
fluid does require the attendance ofa provider with as hemorrhagic disease of the newborn. Infants
resuscitative skills, including endotracheal intuba- deficient in vitamin K may present with excessive
tion. at delivery. The delivery room management of bruising. intracranial hemorrhage, and/or mucosal
infants born through meconium-stained fluid has bleeding, involving the GI tract, umbilical stump,
evolved over time. The most recent evidence-based or circumcision site.
Neonatal Resuscitation Program (NRP) guidelines Some conditions increase the risk of infants de-
recommend against the previous practice of routine. veloping hypoglycemia after birth as they transition
initial oropharyngeal or tracheal auctioning for from the continuous glucose infusion of the placenta
these infants. For nonvigorous infants (poor tone, to extrauterine life. These conditions include, but
ineffective respiratory effort, and/or heart rate < 100 are not lhnited to, prematurity, LGA, SGA, infant of
beats per minute at delivery), the standard resusci- diabetic mother, and .infants with low Apgar scores.
tation protocol of NRP should be completed. The These .infants should have glucose levels checked
most important intervention for most distressed in the hoUI'S after birth and may require additional
or nonvigorous neonates in the delivery room is feedings, oral glucose gel. or supplemental intravenous
optlmizing ventilation. dextrose to stabilize their glucose levels.
INrTIALCARE
RESPIRATORY DISTRESS IN
Vigorous infants should be given to their moth-
THE NEWBORN
ers directly after birth to promote bonding,
temperature stability, and breastfeeding through Early in the first day of life, illness in the newborn
skin-to-skin contact. Shortly after birth, an anti- often lnitially presents with respiratory distress.
biotic ointment should be instilled in the infant's Distress may be due to a number of pathologic
eyes and an intramuscular injection of vitamin K proce&ses, several of which are life-threatening.
should be a.dmini&tered. Ophthalmic antibiotics are Although diagnosis is critical for guiding aubsequent
given universally in developed nations to prevent therapy, immediate medical intervention must take
precedence. All infants in distress should be stabilized lining the alveoli reduces .surface tension, improving
as quicldy as possible; obtaining radiographic/labo- lung compliance and preventing full alveolar collapse
ratory/microbiologytestl and re5Ults must not delay during expiration. Thus, the infant can generate
treatment. Many babies will only need supplemental sufficient inhalation with lower intrathoracic pres-
oxygen. When this is insuflicient, nasal continuous sures. Conversely, surfactant deficiency results in
positive airway pressure (CPAP) may suflice. A small poor compliance, leading to progressive atelectasis,
minority ofpatients will need endotracheal intubation, intrapulmonary shunting, hypoxemia, and cyanosis.
mechanical ventilation, and possibly even additional Because fetal lung maturity is generally attained by
measures to maintain adequate oxygenation and 34 weeks' gestation, RDS is considered a disease of
acid-base balance. Table 2--7 summarizes the clinical, prematurity, and the incidence increases with de-
radiographic, and arterial gas findings associated creasing gestational age. However, RDS does occur
with a few of the more common newborn conditions uncommonly in term and near-term infants, either
presenting with respiratory distress. through incorrect dating of the pregnancy or through
delayed cell maturation/surfactant production. For
MECONIUM ASPIRADON SYNDROME example, the combination of fetal hyperglycemia and
Although the immediate treatment and relative hyperinsulinemia in maternal diabetes may result
clinical significance of meconium·stained amniotic in delayed production of surfactant. Conversely,
fluid are arguable and in flux, it is important to ongoing fetal stress (e.g., preeclampsia) is associated
recognize meconium aspiration s')'DCI.rome (MAS) with accelemted lung maturation.
in a susceptible neonate. MAS consists of delivery Affected infants characterbt:ically present with
through meconium·stained amniotic fluid coupled tachypnea, grunting, nasal .Oaring, chest wall re-
with respiratnry distress and characteristic chest tractions, and cyanosis in the first few hours oflife
radiograph findings (air trapping and patchy atel- (see Table 2--1). Auscultation reveals poor air entry.
ectasis). ln affected infants, the large intrathoracic The diagnosis is confirmed by chest r adiograph that
pressure that accompanies the first inspiration brings reveals a uniform rdiculo1Wdular or ground-glass
meconium from the oropharynx and trachea into pattern and air bronchograms that are consistent
the lungs. Only about 5% of infants born throush with diffuse atelectasis. Conventional therapy for
meconium·stalned amniotic fluid develop MAS. the affected infant includes respiratory support
Severity ranges from mild (tachypnea and/or needing with oxygen, CPAP, and/or mechanical ventilation.
supplementary oxygen only) to severe disease, which depending on the severity of respiratory compro·
requires intubation and mechanical ventilation. mise. Exogenous surfactant may be administered
Though rare, the most severely affected infants via endotracheal tube to high-risk (::$;26 to 28 weeks
may need extracorporeal membrane oxygenation estimated gestation age) or severely affected infants,
(ECMO) support, a type of heart-lung bypass. MAS with the goal of preventing the onset or reducing the
is often complicated by pulmoaary hypertension. severity of RDS. The natural course is a progressive
Because meconium inactivates endogenous surfac- worsening over the first 24 to 48 hours oflife. After
tant, surfactant administration may be beneficial in the initial insult to the airway lining, the epithelium
severely affected infants, who as a group suffer from begins to repopulate with type ll alveolar cells, which
high rates of morbidity (chronic lung disease) and produce surfactant. Subsequently, there is increased
mortality. Survival rates have improved markedly in production and release of surfactant, so there is
recent years, due in part to the use of inhaled nitric sufficient quantity In the air spaces by 72 hours of
oxide to treat the auociated pulmonary hypertension. life. This results In improved IWlg compliance and
resolution of respiratory distress.
RESPIRATORY DISTRESS SYNDROME The best form of treatment is prevention. When
Jleapiratory cllstreu lflldrome (RDS), also referred preterm delivery cannot be prevented, administration
to as layaline membruecliJeue {HMD), results from ofcorticosteroids to the mo~ optimally48 hours
a deficiency of swfactant, a complex phospholipid before delivery, can induce or accelerate the produc·
and protein mixture produced by type n pneumocyte tion of fetal sudactant and minimize the incidence
cells in the pulmonary epithelium. The surfactant of RDS. ln fact, antenatal steroids are administered
..,......'p,_ .._.....,a.--
TULE 2-7. Raspira1Dry Distress in the Newborn
.............. ......... ............

~
-.. ..........
IJndl'lllll
Definition 1'ranlimt lnluffident .....t'actant, Lung infection Aapintion of
pulmonary edema mo.t: commooly in acquirecl before, memnium that remlb
~&om an imlnature lung, during, 01' after birth in obstructiw lung
delayed clearance of c:auJing respiratory dileue, chemical
fetal lung t1uid compromise pneumonitil. and
inactivation of
surfactant
Epidemiology Ooc\11'1 in both tenn More common in Varies depending Uncommon before
and preterm infants; preterm infants on etiology (in utero 37-wk gestation; more
more common in infection, group B common in poattenn
infants delivered via Streptocom~.S, bacterial pregnancies and infants
C-section (especially pneumonia) with perinatal asphyxia
If delivery takes
place before the
onset of labor)
Presentation Presents shortly Presents shortly after Signs of respiratory Present& within 12 h of
after birth with birth with progressive diatreu and/or sepail: birth with progrsaive
tachypnea and tachypnea and presentation may be tachypnea. flaring.
occuionally respiratory distress virtually identical to grunting; raleslrhonchi
grunting and nasal thatf1IIDS on chest examination;
flaring "barrel. chat
Arterial Mild respiratory Respiratory acidosis, Respiratory acidosis, Respiratory acidosis,
blood go aciclosia (J,pH, hypoxemia hypoxemia significant hypoxemia
c:baoges 'tPaco:J, mild- to-
moderate hypoxemia
(..l.Pao:J
Olest Prominent perihilar Homogeneous LocaJized, patchy, Areas of patchy
racliosraph streaking, increa.sed •ground-glass" or widespread atelec:taail, coarse
interstitial markings, appearance oflung consolidation; poasibly irregu]ar den~ities
fluid in the fields because of pleural effusions; interspersed with areas
Interlobar fissures air bronchograms chest radiograph of of hyperinflation
superimposed on pnewnonia because of
widespread atelectasis group B StreptoCOCCIU
v1rtually identical to
that for RDS/HMD
Treatment ~therapy, Respiratory Intravenous antibiotic Respiratory support as
continuous nasal support (e.g.. nasal therapy, respiratory needed; in severe cases
positive airway cannula, mechanical support as needed mechanical ventilation
preuure If needed ventilation) as needed; with high concentration
exogenous surfactant of02 and hJgh mean
administration in airway preMUl'el,
severe caaea inhaled nitrk oxide, or
ECMO
PreYention None .known; Antenatal steroids; Prenatal screening Conakler avoiding
incidence lower exDFDOlll RUfac:tant and treabneDt of the poetmature (alta-
in bablel bom tdmlnlslration at birth mother before/during 41 wk) delivery with
vaglDa11y and thole for high-rille: patienta prqnancy; univenal induction oflabor
bom via C-sectlon ( <26-28 wk EGA) maternal group 8
CollowiDg a period of (prophylactic) Slnptocotx:ru screening
labor
I~
TAILI2·7. Respiratory Distress in the Newborn (continusd)
............
~ long·term
'hnlllllt ........ •upt...
Spontaneous Often minimal when

recovery within days recognized and treated;
........ (.s)
,a...._
..... .... ......
.......
Proposis depends
more on whethes-
.._......
Acute: pulmonary
air leab. Long--tmn
I- with no long·term
complications
bronchopulmonary
dysplasia when
protracted mechanical
~ntilation with high
infection ia pnsent
at other ma (central
nervous system)
prognosi& depends
more on degree and
duration of"Rntilatory
support required;
oxygenation needs chronic luag disease
II a known sequelae
of severe meconium
I aspiration
: Abbreviations: ECMO, axtracorporeal membrane oxygenation: EGA, estimated gestation age; HMO, hyaline membrane disease. l
" " "' "'""'"'''"""""""''''''''''''"'''''"'''''"'''''"'''''"'''''"''''''''''i
: , , , , , . , , , , ,00. , . ,000000000000000• 000. ,000, .000 o 000. ,ooooooo"oo"""'''''''''''''''"'''''''"''''''nooooooooooooooooooooo-ooooooooooooooooooooooooooooooooooooo-ooooooooo""'' " " " ' " " " ' - " ' ' ". .
to all women at risk for pretenn delivery prior to Management of the illness parallels the severity
34 weeks' gestation and sometimes up to 37 weeks' ofthe presentation. Mildly affected infants (the great
gestation. majority) may need no respiratory support or only
supplemental oxygen. Occasionally nasal CPAP is
TRANSIENT TACHYPNEA OF THE NEWBORN used; rarely, intubation and mechanical ventilation
'fianslent tachypnea of the newborn (TTN) is may be necessary for a short time.
relatively common, affecting up to 0.5% of term
newborns. The condition, also tenned rdainedfotal NEONATAL PNEUMONIA
bmg liquid syndrome, is thought to be due to delayed Pneumonia isa commonneonatBI infection. PathogelUi
resorption offetal pulmonary fluid. Normally, more may include those detailed in Table 2-3; however.
than a third of fetal lung fluid is resorbed in the the most common agents are bacterial (group B
few days prior to the onset of labor. The remaining Streptococcus; Escherichia coli; Kkbsiella species).
fluid must be cleared during labor and the first few Initial signs are generally those of respiratory distress;
hours oflife. Disruption of this nonnal reabsorption indeed, the clinical and radiographic presentation
results in excess fluid in the lungs. The respiratory of pneumonia may be indistinguishable from MAS,
distress is generally short lived, resolving in hours to RDS, and TTN. Chest radiograph findings are most
a few days with minimal intervention. Large preterm likely to suggest widespread disease rather than a
infants are at increased risk, as are infants hom by focal or lobar infiltrate. In other cases, early signs
elective cesarean section without preceding labor. may instead be those of neonatal sepsis, including
Multiple additional risk factors include macrosomia, temperature instability, poor feeding, and lethargy.
significant maternal fluid overload, delayed cord Because of the significant morbidity and mortality
clamping, precipitous delivery, multiple gestations, associated with neonatal bacterial infections, the most
and maternal diabetes. appropriate course oftherapy is to obtain a complete
The affected infant presents shortly after birth blood count with differential and blood cultures. Ifthe
with obvious respiratory distress, including sus- white blood cell (WBC) count is concerning (e.g., h1sh
tained tachypnea, nasal flaring, grunting, and chest imma1:1Jre...to-mature cell ratio) or the infant appears
wall retractiom. CyanosiA is uncommon. Results of ill, intravenous ampicillin and gentamicinlcefotaxime
arterial blood gas testing and chest radiograph are should be started empirically. Antibiotics may be
noted in Table 'Jr7. A complete blood count, when narrowed pending culture results and sensitivities,
obtained. is not susgestive of infection. Although generally to complete a 10. to 14-da.ycourse. Infants
the studies listed are helpful, TTN is essentially a may also require varying levels ofrespiratory support,
diagnosis of exclusion. from supplemental oxygen to mechanicalventilation.
LabondDry Evaluaaon
NEONATAL SEPSIS Seemingly unaffected infants who are at increased
Neonatal sepsis is generally divided into early-onset risk (chorioamnionitis, inadequate intrapartum
versus lare-onset sepsis. Early-ODHt sepsis occurs prophylaxis with preterm delivery or with prolonged
anytime from birth to 3 to 7 days. Late-ouet JepsiJ rupture of membranes) and afebrile infants with
affects babies after the first several days oflife through subtle/transient signs of possible early sepsis should
1 month of age. Both illnesses consist of infection have a complete blood count and blood culture
of the blood associated with signs and symptoms drawn. Various algorithms exist regarding the use
of systemic compromise, typically due to bacterial of the WBC count, differential, and serial C-reactive
organisms, although viral and fungal organisms may protein levels to guide •watchful waiting" versus up
cause clinical aepsis. Early subtle signs may hint at to 48 hours ofantibiotic therapy until culture results
the diagnosis (tachycardia, temperature instability, are known. Infants with suspected sepsis should have
poor reeding, decreased tone, apnea, irritability, blood and cerebrospinal fluid (CSF) sent for culture.
lethargy, hypoglycemia). Often, however, neonatal CSF should also be tested for Gram stain, cell count
sepsis presents suddenly and progresses rapidly, in and differential, and protein and glucose levels. A
aevere cases culminating in respiratory failure, septic serum WBC <5,000 or >40,000, a total neutrophil
shock, meningitis (30%), disseminated intravascular count below 1,000, and a ratio of bands to neutro-
coagulation, multisystem organ failure, and death. phils of > 20% all correlate with an increased risk
of bacterial infection. Neonates with organ-specific
EARLY NEONATAL SEPSIS signs and symptoms will need additional testing (e.g.,
Pathogenesis/Epidemiology chest/abdominal radiographs).
In early-onset sepsis, the infant becomes infected
during the intrapartum period with bacteria residing Trelltment
in the mother's genital tract. Group B Streptococcus The treatment ofearly-onset sepsis begins before the
is the most common pathogen; however, universal diagnosis is confirmed via laboratory data because
antenatal screening at 35 to 37 weeks' gestation and the mortality rate is extremely high (up to 25%). The
intrapartum prophylactic administration to colonized patient is treated empirically with a combination of
women have decreased the incidence substantially. ampicillin and gentamicin. This remains the most
Two doses of the antJ.'biotic (penicillin, ampicillin, or effective treabnent against most organisms respon-
cefazolln) must be administered, at least 4 hours apart, sible for early sepsis and is the standard of care for
prior to delivery for prophyJaxis to be considered initial management. Once an organism is identified
adequate. E. coli and Lilterir~ m.onocytogena are also and antibiotic sensitivities are determined, antibiotic
important pathogens in early-onset neonatal sepsis. therapy may be tailored to treat the infecting organism
for a 7- to 14-day course. If meningitis is present,
Risk Factors the treatment is extended. and a third~generation
Predisposing factors for early-onset sepsis include cephalosporin is recommended for improved pen-
premature or prolonged rupture of the membranes etration across the blood-brain barrier. Infants with
(~18 hours), chorioamnionitis, maternal.lntrapartwn unstable vital signs and evidence of septic shock
fever or leukocytosis, and preterm birth. warrant transfer to a neonatal intensive care unit
Clinical Manlfesbrtlans for more specialized management of their disease.
Because the disease has a high mortality and is rapidly
progressive, providers must maintain a high index of LATE-ONSET NEONATAL SEPSIS
suspicion. Infants with subaequent decompensation Late-Oidet ~epa occurs in a full.-term infant who
may initially display the nonspecific signs mentioned was discharged in good health from the normal
earlier. Cyanosis, pallor, petechiae, vomiting. abdom- newborn nursery. The infection may be isolated to
inal distention (ileus), respiratory distress/apnea, and the blood (bacteremia). However, it is not uncom-
hypotension are more worrisome signs. Respiratory mon for hematogenous seeding to result in focal
manifestations in particular are extremely common; infections such as meningitis (25%, usually caused
as previously noted. any infant presenting with re- by group B streptococci or E. coli), osteomyelitis
spiratory distress in the newborn period warrants a (group B streptococci and Staphylococcus aureus),
septic workup and treatment with broad-spectrum arthritis (N. gonorrhoeae, S. aureus, gram~negative
antibiotics until culture results are known. bacteria), and urinary tract infection (E. coli, KkblieUa,
and other gram-negative rods). Infection may also term newborns with hyperbilirubinemia because
start as a urinary tract infection that spreads to the of breast milk jaundice, even when serum bilirubin
blood stream. The presentation, workup, and initial levels exceed numbers at which medical intervention
treatment of late-onset sepsis are similar to that of (i.e., phototherapy) is recommended. Breast milk
early-onset sepsis, but should additionally include jaundice is not the same as brH~tjudbtgj4undice, the
a wine culture and other variations depending on term sometimes used to describe the exacerbation
the most likely site of the infection. of physiologic jaundice in the .first few days of life
because of insufficient breastfeeding.
Jaundice because of a pathologic process does
JAUNDICE not appear any different on physical examination
Bilirubin Is a blle pigment, formed from the degra- than physiologic or breast mille jaundice. However,
dation of heme derived from red blood cell (RBC) identifying neonates withnonphysiolopc jaundice
destruction and ineffective erythropoiesis. This is crucial to preventing long-term morbidity and
initially unconjugated fonn must be conjugated in complications from the underlying disease process
the liver to permit excretion in the bile, stool, and (i.e., anemia, stroke, metabolic disease). Table 2-8
urine. Hyperbilirubinemia manifests as jaundice-a lists factors associated with an increased likelihood
yellowing of the skin, mucous membranes, and of pathologic jaundice. The most common cause of
sclerae. In neonates, jaundice becomes clinically nonphysiologlc unconjugat:d hyperbilirubinemia
apparent when serwn bilirubin levels are> 5 mg/d.L. is ABO incompatibility. Frequent causes of con-
Hyperbilirubinemia may be classified as unconjugated jugat:d hyperbilirubinemia are diseases involving
(indirect), which in neonates can be physiologic or liver pathology (biliary atresia, neonatal hepatitis)
pathologic in origin. and conjugated (direct), which and congenital infections; two additional causes to
Is always pathologic. Conjugated hyperbilirubinemia consider are a--antitrypsin deficiency and galacto-
exists when the dlnct fraction of bilirubin in the semia (Chapter 19).
blood exceeds 2 mg/dL or 15% of the total bilirubin; ABO incoJDpalibility is the most common cause
otherwise, the disorder is cluaified as "unconjugated." of pathologic unconjugated hyperbilirubinemia. It
Expected levels of unconjugated bilirubin may top is most common in infants with type A or B blood
12 msJdL in healthy newborns, with "normal'" values born to type 0 mothers. ABO incompatibility re-
based on gestational and chronologie ages. sults in henwlytk anemia in the newborn because
PATHOGENESIS
Physiologic jaundice and breast milk jaundice are by YULE 2-&. Factors Associated with Increased Risk
far the most common causes of hyperbilirubinemia in That Jaundice/Hyperbilirubinemia Is
the neonate. Ph.yalol.oglc jaundice is due to indirect Pathologic
hyperbilirubinemla, which occurs in the absence of ' • Evidence of jaundice prior to 24 h of age (suspect
any underlying abnonnalities in bilirubin metabo- ! hemolytic disease) '
lism. The jaundice is never present before 24 hours 1· Rise in serum bilirubin level faster than
of age and peaks between days 3 and 5, generally at ; 0.5 mgldLih
or below 12 to 15 mg/dL. Values normalize by 14to
21 days of life. Infants born before term have later
i • ==bilirubin J..evd :<!:75th percentile for I
and higher peak bilirubin levels. 1• Jaundiced infant with hJstory of traumatic dellvery j
Breut milk jauncllee is similar to physiologic l • Need for phototherapy !
jaundice, but presents after the first 3 to 5 days of Penlstent jaun.dioe (longer than 8 d in a term
i,,, • j
!
,.=inin
infant or 14 d in a preterm. infant)
life, and bilirubin levels tend to peak slightly later
(within the first 2 weeks oflife), higher, and remain
elevatedlofi8er. The mechanism ofbreast milk jaun-
l • Jaundice in an ill-appearing infant
an infant with microcephaly or I
j
dice is not completely understood. Some researchers 1• Jaundice a anall for gestational age infant j
have theorized that it is caused by an increase in i.,, • Jaundice in an infant born to Mediterranean or j
enterohepatic circulation from an unknown maternal Asian parent& !
!!
factor in breast mille. The American Academy of 1
,' , • Family hi5tory of hemolytic anemia, liver disease,
Pediatrics (AAP) recommends against routine inter- or sibling with nonphys.iologic jau.ndic:e as a
ruption of breastfeeding in healthy, well-hydrated, :..........~.~.............................................................................................................!
of an isoimmune process. The direct Coombs test clinically apparent jaundice below the umbilicus
detects maternal antibody on the surface of the are likely to have higher levels than those with only
neonatal RBC and will be positive in infants with facial jaundice. It disappears in the opposite direc-
ABO incompatibility. The indirect Coombs test is tion; scleral icterus is generally the last to resolve.
used to identify the spedftc type ofantibody (anti-A.
anti-B, etc.). Additional laboratory indicators include DIAGNOSTIC EVALUATION
an elevated reticulocyte count and a blood smear Regardless of the pre.umptive etiology and classifi-
demonstrating hemolysis and micro•pherocytes. cation (physiologic vs. pathologic), thoughtful step-
Hepatomegaly is uncommon but may be present. wise evaluation of neonatal jaundice is imperative.
Approximately 1CJ6 of newborns develop clinically Infants with signifi.cant clinical jaundice, jaundice in
slgnifi.cant unconjugated hyperbilirubinemia from excess of that expected based on age, and jaundice
ABO incompatibillty. Although the use of photo- in the presence of risk factors noted earlier should
therapy is common in these infants, the incidence have serum total and direct bilirubin measurements
of severe hemolytic disease necessitating exchange drawn. Published nomograms permit stratification
transfusion is rare. of infants into risk categories based on gestational
Rh incompatibility is a more serious type of iso- age, chronologie age in hours, and bilirubin levels.
lmmune hemolytic anemia wherein an Rh-negative Infants who are in the category of high risk for de-
mother who has become sensitized to the antigen velopment of excessive bilirubin levels should have
with a previous pregnancy produces antibodies serial measurements drawn every 4 to 12 hours. The
that react with Rh-antigen on fetal RBCs. The fetus utilization of transcutaneous measurement devices
must be Rh-positive for the process to occur. Ma- has decreased the need for frequent blood draws.
ternal Rh status is determined early in the prenatal The initial measurement should be a serum sam-
period. RhoGAM. a solution of immunoglobulin ple, as transcutaneous devices do not differentiate
G antibodies to Rh-D antigen, binds fetal cells in conjugated from unconjugated bilirubin. Similarly, a
maternal circulation and destroys them. preventing transcutaneous meuurement that reaches the level at
the development ofisoimmunity. lt is administered which medical intervention is recommended should
to Rh-negative mothers at 28 weeks' gestation. The be confirmed with a serum sample.
hemolytic anemia resulting from Rh in.compatl.oil- Figure 2--1 delineates the suggested workup of
lty is generally more severe than that from ABO an infant with suspected nonphysiologic jaundice
incompatibility. Unlike Rh incompatibility, prior that, as previously noted. may be either conjugated
maternal antigen sensitization is not required for or unconjugated in origin. These additional studies
ABO incompatibility. should be selectively considered in infants with
higher-than-expected peak bilirubin levels, rapidly
CLINICAL MANIFESTATIONS rising levels, levels necessitating medical manage-
Hlstury ment. conjugated hyperbilirubinemia, or delayed
It is important to determine the infant's diet (breastfed, resolution of jaundice.
fonnula-fed, or a relative mixture), the number offeeds
in a 24-hour period (goal of8 to 12), and the duration TREATMENT
or volume ofeach feed. Inadequate intake is associ-
The goal in treating unconjugatuJ hyperbilirubinemia
ated with delayed hepatic circulation and excretion
is to avoid kemictenul, or bilirubin encephalopathy.
of bilirubin. and more severe jaundice. The family
Unconjugated bilirubin is normally bound tightly
history should include questions regarding heritable
to albumin in the blood. However, when serum
conditions listed in Table 2·8. Prenatal screens, the
physical examination, and growth parameters should levels of unconjugated bilirubin exceed the binding
capacity of albumin, excess free bilirubin can cross
be reviewed for possible indicatioM of congenital
the blood-brain barrier. Kernicterus is characterized
infection. The length of time the jaundice has been
by yellow staining of the bual ganglia, hippocam-
present , whether it is worsening or improving, and
pus, cerebellum. and various additional brainstem
associated Gl or constitutional symptoms may assist
neurons, resulting in widespread cerebral dysfunc-
in guiding the laboratory evaluation.
tion. Initial clinical features include lethargy and
Physical Examination lrritablllty, progressing to hypotonia, opisthotonos,
In neonates, jaw1dice reliably progresses in a ceph- and seizures. InJimts who survive develop cerebral
alopedal direction. Therefore, those infants with palsy and movement disorders and may also suffer
Clinical )aundloe Follow bilirubin
Direct bllrubln ~ mgld... or

Obtain direct 15% ol total bilubin
bilirubin level (~frld hypertJilitubin
Direct bilirubin <2 mWdL Consider biliary atresia,

or 15% of 10ta1 bilirubin hepatitis, infection,
(unconjugs!fld hyperbilirubinemia) metabolic disease
Positive
Consider hemolytic
process of immune
etiology (ABO/Rh incompatibility)
Normal Consider
or low polycythemia
(central venous hematocrit ~70%)
Evaluate Normal reticulocyte

reticulocyte count, smeau
count,
blood smear
Consider:
• Peri-/postnatal extravascular
blood loss (e.g., bruising,
cephalohematoma, hemorrhage)
Consider pmnatal
• Bactertal sepsis
hemorrhage/blood loss
• Drug reaction
Consider:
• Nonimmune hemolysis
• Inherited red blood cell
membmne delecta (e.g., apherccytosla)
•Thalasaemlas, other hemogloblnopathlas
• For geatatlonal and chronologie aga basad on published American Academy of Pedlatrtce nomograms
!!~~.~!:~.~.~~'!!..!!?.r..~..~~~~~--~~ed nonphyslo~~ ~~~.~~ t~~..MC?n~e··-·-·--·----
from irreversible vision and hearing problems and/ overhydration does not result in more rapid resolu-
or mental retardation. tion of the jaundice. When additional intervention
Orogastric feeding or intravenous fluids are is needed or hydration statta is normal, photother-
beneficial when dehydration is present, although apy and exchange transfusion are the treatment
modalities wed to lower serum unconjugated methotrexate, which works as a folic acid antagonist.
bilirubin levels. In general, infants with isolated cleft lip may have
In July 2()()4. the AAP Subcommittee on Hyper- difficulty forming a seal around the nipple but do not
bilirubinemia published extensive and extremely require feeding modifications to avoid respiratory
helpful clinical practice guidelines regarding the distress. Patients with cleft palate have difficulty
management ofhyperb111rubJnemia. and prevention generating suction, and they are prone to choking
strategies. In addition to the figures cited earlier, with feeds and aspiration pneumonia. Brearrtfeeding
nomograms provide phototherapy and exchange may be difficult, and most affected infants benefit
transfusion treatment guidelines for infants in each from manually repositioning the tongue and feeding
risk group. while seated upright. Many patients also do well with
Special blue Ouorescent tubes are the most effective an elongated.. soft nipple.
light source for providing intensive phototlrerapy. Most cleft lips are repaired a few months after
The light source is placed as close to the infant as birth or once the infant demonstrates steady weight
practical, with lighting above and below ifpoSSlole. gain. Oeft palate repair is usually undertaken at 9 to
The infant should be virtually naked and wearing eye 12 months of age. Complications after cleft palate
protection. Because l.nsensible losses are increased, repair include speech difficulties, dental disturbances,
adequate hydration is critical for assuring sufficient and recurrent otitis media. Although two-thirds of
enterohepatic circulation and increasing urine and palate-corrected children demonstrate acceptable
bile output. Hpossible, the infant should be allowed speech, a hypemasal quality or muffled tone may
to breastfeed. persist in the voice.
Exchange transftulon is recommended for infants
with levels directed in the practice guideline nomo- 11W:HEOESOPHAGEAL FISTULA
grams mentioned earlier, u well u any infant with Incomplete anastomosis of the superior and inferior
a total serum bilirubin > 25 mgldL or clinical mani- portions of the esophagus is known as esophageal
festations ofacute bilirubin encephalopathy. Infants atresia. Eighty-five percent of newborns with esoph-
with isoimmune he molytic disease may respond to ageal atresia also develop a t:ndleoe•ophaaeal
early intervention with intravenous gamma globulin fistula (TEF), which is an (abnormal) communica-
therapy and avoid exchange transfusion. tion between the trachea and the esophagus. This
As noted, elevated serum conjugated bilirubin connection is usually between the trachea and the
levels are never physiologic. Every effort should be lower portion of the esophagus (Fig. 2-2). A majority
made to detennine the cause, reverse the underlying of these cases are sporadic. However, 79' ofaffected
process, and limit complications. Phototherapy in infants have an underlying chromosomal abnormal-
the setting of conjugated hyperbilirubinemia is not ity, and 70% of those cases have another congenital
effective and causes "bronzing" ofthe skin that takes defect. for example, VACTERL syndrome describes
months to resolve. the association of vertebral. anaL cardiac, tracheal,
esophageal, renal, and limb anomalies.
CONGENITAL ANOMALIES
CLEFT UP AND PAlATE
Multiple genetic and environmental factors play a
role in the etiology ofcleft lip and cleft palate. Cleft
lip (with or without cleft palate) occurs in 1 in 1,000
births and is more common in boyB. Cleft palate
occurs in 1 in 2,500 births.
Oeft palates are common in patients with chro-
mosomal abnormalities. Genetic counseling should
be recommended, and amniocentesis for karyotype
and/or microarray should be offered. Women plan- Esophageal atr116ia
ning to become pregnant should receive folic acid wfth distal TEF
(85%)
supplementation and neither smoke nor consume
alcohol. They should also avoid drugs associated with FIGURE Z-2. Esophageal atresia with distal
this malformation. such as anticonvulsants as well as ~~~~~~~~-~--~-~-~!.~..IT.~B.:.............................................................
Neonates with TEF have excessive oral secretions, that permits abdominal contents to enter the thorax
recurrent cough, and respiratory dimess from their and compromiae early lung development. Increased
inability to swallow. Polyhydramnios is often noted compression leads to decreases in both bronchial
on fetal ultrasound because ofobstruction within the and pulmonary artery branching. This results in
GI tract. Diagnosis can be made by placing a feeding lung hypoplasia and pulmonary arterial muscle
tube and obtaining a chest radiograph. Termination hyperplasia, which ultimately leads to pulmonary
of the tube in a blind pouch within the mid-thoracic hyperbmsion. The combination makes this congenital
cavity is highly suggestive of esophageal atresia. defect lethal in many cases. Early symptoms include
When a distal fistula is present, the GI tract will be respiratory distress with decreased breath sounds on
tllled with air. However, in isolated esophageal atresia the affected side, risht-sided (shifted) heart sounds,
without TEF, gas is absent from the GI tract. Infants and a scaphoid abdomen. Diagnosis is sometimes
with TEF but without associated esophageal atresia made via fetal ultrasound; after birth, the defect is
(H-type TEF) may have nompeclfic .symptoms for obvious on chest radiograph.
several months, including feeding intolerance, chronic Initial management consists of immediate in-
cough, recurrent pneumonia, and failure to thrive. tubation and ventilation. as well as placement of a
Surgical correction involves division and closure of nasogastric tube to minimize GI distention, which
the TEF and end-to--end anastomosis of the proximal could further compromise effective lung volume.
and distal esophagus. The most common complications Sometimes conventional ventilation is not sufficient
include dysphagia because ofesophageal dysm.otility to provide adequate oxygen delivery and carbon
and esophageal strictures at the anastomosis site, dioxide excretion; in such cases, high-frequency
which require periodic dilation. Prognosis for these ventilation or ECMO may be needed to manage the
patients is generally good. Significant morbidity is child's pubnonary hypertension. The defect requires
often associated with the presence of associated surgical correction shortly after birth, although the
cardiac anomalies. effects of pulmonary hypoplasia and hypertension
may persist for months to years and cause significant
DUODENAL ATRESIA morbidity for these infants.
Duodenal obstruction may be complete (atresia) or
partial, resulting from either intrinsic blockage (i.e., OMPHALOCELE AND GASTROSCHISIS
intraluminal web) or extrinsic compression (i.e., annular Ompbalocele is an uncommon disorder in which
pancreas). Duodenal atresia results from a failure the abdominal viscera herniate through the umbil-
of the lumen to recanalize following endodermal ical and supraumbillcal portions of the abdominal
epithelium proliferation during the 8th to lOth week wall into a sac covered by peritoneum and amniotic
ofgestation. Similar to TEF, polyhydramnios may be membrane. Large defects may contain the entire GI
noted on prenatal ultrasound. Duodenal atresia is tract, the liver, and the spleen. Polyhydramnios is
usually associated with other malformations, which noted in utero, as is the omphalocele itself in many
account for the majority of morbidity and mortality. cases. Ten percent ofinfants with omphaloceles are
These include cardiac anomalies and GI defects such born prematurely. The sac covering the defect is thin
as annular pancreas, malrotation of the intestines, and may rupture in utero or during delivery. Associ-
and imperforate anus. Duodenal atresia occurs with ated congenital Gl and cardiac defects are common
increased incidence in patients with trisomy 21. and account for the vast majority of morbidity and
After birth, bilious emesis begins within a few mortality. The presence or absence of underlying
hours of the first feeding. Abdominal radiographs genetic disorders guides management and identifies
typically demonstrate gastric and duodenal gaseous prognostic indicators. Interestingly, the absence of
distention proximal to the atretic site. The pylorus liver within the omphalocele strongly predicts an-
separates these areas, and the finding is known as euploidy(~). About 10% to 20% of children with
the double bubble sign. When present, gas in the omphalocele have Beckwith-Wiedemann syndrome
distal bowel suggests partial obstruction. Surgical (exophthalmos, macroglossia, gigantism, hyperln-
correction is necessary. sulinemia, hemihyperplasia, and hypoglycemia).
In contrast, tpUtroKhiU. involves herniation of
CONGENITAL DIAPHRAGMATIC HERNIA the intestine through the abdominal wall (lateral to the
Congenital diaphragmatic hernia results from a umbilicus) with no covering peritoneal membrane.
defect in the (usually left) posterolateral diaphragm It is an isolated sporadic finding in most instances.
42 • BWEPAINTS Pediatrics
A.uociated defects are presentin 5~ to 20% ofcases.

BEFORE DISCHARGE HOME
However. these defects are mostly inteatinal atresias
direcdy related to mechanical and/or ischemic injury Term, well-appearing newborn infants with no
for the exposed bowel Morbidity and mortality are significant risk factors in the pre-/perinatal period
almost entirely related to intestinal dysfunction caused may be discharged at 48 hours of age. Discharge
by in utero injury. The eviscerated bowel typically after 24 hours but before 48 hours of age may be
appean edematous, matted, and foreshortened. It permbsible when sufficient time has elapsed to
is often contained within an inflammatory rind, identify early problems, when the family is judged to
known as the •peel!' This inflammatory state can be well prepared to care for the child at home, and
cause functional consequences, such as impaired appropriate outpatient follow-up is arranged within
gut absorption and prolonged gut motility. The 48 hours of discharge (Table 2-9). Babies born via
pathogenesis of this abdominal waU defect is not cesarean section are not typically discharged prior
clear. Polyhydramnios is typically noted in utero to 72 hours of age because of maternal obstetric
because ofdisruption of gut patency. Gastroschisis comiderations. The infant should have an acceptable
is a surgical emergency, often with staged closure. feeding pattern and should have stooled (within the
first 24 hours oflife) and voided prior to discharge.
BILIARY ATRESIA Jaundice should be assessed. The first vaccination
Biliary atresia is a progressive, idiopat.h.ic, fibro-obllterative against hepatitis B is typically administered prior
disease of the extrahepatic biliary tree that presents to discharge.
with biliary obstruction in the neonatal period. At the hospital. a sample of infant blood is col-
Peraistent cholestasis results in liver fibrosis, portal lected and sent t o a state screening lab to test for a
hypertension, and eventualliwr failure. Conjugated large variety ofillnesses, including some metabolic
hyperblllrubinemia is the earliest finding and al- diseases (e.g., phenylketonuria), siclde cell disease,
ways warrants further evaluation. Liver enzymes are congenital adrenal hyperplasia, and congenital
also signifu:andy elevated. Over the first few weeks hypothyroidism (see Chapter 15). A hearing screen
of life, infants develop clay-colored (light) stools, and a screening test for critical congenital heart
dark urine, and hepatosplenomegaly. Abdominal disease (by pulse oximetry measurement) are com-
ultrasound and nuclear medicine scanning can be pleted as well. These studies are undertaken in the
used to confinn the absence of bile flow from the nursery because early identification is relatively
liver. However, liver biopsy is considered the gold inexpensive compared with the cost of treating
standard for diagnosis. Establishment of a conduit the disease at a later stage. The incidences of these
from the bile ducts into the intestine via surgery conditions range from uncommon to rare, but all
(I<asai procedure) is beneficial in many children; are associated with significant morbidity when
however, the majority require liver transplantation. left untreated.
TABLE 2-1. Newborn Earfy Discharge Criteria

i Discharge prior to 48 h of age may be conaidered appropriate if:
!• the Infant is full~tenn
!• the infant has a normal physical exa.mina:tion
l • the infant has maintained normal vital signa
l• the infant is urinating and .tooling
! • the infant has had at least two consecutive successful feedings (breut or bottle)
!• a risk assessment for hyperbilirubinemia has been completed and appropriate follow~up ensured (must be
i within 2 d of discharge)
!• the circumcision site is healing without bleeding (if applicable)
i • the risk for group B streptococcal. disease has been assessed and addressed
!• maternal prenatal labs are negative/reassuring .
~ • the parentl have been educated regarding Infant feeding expectatlou, the benefits ofbreastfeeding, akin/cord/ 1
l drcwncision care, car seat use, "Back to SleeP: prevention of sh.alcen baby syndrome, etc. l
! • metabolic (state screening), congenital heart disease, and hearing screenings have been completed. and the ~
1 fint hepatitis 8 vaccine lwl been adminiatered i
i • the mother doea not have a politfve drug screen. i5 not an adolescent. and bu a safe home to whlch to return
-············-~····--·············----·---·-·-············-·······~········-·········--·········----------..················----··-··--·-···-···--····················-··
. . . . . .4 . . . . . . . . . . . . . .
l
~
because of their climate or otherwise, are exposed

HEALTH MAINTENANCE VISITS
to very little sunlight.
Infants should be evaluated at a health maintenance Both breast milk and current commercial for-
visit within a week ofdischarge. Many babies are seen mulas provide sufficient iron to infants less than 6
earlier to make sure weight loss is not excessive and months of age. Hemoglobin and hematocrit levels
jawulice, ifpresent, is resolving. Neonates typically dec::rease slowly in the term infant to a "physiologic
lose 5% to 7% of their birth weight in the first few nadir'" sometime between 8 and 12 weeks of life.
days. A 1096 drop is within normal limits but warrants During this period. hemoglobin values u low as
close monitoringand early follow~up. Babies should 9 mg/dL are considered normal. Shortly thereafter,
gain back their birth weight by 14 days of age. the hemoglobin begins to rise in response to infant
The AAP recommends that breutfed infants be marrow production of cells.
started on vitamin D drops (400 IU/d) beginning in
the 6.rst few days oflife. Although it is inarguable that
breast milk provides the best nutrition for infants in
INFANT MORTALITY
the 6.rst year oflife, to say nothing ofits immunologic The infant mortality rate is defined as the number
advantages, the adequacy of vitamin D in breast of deaths prior to age 1 year per 1,000 live births.
milk is not sufficient to prevent some infants from The infant mortality rate in the United States in
developing vitamin D deficiency and even rickets. 2014 was 5.82, slightly decreased but statistically
The risk is highest in patients with dark skin who, unchanged from 2013.
KEY POINTS
• Ophthalmic antibiotics are administered to • When the urethral opening is located along
newborns shortly after birth to prevent con- the ventral penile shaft rather than at the tip,
junctivitis with N. gonorrhea and particularly it Is tanned hypospadias. Chordae Is fixed
C. trachomatis, which Is a leading cause of fibrotic ventral bowing of the penis; It Is often
blindness in the developing world. associated with hypospadias. Hypospadias
• Parenteral vitamin K prevents the development may be associated with other, lees obvious
of hemorrhagic disease of the newborn. genltoutlary anomalies.
• IUGR is divided irto two categories based on • Relractile tBstis wl avtmualy ralocaiB permanently
gestational age at onset. In earty-onset (sym- to the scrotum; no intervention Is necessary.
metric) IUGR, growth is restricted prior to 28 • Abnormal head shape in the newborn may
weeks' gestation, and birth length and head be due to molding, caput succedaneum, or
circumference are proportional to weight. Infants cephalchematoma.
with late-onset (asymmetric) IUGR have sparing • Infanta with choana! atresia develop respiratory
of the (relatively nonnaQ head circumference, distress with cyanosis and/or apnea when the
but length and especially weight are reduced mouth Is occluded (during feeding or pacifier
below what is expected for gestational age. use) or closed (while 1he ilfant iscam or restilg).
• Common benign rashes in newborns and young • Blateral renal ageuesis results in oligohydr.nnios,
infants include sUnon patChes, Mongolian spots, which causes Pottar syndrome, characterized
milia, erythema toxicum, infantile seborrhea, by compression defonnities of the face and
and neonatal acne. limbs and severe pulmonary hypoplasia.
• The ductus arteriosus is often associated with • The vast ma;ority of infants with ADS are bom
a continuous munnur over the second left in- prior to 34 to 35 weeks' gestation. The patho-
tercostal space, especially as It closes in the genesis Is lack of surfactant. The diagnosis is
days after birth. confirmed by a chest radiograph that reveals a
• Persistence of the umbilical stump beyond 8 uniform retlculonodular or "ground-glaae pattern•
weeks of age is abnormal and may signify a and air bronchograms that are consistent with
neutrophil disorder. difluse atelectasis.
• Pnelmonia is a common neotaatallnfection, tv~d • Kernicterus results when high levels of uncon-
group B Streptococcus is the most common jugated bllrubin cross the blood-brain bamer,
pathogen. Initial signs are generally those of resulting In widespread cerebral dysfunction.
respiratory distress; however, both the clinical Infants who survive the immediate effects develop
and radiographic presentations of pneumonia cerebral palsy and movement disorders and
may not differ significantly from neonatal sepsis, may also suffer from vlslonlheartng problems
MAS, ADS, and TTN. and mental retardation.
• Universal antenatal screening at 35 to 37 • VACTERL syndrome describes the association
weeks' gestation for group B Streptococcus of vertebral, anal, cardiac, tracheal, esophageal,
and Intrapartum prophylactic administration to renal, and limb anomalies.
colonized women have deaeased the incidence • Infants with TEF In the absence of esophageal
of early-onset neonatal sepsis substantially. atresia may have nonspecifiC symptoms for
1\vo doses of an appropriate antibiotic must several mon1hs, including chronic cough with
be administered at least 4 hours apart prior feeding and recurrent pneumonia.
to delivery for prophylaxis to be considered
adequate. • Duodenal atresia is associated with a charac-
teristic radiographic finding, the •double bub-
• Neonates with suspected bacterial Infection, ble" sign, consisting of gastric and duodenal
Including neonatal sepsis and/or pneumonia, gaseous distention proximal to the atretic site.
require emergent evaluation and coverage with
ampicillin and gentamicin llltil cultt.n results • Conjugated hyperbilirubinemia is the eeriest
are known. sign of bliary atresia. This is followed by the
development of clay-colored (lght) stools, dark
• Neonatal hyperbilirubinemia Is classified as
urine, and hepatosplenomegaly. Uver enzymes
unconjugated flldirect), which can be physi-
become significantly elevated earty In life.
ologic or pathologic in origin, and conjugated
(direct), which is always pathologic. • Neonates may lose up to 10% of their birth weight
within the first few days of life. Babies should
• Physiologic jaundice describes Indirect hy-
gain back 1helr birth weight by 14 days of age.
perbilirubinemia that occurs In the absence of
any undertying abnonnalltles In bilirubin me- • The AAP recommends that breastfed Infants be
tabolism. Physiologic jaundice and breast milk started on vitamin D drape (400 IU/d) beginning
jaundice are by far the most common causes in the first few days of life.
of hyperblirubinemia in the neonate. The most • Hematocrit levels in the term neonate decrease
common cause of nonphysiologic unconiugated sbwly to a "physiologic nadr' someti118 between
hyperbilirubinemia is /tBO incompatibility. 8 and 12 weeks of life, when hemoglobin values
• Conjugated hyperbilirubinemia Ia often the result as low as 9 mg/dl are considered normal. Iron
of diseases involving liver pathology, such as supplementation before and/or during this nadir
biliary atresia and neonatal hepatitis. is neither Indicated nor beneficial.
CLINICAL VIGNETTES
VIGNmE1 c. Low Dubowitz/Ballard scores

d. Hypoglycemia
1. You are called to the nursery to evaluate a pre- e. Head circumference at the 50th percentile
sumably tenn infant whose weight Is at the 3rd f. Syndromic features
percentile for gestational age. Which of the fol- g. Chronic preeclampsia
lowing hiatory and/or physical findings ia unlikely h. a and d
to suggest prematurity or a pathologic condition I. bandd
as the etiology of this child's •SGA" weight? J, bandc
a. Prenatal care throughout pregnancy
b. Fine, fuzzy scalp hair and visible veins in the ski1
2. The infant is calm when you arrive; so, following VIGNETTE2

a general assessment and review of the vital You are examining a 5-day-old AGA term newbom
signs, you conduct a cardiac examination. You male in your office for his second health maintenance
note a normal cardiac rate. S1 and S2 are normal visit (the first being the initial hospital foUow-up visit
in placement, and the St is appropriately split. shortly after discharge). The mother had prenatal care
Femoral pulses are equal but not bounding. The throughout her pregnancy, the birth was via cesarean
palms and soles have a bluish tint to them, but section {because of a previous cesarean delivery), and
the lips and tongue ara pink. You appreciate a there were no significant pre- or perinatal complications.
medium-pitched systolic ejection murmur, best Weight, length, and head circumference progression are
heard at the left upper stemal border, with radia- as expected. The baby is afebrile and acting normally.
t ion to the back. The liver edge falls 1 em below The infant is exclusively braastfad. There is a healthy
the costal margin. Given this clinical picture. the older biologic sister In the family.
infant's murmur most likely results from which of Although they are not new to parenting, the parents
the following? have some questions about things they did not notice
L Peripheral pulmonic stenosis (PPS) were present when their daughter was an Infant.
b. Critical pulmonary stenosis The Infant has flve evanescent pustules, each on
c. Tricuspid atresia an erythematous base, scaHered over the lower legs.
d. Closure of the ductus arteriosus A similar lesion Ia present on the left wrist and another
e. Tetralogy of Fallot on the right forearm. The parents note that the infant
a The infant has a sacral dimple within the anal had similar "bumps" on his chest, abdomen, and back
verge. You are able to visualize the bottom of the before leaving the hospital. Although he has fewer now,
the parents are concerned that they are not gone yet,
dimple by abducting the gluteal folds. The More
especially because the mother has a history of genital
reflex is symmetric. Two to three beats of clonus
herpes. She did not have visible herpes lesions at the
are present in each ankle. Which of the following
Is the most approprtate next step In the evaluation time of birth. This moming, the infant had the same
bumps on the legs but in slightly different places.
of this Infant's anomaly?
L Sonography of the spine, which should demon- 1. This infant's rash Is most consistent with which
strate any associated vertebral lesion given of the following?
that the infant is <6 weeks of age L Transient neonatal pustular melanosis
b. Referral to a pediatric neurologist as an outpa- b. Erythema toxlcum
tient for a mora thorough examination c. Infantile seborrhea
c. Refemtl to a pediatric neurosurgeon as an d. Milia
outpatient for a more thorough evaluation e. Superficial epidermal herpes
d. Magnetic resonance imaging of the lower
2. The infant's umbilical stump is dry. The mother
spine to evaluate for spina bifida occults prior
states that, although she tries to be very gentle,
to discharge
she has bumped or pulled the cord accidently
e. This finding Is not associated with under1ying while dressing him a few times. She sees dried
neurologic or bony abnormalities
blood around the base. The bleeding was minor
4. The parents are concerned that their baby has oozing only and stopped within minutes without
an irregular head shape. The head is elongated, pressure. She Is afraid she Is going to hurt the
with a boggy area extending over the posterior Infant by traumatically dislodging the stump, and
parietal sutures. The protrusion Is slightly mora she wants to know when It will fall off on Its own.
prominent on the lett. Bruising Is evident In All of the following represent approprtate advice
the enlarged area. Gentle pressure to the area except which of the following?
results in "pitting." Your parental counseling a. Because the practice of saturating the cord stump
would include all but which of the following with alcohol is no longer recommended, the
statements? cord is mora susceptible to traumatic bleeding.
a. The appearance of the head Is due to pres- b. Because the practice of saturating the cord
sura from the pelvic bones and the narrow stump with alcohol is no longer recommended,
vaginal canal on t he head during the birth t he skin at the base of the cord is more sus-
process. ceptible to bacterial infection.
b. The infant has bleeding in the subperiosteal c. The cord should fall off within 3 to 4 waeks.
space. d. If the cord persists beyond 6 to 8 weeks, the
c. The infant is at no increased risk for hydrocephalus. parents should bring nto the physician's attention.
d. The elongation will resolve without intervention. 1. If an umbilical hernia becomes visible following
•· Bruising Is not an uncommon ftndlng In caput separation of the cord, the hemla Is likely to
succedaneum. resolve within a few years without intervention.
3. The father rather sheepishly mentions that he has present to administer oxygen via nasal cannula to keep
noticed that his son has firm "bumps• under both saturations above 90% and order a STAT portable
his nipples. Moreover, the examining physician chest radiograph and arterial blood gas, complete
In the hospital told him that only one testis was blood count, differential, and cultures.
placed within the scrotum. During physical ex-
1. Which of the following conditions is least likely to
amination of the child, you note breast budding.
be the source of this infant's respiratory distress?
Palpation of the scrotum reveals only the right
L Neonatal pneumonia
testis. The left is located distal to the inguinal
II. Choana! atresia
ligament, is equal in size to the right testis, and
is easily manipulated into the left scrotum. Which
c. TIN
d. ADS
of the following statements regarding this father's
concerns is true?
e. MAS
a. The breast budding, or gynecomastia, will 2. Which of the following chest radiograph findings
resolve within 6 months but will reappear would be most consistent with a diagnosis of MAS?
during puberty. L Prominent perihllarstreaklng, lncraasad Interstitial
b. There Is a 50% chance that the retractile testis markings, and fluid In the lntertobar fissures
will need to be repositioned within the Ipsilateral II. Air bronchogram& superimposed on wide-
scrotum surgically. spread atelectasis, creating a •ground-glass"
c. The child should not be circumcised until the appearance
retracted testis is permitted to •drop• in case c. Areas of atelectasis, areas of coa111e irregular
the tissue of the prepuce is needed for repair. densities, dislinct areas of overinflation
d. The breast budding results from the same d. Symmetric, patchy consolidations with uni- or
underlying process as neonatal acne. bilateral effusions
e. Cryptorchidism carries an increased risk for e. Consolidation of one lobe or two contiguous
breast budding and metastatic changes in the lobes only
breast and testicular tissue later in life.
3. The infant is able to maintain oxygen saturation
._ Which of the following is the moat important within the normal range on supplemental oxygen
supplement to provide for this infant at prvsent? and the respiratory rate begina to decline. The ratio
a. Prenatal vitamins through the mother of im~to-mature forms of WBCs is low, and
b. VItamin D the total WBC count is normal forage. Ampicillin and
c. Calcium gentamicin are administered while awaiting results
d. VItamin K of the blood culture. By 48 hours of age, the infant
e. Iron has been weaned to room air and is breastfeeding.
Blood cultures are negative. This clinical picture is
VIGNETTE3 most consistent with which of the following?
You are called to see a neonate In the newborn nursery a. Nosocomial respiratory syncytial virus Infection
who Is about an hour old. The pregnancy was compli- II. TIN
cated by maternal gestational diabetes. Delivery was c. HMO
Induced at 36 weeks' gestation because of dlfflculty d. Apnea of prematurity
managing the gestational diabetes. The infant was e. MAS
delivered by cesarean section for failure to descend,
4. The baby Is discharged from the hospital and
although the obstetrician had to enlarge the initial inci-
follows up at your clinic for regular health main-
sion to remove the infant because of size. Reassuring
tenance visits. Just before the 2-month visit, the
fetal heart tracings were documented throughout the
mother calls about a large, hard bump she has
labor and delivery. "Light meconium• was noted in the
noticed along the middle of the bone at the top
amniotic fluid. Apgar scores were 8 {- 1 for color, -1
of the chest on the rtght side. According to her,
for respiratory effo~ and 9 (- 1 for color). He began
the child is moving both arms the same amount
to cry vigorously as he was dried, but calmed down
and with the same range of motion. Which of the
In his mother's arms and was permitted to stay there
following is the most likely cause of the abnormality
and brwastfeed as vital signs remained stable. Initial
prompting the mother's concern?
measurements placed the growth at "LGA.• Since
admission to the nursery, the Infant's respiratory rate
a. Clavicular fracture at birth
b. Erb palsy
has climbed steadily and Is now at 70 breaths per min-
c. Developmental sho ulder dysplasia
ute. When you arr'ive, you note nasal flaring, grunting
d. Metatarsus adductus
with each breath, and chest wall retractions. There is
e. Potter syndrome
no cyanosis at present. You ask medical peraonnel
VIGNETIE4
vital signs. Social work is consulted for support,

-
A caucasian woman presents to the emergency depart- discharge planning, follow-up, and appropt1ate
ment in labor. She is transferred to the delivery ward. referrals and notifications. At 30 hours of age,
There is no history of prenatal care other than a visit the infant is noted t o be jaundiced. Which of the
at an estimated 16 weeks' of pregnancy. The mother following represents the most appropriate initial
denies use of llllctt drugs, prescr1ptlon medications, screening laboratory workup of this infant?
and alcohol during the pregnancy. However, she is L Transcutaneous bilirubin measurement
combative upon arrival to the delivery ward, and her b. Serum total and indirect bilirubin levels
breath smalls of alcohol. Prenatal testing obtained at c. Blood typing of the infant and direct Coombs
the obstatr1cs clinic Is significant for. (-) HIV, (-) HB- testing
sAg, (- )hepatitis C, blood type A+-,(-) rapid plasma d. Complete blood count and blood smear
reagin, rubella immune, (+) cytomegalovirus (CMV), •· Matemal Rh-antigen testing
(-)swabs for C. trachomatis and N. gono!Thoeas. 3. The Infant's direct bilirubin measurement Is < 1.5
Membranes are ruptured at delivery, which is vaginal mg/dl, but the total bilirubin level is plotted on
and uncomplicated. There Is no clinical suspicion tor the AAP graph and revels that the infant is within
chorioamnionitis. a group that has a high incidence of subsequent
1. Which of the following physical anomalies are need for phototherapy. In addition to further workup,
most consistent with a diagnosis of fetal alcohol you counsel the mother regarding the possibility
syndrome? of phototherapy for the infant. Based on social
L Spina bifida, facial anomalies concerns, the phototherapy, if indicated, will have to
b. Broad nasal bridge, cleft palate, microcephaly take place in the hospital prior to discharge rather
c. Hepatosplenomegaly, lymphadenopathy, than at home. She Is baing discharged tomorrow,
chorioretinitis atthough the infant will remain hospitalized. There
d. Short palpebral fissures, midface hypoplasia, is some concern that she may attempt to remove
smooth philtrum, thin superior vermillion border the baby from the hospital without authorization or
e. cataracts, hearing loss, thrombocytopenic sign the baby out of the hospital•against medical
purpura advice." In counseling her regarding the risks of
untreated hyperbilirubinemia, you are most likely
2. Judging by the sonogram and 1'98ufts of the ma- to discuss which of the following conditions?
turity and neuromuscular rating scales, the infant L Bronzing of the skin
is full term and AGA. The infant's urine is positive b. Polycythemia
for marijuana but no other drugs of abuse. The c. Slow growth
physical examination is entirely normal, and the d. Death
infant formula-feeds well and maintains stable e. Kernicterus
ANSWERS
VIGNETIE 1 Queltlon 1 The physical findings listed in B are consistent with

1.Answer H: prematurity, as are low scores on the neuromuscular
Newboms with weights less than the 1oth percentile and physical maturity rating scales. A head circumfer-
for length of gestation ara termed SGA. Infants can be ence at the 5oth percentile suggests late-onset IUGR,
SGA because of Incorrect dating of the pregnancy; that which may be seen with preeclampsia. Specific chro-
is, the actual gestational age is lower than the recorded mosomal anomalies, congenital malformations, and
gestational age. This is true of infants who are premature inborn errors of metabolism can result in ear1y-onset,
or preterm; their weights may be appropriate for actual symmetric IUGR.
gestational age. Given that this mother had prenatal
care starting early in her pregnancy, it is unlikely that VIGNETIE 1 Queltlon 2
the conception date is off by any significant degree. 2. AnswerA:
If other history, physical examination findings, and As a functional heart munnur, PPS may present in the
laboratory results are normal, the Infant Is (probably) newborn and persist untll2 months of age. The source
just appropriately small, especially if' the mother and is turbulent blood flow where the main pulmonary artery
father are both petite. Hypoglycemia is common in branches into left and right. The turbulence produces
SGA infants, even those without pathology, because a medium-pitched systolic ejection murmur at the
of finite glycogen stores. left upper sternal border, radiating to the back. PPS
Is a benign murmur that does not signify undertytng VIGNETlE 2 Quesllan 1

anatomic disease. lhe liver edge In a term healthy 1.Answer 8:
infant may extend 1 to 2 em below the anterior cos- Erythema toxlcum is an extremely common rash that
tal margin; as long as it is not firmer than expected, is most visible and prominent in Caucasian newborns.
and there is no palpable spleen tip, this is a normal It appears as described earlier, and the lesions dis-
finding. In contrast, critical pulmonary stenosis is a appear and reappear in different places on the skin.
life-threatening cardiac anomaly associated with central Overall, the rash begins centrally and spreads to the
cyanosis In 1tie newborn (evidenced by generalized extremities before resolving. lhe cause has not been
cyanosis, Including blueness of the lips and the tongue). elucidated, and the condition has no known clinical
This newborn has constriction of the distal peripheral significance and resolves without therapy.
vascular system, 1tie end capmaries, which imparts a Transient neonatal pustular melanosis, another
bluish tinge to the hands and feet. This is a normal benign neonatal dermatologic condition, is more
finding in neonates. Tricuspid atresia and tetralogy of common In children with generously pigment ed skin.
Fallot result in central cyanosis in 1tie newborn. Vesicles and pustules are similarly evident, but are
The most commonly encountenKI munnur over the more likely to present on the face as well as the rest
first 3 days in 1tie life of 1tie newborn is the continuous of the body. Unlike those in ery1tiema toxicum, the
murmur associated with closure of the ductus arterio- lesions rupture and then resolve over 48 to 72 hours.
sus. It Is best appreciated in the second left intercostal However, the condition is accompanied by small
space, similar to PPS, but is continuous rather than hyperpigmented maculas that persist for the first
limited to the systolic phase. several months of life.
Infantile seborrhea, also known as cradle cap when
VIGNmE 1 Question 3 it is found on the scalp, is quite bothersome to many
3.Answer E: parents, wno consider it cosmetically undesirable.
Sacral dimples are not present in the majority of newborna; However, it is harmless, generally easy to manage,
however, neither are they uncommon. Sacral dimples and finite (lasting for at most several months). Milia are
which are within 2.5 em of the anal verge, which are tiny waxy epidermal cysts located most often on the
shallow enough to see complete skin closure, which are nose, but are found on the chin and forehead as well.
not covered by hemangiomas or hair tufts, and which They resolve as the skin naturally exfoliates.
are not associated with abnormal neurologic function Herpes Is a life-threatening Infection In neonates.
do not need to be evaluated further. A symmetric Moro However, symptoms of toxicity generally precede
reflex would not be considered particularly helpful, as the rash, and the lesions themselves do not dis-
the lesion associated with pathologic sacral dimples appear and reappear, but remain fixed and scab
is usually limited to the pelvis and lower extremities over as they rupture. Moreover, this mother had no
early in life, and the Moro reflex examines primarily visible herpes lesions at the time of birth and had a
symmetry of the face and upper extremities. A few cesarean section.
beats of ankle clonus is not uncommon in neonates
and is without significance. Asymmetric tone in the VIGNETTE 2 Questian 2
lower extremities is a concerning finding that warrants 2.AnswerB:
further evaluation, regardless of the presence or ab- The recommended •posthospital" care of the umbili-
sence of a sacral dimple. Similarly, a spine that does cal stump has changed in the past decade. Mothers
not extend caudally to a normally positioned coccyx are no longer encouraged to saturate the base of the
bone must be studied further, praterably by magnetic stump several times a day to encourage detachment.
resonance Imaging. No Increase In bactertallntectlons has been reported,
but there Is some anecdotal evidence that 1tie base of
VIGNmE 1 QWIIIan • the cord is more susceptible to bleeding associated
4.AnswerB: with the mild •trauma~ of routine care (dreesing, etc.}.
This infant has caput succedaneum, characterized by Continued oozing without resolution should prompt
marked edema of the scalp tissues. lhe fact that it a visit for medical attention and possible evaluation.
extends over suture lines rules out a cephalohematoma, Most often, the stump detaches within 4 weeks, usu-
or bleeding into the subperiosteal space, in which ally significantly earlier. Persistence beyond 8 weeks
the swelling does not cross suture lines. Bruising is warrants evaluation of neutrophil activity.
not uncommon in cases of caput succedaneum, es- Umbilical hernias may not become evident until
pecially when vacuum extraction is used or the birth separation of the cord, or even later (but usually within
process is prolonged. lhe elongation will resolve over the first 2 to 3 months). The great majority resolve
time without Intervention, and there Ia no associated without Intervention; those that persist beyond 5 years
Increased risk of hydrocephalus. of age may be repaired surgically.
VIGNETTE 2 Quesllan 3 advanced pregnancies. However, this child is LGA,

3.AnswerD: which Is likely due to maternal diabetes but would
Neonatal breast budding, acne, and (in females) also rule out incorrectly advanced dating of the
vaginal bleeding are all related to the presence of pregnancy. MAS is also possible, although unlikely
maternal estrogen. As the •exogenous~ estrogen in in this case given that only •light" meconium was
the baby's system is broken down over the first few present and the fetal heart tracings were reassur-
months, these findings resolve in both male and female ing. Neonatal pneumonia does not typically present
infants. Gynecomastia is 1he presence of excessive this early, but If prolonged rupture of membranes
breast tissue in the adolescent male and may be or chorloamnlonltls has gone unrecognized, early
uni- or bilatet'1ll. As virtually all newborn males have infection is plausible.
breast budding, there is no association with breast
enlargement during puberty. Retractile testes are a VIGNEl'lE 3 QuMion 2
different maHer than cryptorchidism. Retractile testes 2.AnewerC:
will locale themselves within the scrotum without In- Because meconium in the lungs causes airway plugging,
tervention. Cryptorchidism signifies that 1he testicle usually a combination of distinct areas of atelectasis
is ''fixed" outside the scrotum, whether palpable or and over1nflation is appreciated. The findings listed in
not. These testicles are more likely to require surgical answer B create the uground-glass" appearance 1hat
intervention, but even then the rate is much less than is characteristic of RDS. Perihilar streaking with fluid in
50%. Preputial tissue may be needed for repair in a the interlobar fissures suggests that retained fetal lung
male infant with significant hypospadias, but neither a fluid that is interfering with oxygenation. The findings in
fixed testicle nor a retractile one is a contraindication answer D a.. often associated with bacter1al pneumonia;
to circumcision. Cryptorchidism increases the risk It Is uncommon tor neonates to have the appearance
of testicular cancer later in life, even tf the testis is of true, Isolated lobar consolidation unless there Is an
anatomically placed via surgery; however, there is no anatomic irregularity. It is important to note, however,
association with breast budding or the subsequent that results of the radiograph should be interpreted
development of breast cancer. with caution, as any of the first four answers may be
present with more than one condition and the quality
VIGNETTE 2 Question 4 of portable films Is variable.
4.Answer B:
The MP recommends universal administration of vitamin VIGNETTE 3 Question 3
D to infanta who are breastfed in order to prevent the 3.Answer B:
development of rickets. Many breutfeeding mothers TIN, also termed retained fetal lung liquid syndrome,
are encouraged to continue taking prenatal vitamins is a relatively common condition in the tenm newbom.
while breastfeeding in order to ensure sufficient sup- Most infants need only minimal support, such as
plements for themselves and their children; however, supplemental oxygen to maintain saturations. Oth-
these mothers should still provide vitamin D drops to ers may require nasal CPAP. In the rare case, further
their infants. Parenteral vitamin K Is administered in intervention is necessary, but the condition virtually
the hospital to prevent hemorrhagic disease of the always reeolves within the first 48 to 72 hours of life,
newborn. Breast milk provides the recommended levels as 1he retained fluid is resorbed. This infant is at in-
of calcium and iron through at least 6 months of age. creased risk for TIN because of the matemal history
of gestational diabetes. Elective cesarean section,
VIGNETTE 3 Quesllan 1 without a trtal at labor, and LGA weight bottllncrease
1.Answer B: the risk of TIN as well.
Factors In this Infant's history that argue against a Nosocomial respiratory syncytial virus infection
diagnosis include the ability to successfully breastfeed can be problematic in an infant ward but is unlikely in
and stable vital signa noted when he was calm in his this newborn, which stHI has high maternal antibody
mother's arms. Infants with choanal atresia become load based on his age in days. HMO is another, older
apneic or drop their oxygen saturation levels when they name for RDS. RDS takes longer to resolve without
attempt to feed, depending on whether the obstruction Intervention and usually requires more aggressive
is total or partial. Moreover, because newborns are support measures, such as mechanical ventilation,
obligate nose breathers, signs of distress improve unless treated with surfactant. Apnea implies peri-
when they are crying, which forces them to breathe odic cessation of breathing; moreover, this child is
through their mouths. not premature. Although mild MAS could present
Any of the remaining conditions could cause this and resolve in this manner, the preterm and perinatal
Infant's distress. RDS Is most common In Infants who history, along with the mildness at the Wness and 1he
are < 34 weeks' gestation, but can occur In more rapid resolution, makes TTN more likely.
VIGNB'TE 3 Question 4 VIGNETTE 4 Quesllan 2

4. Answer A: 2.AnswarA:
Palpation of the clavicles In a nG~Nborn may produce When an infant of Caucasian ancestry is noted to
crepitus, a creaking sensation under the fingertips be jaundiced at > 24 hours of age, is weDappearing,
consistent with a clavicular fracture. Clavicular fractures is AGA. and has no history of a traumatic delivery,
are more common in large infants born vaginally with then the likelihood of pathologic jaundice, be it direct
associated trauma such as shoulder dystocia This or indirect, is low. Initial screening measurement of
baby was not born vaginally, but the incision had to be total bilirubin with a transcutaneous instrument is
widened to allow removal of the child, suggesting that appropriate and performed routinely on all infan1s
the obstetrician was unable to maneuver the child out prior to discharge in many institutions. However,
initially because of size. lhe "bump"1he moltler is de- if the level is borderline or high or there are other
scribing is most likely a callus formed from healing bone. concerns, a serum level should be drawn because
Erb palsy Is a neurologic deflclency of the upper (a) a serum measurement Is more accurate and (b)
extremity resulting from trauma to the nerve roots of the direct fraction must be calculated from the total
C5-C6 during delivery. lhe affected patient holds the and Indirect measurements to ensure that the patient
arm in an abnormal position, with extension at the elbow, does not have conjugated hyperbilirubinemia, which
internal rotation, and fixed pronation of the forearm. is always pathologic. This mothe~s blood type is A,
lhe arm is held cloae to the body on the involved side. so ABO incompatibility Is not a concern (although
Of note, the grasp reflex is preserved in these infants. there are other antigens on blood cells that can
Developmental shoulder dysplasia is not a described cause incompatibility and hemolytic jaundice, this is
condition in newborns; developmental hip dysplasia uncommon). Infants of mothers with blood type 0 who
is, but this child's abnormality does not involve the are jaundiced should have a blood type and Coombs
hip. Metatarsus is medial curving isolated to the checked. Many hospitals routinely draw this from cord
forefoot. Potter syndrome is a constellation of findings blood with all maternal type 0 blood, or a physician
(compression deformities of the face and limbs, and should order the tests at the same time the serum
pulmonary hypoplasia) resulting from oligohydramnios bilirubin is drawn. Complete blood count and blood
that may occur in the setting of conditions such as smear may be warranted if hemolysis is suspected
lntrautar1ne bilateral renal agenesis. because1he bilirubin Is much higher t han expected,
but this can be drawn later. Maternal Rh-antlgen testing
VIGNB'TE 4 Q...Uan1 takes place at the nrst prenatal vlsh and the status
1.Answer D: would not affect t his pregnancy regardless because
Fetal alcohol syndrome ia the most common pre- the parent is A.. blood type.
ventable congenital syndrome in the United States.
Findings include those noted in answer D as well as VIGNETTE 4 Question 3
growth retardation, microcephaly, and an increased 3.AnswerE:
incidence of joint and digit anomalies, hirsutism, and Although high levels of bilirubin can result in recalcitrant
congenital heart defects. If the mother is intoxicated seizures and death, this is very rare and usually occurs
at delivery, the infant may be lethargic and hypoglyce- late in the process, when it is obvious that there is
mic. Children with fetal alcohol syndrome may suffer something very wrong with the infant. Kernicterus is less
a range of developmental problems as they age, from common now than before the AAP recommendations
mental retardation to developmental delay, learning were universally adopted In 2004, but the r1sk In this
disabilities, and behavior disorders. Infant Is higher given multiple less-than-Ideal social
Spina blflda and facial anomalies can occur with factors. Kernicterus Is sublethal bilirubin encephalopa-
maternal valprolc acid use during pregnancy. Fetal thy, which occurs when serum levels of unconjugated
hydantoin syndrome consists of broad nasal bridge, bilirubin cross the blood-brain barrier, affecting the
cleft lip/palate, microcephaly, and mental retardation. basal ganglia, cerebellum, and hippocampus, among
Hepatosplenomegaly, lymphadenopathy, and cho- other cerebral area. Infants who survive the resulting
rioretinitis can result from maternal toxoplasmosis or lethargy, hypotonia, posturing, and possible seizures
primary CMV infection during pregnancy. Cataracts, virtually always suffer from cerebral palsy and move-
sensorineural hearing loss, IUGR, hepatosplenomegaly, ment disorders and are at increased risk for mental
and thrombocytopenic purpura are associated with retardation and vision/hearing deficiencies.
maternal rubella infection.
Adolescent Medicine
Pr8etl Patel Matkins and Katie S. Fine
•puberty" is defined as the process of hormonal

THE ADOLESCENT OFFICE VISIT
and physical changes whereby the body of a child
matures into that ofan adult, physiologically capable Observing the parent-child interaction is informative,
ofsexual reproduction. "Adolescence;" on the other and the parent should be encouraged to raise any
hand, encompasses the physical changes of puberty concerns with the clinician. However, it is imperative
as well as the cognitive, social, and psychological that the majority ofthe interview and eMminatlon
advances that mark the transition from youth to takes plau without the parent present. Teenagers
adulthood. Some references further subdivide may not be forthright or comfortable discussing
adolescence into an early period (middle school, certain health-related issues when they believe
age 10 to 13 years), a mitldk period (high school, their parents may find out about their responses.
age 14 to 17 years), and a late period (age 18 to 21 Although virtually all states mandate the reporting
years). The developmental tasks of adolescence of suspected abuse, potential harm to self or others,
include the following: and certain infectious diseases (including some
sexually transmitted diseases [STDs]), most also
• The development ofa strong self-identity (defining
provide for confidentiality of information related
the self, maintaining healthy self-esteem}
to sexual activity and substance use/abuse. Some
• Autonomy (self-governance, establishing autonomy}
states allow all adolescents access to medical care
• .Achl.evement (recognizing talents, gifts, contributioos)
without their parents' knowledge; in other states,
• Establishing appropriate peer and sexual rela-
only emancipated minors are permitted this right.
tionships (expression of relationships, lntlmacy.
Emergency treatment should never be withheld
and expectations)
pending parental not:iftcation or approvaL Also, teens
• Transition from relatively concrete th1nldng to
should be counseled about situations in which the
more abstract concepts, such as cause/effect,
clinician may break confidentiality. Some examples
long-term consequences, and complicated moral
include teens disclosing plans tD harm themselves or
dilemmas
others or information related to mandated reporting
Although adolescents are less likely than younger of abuse.
children tD have regular health maintenance visits, Although studies show that adolescents are willing
regular contact with a primary care physician is to discuss high-risk behaviors and preventative care
particularly important in this age group. Many of the issues with their physicians, most teens are uncom-
diseases and injuries that occur in adolescence result fortable initiating these conversations themselves. The
from lifestyle choices and risk-taking that increase acronym HEADSS (Table 3-1) ls helpful in identifying
the risk of morbidity and mortality. Such behaviors pertinent areas in the adolescent soclal history. An
include high-risk sexual activity, eating disorders, indirect, nonjudgmental method of questioning may
substance use and abuse, and actions resulting in be more effective in eliciting an accurate history.
accidental or intentional injury. Some intentional Height, weight, blood pressure, and body mass
injury may be the result ofdepression, such as suicide. index (BMI) percentile should be recorded at every
The leading causes ofdeath in adolescents are motDr adolescent health maintenance visit. Other rec-
vehicle crashes, suicide, and homicide. ommended procedures include yearly depression
51
TABLE 3-1. The Adolescent Psychosocial Histcry: HEADSS

IHome (&m.lly members, relationships, living arrangements)
IEducation (academic performance/educational p.ls)
j Activities (peer relationships, work. and recreational a.ctivitiea)
i Drup (subltaooe UJe/aba~e.lndacling tobacco, alcohoL marijuana, inhalants, Wldt substances, and over-the-
!counter and prescr1ption drugs)
j Sexuality (dating, sexual activity, contraception, sexual orientation)
j Suicide (depreuion. anxiety, other mental health concerns)
i Some experts suggest that a second E should be added to remind physicians to screen for behaviol'8 associated with Eatng
~ disorders and/or Exercise and that a tt;rd S should be included 1o prompt questions concerning Safety ~he po!Bnlial for abuse or
! violent behavior [e.g., gang membership, owning a firaarm]).
:••••••••••••••••••••••••••••••••••••••••••••••••••OOoo•oooooooooooooOoooooo ooooooo Ooooooooooooooooooooo••••••••<oooooooooooooooooooo•o•••••••••••••u••••••••••• •••••••••••••••••••••••••••••••••••••••••••••••••••••••••• •••••"''''''' '''''''''''''"""'''''''""rooooooo<oooooooOoooOoOoOoooo_o:
screening, vision and hearing screening in each In females, the order of pubertal events in sexual
of three stages (early, middle, late) of adolescence, development is thelarche (breast budding), followed
hemoglobin/hematocrit (once in menstruating by development of pubic hair, maximal height veloc-
females), and Upid panel (once between ages 9 and ity, and menarche. Figure 3-2 shows these changes.
11 years, and once between ages 17 and 21 years). The Sexual Maturity Rating (SMR) scale (also
Thberculosis testins is appropriate in individuals called Tanner Staging) is used to determine where an
at high risk (see Chapter 1). The recommended individual is in the pubertal process. SMR stages for
examination and laboratory screening for sexually the male genitalia, female breasts, and male and female
active patients is discussed in the following section. pubic hair are descnoed in Table 3-2 and illustrated
Immunization guidelines are reviewed and up- in Figures 3-3 through 3-5. Pubertal abnormalities
dated frequently by the Centers for Disease Control are addressed in Chapter 15. All teens should have
and Prevention (CDC) Advisory Committee on Im- external genital examination yearly.
munization Practices. Of note, these groups advise About 41" of all high school students and 584Jii of
that adolescents receive the tetanus and diphtheria 12th graders in the latest CDC Youth Risk Behavior
toxoids and acellular pertussis (Tdap) vaccine and Survey (2015) reported that they had engaged in
meningococcal conjugate vaccine (MCV) at the sexual intercourse. Almost 7% of teens reported
11- to 12-year health maintenance visit. Human forced sexual intercourse. All teens should be asked
papillomavirus (HPV) vaccine can be given as early ifthey are attracted to the same gender, the opposite
as age 9 years and is either a two· or three-dose
series based on the age of completion (two doses if Age (years)
completed by age 14 years). 8 9 10 11 12 13 14 15 16 17
spurt~
SEXUAL DEVELOPMENT/
REPRODUCTIVE HEALTH Height
As mentioned, puberty refers to those biologic Testicular volume (mL)
changes that lead to reproductive capability. The 4-6 &-10 10-16 16-215
events of puberty occur in a predictable sequence,
but the timing of the initiation and the velocity of
Genitalia size 2 s 4 s
the changes are highly variable among individuals. (Tanner s1age)
The integration of the pubertal changes into the
individual's self-identity is important to successful Pubic hair 2 s 4 5
(lanner stage)
progression tluough adolescence.
In males, the initiation sequence of sexual de-
8 9 10 11 12 13 14 15 16 17
velopment is testicular enlargement, followed by
Age (years)
lengthening of the penis, pubic hair growth. and
achievement of maximal height velocity. This pro- FIGURE 3-1. Sequence of pubertal events in the average
gression is depicted in Figure 3-1. ~~~~.~.~)..!!].~!.~.:...................................................................................................
Chapter 3 I Adolescent Medicine • 53
Age (years) health care for se:xually active adolescents includes

8 9 10 11 12 13 14 15 16 17 additional examination procedures and laboratory
screening. Annual screening tests recommended for
sexually active female adolescents include gonorrhea
and chlamydia studies, serum testing for mv and
Height spurt syphilis (rapid plasma re.agin [RPR]), careful visual
examination of the external genitalia., and a wet mount
Menarche ofvaginal fluids for yeast, bacterial vaginom (BV), and
Trichomonas vagint~lia. Rapid 7nchomonas testing
should also be considered. Testing for chlamydia and
Breast 2 s .. s gonorrhea may be vaginal or cervical nucleic add
(Tanner stage)
amplification test (NAAT) or urine NAAT. Culture
Pubic hair 2 3 .c 5 techniques are available but take longer for results
(Tanner stage) and may not be as accurate. NAAT is not approved
for testing oral or anal sites. HPV is the most common
8 9 10 11 12 13 14 15 16 17 STD in adolescents. About 80% of sexually active
Age (years) persons will be exposed to HPV in their lifetime, and
FIGURE 3-2. Sequence of pubertal events in the average although most cases will resolve without symptoms,
~-~~~~-~)._~-~~:............................................................................................... HPV may manifest as visible genital or oropharyngeal
warts. The virus is responsible for almost all cases
gender, or both genders or unsure when taking a of cervical and anal cancers and is associated with
sexual history. Teens should also be asked if they vulvar, vaginal. penile, and non-tobacco-related oral
are comfortable with their assigned gender. Sexual cancers. Bimanual pelvic examinations are no longer
health questions should be posed in a nonjudg- recommended unless the patient has symptoms of
mental. manner with an open attitude. Preventative pelvic inflammatory disease (PID), an abdominal mass,
TAIL! 3-1. Secondary Sex Characteristics: Tanner Sexual Maturity Rating Scale
i lhlst DfVfltJpment (FetHJt)
IStage I Preadolescent; elevation of papilla only
!Stage II Breut bud beneath the areola; enlargement of areolar diameter
IStage m Further enlargement and elevation of breast and areola
j Stage IV" Projection ofareola to form secondary projection above contour ofbreut
IStage V" Mature atap; amooth breast contour
IGenltBI/Jeve/opmflnt (11a/e)
! Stage I Preadoleacent
IStage II Enlargement of scrotum and testes; skin of scrotum reddens and changes in texture
IStage Dl Enlargement ofpenis, particularly length; further growth ofteates and ac:rotum
!
~ Stage IV Increued alze of penis with growth in thickness and development of gl.ana; further enlargement of
! and acrotum and increaaed darkening of scrotal skin
testes
IStage v Adult genitalia

1Pubic HBit{MI/f lllld ,.,..)
j Stage I Preacloletc:ent (no pubic hair)
l Stage U Sparse growth oflongeJ< slightly pigmented hair, chiefly at hue of penis or along labia
1Stage m Inaeulngly darkeJo ~and more curled hair apreada over Junction of pubis
! Stage IV Adult-type pubic hair with no apread to medial surface of thighs
j Stage V Adult in quantity and type with apread to thighs
i •stages IV and V may not be distinct in some patients. l
:.,.,,• .,.,,uooooooo 0000000 ooooo• o••••••• ••••••• "''"' »oooooooooooo •••••••••••••• •••••••• ••••••••••••••••••••••••••n••••••••••••••••••••-oooooooooooo oooooooO.oooooooooooooo 0000000 oooooooooooooo ooooooo ' '''''''''"' ' ' " "' " ••••••••••••••••••••• •••••••••••••o.•••••••••••n•••••nooooonoi
._ '·
lll
FIGURE 3-3. Pictorial representation of Sexual Maturity Rating (Tanner) stages of male genital and pubic hair
~-~!.~!?.~~~~:...........................................-...................................--·-··-····-··-······-···············-·····..·······...................................._.....................................................
Earty Late
Child Prepubertal pubescent pubeecent Adult
Tanner
stage 1 2 3 4 5
\ I
/
'\--I
T
T
or uncontrolled bleecUns. Papanicolaou smears are and height. Amenorrhea is not a required criterion
recommended starting at age 21 years. Adolescent fOr the diagnosis of anorexia nervosa. It is postulated
males who are sexually active should have yearly thatexternal or internal psychological and/or social
sexually transmitted infection testing, including stressors superimposed on an inherited wlnerabillty
urine-based NAAT for gonorrhea and chlamydia and lead to the development of anorexia, although its
serum HIV and RPR. Rapid Trichomonas testing or etiology is likely multifactorial.
wet prep should be considered if penile discharge Binge eating, followed by some compensatory
is present. Screening for young men who report behavior to rid the body of the ingested calories,
same-gender sexual contact may include anal and is the hallmark of "bulimia nervosa~ To meet the
pharyngeal cultures for STDs, and hepatitis B serology criteria, patients must have at least one episode
should be corWdered in nonimmuni.zed patients. of binge/purge a week for 3 months. Patients may
HIV and syphilis serology should be offered yearly to purge (induce vomiting or take laxatives) or use other
all sexually active adolescents. Per CDC guidelines, methods (fasting, intense exercise).
herpes testing should be limited to symptomatic Many patients with eating disorders do not meet
patients. In addition, all patients who are sexually the DSM-V criteria of anorexia nervosa or bulimia
active should be offered counseling at each health nervosa but have disordered thoughts about food,
maintenance visit regarding contraception and the including dietary restrictions and/or binge/purge
use of condoms. Emergency contraception should behavior. Related conditions include Avoidant/
be discussed with both male and female patients. Restrictive Food Intake Disorder, Binge-Eating
Disorder, Body Dysmorphic Disorder, and other
specific/nonspecific eating disorders.
EATING DISORDERS
PATHOGENESIS EPIDEMIOLOGY
Adolescents may become preoccupied with body image Estimates of the incidence ofanorexia 1n developed
during adolescence. "'Anorexia nervosa• is an eating countries range from 1 in 200 to 1 in 2,000 adoles-
disorder characterized by impaired body image and cent females. Bulimia is more common. affecting
intense fear of weight ga1n (or behavior consistent 1% to 2% of Western young women. Depending on
with avoidance of weight gain), culminating in the diagnostic criteria used. the prevalence of eating
refusal to maintain appropriate body weight for age disorder not otherwise specified is estimated to be
between 0.8% and 14%. Up to 1096 of patients with Patients with bulimia may be of normal weight
eating disorders are male, although the percentage or overweight. Frequent self-induced vomiting (if
may be higher; the data may reflect underrecognition present) may result in calluses on the backs of the
or aversion to seeking care. knuckles, eroded tooth enamel. and parotid gland
enlargement. However. many patients with bulimia
RISK FACTORS can induce emesis without gagging.
Risk factors for eating disorders are multifactorial
and include positive family history and female gender. DIFFEREN11AL DIAGNOSIS
There is a genetic component, but the mechanism Adolescents who participate in certain athletic ac-
ofgenetic influence is unknown. It is likely that the tivities (ballet, wrestllng. gymnastics, cheerleadlng,
development of an eating disorder involves genetic cross.country, and track) inwhich weight gain is thought
factors, environment, and experience as well as to negatively impact performance may manifest some
neuroendocrine factors. Both anorexia and bulimia ofthe behaviors associated with eating disorders such
are more commonly diagnosed in Caucasians than in as purging and severe calorie restriction.
other ethnic groups, but data may reflect diagnostic The marked weight loss seen with anorexia may
or research bias and/or access to care issues. Person- cause the clinician to consider malignancy, inflam.
ality risk factors associated with anorexia nervosa matory bowel disease or malabsorption syndromes,
include intense preoccupation with appearance, low and other chronic diseases (i.nfections, endocrine
self-esteem, and obsessive traits. disorders). The differential diagnosis for vomiting
(bulimia) is discussed in Chapter 14.
CLINICAL MANIFESTATIONS
History DIAGNOSTIC EVALUATION
Patients with anorexia may present with constipation,
Anorexia and bulimia are both clinical cliagno3es. Lab-
syncope, upper or lower gastrointestinal discomfort,
oratory studies are used to assess the need for specific
and/or periodic episodes ofcold. mottled hands and
medical interwntion rather than to confirmthe disease.
feet. Patients may report bloating or "fullness• after
Table3--3listsdiagnostic tests that are used to rule out
eating, which may be .related to inadequate caloric
or quantify certain conditions associated with anorexia
intake and subsequent delayed gastric emptying. If
nervosa and bulimia nervosa. Re&eding syndrome is
the chief complaint is weight loss, this invariably
rare and is ll&IIOciatedwith arrhythmia because ofdrop
comes from the parents rather than from the ado-
in serum phosphorus and prolonged QTc.
lescent; patients with anorexia generally do not view
their behavior as abnormal. Bulimia does not usually TREATMENT
produce specific symptoms, although these patients
The treatment for eating disorders is multifactorial
are significantly more likely than their peers to suffer
and includes nutritional support, behavioral therapy
from depression. Younger patients with eating dis-
and psychotherapy, and correction of any medical
orders are more likely to have psychopathology such
complications resulting from the severe weight loss
as depression. obsessive compulsive disorder, and
anxiety. All patients should be asked about self-harm or purging. Refeeding syndrome is a rare but paten·
tially serious complication associated with anorexia
(such as cutting) and suicidal ideation. Patients may
treatment, resulting in arrhythmia because ofdrop in
be brought to the physician because they have been
serum phosphorus and prolonged QTc. Family-based
caught purging or because their behavior has been
treatment (Maudsley approach) is evidence-based
reported by someone else.
treatment for anorexia nervosa or bulimia nervosa. and
Physical Examination cognitive behavioral therapy may be used for patients
Adolescents who suffer from anorexia may be severely with bulimia nervosa. Indications for hospitalization/
underweight (usually with a BMI <17) and appear inpatient therapy are noted in Table 3-4. Research is
cachectic. Growth charta should be reviewed, as ongoingas to whether psychotropic medicines (par-
the patient may present with •normal• BMI delpite ticularly selective serotonin reuptake inhibitors) are
significant weight loss. Vital signs often reveal hypo- useful in the treatment ofthese diseases. Psychotro-
thermia, bradycardia. and orthostatic hypotension. pic medication, if indicated. should start after some
The skin may be dry, yellowish. and hyperkeratotic. psychological therapy and nutritional management.
Thinning of scalp hair, increased lanugo hair, cool Atypical antipsychotics at low doses may assist with
extremities, and nail pitting are additional signs. eating disorder thoughts. Full recovery maybe in the
T.ULE w. Suggestsd Laboratory Tests for Adolescents with Eating Disorders

l...,
l ARIWilnts
'j Complete bloocl oount Neutropenla; also anemia aod thrombocytopenia
l Serum electrolytes Hypokalemiathypoc:hloremia/alblolil (ifpurging or laxative or diuretic
abuae}; hyponatremia (due to manipulation of water lntalce or laxatlve use)
!BUN Increased BUNfc:reatinine (dehydration or renal dysfUnctl.on)

i Glucose Normal or low
!Calcium/phosphate/magnesium Normal or low (due to malnutrition)
IElectrocardiogram Bradycardia, T·wave inversions, ST depression (anorexia), prolonged
QTc interval
!i I'Btitmts with Antnxia
i ESR• Normal or low
Iurinalysis Protelnurea from muscle breakdown; reduced speclfic gravity from
~ Uver function
exressive water intake
tests Elevated
\ Cholesterol Elevated; can occur with nutritional releeding
!Serum protein/albumin, prealbumin Low from poor nutrition
i TSH/fr,t Normal/normal to low; sign of hypothalamic dyafunction
1Ptllisnll • Bllfmla
j Serum amy.laae, lipase Elevated ifvomiting
! "Useful for ruling out other conditions in the differential.
~ Abbreviations: BUN, blood urea niiTOgen; ESR, erythrocyte sedimentaOOn rate; fT , free thy!Oldne; TSH, thyroid-stimulating hormone. ~
----··-0<-·········-·······..···········...········-....·······~·········~········-······-·-······-·······-······-····--·--····4 ·---··-···························-·······-·--~···-~·--·-----
TlllR M Aoorexia arxt Bulimia: Indications fiJ' POssible range of several months to several years and should
HOSI)IIatzatlon or Higher Level of Care focus on strategies for ongoing disordered eating
thoughts. PubUshed mortallty rates for anorexia
!Both Conditions nervosa are about 4% and for bulimia nervosa about
! Failure to improve with outpatient therapy; refusal of 3.9%, although this includes all ages.
! treatment
IHypokalemia (serum potusl.um. < 3.2 mmol/1.)
SUBSTANCE USE AND ABUSE
! Hypochloremia (serum chloride < 88 mmol/L)
j Cardiac arrhythmia.a/prolonged QTc interval! •orug use" is defined as the intentional use of any
!bradycardia substance that results in the alteration of the phys-
j Medical complications requiring inpatient ical. psychologic::al, cognitive, or mood state of the
!intervention such u esopl\aieal tears individual despite the potential for personal harm.
Patients become addicted when they begin to use
ISyncope the drug in a compuls.ive, dependent manner despite
j Suicidal ideation or other rrumtal health emergency significant functional impairment (drug abuse).
j Anotull This addiction can result from physical tkpentkna
! ~fl~~~ <OOin~<~~ l (physiologic symptomaofwithdrawal when the drug
! sleeping; orthostatic: vital sip j is removed) or pS'fchological dependence. Adoles-
I Continued weight losa; inability to comply with ! cents may have poor impulse control and prefer
instant gratification, leading to higlHisk behavior
! treatment plan !
such as drug experimentation. Various substances
INeed for enteral nutrition (food refusal) ! that are used and abused by adolescents are listed
!..~.~~.~.~~~~. ~.~.~. . . . . . . . . . . . . . . ... . . . . ... . . . ...! in Table 3-5.
TilLE M. Substance Use: Clinical Manifestations of Acuta Intoxication and Chronic Use
1........._ .,...,......,........ ............... Clnlcll . .lllfllll...,.af

l*wnlcllll
~~ Red.IKled inhibition, impaired N~tluabed Poor coortiJnatioo; llll.trldooal
coordination. poor judgment; llkiD, aluggiah pupils. deficiencies; cirrhosis of the
prosreaing to slurred .peech. decreued reflexes, lmrt impaired cognition;
ataxia, confuaion. coma, and hypoglycemia phyRcal dependency; i.mpain!d
I reapfntory depression work. peer. funily relationships
I~
Euphoria. relaxation, loud Drowsiness,ll.owed Reduced attention span;
talklng. hunger. impaired reaction timer., tachycardia. c:Umin1ahed short-term memory;
cognition: progressing orthostatic hypotension, impaired learning: psychological
to mood inatability and injected conjunctiva, dry dependency
hallucination& mouth
iMDMA Sense ofhapplneu, enhanced Hyperthermia, hypertellllon, Impaired abort-term and
I (•awy)
wel1-b~ progreulon to
agitation, conftulo.n. &hock
tachycardia, tachypnea.
dilated pupils, agitation,
long-term memory; (rarely)
hallucinogen persiating
hyponatremia perception diaorder
!Cocaine/ Elation. increased alertness Delirlwn, hyperthermia, Destruction of nasal septum
I amphetamines and activity, lnlomnia,
anxiety; progreasing to
dry mouth, tachyardia,
hypertenr.lon, dilated puplls,
(if nasal ad.m.l.nimatl.on of
cocaine); psycllological addictlon
dellrlum. chest pain, hyperreflexia, tremor• (amphetamines, pre1crlption and
pi}'Choala, Jeizures, coma otherwise, and cocaine)
I PCP Euphoria or anxiety, passive
to violent mooclawtnp,
Restleuneu, labile affect,
hyperthermia. tac:hycardia,
Depreuion; impaired memory
and cognitiono dl8ordeml
lmpa1.recl c:opltion. ataxia. hypertension, thuhJns, articulation; physlcal
i baDuclnatlonl; progrealng
to psychosll, leaJo respiratory
nystagmus, small pupill,
Impaired coordlnatlon.
clepend.eru:y
ilhll.-....
: (including
clepLeMl.on. and death
Euphoria, increased
alertness; progressing to
seizures
Resdeuneu,labileafiect
hyperthermia, tachycardia,
Emotional lability; exacerbation
of depression, schizophrenia;
~ LSD) nausea, anxiety, paranoia. hypertension, flushing, flashbacks; ill-defined changes in
~
baDuclnationa, seizures, coma warm skin, dilated pupils the brain
with injected conjunctiva,
i-
i
Euphoria followed by
sedation: impaired cognition,
nausea/vomiting, stupor,
hyperrefl.exla
Altered (depressed) mental
status, hypothermia,
decreased respiratory rate.
Ph')'lical addiction with marked
wi.thdmvalsyndrome of
restleune11, insomnia, vomiting,
respiratory depreuion, coma hypotellllo.n. pinpoint muscle pain. leg shaldng
unresponsive puplls
llnholant. Euphoria, impaired Agitation or stupor, .slurred Short, term memory loss,
cognitive impairment; loss of
judgment; progressing to speech, nystagmus/eye
I~
hallucination&, psychosis, watering, rhinorrhea. aenae of smello emotional lability;
seizures, coma increued saliva changes in articulation and gait
Rapid inaftae in mulde Gynecomaatia, acne, Teltic:ular ~jaundice;
I- mua, Jtamina (over montha),

mood inltabllity
hypertemion, hair lou;
aggres.ive behavior (over
weeblmonths)
llbmted height growth;
pi)'Cholosical dependency
EPIDEMIOLOGY Evidence-based screening regarding tobacco,

Unfortunately, substmce use among adolescents is not alcohol, and substance use should be completed at
unoommon. In the 2015 Youth Behavior Survclllance every annual adolescent viait, along with appropriate
System survey, 32.8% had drunk alcohol within the last intervention when indicated.
30 days, 38.6% had ever wed marijuana. and 31.~ had
DIAGNOSTIC EVALUAnON
used t.obacoo products ofany type including chewable
tobacco and '\raping"; 5.2CJli had tried cocaine; '7% had Although drug testing is widely available through
tried inhalants; 6.2% had used heroin, and~ had used many labs and even over the countEr, most office
hallucinogenic drugs. Marijuana is the most commonly settings are not doing accurate drug screens, which
used "illicit'" drug in the United States, but alcohol is involve checking urine temperature, specific grav-
the most commonly abused substance by teens in the ity, etc. Testing an adolescent at the request of the
country. Data are stillbeing gathered regarding howth.e parents without the patient's knowledge is strongly
marked national in.m!ase in heroin use and overdose discouraged; attempts should be made to involve the
&talities has affected the older adolescent population. teen in the discussion and obtain consent for any
recommended diagnostic studies. Involving parents
RISK FACTORS is also very important. If parents have concerns of
Risk factors and protective factors related to substance substance use or abuse, dlscusslon with the teen is
use in adolescents are listed in Table 3-6. appropriate.
CLINICAL MANIFESTATIONS MANAGEMENT

The clinical manifestations of acute intoxication Patients suspected of drug/alcohol dependence
with the substances ofinterest are listed in Table 3-5. should be referred to an addiction specialist and may
Management is addressed in Chapter 20. require Intensive inpatient or outpatient therapy.
Adolescents who use tobacco must be encouraged
to quit and supported in doing so. If the patient is
TOLE M. Risk Factors for Substance Use
interested in smoking cessation, nicotine replacement
lllllt:lt l1rufl therapy (•the patch.• gums, etc.) may be offered. Some
lGenetic predlapoaltion (Cor acldictico) adolescents may require more intensive behavioral
i Use of illicit substances by family and friends therapy or presalptlon medication such as bupro-
IEuy aazu to illicit mbllt:anca or presaiption drugs plon. Motivational interviews should be integrated
into any discussion of behavioral changes.
~ Low leYels of parental involvement and support
I Poverty
VIOLENCE IN THE ADOLESCENT
i Academic failure
POPULATION
IAlc:olrol
lGenetic prec:Uapolition (Cor alcoholism) EPIDEMIOLOGY
i Use and abuse of alcohol by parents, peers Unintentional injuries are the leading cause ofdeath
iLow levelJ ofparental involvement in the adolescent population. This includes primarily
motor vehicle collisions, but also drowning and other
i TDbl«o accidental events. Homicide and suid.de are second
Parental smoking and tobacco use and third on the list, respecti~. Adolescents may
Euy acceu to c.lgatettes, other tobacco products, be victimA of violence (including bullying), perpetra-
e-dgarettea tors ofviolence against others, and/or intentionally
No restridions on smoldng In the home harmful to themselves.
~ ~~-
RISK FACTORS
Individual risk factors Cor violent behavior includ.e
previous arrest for juvenile aime, early expomre to
violenre (interpersonalviolenre and in the media), being
I.Academic achievement ·,,,,1
a victim ofabuse, drus and alcohol use. and academic/
schoolfailure. .Ahhoughyoung women are more likely
~ Allllociation with abstinent peen l
••••••••••••••••••••••••••••••••••••••••••••••••••••••••oooooo.,oooooooooooooo•••••••••••••oouooooooooooo.,oooooooo""'"""""'"'•••~.,: than young men to report experiencing sexual abuse.
adolesamt males are far more likely to be the victims and, ifthese are positive, suicidal ideation. It should
and perpetmtors ofviolent acts. Other factors associated be noted that children and adolescents with depres-
with an in.crea&ed likelihood ofviolent behavior include sion may present with irritability instead of •tow
low socioeconomic status and easy~ to guns. mood• or sadness, and may self-medicate with illicit
The strongest risk factor associated with at- substances. Several adolescent depressive screening
tempted suicide is a • prior attempt.• Othet- factors tools have been validated in tlu! clJnical setting. Those
that increase the likelihood of attempted suicide patients who admit to having a plan for suicide are
include an existing paychiatric disorder (depression, at particular risk. Serious harm to self or others is a
etc.), substance abuse, a history of being abused, a reason to break confidentiality.
family history of a major affective disorder and/or
suicide, and a recent life stressor. Adolesants who MANAGEMENT
live in homes with firearms have a 10-fold greater Encouraging parents to Umit exposure to violence
risk ofcompleted sukide than do their peos. in the media should be part of preventative health
counseling beginning in the toddler years. Securing
CLINICAL MANIFESTATIONS mental health services for the affected adolescent
Physicians and other health care personnel who (and social services for the family) may provide the
interact regularly with adolescents are in a position support needed to make the transition to a productive
to question them about whether they feel safe and adulthood and limit involvement with the juvenile
whether they have witnessed or been the victims justice system.
ofaggression. Asking how patients deal with angei; As previously mentioned, doctor-patient confiden-
if they have ever been in a fight, if they have been tiality does not extend to information that suggests
suspended from schooL and whether there is a gun the potential for immediate harm. Any patient who
In the home may also open avenues of discussion. attempts suicide, even if the attempt is interpreted
All adolescent patients should be screened for as merely a •gesture;' should undergo immediate
anxiety and depression (sadness, despair, hopelessness) psychiatric evaluation and may need hospitalization.
KEY POINTS
• It is recommended that menstruating female females. Contraception counseling should be
adolescents receive hemoglobin/hematocrit conducted at each health maintenance visit.
at least once during adolescence. Vision and • Eating disorders may occur in teens of all
heaJ1ng should be assessed every 3 years. genders and ethnlcltles. Growth charts should
Height, weight, BMI, and blood pi'86Sure as well be evaluated for changes yearly or as indicated
as depression acreenlng and sexual risk factors by symptoms. Differential diagnosis includes
should be 88&essed at each health maintenance Inflammatory bowel disease.
visit. Lipid screening should occur at least twice
during adolescence, and tuberculosis screening • Marijuana is the most commonly used illicit
should be based on risk factors. drug In the United States; alcohol Is the most
commonly used substance by teens.
• In males, the Initiation sequence of sexual de-
velopment Is testicular enlargement, followed • Patients who are smokers should be encouraged
by pubic hair growth, penile lengthening, m1d to quit at each health visit. Those who express
attainment of maximal height velocity. interest in doing so should be offered nicotine
raplacement therapy, behavioral therapy, social
• In females, the order of pubertal events in sex-
support, and On some cases) bupropion.
ual development Ia 1helarche (breast budding).
folowed by pubic hair growth, attainment of • Traumatic injury Is the leading cause of death
peak~ velocity, m1d menarche. in the adolescent population.
• Adolescents who are sexually active should be • Adolescents who live In homes with a 1'ir8arm
offered testing for gonorrhea and chlamytla, Hiv, have a 10-fold graater risk of completed suicide
and syphilis (APR) at least yearty. Screening for than do their peens with depression and no
T. vag/nails Ia 1'8C0mmended for sexually active firaarm in the home.
CLINICAL VIGNETTES
VIGNETTE1 1. Which of the following tests would most likely

A 1 5-year~old female comes Into your clinic complain- con11rm 1he etiology of the diagnosis?
ing of constipation. You note that she has lost 15 lb L Wetmount
since her last clinic visit 8 months ago. She is 67 in b. Urine NMT
and weighs 102 1b. Hercunant BMI Is 16. When asked c. Herpes culture
about It, she states, •1•m trying to be healthier." On d. Urine pregnancy test
her examination, her temperature Is 97.4•F, respiratory e. Bimanual examination
rate is 14 breaths per minute, pulse is 40 beats per 2. Your evaluation reveals colnfectlon with Chlamydia
minute (bpm), and blood preBSure is 110182 mm Hg. trachomatls and Neisseria gonon'hoeae. Which of the
Orthostatic blood preBSures and pulses are as follows: following Is the treatment of choice for this patient?
osno
Lying: 1 mm Hg, pulse 40 bpm L Ceflxime 200 mg by mouth once a day for 5
Sitting: 100/65 mm Hg, pulse 55 bpm days and azithromycin 100 mg by mouth twice
Standing: 95160 mm Hg, pulse 65 bpm a day for 7 days
She is thin wtth cool extremtties and light, downy b. Azithrornycin 2 g by mouth, single dose
hair on the back of her neck. On further investigation, c. Ceftriaxone 250 mg IM, single dose and azi-
you discover she has not had a period in 4 months. thromycin 1 g by mouth, single dose
1. What is the most likely diagnosis? d. Ceftriaxone 250 mg IM, single dose and doxycy-
L Hyperthyroidism cline 100 mg by mouth, twice a day for 14 days
b. Irritable bowel syndrome e. Doxycycline 100 mg by mouth twice a day
c. Anorexia nervosa for7 days
d. Bulimia nervosa 3. Which of the following Is the most serious acute
e. Body dysmorphic disorder complication of this illness, if it remains untreated?
L Dyspareunia
2. What isthe most appropriate next step in her care?
L Hospitalization
b. Infertility
b. Referral to a dietician c. Endometriosis
c. Outpatient behavioral therapy d. Tubo-ovarian abscess
d. Laboratory assessment including complete blood e. Cervical cancer
count (CBC) and basic metabolic panel (BMP) 4. Which of the following signs is pathognomonic
.. Emergent psychlatrtc evaluation for this complication?
L Dyspareunia
3. The patient continues to return for follow-up af-
b. Cervical motion tenderness
ter her lnltlal1re81ment. Three months later, she
c. Chronic pelvic pain
remains amenorrheic. What Is the likely cause of
d. Endocervical ulcers
her amenorrhea?
e. Dysmenorrhea
L Infertility
b. Polycystic ovarian syndrome VIGNal'f3
c. Premature ovarian failure A 14-year-old male comes to your office with his mother
d. Hypothalamic dysfunction due to chronic
for a health maintenance visit. He has not been in the
malnutrition
office since he was 9 years old. Before that time, he
e. Anemia had been seen regularly and had been up-to-date on
VIGNETTE2 all immunizations. His mother states that he has been
more distant than usual, but has no other concerns.
A 16-year-old female comes Into your office com-
On physical examination, his vital signs are normal
plaining of vaginal discharge. She has regular perl-
and his examination Is unremarkable.
ods, the last of which was 1 week ago. She has had
three sexual partners In the last year. On physical 1. Which of the following vaccinations should be
examination, her temperature is 98.7°F, respirat ory offered at t oday'& v isit?
rate is 15 breaths per minute, pulse is 72 bpm, and L Tdap, MCV, HP\f, seasonal influenza
b lood pressure is 102fl8 mm Hg. Her abdominal b. Tdap only
examination is benign. Examination of the external c. MCVonly
genttalia reveals a whitish, mucopurulent discharge, d. Tdap and HPV
but no lesions or ulcers. e. HPV, MCV, and seasonal influenza
2. Upon asking the mother to leave the room for 1. Which of the following is the most likely diagnosis?
confidentiality reasons, you conduct the remain- a. Acute psychosis
der of the health maintenance Interview. Durtng b. Cocaine use
the HEADSS assessment, you discover that your c. Cannabis use
patient has thoughts about suicide and has made d. Amphetamine ingestion
a plan on how to do eo in the past. What is the e. Inhalant use
most significant risk factor for attempting suicide?
2. Which of the following samples provides the most
a. History of abuse likely confinnatory test?
b. Having a gun in the home
L Blood
c. Depression b. Urine
d. A prior suicide attempt
e. History of parent committing suicide
c. Hair
d. Oral secf'9tlons
1 Your patient aska you not to tell his mother about e. Skin
his suicidal thoughts. He states that this "would
really upset her.~ Befol9 the visit, you had 19Viewed
s. If this patient continues to engage in use of the
drug In question, he Is at an Increased risk for
your confidentiality policy with both the patient
which of the following?
and the parent. What is your role as the physician
a. Dropping out of school
in this situation?
b. Use of other illicit drugs
a. Report the patient to the police c. Criminal behavior
b. Reveal your concerns to the parent and refer
d. a and b only
for emergent psychiatric evaluation
e. a, b,and c
c. Uphold the patient request
d. Encourage the patient to tell his mother 4. You see the patient 6 months later In clinic. He
a. Consult the ethics committee emergently reports that his grades are dropping, yet he does
not seem bother9d by this change. On further
VIGNETTE. questioning, the patient states that he has contin-
You are in the emergency department on a Friday night ued to use cannabis drug recreationally but does
when a 17-year-old male with altered mental statu8 ia not spend exceesive time acquiring the drug. In
brought in by his mother. His mother states that she between uses of the drug, he does not experience
heard him come home after his curfew and found him in any sleep or mood disturbances. What condition
the kitchen. He seemed somewhat disoriented and was best characterizes this patient?
snacking on dinner leftovers. On physical examination, a. Repeated intoxication
his temperature is 99°F, respiratory rate 20 breaths per b. Drug abuse
minute, pulse 112 bpm, and blood pressure 130/90 mm c. Drug dependence
Hg. He responds slowly to your questions, and you note d. Conduct disorder
that his eyes are InJected and his oral mucosa Is dry. e. Dysthymia
ANSWERS
VIGNETTE 1 Question 1 Patients with bulimia nervosa are often of normal

1.AnswerC: weight, but sea themselves as overweight. On physi-
The DSM-/V criteria for anorexia nervosa includes cal examination, they may have dental caries/enamel
the following: the refusal to maintain body weight at erosion, swollen parotid glands, and calluses across
or above minimally normal body weight for age and the knuckles from forceful vomiting (Russell's sign).
height; intense fear of gaining weight or becoming Irritable bowel syndrome Is considered In the dif-
fat despite being underweight; distorted perception ferential diagnosis, but these patients will often also
of body weight and shape; and amenorrhea. Many have iSsues with diarrhea and abdominal pain. They
patients will have a BMI below normal; this patient's do not have amenorrhea. In hyperthyroidism, patients
BMI Is less than the 3rd percentile for age. Associated may have irregular periods and weight IOSB, but they
symptoms Include fatigue, dry skin, lanugo, hypoactive generally have an increased appetite, heat intolerance,
bowel sounds, constipation, earty satiety, bradycar- an increase in bowel movements, and possibly a goiter
dia, orthostatic hypotension, sensitivity to cold, and on examination. Lastly, body dysmorphic disorder is
difficulty concentrating. defined as a preoccupation with an imagined defect in
one's body or a disproportionate concern with a very the most likely diagnosis in this patient. A wet mount
sUght physical anomaly. These patients generaUy have would be helpfUl to look fer BV, which usually presents
completely normal vitals and physical examinations. with a fishy-smelling, thin, white discharge. Clue cells
on the wet mount would be diagnostic of BV. A rapid
VIGNETTE 1 Quasllon 2 Tl1chomonas test would diagnose r vaglnalls, which
2. Answer A:. tends to cause a green, frothy, foul-smelling discharge.
The following criteria qualify a patient with anorexia A pregnancy teet is indicated, but would not reveal
nervoaa to be admitted to the hospital: severe mal- the cause of the clinical findings. On examination, our
nutrition, dehydration, electrolyte instability, cardiac patient did not have the classic painless chancre on
dysrhythmia, arrested growth and development, failure her vagina (sign of primary syphilis); thus, the RPR will
of outpatient beatment, acute food refusal, psychogenic not confirm the most likely diagnosis.
emergencies, and/or physiologic instability. Physiologic
instability is defined as the following: VIGNETtE 2 Question 2
• Severe bradycardia (heart rate < 50 bpm during 2.AnswerC:
day or <45 bpm at night) Based on current CDC recommendations, the first-line
treatment for cervicitis In the outpatient setting Is cef-
• Hypotension (blood pressure < 80/50 mm Hg)
trfaxone 250 mg IM In a single dose and azJthromycln
• Hypothermia (temperature < 96°F) 1 g oral In a single dose.
• Orthostatic changes in pulse (> 10 bpm) or blood
pressure (>20 mm Hg) VIGNETTE 2 Question 3
CBC and BMP are helpful baseline labs to look for 3.Answer 0:
anemia and electrolyte abnormalities, but the patient's Tuba-ovarian abscess can result from PID (Chapter 10)
bradycardia and positive orthostasis are of greater and is an indication for hospitalization. Infertility may
ooncem. All eating disorder patients should have a be a complication of untreated N. gononhoeae and
dietician, therapist, and sometimes even a psychiatrist C. trachomatn. Endometriosis is the presence of
involved in their care, but the most important thing to endometrial glands and stroma in extrauterine sites.
do first for this patient is to hospitalize her for unstable This disorder is caused by genetic and immune factors
vital signs. as well as possibly retrograde menstruation. It is not
associated with cervical Infections. Cervical cancer Is
VIGNETTE 1 Question 3 a complication of Infection with HP\1.
3.Answer 0:
Hypothalamic dysfunction due to chronic malnutrition VIGNETTE 2 Question 4
leads to amenonhea. Patients who remain amenor- 4. Answer B:
rheic for 8 months or greater are at an increased riak Cervical motion tenderness is defined as unpleasant or
of osteopenia and osteoporosis; however, treatment severe discomfort during bimanual examination of the
should focus on weight recovery. It is still possible for cervix and is indicative of an inflammatory process of
a patient to become pregnant despite an amenorrheic the pelvic organs. It is also called the "chandelier sign•
state. Furthermore, fertility is generally restored in re- because patients may "jump off the table" because of
covered anorexics. Polycystic ovarian syndrome and the pain. Dyspareunia (pain with coitus) may certainly
premature ovarian failure may be causes of second- be associated with PID but also occurs with urinary
ary amenorrhea, but should not result from anorexia tract disease, poor lubrication, endometriosis, and a
nervosa. Anemia Is present In roughly one-third of wide variety of other disorders. Chronic pelvic pain
anorexic patients but Is not associated with the status may result not just from gynecologic causes, but also
of amenorrhea. from urinary, gastrointestinal, somatic, and oncogenic
causes. Endocervical ulcers may occur In PID as well
VIGNETlE 2 Quesllon 1 as In simple cervicitis. Dysmenorrhea (pain with pe-
1.Answer B: riods) is cau&ed by prostaglandin production during
Urine NAAT would reveal the cause of her cervicitis. menstruation and is not a sign of PID.
The patient most likely has cervicitis caused by either
N. gononhoeae or C. trachomatfs. These organisms VIGNETTE 3 QuiBtion 1
are often copathogens. This diagnosis is more likely 1.AnswerA:
due to the history of multiple partners and the type of Between the ages of 11 and 12 years, the recom-
discharge. Urtne NAAT Is the best method for diagnosing mended vacclna1ions are Tdap, MCV4 (quadrivalent),
N. gonontJoeae and C. trachomatls. It Is more rapid HP\f, and the seasonal Influenza vaccine. The Tdap
and sensitive than cultures. Although any of the tests should be followed by a tetanus and diphtheria toxolds
would be beneficial as screening examinations In a (Td) booster every 10 years thereafter; administration
sexually active teenager, not all of them would lead to of the Td for an Interval of less than 1a years, even In
response to a tetanus-prone injury, is unnecessary. The reaction times, and increased appetite. Physiologic
HPV vaccine Is generally started at or after 11 years signs Include tachycanila, orthostatic hypotension,
of age and Is a three-shot series. A yearly Influenza Injected conjunctiva, and dry mouth. Acute psychosis
vaccine is also recommended. Is the disruption of perception of reality characterized
Recommendations regarding the administration by thought disorganization, hallucinations, and/or
schedule for MCV4 have recently been updated. delusions. This patient's history does not support this.
Adolescents should initially be vaccinated at 11 to 12 Alcohol will cause impaired judgment and coordination,
yeara of age. followed by a booster at age 18 yeara. slurred speech, nauseaf\lomiting, sluggish pupils, and
If the adolescent receives the first dose at 13 to 15 flushed skin. Amphetamine ingestion may cause acute
years, a on~time booster should be administered at anxiety, insomnia, tachycardia. hypertension, and dilated
age 18 to 18 years (or up to 6 years after the first dose). pupils. Last, with inhalant use, teens may experience
euphoria, impaired judgment, agitation, nystagmus,
VIGNmE 3 Question 2 and increased secretions (eye, nose, mouth).
2.Answer D:
The lastS in the HEADSS assessment stands for sui- VIGNETlE 4 Quesllan 2
cide. Risk factors for suicide Include mental Illness, a 2.Answer B:
family history of mood disorder or suicide, and a history Urine, blood, hair, and oral ftuld can all be used to test
or physical or seXl.lal abuse. However, the largest risk for cannabis Intake. Urine te6tS are Inexpensive and
factor for suicide Is a prior suicide attempt. Previous widely available and therefore are the most commonly
attempts at suicide can increase an individual's risk used test. The screen is first performed with a sensitive
of suicide by 30 to 40 times. Precipitating factors for immunoassay test. Positive resuHs are followed up
suicide include access to means (such as having a with more specific teste. Skin sampling is not used
gun}, exposure to suicide, alcohol and drug use, social to test for cannabis. Marijuana can be detected for 7
stress and isolation, and behavioral factors. to 10 days after use in a nonchronic user.
VIGNmE 3 Q...Uon 3 VIGNET1E 4 Qu88tion 3

a. Answer B: a Answer E:
Confidentiality is an important component of the Marijuana is considered the ~gateway drug• because
adolescent health visit. It buUds trust and fosters an users are more likely to try additional Ullclt drugs.
environment In which the teen can begin to manage his The chronic use of martjuana also results In reduced
or her own health care. However, If certain lnfonnatlon attention span, diminished short-term memory, and
Is reported that puts the patient at risk, conftdentlallty Impaired learning. These symptoms place the patient
may be broken. Cases for which confidentiality may at an increased risk for school dropout. U.t, some
be broken include child abuse/neglect, reportable studies have shown significant correlation between
sexually transmitted infections, homicidal ideation, increased marijuana use and the number of crimes.
violent injuries, rape, and suicidal ideation or plans to
commit suicide. Laws regarding confidentiality vary VIGNETlE 4 Question 4
by state, so it is important to review the laws in your 4.Answer B:
state. All states permit break in confidentiality if the Abuse implies that the patient's use of the drug is
patient is judged to be an imminent danger to himself interfering with work, school, and home. It also can
or herself or to others. include recunent legal problems, use in hazardous
The patient in question has confessed to suicidal situations, and persistent use despite problems with
Ideation as well as a plan. It Is Important to refer him interpersonal relationships.
for emergent psychiatric evaluation, which would Dependence, on the other hand, Is marked by
also require raveallng the Information. This lnfonna- tolerance to the drug, Increased time spent acquiring
tlon cannot be kept secret. The pollee do not need the drug, unsuccessful attempts to stop, and per-
to be involved, as they would be in a case of child sistent use despite knowledge that adverse physicaV
abuse. Trusting the child to tell his or her mother is psychological symptoms are caused by the drug.
not appropriate because the child needs immediate Because our patient is showing significant impainnent
help. Waiting on a decision from the ethics committee in school, he is beyond the classification of repeated
would delay treatment. intoxication. Children with conduct disorder often en-
gage in repeated delinquent activities such as fighting
VIGNmE 4 Q..Uon 1 and stealing. Dysthymic disorder is characterized by
1.Answer C: depressed mood for at least 2 years that is present
Cannabis, when either inhaled or ingested, can cause most of the day and more days than not. Patients with
symptoms of euphona, impaired cognition, slowed dysthymia can also develop poor school performance.
Nutrition
Trisha Lewin and Katie S. Fine
Good nutrition is essential for optimal physical fortifier. Newborns feed on demand, usually every 1
growth and intellectual development. A healthy diet to 2 hours. Neonates typically lose up to 10% oftheir
protects against disease, provides reserve in times birth weight over the first several days; formula-fed
of.stress, and contains adequate amounts of protein, babies regain that weight by the second week of life,
carbohydrates, mbl, vitamins, and minerals. Children whereas breast:&d babies may take about a week longer.
with vegan diets (ingesting no animal products) are Healthy infants automatically regulate intake to meet
at risk for vitamin Br1 deficiency and, if exposed to caloric demand for basic metabolism and growth.
inadequate sunlight, for vitamin D deficiency as All infant formulu contain the recommended
well. Iron supplementation/fortification should be amounts of vitamins and minerals. Cereals and
considered for both vegan and lacto-ovo vegetarians. stage 1 baby foods can be added to the infant diet
Infant feeding intolerance, failure to thrive (PTT), between 4 and 6 months of age. Age-appropriate
iron deficiency anemia (Chapter 12), and obesity are solids should be fed only by spoon, rather than
the most common pediatric conditions associated mixed in a bottle of formula. When introducing new
with malnutrition in the developed world. foods, only one novel product should be introduced
In order to usess a child's nutritional statu and at a time to evaluate for potential adverse reactions.
growth, pediatricians follow the patient's growth Whole-fat cow milk may be introduced at 12 months
chart. Growth charts represent cross-sectional data and should continue until 24 months unless the
from the National Center for Health Statistics. The child is overweight/obese or there is a strong family
patient's weight, height, weight-for-length (before 2 history of cardiovascular disease, in which case 2%
years of age), and body mass index (BMI; weight in milk should be offered instead. It is appropriate to
kilograms divided by height in meters squared, after transition all healthy children to 2% milk (or lower)
2 years ofage) are recorded as points on the chart at after 24 months of age. Infants and children sent to
each health maintenance visit. Separate growth charbl bed with a bottle containing anything but water are
are generated for preterm infants and children with at risk for milk-bottle teeth caries.
certain genetic disorders, including Down syndrome
and Turner syndrome. BREASlREDING
The American Academy of Pediatrics recommends
exclusive breastfeeding during the first 6 months
INFANT FEEDING ISSUES of life and continuation of breastfeeding during
Infant feeding addresses the physical and emotional the second 6 months fur optimal infant nutrition.
needs ofboth mother and child. Babies double in weight Studies have shown that breastfed infanb have a
by age 4 to 5 months and typically triple their birth lower incidence of infections, including otitis media,
weight by their first birthday. Height reaches twice pneumonia, sepsis, and meningitis. Human milk
birth length by age 3 to 4 years. Although breastfeed- contains bacterial and viral antibodies (secretory
ing is almost always preferable, many commercially immunoglobulin A) and macrophages. Lactoferrin
prepared iron-fortified formulas provide appropriate is a protein found in breast milk that increases the
calories and nutrienb. Preterm in&nbl require spe- availability of iron and has an inhibitory effect on
ci£ically balanced formula or breast milk with added the growth ofE&cherichJa coli. Breastfed infanbl are
15
88 • BLUEPRINTS Pedlatr1cs
less likely to experience feeding difficulties associated or wheezing. A severe local allergic reaction within
with allergy (eczema) or intolerance (colic). the bowel results in colitis, indicated by anemia
Breastfed infants should receive oral vitamin D and/or obvious blood in the stools. Other possible
supplementation beginning within a week after birth nonspecific symptoms include vomiting, irritability,
to prevent rickets, a condition in which developing and abdominal distention.
bone fails to mineralize because of inadequate
Differential Diagnosis
1,25.dihydroxycholecaldferol Dark-skinned infants
Infectious gastroenteritis, necrotizing enterocolitis,
and those at extreme latitudes are at increased risk.
intussusception. intermittent volvulus, cellae dis-
Rickets in breastfed infants becomes clinically and
ease, cystic fibrosis, chronic protein malnutrition,
chemically evident in late infancy (Table 4-1). Rickets
aspiration. and eosinophilic enteritis should be con-
due solely to vitamin D de6dency begins to respond
sidered. The most common condition mistaken for
to supplementation within weeks. It is recommended
milk protein intolerance is coUc, which is generally
that all children receive a minimwn of 400 IU of vi-
limited to infants 3 weeks to 3 months of age. Colic
tamin D daily. According to the American Academy
is a syndrome of recurrent irritability that persists
of Pediatrics, breastfed infants may require fluoride
for several hours, usually in the late afternoon or
supplementation ifthe concentration of the mineral
evening. During the attacks, the child draws the knees
in their main water source is extremely low.
to the abdomen and cries inconsolably. The crying
In developed countries, mothers with HIV infec-
resolves as suddenly and spontaneously as it begins.
tion or untreated active tuberculosis and those who
are using illegal drugs should not breastfeed. Other nutment
contraindications include infants with galactosemia Exclusive breastfeedJns during the first year of lJfe
and certain maternal medications (antithyroid agents, eliminates the problem posed by cow milk protein
lithium, isoniazid. and most chemotherapy drugs). intolerance, except in severely allergic infants. If
there is no evidence of any underlying disease in
INFANT FEEDING INTOLERANCE formula-fed infants with characteristic symptoms,
Feeding intolerance may lead to food aversion and substitution of a protein hydrolysate (extensively
FTT; the most significant cause is cow milk protein hydrolyzed) formula is recommended because as
intolerance or allergy. many as 109(, to 1'7% ofchiJdren with mw milk protein
allergy are also intolerant of soy protein.
Clinical Mannestallons
History and Physical Examination MALNUTRmON
Feeding intolerance may present with any nwnber Malnutrition is defined as an imbalance between
of clinical manifestations. Malabsorption is char- nutrient requirement and intake, resulting in cumu-
acterized by poor growth and chronic, nonbloody lative deficits of energy, protein, or micronutrient&
diarrhea. Allergy may be accompanied by eczema that may negatively affect growth. development,
and other relevant outcomes. Malnutrition is often
characterized as acute, which primarily affects weight,
TABLE •1. Clinical and L.abaratory Manifestations
or chronic, which typically manifests as stunting (a
of Rickets
reduction in the rate oflinear growth). Malnutrition
iCraniotabes (thinning ofthe outer skull layer) ' can present as weight greater than 1 standard de-
! Rachitic rosary (enJarsement ofthe costochondral viation below the median (Z score < -1) or falling
!JUDCtlons) off a previously established growth curve. It is not
j Epiphyseal enlargement at the wrists and ankles uncommon fur a child to cross a growth percentile
j Delayed clotdns of abnormally large fontanelle curve between 9 and 18 months of age, as growth
begins to relate more closely to genetic potential
rather than maternal nutrition during pregnancy.
li Bowlegs
Delayed walldns
!':
,_
In particular, breastfed infants have steeper weight

INormal-to-low serum calclum curves than formula-fed infants initially, but often
ILow serum phosphol'UI
!:,_
have a normal and anticipated percentile drop in

~ Elevated serum alkaline phoaphatase ~ weight once cow's milk and solid foods are started.
However. a growth curve that flattens or decreases
~--~-~--~~-~!!~~!. . . . . . . . . . . . . . . . . . . ....! across one or more growth percentile curves is cause
Chapter 4 I Nutrition • fi1
for concern. Risk factors for malnutrition include low caretaket; withdrawn, or excessively fearful often have
birth weight, low socioeconomic status, physical or contributing psychosocial issues. F'mdings suggestive
mental disability, and caretaker neglect. Malnutri- of physical abuse or neglect (see Ol.apter 20) should
tion is often associated with developmental delay, be sought and documented.
particularly if it occurs during the first year of life A complete physical examination. with careful
when brain growth Is maximal attention for dysmorphism. pallor, bruising, cleft
palate, rales or crackles, heart murmurs, and muscle
Dlffanntlal Diagnosis tone may suggest the etiology.
Malnutrition may result from inadequate caloric
intake, excessive caloric losses, or increased caloric Diagnostic Evaluation
requirements. MostCIUe8 ofmabtutrltion in d~ped Information obtained from the history and phyaical
coUIItriu are nonorganic (or psychosocial) in origin; examination determines the direction of further di-
that is, there is no coexistent mecllcal disorder. Neglect agnostic workup. Any child with malnutrition should
is a common form of psychosoclal malnutrition. The receive a oomplete blood count, serum electrolytes,
list of organic diagnoses predisposing to malnu- blood urea nitrogen and creatinine, protein and al-
trition is extensive, and virtually all organ systems bumin meuurements, urinalysis, and urine culture.
are represented (Table 4-2). Organic malnutrition Bone age films may also be helpful in children beyond
virtually never presents with isolated growth failure; infancy. Severely malnourished children and patients
other signs and symptoms are generally evident with with suspected nonorganic malnutrition should be
a detailed history and physical examination. admitted to the hospital. Adequate catch-up growth.
during hospitalization on a regular diet is virtually
Clinical Manlfasta11ons diagnostic of psychosocial malnutrition.
HlsttJry
The caretaker must be questioned in detail about OBESITY
the child's diet, including how often the child eats, When a pediatric patient's BMI is greater than the
how much is consumed at each feeding. what the 95th percentile for age, that individual is considered
child is fed, how the formula is prepared, and who obese. A child whose BMI falls between the 85th and
feeds the child. Information regarding diarrhea, fatty 95th percentiles is considered overweight. According
stools, irritability, vomiting, food refusal, ability to to the most recent U.S. National Health and Nutrition
vigorously complete a reeding, and polyuria should be Examination Survey, about 13 of2- to 5-year-old
documenred.. Recurrent infections sugge~t congenital children, l94j6 of6- to 11-year-old children. and 21%
or acquired immunodeficiency. Constitutionalgrowth of 12- to 19-year-old children are obese. A period
delay can usually be diagnosed by family history of adipose cell proliferation occurs from age 2 to 4
alone. Foreign and domestic travel, source of water, years and again during puberty, placing pediatricians
and dewlopmental delay are occasionally overlooked in an ideal position to affect their patients' health
topics. The psychosocial history includes questions well into adulthood
concerning the caretaker's expectations ofthe child.
parental and sibling health. financial security, recent
Clinical ManlfBB1Btlons
major life events, and chronic stressors. Although the root cause is simply caloric intake in
excess ofexpenditure, several factors contribute to the
Physical Examination risk ofbecoming obe~e, includins senetic, parental.
Weight, height, and head clrcumference should be family, and lifestyle issue8 (Table 4-3). Therefore, it
reoorded on an appropriate growth chart. Relatively is critical to obtain a detailed history and perform a
recent growth failure is usually Umited. to weight complete physical examination. The history should
alone, whereas height and (later) head circumference consist ofa thorough review ofsystems and relevant
are also affected in chronic deficiency. Severely de- family history. In addition, the social history should
prived children may present with lethargy, edema, include not only dietary history but also activities and
scant subcutaneous fat, atrophic muscle tissue, self-esteem. The social and psychological consequences
reduced skin turgor, coarsened hair, dermatitis, and of being a "fat" child may be particularly damaging
distended abdomen. to self--esteem at a critical age. Weight-for· length
Observation ofcaretaker-child interactions and or BMI should be calculated, and blood pressure
feeding behavior is criticaL Children who are list- should be obtained A physical examination should
less, minimally responsive to the examiner and/or be completed to screen for comorbidities, although
TABLE ..2. Diffemntial Diagnosis af Malnutrition

i floiJotpnlc
INeglect
i Abule Incorrect preparation of fo.nnula
l Qrdiac
j Congenit al heart malformations
I
I68ltrDinltlltin
! Malabsorption Inflammatory bowel disease
!Cow milk protein intolennce/allergy Celiac di.leue
IGastroesophageal reflux Hirschsprung disease
! Pyloric stenosis
! Pulmonlty
ICystic fibrosis Chronic aspiration
i Bronchopulmonary dysplula Respiratory lnaufficJ.en.cy
!lntectJous
IHIY Intestinal parasites
ITuberculosis Urinary tract infection
!Chronic gastroenteritis
~ NtltJnaiiJI
IPrematurity
I
Congenital or perinatal infection
~ Low birth weisht Congenital synclromea
i EntkJcrfnl
!DiabetD mellitua Adrenal iJuufficieru:y or excaa
! HypothyroidWn Growth hormone deftdency
I NfurriDgic
~ Cerebral palsy Degenerative disorders
I Mental retardation Oral-motor dysfunction
! Renal
IRenal tubular addosla Chronic renal J.nsufBdency
IOther
!Inborn erron of metabolism Immunodeficiency syndromes
i Malignancy Collagen VB!Icular diseue
!
!..~. ~~. . . . ... . . .. . . .. . . .. . . . . . . . . . .. . . .. . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . ... . . .. . . .. . . . . . .. . . .. . . . . . . . . . .. . . .. . . . . . . . . ... . . . . . . . . . .. . . . ..
obese patients of normal or above-average height and renal function tests. The workup of the short
are unlikely to have a pred.laposlng health condition. obese child should include consideration ofendocrine
disorders (hypothyroidism, Cushing syndrome),
Diagnostic Evaluation
genetic syndromes, and hypothalamic tumors.
Although there are no universally accepted current
guidelines, if there is a cUnica1 suspicion or strong Complications
family history ofcomorbidities, a laboratory workup Metabolic I}'Ddrome is the combination ofobesity,
should be considered. This would include a fasting hypertension, insulin resistance, and dyslipidemia
lipid protein analysia and metabolic profile with (increased trigly<lerides, decreased high-density lipo-
fasting glucose, glycosylated hemoglobin. and liver protein levels, and relatively high levels ofabnonnally
Chapter 4 I Nutrition • 89
TAIL! 4-3. Risk Fac1Drs for Obesity in Children syndrome. Other potential complications ofobesity
include depression, hypertension, obstructive sleep
j Overweight parent(s)
apnea, gallbladder disease, slipped capital femoral
l~.!c=
epiphysis, and early-onset puberty in females.
Treatment
ILow parental education level 1.,,_
Obesity is treated by setting reasonable goals for
~~t
the patient, by altering caloric intake/dietary habits,
developing a regular exercise program, reducing
!j Increased length atTV
childof 3 y viewing _1',,,':,_
screen time (television, video games, computers),
and behavioral modification (setting limits and
j Poor dietary choices monitoring self-control). Careful attention must
l..~--~~o/..~~~......................................................................................1 be paid to maintaining patients' growth and devel-
opment while at the same time reducing their BMI
dense low-density lipoprotein particles). Rates of over time. Surgical options and appetite suppressants
type 2 diabetes, cardiovascular disease, and fatty are currently considered inappropriate for use in the
liver disease are increased in patients with metabolic pediatric population.
KEY POINTS
• The American Academy of Pediatrics racom- • The healthy formula-fed Infant with presumed
mends exclusive breastfeedlng during the first cow milk protein Intolerance should be switched
6 months of life, with continued breastfeeding to a protein hydrolysate formula rather than one
through age 12 months. formulated with soy protein.
• Exclusively breastfed infants should be sup- • Most cases of malnutrition in developed coun-
plemented with 400 IU vitamin D beginning in tries are due wholly or in large part to neglect.
the first week of life. • Children with BMis greater than the 85th
• Newborns initially lose weight, but should percentile for age are considered overweight.
ultimately regain to their birth weight by the • Metabolic syndrome (obesity, insulin resistance,
third week of life. dyslipidemia, and hypertension) increases the
• Cow milk protein Intolerance can result In colitis rtsk tor the development of type 2 diabetes and
and poor weight gain. cardiovascular disease.
• The sporadic nature and sudden onset of colic
usually distinguish this condition from feeding
intolerance.
CLINICAL VIGNETTES
VIGNETtE 1 and urine output. His weight today is 2.37 kg. This is
the mother's first child and she has several questions.
A 6-day-old term newborn comes to your otnce for
a well-child visit. The Infant had no problems at birth 1. The mother Is concerned that her baby has
and was released from the hospital with his mother. lost weight since birth. How can this best be
His birth weight was 2.5 kg. The mother is exclusively explained?
breastfeeding every 1 to 2 hourt~ and each feeding takes L The infant is not receiving enough milk and
approximately 30 minutes. She feels that her milk has the mother needs to breastfeed more often.
come in and believes the breast empties after each b. The infant is not receiving enough milk and
feed. Today, the infant appears well with normal stools the mother needs to supplement with formula.
c. The infant is not receiving enough milk and the at meal times and mostly eats snacks during the day."
mother needsto feed for a longer period of time. In addition to her mother, the girl Is occasionally cared
d. The lnfan11a feeding appropriately, and there Is for by her grandmother IMng in the household as well
no reason to be concerned at this time. as a neighbor who "doesn't really cook.• Her mother
19Ceives Vlomen, Infants, and Chilchn (WIC) food cou-
2. The mother has always heard that breastfeeding
pons; however, she rarely utilizes 1hose for fruits and
is best. She wonders if she needs to supplement
vegetables because her daughter won't eat them. The
her breast milk with anything at this time. What
girl has no documented history of coughing, vomiting,
would most likely be your response?
gagging, drooling, or diarrhea. She was recently seen
a. The Infant does not need any supplements.
by her pediatrician for mild abdominal pain after not
b. The Intent needs 400 IU of vitamin D dally.
stooling for a week. Her mother was given a prescription
c. The Infant needs meats, fruits, and vegetables for polyethylene glycol at that time which she never filled
three times a day.
because the problem resolved on its own.
d. The infant should be supplemented with formula.
s. The mother retums at the infant's 2-month visit. 1. Based on the history given, this child's risk factors
She returned to work and stopped breastfeedlng for malnutrition include:
2 weeks ago. She Is feeding the Infant formula, L Low socioeconomic status
but Is concerned because she noticed streaks of b. Low birth weight
blood In his stool. Otherwise, the Infant has been c. Mental disability
well, and the mother has no other concerns. You d. All of the above
suspect milk protein intolerance. What would
2. Which of the following is the most likely nonorganic
most likely be your recommendation at this time?
reason for this child's poor growth?
L Start breastfeeding again.
L Incorrect preparation of formula
b. Replace the infant's formula with a soy-based b. Malabsorption
formula. c. Inadequate amount fed
c. Replace the infant's formula with a protein d. Abuse
hydrolysate formula.
d. Replace the Infant's formula with cow's milk. :l. The mother is asking if her recent issues with con-
stipation could be the causa of her malnutrition.
VIGNEITE2 What would be the best response?
A 4-year-old glrl ls brought Into your oftlce for a health L Yes, mild constipation that resolves without
supervision visit alter her preschool contacted family Intervention could be contributing to her growth
services. She was born full term at the 50th percentile trends and should be examined.
for weight and length. Her weight is cunently at the 5th b. No, although severe constipation can affect
percentile, wheruas her height is at the 85th percentile. appe1ile, mild constipation usually does not.
When asked about her growth, her mother is not con- c. Yes, malabsorption can present as constipation.
cerned. Her mother reports that Mshe won't sit down d. No, only vomiting can lead to malnutrition.
ANSWERS
VIGNEITE 1 Quesllan1 breast milk with formula. As previously noted, this

1.AnswerD: Infant's weight Is within a normal range for his age,
In 1his case, the mother appears to be feeding the infant and the mother Is breastfeedlng appropriately.
normally. Neonates 1ypically lose up to 10% of their
birth weight over the fim several days; formula-fed VIGNETlE 1 Quasllan 2
babies regain that weight by the second week of life, 2.AnswerB:
whereas breastfed babies maytake about a week longer. All infants require supplementation of vitamin D to
Healthy infanb automatically regulate intake to prevent rickets. The recommended value is 400 IU of
meet caloric demand for basic metabolism and growth. vitamin daily. This is almost always added to infant
Typically, infants feed on demand every 1 to 2 hours. formulas; however, exclusively breastfed infants require
This mother is feeding her infant in this manner. Thirty supplementation from birth.
minutes is sufficient time to empty milk from breasts. In Additional foods should not be added until 4 to 6
general, there are vary few Indications to supplement months of age, when the infant may begin to take baby
Chapter 4 I Nutrition • 71
food (cel'881, vegetables, fruits, and meats) by spoon. Nutrition Assistance Program or other early childhood
The infant is not developmentally ready to coordinate education programs can relnforoe nutrition education
swallowing solid foods until this time. Finger food Is and offer more stability to femmes. With a birth weight
added around 9 months of age. As previously noted, and length at the 50th percentile, she was average
this infant is suffic iently fed and does not require for gestational age. Given that she is 4 years old and
supplemental formula. attending preechool, a mental disability is unlikely.
VIGNETlE 1 Quldon 3 VIGNETlE 2 Qu..tlon 2

3.AnswerC: 2.AnswerC:
The infant's history suggests milk protein intolerance, The poor growth of this girl is likely due to a lack of
given that his symptoms started after beginning infant meal time feeding structure or a wide variety of healthy
formula. The first-line treatment is replacing the infant's foods. At an age where a caretaker should be guiding
formula with protein hydrolysate formula. types and amounts of food a child consumes, her care-
Infants who are being breastfed exclusively can givers seem to have a mora neglectful feeding style.
sometimes show signs of milk protein intolerance if the This results in lack of attention to the child's hunger
mother Ingests milk products. Even If the mother was not cues and forces the child to appropriately feed herself.
Ingesting milk products, she quit breastfeedlng several Because there Is no mention of the girt consuming
weeks ago. Breastfeedlng requires a demand to make formula and her age would suggest she would not be,
a supply, and It Is likely that the mother Is no longer It Is not expected that Incorrect formula preparation
able to produce milk. Soy-based formulas are nat the is the cause of her poor growth. Her mother denies
recommended treatment for milk protein intolerance. any symptoms of malabsorption such as vomiting or
Many patients with milk protein intolerance also have diarrhea. Although the family appears to have minimal
an intolerance to soy protein. Cow's milk is also not involvement in the feeding of the child, there is no
an option, as this is what is causing the intolerance. In mention of concern for abuse at this time.
babies without cow milk protein allergy, regular cow's
milk (rather than formula) is started at 1 year. VIGNETtE 2 Qu...ion 3
3.Answer B:
VIGNETIE 2 Question 1 Mild constipation is not uncommon in younger chil-
1. AnswerA: dren, especially those with Umlted variety In their
Families receiving WIC coupons qualify based on food choices. In most cases, mild constipation can
ftnanclal need. WIC Is designed as a supplemental be treated through diet modlftcatlon, Increased ftuld
nutrition program for low-Income women and children Intake, and stool softeners. Because the girt was
up to age 5. This program is nat supposed to provide able to stool without using the polyethylene glycol,
the entire souroe of food for a family. Low socioeco- her issues with constipatiOn appear to be minor. Mild
nomic status may impact access to nutrient-dense constipation is not likely to cause malnutrition. Given
food as well as sufficient amounts of food to feed a lack of vomiting, diarrhea, and abdominal pain,
those in the houaehold. Enrollment in the Supplemental malabsorption is unlikely.
Fluid, Electrolyte, and
pH Management
Natale V. Roebuck, Katie S. F11e, and Z. Leah Harris
An example of calculating maintenance fluid

INTRODUCTION
requirements for a 22-kg child is as follows:
Electrolyte homeostasis, fluid distribution, and pH
balance are critical to the maintenance of normal
Daily rate: (100 mL/kg/day x 10 ks) + (50 mL/
ksJday X 10kg) + (20mL/kg/day
physiology. Those organs that provide compensation
X 2 kg) = 1,540 mL/day
for disturbances in these systems (kidney, liver, gut,
skin) are less effective in infants because of their Hourly rate: 1,540 miJday + 24 hr/day =
relative immaturity. The younger the patient, the 64miJhr
more intolerant he or she is to challenges to these
systems, and the more careful physicians need to be
"4-2-1" Sho~cut method: (4 mL/hr X 10 kg) +
(2 miJhr X10 kg) +
introducing electrolyte and fluid challenges.
(1 miJhr X 2 .ks) =
At birth. free water accounts for 90% of body
62mL/hr
weight, largely because of proportionally higher
extracellular fluid (ECF) volume. Body composition For each 100 mL of maintenance fluids, a child
changes dramatically over the first year of life as needs 3 mEq of sodium and 2 mEq of potassium,
muscle mass increases. By 1 year of age, a child's as well as a carbohydrate source (dextrose). For the
total body water (TBW) approaches the adult level aforementioned example, the child would require
of 60CJ6 body weight. 46 mEq ofsodium (3 mEq X 1,540 mL/100) and 31
mEq of potassium (2 mEq X 1,540 mL/100) if you
were assuming no abnormal electrolyte losses. In
MAINTENANCE FLUIDS general, one.half normal saline with 5% dextrose
Fluid losses may be categorized as either sensible or (one-quarter normal saline with 10% in infants) and
insensible. Sensible losses include water and solute 20 mEq/L KCl meets maintenance electrolyte needs
lost from urine, stool, and other measurable losses. for healthy children and provides enough calories
Unmeasurable losses from slcin and lungs are clas· to prevent catabolism for a short period of time.
sified as insensible; in healthy individuals, these are Normal saline with 5% dextrose and 20 mEq/L KCl
relatively constant. Insensible losses can be estimated is often used in adolescents and adults, although this
at 500 rnL/m2 body surface area per day. provides more chloride than is required for mainte-
The amount of fluid needed to maintain normal nance needs. Ringer's lactate is a good alternative in
body function is directly related to caloric expendi· a child making urine with a normal chloride value.
ture, which, in tum, is related to a child's weight. The Children who require hospitalization, however,
Holliday·Segar method is useful for approximating may not have the same maintenance electrolyte
daily maintenance fluids: 100 mL/kg/day for the first needs as the previously described healthy child,
10 kg, plus 50 miJkg/day for the next 10 kg, plus 20 and "maintenance" intravenous (IV) fluids should
miJkglday for each additional kilogram thereafter. be prescribed with caution and close monitoring
The "4-2·1 ru1e• is often more practical to calculate of serum electrolyte values. Pediatric patients with
an hourly rate: 4 mL/kg/hr (.first 10 kg body weight), pulmonary or central nervous system (CNS) disease,
2 miJkglhr (second 10 kg body weight), and 1 mL/ and those in the intensive care unit (ICU) or postop-
kg/hr (each additionallcllogram). erative unit, are known to have a higher production
72
Chapter 5 I Fluid, Electrolyte, and pH Management • 73
of antidiuretic hormone (ADH) and therefore tend Hypotension, a sensitive early indicator in adults,
to retain water. making them at a higher risk for is a very late and ominous finding in children. The
hyponatremia. These children have been shown to dehydrated and acidotic child will compensate with
have a higher incidence ofiatrogenic hyponatremia respiratory alkaloais and hyperventilation (Kussmaul
when they receive hypotonic (0.2% or 0.45% normal respirations), important signs of systemic acidosis.
saline) as a maintenance fluid. rather than isotonic
(0.996 normal saline). The use ofisotonic 0.9% saline Diagnostic Evaluation
Serum electrolyte levels help guide the choit:e offluid
has not been shown to increased incidence of hy-
composition and the rate of replacement. Dehydra-
pernatremia or fluid overload. Therefore, although
tion may be isotonic, hypotonic (hyponatremic),
the above-mentioned math. holds true for most
or hypertonic (hypernatremic), depending on the
healthy children. recent studies have shown that it
nature of the fluid lost and the replacement fluids
is not always the case in hospitalized ch.il.dren. and
provided by the caretaker.
that isotonic (0.996 normal saline) is the safer and
more appropriate maintenance fluid in many cases.
Isotonic dehydration is the most common
form and suggests that either compensation has
DEHYDRAnON occurred or water losses roughly parallel sodium
Dehydration in the pediatric patient is usually sec- losses. Hypotonic (hyponatremic) dehydration is
ondary to acute losses, typically from vomiting and! defined by a serum sodium level that is lesser than
or diarrhea. Infants and toddlers are particularly 130 mEq/L. Children who lose electrolytes in their
.susceptible because of the limited ability of the im- stool and are supplemented with free water or very
mature kidney to conserve water and electrolytes, dilute juices may present in this manner. Hypertonic
and because of the child's dependence on caretakers (hypernatremic) dehydration (Na ~ 150 mEq/L) is
to meet his or her needs. When addressing dehydra- uncommon in children, but implies an excessive loss
tion. it is Important to consider maintenance fluid of free water compared with electrolyte loss (e.g.,
needs as well u replacement of the initial deficit diabetes i.n&ipidus).
and ongoing losses. Other electrolyte and osmotic abnormalities are
frequently present in dehydration states. Usually, the
Clinical Manlfe&tatlons serum bicarbonate concentration is decreased seoon.d-
Hlgtmy ary to metabolic acidosis from tissue hypoperfusion
A careful history limits the differential diagnosis and subsequent generation of lactate. Conditions
list and provides information concerning the acuity, with bicarbonate losses will result in acidosis with a
source, and quantity offluid lost, all ofwhich influence normal anion gap (see Metabolic Acidosis section).
treatment. Recent weight loss and decreased urine Conversely, prot:ract:ed vomiting may result in metabolic
output are important benchmarks of the degree of alblosis and a high bicarbonate level because ofacid
deficiency. The color, consistency, frequency, and lost from gastric secretions (see Metabolic Alkalosis
volume of stool and/or emesis may influence initial section). With significant dehydration, perfusion of
diagnostic and therapeutic measures. all organs is compromised. but serum biomarkers of
Many chronic medical illnesses may present acutely kidney impairment are most frequently tracked. This
with dehydration, including diabetes, metabolic will be reflected in elevations ofthe serum blood urea
disorders, cystic fibrosis, and congenital adrenal nitrogen (BUN) and creatinine (Cr) levels as glomerular
hyperplasia (CAH). Polyuria in the presence of filtration rate falls. A BUN/Cr ratio greater than 20 is
physical signs of dehydration may indicate diabetes consistent with intravascular depletion and prerenal
mellitus, diabetes insipidus, or renal tubular acido- failure. An isolated rise in BUN is suspicious for an
sis. Children who refuse to drink because of severe occult hemorrhage.
oropharyngeal pain may also become significantly
Treabnant
dehydrated.
Oral rehydration therapy (ORT) is the preferred
Physical Examination treatment for mild-to·moderate dehydration. The
There is no single physical or laboratory finding that World Health Organization recommends that ORT
will accurately assess a patient's degree of dehydra- solutions contain 90 mEq/L sodium. 20 mEq/L
tion (Table 5-1). It is important to remember that potassium, and 20 giL glucose. Commercial prepa-
a child's primary initial mechanism of compensa- rations that approximate these concentrations are
tion for decreased plasma volume is tachycardia. available. Free water may precipitate hyponatremia
TABLE ~1. Clinical Estimation of Degree of Dehydration

!..................
IWelgbt lou (")- <5
........
5-10
.....
> 10
1 WWSiprl
i Heart rate t tt
!Respiratory rate Normal Normal Jncreued
!Blood preuure Normal Normal (orthostulJ)
!Skin
1Capillary re8ll(s) <2 2-3 >3
i
j Mu.coWJ membrane& Nonnal/dry Dry Dry
i Anterior fontanelle Normal Depre11ed Depreued
i Eyes
ITearing Normal/absent Absent Absent
Appearance Normal Sunlc.en Sunken
Mental statu& Normal Altered Depreued
I.Jibi.Wues
Urine osmolarity 600 mO.m/L 800 mOsmJL Maximal
Urine specific gravity 1.020 1.025 Maximal
1Blood U11!8 nit.ropn <20 Elevated High
L~~~~~-······--. . . . .. . . --.. . . . . . . ...-.. . .~~~. . .... ........_ . _. . . .~.~~~--·-·-·. -~~~~'-~~~~~-. .-

.lnfanls w illelChibit gn~~~tBr weight loss per degree of dehydration (5% mild, 1~ mod~m~ta, 15% IICM!f9), whenlas adolescents will
exhbit less weight lOB& per degl88 of dehydration (3% mild, 5% to 6% moderate, 7% to 9% 88Y818).
and is contraindicated. ORT is labor intensive, re- milliliter with IV fluid comparable in ele<:trolyte
quiring small volumes offluid given very frequently, content to that being lost.
particularly in the child with nausea and vomiting. For example, an 18rkg infant with a normal serum
Administered correctly, it is extremely effective. sodium who is judged to be 10% dehydrated has lost
Severe dehydration leads to life-threatening hy- an estimated 2,000 mL offluid (1,000 mL = 1 kg). Half
povolemic shock. Children in hypovolemic shock the deficit is replaced over the first 8 hours, with the
should receive 20 m.L/kg IV boluses of isotonic balance given over the next 16 hours. Maintenance
fluid (normal saline or Ringer's lactate) until they therapy must also be included. The child received
produce urine and their blood pressure normalizes a 20-mL/kg bolus initially.
(see Chapter 20). Both fl.ulds are isotonic, resulting in
1. 2.000 mL/2 = 1,000 mL (one-half the total
improved intravascular volume without fluid shifts.
deficit); 360 mL (20 rnL/kg) has already been
The clinical estimation ofthe degree ofdehydration
replaced. Therefore, 640 mL is given over the
and serumelectrolyte studies tailor subsequent man- first 8 hours at 80 rnL/hr. This should be added
agement. More recent concerns over hyperchloremia
to the 56 mL/hr the child requires to meet
are resulting in a shift in practice and increased
maintenance needs. Rate = 80 mL/hr + 56
preference for Ringer's lactate.
mL/hr = 136 mL/hr.
Most deficits are replaced over 24 hours, with half
2. The second half {1,000 mL) is replaced over
given in the first: 8 hours and the rest over the next
the next 16 hours {63 mUhr) along with the
16 hours. One notable exception is the child with
maintenance rate (56 mL/hr). Rate = 63 mL/
hypernat:remic dehydration. in whom the deficit
hr + 56 mL/hr = 119 mL/hr.
should be replaced over 48 to 72 hours to prevent
excessive fluid shifts and cerebral edema. Ongoing The composition of the replacement Bu1d varies
losses (usually in stool) are replaced milliliter for depending on the initial laboratory values. N fluid
should not conblin potassium Witil the patient urinates. Treatment

Replacement of bicarbonate may be indicamd ifthere Dehydration is treated with fluid resuscitation as
is a known loss ofbicarbonate or ifthe pH and serum diJcussed previcrualy, with additional attention to the
bicarbonate levels remain dangerouslylow aftecinitial repJacementofthe sodium deficit. Hyponatremia due
isotonic boluses. Ingeneral. ongoing pstrointestinal (G1) to normal or inaeased TBW states such as SIADH or
losses are replaced with one-half normal sa1Jne. Urine renal failure requires fluid restriction and treatment of
electrolytE and osmolality studies should be obtainedif the underlying dJsorder.A.drenalinmffidencyi.s treated
ongoing losaes remit from an abnormal renal proreas. with fluid resUicitation and stress..cfose hydrocortisone.
Patients with profound hyperglycemia or elec- The cautious use of 3% hypertonic saline is limited to
trolyte disturbances due to an ongoing underlying life..threatening situations (Le., altered mental status,
pathologic process (e.g., diabetic ketoaci.dosis [DI<A]) seizures). Rapid correction to a serum sodium of 130
may require more specialized management discussed mEq/L is indicated and can be achieved with a 3 to 5
elsewhere in this text. mL!kg infusion of3% hypertonic saline. Once correcred
ID 130 mEq!L, the remaining serumsodiwn correction
HYPONAntEMIA should not exceed 1 to 2 mEq/Lihr because of there-
Hyponatremia (serum sodium level< 130 mEq/L) may ported risk ofcentral pontine myelinolysis (CPM)-a
occur in the face of deaeased. normal, or Increased condition that is often discussed but rarely apparent.
total body sodium content, re1lected in the volume
status of the patient. In children, the most rommon HYPERNATREMIA
settingis dehydration, a hypovolemic state. Euvolemic Hypernatremia is WlCOmmon in children in the
causes include a syndrome ofinappropriate secretion of absence ofdehydration. The infant with congenital
antidiuretic hormone (SIADH), adrenal insufficiency. diabetes insipidus frequently presents in thi.a manner.
and excessive free water intake (as can be seenwith the Either the lack of ADH or the kidney's inability to
dilution ofinfant formula). 0\ronic renal insufllclency, respond to the hormone results in inappropriately
congestive heart failure, and cirrhosis are volwne-e~t dilute urine and excessive free water loss. Signs and
panded states associated with hyponatremia. symptoms include muscle irritability, weakness, and
lethargy. Seizures and coma are the major complica-
Clinical Manlfe&tatlons
tions. Hypernatremic dehydration is treated with the
Hlgtmy Blltl PhyB/c81 Examlnstlon infusion ofisotonic saline. Serum sodium correction
The severity of clinical manifestations depends on should not exceed 1 to 2 mEq/Lihr because of the
both the level of sodium in the extracellular space risk: of cerebral edema.
and the rate ofchange from normal Falling levels that
occur over several days are better tolerated than rapid HYPERKALEMIA
losses. Anorexia and nausea are early, nonspecific Normal serum potassium values range from 3.5 to 5.7
complaints. Neurologic findings include confusion, mEq/L; a measurement of5.8 mEq/L or greater is con-
lethargy, and decreased deep tendon reflexes. Sei- sidered hyperlcalemia. In children, the most common
zures and respiratory arrest are late, life-threatening cause ofan abnonnally high potassium. level is artffiw.
complications that are more likely to be present as tual hyperkalemia, due ID hemolysis ofred cells during
serum sodium falls below 125 mEq/L. sample collection. This can be profound in patientswith
Diagnostic Evaluation leukemiaor very hJ8hlevels offragile cella that are prone
The laboratory workup of hyponatremia should to lyse in sampling. Transcellular shifts in hydrogenions
include serum electrolytes, glucose, BUN and Cr, inaease serum potassium without changing total body
serum osmolality, liver function tests, protein, and content; for every unit (0.1) reduction in arterial pH,
lipid levels. Urine studies can also be helpful. par- pJasma potassium increases 0.2 to 0.4 mEq!L. Disorders
ticularly specific gravity and urine sodium and Cr and medicati.ODJ that int:erfere with renal excretion of
concentrations. These laboratory values quantitate the electrolyt2 precipitate true hyperkalemia.
the severity of the deficit and may suggestan under-
Differential Diagnosis
lying cause. The measured serum sodium needs to
The common causes of hyperkalemia include the
be •corrected" in the setting of hyperglycemia. For
following:
every 100 mg/dL rise in glucose above a normal blood
glucose of 100 mg/dL, 1.6 mEq Na must be added to • Acidosis
the musured value to get the true serum sodium. • Severe dehydration
• Potassium-sparing diuretics (spironolactone) a valuable tool in the anuric patient with renal insuf-
• Excessive parenteral infusion ficiency and hyperkalemia. Cation exchange resins
• Renal failure (e.g., Kayexalate), loop diuretics (e.g., furosemide),
and hemodialysis are the only measures that actually
Other less common but important conditions to
remove potassium from the body.
comider include the following:
• Adrenal corticoiddeficiency (i.e., Addison disease) HYPOKALEMIA
• Renal tubular acidosis Hypoblemia in the pediatric population is usually
• Massive crush injury with rhabdomyolysis encountered in the setting of alkalosis secondary
• ~Blocker or digitalis ingestions to vomiting, the administration of loop diuretics
• Excessive supplementation (furosemide), or DKA. Signs and symptoms include
weakness, tetany, constipation, polyuria, and poly-
Clinical Manifestations
dipsia. Muscle breakdown leading to myoglobinuria
Paresthesias and weakness are the earliest symptoms;
may compromise renal function. ECG changes (pro-
flaccid paralysis and tetany occur late. Cardiac in-
longed Q-T interval, T-wave flattening) are noted at
volvement produces specific progressive electrocar-
levels :s;2.5 mEq/L; cardiac arrhythmias (ventricular
diogram (ECG) changes; T-wave elevation ("peaking")
tachycardia/fibrillation) can occur and are more
is followed by the loss ofP waves, widening QRS
likely if the patient is being treated with digoxin.
complexes, and ST segment depression (see Fig. 5-1).
Blood pressure changes and urine electrolyte content
Ventricular fibrillation and cardiac arrest occur at
assist in diagnosis {Fig. 5-2). Treatment consists of
serum levels greater than 9 mEq/L.
correcting pH (when increased) and replenishing
Treatment potassium stores orally or intravenously.
True hyperblemia represents a medical emergency.
Calcium gluconate infusion protecb the heart by HYPERCHLOREMIA
stabilizing the myocyte cell membrane. The infusion Chloride, an anion distributed across TBW, is an
ofsodiwn bicarbonate or insulin (and Jlucose) drives important regulator in acid-base balance, the trans-
potassium into the cells. Hyperventilation (alkalosis) mission of nerve impulses, and the dynamics offluid
prompts the transfer ofhydrogen ions out of the cell shifts. Normal serum chloride levels ratl8e from '77
inexchange Cor pot:assium ions, effectively lowering to 107 mEq/L. Abnormalities are rarely found in the
the serum potassium. Nebulized albuterol can also isolation ofother electrolyte disturbances as chloride
prompt the transfer of potassium into the cell and is homeostasis is maintained as a side effect ofsodium
homeostasis. Elevated levels of chloride are often
found in the setting of a normal anion gap meta-
SERUM K bolic acidosis. In pediatrics, this is seen in patients
Depressed ST segment with severe diarrhea, laxative abuse, proximal and
<2.5 mEq/l Dlphaslc T wave distal renal tubular acidosis, and long-tenn use of
Prominent U wave carbonic anhydrase inhibitors (e.g., acetazolamide).
~ PrnloogodQ-TI-.. Hyperchloremia is mo.st often encountered in the
Normal
postresuscitation phase of pediatric critical illness
after large amounts ofisotonic saline administration.
Hyperchloremia in patients with septic shock can
>6.0mEq/L ~ TaiiTwave
be associated with an increased risk ofacute kidney
injury. Symptoms are often attributable to the asso-
>75ofqA_~
ciated acid-base and electrolyte disturbances asso-
Long PR interval ciated with hyperchloremia rather than to chloride
Wide QRS duration itself. Treatment is typically aimed at correcting the
TallTwave
underlying condition or limltJns additional chloride
supplementation if possible.
_____A A Absent P wave
>9.0 mEq/l - V - Sinusoidal wave HYPOCHLOREMIA
FIGURE 5-1. EJec1rocardiogram findings consistent with Hypochloremia is also not typically found in isola-
-~--~-~-~-~p~~-~~-~--~-~~..~.Q:......................................................... tion. Low chloride levels are often due to balance
Hypolallamla
!
Blood preasure
B~
/ ~ Nwm~
1. RenOIIUCular dlaeasa 1. Renal tubular acidosis 1. Skin loleea

2. Excess renin 2. Fanooni syndrome 2. Galtrolnleltlnal
3. Congenital adrenal 3. Bartter syndrome lol8u
hyperplasia 4. Antibiotics a. Hlgh-carbohydl'llle
diet
4. Cushing tyndrome 5. Diunrtics
15. Exce8s mineralocorticoid
4. Enemllluatlw abuN
6. Alkaloala
5. Anorula nerYOea
7. Increased insulin
.~.~.~.~~.~.~..~~!~~!~..~~..~.1?.~~.~~.~:.....-.............................................................................................................................
ofblood pH and hydrogen ion homeostasis. Hypo- the energy source for cellular function. This can
chloremia is commonly associated with the state lead to si8nificant dysfunction in cardiac contrac-
of metabolic alk8losls, either primary (such as the tility, muscle weakness, hematologic and leukocyte
infimt with pyloric stenosis and severe vomiting) or dysfunction, stupor, coma, and death. Children who
secondary as with compensation from respiratory are malnourished and suffer from starvation or
acidosis, which is described in greater detail later eating disorders are at particularly high risk once
in this chapter. Within the pediatric population, it they are treated. It occurs as a result of refoeding
is most commonly found in patients with signifi- syndrome, where a patient receives nutrition after
cant GI losses from vomiting, patients with cystic a prolonged period of starvation or critical illness
fibrosis who have dysfunctional chloride channels, and his or her metabolism shifts from the utilization
or chronic respiratory acidosis. As with sodium, of fatty acids and amino acids to the production of
exposure to loop diuretics (e.g., furosemide) can glycogen, fat, and protein. The intracellular stores
precipitate renal wasting of chloride. of phosphate and other essential electrolytes (like
magnesium and potassium) are rapidly depleted.
HYPOPHOSPHATEMIA
Phosphate is an important polyatomlc ion found Treatment
The treatment of hypophosphatemia includes in-
in our bodies mostly in bone and intracellularly as
creased intake or supplementation of the mineral
adenosine phosphates (adenosine monophoaphate,
and ensuring nutritional content. It is also important
adenosine diphosphate, and adenosine triphosphate
to remove or reduce any offending drug exposures
[ATP]), as well as the building blocks of DNA and
like diuretics. In the case of refeeding syndrome,
RNA. Normal serum levels ofinorganic phosphorous
an important aspect of treatment is to stop or slow
range from 3.4 to 4.5 mg/dL. Hypophosphatemia
down the advancement of feeds until electrolytes
can occur in the setting of metabolic stress from
critical illness, malnutrition, treatment of DKA, normalize.
hyperparathyroidism, chronic diarrhea, or chronic HYPERPHOSPHATEMil
diuretic use.
Pathologic elevations in phosphate occur most fre-
Clinical Manif8Btations quently in the setting of renal dysfunction, but can
In critically low levels of serum phosphate, pa- also occur in hypoparathyroidism, the presentation
tients can experience symptoms associated with of DKA, crush injuries, and rhabdomyolysls with
decreased availability of the electrolyte to supply muscle breakdown. Where ofum even significant
elevations do not cause symptoms, severe and per- ACio-BASE PHYSIOLOGY

sistent hyperphosphatemia can lead to profound The ECF pH (the negative logarithm of the hydrogen
serum hypocalcemia as well as skin and systemic ion concentration) is maintained in a very narrow
calcificationwith severe itching. Treatment includes range (normal 7.4),Jargely as a result of the bicar·
avoldint; high phosphate- containing foods such as bonate buffer system. Hydrogen ions (H+) combine
milk, soda, and chocolate. Dlalysis is important to with bJcarbonate (HC03 - ) to form ~co,. whJch is
treat the patient with severe renal dysfunction. but transformed into water and CO:a (carbon dioxide).
it has only limited ability to reduce serum phos- Maintenance of the molecular components of this
phorous, and so phosphate binders (e.g., sevelamer buffer system is performed by the kidney6, which
and lanthanum) are also utilized to reduce systemic control excretion of HC011- , and the lung~, which
absorption. expire C02• The physiologic response to the challenges
of the acid-base equilibrium is termed "'compensa·
CALCIUM AND MAGNESIUM HOMEOSTASIS tion." The addition or production of excessive H+,
Calcium has several different functions in the body, the loss ofHC09 -, or abnormal renal or pulmonary
ranging from key roles in intracellular signaling and function can all affect this buffering system and lead
muscle contraction to providing the mineral matrix to acid-base disturbances.
of the skeleton. Calcium regulation and associated
disorders are discussed in detail in Chapter 15. METABOLIC ACIDOSIS
Like calcium, magnesium (Mg) is a divalent cation Metabolic acidosis (pH s 7.35) results from the loss
found both intracellularly and in the serum, as well of HCOa- or the addition ofH+ in the ECF. It is the
as cornplexed within the skeletal system. Magnesium most common acid-base disorder encountered in
is frequendy used as a cofactor in several enzymatic the pediatric population. Causes include increased
processes, notably those involved with the use and acid intake or production. decreased renal excretion
generation of ATP. It also plays a role in membrane of acid, and increased renal or Gl bJcarbonate loss.
potential, making it important in neuromuscular Respiratory compensation begins almost immediately
and cardiovascular function. Normal serum mag- as~ falls because of increased ventilation; maximal
nesium is typJcally 1.6 to 2.4 mg/dL, although about compensation is complete within 24 hours. In the
two-thirds of total body magnesium is stored within presence of a metabolic acidosis, Wmter's Formula
bone, where it is available for release when needed. can predict the expected Pac~ = 1.5 X HCOa- + 8
Hypomagnesemia can be a result of inadequate ( ±2). Ifthe measured Paco:a is higher than expected.
intake or absorption or increased renal losses. then there is a concurrent primary respiratory acido-
Depletion of magnesium frequently leads to both sis. Ifit is lower than expected. there is a concurrent
hypocalcemia and hypokalemia. Thus, the signs primary respiratory alkalosis (see Respiratory Acidosis
of hypomagnesemia can include neuromuscular and Alkalosis section).
irritability and tetany normally aHociated with hy-
pocalcemia. ECG changes such as flattened T waves Clinical Manifestations
and a widened QRS complex can be seen. Careful Hyperpnea is the most consistent clinical finding in
review of the patient's history and measurement of metabolic acidosis, as demonstrated by Kussmaul
serum and urine electrolytes can aid in the diagnosis breathing in DKA. Severe acidemia affects multiple
of the underlying cause, and replacement therapy is organ systems: cardiac contractility is impaired,
then tailored according to whether the problem is cardiac output is reduced, and the heart becomes
acute or chronic in nature. vulnerable to arrhythmias. Protein breakdown is
The kidney is able to excrete excess magnesium accelerated. and mental status changes occur. Other
easily, making hypermagnesemia a relatively uncom· signs and symptoms are specific to the underlying
mon problem. provided renal function is normal disorder. Important laboratory studies include serum
In&nts born to mothers receiving m.agnesi.um therapy electrolytes, BUN, Cr, glucose, venous or arterial
for preeclampsia or tocolysis frequently show signs blood gas, and urine dipstick for pH and glucose.
of hypermagnesemia at delivery, including muscle These studies help quantify the acidosis and may
weakness, respiratory depression. and lethargy. IV suggest the causative condition. The difference
calcium infusion may help mitigate the symptoms of between the sums of the measured cations (Na+ +
hypermagnesemia, but in cases of toxic overload or r ) and anions (Cr + HCOs- ), termed the anion
renal failure, hemodialysis may be necessary. gap, is normally 12 ± 4; Table 5-2 lists conditions
TAILI &-2. Changes in the Anion Gap

!.................
IHypokalemia
!Hypocalcemia Renal tubular acldoais
IHypomapaemla Hyperalimentation H~
j Hyperphosphatemia Hypoaldosteronl&m Hypoalbumin.emJa
' Lithium ingestion
: Methanol inpstion
IUremia/renal failure
!Diabetic ketoacidosis
!Pan.ldehyde lnpltion
1 Iron/Isoniazid Ingestion
IInborn errors of metabolism

j Lactic addosia
!Ethylene glycol, ethanollngeltion
~~
..~.~~~!.~.~~~.........................................................................................................................................................·-············-·······...········-············-············-··················-.!
mnemonic MUDPIL.ES Is helpful lor recalling several clinical conditions tho! 1'89Uit In metabolic adaosls With a high anion gap.
associated with changes in the anion gap. A normal chloride losses in the sweat. Other causes include
anion gap inthe setting of acidosis suggests GI losses laxative abuse and other chloride--wasting diarrheas.
of HC03 - or renal wasting, as in the case of renal Diagnosis and resolution of the underlying disorder
tubular acidosis. guide management dedsions. Volume expansion and
chloride replacement correct the alkalosis unless it
Treatment
results from disorders of mineralocorticoid excess
Management of the child with metabolic acidosis is (e.g., renal artery stenosis, adrenal disorders, steroid
tailored to correction ofthe underlying cause, espe-
use); potassium supplements are also necessary in
cially in cases with an elevated anion gap. Sodium
these cases. Complications ofsevere alkalosis include
bicarbonate therapy should be reserved for extreme
reduction in coronary blood flow and arrhythmias,
cases in which the serum pH is lesser than 7.0 and
hypoventilation, seizures, and decreased potassium,
the cause is unknown or slow to reverse (i.e., many
magnesium. and phosphate levels.
forms of normal anion gap acidosis). Boluses of
sodium bicarbonate are reserved for extreme situ-
RESPIRATORY ACIDOSIS AND ALKALOSIS
ations; in general. the infusion should be slow and
relatively isotonic. Patients receiving alkali therapy Normal Pa~ levels range from 35 to 45 mm Hg.
require frequent monitoring of blood pH, sodium., Any process that causes respiratory insufficiency
potassium, and calcium. Complica:ti.oru; include alka- (CNS depression, chest wall muscle weakness,
losis (overcorrection), hypokalemia. hypernatremial pulmonary or cardiopulmonary diseases) results
hyperosmolarity, and hypocalcemia. in C02 retention and a primary elevation in the
Pa~ termed •respiratory acidosis!' The kidney
METABOLIC AUW.OSIS responds by generating new bicarbonate in the
Metabolic alblosis (pH ~ 7.45) is much less common collecting duct and distal tubule, producing a rise in
than acidosis in children. "'Contraction• a.lkalosis the serum bicarbonate measurement (compensatory
results from the loss of fluid high in H + or as a.-, metabolic alblosis). This process is slower than the
may occur with protracted gastric vomiting (pyloric respiratory compensation that occurs in metabolic
stenosis, bulimia) or chronic thiazide or loop diuretic acidosis, taking several days to complete. Thus.
administration. Patients with cystic fibrosis may severe acidosis due to acute respiratory failure may
develop metabolic alkalosis because of excessive require ventilatory support.
Respiratory alkalosis results from a primary re- in an elevated respiratory rate. The kidney responds
duction in the Paco21 typically as a result ofincreased by increasing the urine bicarbonate concentration
ventilation. Common etiologies include hypoxia, (compensatory metabolic acidosis). Management
restrictive lung disease, medications (particularly consists mainly of identifying and treating the un-
aspirin toxicity), and CNS abnormalities that result derlying cause.
KEY POINTS
• Tachycardia is an early sign of dehydration • Serum sodium levels need to be •corrected"
in children. Hypotension occurs very late in in the setting of hyperglycemia.
children, and its absence does not rule out • Neither hyponatremia nor hypernatremia should
significant dehydration requiring intervention. be corrected too quickly because of the risk of
• If IV fluids are required, lnltlal20 mUkg boluses severe CNS complications.
of nonnal saline or Ringer's lactate should be • Hyponatremia can be rapidly corrected to 125
given until the patient's condition stabilizes. mEq/L to minimize seizure potential with 3%
• In the dehydrated child unable to take fluids saline.
by mouth, the fluid and electrolyte deficit • Progressive ECG changes associated with
must be replaced, In addition to providing hyperkalemia include peaked T waves, loss of
dally maintenance fluid and the replacement P waves, and widening of the QRS complex.
of ongoing losses.
• Emergent treatment for life-th!Mtening hyper-
• Recent literature supports the use of isotonic kalemia includes hyperventilation and calcium
fluid (0.9% normal saline) as maintenance fluid gluconate, sodium bicarbonate, and/or insulin/
in hospitalized children, particularly those who glucose infusion.
are In the ICU or are recovering from a surgical
• The equation Pac~ = 1.5 x HC08 - + 8 (±2)
procedure.
can help distinguish between primary and
• Potassium should not be added to replace- secondary metabolic acidosis.
ment or maintenance fluids until urine output
• An increased respiratory rate is the most con-
is assured.
sistent physical finding in metabolic acidosis.
• Hyponatremia in the pediatric patient is most
• IV NaHC03 (sodium bicarbonate) should be
frequently due to dehydration; other causes
used only when acidosis is severe or difficult
include SIADH, water intoxication, renal or heart
to conect and ventilation Is secured.
failure, and adrenal insufficiency.
CLINICAL VIGNETTES
VIGNmE1 refill and does not appear dehydrated. Her muscle

tone Is noticeably diminished with decreased deep
A 2-month-old female is brought to the emergency
tendon reflexes.
department for lethargy. The baby was born at
term and has been in good health until today. There 1. Which of the following is a good estimate of this
has been no fever or other sign of infection. Upon infant's daily fluid and electrolyte requirements?
reviewing the family's social situation, you discover L 220 ml water, 16.5 mEq sodium, 11 mEq
that they have recently become homeless and are potassium
•stretching out• the Infant's powdered formula to make b. 220 ml water, 6.6 mEq sodium, 4.4 mEq
It last longer. She weighs 5.5 kg (75th percentile). potassium
On physical examination, she Is thin and difficult to c. 550 ml water, 16.5 mEq sodium, 11 mEq
arouse. She is tachycardic but has brisk capillary potassium
d. 550 ml water, 6.6 mEq sodium, 4.4 mEq 2. Two days later, he returns to the emergency
potassium department with continued vomiting and now
1. 1,1 00 ml water, 33 mEq sodium, 22 mEq frequent watery diarrhea. He now weighs 10.8
potassium kg, his heart rate Is 145, and his blood pi'8SSUra
2. You ask the mother to clarify how she is preparing is 92/58. He has dry mucous membranes and his
the formula and learn that she is diluting the formula extremities are slightly mottled with capillary refill
to less than half its recommended concentration. at about 3 to 4 seconds. Which of the following
On the basis of this information and the presenta- fluids and routes is most appropriate for initial
tion of the baby, which of the following electrolyte management of this patient?
1. Oral rehydration solution in small, frequent
abnormalities Is most likely to be present?
volumes
L Hypocalcemia
b. Hyperglycemia b. One-half normaJ saline with 5% dextrose at
c. Hyponatremia 44 mLJhr
d. Hypomagnesemia c. One-half normal saline with 5% dextrose, 240
mlbolus
e. Hyperchloremia
d. 10% dextrose In water, 240 ml bolus
3. The Infant suddenly begins to have a generalized e. Normal saline, 240 ml bolus
tonic-clonic seizure. You and the staff begin
stabilization as laboratory results return: sodium 3. You opt to continue this patient's fluid and electro-
120 mEqll.., potassium 4.9 mEq/l., chloride 92 lyte management with IV rehydration. You plan to
mEq/4 bicarbonate 18 mEq/L, calcium 9.4 mgl replace half of his deficit over the first 8 hours and
dl., magnesium 2.1 mEqll.., and glucose 84 mgl the second half over the next 16 hours. What fluid
dL Which of the following is the most appropri- and rate will best replace his losses and account
ate method for correcting the electrolyte deficit for maintenance needs for the first 8 hours?
in this patient? a. One-half normal saline with 20 mEqll.. KCI and
1. Water restriction 5% dextrose, 45 ml.lhr
b. 2 ml.Jkg bolus of 10% dextrose in water b. Normal saline with 40 mEq/L KCI and 5%
c. IV normal saline at maintenance rate over a dextrose, 90 mLJhr
3- to 4-day pertod c. One-half nonnal saline with 5% dextrose,
d. Administration of desmoprassln 150 mllhr
1. Infusion of hypertonic saline d. Normal saline with 10% dextrose, 90 mllhr
t . Nonmal saline with 80 mEq KCI and 10%
VIGNET1E2 dextrose in water, 150 ml.lhr
A father brings his 18-month-old son to the emergency
department with a chief complaint of vomiting. The VIGNET1E3
child has had four bouts of emesis beginning this You are called to examine a 6-year-old gir1 in the
morning and has been able to take only a few sips of emergency department for a chief complaint of ab-
juice by mouth without vomiting. He has had no fever, dominal pain and fatigue. On taking the history from
but had one loose bowel movement just before arrival. the parents, you learn that the child has had urinary
His weight is 12 kg. On physical examination, you see frequency for several days, and today developed vague
an alert but tearful child. His heart rate Is 11 0 beats abdominal pain with nausea and vomiting. You note on
per minute (bpm) and blood pressure is 98162 mm entering the room that the child is sleeping deeply, but
Hg. His oral mucosa is tacky, his diaper Is wet, and breathing rapidly at about 30 breaths per minute. On
his abdominal examination is unremarkable. After a examination, you note tachycardia, delayed capUiary
thorough ravlew of systems and physical examination, rami, and dry mucous membranes and tell her parents
you feel he most likely has viral gastroenteritis. she looks dehydrated. This surprises them, as they
feel like •she Is always drtnklng.• A nurse brings you
1. Which of the following is the most appropriate the girl's urtnalysls results, which are strongly positive
initial approach to fluid and hydration manage-
for glucose and ketones. You decide to oonftrm your
ment in this child?
diagnostic suspicion with further laboratory testing.
L Water In small sips with a goal of 1.5 ozlhr
b. Electrolyte solution In small sips with a goal 1. The electrolyte panel returns with the following
of 1.5 ozlhr results: sodium 132 mmoVL, potassium 5.0 mmoi/L,
c. Electrolyte solution In small sips with a goal chlortde 104 mmoVL. and blcarbonate10 mmoVL
of 5 ozlhr What Is this child's anion gap?
d. Immediate IV access for fluid rasuscltatlon L4
e. Placement ofa nasogaatric tube for enl8nll feeding II. 8
c. 15 2. You obtain an ECG that raveals tall, peaked Twavas.

d. 23 The patient remains alert and without slgnlftcant
e. 42 distress other than his pain and weakness. Which
of the following Is the most appropr1ate next step
2. An arterial blood gas is obtained, with the following
in his management?
results: pH 7 .24, PaCo2 19 mm Hg, bicarbonate
8 mEqll, Pa~ 95 mm Hg. Which of the following
a. Infusion of calcium gluconate
b. Administration of furosemide
best describes this child's acid-base status?
a. Respiratory acidosis, compensated c. Infusion of sodium bicarbonate
d. Immediate hemodialysis
b. Metabolic acidosis, compensated
c. Respiratory alkalosis, overcompensated e. Consultation with a pediatric nephrologist
d. Metabolic acidosis with concurrent respiratory a The patient's ECG normalizes after Initial therapy.
acidosis Of the following therapeutic options for managing
e. Respiratory acidosis, uncompensated hyperkalemia, which ia the only intervention that
will actually remove excesa potasaium from the
3. A fingerstick blood glucose retums with a resun
body?
of 400 mgldl. What Impact, If any, does this
L Infusion of insulin and glucose
lnfonnatlon have on the previously reported
b. Nebulized albuterol
electrolyte resuns?
a. The sodium Is artificially low and should be c. Infusion of sodium bicarbonate
d. Infusion of calcium chloride
corrected to a value of 137 mEq/L.
b. The sodium is artificially high and should be
e. Administration of a cation exchange resin
corrected to a value of 127 mEq/L. VIGNETTES
c. The potassium is artificially high and should A 7-day-old tarnal a presents to the emergency depart-
be corrected to a value of 2.5 mEqll.
ment with 2 days of progressive vomiting, lethargy, and
d. The bicarbonate is artificially low and should
poor oral Intake. Parents report the baby being born
be corrected to a value of 16 mEq/L.
at 40 weeks gestation at 3.8 kg with no complications
e. There is no effect on 1he previously reported
and was discharged on day of life two, bruaatfeeding
results.
well w ith minimal weight losa. Current weight is 3.0
VIGNETTE4 kg and on physical exam, the infant is pale, lethargic,
tachypneic, and tachycardic. Further exam reveals a
A 16-year-old male Is admitted to the hospital w ith
capillary refill of 4 to 5 seconds and weak pulses. Her
rhabdomyolysls after starting football practices.
heart rate is 190 bpm and blood pressure is 50/28.
He had been having severe muscle pain for 3 days
before presentation but did not tell his parent or 1. Which of the following is the most appropriate
coach for fear of losing his spot on the team. He initial management in this child in shock after
had a particularly strenuous practice last night. access is obtained?
He was brought to the emergency department this L Attempt oral rehydration via syringe feedings
morning after finally telling his mother that he had in small, frequent volumes.
voided only a small amount of urine, which was b. Normal saline bolus, 76 ml
deep brown in color. He also complains of muscle c. One-half normal saline with 5% dextrose, 100
tenderness, as well as weakness which seems much ml bolus
worse than the previous day. The patient's initial d. One-half normal saline with 5% dextrose at
laboratory studies return with the following results: 12 mllhr
sodium 136 mEq/L, potassium 7.3 mEq/l, chloride e. One-half normal saline with 5% dextrose at
104 mEq/l, bicarbonate 19 mEq/l, BUN 38, Cr 2.8, 62 mllhr
glucose 138 mg/dl, calcium 8.4, magnesium 1.9
2. You obtain laboratory values that reveal sodium
mEq/l, phosphate 5.1 mEq/L, and creatine kinase
132 mmoVL, potassium 5.6 mmoVL, chloride 89
30,000.
mmoVL, bicarbonate 14 mmoVL, and glucose
1. Which of the following metabolic disturbances 38 mgldl, making you concerned for salt-wasting
notable in this patient presents the greatest risk congenital adrenal insufficiency. In addition to
tor immediate, life·thraatening complications? hydrocortisone, what additional therapy Is urgently
a. Hyperglycemia Indicated In this Infant?
b. Elevated Cr a. Dextrose and Insulin Infusion for hyperkalemia
c. Hyperkalemia b. Sodium bicarbonate infusion for correction of
d. Hypocalcemia hyponatremia and acidosis
e. Hyperphosphatemia c. Cation exchange resin for hyperkalemia
d. 1 oz ORT every hour for hypoglycemia is corrected too rapidly, what life-threatening
e. 15 ml 10% dextrose In water for hypoglycemia complication Is he at risk for?
L Cerebral edema and CNS dysfunction
3. Following your interventions, the infant's exam
b. Ventricular arrhythmias such as ventr1cular
improves, so that the heart rate is now 155
fibrillation
bpm, blood pressure 70/40, capillary refill 3 to
c. Renal failure
4 seconds, and the baby is crying and much
d. Hyperkalemia
more vigorous. Which of these choices is the
approptiat e initial fluid prescription to provide
e. CPM
for rehydration? 2. After Initial 20 mllkg normal saline bolus, you
L Normal saline with 5% dextrose at 12 mL/hr begin rehydration over the next 2 days. Which
b. On~half normal saline w ith 20 mEq/L KCI at of the following Is the fastest allowable rate at
56 mL/hr which to decrease hie serum sodium over this
c. Normal saline with 10% dextrose at 56 ml/hr time period?
d. Normal BBiine with 5% dextrose at 65 mL/hr 1. 2 mEq/L decrease every 6 hours
e. On~half normal saline with 20 mEq/L KCI at b. 2 mEq/L decrease every 1 hour
12 mllhr c. 5 mEq/L decrease every 2 hours
d. 2 mEq/L decrease every 12 hours
VIGNETTE& e. 4 mEq/L decrease every 12 hours
A previously healthy 5-year- old male is brought into
3. His stool tests positive for giardia infection and
the emergency department with 4 days of watery
treatment is started. You expect him to have
diarrhea after a camping ttip. Parents report he has
ongoing watery stool losses until hie treatment is
been having 10 to 16 watery stools per day and par-
effective. In addition to administering maintenance
ents have encouraged drinking many sports drinks to
fluid and calculating rehydration fluid, how should
keep up with his losses. He Is 18 kg. Physical exam
your treatment account for additional stool losses
shows he Is tired, but Interactive wtlh exam, he has
while you treat his infection?
a soft abdomen, and a heart rate of 120 bpm at rest,
1. Add an additional10 mllhr one-half normal
with a blood preeaure of 98185 and a capillary refill
saline to the continuous infusion.
that is leas than 3 seconds. Parents are concerned
b. Have the patient drink ORT every hour to
that the diarrhea is persistent and his urine output
replace stool losses.
has decreased the past day. Your exam is consistent
with mild dehydration due to infectious diarrhea so
c. Replace stool milliliter tor milliliter wllh one-quarter
normal saline w ith 20 mEq/L KCI until stool
labs are sent.
output decreases.
1. The electrolyte panel returns w ith the following d. Replace stool milliliter for milliliter via IV with
results: sodium 154 mmolll, potassium 3.2 mmoVL. Ringer's Lactate until stool output decreases.
chloride 120 mmoi/L, bicarbonate 16 mmoi/L, e. Have the patient drink milk milliliter for milliliter
and glucose 98 mgldL. If this patient's sodium every hour to replace stool losses.
ANSWERS
VIGNETlE 1 Question 1 VIGNETTE 1 Qu...lon 2

1.AnswerC: 2.AnswerC:
Maintenance fluid requirements can be estimated on Dilution of formula is an unfortunate cause of hypo-
the basis of body weight using the Holliday-Segar natremia in infants. The electrolyte imbalance results
method . An individual requires 100 mUkg/ day for from a combination of immature kidney function and
the first 10 kg of body weight, 50 mllkg/day for excessive free water intake. The symptoms of hypo-
the next 10 kg, and 20 mUkg/day thereafter. This natremia may be subtle but become more apparent
patient, weighing 5.5 kg, requires 100 x 5.5 = 550 as the deficit grows. Hypotonia and hyporeflexia are
ml daily. Sodium and potassi um are estimated common. Lethargy (confusion in older children) may
on the basis of this fluid requirement. For every also be seen. Seizures and coma are late findings and
100 ml fluid per day, 3 mEq sodium Is required Imply a huge sodium deficit.
(5.5 x 3 = 16.5) and 2 mEq potassium Is required Both hypocalcemia and hypomagnesemia are
(5.5 X 2 = 11). characterized by hyperreflexia and paresthesias.
Hyperglycemia may go undetected in children and VIGNETTE 2 Quesllan 2

adults, with fatigue and polyuria being the most com- 2.Answer E:
mon signs. Hyperchloremia Is typically asymptomatic The child in the vignette is appropriately assessed as
and Is either the result of concomitant hypernatremla being moderately dehydrated. His somnolence and
or a loss of bicarbonate ~n the case of a metabolic tachycardia with normal blood pressure suggest that
acidosis with a normal anion gap). he is already in compensated hypovolemic shock.
Correction ofdiminished intravascular volume is best
VIGNETTE 1 Questlan 3 accomplished with bolus infusions of isotonic fluid,
3.Answer E: such as normal saline or lactated Ringer's. Colloidal
In cases of hyponatremia that have progressed to solutions such as albumin can also be used. Twenty
milliliter of fluid per kilogram of weight should be used
serious CNS symptoms, such as seizures or coma, the
use of hypertonic saline tc rapidly increase the serum as an initial volume expanded; repeat boluses may be
sodium is indicated. Raising the serum sodium by 4 necessary tc stabilize the patient.
Oral rehydration Ia effective In a mildly to moderately
to 6 mEq will typically stop seizure activity. Correction
should progress slowly from that point at a rate of dehydrated patient who Is stable, but Is not appro-
about 10 mEqlday to avoid CPM. priate for a hypovolemic patient who requires rapid
Water restriction Is useful in the 1reatment of hypona- intravascular expansion. Likewise, placing the child on
tremia resulting from SIADH but not for a solute-depleted maintenance IV fluids does not provide the necessary
s1ate as is presented here. The prevision of dextrose volume to stabilize the patient. The fluid chosen for
intravenously is appropriate in symptomatic hypogly- volume replacement should not contain dextrose.
Dextrose is rapidly taken up by the cells, resulting in
cemia, which can present with seizures, but this child's
glucose level Is normal. Slow correction over 2 to 3 days an effectively hypotonic solution that could lead to
Is a good strategy for managing hyponatremia without complications, including cerebral edema.
severe neurologic symptoms but will not acutely help
this patient. Desmopressln (a synthetic form of ADH) VIGNET1E 2 Qu88tian 3
will decrease the sodium further as it increases water
3.AnswerB:
reabsorption in the renal collecting ducta.
A plan for IV 1'8hydration begins with the calculation
of maintenance needs. On the basis of his 12-kg
VIGNETTE 2 Questlan1 •rehydrated" weight, he requires 1,100 mUday, or
1.Answer B: about 45 mllhr, for maintenance (100 ml.Jkg for the
The child described In the vignette Is certainly at risk ftrs11 0 kg, 50 mllkg for the next 2 kg). Sodium and
for developing dehydration, but at this point he can potassium requirements for the day ara 33 and 22 mEq,
only be described as mildly dehydrated. His vital respectively (3 mEq per 100 ml fluid for sodium and 2
signs are all within normal limits and he continues to mEq per 100 ml fluid for potassium); 33 mEq sodium
produce tears and urine. The preferred method for per 1,1 00 mL is equal to 30 mEq!L, or approximately
fluid management in this scenario Is the use of an oral one-fifth normal saline, and 22 mEq potassium per
solution to provide maintenance fluid and electrolytes. 1,100 mL is equal to 20 mEq/L.
Many commercially prepared solutions are available Next, the deficit must be accounted for. Using his
for use. The child's hourly maintenance fluid rate as weight loss as a guide, his deficit is approximately
estimated by the Holliday-Segar method is (1 00 mU 1,200 ml, which is divided into two 600 ml deficits for
kg x 10 kg + 50 mUkg X 2 kg)/24 hours = 46 mU your plan. A total of 240 ml was given as bolus fluid,
hr, which is approximately 1.5 oz (30 ml = 1 oz). It is so 360 ml remains to be given over the firs1 B hours,
reasonable tc monhor the parent's ability to provide resulting In an additional 45 mllhr. Adding this to the
the solution In the acute care setting. If the child tol- maintenance rate gives a total rate of 90 mllhr.
erates the solution without vomhlng, he or she can be Eleclrolyte content In a replacement fluid for a de-
discharged home with cloee follow-up. hydrated patient is estimated on the basis of the nature
Pure water should not be used for maintenance of fluid losses. In general, isotonic dehydration from Gl
hydration, as it lacks the solutes needed for homeo- losses rasutts in electrolyte deficila comparable to a fluid
stasis and can precipitate hyponatremia. A goal of 5 between half normal and normal saline. The use of normal
oz every hour is excessive and might precipitate more saline is a good approximation ofthe final fluid accounting
vomiting in this case. Nasogastric administration of for both the deficit replacement and maintenance needs.
fluid or formula is not recommended, and it would be .Additional potassium above maintenance needs can
unreasonable to expect the parent to maintain the be added to the fluid to account for potassium losses,
tube as an outpatient. IV fluid hydration would be but should not exceed 40 mEqll.. in acute dehydration
appropriate if oral rehydration fails, but is not firs1-line in a patient who is making urine. Five percent dextrose
tr&atment in cases of mild dehydration. is added as a caloric substrate to pt'8\fent catabolism.
VIGNETTE 3 Quesllan 1 confounded by hyperglycemia in the case of sodium.

1. Answer D: In truth, whole-body potassium Is depleted as a result
The anion gap conceptually represents the unmeasured of the child's diuresis, but potassium Is shifted to the
anions in the serum. The anion gap is calculated aa extracellular space as a result of the ongoing acidosis.
the difference between the measured cations (sodium The acidosis likewise depletes serum bicarbonate, but
and potassium) and anions (chloride and bicarbonate). measurement of this and potassium are both accurate
In the aforementioned example, the gap is (132 + 5) in the setting of hyperglycemia.
- (104 + 10) = 23. The anion gap is typically 12 ±
4. This patient has a high anion gap; the differential VIGNETlE 4 QuKIIon 1
diagnosis for an elevated anion gap in the setting of 1.Answarc:
acidosis can be found in Table 5-2. Rhabdomyolysis and resultant acute renal failure can
be responsible for alterations in many electrolytes.
VIGNETTE 3 Quesllan 2 Although all of the answer choices are present in this
2.AnswerB: scenario, it is hyperkalemia that should be considered a
The determination of an acid-base abnormality Is greatly medical emergency. Initial symptoms of elevated serum
aided by the clinical scenarto. Polyuria, polydipsia, and potassium Include weakness and pal'881heslas of the
hyperglycemia are symptoms suggestive of type 1 diabetes extramltles. Untreated, It can lead rapidly to ventricular
mellitus, and in this case, ketonuria and decreased pH tachyarrhythmlas and cardiac 81T81t.
lndicab:l that the child is in DKA. The blood gas should Hyperglycemia Is common In patients with severe
be evaluaiBd with this information in mind. The reduced illnees, but is not life-threatening. Serum Cr is a useful
pH indicatBs an acidemia, and decreased bicarbonate marker to eetimate renal function and, when elevated,
and~ suggest that the process is metabolic in origin. suggests renal insufficiency. This patient's renal failure
Appropriate respiratory compensation can be determined must be addressed as it likely is contributing to hyper-
with the fcnnula Pro.! ± 2 = 1.5 x bicarbonate + 8, which kalemia, but management of the potassium must be
is satisfied in this example. Although mixed acid-base handled first. Hypocalcemia and hyperphosphatemia
derangements are common, a concurrent respiratory are frequently encountered in rhabdomyolysis, as free
acidosis with this patient's metabolic acidosis would serum calcium binds to damaged muscle fibers and
result In a higher ~ than would be expected on the phosphate Is released from the muscle cells. Hypocal-
basis of the aforementioned formula. cemia may also lead to widening of the QRS complex
A respiratory acidosis would result In an elevated and development of arrhythmias, but not as acutely
Peat on blood gas analysis. Acute renal compensa- as In cases of hyperkalemia. Hyperphosphatemla can
tion for a respiratory acidosis results in an increase worsen acidosis, but not to a life-threatening extent.
in bicarbonate concentration by 1 mEq/L for every
10 mm Hg rise in P~. Maximal compensation over VIGNETTE 4 Qua.tlon 2
3 to 4 days allows an increase in the bicarbonate 2. Answer A:.
concentration of 4 mEq/L for every 10 mm Hg rise in ECG changes in a patient with hyperkalemia are
Peat. Although a respiratory alkalosis would resuH in ominous findings requiring immediate intervention.
a decreased Pc.».! and bicarbonate, the kidneys will The earliest sign of cardiac involvement is typically
not "overcompensate" for the alkalosis. the development of peaked T waves, followed by the
disappearance of P waves and widening of the QRS
VIGNETI'E 3 Question 3 complex. Ultimately, a sinusoidal pattern or ventricular
3. Answer A:. fibrillation evolves if the hyper1<alemia continues.lhe
Extreme alteration in serum solutes can disrupt routine stabilization of cardiac muscle cell membranes is
laboratory testing, particularly In the case of sodium. accomplished with the Infusion of calcium salts and
In the case of hyperglycemia, the sodium Is artificially should be the first prlortty In treating the hyperkalemia.
low. The value can be corrected by adding 1.6 to the Diuresis with furosemide In the healthy patient can
measured sodium value for every 100 mg/dL glucose decrease potassium, but does not have any immediate
above the normal value of 100. In the above-mentioned benefit in stabilizing the patient. Sodium bicarbonate
example, this results in a value of 4.8 added to the temporarily drives potassium from the serum into the
measured sodium, or a corrected sodium of 137 intracellular space by treating the acidosis, but does
mEq/L. Additional states in which the measured not reduce myocardial excitability. Hemodialysis is one
sodium is artificially low include other hyperosmolar method by which excess potassium can be removed
states, such as in the administration of mannitol, or in from the body, but is reserved for cases in which
hyperproteinemia or hypertriglyceridemia. medical management and temporizing measures fail.
The child with DKA, as in the vignette, suffers from The patient in the vignette may require the attention
several electrolyte derangements. However, labora- of a specialist for his acute renal injury, but needs
tory measurement of the serum electrolytes is only immediate therapy for his current condition.
VIGNB'TE 4 Question 3 fluid rate as estimated by the Holliday-Segar method

3.Answer E: is (100 ml.lkg X 3.8 kg)/24 hours = 15.8 mllhr. His
Once cardiac membrane potentials have been 1961ored deficit Is estimated by the difference In presentation
with IV calcium, potaaaium must be shifted out of the weight from birth weight and Is 800 ml, divided Into two
ECF space, either into the cells or out of the body. A 400 ml for the purposes of rehydration calculations.
cation exchange resin, such as Kayexalate, can be given Initial bolus fluid of 76 ml means you will be replacing
orally or rectally to eliminate potassium from the colon. an additional 324 ml over the next 8 houra, making
Hemodialysis or hemofiltration can also be used to the additional rat e of 40.5 mUhr, and a total rate of
remove potassium but carry higher risk, require greater approximately 56 mLJhr. Ten percent dextrose fluid is
resouroes, and thus are reserved for extreme situations. appropriate for a neonate, given the higher glucose
Both insulin and albuterol stimulate the action of the infusion rates needed to maintain normoglycemia,
sodium-potassium ATPase that exchanges intracellular and isotonic fluid should be provided in the setting
sodium for extracellular potassium. These affects are of hyponatremia and rehydration.
temporary, and excess potassium will eventually return
to the serum. Sodium bicarbonate Indirectly acts to VIGNETlE B Quesllan 1
lnci'88Se the sodium/potassium gradient by relieving 1.Answerk
acidosis and thus Improves the exchange. Galcium Although many of this patient's electrolytes are
chloride can be used to reduce myocardial excitability noted to be abnormal, the sodium derangement puts
but has no effect on the serum potassium directly. him at high risk if this abnormality is corrected too
quickly. Cerebral edema and CNS dysfunction are
VIGNmE 5 Q...Uon 1 the most common complications of rapid correction
1.AnswerB: of hypernatremia due to fluid shifts from extracellular
The child described in the vignette has vital signs and to intracellular space in an effort to maintain sodium
delayed capillary refill concerning for shock. The most homeostasis. Ventricular arrhythmias can occur with
appropriate rasponM to this child in shock is to provide rapid potassium infusion. CPM occurs with rapid
rapid ftuid resuscitation in the fann of a crystalloid ftuid correction of hyponatremia, but can depend on the
bolus of 20 ml.Jkg of normal saline. (Remember: AJ~ rate of rise and length of chronicity of the electrolyte
Breathlng -Cin::ulatlonl~ An attempt at oral rehydration disturbance.
would likely be unfeasible In a lethargic chUd with poor
oral Intake and would not provide appropr1ate c:trculatory VIGNETlE 6 Quedan 2
support. Hypotonic fluid should never be uaed for volume 2.AnswerB:
resuscitation, given the risk of rapid sodium shifts. The maximum speed at which you can safely correct
a sodium derangement is a change by 2 mEq/L every
VIGNB'TE 5 Q...Uon 2 hour; however, many providers will calculate the free
2.Answer E: water deficit and rehydration In order to correct the
CAH is a group of autosomal recessive diseases that sodium no faster than 1 mEqll every hour, because
can present at many ages because of excessive or of the profound risk of CNS injury.
deficient production of steroids. The most classic, 21-hy-
droxylase deficiency, Is a salt-wasting CAH. Patients VIGNETlE B Question 3
often present at 1 to 2 weeks of life in adrenal crisis 3.Answer D:
with hypovolemic shock and electrolyte abnormalities. Ongoing Gllosses must be accounted for by directly
In addmon to supportive care, these children require replacing output with fluid that contains a similar
stress doses of mineralocorticoid and glucocorticoid content of electrolytes. Diarrhea typically contains
replacement, typically In the form of hydrocortisone. approximately 40 to 110 mEq/L sodium, 10 to 110
Severe hypoglycemia can lead to lethargy, seizure, mEq/L chloride, 10 to 80 mEq/L potassium, and 30
and coma and should be reversed quickly while the mEq/L bicarbonate. Ringer'S lactate contains similar
steroids are being supplemented. IV supplementation concentrations of sodium and potassium as what is
with dextrose in water can be administered using a being lost and is an ideal Gl replacement fluid for di-
shorthand "rule of 50.• Administer 2 to 4 mL.Jkg of arrhea or emesis. Sometimes, additional bicarbonate
25% dextrose or 5 mllkg of 10% dextrose to bring needs to be provided to account for the bicarbonate
the serum glucose back into a normal range. Many lost in severe diarrhea affecting acid-base balance.
times, continuous dextrose containing fluids will need Patients with ongoing Gl distress typically cannot
to be started to maintain normoglycemia. tolerate enteral rehydration or replacement right
away, and sometimes this can lead to a worsening of
VIGNB'TE 5 Question 3 osmotic diarrhea or malabsorption following Infection
3.Answer C: especially If the patient Is given high sugar-containing
The calculation of maintenance needs forth Is Infant Is juices during recovery. It Is bast to use the gut when
based on his birth weight. The child'S hourty maintenance symptoms have Improved.
Pulmonology
Maria V. T~uevara, Susanna A. McColley, and Katie S. Fine
Respiratory d.i.seues are among the leading causes of 5 to 6 years). The data generated are dependent on
death in young children worldwide, and respiratory patient effort and technique, and training ofsubjects
symptoms are a complaint in a majority of pediatric is necessary before reproducible data are obtained
sick visits. Although these .symptoms are usually In older children, microscopic examination
related to acute (most often viral) infection, they and culture of expectorated sputum may yield
may be a consequence of congenital or acquired important information, although the results are
pulmonary disorders. Respiratory disorders specific often somewhat equivocal due to contamination
to the newborn period (including bronchopulmonary of the specimen with saliva or upper airway secre-
dysplasia) are discussed in Chapter 2. tions. Oropharyngeal swab cultures are utilized for
The primary function of the lungs ill the excllange monitoring patients with cystic fibrosis (CF), but
of oxygen and carbon dioxide between the blood and neither oro- nor nuopharyngeal swabs are indicated
the atmosphere. Many abnormalities can affect thia in other conditions.
exchange adversely, including airway ob!ltruction, Bronchoscopy-the direct visual examination of
restrictive lung disease (reduced compliance of the the airways-ill a powerful diagnostic tool for the
lungs and/or chest wall), ventilation-perfusion mis- evaluation ofairway structure and dynamics, as well
match, and abnormal respiratory control Effective as to obtain specimens from the lower airways. Rigid
respiration requires proper interaction between or flexible instruments of appropriate size may be
the respiratory, cardiovascular, and central nervous used. In general, flexible instruments are best for
systems, with adequate support from the musculo- evaluation of the bronchi (but not for extraction
skeletal system. of aspirated foreign bodies) and airway dynamics;
rigid instruments, preferred for evaluation of the
larynx, give a more detailed image of diatal airways,
DIAGNOSTIC TECHNIQUES IN but anatomic distortion occurs because the rigid
PEDIATRIC PULMONOLOGY instrument does not follow the anatomic pathway
A standard chest radiograph is a vitally important tool (and it ill necessary to extend the neck and lift the
in the evaluation ofchildren with respiratory disor- mandible/tongue base). Aspirated foreign bodies are
ders. Airway films provide visualization of the trachea typically removed via rigid bronchoscopy.
and nasopharyngeal airway. Computed tomography
{CT) studies yield more detailed information and
UPPER AIRWAY OBSTRUCTIVE
can be combined with vascular contrast. Radiation
DISEASE
dosage should be considered before ordering a CT
scan. The images obtained are influenced by body The upper airway extends from the nostrils to the
position and stage of inspiration or exhalation. thoracic inlet. In general, obstruction of the upper
Pulmonary function testing measures lung vol- airway leads to ilupimtory obstruction and aasociated
ume and rates of airflow, permitting assessment of abnormal inspiratory breath sounds such as strldolf
lung capacity and airway obstruction. Pulmonary whereas obstruction below the thoracic inlet results
function tests (PFTs) are generally performed only in ~iratory obstruction and abnormal breath sounciA
in patients old enough to cooperate (older than age .such as wheezing.
UPPER AIRWAY OBSTRUCTION IN THE specific structures involved, the degree of muscle
NEONATE/YOUNG INFANT tone, and the rate of air flow. In general, obstruction
Choanal atresia or stenosis (narrowing of the nasal in the subglottic space results in a high-pitched,
passages) can be life-threatening in newborns. who monophonic stridor. Obstruction above the glottis
are obligate nose breathers. Maruh'bular hypoplasia produces a more variable, often fluttering stridor
results in posterior displacement of the tongue that typically varies considerably with position of
(glossoptosis). Some children (typically those with the head and neck. Upper airway obstruction is
genetic or metabolic conditions such u trisomy 21 often more pronounced during feeding and activity,
or hypothyroidism) have large, obstructive tongues especially in neonates.
(~n~Jcrogl0$8ia). Vocal cord paralysis can be unilateral Diagnostic Evaluation
or bilateral, and congenital or (more frequently) Diagnostic evaluation of upper airway obstruction
acquired. Laryngeal webs are uncommon congenital involves assessment of the severity ofthe physiologic
lesions, part of the spectrwn oflaryngeal atresia, and disturbance and identification of the etiology of
are often a.ssoclated with respiratory symptoms, The the obstruction. Physiologic studies include pulse
severity of symptoms is related to the degree of the oximetry (which measures oxygen saturation in
airway obstruction caused by laryngeal webbing, peripheral blood) and blood gas analysis (which
and may initially present as respiratory distress in also measures blood pH and carbon dioxide level).
the delivery room that resolves following intubation. During severe obstruction, oxygen saturation can
Laryngomalacia due to redundant and floppy remain within normal limits despite a signiftcant
supraglottic structures is the most common cause of rise in carbon dioxide levels. Patency of the nasal
congenital stridor. Signs and symptoms often occur airway is confirmed by passage ofa suction catheter
within the first 2 weeks of life, but presentation. through each noatril or by instillation of radiographic
progression, and outcomes are variable. Although contrast material Radiographs of the nasopharynx
symptoms usually resolve with growth over the first 1 and neck can be helpful. but flexible bronchoscopy
to 3 years oflife, severe cases can be associated with is often required to definltively evaluate the anatomy
dysphagia, failure to thrive, dyspnea, cyanosis, and and dynamics of the upper airway. The sound of
even cardiac failure, and may require repair. Sub- the cough can yield important clues-the absence
glottic masses (hemangioma or cyst) often present in of a sharp •gtottalstop" (often noted by parents as a
the first year oflife. Ha1f ofchlldren with subglottic weak cough) indicates that the vocal cords cannot
hemangioma have a cutaneous hemangioma. although close normally.
most children with cutaneous hemangioma do not
have airway involvement. Subglottic stenosis is rarely Treatment
congenital; acquired stenosis should be considered in The treabnent of upper airway obstruction depends
any child who has been Intubated, even briefly. It is on specific findings. Following definitive exclusion
typically characterized by a narrowing of the upper of more serious pathology, most in&nts with laryn-
airway extending from just below the vocal folds to gomalacia or unilateral vocal cord paralysis may be
the lower border of the cricoid cartilage and is best periodically monitored without specific intervention.
assessed by rigid airway endoscopy. Children pre- Ifthe airway obstruction is severe (e.g., hypoxemia,
senting in the first year oflife with persistent stridor failure to thrive, feeding clJfficulties), provision ofan
and/or hoarseness most commonly have either vocal artificial airway and/or other surgical intervention
cord paralysis or laryngeal papillomatosis. Vascular may be warranted. In these cues, tracheostomy
compression of the trachea at the thoracic inlet by provides an effective and safe solution until more
an anomalous vessel or vascular ring is a relatively definitive treatment can be provided.
common cause of upper airway obstruction in the
UPPER AIRWAY OBSTRUcnON IN THE
first year oflife.
OlDER CHILD
Clinical Manifestations Children beyond the first year of life may have
Clinical manifestations of upper airway obstruction upper airway obstruction as a result ofa congenital
1nclude noisy inspiration, increased work of breath- lesion, but acquired lesions are much more likely.
ing (nasal flaring, the use of accessory muscles), and Large adenoids and tons.iJs often result in inspira-
retractiollll (often suprasternal). The character and tory obstruction, with symptomatic exacerbations
intensity of the noise depend on the location and during periods of viral respiratory infection. Nasal
Chapter 8 I Pulmonology • 89
obstruction can be caused by a foreign body, polyps, pressure is indicated for cases in which surgery is
or allergic rhinitis. There are many infectious causes contraindicated or fails to resolve sleep-disordered
of acute upper airway obstruction, including acute breathing.
laryngotracheitis and peritonsillar or retropharyngeal
abscess. The timing of symptom onset and presence
LOWER AIRWAY OBSTRUCTIVE
and severity of fever will assist in distinguishing
DISEASE
infectious from noninfectious conditions. It is im-
portant to remember that aigns and symptoms from Because intrathoracic airways narrow during exha-
congenital malformations are often present at birth lation, any form oflower airway obstruction is more
but may develop over time, especially when stenosis apparent during exhalation. Wheezing results from
or vascular compression limits airway growth. turbulent air caused by the intrathoracic obstruc-
tion of virtually any type. Although most patients
OBSTRUCTIVE SLI:EP APNEA with asthma wheeze, not aU patients who wheae
Many children have upper airway obstruction have asthma. The most common lower airway ob-
only during sleep, as a result of normal physiologic structive diseases in childhood are asthma and CF.
changes in upper airway muscle tone. Most affected Primary ciliary dyskinesia (PCD), a rarer entity, is
children have some degree ofanatomic obstruction also an obstructive disease with symptom onset in
(i.e., large adenoids and/or tonsils, or tongue base childhood. Children with PCD almost always have
[glossoptosis or Ungual tonsillar hypertrophy]). daily rhinorrhea, and often have a history of transient
Craniofacial abnormalities are less common but tachypnea of the newborn.
are also associated with airway obstruction during
sleep. Snoring is present in almost all cltildren with AS111MA
obstructive sleep apnea syndrome (OSAS). Symptoms Asthma is a heterogeneous, chronic disorder of the
of OSAS include restless sleep, respiratory pauses airways characterized by revmlbk airway obstruction,
and gasps, poor growth, behavioral problems, en- inflammation, and bronchial hyperresponsiven.ess.
uresis, and poor academic performance. Daytime Diagnosisia based on recurrent symptoms and respon-
somnolence is rarer in children than in adults with siveness to bronchodilator and/or anti-inflammatory
OSAS, but can occur in adolescents, or in children agents. Bronchospasm, which results from smooth
with severe disease. OSAS associated with. marked muscle constriction, may occur in response to aller-
obesity (obesity-hypoventilation syndrome) can lead gic, environmental, infectious, or emotional stimuli
to daytime hypoventilation with severe complications, Common precipitants include upper respiratory
including pulmonary hypertension, congestive heart infections, pet dander, dust mites, weather changes,
failure, and even death. exercise, cigarette smoke, and seasonal or food allergens.
Polysomnography is the diagnostic study ofchoice, Cellular mediators of inflammation are recruited to
and measures respiratory muscle activity, air flow, the lower airway mucosa and submucosal structures,
oxygen saturation, sleep stage, and heart rate. End inciting mucus production and mucosal edema, further
tidal carbon dioxide measurement is critical for increasing airway hyperresponsiveness. The inflam-
pediatric sleep studies, as partial obstruction (ob- matory response typically involves both immediate
structive hypoventilation) is a very common pattern and late-phase components; the latter results in the
ofsleep-disordered breathing in studies. Standardized prolonged nature ofan asthma exacerbation.
definitions allow measurement of the type of phys- Asthma severity is classified on the basJs of the
iologic disturbance, defined as CDttral, obstructive, degree ofimpairment before the initiation ofappro-
or mkred, as well as its severity, on the basis of the priate therapy (Tables 6-1 and 6-2). Following the
frequency ofepisodes, the attendant aberrations in initiation of treatmenlf asthma control is monitored
oxygen and carbon dioxide measurements, and sleep in two domains: impairment (current symptoms and
disruption. The treatmentofOSAS should be directed lung function) and risk (future exacerbations and
toward reducing anatomkal airway obstruction. The medication sideeffects) (Tables 6-3 and 6-4). Assessing
removal of tonsils and/or adenoids is most commonly and maintaining control is more important than as-
performed. The oralleukotri.ene receptor antagonist signing severity classification. Additional information
(LTRA) montelulwt and intranasal corticosteroids regarding the 'lJXTl Expert Panel Report 3 Guidelines
have been shown to improve respiratory parameters for the diagnosis and treatment ofasthma can be found
in mild pediatric OSAS. Continuous positive airway at www.nhlbi.nih.gov/guidelines/asthma/index.htm.
TABLE &-1. Classifying Asttlma Severity and Initiating Therapy in Children (Ages 0 to 11)
lnlwmlllllnl Mild Mad....

Ages 0-4 Ages 5-11 Ages 0-4 Ages 5-11 Ages 0-4 Ages 5-11 Ages0-4 Ages5-11
Impairment Symptoms :S2d/wk >2 dlwk but not daily Daily 1lrroughouttheday
Nighttime 0 :S2X/mo 1-2X/mo 3-4X/mo 3-4X/mo >lX/wkbut >lX/wk Often 7X/wk
awakenings not nightly
Short-acting J}:z- :S2d/wk >2d/wkbut >2d/wk Daily Several times per day
agonist use for not daily but not
symptom control daily and
not more
than once
daily
Interference with None Minor limitation Some limitation Extremely limited
normal activity
Lung function- N/A NonnalFEV1 N/A >80% N/A 60%-80% N/A <60%
FEV1 (% between >80% 75%-80% <75%
predicted) exacerbations
or peak flow >80% during
(personal exacerbation
best)-FEV1/FVC >85%
Risk Exacerbations 0-lX/y 0::2 0::2X/y
requiring (see notes) exacerbations (see
oral systemic in6mo notes)
corticosteroids requiring Relative
(consider severity oral annual
and interval since systemic risk may
last exacerbation) corticosteroids, be related
or =::4 to FEV1
wheezing
episodes/! y
lasting >1 d
AND risk
factors for
persistent
asthma
Recommended Step 1 (for both age groups) Step 2 (for both age groups) Step3: Step 3: Step 3: Step 3: '
step for Consider a Medium-dose Consider Medium-dose l
initiating short course of ICS option a short ICS option OR i
therapy. (See oral systemic and consider a course Step 4, consider !
"Stepwise corticosteroids short course of of oral a short course !
Approach for oral systemic systemic of oral systemic !
Managing corticosteroids corticosteroids corticosteroids !
Asthma• for
treatment
steps.) The
stepwise
approach is
meant to assist,
not replace,
I
the clinical
decision-
making
required to
meet individual I
patient needs.
In 2-6 wk, depending on severity, evaluate the level of asthma control that is achieved. :
Children 0-4 y old: If no clear benefit is observed in 4-6 wk, stop treatment and consider alternative diagnoses or adjusting therapy. l
Children 5-11 y old: Adjust therapy accordingly. !
Asthma severity is determined by both impairment and risk. Assess impairment domain by caregiver's recall of previous 2 to 4 wk. Again severity to the most severe category in which any feature '
occurs. The frequency and severity of exacerbation may fluctuate over time for patients in any severity category. At present, there are inadequate data to correspond the frequencies of exacerbation !
~~~~~;~~~~~~~~~~~~~~~~~~~~~~~--!
·~
TABLE 1-2. Classifying Astllma Severity and Initiating Treatment (Ages ~12)
Cempananll of Savartty CIIISSIIIcldlon of Aslh1111 Sav8rlly ~ 12 J of Age
l'lnlllllnt
lnlllrmlllent Mild Madame Sewere
Impairment Symptoms :s;2 d/wk >2 d/wk but not Daily ~oughouttheday
daily
Normal FEV1 /FVC: Nighttime :s;2X/m 3-4X/mo > 1 X/wk but not nightly Often 7X/wk
awakenings
8-19y85% Short-acting ~- ::>2d/wk >2 d/wk but not Daily Several times per day
agonist use for daily, and not
symptom control more than 1 X on
(not for the any day
prevention of EIB)
Interference with None Minor limitation Some limitation Extremely limited
normal activity
Lung function • Norma1FEV1 • FEV1 > 80'J6 • FEV1 > 60CJ6 but <80'J6 • FEY1 < 60CJ6 predicted
between predicted predicted • FEV1/FVC reduced >5%
exacerbations • FEV1/FVC • FEV1/FVC reduced 5'16
• FEV1 > 80% normal
predicted
• FEV1 /FVC normal
Risk Exacerbations 0-lX/y (see note) ~2X/y (see note)
requiring oral
systemic
corticosteroids
Consider severity and interval since last
exacerbation.
Frequency and severity may fluctuate over
time for patients in any severity category.
Relative annual risk of exacerbations may be
related to FEY1•
Recommended step for initiating Step 1 Step 2 Step 3 and consider a short Step 4 or 5 and consider a short course of
treatment. (See •stepwise Approach for course of oral systemic oral systemic corticosteroids
Managing Asthma" for treatment steps.) corticosteroids
In 2-6 wk, evaluate the level of asthma control that is achieved and adjust therapy accordingly.
The stepwise approach is meant to assist, not replace, the clinical decision-making required to meet indMdual patient needs.
The level of severity is determined by 1he assessment of both impairment and risk. Assess impairment domain by patients/caregivers 2 to 4 wk and spirometry. Assign severity to the most
severe category in which any feature occurs. At present, there are inadequate data to correspond 1he frequencies of exacerbations with different levels of asthma severity. In general, more
frequent and intense exacerbations (e.g., requiring urgent, unscheduled care, hospitalization, or ICU admission) indicate greater underlying disease severity. For treatment purposes, patients
who have had 2:2 exacerbations raquiring oral systemic corticosteroids in the past year may be considered the same as patients who have persistent asthma, even in the absenca of
impairment levels consistent with persistent asthma.
Abbreviations: EIB, exercise-induced bronchospasm; FEV1 , forced expiratory volume in 1 second; FVC, forced vital capacity; ICU, intensive care un~.
Adapted from 2007 Expert Panel Report 3 Guidelines for the Diagnosis and Treatment or Asthma. Available online at http://www.nhlbi.nih.gov/guidelines/asthmalindex.htm.
·~
I! TABLE &-3. Assessing Asthma COntrol and Adjusting Therapy in Children (Ages 0 to 11)
Assas- Allllm1 Cenlnll1nd AdJ..- Therapy In Cbll*al
Well Cenlnllled Nat Well Canlraled Very Paarty Canlralled
Ages0-4 Ages5-ll Ages 0-4 Ages 5-11 Ages0-4 AgesS-11
Impairment Symptoms :s;2 d/wk but not >2d/wk >2d/wkor Throughout
more than once multiple times on the day
on each day :s;2d/wk
Nighttime awakenings :s;1X/mo >1X/mo ~2X/mo >1X/wk ~2X/wk
Interference with normal None Some limitation Extremely limited

activity
Short-acting ~-agonist use :s;2d/wk >2d!wk Several times per day
for symptom control (not for
the prevention of EIB)
Lung function
- FEV1 (predicted) or peak N/A >8096 N/A 60%-8096 N/A <60%
flow personal best >8096 75%-80% <7596
-FEV1/FEV
Risk Exacerbations requiring oral 0-1X/y 2-3X/y ~2X/y >3X/y ~2X/y
systemic
Reduction in lung growth N/A Requires long- N/A ~uation N/A Evaluation requires long-
term follow-up requires long-term term follow-up care
follow-up care
Treatment-related adverse Medication side effects can vary in intensity from none to very troublesome and worrisome. The level of intensity does
effects not correlate to specific levels of control but should be considered in the overall assessment of risk.
Step for initiating therapy. {See •stepwise • Maintain current step Step up 1 Step up at least 1 • Consider a short course of oral systemic
Approach for Managing Asthma"' for • Regular follow-up every 1-6 mo step step corticosteroids
treatment steps.)
The stepwise approach is meant to assist, not • Consider step down if well • Step up 1-2 steps
replace, the clinical decision-making required controlled for at least 3 mo
to meet individual patient needs
Before step-up:
• Review adherence to medication, inhaler technique, and environment control. l
• If alternative treatment was used, discontinue it and use preferred treatment l
for that step. Reevaluate the level of I
asthma control in 2-6 wk i
§}:~~~
Children 5-11 y
old: Adjust therapy l
~~~7"'1
The level of control is based on the most severe impairment or risk category. Assess impairment domain by the patient's or the caregiver's recall of previous 2 to 4 weeks. Symptom assessment for
longer periods should reflect a global assessment, such as whether the patient's asthma is better or worse since the last visit. At present, there are inadequate data to correspond the frequencies of ·
==~~~=: ::~=~sc::7:::::::~:;l::~:~:o:::~vo::~i:n1s::::~::·:~u:~::::~:~~~:::~~ecda::it::~a~::::li:~~~e~
Adapted from 2007 Expert Panel Report 3 Guidelines for the Diagnosis and Treatment of Asthma online at http://www.nhlbi.nih.gov/guidelines/asthmalindex.htm.
admission) indicate poorer ... ~'.
................................................................................................................................................................................................................................................................................................................................................................................. ........................................................
·~
98 • BLUEPRINTS Pediatrics
TABLE 6-ol. Assessing Asthma Control and Adjusting Therapy (Ages ~12)
CoillpiiAitl af Cenlnll lat. . c.INIIII

Impairment Symptoms S2d/wk >2dlwk Throughout the day
Nighttime awaken1np S2X/mo 1-3></wk ~4></wk
Interfilrence with None Some limimtion Extremely limited

nonnal activity
Short-ac:tinJ ~-agoniat S2d/wk >2dlwk Several times per day
use for symptom
control (not for the
prevention ofEIB)
FEV1 or peak Bow >80% predl.ct:ed/ 60"--80'.16 predicted/ <60% predicted/
personal best personal best personal best
Validated questlonnaira 0 1-2 3-4
ATAQ s0.75"' <!:1.5 N/A
ACQ 0!:20 16-19 SIS
Acr
Risk Exacerbationa 0-IX/y :<!:2X/y(see note)
requlrlng oral systemlc
Conaider severity
corticolteroida
and interval Iince laat
exacerbation
Progreuive loa oflung Evaluation requires long-term follow-up care
function
Treatment-related Medication side effects can wry in intensity from none to very
adverse eft'ects troublesome. The level of intensity does not correlate to specific l.eveiB of
control but should be conaidered in the overall a.uessment of rialc.
Recommended action for treatment. • Maintllin current • Step up to lltep • Consider a
(See •stepwise Approach for step • Reevaluate in 2-6 short coune of
M.ana8ing Asthma" .for treatment • :Regular Collow-up wk oral systemic
steps.) at every 1-6 mo to • For side effects, cortlcosteroids
maintain control consider • Step up 1-2 steps
• Consider step down alternative • Reevaluate in 2 wlc:
ifwell controlled for treatment options • For side effects,
at least 3 mo consider
alternative
treatment options
!•ACQ values of 0.76 to 1.4 an1 lndetenninale regarding well-controlled asthma.
! The stepv.ise approach Is meant to assist, not replace, the cllnlcel decision-making required to meet "dMduBI patient needs. The
! level of control Is based on the most seYere lmpUment a rlsk category. Assess lmpelnnent domain by the patient's recall of previous
i 2 to 4 wk by sprometry a peak flow measuRIS. Symptom assessment for longer periods shoUd rellect a global assessment, suctJ
!as inquiring whether 1hepatient's asthma is better or worse since the last visit. At present. there an1 i'ladequate data to correspond
: the frequencies of axaoerblltions wth dllerent lewis of asthma controL ~ general, I'T10f8 frequent and intense exacerbation& (e.g.,
! reqWi~ urgent, unscheduled care, hospitalization, a ICU admission) indcaiB poorer disease control. For treatment purposes,
j patients who had 0!!:2 eDCaCerbations requiring oral systemic corticosleroid8 in the past year may be considered the same as patients
j who have not well·controlled as1hma. even h the absence of inpaiment I8V'8Is consistent with not well-controlled asttma.
j ATAQ, Asthma Therapy All8eBsment QuestionnairaC; ACQ, Asthma Control QuestionnairBO; Per, Asthma Control Test; Dilferance:
! 1.0 ftlr the ATAQ; 0.5 for the ACQ; not dBlennined for the !>Cr.
!a..tor. ftlp-up In the...,:
! Review adherence to medication, inhaler technique, ei'Nironmental control, and comorbid conditions.
! If an aftemativa treatment option was used in a smp, disoontinue and use the prefern!d treatment for that step.
~ .Abbr!Mallons: EIB, I!OCIII'dse-nduoed bronchospa9m; FE\11 , forced expntory vohme In 1 second; IOU, lntensMI cere unft; NIA, not apploable.
! Adapted from 2007 Expert Panel Report 3 Guldelln118 for the Diagnosis and Treatment of Asthma. Available online at http:llwMY.nhlbl.nlh
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: , ,00000000000000000000000_ , 00000000000
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1
Epidemiology Clinical Manifestations

Asthma is the most common chronic disease in US In children with asthma, the history may reveal
children. a common reason for pediatric hospit:a.l- wheezing and protracted cough with viral reApira-
izations, and a global health concem. Its prevalence tory infections. Other signs and symptoms include
is increasing despite advances in therapy. &. many prolonged respiratory infections, reduced exercise
as 15% to 20% of children in the United States will tolerance, and frequent or persistent day or nighttime
be diagnosed with asthma at some point in time; in coughing. Children with acute exacerbations pres·
some high·risk populations (African American race ent in respiratory distress with dyspnea, wheezing,
and Hispanic), the prevalence can reach 25%. More subcostal retractions, nasal flaring, tracheal tugging,
than 50% of patients present before 6 years of age. and a prolonged expiratory phase resulting from
but many children with wheezing in the first years the obstruction of airflow. Cyanosis is uncommon.
of life do not ultimately have astluna. making early The absence of wheezing (i.e., poorly heard breath
definitive diagnosis difficult. Boys are affected more sounds) during an acute exacerbation is an ominous
often than girls before adolescence; thereafter, the sign, indicating severe airway obstruction with very
ratio is reversed. limited air movement. Mental status changes sug-
gest significant hypercarbia and/or hypoxemia with
RiSk Factors impending respiratory failure.
Riak factors for the development ofasthma include
genetic predisposition (a parent with asthma or Diagnostic Evaluation
allergy), atopy, cigarette smoke exposure, living Most children with asthma have normal physical
in urban areas in poverty, and African American examinations when not in exacerbation. In children
race and Puerto Rican ethnicity. Upper respiratory older than 6 years, PFTs can measure the degree
tract infections with certain viruses, including of airflow obstruction at baseline and during ex-
rhinovirus and respiratory syncytial virus, occur- acerbations. However, many children with asthma
ring in genetically susceptible children at certain will also have normal lung function when not
critical times in early life are also thought to play acutely UL An inhalation challenge test with an
an important role. 88ent that induces bronchoconstriction in those
with airway hyperreactivity (e.g., methacholine)
Dlffenntlal Diagnosis can be useful in helping diagnose asthma, but does
When a child presents with wheezing and respiratory not differentiate causes of airway hyperreactiv-
distress, the differential diagnosis includes asthma ity. Patients with persis~nt asthma should have
and other causes of intraluminal inflammation PFT at least once a year in order to monitor for
and/or retained or excessive secretions (bronchi- change and to help adjust therapy. Baseline chest
olitis, gastroesophageal reflux with aspiration, CF, radiographs may show mild hyperinflation and/
H·type tracheoesophageal fistula, PCD); intralu· or increued bronchial markings. Home peak flow
minal masses (foreign body aspiration, tracheal or (PF) monitoring may be useful for patients with
bronchial tumors, or granulation tissue); dynamic moderate-to-severe asthma or those who poorly
airway collapse (tracheobronchomalacia); intrinsic perceive their symptoms. PF meters are small,
narrowing (congenital or acquired stenosis) or portable, and easy to use. They measure how fast
extrinsic compression (vascular ring, mediastinal a patient can forcibly expire air after a maximal
lymph nodes or masses). These diagnoses should inhalation; decreased readings indicate obstruction
abo be considered in patients whose wheezing to airflow. Reductions to 5006 to 80" of predicted
fails to respond to appropriate medical treatment. values indicate mild-to-moderate disease exacer-
Wheezing can occur with anaphylaxis and angio- bation; readings less than 30% of predicted values
neurotic edema at any age. Cough-variant asthma are associated with severe obstruction. PF meters
produces a chronic cough that may be triggered by are heavily dependent on effort and technique, and
exercise or noted primarily at night during sleep; are, therefore, variably reliable.
wheezing may or may not be present. Most children Chest radiography is not indicated for mild-to-
with cough-variant asthma have normal spirome- moderate asthma exacerbations. During acute exacer-
try and radiography. Improvement with P-agonist bations, the chest radiograph demonstrates significant
and inhaled corticosteroid (ICS) treatment helps hyperinflation and occasionally focal or subsegmental
confirm the diagnosis. atelectasis (Fig. 6·1).
FIGURE &-1. PA and lateral chest radiographs of

a 3-year-old patient obtained during an asthma
exacerbation test demonstrates severe hyperinflation,
increased anteroposterior diameter of the chest, a
~~P~--~-~h~~~!~areas of atelectasis..:..
Tralllment such as alburerol are used for quick reliefofsymptoms

With appropriate therapy and good adherence, and for the prevention ofsymptnms during exercise.
most patients with persistent uthma can remain These agents reduc:Je smooth muscle constriction and
symptom-free with few exacerbations. The most are administered via inhalation. Long-acting jl-agonists
effective treatment .is the appropriate use of daily (LABA) (salbutamoL formoterol) have a much longer
anti-inflammatory medication in accordance with onset ofactJon in additl.on to a longer duration ofaction.
published guidelines. Tobacco smoke should be so should not be relied upon for quick relief. LABA
strictly avoided. Screening for environmental tobacco are not appropriate for monotherapy and should be
smoke exposure and parental smoking cessation used only in patients who cannot be controlled on ICS
counseling for parents who smoke should occur alone or with the addition ofother anti-inflammatory
at every visit. Removal of allergens and irritants medications. for the prevention of exercise-induced
(triggers) from the patient's environment is an bronchospasm. ~2-agonlsts should be gl.ven 5 to 20
important adjunctive strategy; this may include minutes before vigorous activity. The overuse of in-
specific strategies for reducing dust mite, mold, haled bronchodilaton may result in tolerance to their
and pet exposure in patients with documented al- therapeutic effucts, contributing to asthma morbidity
lergies. The National Institutes of Health has issued and mortality.
guidelines for the pharmacologic management of ICS therapy is the most effective treatment for
asthma on the basis ofdisease severity and control chronic asthma and provides excellent control in the
(Tables 6-5 and 6-6). majority of patients. Topically active ICSs typically
The mainstaysofmedical maintenance therapyinclude haw wry low systemic bioavailability and result in
dailymedicationssuchasiCSs,long-actingjl-2-adren- few systemic adverse effects. Options include be-
ergic agonists, and LTRAs. Long-acting ~2-agonists are clomethasone, budesonide, ciclesonide, flunisolide,
indicated for patients with moderate-to-severe persistent fluticasone, and mometasone. Products include
asthma, especially when ICSs alone do not result in solutions for nebulization. traditional metered dose
good controL In contrast, short-acting jl-2-agonists inhalers, and breath-actuated inhalers, including dry
TABLE 1-5. Stepwise Approach for Managing Asthma Long Term in Children (Ages 0 to 11)
Step1 Step2 Step3 Step4 StepS Step&
lntermittBnt Asthma P8rsistsntAsthma: Daily Medicatiolf
Children 0-4 y Preferred SABA as needed Low-dose ICS Medium-dose ICS Medium-dose High-dose ICS High-dose ICS + oral
of age ICS + [LABA or +[LABAor corticosteroids ICS +
Montelukast] Montelukast] [LABA or Montelukast]
Alternative Cromolynor
Montelukast
Each step: Patient education and environmental control
Quick-relief SABA as needed for symptoms. The intensity of treatment depends on the severity of symptoms.
medication With viral respiratory symptoms: SABA q 4-6 h (longer with physician consult). Consider a short course of oral systemic
corticosteroids if exacerbation is severe or if the patient has a history of previous severe exacerbations.
Children 5-11 y Preferred SABA as needed Low-dose ICS Lose-dose ICS + Medium-dose ICS High-dose ICS + High-dose ICS + LABA
of age [LABA, LTRA, or + LABA LABA + oral corticosteroids
theophylline] or
medium-dose ICS
Alternative Cromolyn, LTRA, Medium-dose High-dose ICS High-dose ICA + [LTRA
nedocromil, or ICS + [LTRA or +[LTRAor or theophylline] + oral
theophylline theophylline] theophylline] corticosteroids
Each step: Patient education, environmental control, and management of comorbidities
Steps 2-4: Consider subcutaneous allergen immunotherapy for patients who have persistent, allergic asthma
Quick-relief SABA as needed for symptoms. The intensity of treatment depends on the severity of symptoms: up to 3 treatments at 20-min
medication intervals as needed. A short course of oral systemic corticosteroids may be needed.
Caution: The increasing use of SABA or use > 2 d a week for symptom relief (not for the prevention of EIB) generally indicates
inadequate control and the need to step up treatment.
•consult with asthma specialist if Step 3 care or higher is required. Consider consultation at Step 2.
Children 0 to 4 Year~J of Age
The stepwise approach is meant to assist. not replace, the clinical decision-making required to meet individual patient needs.
If an alternative treatment is used and the response is inadequate, discontinue it and use the preferred treatment before stepping up.
If clear benet~ is not observed w~hin 4 to 6 weeks, and if the patient's/family's medication technique and adherence are satisfactory, consider adjusting therapy or an alternative diagnosis.
Studies on children 0 to 4 years of age are limited. Most recommendations in this age group are based on expert opinion and extrapolation from studies in older children.
Children 5 tr:l11 Year~J of Age
The stepwise approach is meant to assist, not replace, the clinical decision-making required to meet individual patient needs.
If an alternative treatment is used and if the response is inadequate, discontinue it and use the preferred treatment before stepping up.
Theophylline is a less desirable alternative due to the need to mon~or serum concentration levels.
Rationale for recommendations in this age group is available at the NIH website.
Alphabetlcalll•tlng I• u•ed when more than one treatment option I• ll•ted within either preferred or alternative therapy.
Abbreviations: EIB, exercise-induced bronchospasm ICS, inhaled corticosteroid; LABA, inhaled long-acting 112 -agonist; LTRA, leukotriene receptor antagonist; oral corticosteroids, oral systemic corticosteroids;
NIH, National Institutes of Health; SABA, inhaled short-acting ~ 2 -agonist.
II , Adapted from 2007 Expert Panel Report 3 Guidelines for the Diagnosis and Treatment of Asthma.
100 • BLUEPRINTS Pediabics
: ..........
TAII.IIHI. Stepwise Approach for Managing Asthma (Ages ~12)
All*- ........... . . - : ....,. . . ......

CDMult rrflll..,. ... t If Step 4t21e tJI' h/fllllr,.requln/d.
i,,,:,_
1
r
'.
CiDnsldeT amulaUttJ., Slrlp 3
l Step 1 Step 2 Step 3 Step 4 Step 5 Step 6 Step ap 1f needed
! Preferred:
= =bl
Preferred: Preferred: Preferred: Preferred: Preferred: (first. check
j SABA as Low-d01e ICS Low-dose Medium- High-dOle High-doae ICS adherence,
~~r: =~~ ~- ~
!needed
I
'
~";!"' ~ E;~~.
LTRA, theophylline,
EB =L ~b
allergies possible (and
~&d~~~~~~:~::~~~~~ ~~~·!
! >Steps 2-4: Consider subcutaneous allergen immunotherapy fur patients who hav.~ allerJic uthma (tee notes) !
! The
alternative trvatment
stepwise Ia uaed
approach and to
Ia meant I'I!BPonse Ia lnad11t1uate,
assist, not !11place, thediscontinue It and use the!11Qulred
clinical decision-making pravi'Ridtotrealment beforepaUerrt
,._.lndMdual stepping up. Zlleuton
naeda. It
i is e less arable altemative due to limited studies ea edjunctive th8111py end the need to mon~gr liver function. Theophylline reQuirus
,
'·!',,,',
',,,',_ ,,':,'
! the monitoring of serum concantndion levels. In Step 8, before oral corlioostatlids ara intnxlucad, a bial of high-dose ICS + LABA +
! aith8f LlRA, 1heophytline, gr zilauton may be considered, although this approech hall not~ studied in clinical ttials. Rationale tor
1raoommendatlons for pnlfe1T11d therapies In this age group Is IMIIIeble 1111 the NlH wobs~e.
~ A•....Uc:.l onter le ueed when moN luln one n.tment opUon le lilted wfthln eltt.r ,.,.,..d 01 ahlmlltlve theniPJr
! Abbi1Mationa: ICS, inhaled corticosteroid; LABA, long-acting Pz-agonist; LTRA. leukiJtriene 18Ceptgr antagonist; NIH, National Institutes of
j Health; SABA, inhaled short-acting Pragonist.
!..~~.~ 2_?.~?...~.~~..~.~..~~~~~~~..~~.~.?..~~..~~..!~.!..~~-~~~~~:.........- ....................-...................................._,_..,_J
powder inhalers. The selection of the dosing form Montelukast is approved for infants and very young
is more important than the drug itself. Young chil- children, whereas zafirlukast is approved only for
dren do not generate an adequate inspiratory flow children over 5, A3 monotherapy, these agents are
rate for breath actuation in many devices. When most effective in younger patients and those with
traditional metered dose inhalers are used, a spacer a shorter duration of asthma. LTRAs provide some
with a mask (for younger children) or mouthpiece protection from exercise-induced bronchospasm
(for older children) is essential to assure adequate and reduce symptoms of allergic rhinitis.
delivery to the airways. Measurable decreases in Theophylline, once a commonly prescribed oral
linear growth occur in chlldren usJng daily ICSs, bronchodilator, is no longer a first-line treatment
especially at high doses in children under 2 years option. Theophylline may be poorly tolerated, has
old. Otherwise, when budesonide and fl.uticasone significant interactions with multiple other medications,
are used at low doses, linear growth velocity declines and requires drug-level monitoring. It is presently
initially but then rebounds, resulting in only a small reserved for use as an add-on therapy in patients who
reduction in final heisht (<1.5 em). Short courses do not respond to ICS, LABA. and LTRA therapy;
oforal steroids (3 to 1 days) are used for acute ex- intravenous aminophylline is sometimes used in the
acerbations; long-term use is reserved for severe, intensive care setting during severe exacerbations.
persistent, poorly controlled asthma. Patients (~6 years old) with severe allergic asthma
LTRAs (montelukast. zafirlukast) are oral med- that is poorly controlled with the use ofiCS, LABA,
ications that may be used for the initial treatment and LTRA may benefit from treatment with omali-
of mild persistent asthma. They can also be used as zumab, an.iniectable monoclonal antibody directed
add--on medications to an ICS to improve control against IgE. This treatment is expensive and must
be given every 2 to 4 weeks. Newer monoclonal children is relatively low in developed countries and
antibody-targeted therapies include reslizumab has .stabilized in the past several years. Factors that
and mepolizumab, which block interleukin-5, a increase the risk of death include noncompliance,
signaling protein crucial in the development and poor recognition of symptoms, delay in treatment,
release of eosinophils from bone marrow. These history of intubation, African American race, and
agents are effective for the management of severe steroid dependence.
eosinophilic asthma.
Mild-to-moderate exacerbations are managed by CYSTIC FIBROSIS
the addition ofshort.acting inhaled bronchodilators Pathogenesis
to maintenance drugs. Additional steps may include CF is an inherited multisystem disease caused by
quadrupling the maintenance dosage of inhaled absent or poorly functioning cystic fibrosis trans-
steroids for 7 to 10 days or initiating a 5-day course membrane regulator (CFTR) protein. CFTR is a cell
of oral steroids. Moderate-to-severe exacerbations membrane protein that functions as a cAMP-activated
usually require an emergency department visit, and chloride channel on the apical surface of epithelial
in some cases, hospitalization. cells. This channel is nonfunctional in patients with
Children who present to the emergency department CF, so chloride remains sequestered inside the cell
with an acute exacerbation are initially assessed for Sodium and water are drawn into the cell to main-
airway patency, work of breathing, and oxygenation. tain ionic and osmotic balance, resulting in relative
Pulse oximetry is a simple, rapid screen for hypoxemia; dehydration at the apical surface of the cell. This
patients with persistent desaturation (Spo21 92%) results in abnormally viscid secretions and impair-
after initial treatment with a short-acting broncho- ment of mucociliary clearance. The most significant
dilator are likely to need more aggressive treatment symptoms occur in the respiratory tract, pancreas,
and hospitalization. Patients In severe respiratory and sweat glands.
distress require blood gas measurements to assess Epidemiology
for increasing Paco21 a sign ofimpending respiratory CF is acquired via autosomal recessive inheritance,
Wlure. A normal Pac~ in the face of tachypnea with a disease frequency ofapproximately lin 3,500
and fatigue is an ominous sign because the Pac~ Caucasian births. It is seen in virtually all races
should be well below 40 mm Hg in a tachypneic and ethnicities, at variable frequencies, and with a
patient. Nebulized bronchodilator& are administered different distribution ofgene mutations. More than
frequently (every 20 minutes or continuously) for 2,000 distinct gene sequence variants have been de-
severe episodes. The delivery of multiple inhalations scribed in the CFTR gene, but the disease liabilityof
of j}-agonists by a metered dose inhaler with a valved most remains undefined. Worldwide, 701J6 of known
holding chamber is as effective as nebulized therapy. mutant alleles involve a single nucleotide deletion
Ipratropiwn, an anticholinergic agent, may provide (Phe-508del). The median life expectancy is currently
additive relief of symptoms in those patients with in the mid-to-late 40s in developed countries and
severe obstruction, as measured by peak expiratory has increased dramatically in the past four decades.
flow (PEF) or spirometry. The drug is usually given
mixed with alburerol Subcutaneous or intramuscular Clinical Manifeslations
epinephrine and intravenous magnesium sulfate can HitltOry and PhysicBI Examination
rapidly reduce airway obstruction in severely affectEd Table 6-7 lists the most common presenting signs
patients who may be too fatigued or uncooperative and symptoms of CF. In the past few years, a ma-
to use inhaled albuterol Corticosteroids, adminis- jority of new diagnoses of CF have been associated
tered orally or intravenously, are indicated for the with positive newborn screening tests in the United
treatment ofacute exacerbations that fail to improve States and many developed countries. Newborn
significantly after the first albuterol treatment in the screening is not always positive, however, and any
emergency department. Children who do not have infant with a sibling with CF, meconium ileus, or
significant resolution ofsymptoms after several hours other signs and symptoms should have a sweat test.
(status utlunaticus) and those requiring ongoing The entire respiratory tract is affected, including
oxygen therapy should be hospitalized for continued the nasal passages, sinuses, and lower airways. Na-
treatment and close observation. sal polyps in any pediatric patient should prompt
Despite advances in therapy, some patients still further testing for Cf. Sinwitis or radiographic
die from asthma. The mortality rate for asthma in opacification of the sinuses is extremely common.
aureus and H~~DFWphihu influmz~. Pseudomonas

1'llllJ: 8-7. Clinical Manif&stations at Cystic Rbrosis
aeruginosa occun in up to 2596 of infants in the
!Chronic S/nopulmonlltyIJIIBIItM first~ of l..ifu and becomes more frequent in late
!Peniltent colonlzation/1n with patbogeDs childhood and early adolescence. Historically, more
1typical ofCF Juns cliJeaJe, including than 90% of patients eventually acquired chronic P.
Stllplr.yloc«au aureiU aeruginosa infection. Eradication strategies over
i ~~ (nmcoidand DOIUDllt'llid) the last decade have markedly changed this, and P
aeruginosa is no longer the moat common organism
1 Nontypeable HumophUru bt~
isolated from airway cultures in CF. Colonization
I ;:::~~=~:::: with Burkholderia cepacia may be associated with

accelerated pulmonary deterioration and early death.
~ Endobn1ndrlll,__ MMifNtMI /IJ but this depends on the spedfic species; for example,
I =~=::u:~n
Burkholderia ce1WCepacla and BurlcJwlderia dolosa
are more pathogenic thanBundwlderia multivorans.
Gastrointestinal manifestations include pancre-
!,',,_1 Radiographic abnormalities - - - - - - atic insufficiency in 8596 to 9096 ofaffected patients,
Evidence of obatruction on PFTa bowel obstruction and rectal prolapse, and hepatic
cirrhosis. The loss of pancreatic enzyme secretion
1,,_ Digital clubbing
leads to decreased fat absorption; parents may
Chronic sinus disease
notice that the child's stools are large, bulky, and
l Nual polypa
fo~smelling. Later, stool becomes extremely dense,
! Radiographic changes sometimes leading to distal intestinal obstruction.
i /ntutiniJJAllnorm.mies Failure to thrive is the most common manifestation
!Meconium ileus of untreated CF in infants and children. Meconium
ileus (neonatal intestinal obstruction in the absence
~ E.xoaine panc:reatic insufficiency
ofanatomic abnormalities) oa:un in 1596 to 2096 of
l Diltallotectfnal obstruction infants with Cf and ia virtually pathognomonic for
iRectal prolapse CF. CF-related diabetes (CFRD) occurs because of
! Recurrent pancreatitia reduced insulin secretion and increased peripheral
iChronic hepatobWary dJJeue manifeated by clinical insulin resistance, making it distinctly different from
Iand/or laboratory evidence of type I or type II diabetes mellitus.
=~=:~:
!
__
The clinical presentations ofCF are most often related
IE:~==---n_)
to the elevated sweat chloride concentration, pan-
creatic insufficiency, and respiratory tract findings.
Over the last decade, the availability of newborn
screening has led to most diagnoses in infants be-
ing found because of a positive result. Quantitative
IObstructive azoospennia In males pilocarpine electrophoresis sweat chloride testing
i Reduced fertlllty In females remains the gold standard for the diagnosis ofCF and
llllmbDIIt;AIInflmMIIIJ8I should be performed even when two cJisea.se.causing
CFTR gene mutations are identified on a newborn
i Salt-loui)'Ddromes screening gene mutation panel. A level that is greater
i Acute aalt depletion than 60 mEq/L is considered highly indicative of
i Chronic metabolic alblolia CF, but false positives and false-negative tests can
~ AbbnMations: CF, cystic fbcsis; PFT, ptJlmorwy function tests. l occur. Intermediate sweat chloride values are seen
!-·--~---·······-·---···-·----·-----·
in patients with milder CFTR gene mutations and
are increasingly seen in infants who present with a
Mucus stasis and ineffective clearance lead to bacte- positive newborn screening test. Infants with per-
rial colonization and frequent pneumonia&. Typical sistently intermediate values and fewer than two
early childhood pathogens include Staphylococcus disease-causing CFTR mutations are diagnosed
with CF-related metabolic syndrome (CRMS) or syndromes. Water-soluble forms offat-solublevitamins

CF screen positive, indeterminate diagnosis, terms are indicated early in life. Although breutfeeding is
that are used interchangeably. Infants with CRMS recommended, some infants require fortification of
may develop 11Ulllifestations of CF. and should be breast milk or formula to achieve nonnal growth.
periodically evaluated by a CF specialist. Sweat CF is associated with increased energy demands
testing requires signi.ficant training of personnel, throughout the life span, with calorie requirements
and should be performed in specialized centers of 1.20% to 20006 ofthat of healthy children or adults.
with experience and expertise. Genetic and prenatal When this cannot be achieved through a high-calorie,
testing are often employed. Some mutations retain liberal-fat diet, supplemental tube feedings are used
some CfTR function. in which case pancreatic suf- to optimize intake. Preschool children with weight
ficiency is often present. If at least 10% of nonnal and height lower than the 50th percentile are at a
CFTR activity is present, the individual may remain higher risk for death before adulthood, although a
symptom-free, or have a late onset ofcharacteristic body mass index of at least the 50th percentile in
respiratory diaease. children is associated with higher lung function. By
In spite ofearly identification and treatment that extension, achieving weight, length, and weight:length
reduces Cf morbidity and mortality, CF remains a percentiles at or above the 50th percentile by the
progressive disease. Over time, chronic airway infec- second birthday is desired.
tion results in bronchiectasis, fibrosis, parenchymal Pulmonary preventive strategies require effec-
loss, and the characteristic bleb formation found on tive airway clearance. Chest physical therapy, given
chest radiographs (Pig. 6-2). Spirometry is usually manually or utilizing high-frequency chest wall
normaJ in young children who are well treated and oscillation or positive pressure techniques, vigorous
then demonstrates obstructive, and. in late-stage exercise, and frequent coughing mobilize secretions
disease, restrictive changes. and reduce infectious exacerbations. Bronchodilator
use is associated with improved lung function. Re-
Treatment combinant human deoxyribonuclease (rh-DNue),
In early life, the most important Intervention is the administered via nebulization daily, breaks down
provision ofpancreatic enzyme replacement therapy
sticky DNA complexes present in mucus as a result
and salt to avoid malnutrition and salt-depletion of white blood cell accumulation and deterioration.
Alternate month-inhaled antlpseudom.onal antibi-
otics, including tobramydn and aztreonam lysine,
are indicated for patients chronically infected with
Pseudomonas. Three times weekly azithromycln, in
addition to inhaled antibiotics, leads to additional
benefit. Inhaled hypertonic (7CJ(,) saline improves the
hydration ofairway secretions, improves pulmonary
function. and reduces exacerbation frequency.
Acute pulmonary exacerbations are often triggered
by viral infections, which lead to bacterial overgrowth.
Exacerbations are treated with more frequent chest
physiotherapy and antibiotics, which may be taken
orally if the exacerbation is mUd and the organisms
are not resistant. Frequently, however, exacerbation
must be treated with intravenous antibiotics, often
in combination. Although antibiogram sensitivities
may be useful in guiding therapy, they are not pre-
dictive of clinical response in patients with chronic
P. aeruginosa infection.
Current strategies of correcting the basic defect
are focused on specific gene mutations. New ther-
FIGURE &·2. Chest radiograph in this adolescent mala apies known as CFTR modulators include ivacaftor,
with cystic fibrosis demonstrates marked chronic a CFTR potentiator, effective against gating, and
disease and bleb formation. partial function and splicing mutations that create
proteins that reside in the apex of the epithelial cell. PRIMARY CILIARY DYSKINESIA
Ivacaftor monotherapy is effective for approximately PCD is an autosomal recessive disorder ofciliary ul-
8~ of CF patients. The phe-508del mutation. present trastructure/function in which muoodliary clearance
in 70% of the Cf patients worldwide, has a severe is markedly impaired secondary to ciliary dysfunc-
folding defect that is improved with the CFTR cor- tion. Failure to clear secretions leads to bronchial
rectors lumacaftor and tezacaftor, which are given obstruction. sinusitis, chronic otitis media, and
in combination with ivacaftor. These agents improve recurrent respiratory infections. Lower respiratory
pulmonary function and reduce infectious exacerba- track symptoms may be similar to those of CF or
tions in patients with responsive mutations, and also asthma. Recurrent or chronic otitis media, daily
have positive effects on nutrition and health-related rhinorrhea, and a history of transient tachypnea of
quality oflife. Reduced pulmonary function decline in the newborn are much more oommon in PCD. Be-
treated patients suggests that they may also improve cause cilia are important in left-right orientation of
survival in CF. Research. is underway to identify more organs during development, organ placement (aka
effective therapies and new modulators effective for •situsj is reversed (situs inversus) in 50% of cases.
patients with other CFTR mutations. Reduced sperm motility causes male infertility, and
CFRD prevalence increases with age; CFRD women with PCD may experience reduced fertility,
should be routinely screened for using an oral glu- increased rates of miscarriage, or ectopic pregnancy.
cose tolerance test. Treatment is with insulin; dietary In very rare instances, PCD may be associated with
restriction is not advised. Regular HbA1c monitoring hydrocephalus, a condition in which excess fluid in the
and screening for diabetes complications should be ventriclea ofthe brain causesthem to be enlarged. The
performed in accordan<:e with guidelines for other diagnosis is made by the demonstration ofabnormal
types of diabetes mellitus. or absent ciliary movement or beat frequency under
Hemoptysis is an alarming development that lisht mi.croscopy and/or ch.aracteristic ultrastructural
usually occurs in patients with severe bronchiec- changes in samples of ciliated cells obtained from
tasis. Frequent coughing and inflammation lead to scrapings ofthe nasal or bronchial epithelium. About
erosion of the walls of bronchial arteries in areas of 60% to 70% of patients with proven PCD have at
bronchiectasis, and expectorated sputum becomes least one PCD-causing gene mutation identified on
streaked with blood. Minor hemoptysis is often a gene mutation panel Nasal nitric oxide is markedly
considered a sign of infection and can be managed reduced in PCD, and is used to augment diagnosis
with close monitoring. antibiotics, and increased in research settings. Pulmonary therapy includes
vibunin K supplementation for mild-to-moderate ~·agonist therapy airway clearance, butclinical trials
cases. Frank hemopt}'U with a blood loss of more of PCD· specific therapies are just beginning. Most
than 500 mL in 24 hours (or more than 300 mL/day patients with PCD develop bronchiectasis by the end
for 3 days) represents an emergency that requires of the second or third decade oflife.
bronchial arterial embolization.
Spontan~Wus pneumothorax is another potentially OlltER CAUSES OF AIRWAY OBSTRUCTION
life-threatening complication ofCF. It is usually man- IN CHILDREN
ifested by the sudden onset ofsevere chest pain and Congenital .Abnonnalllles
breathing difficulty. Small pneumothoraces may be Congenital tracheal stenosis results from abnormal
treated with supplemental oxysen and pain medication. tracheal cartiJage ring&, lacking a normal posterior
Larger pneumothoraces require the placement ofa pan membranosa. The affected segments ofthe tra-
chest tube. Approximately half of pneumothoraces chea grow more slowly than the rest of the trachea.
recur unless pleurodesis is perfunned. most often There may be a •washing machine" inspiratory and
using thoracoscopy. expiratory noise, hypoxemia. failure to thrive, and
In advanced disease, progressive airway obstruc- other symptoms. More than 90~ of patients with
tion, hypoxemia. and hypercapnia lead to pulmonary complete tracheal rings will require surgical inter-
hypertension and cor pulmonale. For CF patients vention. Patients should be thoroughly investigated
with a predicted life expectancy limited to 1 to 2 for other congenital anomalies (especially of the
years, lung transplantation is a viable option. Sur- heart and great vessels) before surgery; both imaging
vival postlung transplantation is improving, and is techniques and direct airway visualization may be
currently approximately 67~ at 5 years and 50~ at needed. In other oongenital anomalies, the trachea
lOyears. and/or main bronchi are compressed by abnormal
vascular structures (double aortic arch, aberrant left Lung volume measurements by plethysmography or
pulmonary artery, enlarged pulmonary arteries). A nitrogen washout are necessary to diagnose restric-
right aortic arch typically compresses the proximal tive disease, because severe obstruction is associated
right main bronchus. Children with these vascular with a reduction in forced vital capacity.
anomalies often have wheezing or respiratory distress. Pectus excavatum ls a depression, and pectus
Tracheomalada is a common cause of expira- carlnatum is an outward deformity of the sternum.
tory airway obstruction in children and is due to a Severe congenital forma of these malformations
widening of the posterior membranous portion of may result in restrictive lung disease as a remit of
the trachea. The result is dynamic airway collapse mechanical interference with normal respiration,
during exhalation. seen at rest or only with coughing but usually these deformities are more cosmetic than
or forced exhalation. depending on severity. These functional. Severe scoliosis has a greater effect, with
children typically have a harsh, brassy (•croupy") restriction as well as airway compression. Marked
cough and are often misdiagnosed as having recur- obesity, a risk for upper airway obstructiw disease,
rent croup. Tracheomalacia is seen after a repair of may also cause restrictive lung disease. Neuromus-
esophageal atresia with tracheoesophageal fistula. cular disease results in restrictive lung disease as
Most children with tracheomalacia require no in- a consequence of insufficient respiratory muscle
tervention. but there are surgical procedures that strength (Gu111ain-B~ syndrome, muscular dys-
can benefit chlldren with severe tracheomalacia trophy, spinal muscular atrophy).
resulting in complete airway collapse and cyanotic Any large Lesion that occupies intrathoracic space
episodes. Wheezing due to tracheomalacia may be will interfere with normal pulmonary expa.n.sion.
made worse by treatment with a ~agonist, which Pleural effusion, pericardial effusion, chylothorax,
makes the posterior tracheal membrane more flaccid hemothorax, pneumothorax, chest wall tumors,
(and thus more lilcely to collapse during exhalation). mediastinal masses, consenitallobar emphysema,
A paradoxical response to bronchodllator treatment cystic adenomatous malformations, diaphragmatic
should always raise the suspicion of tracheomala- hernias, and pulmonary sequestrations compete
da. Some children may respond to anticholinergic with normal lung for thoracic space, resulting in
therapies such as ipratropium bromide. restrictive pulmonary compromise.
Bronchomalada may occur in isolation or in Diffuse lung disease, also known u Oill.D (children's
chll.dren with trach.eom.alada, and ls the result of interstitial lung disease), refers to a group ofgenetic
either poor cartilage (in central bronchi) or poor or acquired disorders characterized by tachypnea,
elastic recon in the tissues surrounding the (more hypoxemia, cough, wheezing, and radiographic
peripheral) bronchi, resulting in dynamic bronchial abnormalities. Restrictive, or mixed obstructive,
collapse on exhalation. Affected children are frequently physiology is characteristic of these disorders. A
misdiagnosed as having asthma, but show a poor number of rare diseases lead to interstitial changes,
response to bronchodilator and steroid. including neuroendocrine cell hyperplasia ofinfancy
Congenital and dynamic airway anomalies are (referred to as NEHI syndrome), pulmonary interstitial
most conveniently and definitively diagnosed by glycogenosis, and surfactant abnormalities. Chronic
bronchoscopy. The bronchoscopic evaluation must interstitial lung disease secondary to multiorgan
be performed under spontaneous breathing, as systemic disorders such as lupus erythematous,
positive pressure ventilation or very deep sedation/ sarcoidosis, and other rheumatologic disorders also
anesthesia will mask the dynamic changes of the presents with diffuse lung disease, as can chronic or
airway during exhalation. recurrent pulmonary aspiratiotL Recurrent episodes
of chest syndrome in siclde cell disease also cause
diffuse lung disease (see Chapter 12).
RESTRICTIVE LUNG DISEASES Pulmonary hemosiderosis is caused by the ab-
Physiologically, restrictlve lung diseases result from normal accumulation of hemosiderin in the lungs
reduced compliance ofthe chest wall or ofthe lung. due to chronic diffuse alveolar hemorrhage. It may
This results in a reduction in most Lung volume be idiopathic or secondary to other inflammatory
measurements, including functional residual ca- or autoinunune disorders causing bleeding into
pacity, tidal volume, and vital capacity. Restrictive the lung. Diagnosis is based on the presence of
lung disease is much less common in the pediatric hemosiderin-laden macrophages (siderophages)
population than obstructive pulmonary disorders. in bronchial washings or gastric aspirates. Clinical
manifestations of pulmonary hemosiderosis may in- are important but often not diagnostic, because most
clude recurrent pulmonary infiltrates and a microcytic aspirated objects are radiolucent. It is imperative that
hypochromic anemia with elevated reticulocyte count. radiographic studies utilize optimal techniques for the
Patients with hemosiderosis are often mistakenly detection offoreign bodies; bllateral decubitus films
diagnosed clinically to have recurrent pneumonia. may show unilateral air trapping during expiration.
When frank hemoptysis or hematemesis is present, Bronchoscopy is necessary for definitive diagnosis
endoscopic evaluation may allow the identification or exclusion. Rigid bronchoscopyis indicated for the
ofa vaacular abnormality and subsequent treatment removal ofa known foreign body. Small foreign bodies
The symptoms of restrictive lung disease may be can remain in the lower airways for years, causing
subtle until the process is relatively advanced. Exercise persistent/recurrent pneumonia. atelectasis, chronic
Intolerance, tachypnea. and eventually dyspnea at cough. and bronchiectasis.
rest are common. Space-occupying lesions may or
may not be detected by chest auscultation (noting
APNEA AND BRIEF RESOLVED
decreaBed breath sounds over the affected area) and
UNEXPLAINED EVENTS
may be seen on chest radiographs or ~n on an
echocardiogram. Progressive restrictive disease can Apnea is defined as the cessation of breathing for
lead to chronic respiratory insufficiency. Pulmonary longer than 20 seconds, or pauses of any duration
hypertension may result; a characteristic accentuated associated with color changes (cyanosis, pallor),
pulmonic component of the second heart sound hypotonia, reduced responsiveness, or bradycardia.
occurs in severe disease. Echocardiography is usually It may be central (neurally mediated), obstructivtJ, or
the diagnostic method ofchoice. Oubbing offingers mixed. Apnea is not a diagnosis but rather a potentially
and toes may be noted. dangerous sign requiring appropriate evaluation to
define the underlying cause. In contrast to apnea of
prematurity, apnea of infancy occurs In full-term
ASPIRATION SYNDROMES infants. Table 6-8 lists some of the more common
The larynx protects the lower airways from aspira- potential causes.
tion of liquids and/or solids. Vocal cord closure and The term •apparent life..threatening event"
coup are vitally important protective reflexes, and has been replaced by a new term. briefresolved
abnormal function ofeither can result in aspiration. unaplaln«< event (BRUE). BRUE is defined as an
Reduced sensation, impaired vocal cord mobility, event occurring in an infant younger than 1 year
or structural defects (laryngoesophageal cleft, of age, characterized by cyanosis or pallor; absent,
tracheoesophagealfi.stula) can result in aspiration. reduced, or irregular breathing; marked changes
Aspiration of liquids (saliva, ingested liquids, or in tone (increased or reduced); and altered level of
gastric contents resulting from gastroesophageal responsiveness. These events are frightening to the
reflux) leads to cough. bronchospasm. inflammation, caretaker, who often believes that the child would
infection, and, if persistent, to bronchiectasis and have died without intervention (vigorous stimulation,
fibrosis. The diagnosis of recurrent aspiration can cardiopulmonary resuscitation).
be supported by radiographic (video swallow) or The goal of diagnostic evaluation is to identify
endoscopic studies. There is no definitive marker for the treatable causes of symptoms, with a focus on
aspiration, unless the aspiration is directly observed. life-threatening causes. Table 6--8lists potential tests
Children with uncontrolled gastroesophageal reflux to be considered depending on the results of the
are at risk for aspiration and often have persistent/ history and physical examination. In approximately
recurrent respiratory symptoms (cough, wheeze, half ofcases, no predisposing condition is ever found.
recurrent pneumonias). Management involves treating the underlying
Acute aspiration ofa solid object is common inyoung disorder. When no treatable cause can be found,
children, especially between ages 1 and 4. Presenta- the infant may be placed on a home monitor that
tion may result in cotJ8hing, choking, wheezing. and senses chest movement (breathing) and heart rate
respiratory distress. Specific sympmms and severity and sounds an alarm when the child becomes apneic
depend on the size of the object and where it lodges or bradycardic. BRUE does not raise an infant's risk
in the airway. Moat events are not witnessed. so a high of dying of sudden infant death syndrome (SIDS),
degree ofclinical suspicion is required in cases where a which may be why home monitors have never been
sudden onset ofsymptoms occurs. Radiographic studies proven to reduce the likelihood of SIDS.
TOLl a-a. Brief Resolved Unexplained Events

!Ca- --------------- ~~D~...a . . .__________________
lWet:IIDul
ISepail CBC/blood culture
j Meningitis LP
! Pneumonia Chest radiograph
IPertuuia PCR or fluol'eiCZilt antibody ltainblg
IRespiratory sync:yt1al virus infection PCR or fl.uoreiiCellt antibody staining
! lleunJitJg/c
! Seizures EEG
!Central apnea Polysomnography
!! Intraventricu.lar hemorrhage Cranial ultrasound
i Retlp/nlloly
!Airway oMtru.ctlon Airway radiographJ or bronchotcopy
!Aspiration Swallowing study
!t:anliac
j Arrhythmias ECG
!GlltlltrJintBit
j Gastroao~al reflux Barium swallow or pH/impedance probe
!Oftltr
IMetabolic disorders Thsb fur inborn enors of metabolism
i Electrolyte dllorders Electrolyte panel/blood gtueo~e
!Abate SkeletalllllrftY/.fundoscop1c exam
i Abb!WaUons: CBC, complete blood count; EOG, electrocardiography; EEG, electroenoephe.lography; LP, lumbar puncture; PCR,
! polymerase chain reaction.
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KEY POINTS
• Infants with bilateral ctloanal atresia often present are the treatment of choice for symptom control
with life-threatening respiratory distress in the and avoidance of exacerbations for patients
delivery room, although oxygenation improves with persistent asthma.
when the Infant Is crying. • The disappearance of wheezing with increased
• Severe obstructive sleep apnea can result in respiratory dlstn188 slgnalslncl"'888d obstruction
cor pulmonale, whlctl may be fatal. rather than Improvement.
• The three main components of asthma are • CF Is a disorder ot eplthellallon transport
revenalble airway obstruction, increased airway affecting the lungs, sinuses, pancreas, sweat
responsiveness, and Inflammation. Disease and salivary glands, Intestines, and reproductive
saverity is classified befora the onset of 1raat- system. Befont ttle advant of newborn screening,
ment as Intermittent, mild persistent, moderate fal~a to thrive, chronic cough, and steatorrhea
persistent, and severe persislant, although the ware the most common preae11tations of CF
control of dlseaae at IllY severity level is a 11'101'8 in children. Because false-negative newborn
important concept. screening tests occur, these symptoms sho~
• Inhaled bronchodllatcn are the treatment of sUII prompt diagnostic testing for CF. Maconlwn
choice In an acute asthma exacerbation. ICSs ileus in the neonate Is virtually pathognomonic.
• A diagnoeie of CF Ia made by an elevated • Persistent wheezing that does not 1'86p0nd to

sweat chloride level i"' the presence of sugges- conventional medical treatment should raise a
tive clinical symptoms or a positive newborn strong suspicion far anatomic abnonnalities or
screening test. for an 89pirated foreign body.
• BRUE does not Increase the risk of sudden infant
death, and the uae of home apnea monitors
does not reduce the risk of SIDS.
CLINICAL VIGNETTES
VIGNmE1 L Oral corticosteroid (prednisone)

A 4-year-old male with a history of asthma presents to b. Intravenous aminophylline
the emergency department with a chief complaint of c. Intramuscular ceftrtaxone
cough and shortneu of bresth. Physical examination d. Supplemental oxygen
reveals an afebrtle child In mild dls1rels with a rasplratory e. ICS
rate of 40 b,.-ths per minute, an occasional dry cough,
VIGNETTE2
and diffuse, symmetric wheezing on auscultation. He
looks worried. There Is no history of a choking episode A 2-year-old male comes to your primary care office
before the onset of wheezing, and 1he child haa no with the complaint of daily cough since the first few
history of anaphylaxis. months of life. When he is Vetr'f active physically. he
sometimes wheezes. He has an uncle with asthma,
1. Which of the following studies Is most approprtate and his parents have treated his wheemg with the
tor an lnmal assessment of the severity of this uncle's bronchodilator inhaler without improvement
patient's acute episode? He has two oldersmlings who are healthy. On physical
a. Chest radiograph examination, his height Is at the 3oth percentile for
b. Complete blood cen count age, his weight ia below the 5th percentile for age,
c. Pulse oximetry and his chest is slightly hyperinftated. Auscultation
d. Sputum culture of the chest is normal. His abdomen is protuberant,
e. Respiratory viral culture but no organs or masses are palpable. While In the
2. Following one treatment with a short-acting examination room, he nua his diaper with stool, and
~-agonist (albutero~. the patient has improved the odor Is extremely foul. His mother notes that his
only slightly. The S~».~ is 92% in room air, and stools are always large and sometimes have orange
the patient still has diffuse wheezing. Which of oil in them. Your initial evaluation includes a chest
the following treatments is most likely to improve radiograph, which reveals mild hyperinflation and
respiratory signs and symptoms within the next bronchial thickening but Is otherwise unremarkable.
30 minutes? 1. Which of the following Is highest on your differ-
a. Albuterol ential diagnosis list?
b. Albuterol plus ipratropium L Asthma
c. Oral theophylline b. Tracheoesophageal fistula
d. Intravenous aminophylline c. CF
e. Intramuscular epinephrine d. PCD
t. Bronchiolitis
3. After receiving the above-mentioned treabnent,
the child improves somewhat cinically, but stil 2. On the basis of the preeeutatlon, what Is the first
has wheezing, subcostal retractions, and mild 'test you should perfonn?
tachypnea. His respiratory rate has dec:reas8d to a. cr of the chest
26 breaths per minute, and he can talk In phrases b. QuWJtitative piocarpine iontophoralia sweat teat
and short sentences. His SIX>2 on room air Is now c. Barium enema
96%. He Is more alert and active. Which of the d. Complete blood count with quantitative serum
following interventions is indicated at this time, immunoglobulin levels
if not already administered? e. CFTR gene mutation panel
3. The sweat test 111su1t is indatarminate at 50 mEqJL onset of wheezing. He has eaten peanut butter
Which of the following Is the most appropriate in the past without incident. The decubitus film
next response? reveals failure of the left lung to empty when the
L Measure pencreatlc enzyme concentration In child Is lying on the left side. Given the posnlve
a duodenal aspirate. results of the study, we now have a reasonably
lb. Send blood for CFTR genotyping. firm diagnosis of foreign body aspiration, most
c. Reasaure the family that the sweat test is neg- likely a peanut (or peanut fragmen1). Which of the
ative and the child does not have CF. following represents the most appropriate next
d. Initiate pancreatic enzyme therapy and refer step in diagnosis/management?
to a CF specialist. L Administration of bronchodilators and chest
e. Send the child to a research center for measuring physiotherapy to help the child expectorate
nasal mucosal electrical potential difference. the putative peanut
b. Admission to the hospital for observation while
VIGNETTE3 waiting for the foreign body to be coughed out
A 2-year-old male begins coughing and wheezing while spontaneously or to dissolve in situ
at a birthday party. Physical examination reveals coarse c. Performance of flexible bronchoscopy as soon
wheezing but no other abnormalities. Breath sounds as possible
are equal. He has no personal history of asthma, but d. Performance of rigid bronchoscopy as soon
his father Is described as a severe asthmatic. The aa poaaible
child exhibited no symptoms of a respiratory infection e. Admission for observation, with nothing by
before the party. mouth and intravenous fluids orders overnight,
and scheduling a rigid bronchoscopy for the
1. What Is the most appropriate diagnostic technique
next morning
In this slbJatlon?
L Postertorantertor (PA) and lateral chest radiographs 3. The next morning, the child Is taken to the oper-
lb. Administration of a bronchodilator aerosol, ating room and a piece of peanut Is removed via a
with subsequent reasaeesment of breath rigid bronchoscopy. What is the most appropriate
sounds follow-up for this child?
c. Bilateral decubitus chest radiographs L No follow-up is needed; bronchoscopy removed
d. Magnetic resonance imaging (MRI) scan of the peanut.
the chest b. Repeat chest radiograph in approximately 1
e. CT scan of the chest week.
c. Perform PFTs.
2. New history is now obtained that the child was
d. Perform a chest CT scan.
seen with peanuts In his hand just before the
ANSWERS
VIGNETTE 1 Question 1 is not affected by a knowledge of viral etiology unless

1.AnswerC: this is the first documented episode of wheezing.
Hypoxemia, when preaent,lncllcates a severe episode of
obstructive lung disease or the presence of a comorbld VIGNETTE 1 Question 2
condition such as atelectasis or pneumonia. Hospital 2.AnswerB:
admission is indicated for hypoxemia that persists after Albuterol pluslpratroplum Is moN effective than albutarol
appropriate initial interventions. In the absence of fever alone for patients who have mora seve111 bronchospasm,
or localized physical findings on chest auscultation, a such as those who fall to Improve slgnmcantly after
chest radiograph Is of little diagnostic value in acute a single albuterol treatment. Oral theophylline and
asthma. Complete blood cell count is also unlikely to intravenous aminophylline, although often effective in
yield any information relevant to management Although cases of mon. severe, chronic asthma, are no longer
sputum examination might provide information such recommended for acute treatment; albutarol is both
as the presence of eoslnophils, acute management is more effective and safer. Although intramuscular
not likely to be affected. Moreover, most 4-year-olds epinephrine results in significant bronchodilation, its
cannot expectorate sputum. Although rhinovirus is a use is reserved for extremely severe bronchospasm,
major cause of wheezing, treatment of the acute episode such as when a patient is unable to cooperate with
the administration of Inhaled ~-agonist or is moving treatment should never be delayed pending diagnostic
into raspiratory failurelai'T8st. conflrmaHon. Sweat testing should be performed In a
center wnh significant experience and expertise w ith
VIGNETTE 1 Q...tlan 3 the technique.
3. Answer A:. Measurement of pancreatic enzyme concentrations
The efficacy of ICSs in acute asthma has been studied, in duodenal fluid ia a uaeful {although difficuH) t est of
but systemic administration is the preferred and more pancreatic function, but is invasive and is rarely used
effective route. As ind icated previously, aminophylline for diagnostic purposes. CFTR genotyping can be
is rarely used for t he treatment of asthma in the acute done, even as a primary d iagnostic tool, but is more
setting. In the absence of c linical infection, antib iotics expensive and takes longer than sweat t esting.
have no role in the treatment of acute asthma. Sup- In patients w ith CF, there is an e levated e lectrical
plemental oxygen can act as a weak bronchodilator, potential difference across the respiratory mucosa
but this patient's pulse oxygenation measurement, (nose and airways) that is a reflection of the inherent
respiratory rate, work of breathing, and mental status abnormality in electrolyte transfer. This is sometimes
have improved, so oxygen is no longer indicated. a useful adjunctive diagnostic tool in patients with
atypical presentations, and Is used In research settings,
VIGNETTE 2 Quesllan 1 but the procedure Is cumbersome and Is not routinely
1.Answer C: used In clinical practice.
The correct choice Is CF. A major clue Is the failure to
thrive and the foul-smelling stools, which accompany VIGNETTE 3 QuaatiGn 1
maldigestion and malabsorption. Asthma can cause 1.AnswerC:
cough and wheezing but should not result in failure The correct choice is bilateral decubitus chest radio-
to thrive or foul-smelling stools, and the wheezing graphs. The most likely diagnosis, and the one which
would be expected to respond to bronchodilators. A is most urgent in t erms of immediate therapeutic in-
tracheoesophageal fiStula will lead to chronic cough, tervention, is foreign body aspiration. Most aspiration
typically associated with feedings, and possibly recur- events in toddlers are unwitnessed . In the context of
rent pneumonias, b ut not impaired digestion. PCD is a party, with many c hildren and often chaotic activi-
not associated w ith malabsorption. Bronchiolitis is an ties, the potential for the aspiration of a small (food)
acute process that s hould resolve within a week or two. object Is higher than usual, especially because many
well-meaning adults will put out candles, peanuts, and
VIGNETTE 2 Quesllan 2 other small obJects. The decubitus films will reveal
2.Answer B: air trapping as the result of the fo~elgn body blocking
The sweat test is the most reliable and rapid d iagnostic egrass of air from one lung, even when the obstruc-
test for C F. A chest scan may be indicated later in the tion is not complete and inspiration sounds normal
disease process to assess bronchiectasis, although (the central wheezing may be difficult to lateralize
standard chest radiography is currently recommended with a stethoscope). The dependent lung, if the main
fer disease monitoring. Because the underlying disorder bronchus is blocked, will not deflate, thus revealing
is not associated with an Intestinal anatomic anomaly, the presence of the obstruction. On the contrary, PA
a barium enema would not yield any additional infor- and lateral radiographs are snapped at full inspiration
mation. A complete blood count and immunoglobulin and will often appear nonnal.
levels are initial steps In the evaluation of immunode- It would not be unreasonable to administer a
ficiency, but symptoms are more suggestive of CF. A bronchodilator, but this can often give a false sense
CFTR gene mutation panel is indicated because it may of security. Foreign objects in the airways may also
directly affect treatment with modulators. However, not move from one to another location, especially In the
all patients w ith CF will have the causative mutations first hours after the aspiration event, and auscultation
Identified by a mutation panel, so It should not be Is not a reliable Indicator of foreign body aspiration.
relied on for the Initiation of treatment. MRI and CT scans are unlikely to reveal a small
foreign bodly, and both are muc h more expensive
VIGNETTE 2 Q...tlan 3 than plain films.
3.Answer D:
Tl98tment is indicated in a child who has symptoms VIGNEnE 3 Question 2
of CF and an intennediate sweat chloride value. 2.Anawer E:
Furthermore, chronic malabsorption and low serum This child has just been at a party, and his stomach
protein levels can cause spurious reduction of sweat surely contains a fair amount of food, which places
chloride levels. In a symptomatic child, including an him at significant risk when undergoing anesthesia
infant with a positive newborn screen and poor growth, induction. Only in cases of s ignificant respiratory
distress and a high risk of complete airway obstruction patient, but not without the ability (and preparation) to
should such a child be taken directly to the operating proceed Immediately to rigid bronchoscopy. Flexible
room for endoscopy. bronchoscopes do not permit safe and effective IWTloval
The use of cheat physiotherapy to help expecto- of most foreign bodies and should not be used tor this
rate a foA:~ign body is contraindicated unless theA~ purpose except in very specific situations.
is definitive evidence that the foreign body is quite
small and cannot be extracted with a bronchoscope. VIGNEJTE 3 Qu-'lon 3
Children have died from complete airway obstruction 3.Answar B:
when a foreign body had lodged in the larynx after Nuts are sometimes aspirated whole, but more often
being coughed up from a more peripheral location. they are aspirated in multiple fragments. It is common
It is appropriate to admit the child to the hospital for to find more than one significant fragment of an aspi-
observation while awaiting safe transport to another rated nut in the airways, and most bronchoscopists
facility where rigid bronchoscopy can be performed know to look for them on the first procedure. How-
(if not at the initial facility), but allowing the child to ever, small fragments may lodge out of sight of the
cough up the foreign body (presumed in this case to bronchoscopist and produce problems later in smaller
be a peanut) places the child at grave rtsk. Most for- airways. Such fragments will most often lead to the
eign bodies will not disintegrate, and many will swell formation of granulation tissue, bronchial obstruction,
as they absorb moisture, thus producing more airway and atelectasis, which usually become evident on
obstruction. Granulation tissue often forms around a subsequent chest films.
foreign body that has been in place for more than a Pulmonary function testing is not suitable for
dayorao. 2-year-olds, as childrvn of this age are developmentally
Flexible bronchoscopy is a very important and unlikely to undemand the verbal instructions. A chest
useful procedure for the diagnosis of a foreign body CT scan is not indicated and cannot be used to identify
aspiration and could be used as a first step in this radiolucent foreign bodies.
Infectious Disease
Leena B. Mithal and Katie S. Ana
Remarkable advances in the diagnosis, manage- FEVER OF UNKNOWN ORIGIN

ment, and prevention of infectious diseases have
occurred during the past century. Specific treatment The meaning offoyer ofunknown origin (FUO) can
of bacterial illnesses began with the introduction vary, but generally implies daily fever with temperature
of sulfonamide& in the 1930s and penicillin in the greater than 38.3"C {101"F) for prolonged duration (8
1940s. Newer classes of antibacterial agents include or more days), and uncertain etiology after history,
semisynthetic penicillins, tetracyclines, macrolides, physical examination, and preliminary laboratory data.
fluoroquinolones, aminoglyrosides, carbapenems,
and five generations of cephalosporins. Antifungal, DIFFERENTIAL DIAGNOSIS
antiviral, and antiparasitic agents have also been FUO in the pediatric population is usually a com~
developed. Other agents for the prevention and mon disorder presenting in an uncommon manner.
treatment of infections include specific antibodies, Overall, infectious etiologies are more common than
intravenous (IV) immunoglobulin, phagocyte-stim- rhewnatologic ones, which are more common than
ulating factors, and interferons, Vaccines have led oncologic disorders as a source for FUO. Diagnostic
to a dramatic decline in certain infectious disease&. considerations include the following:
Smallpox was eradicated worldwide in 1977, and
• Infection: Sinusitis, osteomyelitis, intra·abdom·
poliomyelitis was eliminated from the United States
inal abscesses, endocarditis, hepatitis viruses,
in 1979. The annual incidence of measles, mumps,
cytomegalovirus (CMV), Epstein- Barr virus
rubella, diphther ia, and Htumophilw influenztu
(EBV), cat-scratch disease (bartonella), brucellosis,
type b meningitis has decreased by more than 98%
Rocky Mountain spotted fever (RMSF) and other
because ofvaccine use in the United States, However,
rickettsial infectious, enteric fever (typhoidal
measles in particular is now making a comeback
Salmonella), tuberculosis, HIV
because of widespread geographic pockets with high
• Connectil'e tissue diaeue: Juvenile idiopathic
rates of parental vaccine refusal..
arthritis, systemic lupus erythematosus
Unfortunately, new pathogens continue to emerge.
• Mallpancy: Leukemia, lymphoma, neuroblas·
Severe acute respiratory syndrome appeared early
toma, sarcoma
in the new millennium, caused by a previously un-
• Other: Inflammatory bowel disease, Kawasaki
known coronavirua. In 2009, a novel HlN1 strain of disease, drug fever. hemophagocytic lymphoJUstio.
influenza emerged and spread rapidly throughout the
cytosis, periodic fever syndromes, thyrotoxicosis,
world. Equally disconcerting is the rapid emergence
sarcoidosis, and factitious fever
of resistance to known antibiotics (e.g., methicillin-re-
sistant Staphylococcus all1Y!W, penicillin-resistant
Stmptococcus pneumoniae, multidrug resistant
Mycoba~rium tuberculosis, and gram-negative Histury
bacteria with few to no effective antloiotic options). A history of associated complaints such as red eyes,
Thus, after 100 years of progress against infectious joint or limb pain, and gastrointestinal symptoms can
diseases, the current challenges are every bit as be informative and narrow differential diagnOJis. Ex~
formidable as at the beginning of the last century. posure history including travel history, sexual history,
-
112
Chapter 7 I Infectious Disease • 113
contact with animals, tick bites, trauma, and food for routine use in infants, the incidence of all in~
can provide clues, Antecedent illness, weight loss, vasive pneumococcal infections has decreased by
trauma.. and family history are important areas of approximately 8096 for children younger than 24
inquiry. Details offever history such as fever patterns months of age. A 13-valent pneumococcal vaccine
(constant, recurrent, cyclical) occasionally suggest introduced in 2010 has replaced PCV7 for universal
particular diagnoses. A thorough history and physical administration in the United States.
examination (usually after repeated encounters) will In contrast, sepsis implies bacteremia with evidence
reveal the diagnosis in more than halfofthe children of a systemic inflammatory response (tachypnea,
in whom a cause of the fever is found. tachycardia, etc.) and altered organ perfusion. M-
fected children appear toxic and may develop shock.
Pllylical Examination The cause ofsepsJs varies by age. In neonates, group
Conjunctivitis, lymphadenopathy, raah. joint tender- B streptococcus (Streptococcus agalacdtu), enteric
ness or effusion, oral ulcers, thrush. heart murmurs, gram-negative bacilli (Escherichia coli), and Listeria
hepatosplenomegaly, masses, abdominal tenderness, mo1fOC1topna are most prevalent. In older children
bony tenderness, limp, and mental status changes may up to 5 years of age, S. prreumoniae predominates,
suggest a specific cause and guide further evaluation. in addition to group A streptococcus (GAS [Strepto--
coccus pyogenes]), S. aureus, Neisseria menlngitidls.
DIAGNOSTIC EVALUATION
S. aureus Js a more common pathogen in children
The initial evaluation can be performed in the outpatient more than 5 years ofage. Less conunon causes include
setting in older, well-appearing children. Neonates Salmonala specieJII, PMudomontu aeruginosa, and
and ill~appearing children require hospitalization. viridans group streptococci.
Screening laboratory tests include complete blood The evaluation ofthe child with suspected sepsis
count (CBC) and differential, serum electrolytes, includes cultures from the blood, urine, and cere-
blood urea nitrogen (BUN) and creatinine levels, liver brospinal fluid (CSF [if meningitis is a concern]). A
function tests including transamlnases, and urinalysis chest radiograph is obtained if respiratory signs or
(UA). Bacterial cultures should be obtained from the symptoms are present. Initial empiric antimicrobial
specimens of blood, wine, and possibly diarrheal therapy is selected on the basis of the age of the
stool Additional tests to consider include erythro- child, the likely etiologic agents, and any identified
cyte sedimentation rate (ESR), C-reactive protein, foci of i.nfection.
and specific serologic tests such as antibody studies
for infectious pathogens such as cat-scratch disease,
ACUTE OTITIS MEDIA
EBV, CMY, or others. A chest radiograph may reveal
infiltrates, lymphadenopathy, or muses. Skin testing Suspected or confirmed acute infection of the middle
for tuberculosis is performed as indicated. More ear accounts for frequent outpatient pediatric sick
expensive and invasive studies may be warranted visits. The middle ear is normally sterile; a patent
on the basis ofexam findings and screening results. but collapsible eustachian tube allows fluid drain-
Usually, children recover without sequelae even if age from the middle ear into the nasopharynx but
no etiology is determined. nonnally prevents the retrograde entry of upper
respiratory flora. In children, the angle of entry,
short length, and (in some patients) decreased tone
BACTEREMIA AND SEPSIS
of the tube (eustachian tube dy1junction) increase
Bacteremia is the presence of bacteria in the blood. susceptibilityto infection. When the eustachian tube
Bacteremia Js further described as occult if it oc- is further narrowed by edema from a concurrent viral
cur• in a well-appearing child without any obvious upper respiratory infection (URI), secretions (and
source ofinfection, The risk of occult bacteremia is bacteria) from the nasopharynx can accumulate in
highest (1.596 to 2.5%) in children between 2 and 24 the middle ear.
months of age often with fever greater than 39.<rC
and leukocytosis. Most episodes are caused by S. EPIDEMIOLOGY
pneumonlae and resolve spontaneously. Rarely, Acute otitis media (AOM) is most common in children
localized infection (e.g., meningitis, pneumonia) 6 to 24 months ofage. VJ.I"USes (respiratory syncytial
oa:urs. Since 2000, when a conjugated seven~valent virus [RSV], influenza viruses, human metapneum~
pneumococcal vaccine (PCV7) was recommended virus, picornaviruses, coronaviruses, adenoviruses)
are a common cause ofAOM. Bacterial infection or topical antibiotic drops. A tympanic membrane that
superinfection is common. Bacterial causes include is erythematous without any other signs of disease
S. p•umonitu, nontypeable R lnflue'lfZIU, an.dMo· may be caused by vigorous crying and should not
raxella catarrlrali&. Unfortunately, approximatelySOIJ6 be considered AOM.
of S. pneumonlae isolates are resistant to penicillin
and many apecia of H. influenzae and moat M. lnatment
catarrhalis produce P·l.a.ctamase. Because more antibiotics are prescribed for AOM
than any other pediatric condition, and because
RISK FACTORS antibiotic resistance is a growing concern, both
Risk factors for AOM are age, exposure to tobacco the Centers for Disease Control and the American
Bmoke, lack of or limited breastfeeding, day·care Academy of Pediatrics have issued guidelines for
attendance, allergic disease, craniofacial anomalies, the treatment of AOM. Patients younger than 24
immunodeficiency, and a family history with possilile months of age, patients thought to be at risk fo.r
genetic factors. poor follow-up, ill· appearing patients, and any
patients with chronic lllnesses (including immu-
CLINICAL MANIFESTATIONS nodeficiencies) or recurrent. severe, or perforated
Children may have local or systemic complaints AOM should be prescribed antibiotics for 10 days.
o.r both. Nonspecific signs include fever, fussiness, High~ose amoxicillin is the recommended first·line
headache, or poor feeding. Ear pain is a common treatment. For patients who have been treated with
complaint, which in smaller chlldren may present antibiotics within the last month, with concurrent
as ear rubbing, but is not universally present. purulent conjunctivitis, or with a history of recur·
rent AOM unresponsive to amo:xicillin. amoxicillinl
History and Physical Examination
clavulanate is recommended. Alternate choices in
AOM is frequently preceded by the symptoms of
those with penicillin hypersensitivity include oral
URI (cough, rhinorrhea, congestion). On phymcal
second- or third· generation cephalosporin or in-
examination. the affected tympanic membrane ap.
tramuscular (IM) ceftriaxone. Children older than
pea.rs bulging, opaque, and erythematous with an
24 months with less severe disease may be ofrered
aberrant lisht reflex. Pneumatic otoscopy reveals
the choice of immediate antibiotic therapy versus
reduced tympanic membrane mobility. The diagnosis
pain control and watchful waiting. Children who are
of AOM should be made only when there is an acute
untreated initially should have a mechanism in place
history of symptoms and a bulging, poorly mobile
to ensure follow· up and begin antibiotic therapy if
tympanic membrane is noted in the presence of the
worsens or there has been no improvement within
signs oflocal or systemlc inflammation. Perforation
48 to 72 hours. Patients with perforated tympanic
of the TM can occur from AOM, often accompanied
membranes in addition to AOM should receive oral
by purulent drainage in the canal.
(and possibly topical) antibiotics at initial diagnosis.
Dlffarentlal Diagnosis Most spontaneous perforations caused by AOM
Otitis media with effusion (OME) or serous otitis is resolve within 24 to 72 hours.
diagnosed when there is apparent fluid behind the The most common complication ofAOM is OME,
tympanic membrane (reduced mobility on pneumatic which follows virtually all cases of AOM and takes
otoscopy) but no evidence ofinflammation (tympanic a variable amount of time to resolve. Children with
membrane translucent/gray, no fever, no evidence of OME that persists longer than 3 months should be
ear pain). Myringitis is inflammation of the eardrum referred to an otolaryngologist. Chronic OME may
accompanied by normal mobility. This condition increase the risk of hearing lou and delay oflanguage
often accompanies a viral URI. Neither OME nor acquisition. Tympanostomy tubes may also be con·
myringitis responds to antibiotic treatment. Otitis sidered for chlldren with frequent episodes of AOM.
exterM (inflammation ofthe external ear canal) also Complications offrequent episodes of AOM include
causes ear pain; however, the tympanic membranes excessive scarring (tympanosclerosis), cholesteatoma
should appear normal on physical examination. The formation, and chronic suppurative OM.
pain of otitis externa is exacerbated by manipulation Mastoiditis (infection of the mastoid bone of
ofthe external ear, and the ear canal appears erythem- the skull) is a potentially severe but uncommon
atous, often with patchy areas of purulence. Otitis complication of AOM characterized clinically by
externa. often called swimmer's ear, is treated with revel; postaur.icular tenderness and erythema over
the mastoid bone, and anterior displacement of the are noted on the palms and soles (and occasionally
external ear. Mastoiditis is treated initially with IV on the buttocks), the more inclusive name hand-
antibiotics; surgical drainage may also be required. foot-and-mouth disease is used.
SINUSITIS STREPTOCOCCAL PHARYNGITIS

The maxillary and ethmoid sinuses are present at Group A ~~hemolytic streptocoa:i (GAS;S. pyogenes)
birth; the sphenoid and frontal sinuses develop later in are the most important cause ofbacterial infection of
childhood. The spectrum of pathogens responsible for the throat. Antimicrobial therapy for streptococcal
sinusitis is virtually identical to that for OM. Sinusi.tis disease is recommended because of the frequency
is ofren difficult to diagnose in a young child because of suppurative (peritonsillar abscess, retropharyn-
the classic symptoms of headache, facial pai.n. and geal abscess) and nonsuppurative (rheumatic fever)
sinus tenderness may be absent or difficult to artic- complications.
ulate. There are suggestive clinical courses of acute
EPIDEMIOLOGY
bacterial sinusitis including: (a) persistent respiratory
symptoms (> 10 to 14 days) without improvement, Strep throat most commonly afflicts school-aged chil-
including either nasal discharge (clear or purulent) dren and adolescents. The organism is spread person
or a daytime cough, (b) severe symptoms including to person through 1nfected. oral secretions. At any
high fever and purulent nasal discharge for at least 3 one point in time, approximately 10% to 15% of well
days, and (c) worsening symptoms (respiratory, new children carry GAS as part oftheir nonnal oral flora.
headache, or fever either new or after initial improve-
ment). The differential diagnosis includes viral URis,
allergic rhinitis, and nasal foreign body. Sinusitis is HlsiDry and Phy&lcal EXamination
primarily a clini.cal diagnosis. Radiologic studie5 of Cassie symptoms include sore throat, fever, headache,
the sinuses may be useful in older children when there malaise, nausea, and occasionally abdominal pain.
is a poor response to therapy and the diagnosis is in Physical examination reveals enlarged. erythema-
doubt. Sinus aspiration may be needed for recurrent tous, exudative tonsils, and tender anterior cervical
or refractory disease. Antibiotic coverage is similar to lymphadenopathy. Petechiae may be present on the
that for AOM (10 to 14 days), although longer therapy soft palate. Rhinorrhea, hoarseness, and coughing,
at least 3 weeks is indicatEd for chronic sinusitis. Com- the hallmarks of viral URis, are notably absent. The
plications are uncommon but include bony erosion, diagnosis ofscarlet fever is made when a characteristic
orbital cellulitis, and intracranial extension. Children erythematous, "sandpaper-like" rash accompanies
with recurrent or chronic severe sinusitis should be the fever and pharyngitis. The rash commonly be-
evaluated for cystic fibrosis, ciliary dyskinesia, or gins on the neck, axillae, and groin, spreads to the
primary immune deficiency. extremities, and may desquamate 10 to 14dayslater.
DlffaranUal Diagnosis
HERPANGINA Differentiating viral pharyngitis and infectious mono-
nucleosis from streptococcal pharyngitis on the basis
Herpangina is a symptom complex caused by of clinical symptoms may be impossible; definitive
enteroviruses (including groups A and B coxsack- diagnosis requires either throat culture, antigen
ieviruses and other enterovirus serotypes). It is detection. or nucleic acid detection test for GAS.
typically diagnosed during the summer and fall in
younger children. Initially, the patient develops a Diagnostic Evaluation
high fever and very sore throat. On examination. Therapeutic dedslons should be based on throat
characteristic vesicular lesions that progress to ul- culture or rapid anttsen-detection test results. The
cers are scattered over the soft palate, tonsils, and specificity of most rapid antigen tests is greater than
pharynx. Primary herpeticgin.givo•tomatitU (caused 95% (compared with throat culture}, so false-poaitive
by herpes simplex virus [HSV]) presents in a similar test results are rare. The sensitivity of rapid antigen
manner, although the lesions are generally more tests is more variable and is highly dependent on
widespread and notable over the gums, lips, and the quality of the throat swab specimen. Therefore,
mucosa. Herpangina is self-limited (5 to 7 days) and a negative rapid antigen test should be confirmed
requires no specific therapy. When similar lesions by a throat culture. Molecular testing (nu.cleic acid
ampli6cation/polymerase chain reaction [PCR]) or stenosis. Acute episodes respond favorably to

has high sensitivity and if available .,in house,• it is antibiotics, anti-inflammatory drugs, and cardiac
reasonable to forego throat culture. management. ARF may recur after the initial episode;
thus, individuals diagnosed withARF should receive
Treatment Ions-term prophylactic penldllln therapy to prevent
Patients with docume nted GAS pharyngitis should the recurrence ofGAS infection and ARF.
receive a 10-day course oforal penicillin (or amoxicillin Acute poststreptococcal glomuulonephritis may
or a single dose of IM benzathln.e penicillin G) to follow either GAS pharyngitis or skin infection
hasten symptom resolution. reduce transmissibility, (cellulitis) and is not prevented by antibiotic therapy.
and prevent acute rheumatic fever (ARF). A clinical Clinical manifestations follow infection by approx-
isolate of GAS resistant to penicillin has never been imately 10 days and include hematuria, edema,
documented. Oral second- or third-generation oliguria. and hypertension. Complement (C3) levels
cephalosporins (if mild allergy), azithromycin. and are low. Treatment consists of penicillin therapy and
clindamydn are acceptable alternatives for children diuretics; steroids are rarely indicated. In contrast
allergic to penicillin. The treatment of scarlet fever to affected adults, the majority of affected children
is identical to that for streptococcal pharyngitis. recover without renal sequelae.
ARF occurs about 3 weeks after streptococcal
pharyngitis in a small percentage of untreated pa-
tients. ARF is an inflammatory condition involving INFECTIOUS MONONUCLEOSIS
connective tissues of the heart (carditis, valvular
destruction), joints (migratory polyarthritis), PATHOGENESIS
and sometimes the central nervous system (CNS Infectious mononucleosis is a disease characterized by
[transient chorea]). Diagnosis rests on fulfilling the fever, tonsillar pharyngitis, and lymphadenopathy that
Jones criteria (Table 7-1). Initially, fever, dyspnea. occurs in older children and adolescents when they
cardiac murmur, and arthritis predominatei Ions- develop a primary EBV infection. Other pathogens,
term morbidity results from valvular destruction notably CMY, acute }{[Y, and rarely T~plasma
with consequent mitral or aortic valve insufficiency gondii, can result in a similar clinical picture.
TilLE 7•1. Revised Janes Criteria for ttle Diagnosis of ARF

lllniiiiiARF ............. '5 'IIIIa- •GM .... PI.. ._MIIIDrlllnlllll....ll!l•....; ; - - - - -
!lllnlfwllllliw
1Carditis
................
Clinical Positive throat culture for GAS or
i Polyarthritis (low-rilk population") Fever PoBitive rapid antigen tl!llt or
! Monoarthritia or polyarthritis or polyarthralgia
i (moderate· or high·rilk populations)
l 0\orea Increued streptococcal antibody
ti~
IErythema marginatum
i Subcutoneouonodul"
Elevated ESR or
C-reactive protein
Prolonged PR interval
onECG
i Diagnosis of NlF requl1118 two major a one major and two miner crlterfa plus supporting evidence of antecedent group A
1streptococcal Infection.
i •According to I'8Vi8ed criteria May 2015, low-risk populations are those with an ARF incidence s2 per 100,000 school·aged children !
i or with an all-age rheumatiC heart di8ease prevalence o1 s1 per 1,000 population per year. !
!• Antibody tests indude antislreptolysin-Q, anti-DNase B, antihyaluronidase, or antistreptokinase. !
iAbbreviations: AAF, acute rheumatic feller: ECG, electrocardiography: ESR, erythrocyte sedimentation rate: GAS. group A l
l. ~~~~.~:..... .... . . . . . . . . . . . . .... . .. . . . . . . . . . ... . . . . . . . . . . . . . . . . . . . . . . . . . ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . .... . ... . ... ..... . . . . . . . . . . . . . . . . . . . . . . . ...J
EPIDEMIOLOGY Diagnostic Evaluation

Transmission OCCW'5 by mucosal contact with in&cted Lymphocytosis and sometimes leukopenia may be
saliva (hence the term "kissing disease•) or possibly present. Lymphocytes account for more than 50~ of
genital fluids. A majority of people are infected leukocytes, and usually more than 101J6 are atypical
with EBV and seroconvert in early childhood. Such lymphocytes. A heterophile antibody (or mono-
early infections are generally asymptomatic or mild spot) test allows rapid detection ofEBV-assoclated
in immunocompetent hosts, although prolonged mononucleosis in the outpatient setting; however,
fever and the mononucleosis syndrome can occur it has limited sensitivity in younger patients (<4
in younger children as well. years of age). Specific serologic antibody testing
is available for EBV (Fig. 7-1) and CMV, typically
CLINICAL MANIFESTATIONS IgG and IgM. Other laboratory findings may
History and Physical Examination include thrombocytopenia and elevated hepatic
transaminase levels.
The predominant symptom is umally an exudative
pharyngitis. ~ generalized lymphadenopathy,
Treatment
and profound fatigue occur. Although the pharyngitis
The disorder is typically seH-limited, requiring
usually resolves within 1 to 2 weeks, the malaise may
persist for several weeks. Other manifestations include only supportive care. Activity restrictions (ie., no
splenomegaly, palatal~ jaundke, and rash. Pa- contact sports) are advised until any associated
tients infected withEBV who are misdiagnosed with a
splenomegaly resolves because of the possibility
of splenic rupture.
bacterial infection and receive amoxicillin or ampicillin
Rare but serious complications include upper
are lilcelyto manifest a generalized maculopapular rash.
airway obstruction (treated with corticosteroids),
Differential Diagnosis splenic rupture, and meningoencephalitis. Bacterial
Classic mononucleosis caused by EBV accounts for deep pharyngeal infections may sometimes follow
most cases. Other infectious agents that cause similar EBV infection, and thus, the presence of uvular
symptoms include CMv, T. gondll, human herpesvirus deviation, drooling, trismus, and neck pain must be
6, adenovirus, acute HIV, and hepatitis B. Pharyngitis evaluated promptly. Immunocompromised individ-
caused by GAS is difficult to distinguish from that uals are at risk for severe disseminated disease and
of viruses without laboratory studies. lymphoproliferati.ve disorders.
I Heterophile Antibody I
Primary Infection Convalescent serology
+ +
''' Early antigen VCA-IgG
',, ~
, .... ._ ~:~.arr nuclear antigen
~\8\IY'-'
/ I ---·---·-:>---- ' '

2 4 2 4 6
Weeks Months
Time following onset of illness
!~.~~-~.!~.~-~ -~P.~~~-~-~-~..?!..~!~.~...~.~-~~-~..§.~Y..!~~~JY.~:..§.~:~~!..9..~!~..~.!~.~~).:.............................................................
CROUP
Acute laryngotracheobronchitis, commonly called
croup, refers to virus-Induced inflammation of the
laryngotracheal tissues, resulting in a syndrome of
upper airway obstruction. Croup usually is caused
by parainfluenza viruses, but can also re.ault from
other viruses, such as influenza and RSV.It is most
pronounced in yoq children (6 to 36 months of age)
because of the narrow caliber of the airway below
the vocal cords (subglottic region). In.ci.dence peaks
during the late fall and winter. At its most severe,
the disease progreues to partial or total airway ob-
struction; fortunately, this is extremely rare.
Children typically experience the sudden onset ofa
hoarse voice, barky (seal-like) cough. and inspiratory
stridor, which may progress to respiratory distress.
There is often a prodrome consisting of low-grade
fever and rhinorrhea 12 to 24 hours before the on-
set of stridor. Respiratory compromise varies from
minimal stridor with agitation to severe distress with
tachypnea, hypoxia, nasal flaring, and retractions.
Dlagna&llc Evaluation
The diagnosis umal1y is made on the basis ofclinical
findings. Ifobtained. anteroposterior neck and chest FIGURE 7-Z. Croup in a 3-year-old child. Note the
radiographs may reveal a tapered, narrow subglottic =~~!?.!.~.~!~!].~..!.~.~!~~~.~..~.~~.~!!?..~!~~~~~.:.....................
airway (steeple sign; Fig. 7-2).
Dlff8rentlal Dlagnosll cricothyroidotomymay be performed ifan endotra-

The differential diagnosis ofupper airway obstruction cheal airway cannot be secured in the face of rapidly
(Chapter 6) includes epiglottitis, bacterial tracheitis, progressive obstruction. rv ampidllin-sulbactam or a
foreign body aspiration, anaphylaxis, and acute third-generation cephalosporin provides appropriate
angioedema. Epiglottitis consists of inflammation empirical coverage until the organism is identified by
and edema of the epiglottis and aryepiglottic folds, culture and sensitivities are known. The incidence of
typically from bacterial infection. It is considered a epiglottitis has decreased markedly since the advent
llfe...threatening emergency because ofthe propensity of routine administration of the H. influenzae type
of the swollen tissues to result in sudden and irre- b (Hib) vaccine in the late 1980s. Cases caused by S.
versible airway occlusion. Most cases occur during pneumoniae, GAS, and S. aureus are also reported.
the winter months in children 3 to 5 years of age. Failure to maintain current Hib vaccination status
Fewr, sore throat. hoarseness, and progressive stridor is the biggest risk factor for developing epiglottitis.
develop over 1 to 2 days. On examination., the child
appears toxic, drools, and leans forward. with chin Treabnent
extended to maximize airway patency. Lateral neck Most children with croup never beoome symptomatic
radiographs show "'thumbprinting" of the epiglottis enough to prompt a visit to the pediatrician. Cough
(Fig. 7-3). Although radiographs may aid in diagnosis, and stridor respond well to cool night air or humid-
they are not recommended because they delay ap- ity, and the disease resolves over 4 to 7 days. In the
propriate care. The child with suspected epiglottitis emergency department, stridulous infants receive cool
requires timely transport to the operating room mist, nebulized racemic epinephrine, and oral, IV, or
and emergent endotracheal intubation. Emergency 1M corticosteroids. Impending respiratory failure and
RISK FACTORS
Children with chronic lung disease, congenital heart
disease, neurologic disease, congenital or acquired
immunodeficient states, and preterm infants are
more susceptible to severe disease. Hospitalization
rates peale between 2 and 5 months ofage, but a. large
proportion of hospitali:zations occur in children of
more than 6 months of age.
HI&1Dry
The acute illness lasts for 5 to 10 days, followed by
gradual recovery over the next 1 to 2 weeks. Infected
neonates may develop life-threatening apnea. Infants
initially present with fever, cough. and rhinorrhea
followed by progressive respiratory dJstress. Household
contacts usually have upper respiratory symptoms.
Children in daycare or with older siblings are at a
higher risk of acquiring RSY.
Physical EXamination
Physical findings include fever, tachypnea, and
mild-to-severe respiratory distress. Wheezing.
rhonchi. cracldes, and accessory muscle use during
respiration (tugging, retractions, nasal flaring) may
be noted. ill infants may be restless or lethargic.
RBUR£ 7-3. Epiglottitis in a 4-year-old child with massive Hypoxia is common in severely affected patients.
edema of 1he epiglottis, thickened aryepiglottic folds,
and effacement of the valleculae. Dlffllnnllal Diagnosis
The wheezing associated with bronchiolitis may be
difficult to di.stingui..sh from asthma or airway foreign
airway obstruction constitute medical emergencies body in older infants. The causes of the recurrent
and are addressed accordingly (Chapter 20). episodes of wheezing include vucular rings, cystic
fibrosis, and clllary dyskinesia.
BRONCHIOLITIS Dlagnos11c Evaluation
Rapid assays from nasal secretion samples exist for
PATHOGENESIS RSV, influenza A and B, and many other respiratory
Bronchiolitis is an acute viral lower respiratory tract pathogens. Chest radiographs should be obtained for
infection that results in inflammatory obstruction more severely affected patients and for those with
of the peripheral airways. There is a predominantly recurrent or unexplained wheezing. Findings consis--
lymphocytic infiltrate into the peribronchial and tent with bronchiolitis include lung hyperinflation.
peribronchiolar epithelium that promores submucosal peribronchial thickening ("cufllng"). and increased
edema. Intraluminal mucous plugs and cellular debris interstitial markings.
accumulate because ofimpaired mucocilmry clearance.
Treabnent
EPIDEMIOLOGY Hypoxic or ill-appearing children require hospital-
RSV causes the majorityofcases; rhinovirus, parain- ization. Children with normal oxygen saturations,
fluenza, influenza, human metapneumovlrus, adeno- minimal respiratory distress, good fluid intake, reli-
virus, and coronavirus are also responsible viruses. able caretakers, and good follow-up may be treated
Bronchiolitis typically occurs between November and as outpatients.
April Almost all children are infected with RSVby 2 Most hospitalized infants require onlysupportive
years of age. and recurrent infections are common. care (oxygen, fluid support) for their self-limited
illness. Corticosteroids are not effective and are not months. Infants with severe di5ease may present with
indicated. P-Adrenergi.c agents are not recommended apnea or the typical paroxysmal cough followed by
for routine care of first-time wheezing associated. choking and prosressive cyanosis. The characteriJtic
with bronchiolitis. Palivizumab, an 1M RSV mono- whoop .Is absent in very young infants because they
clonal antibody, provides passive prophylaxis and is cannot generate sufficient negative inspiratory force.
recommended during the winter months for selected Adolescents and adults can also be infected with
patients younger than 2 years of age who are at risk pertussis and usually present with nonspecific upper
for severe disease. These patients include those respiratory symptoms and a protracted cough.
with hemodynamically significant congenital heart
Dlagnodc Evaluation
disease or with chronic lung disease of prematurity
Nasopharyngeal secretions contain the organism,
requirq medical therapy within the 6 months be-
fore the start of the RSV season. Palivizumab is also which may be detected by PCR or culture. A chest
radiograph is usually normal. but nonspecific infil-
recommended for select infants born prematurely
trates may be seen. If CBC is sent, leukocytosis with
(<29 weeks' gestation) or with certain underlying
lymphocytic predominance is often seen.
conditions such as chronic lung disease or congenital
heart disease. Treatment
The mortality rate for hospitalized patients Young infants (<4 months) with severe disease should
with RSV is less than 196. Children with congenital be hospitalized to manage apnea, cyanosis, hypoxia,
heart defects, chronic lung disease, and immuno- and feeding difficulties. Erythromycin or azithromycin
deficiency fare particularly poorly. Complications shortens the duration of illness ifgiven early in the
include dehydration, bacteriaUaspiration pneumo- catanbalpluue. After the coughing paroxysms begin.
nia, apnea, and respiratory failure. Patients with ant:J.'biotics do not affect the oourse of illness but are
documented RSV bronchiolitis may have more recommended to reduce the period of infectivity.
airway hyperresponsiveness later in life than the A 14-day course of erythromycin or a 5-day course
general population. of azithromycin eradicates the organism from the
nasopharynx and respiratory tract. Household and
PERTIJSSIS other close (day care) contacta require chemoprophy-
laxis with erythromycin or azithromycin regardless
Infection with BordeteUa pqtussls causes a URI of immunization status.
and persistent cough in adults but may result in
life-threatening respiratory disease in neonates
and infants. The organism is spread via aerosolized PNEUMONIA
droplets expelled during intense coughing. The agent
is highly infective among unimmunized hosts. The PATHOGENESIS
vaccine is 95% effective against severe disease, but Pneumonia refers to an acute inflammatory process
immunity wanes significandy within several years, occurring in the lungs. It may be infectious or non-
requiring booster doses. infectious. Inflammation can occur in the alveolar
space, the alveolar walls (interstitial pneumonia),
CLINICAL MANIFESTATIONS and/or the bronchi.
Fever is uncommon or low-grade in patients with EPIDEMIOLOGY
pertussis. The claaaic presentation in young children The age of an immunocompetent child suggests an
is '"whooping cough: The catarrhal phase follows a etiologic organism (Table 7 -2). VIrUses are the most
7- to 10-dayincubation period and consist& of 1 to 2 common cause of pneumonia in young children.
weeks of low-grade fever, cough, and coryza. Then Chlamydia trachomatis pneumonia manifests at 2
comes a 2- to 8-weelc~smal phase characterized to 3 months of age in infants born to women with
by intense spasms of coughing followed by sudden untreated genital C. tNdtomatU infection. S. Jl'leuntO-
inhalation, which produces the characteristic whoop. niae should be considered in any community-acquired
Posttussive emesis is common. Facial petechiae and lower respiratory tract infection. Mycoplasma
scleral hemorrhages can develop because offorceful pneumoniae pneumonia is uncommon in children
coughing. Most symptoms remit during the conva- younger than 5 years but, along with Chlamydophila
launt phase, but the cough may persist weeks to (Chlamydia) pneumonlae, becomes a more frequent
I
TIILI 7·2. Causes of Infectious Pneumonia by Age
1<1•
Group 8 atreptoc:ocd
111111
StrqltOctNXIU
......,
s. p11tfiRIItmi4t!'
lclloal...,....,..;
~ J1'1f11111101dM
Jnl
pU~~molfia6'
j Eschmchl4 coU/grarn- Haemophlbu lltjtlwrue H.llf/lr~enr.tn Ch/4mydophU.

l negative enteric badDi plfMUP~Difiae
I H.~UtU Sft'qltxH:occus J110leiCeS S. JI10#MS (GAS) S. P'""""'lfia6'

(GAS)
!S. p~rermwniu MoTWUJlla catarrhalis M. cattur/uJli.& H.injl~
i I.Uterls morwcyto,ma Bol'fler.eU. pmuuu M. pneumonlae S.pyo,.na

ICytomegalovirus Chlamydia tmchomat;s6 Staphylococcus t~umu S. arR"eJU
!Herpea aimplex viruJ Ureaplamul uretllytlcum 6
Mycobact.erium hlbemdoli.& M. tuberculoli.&
! U urealytlcum Vlruaes' Viruses• Vlrwlea"
Is. 4lU'eUI
!•Most common cause of bacterial pneumonia In this age group.
! Althol.(lh acquired per1nataJiy, theee Infections often do not present as pneumonia until after 1 month at age.
b
L~!~!.~.~-i-~--~~-~~--~-~!.~.~~-.!~.~~-~~-~-~~-~~-~-·..~~-~--~~~-~:........................................................................................................................j
and important pathogen in school-age children and and young children with bacterial pneumonia may
adolescents. Less common bacterial causes include present with nonspecific constitutional complaints,
nontypeableH. injluenzae, GAS, M. catarrltalil, and including fever, irritabllity, poor feeding, vomit-
S. aureus. In patients with underlying condltl.onJ such ing, abdominal pain, and lethargy. Abrupt onset
as cystic fibrosis or immunodeficiency, P. auugi1wsa of fever, chills, dyspnea, cough, and chest pain
can be a pathogen. is typical Productive cough is more common in
older patients. M. pneumoniae and C. pneumoniae
RISK FACTORS pneumonia present initially with fever, headache,
Conditions associated with an increased risk of and myalgia. These symptoms gradually subside
bacterial pnewnonia include the following: over 5 to 7 days, whereas coughing increases and
• Chronic lung disease, including cystic fibrosis, persists for 2 weeks or more.
bronchopulmonary dysplasia, and asthma Physical Examination
• Neurologic impairment (swallowing dysfunction Any indication of respiratory distress can signal
or neuromuscular disease) pneumonia, although tachypnea and dyspnea are
• Gastroesophageal reflux with aspiration ofgastric most common. Tachypnea out of proportion to fever
contents is an important clue to pneumonia in the young child.
• Upper airway anatomic defects (tracheoesophageal Diffuse wheezing and cracldes suggest involvement
fistula, cleft palate) of multiple areas of the lwtg, characteristic of viral
• Hemoglobinopathies (including sickle cell anemia) or atypical (M. pneumoniae, C. pmrumoniae, C.
• Congenital heart disease trachomati&) pneumonia. Focal findings such as
• Inununodeficiency or immunosuppressive therapy focal cracldes or decreased breath sounds, dullness
to percussion, egophony, and bronchophony suggest
CLINICAL MANIFESTATIONS lobar pneumonia ofbacterlal origin. Pneumonia can
Hlstury also present with only fever and tachypnea in the
Vrral pneumonia develops gradually over 2 to 4 absence ofchest findings.
days. It is usually pr eceded by upper respiratory Cyanosis is uncommon except in severe disease.
symptoms such as cough, rhinorrhea, postnasal Approximately 1096 ofpatients withM. pneumoniae
drip, coryza, and low-grade fever. Infants with infection develop a rash, usually macular and ery-
pneumonia caused by C. trachomatis are afebrile thematous or urticarial; erythema multiforme has
and have conjunctivitis and a staccato cough. Infants also been reported.
Dlffarentlal Diagnosis Any child with persistent hypoxia (which necessi-

Pneumonia is much more common in the pediatric tates oxygen therapy), moderate-to-severe respiratory
population than are other conditions with similar pre- distress, and/or hemodynamic instability requires
sentations, including congestive heart failure, chemical hospitalization. IV antibiotic options for bacterial
pneumonitis, pulmonary embolism. sarcoidosis, and pneumoniainclude ampldllin. ampldllin/sulba.ctam.
primary or metastatic malignancy. With worsening cllndamydn. cefuroxime, ceftriaxone, azithromydn,
fever or cough afrer viral URJ. bacterial pneumonia and vanmmycindependingon the suspected pathogens
must be considered in addition to acute sinusitis. and community!IWICeplibilitypattems. Neonates with
Dlagnastlc Evaluation suspecb:d bacterial pneumonia reo:ive additional workup
Oumbar puncture) and are started on ampicillin and
A thorough history and physical examination usually
suggest the diagnosis. Sputum culture is not likely to cefotaxime (or gentamicin if the CSF is sterile). Most
be helpful. Chest radiograph remairuJ an excellent test viral infections are self-limited. Patients with severe
disease (bacterial or viral) may .require supportive
for clefinins the extent and pattern ofinvolvement and
therapy, including mpplemental oxygen and intubation.
assessing related complications (i.e., pleural effusion,
pneumatocele). Bactedal pneumonia usually causes The most frequent complication is the development
of a pleural effusion large enough to compromise
lobar consolidation. Diffuse interstitial infiltrates
suggest viral or atypical pneumonia, although chil- respiratory effort. Empyema results when purulent
dren with Mycoplasma pneumonia may have lobar fluid from an adjacent lung infection drains into
the pleural space. Pleurocentesis (with possible
consolidation. Aspiration pneumonia is typically
chest tube placement) provides rapid relief. Surgi-
located in the right middle or right upper lobe.
cal thoracotomy is sometimes necessary to remove
In selected chlldren with pneumonia, laboratory
loculated infections or necrotic tissue. Anaerobic
evaluations are indicated to try to identify a specific
pathogen. When a large pleural effusion is present, bacteria contribute to lung abscesses and should be
the pleural fluid should be drained and sent for cell covered in aspiration pneumonias.
counts, Gram stain. and culture. When a child with
a high fever is hospitalized with pneumonia. a blood
MENINGITIS
culture should be considered. When influenza is
circulating locally, rapid influenza testing is helpful PATHOGENESIS
in guiding decisions about antiviral therapies. C.
Many pathogem can infect the leptomeninges and
trachomati.s pneumonia is diagnosed by direct flu-
CSF. Vual meningitis is typically an acute, self-limited
orescent antloody, PCR testing, or a tissue culture
illness, although viral meningoencephalitis can
of conjunctival or nasopharyngeal specimens. M.
cause permanent sequelae. Bacterial meningitis is a
pneumonieu can be noted by the PCR ofspecimens
obtained by nasopharyngeal swab or by specific
life..threatening condition associated with substantial
morbidity and mortality. The term "aseptic menin·
antimycoplasmal IgM antibody determination.
gitis" refers to meningeal inflammation caused by
However, these lgM antibodies persist in serum
an antigenic stimulus other than pyogenic bacteria
for several months and may not represent current
(e.g., enterovirus or Lyme disease).
Infection. Cold·agglutinin titers are elevated not only
in.M. pneumonlu infections but also in many cases EPIDEMIOLOGY
of viral (and some cases of bacterial) pneumonia.
The likely etiology of meningitis depends on age
Tntatment (Table 7·3). Beyond the neonatal period, in the postvac-
Therapy depends on the most likely pathogen. In cine era, viral meningitis is much more common than
the outpatient setting, high-dose amoxicillin or bacterial meningitis. Both infants and older children
amoxicillinlclavulan.ic acid is appropriate for most are at risk for meningitis caused byenteroviru&es (the
cases of bacterial pneumonia when antibiotics are most common cause ofviral meningitis). Enteroviruses
thought to be necessary. Erythromycin, azithromy· prlmarily circulate in the late summer and early fall
cin, or cl.arithromycin is recommended for so~d Overall, S. pneumon.iM and N. ~Mningitidis are the
"'walking pneumonia" caused by M. pneumonku or most common bacterial pathogens. Neonates and
C. pneumoniae. Azithromycin or erythromycin is children younger than 3 years are at highest risk for
used to treat infants with pneumonia caused by C. bacterial meningitis. Infants in the first few months
trachomatis. of life can develop late-()nset GBS meningitis and
TIILI 7-3. Causes of Meningitis by Age

1<1• 141110 1 ...... , ........,....,,.;,rt
IGroup 8 atreptoc:ocd EM:Irerlchlla CtJll s.~ s.~
, E.roU s. p~llmbllitu Neiuerla menlngltldU N. nunbtfltidl&
~ Other gram·oegative Ente~ Entenmruses Eoteroriruses
l badl1i
1Herpesllmplex virul Group 8 streptococci Borrelia burgdorftrl B. blllfdorftrl
!LUtm. monocytotua Humophlllu ltifl~ru H.~typeB•
types•
!S. prunmwniru
!•Rare n Immunized populations.
: •••••••••u . . . .. . .. . .. . .. . .. . .. . .. . .. . .. . .. . . .. . .. .. . .. . .. . .. . .. . .. . . . . .. . .. . .. . . . . .. . . .. .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . .. . .. . . . . .. . . .. .. .. . . . . . .. .. . . .. .. .. .. . .. . .. . . .. . .. .. . . . . . . . .. .. . . .. . .. . .. . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. .
have higher rates of gram-negative pathogens than PhySical Examination

older children. The Hib vaccine has nearly eliminated Patients with bacterial meningitis often appear toxic
H. influenzae type b meningitis in the United States, and may be hypertellSive, bradycardic, and even apneic.
although other types still do cause cases of meningi- In older children, the signs ofincreased intracranial
tis. Lyme meningitis, caused byBorrelia burgdorfori, pressure include vomiting, cranial nerve palsies, and
usually affects school-age children and adolescents. papilledema. Nuchal rigidity and positive Kernig
Rare causes of men.ingitis and meningoencephalitis (flexion of the leg at the hip with subsequent pain
include HSV and M. tubuculosis (most commonly on knee extension) and Brodzinski (involuntary leg
in infants), S. aunus, Cryptococcus neojormans, flexion on passive neck tlexlon) signs are markers
mosquie&-bo~ virusu, and EBY. for meningeal irritation. These findings are rarely
present in children younger than 1 year. Infants may
RISK FACTORS present with a bulging fontanelle. A rash is often
Risk factors for bacterial meningitis are the same presentwithN. meningitidU (petechial or purpuric)
as those for sepsis, because most cases result from and Lyme (erythema rnigrans) CNS infections.
hematogenous seeding. Direct invasion occurs as
a result of trawna, mastoiditis, sinusitis, and ana- Dlffarantlal Diagnosis
tomic defects in the scalp or skull. In the neonate, The differential diagnosis includes encephalitis,
low birth weight, prolonged rupture of membranes, which may develop concurrently or subsequently
and ch.orioamnionitis predispose to septicemia and (Chapter 9). Other conditions that may present with
meningitis; myelomeningocele also increases risk. a similar clinical picture include drug intoxication
or side effects, recent anoxia or hypoxia, primary or
CLINICAL MANIFESTATIONS metastatic CNS malignancy, brain abscesses including
subdural empyema, bacterial endocarditis with septic
History embolism, intracranial hemorrhage/hematoma, ma-
The classic symptoms of .meni:ngltis include nausea,
lignant hypertension, and demyelination disorders.
vomiting, photophobia, initability, lethargy, head-
ache, and stiff neck. Vtral meningitis is preceded by Diagnostic Evaluation
a nonspecific prodrome offever, malaise, sore throat. CSF analysis is diagnostic. Tests include cell counts
and headache. Unless complicated by enrephalitis, and differential. Gram stain, glucose and protein
the symptoms of most viral CNS infections generally levels, and culture. Bacteria may be detected on
resolve ova" 2 to 4days and may improve after lumbar Gram stain in cues of bacterial meningltis, although
puncture (LP). In bacterial meningitis, the prodromal their absence does not exclude the diagnosis. PCR
phase is absent and the rever is generally quite high. assays for CSF HSV and enteroviruses are available
Mental status changes. headache. focal neurologic signs. and are highly sensitive and specific. Table 7-4 de-
ataxia. seizures, and shock are not uncommon. Lyme scribes CSF findings that suggest a specific etiology.
meningitis Is characterized by low-grade~ head- Because of the potential for brainstem herniation,
ache, stiffneck, and photophobia developing over the LP should not be attempted in a child with focal
course ofl to 2weeb. Cranial nerve palsies may occur. neurologic deficits and/or increased intracranial
1'AIIU 7-4. Cerebrospinal Auid Findings Suggasting GASTROENTERITIS

a Specific Etiology for Meningitis in
Pathogens cause diarrhea by a variety of mecha-
Childhood
nisms. For example, some bacteria invade intestinal
! C.llnlpllllll flllll tissue directly, whereas others secrete injurious
!.......... ...._... VINI
toxins before or after ingestion. Viruses, parasites,
l White blood cells 100-1,000 5-500 and protozoa are also capable of inflicting disease.
j (permm') Excessive stooling causes dehydration, inadequate
i Neutrophlh >75~ <5091'.· nutrition. and electrolyte abnormalities, all of which
are poorly tolerated in infants and small children.
~Protein 'tt Normal or 't
!
~Glucose J. or U Normal CLINICAL MANIFESTATIONS
! •Nautrophlls may predominate early In the course of viral History
! menii"'Clltls.
!t mild increase; tt, moderate or severe increase; .1., mild
The history should include information about symptoms
l..........................................................................................................................................
decrease; .1..1., moderate or sswre dec:rea8e. in other family members, recent traveL medication
: :
use, inunune status, day care attendance, source of
drinking water, contact with animals, dun.tion of
symptoms, vomiting, fever, and the number, color,
and character of stools.
pressure until an expanding mass lesion is excluded
The most common bacterial causes of gastro-
by computed tomogn.phy or magnetic resonance
enteritis include Salmonella species, ShlgeUa species,
imaging. Other contraindication& to LP include
E. coli, Yersinia enterocolitica, and Campylobacter
cardiopulmonary instability and skin infection
j~juni; V'wrio cholerae may be acquired during travel
overlying the LP site.
to developing nations and from eating undercooked
Treatment GulfCoast shellfish. Patients with bacterial diarrhea
When the diqnoais ofviral meningitis is unequivocal present withfever. significant abdominal cramping,
and without compllcations, hospitalization is gen- malaise, and tenesmus; vomiting is less common.
erally not necessary. If bacterial meningitis cannot The stools contain mucus and maybe guaiac positive
be excluded, the patient should be hospitalized fur or streaked with blood. Occasionally, children with
empiric N antibiotic therapy. shigellosis present with neurologic manifestations
Vancomycin plus a thi.rd~generation cephalosporin (lethargy, seizures, mental status changes). Salmonella
(cefotaxime or ceftriaxone) achi.eves therapeutic levels species are capable ofinvading the bloodstream and
in the CSF and provides a broad·spectrum coverage of causing extraintestinal disease, including meningitis
the most likely pathogens in infants and older children. and osteomyelitis (particularly in infants and children
Neonates should be treated with ampicillin to cover with sickle cell anemia). Shigella dysenteriae and
group Bstreptococci andL. monocytogenu, cefotaxime E. coli 0157:H7 produce an enterotoxin (Shiga or
is added to cover gram~negative pathogens. Once an Shiga-like toxin) associated with hemolytic uremic
organism and its susceptibility pattern are known. syndrome, a serious complication consisting of
antibiotic coverage may be adJusted. The course of microangiopathic hemolytic anemia, nephropathy,
therapy for bacterial meningitis is usually 10 to 14 and thrombocytopenia. Up to 30% of individuals
days. Exceptions include meningococcal meningitis infected with Y. enterocolitica develop subsequent
(5 to 7 days), Lyme meningitis (14 to 28 days), and erythema nodosum. In some patients, particularly
neonatal meningitis (depending on the pathogen. those with Yenlnia, severe pain localizes to the right
14to21 days). lower quadrant, creating a •pseudoappendicitis•
The current mortality n.te for bacterial meningitis picture. Some cases of Guillain·Bar~ syndrome
is approximately lzyJ(, for neonates and less than 1096 are associated with C. jejuni infection.
for infants and older children. However, a larger In cholera, the stools quicldy become colorless
peroentage (up to 351}6 ofaffected neonates and -1696 and flecked with mucus, termed •fit:e.water• stools.
ofchildren) experience some persistent neurologic Severe diarrhea leading to hypovolemic shock may
deficit, most commonly hearing loss, developmen· develop in hours to a few days.
tal or Intellectual disability, motor incoordination, Clostridium dlfflclk produces toxins that cause
spasticity, seizures, and hydrocephalus. antibiotic--associated diarrhea and pseudomembranous
colitis. Colonization by toxin-producing strains samples from different times .should be examined for
without symptoma is common in infants younger cysts. Immunofluorescent antibody detection in stool
than 1 year of age. can also be used to diagnose G. Iamblia infection.
Rotavirus is the major cause of nonbacterial Abdominal radiographs, if obtained. are generally
gastroenteritis in infants and toddlers throughout normal or nonspecific. Endoscopic biopsy may be
the world. Infections peak in the cooler months. indicated if 1he diarrhea becomes chronic and no
Complaints include profuse diarrhea, vomiting. etiology has been identified.
and low-grade levu Severe diarrhea may lead to
significant dehydration. acidosis, and electrolyte Treatment
disturbances. Noroviruses cause similar episodic Treatment incorporates oral rehydration whenever
outbreaks of vomiting and watery diarrhea in all possible; aggressive parenteral therapy may be re-
age groups. quired in severe cases. Antidiarrheal agents are to
Giardiasis is the most commonly reported in- be avoided in children.
testinal parasitic disease in the United States. More Unless the patient is a febrile infant younger than 3
water-related outbreaks of diarrhea are caused by months or appears toxic, antibiotics should generally
Giardia Iamblia than any other organism. The illness be withheld pending culture results. Antibiotic therapy
presents with frequent. :foul-smelling. watery stools prolongs SalmoneUa shedding and should be reserved
that rarely contain blood or mucus; abdominal pain, for bacteremia or extraintestinal dissemination and
nausea, vomiting, anorexia, and flatulence often ac- fur high-risk patients with noninvasive p.st:roenteritis,
company the diarrhea. Symptoms generally resolve including infants less than 3 months of age and im-
within 5 to 7 days, although some cases linger for munocompromised penons.Antibiotics may enhance
more than a month. Patients with chronic giardiasis ~likelihood of~ development ofhemolyticuremic
are at risk for failure to thrive reaulting from ongoing syndrome among patients with diarrhea caused byE.
malabsorption. coli 0157:H7. 'liimethoprim-sulfamethoxazole or
azithromycin is often effective in treating shigellosis.
Physical EXamination Azlthromydn. ceftriaxone, or clprofioxadn is the
The main goals of the physical examination are treatment of choice for C. jejuni unless 1he isolate
estimating the degree of dehydration (Chapter 5), is suaceptible to trimethoprim-sulfamethoxazole
judging the stability of the patient's condition, identi- or ampicillin/amoxicillin. Patients with C. dqficile
fying findings that may point to a specific infectious enterocolitis usually improve with suspension of
or noninfectious etiology, and ruling out a surgical antibiotic therapy, but if treatment is warranted.
condition. metronidazole is the medication of choice for initial
treatment Patients with giardiasis are also treated
Dlffarantlal Diagnosis with oral metronidazole.
Acute diarrhea in childhood is usually caused by As long as the patient does not develop hypovolemic
infection. Other conditions associated with diarrhea shock, prognosis for full recovery is excellent. Even
include malabsorption, celiac disease, anb."biotic use, in life-threatening cases, appropriate management
cystic fibrosis, and inflammatory bowel disease. often prevents permanent sequelae.
Electrolyte and renal function studies (Na, I<. a,
PINWORM INFECTION
HCOg, BUN, creatinine) guide replacement therapy in
significantly dehydrated children, in combination with The roundwormEnterobiusvermicularis causes pin-
symptoms and examination (Chapter 5). Blood. mucus, worm infection. Preschool and school-aged children
and fecal leukocytes sugest a bacterial origin fur the have the highest rates of pinworm infe<:tion. Itching in
illness. Blood culture should be performed at the time the perianal and vulvar regions is a common presenting
ofinitial evaluation ifbacterial disease is suspected. symptom. Examination may be normal. Diagnosis
Bacterial stool culture results take several days but can be established by touching the perianal skinwith
are helpful in determining the need for antibiotics. transparent adhesive tape to collect anyeggs; the tape
If there is a history of antibiotic use, stool should be is then applied to a glass slide and examined under a
tested fur C. dijficile toxins A and B. Rapid antigen low-power microacopic lens. Very few ovaare present
testing is available fur rotavirus. IfG. Iamblia or other in stool; therefore, stool ova and parasite examinations
parasite/helminlh infection is suspected, multiple stool are not recommended. The drugs ofchoice are pyrantel
pamoate or albendazole, given in a single dose and HBV infection to replicate. HBY and HCV can
repeated in 2 weeb. Pinwonn infections may duster persist for many years following acute infection.
in fmillies, and therefore all household member.s are This •carrier state" is associated with the develop-
often treated as a group. Reinfections are common ment of hepatocellular carcinoma. The incidence
and may be treated in the same manner as the first of hepatitis B infection is low in the pediatric
infection. Handwashingis the most effective method population because of routine vaccination against
of preventing pinwonn infection. hepatitis B in infancy.
RISK FACTORS
HEPATITIS IV drug users and those who have unprotected sex
PATHOGENESIS with multiple partners are at an increased risk of
contracting HBV, HCV, and HDV. Transmission by
Acute hepatic inflammation in children can be caused
transfusion ofcontaminated blood or blood products
by a large number of infectious and noninfectious
is exceedingly rare in the United States. Risk factors
etiologies. Primary hepatotropic viruses include
for HAV and HEY include foreign travel, poor sani-
hepatitis A virus (HAV), hepatiti.s B virus (HBV),
tation, and contact with other children in day care.
hepatitis C virus (HCV), hepatitis D virus (HDV),
and hepatitis E virus (HEV). Table 7-5 compares
the features ofHAv; HBV, and HCV, the three most
common pathogens. Hlstury
Perlnatally infected lnfuts are usually asymptomatic.
EPIDEMIOLOGY The likelihood ofsymptoms increases with age. The
HAY and HEY are acquired via fecal-oral trans- clinical sigm of acute hepatitis infection include
mission. The incidence of hepatitis A infection nonspecific symptoms: anorexia. low-grade fever.
among US children is decreasing because of the malaise, nausea, vomiting, abdominal pain and signs
addition of routine vaccination against hepatitis A ofclinical hepatitis such as jaundice and dark urine or
in infancy. HBV, HCY, and HOY are transmitted fulminant hepatitis with liver failure. Children with
by percutaneous or mucosal exposure to infectious HAV and HEY may also have diarrhea. Howeve~ a
body fluids (including sexual transmission) and wide range ofseverity exists, and as many as 30% to
by vertical transmission from an infected mother 70% ofinfected children are asymptomatic. HBV and
to her infant. HDV consists of RNA genome and HCV infection are often silent, in that the patient may
&-protein antigen. It is a •defective" virus in that it complain of no symptoms unless chronic infection
requires the presence of an active acute or chronic has caused significant hepatic damage.
TABLE 7-1. Viruses Responsible for Hepatitis: Comparison and Summary

!........ H...... A
-----
lllplllllll lllpdiiiC
IVJ.rUS type RNA DNA RNA
j Incubation (d) 15-48 43-180 15-160
! Period of infecttvity
:
Late incubation to early When HBIAg seropositive Unknown
aymptomatl.c state
iFulminant hepatitis < 1'.11i 1'.111-3'.111
1"
IChmnk.- No <5'.11i rX adults; 25"-SO'.IIi
ofinfants and young
children <Sy old; 90'.IIi
5596, 80% of perinata]ly
acqu1recl
perinatal1y acquired
1---- Anti-HAY lgM HB&Ag, HBeAg, anti-HBs,

anti-HBc, anti-HBe
! AbbriJ\IIatlons: anti-HBo, total antibody to hepatitis B core antigen; anti-HBe. total antibody to hepatitis B a antigen; anti-HBs, total
j antibody to hepatitis B Sl6faoe antigen; HAV, hepatitis A 1tirus; HBeAg, hepatitis Be antigen; HBsAg, hepatitis B surface antigen;
Anti-HCV antibody,
HCV PCR
!:..................................
HCV. hepatitis C virus; PCR, polymerase chain reaction.
............................................................._....._...........................................................................i
~··················"'" '''''' '''"'-''''''''''''""""''''''''''''''''''''''''''""""""""""""""""" """""""""""" ;
Liver enzymes are uniformly elevated in hepatitis.
Because the clinical manifestations are so similar,
specific serologic tests are indispensable for securing
lgG-anti-HAV
- -t'l-
' -- an aa:urate diaposia. The presence ofanti-HAV IgM
antibody confirms HAV lnfection (Flg. 7-4). Tests are
also available to detect antibodies to the &-antigen.
Three difrerent particles may be found in the serum
of patients infected with HBY. The Dane particle is
lgM-anli-HAV the largest, made up of a core antigen (HBcAg) and
Jl
envelope antigen (HBeAg) surrounded bya spherical
II shell of HBsAg ("surface•) particles. Figure 7-5 and
- 1 2
Incubation period
Weeks
3 4 5 6 7 8 3
Mon1hs
6 9 12 2
Years
3
Table 7-6 present the clinlcal course and serologic
markers important in diagnosing HBV disease stage.
Anti-HBs antl.oodies herald resolution ofthe illness
Time alter exposure and confer lifelong immunity.
-~~-~~-~.!~.T.Y.P.!~.~!..~-~-~~..?.!.~~~~--~-~~~-~:......................... HCV antibody is present in both acute and
chronic infection. HCV RNA can be detected by
PCR within 1 week of infection, whereas the "'win-
dow period" from infection to antibody response
PlrySical Examination for HCV may be as long as 12 weeks. Therefore,
Scleral icterus and jaundice may or may not be the presence of HCV RNA in the absence of an
present. Other possible signa and symptoms include antibody response indicates acute infection. Re-
hepatomegaly and right upper-quadrant tenderness. covery is characterized by the disappearance of
A benign-appearing rub and other extrahepatic HCV RNA from the blood.
manifestations such as arthritis may appear early
PI"Bftntton
in the course of hepatitis B.
Both active and passive forms of immunization are
DlfrerenllaJ Diagnosis available, depending on the source of infection. HAV
EBV, CMV, enterovirus, and other viral infections immunization is recommended for all children in
can also cause hepatitis, but other organ systems the United States. Immune globulin prevents hep-
are usually involved. Jaundice may also result from atitis A clinical disease when administered within
autoimmune hepatitis, metabolic liver disease, biliary 14 days of exposure. The HBV vaccine series is also
tract disorders, and drug ingestions. recommended for all children in the United States.
Symptoms
HBaAg anti-HBa
_ ...~ Total anti-HBc

' , - - - HBsAg
,' \ ., lgM anti-HBc
1 , - - - anti-HBs ,...---
-·-·-
FIGURE Hi. The course of acute
hepatitis B. anti-HBc, total antibody
to hepatitis B core antigen; anti-
,'
,
\
\, ~
\ I
/
/ --
HBe, antibody to HBeAg; anti- ' I
HBs, antibody to HBsAg; HBeAg, '\ I
hepatitis B e antigen; HBsAg, I
hepatitis B surfaoe antigen; lgM, 0 4 B 12 16 20 24 28 32 36 52 100
!.~-~~~~-~!~.~~.!!~..~.:.............................................. Postexposure (wk)
TAll! 7-8. Comparisons of Disease States in HBV

!-r.t AadiiHft -t.IHft Gniii:HIV
!H&Ag + +
!Anti-H& +
i ADti-HBc + ± ±
IHBeAg ± ±
i Anti-HBe + ±
i
~ Abbrso.llatlons: anti-HBe, total antlboctf to hepetltls B core antigen; anti-HBe, total antibody to hepatitis B e ant199n; anti-HBs, total
i antibody to hepetltls B SYfaoe antigen; HBeAg, hepe.tltls Be antigen; HBsAg, hepatitis B surfaoe antigen; HB\1, hepatitis B ltirus. ,
:ooooooooooooooooooOOooooooo•ooooo"""'""''"""""" '""" ' ' ' ' ' ' " ' " " ' '''"''''''''''''''''''''''''''''"'''''''"'''' '"'' ' '' " ' ' ' '' '''''''''''"' ' ' ' '' ' '' '''''''''''''''''''n'''''n'OO'''""'"''"""' ' '" ' "" " " "' ' '' ' ' " " ' '' ""''''''''''''''''''''''''''''''''''''''''''''' ' ' ' '"
Infants ofinfected mothers (or ifmother's infection EPIDEMIOLOGY

status is unknown) should receive both the vaccine Syphilis in the pediatric population may be acquired
and the HBV immunoglobulin at delivery to prevent in utero (congenital syphilis) or through sexual con-
the disease and development of the carrier state. tact. The incidence of syphilis has increased sharply
Prognosis over the past few decades. Coinfection with other
The prognosis for patients with hepatitis depends STI.s is common.
on the virus responsible.
RISK FACTORS
• HAV: Very few patients develop fulminant hepatitis, Neonateshom to mothen with untreated infections are
but the mortality rate among those who do is high.
at risk for congenital syphilis. Adol.escents and adults
• HBV: HBV may persist as chronic hepatitis, and who have unprotected sex with an infected partner
the course may be relatively benip or more severe. or multiple partners are at risk for primary syphilis.
Ouonic persistent hepatitis B is charact.erlzed bylittle
ceUular inf1a.mmation and usually resolves within
1 year. Chronic active hepatitis is more aggressive,
progressing to cirrhosis and increasing the risk of HlslDry and Physical Examination
hepatocellular carcinoma. Chronic infection is Approximately half of infants with congenital
more likely among infected children than adults. syphilis die shortly before or after birth. Those who
• JIDV: When liDV andHBV are acquired simulta- survive are often asymptomatic at birth but develop
neously, the recipient is at a greater risk for more symptoms within 1 month if untreated. Infants
severe chronic hepatitis B and fulminant hepatitis with congenital syphilis may have hepatomegaly,
associated with a higher mortality rate. When an mucocutaneous lesions, jaunclice, lymphadenopathy,
individual is infected with IIDV on top of preex- and the characteristic snuffles (nasal discharge).
isting HBV, acute exacerbation and an accelerated Long-term sequelae include deafness and mental
course result. The risk of progressing to cirrhotic retardation.
liver disease is also increased when JIDV is present. Syphilis acquired through sexual contact progresses
• HCV: About half of those infected with HCV through three stages. After approximately a 3-week
develop chronic hepatitis, with an increased risk incubation period, infected individuals enter the
for cirrhosis and hepatocellular carcinoma. primary stage ofsyphilis, characterized by the classic
• HEV: HEY does not appear to result in chronic chancre at the inoculation site: a well-demarcated,
hepatitis. firm, typically painless genital ulcer with an indurated
base (Appx. Fig. A-17). Because the lesion heals
spontaneously within weeks, patients with primary
SYPHILIS syphilis often do not seek medical attention.
Syphilis is primarily a sexually transmitted infection Untreated patients may develop secondary syphilis,
(STI) resulting from infection with the spirochete manifested most commonly by widespread dermato-
Treponema pallidum. logic involvement coinciding with the dissemination
of the spirochete throughout the body. The typical suggest neurosyphilis. A positive CSF VDRL is
rash consists of generalized (including the soles diagnostic. Untreated infants may develop anemia,
and palms) erythematous macules and papules thrombocytopenia, and radiographic abnormalities
(Appx. fig. A-18). Some patients also develop sys- of the long bones.
temic symptoms including fevet malaise, pharyngitis,
mucosal ulcerations, headache, and generalized Treabnant
lymphadenopathy; patchy alopecia is also associated Parenteral penicillin G (1M or IV) remains the treat-
with secondary syphilis. The symptoms ofsecondary ment of choice for any stage of infection and fully
syphilis resolve in 1 to 3 months. eradicates the organism from the body.
About one-third of untreated patients develop
late manifestations or tertiary syphilis years after
primary exposure. Tertiary syphilis is rare in the GENITAL HERPES SIMPLEX
pediatric population. Granulomatous lesions called VIRUS INFECTION
gummas destroy surrounding tissues, especially in the Genital herpes results from infection with HSV type
skin, bone, heart, and CNS. Unfortunately, tertiary 2 (historically more common in recurrent genital
syphilis may occur without any previow primary or disease) or type 1. Small mucosal tears or skin cracks
secondary manifestations. are inoculated with the viru during sexual activity.
Dlffanntlal DlagnDIIs Herpes is one of the most common sexually acquired
Syphilis is one of the great masqueraders, a disease diseases; about 20% ofadults have a history sugges-
with a wide spectrwn ofpresentations. The presence tive of prior genital herpes infection. Transmission
of the rash, ifcharacteristic, greatly aids in diagnosis. of HSV from mother to infant at the time of birth
may result in devastating infection in the newborn.
Diagnostic EValuation
Otancre scrapings (and mucosal secretions in CLINICAL MANIFESTATIONS
infected neonates) demonstrate rapidly mobile or- History and Physical Examination
ganisms moving in a rork.screw-like motion under Aften variable incubation period (2 to 14days). genital
dark-field microsropy. Aspiration ofenlarged lymph burning and itching progress to vesicuJarlesions and
nodes may also yield the organism. Roth the venereal then painful shallow ulcers thatheal without scarring
disease research laboratory (VDRL [developed by (Appx. Fig. A-19). ~pharyngitis, headache, and
the Venereal Disease Research Laboratory of the malaise may accompany the primary episode. After
U.S. Public Health Service]) and the rapid plasma acquisition, the virus ascends peripheral nerves to
reagin (RPR) are excellent blood screening tests for dorsal root ganglia, where it may lie latent or recur
high-risk populations, providing rapid, inexpensive, periodically. Recurrences have fewer symptoms than the
quantitative results. Roth are nontreponemal tests primary episode, and asymptomatic shedding occurs.
for antibodies to a lipoidal molecule rather than the Individuals with genital herpes should be counseled
organism itself. Both are considered highly sensitive that HSV can potentially be spread to their sexual
when titers are high or when the test is complemented partners even when genital lesions are not present
by historical or physical evidence of the disease.
However, infectious mononucleosis, connective DIAGNOSTIC EVALUAnON
tissue disease, endocarditis, and tuberculosis may Giant multinucleated cells with intranuclear inclusions
all result in false-positive VORL and RPRresults. By are found in scrapings from the ulcer base (Tzanck:
contrast, treponemal teats, such as the fluorescent testing); howeveJ; this classic histologic test is not
treponemal antibody absorption (fTA-ABS) and rerommended because oflow sensitivity. Options for
T.paUidum particle agl:utination (TP-PA), are much HSV testiJ18 are (1) viral culture from the active lesions,
less likely to producefalse positives. A positive screening which grows within 1 to 4 days and (2) molecular
VDRL or RPR coupled with a positive FTA-ABS or testing with PCR. Direct fluorescent antibody staining
TP-PA in a newborn or sexually active adolescent is from the lesion is also available. Serum tests for HSV
virtually diagnostic of untreated syphilis. Nontrepo- (type-common and type-specific) lgG antibodies are
nemal tests may become negative after treatment. not routinely reromme nded They may be negative
whereas treponemalatudies remain positive for life. early in primary infection. However, ifpositive, HSV
Neonates with suspected congenital syphilis type 2-specific IgG is weful in confirming a clinical
require LP. CSF pleocytosis and elevated protein diagnosis of genital herpes.
TREATMENT • Oral temperature greater than 38.3•c (lOl"F)

Oral antiviral agents (including acyclovir) diminish • The presence of white blood cells (WBCs) on
the lensth of both symptoms and shedding but do saline microscopy of vaginal secretions
not eradicate HSV. They have limited efficacy in • Mucopurulent cervical or vaginal discharge
recurrent episodes. Con tinued prophylactic use of • Laboratory evidence of cervical infection with N.
oral acyclovir or valacyclovir prevents or reduces gonorrhoeae or C. trachomatis
the frequency of recurrences. Patients should be • Elevated ESR and/or C-reactive protein
counseled regarding the potential to spread HSV to
others even without active or visible genital lesions. HISTORY AND PHYSICAL EXAMINA110N
Other symptoms include cramping, vaginal discharge
or bleeding, nausea/vomiting, and malaise. The
OTHER SEXUALLY TRANSMITTED
physical examination may be positive for peritoneal
INFECTIONS
signs if severe.
Infections with. Ne13serla gonon-hoeae (gonorrhea),
C. tmchomatis, 1Wchomonas vaginalis, and human DIAGNOSTIC EVALUATION
papillomaviruses are covered in Chapter 3. Nucleic acid amplification tests (NAATs) are sensi~
tive and specific for both gonorrhea and chlamydia.
PELVIC INFLAMMATORY DISEASE If a patient is suspected of having PID, she should
be offered testing for syphilis, HIY, and other STis.
Pelvic inflammatory disease (PID) is a constellation of Often, a specific pathogen responsible for PID is
symptoms and signs related to the ascending spread of not identified because PID is an upper genital tract
pathogenic organisms from the lower female genital disease, whereas samples are routinely obtained
tract (vagina, cervix) to the endometrium, fallopian from the lower tract.
tubes, and contiguous structures.
Dlffarenllal Diagnosis
EPIDEMIOLOGY Other gynecologic conditions and intra~abdominal
PID is generally polymicrob.ia], with C tmchomati8 pathology are included in the d.i1ferential diagnosis:
and N. gonon-hoeae the most commonly isolated
• Gynecologic: mucopurulent cervicitis, ectopic
organisms. Other potential causes of PID include
pregnancy, ruptured ovarian cyst, septic abortion,
anaerobes and enteric gram~negative bacilli. Barrier
endometriosis
contraceptive methods provide some protection.
• Nongynecologic: appendicitis, pyelonephritis,
N. gonon-hoeae or genital C. tmchomatis infection
inflammatory bowel disease
in a prepubertal chlld strongly suggests sexual abuse.
Patients with suspected PID should always re-
RISK FACTORS ceive a pregnancy test because treatment may need
Adolescence is a period of increased risk for the de- to be altered and because ectopic pregnancy is a
velopment ofPID because ofthe presence ofcervical life-threatening condition that must be ruled out.
ectopy (the extenaion of columnar cells that line the
endocervical canal onto the external cervix) and the TREATMENT
increased incidence of high-risk behavior during the Patients with clinical PID should be treated for both.
teenage and young adult years. Risk factors also include N. gonorrhouu and C. tmchomatis. Coverage against
.sexual intercourse with multiple partners, unprotected anaerobes (such as metronidazole and clindamycin)
intercourse, and a preexisting mucosal sn and other gram·negative organisms is often added.
Patients with mild~~moderate PID may receive
CLINICAL MANIFESTATIONS outpatient therapy. A single close of a Jong~acting
The clinical diagnosis of PID is made in a sexually parenteral third-generation cephalosporin, such as
active woman with. pelvic or lower abdominal pain ceftrlaxone, combined with a 14-day course oforal
and evidence of cervical motion, uterine, or adnexal doxycycline, is recommended. The duration ofdox-
(ovaries) tenderness on exam. Additional criteria ycycline therapy (14 days) is longer for patients with.
are often used to support the diagnosis of PID and PID than for those with uncomplicated gonorrhea or
increase specificity. Additional criteria: chlamydial infections \7 days). Oral metronidazole may
be added to this dual therapy regimen. All patients motile trichomonads. Male partners may have
who are releued for outpatient treatment should dysuria and/or penile discharge. Oral metronidazole
return for a follow-up visit within 72 hours. Sexual is the treatment of choice for patients and their
contacts need to be treated to avoid reinfection. sexual partners.
Indications for hospitalization include severe
illness, vomiting, pregnancy, lack of response to Bacterial Vaginasis
oral medications, blood pressure instability, or a Bacterial vaginosis, Ions thought to be harmless, is
possible surgical condition. These patients should now known to increase the risks ofPID, chorioamni-
receive N antibiotics, including cefotetan or cefoxitin onitis, and premature birth. Its microbiologic cause
plus doxycycline. An alrernative regimen consists of has not been clearly delineated, but concentrations
clindamycin and gentamicin. Within 24 to 48 hours of Gardn.erella vagiMlis, Mycoplasma hominis,
of sustained clinical improvement, these patients and various anaerobic organisms are increased in
may be transitioned to oral therapy. the vagina. In contrast, concentrations ofLactoba-
Women with repeated episodes ofPID may have cillus species are decreased. The epidemiology of
problems with fertility. Other gynecologic complica- the disease suggests sexual transmission. Infection
tions include increased risks for ectopic pregnancy, is usually asymptomatic except for a thin, white,
dyspareunia, chronic pelvic pain, and adhesions. foul~smelling discharge that emits a fishy odor
N. gon.orrhoeae is capable of invading the blood- when mixed with potassium hydroxide. The clinical
stream and thus any organ system. Joint involvement diagnosis is based on patient history (much more
is most common. The arthritis may affect only one common in sexually active females), the appearance
joint or may be polyarticular and migratory with and odor of discharge, a vaginal pH greater than
associated tenosynovitis and skin lesions. Although 4.5, and characteristic clue cells on the wet prep
C trachomatis seldom causes systemic illness, (squamous epithelial cells with smudged borders
untreated individuals may go on to develop Reiter caused by adherent bacteria). Oral metronidazole
syndrome (a constellationof urethritis, conjunctivitis, effectively cures the infection. Concurrent antibiotic
and arthritis). Fitz.-Hugh-Curtis syndrome, a form of treatment of male partners seems to have no effect
perihepatitis, is a known complication of infection on recurrence rates.
with either organism.
Vaginal candidiasis
Vulvovaginal candidiasis is not an STI. All women
WLVOVAGINAL INFECTIONS are colonized with Candida; however, factors such
as antibiotic use, pregnancy, diabetes, immuno-
Bacterial vaginosis and Candida vaginitis are
suppression, and oral contraceptive use predispose
bothersome but relatively benign vaginal infections
women to candida! overgrowth. Signs and symptonu
manifested by changes in the amount and character
include a thiclc white vaginal discharge with vaginal
of vaginal secretions. T. vagln.alls, a sexually trans-
itching and burning. Yeast and pseudohyphae are
mitted pathogen, also causes vulvovaginal infection.
evident on wet preparation treated with potassium
All three are easily diagnosed during the office visit
hydroxide. Over-the-counter topical antifungal
by an examination of vaginal fluid samples.
creams are safe and generally effective. A single dose
CLINICAL MANIFESTATIONS AND TREATMENT of oral fluconazole is an alternative.
Trichomoniasis
URETHRITIS
Trichomoniasis results from sexually transmitted
T. vagiMlis, a mobile flagellated protozoan. Most Urethritis is inflammation of the urethra caused
infected individuals remain asymptomatic. Typical by infection with an STI. It occurs much more
.symptoms in women include a malodorous, frothy commonly in adolescent males than females. N.
graydischarge andvaginal discomfort Some patients gono"hoea~J and C. trachomatU are the most im-
also develop dysuria and vague lower abdominal portant pathogens. Mycoplasma grmitalium and T.
pain. The cervix and vaginal mucosa may be either vagina/is also cause urethritis. Symptoms include
normal or visibly irritated and inflamed A fresh urethral discharge, itching, dysuria, and urinary
wet preparation of the vaginal fluid reveals poly- frequency. Asymptomatic infections are common.
morphonuclear leukocytes and the characteristic The disease is diagnosed by notation of at least
one of the following: mucoid or purulent urethral at risk include patients who received multiple units
discharge; positive leukocyte esterase test or WBCs of blood products (e.g., hemophiliacs) before 1985,
on microscopic examination of a first-void urine; victims of sexual abuse, and adolescents who engage
or gram-negative intracellular diplococci on Gram in high-risk behaviors (IV drug use or unprotected
stain. Patients with suspected urethritis should be sexual activity with multiple partners).
offered testing for other STis including syphilis and
Hrv. If available, specific diagnostic testing for N. CLINICAL MANIFESTATIONS
gonorrhoeae and C. tTtlelromati& (e.g., NAATs on urine History and Physical EXamination
or urethral swabs) is recommended. Treabnent for HIV may present in infanta and children with any
gonococcal urethritis is dual therapy with 250 mg one or several ofthe following signs and symptoms:
1M ceftrlaxone and either one dose oforal azithro- generalized lymphadenopathy, hepatomegaly, sple-
mycin or 7 days of oral doxycycline. If gonorrhea nomegaly, failure to thrive, recurrent or chronic
has been ruled out, then the patient may be treated diarrhea, oral candidiasis, Pneumocystia jiroveci
with one dose oforal azithromycin or 7 days of oral pneumonia (PJP), and parotitis. They can also develop
doxycycline. Azithromycln is preferred because it lymphoid interstitial pneumonia (LIP). Regression
provides better coverage forM. genitalium. in developmental milestones and progressive en-
cephalopathy may occur. Recurrent, often severe,
bacterial and opportunistic (fungal, disseminated
HIV AND AIDS HSV or CMY, and Mycobactmum avium) infections
HIV is a retrovirus that infects CD4+ T-lympho- are the halhnark of the acquired helper T -lymphocyte
cytes. HIV produces a wide range of clinical man- immunodeficiency.
ifestations in children. the most severe of which is A significant percentage of infected adolescents
AIDS. A child is defined as having AIDS when an present with a mononucleosis~type "acute retrovi-
AIDS-defining illness occurs (see later) or when ral'" syndrome within 6 weeks of HN acquisition.
the CD4+ lymphocyte count is less than a defined Symptoms and signs include sore throat, fatigue,
number or percent for age (e.g., <200/mm3 for fever, rash. and cervical or diffuse lymphadenopathy.
children older than 12 years). PJP and UP are two of several AIDS-defining
illnesses in the pediatric population. When any of
EPIDEMIOLOGY these conditions occurs, the child is considered to
The c:Usease is more common in urban populations, have AIDS regardless of the absolute CD4 T-lym-
lower socioeconomic classes, and racial minorities. phocyte count.
Most infections in children are acquired in utero or
perinatally (>90%). The risk of HN transmission DIFFERENT1Al. DIAGNOSIS
from an untreated seropositive mother to her fetus is HIV can have variable presentations; the virus can
approximately 25%. Treatment ofInfected pregnant affect any organ system, and symptoms are often
women with zidovudin.e (AZT; a reverse transcrip- nonspecific. A high degree of suspicion is required
tase inhibitor) alone or in combination with other to diagnose the disease at an early stage when it is
antiretrovirals during the second and third trimesters, most easily managed successfully.
followed by treatment of the infant for the first 6
weeks of life, reduces the vertical transmission rate DIAGNOSTIC EVALUATION
to less than 2%. Asymptomatic IllY-positive women Infants born to HIV-posl.tive mothers are seropositive
may not realize they are infected, and therefore they for matemally derived IgG antibodies to the virus
often do not receive therapy. (i.e., EUSA and Western blot testing are positive);
As a group, the adolescent population has the the.se teats are not helpful in children younger than
most rapidly increasing rate of HIV infection in the 18 months. Ifthe mother is HIV positive, HIV DNA
United States. PCR of the infant's blood should be performed at
birth. Ifthis test is positive on two separate occasions,
RISK FACTORS the infant is considered IllY positive. Negative tests
Risk factors include birth to an HIV-positive mother, should be repeated at regular intervals (2 to 3 weeks,
birth to a woman who uses IV drugs and shares 1 to 2 months, and 4 to 6 months ofage). Almost all
needles, and birth to a woman with multiple sexual HIV-infected infants have positive HIV DNA PCR
partners who does not practice safe sex. Other groups results by 1 month of age.
TREATMENT is discussed further in Chapter 10. Mumps does not

The standard ofcare consists of nucleoside analogue have a rash but may be considered when a child or
reverse transcriptue inhibitor drugs such as AZT and adolescent presents with parotid gland swelling
3TC (Iamivudine), nonnucleoside analogue reverse (parotitis). However. in fully immunized patients,
transcriptase inhibitors, protease inhibitors, and in- parotitis is more often caused by other viruses (Le.,
tegrase inhibitors. Trimethoprim-sulfametb.oxazole parainfluenza viruses, influenza A virus, 1-ITV), S.
provides prophylaxis against PJP, the most common aureus, or salivary duct stones.
opportunistic infection. New pharmacologic therapies Roseola and erythema in.fectiosum are generally
have drastically improved the chances ofconverting benign in children. The peak of roseola is between
HIV infection from a disease of near-certain death 6 and 24 months of age. Infants and children with
to a chronic Ufelong condition. roseola may present with 3 to 7 days offever higher
than 39.0"C (103.0"F). The rash initially appears
on the trunk as the fever resolves, establishing the
VIRAL INFECTIONS OF CHILDHOOD clinical diagnosis. Erythema infectiosum is caused
Vll'al infections are quite common in the infant by human parvovirus Bl9, which infects red blood
and young child but decrease with age because of cell precursors. In a child with hemoglobinopathy,
acquired immunity. Table 7-7 describes the typical a transient aplastic crisis precedes the onset of the
presentations and complications of some viral ill- "slapped cheeks" rash. Arthritis is observed more
nesses in children. often in adult women than in children.
Measles, mumps, rubella, and varicella (chickenpox)
have all decreased because live attenuated vaccines
are routinely administered to prevent them. Measles,
I;t•I3 :,,,~ t•lm i f;il: () il•i I j w•• i a'~ 3;.
rubella, and chickenpox present with characteristic RMSF is a tick-borne disease caused by Rickettsia
rashes that permit reliable clinl.cal diagnosis. Chickenpox rickettsii, a gram-negative intracellular bacterium.
TilLE 7-7. Presentations and Complications of Childhood Viral Illnesses

l•• ...._ ......... C.p.IIGIIIIIIa
l Measles Confturnt. erythematous Coryza. oougtl. Pneumonia. myocarditis,
! maculopapular ruh that conjunctivitis, Koplik encephalitis; rare:
I ;:::::::l;'(!p~ =:::::::e~mucosa ;:p~

.1! Mumps : : :-20) Swollen IBlivary glands, Orchitis, pancreatitis; rare:
e~~~pecially parotid glands meningitis, encephalitis
IRubella Similar to mea&les but Suboccipital and Polyarticular arthritis
does not coalesce posterior auricular or arthralgias; rare:
i lymphadenopathy encephalitis
IRoseola (human
~ herpesvirus 6)
Maculopapular (Appx.
Fig. A-21)
High fever resolve. u rash Febrile seizures; rare:
appears men.lngoencephalitis I~
Facial erythema giving Transient aplastic
•slapped cheeks• crisis in child with
appearance followed by hemoglobinopathy
spread to extremities in
reticular pattern (AppL
fts.A-22)
As initial lesions resolve, Secondary bacterial
new crops form. so infection; rare:
that lesiom in different pneumonitis, cerebellar
over; begins on face and stages are observed ataxia. encephalitis,
spreads to extremities simultaneously hepatitis
hooo•oo,.o•ooooooooooo• • oooo• • ooooO >oooo>> ooooooooo. , •o•••••ooooo•• •••••••••••••••••••••••••••••••••••nooon•••••••••••• ••••••••••n••••••• ••••••••••••••••••ooooo>ooooooooooooooooo•oooo.,oooo.,oooooooooooO oooooOoooooooooooooooooo oooooooooooo•ooooo• ooooonoooooooooooooooooooooo•oooon oo:
Rickettsiae are introduced into the skin by a tick DIFFERENTlAL DIAGNOSIS

bite and subsequently spread via the lymphatics and RMSF presents similarly to ehrlichiosis (another
blood vessels. They invade and multiply within the tick-borne illness) and meningococcemia. Because
endothelial cells of blood vessels, causing increasing approximately half of patients with RMSF and ehrli-
vascular permeability (vasculitis). chiosis do not remember being bitten by a tick. initial
antibiotic therapy for patients with these suspected
EPIDEMIOLOGY ill.nesses and no tick history should include coverage
RMSF occurs more often between April and Sep- for N. menlngitidis u well. Atypical measles may
tember in tick-infested areas of the south Atlantic present in a similar fashion; knowledge of a local
states (but has been reported year round). With outbreak should clarify this diagnosis.
Increased travel. RMSF acquired in endemic areas
may present elsewhere. Despite the name, none of TREAtMENT
the top 10 states reporting RMSF is near the Rocky Treatment with doxycycline is effective in all age
Mountains. Tick vectors include the wood tick and groups. Cefot:axime or ce:ft:riaxone should be added
dog tick. if meningococcemia is a pouibility. IfRMSF is sus-
pected, antibiotics must not be withheld pending
RISK FACTOR
laboratory results. Mortality is higher when treat-
The most significant risk factor is residence in or ment is delayed.
travel to an endemic area during times of the year
when ticks are most active.
LYME DISEASE
CLINICAL MANIFESTATIONS Lyme disease is a tick-borne illness resulting
Hlstary and Phplcal Examination from infection with the spirochete bacterium B.
The classic presentation of RMSF includes fever. burgdorfori. The pathogen lives in deer ticks and
headache, and rash. Symptoms develop approximately black-legged ticks.
7 days after a tick bite. Initial symptoms often are
nonspecific and include fever, chills, headache, EPIDEMIOLOGY
malaise, nausea, vomiting, and mya1gias. The rash Although cases have been reported across the country,
begins on the second to fifth day and consists of most occur in southern New England. southeast-
blanching, erythematous, macular lesions that prog- em New York. New Jersey, eastern Pennsylvania,
ress to form petechiae or purpura (Appx. Fig. A-24). Maryland. Delaware, Minnesota. and Wisconsin and
It characteristically appears initially on the wrists surrounding areas. The incidence of Lyme disease
and ankles and spreads proximally to involve the is highest among children 5 to 9 years of age. Most
trunk and head over several hours. Typically, the cases occur between April and October.
palms and soles are involved as well. The rash is
absent in about 10% of patients and may not be RISK FACTORS
present when an ill child first presents to care. Individuals with increased occupational or rec-
Children may have some impairment of mental reational exposure to tick-infested woodlands in
status (confusion) and occasionally encephalitis endemic areas are at highest risk for Lyme disease.
or focal neurologic findings. An infected tick must feed for more than 48 hours
to transmit B. burgdorforl.
DIAGNDSnC EVALUATION
Although immunofluorescent staining of skin bi- CLINICAL MANIFESTATIONS
opsies taken from rash sites may demonstrate the History
organism, there is no reliable diagnostic test that Most patients do not recall a tick bite. The clinical
becomes positive early enough in the course of the manifEstations depend on the stage ofthe disease: early
disease to guide therapy. Thus, the clinician must localiud, earlydiuemina~ orlate. Erythema migrans,
maintain a hlsh suspicion for the disease. Antibod- the manifestation ofearlylocalizeddisease, appears at
ies to confirm the clinical diagnosis are detectable the site ofthe tick bite 3 to 30 days after the bite. The
approximately 10 days after symptom onset. Key rash begins as a red macule or papule and progressively
laboratory features include thrombocytopenia and enlarges to form a large, annular, erythematous lesion
hyponatremia; however. normal values do not ex- with central clearing (resembling a bulls-eye) up to 10
clude this infection. em in diamet:e& The skin lesion ofmn is accompanied
by feve~t malaise, headache, arthralgias, and myalgias. antibody testing. Early locaJized Lyme disease is a
Early disseminated Lyme disease (weeks after the tick clinical diagnosis, based on suggestive history and
bite) may manifestas multiple erythema migrans lesions the characteristic rash on physical examination.
(Appx. fig. A-25), cranial nerve palsy, meningitis, and Lyme lgM titer is elevated several weeks after the
carditis (heart block). Systemic symptoms including tick bite. Early emplrlc treatment can cause this
headache, low·grade fevel; arthralgia, and myalglas response to be absent and thus diagnosis may not
are also common during the early disseminated stage. be able to be confirmed later on. Antibodies to B.
The most common manifestation oflate Lyme disease bw-grlorfori cross-reactwith other infectiotu agents,
(>6 weeks after tick bite) is monoarticular arthritis, particularly other spirochetes (including syphilis).
usually involving the knee. The VDRL and RPR tests remain negative in patients
with Lyme disease. Two·tiered testing algorithm is
Physical Examination standard, including an antibody screen followed
Children with early disseminated Lyme disease may by Western blot to confirm specific positive IgM
have multiple erythema migrans lesions, faclal nerve or lgG bands. Cardiac involvement, usually in the
palsy, or signs of meningitis. Late disease may present form ofconduction abnormalities, is rare but can be
with swollen and tender joints.
diagnosed by ECG in conjunction with supporting
history and antibody studies. CSF is obtained ifthere
DIFFERENTIAL DIAGNOSIS is concern for Lyme meningitis, demonstrating CSF
The differential diagnosis depends on the presenta- pleocytosis and CSF Lyme ant:J.oodies.
tion. When the rash is atypical, it may be confused
with erythema multiforme or erythema marginatum TllEATMENT
(seen in ARF). The differential diagnosis ofarthritis Treatment ofearly localized Lyme disease prevents
also includes juvenile idiopathic arthritis, reactive early disseminated and late disease, including men-
arthritis, and Reiter syndrome. The differential ingitis and arthritis. Younger children can be treated
diagnosis of Lyme meningitis includes other causes with oral amoxicillin or cefuroxime. Children older
of aaeptic meningitis. than 8 years should receive oral doxycycline. Patients
with vomiting, persistent arthritis, cardiac disease, or
DIAGNOSTIC EVALUATION neurologic involvement warrant parenteral therapy
Testing for Lyme disease ln the presence of vague or with ceftriaxone. A small minority of patients con-
nonspeclfic complaints is not helpful; false·positive tinues to experience low-grade symptoms despite
test results can occur, especially with enzyme-linked appropriate therapy; however,long·tenn antibiotic
immunosorbent assay (ELISA) or immunofluorescent treatment is not helpful in this population.
KEY POINTS
• The three most common bacteria implicated in decisions should be based on throat culture or
AOM areS. pneumonlae, nontypeable H. influ- rapid antigen-detection test results. Penicillin/
enzae,andM. catanhal/s. lnAOM, thetympanic amoxicillin is the antibiotic of choice for GAS
membrane Is bulging, opaque, and erythematous, pharyngitis.
with diminished mobility. Symptom onset is • Classic infectious mononucleosis is caused by
acute. High-dose amoxicllin is the appropriate EBV. Clinical manifestations Include exudative
first-lne treatment for moat cases of AOM. pharyngitis, generalized lymphadenopathy,
Tympanostomy tubas should be considered fever, and profound fatigue in older children
for children with recurrent episodes of AOM. and adoleacentB. Helpful laboratory findings
Chronic etfuaions and recurrent infection may include lymphocytosis with a high percentage
predispose to pamanent conductive hearing {10%) of atypical lymphocytes and a positive
loss and language delay. heterophile antibody test.
• Children with pharyngitis should not be 1reated • Children with croup develop a hoarse voice,
with antibiotics empirically because most barky (''seal-llkej cough, and stridor, which
episodes are caused by viruses. Therapeutic may progress to respiratory distress. Infants
with severe stridor are treated with corticoste- However, a wide range of severity exists and
roids and nebulized epinephrine. The typical a large subset of Infected children are asymp-
patient with epiglottitis, a life-t hreatening tomatic. HAV and HEV are spread via fecal-oral
emergency, has a toxic appearance, with transmission. HBV, HCV, and HDV are transmitted
drooling and severe, progressive respiratory through infected bodily fluids. Uver enzymes
distress. When epiglottitis is suspected, the are uniformly elevated In hepalitia. Because the
chi d should be transported to the operating clinical manifestations are so similar, specific
room for endotracheal intubation and direct serologic testa are Indispensable for securing
visualization of the epiglottis under general an accuate diagnosis.
anesthesia. • Syphilis may be transmitted 1ransplacentally
• The classic presentation of bronchiolitis in- or sexually. Neonates with congenital syphilis
cludes fever, wheezing, tachypnea, rhinorrhea, present with snuffles, hepatosplenomegaly,
and 1"88plratory distress. Apnea is a frequent mucocutaneous lesions, jaundice, and lymph-
presentation In necnatea. Prophylactic admin- adenopathy. The VORL and RPR are excellent
istration of pallvlzumab, an IM RSV monoclonal screening tests but may produce false positives.
antibody, Is indicated during the winter months Parenteral penicillin G Ia the treatment of choice.
tor selected patients younger than 24 months • The diagnosis of PID Is clinical, based on history,
who were born prematurely (<29 weeks' gesta- physical examination, and supporting laboratory
tion), or who have hemodynamically significant results. C. trachomstls and N. gononhoeae are
congenital heart disease, or who have chronic the most commonly Isolated organisms in PI D.
lung disease of prematurity requiring medical A single dose of a parenteral cephalosporin (for
therapy within thee months before the sta1 of N. gonorrhoeae) and 14 days of oral doxycycline
the RSV season. (for C. trachomatls) are appropriate outpatient
• S. pneumonlee Is the most common cause therapy for mild PID, while considering addi-
of bacterial pneumonia In most age groups. tion of anaerobic coverage (metronidazole) in
M. pneumon/Be and C. pneumoniae should be some cases.
considered In older children and adolescents. • Most HIV infections In children are acqlired in
• Meningitis may be septic (bacterial) or aseptic. utero or perinatally. lnt.rts born to HIV-positive
Lumbar puncnn and CSF studies are Invalu- mothers are seropositive for maternally derived
able In the diagnosis and development of a lgG antibodies to HIV; thus, the ELISA and
treatment strategy for meningitis. Appropriate Western blot are not helpful in children younger
empirical antibiotic choices for presumed bac- than 18 months. The HIV RNA PCR should be
terial meningitis are ampicillin and cefotaxime or used in this population.
gentamicin On the neonate) and vancomycin and • The classic presentation of RMSF includes fe-
a third-generation cephalosporin On the child). ver, headache, and rash. The disease Is rapidly
• Infectious dlall'hea may be bacterial, viral, progressive, and there Is no laboratory test
parasitic, or toxin-mediated. Children with that becomes abnormal soon enough in the
shigellosis may present with mental status disease process to guide therapy. Treatment
changes. S. dysentar/ae and E. coli 0157:H7 (doxycycline) should be started on the basis of
are associated with hemolytic uremic syndrome. clinical suspicion alone.
Most bacterial and all viral gastroenteritis are • The classic rash of Lyme disease Is erythema
self-limited In healthy chHdren and antibiotics mlgrans. Lyme disease Is treated with oral
sa not necessary. amoxicil in in children younger than 8 years and
• The clinical signs of acute hepatitis include with oral doxycycline In older children. Lyme
anoraxla, nausea, malaise, vomiting, jaundice, meningitis may be treated with IV ceftriaxone
dark urine, abdominal pail, n low-grade fever. or oral doxycycline.
CLINICAL VIGNETTES
VIGNETTE1 In day care and has not been able to go the last 2
Ar1 8-year-old boy presents to your office with a 3-day days. Findings on physical examination include a
history of favars, sore throat, and headache. His mother temperature of38.5°C, a respiratory rate of 30 breaths
also states that he occasionally has been complaining per minute, a pulse of 11 0 beats per minute (bpm),
that his abdomen hurts. This morning, the boy's mother and a blood pressure of 100160 mm Hg. He appears
noticed that he has developed a red, bumpy rash on to be nontoxic but in moderate respiratory distress
his neck and under his arms. On physical exam, he is with inspiratory stridor and hoarse cry. On lung aus-
nontoxic but uncomfortable appearing. His tonsils are cultation, he has transmitted upper airway sounds and
erythematous and enlarged with visible exudates, and moderate aeration bilaterally. He has tracheal tugging
he has several peteChiae on the aoft palate. He has a and subcostal retractions. He has no significant past
few tender anterior cervical lymph nodes and an ery- medical history and has not been ill in the recent past.
thematous, papular rash most prominent on the neck He has no allergies to medications and is up-to-date
and in his axilla. His cardiopulmonary exam is normal on his vaccinations. No one at home is sick.
and his abdomen is nontender and benign. You suspect 1. Which of the following organisms is most likely
scarlet fever and perform a rapid antigen test in the office. to be the cause of the child's Illness?
1. While waiting for the test reeult8, you explain to the L Respiratory syncytial virus
patient's mother that 1tle organism which is most b. Parainfluenza type 1
likely responsible for this infection, if bacterial, is C. Bordetella pertUssiS
which of the following? d. Haemophilus influenzae type B
a. GroupA streptococcus (Str8ptococcus pyogenes) e. Mycoplasma pneumoniae
b. Group B streptococcus (Streptococcus aga/sctiee) 2. Of the following diagnostics, which is the first
c. Streptococcus pneumoniae step and Important In the Initial management of
d. Staphylococcus auraus this patient?
•· Vlrldans group streptococcus L Oxygen saturation
2. Within a few minutes, the patienrs rapid test returns b. Chest x-ray
and Is read as negative. The following day, the c. CBC with differential
patient's 1tlroat culture retuma positive for GAS d. Lateral neck x-ray
infection. You call1tle boy's mother to discuss e. B. pertussis nasopharyngeal PCR
p188Cribing antibiotics to treat the infection. Which 3. Which medication would be the best choice acutely
of1tle folloWing Is the most Important diagnostic
to Improve this child's condition?
test to perfonm next? a. Azithromycin
L Throat culture
b. Dexamethasone
b. Antistreptolysin-a (ASO) titer c. Nebulized albuterol
c. Blood culture d. Ceftriaxone
d. Monospot test
e. Amoxicillin
e. No further testing is recommended.
3. If 1tle child is treated appropriately, which of the VIGNETTE3
following is 1tle least likely to be affected? You are an intern seeing a 16-year-old female in the
L Duration of symptoms emergency department presenting with a chief complaint
b. Development of ARF of lower abdominal pain. She has been Ill for the past
c. Risk of transmission 4 to 5 days with worsening of her pain and fevers to
d. Devulopmentof postatruptococcal glomerulonephritis 102°F since yesterday. The pain is described as sharp,
e. Abscess formation constant, and present "all over.. her lower abdomen.
She denies back pain. She has had little appetite and
VIGNETTE2 has vomited twice since the pain started. She has
An 18-month-old boy presents to the emergency also had a foul-smelling, white vaginal discharge for
department of your office with 3 days rhinorrhea and the past week and burning with urination. Before this
2 days of nonproductive hoarse cough, malaise, and illness, she has been healthy. She is sexually active
fever. His mother says his cough Is worsening and with one partner, takes oral contraceptive pills, and
she thinks he Is breathing fast and acting tired. He Is uses condoms •most of the time." Her last menstrual
period was 2 weeks ago. On your examination, she very tired. They report no respiratory sympt oms.
Is mildly dehydrated and uncomfortable appearing. His vital signs In the emergency department are as
Her cardiac and pulmonary exams are normal She follows: temperature, 39.7°C; heart rate, 105 bpm;
has tendemess to palpation diffusely over her lower BP, 112180 mm Hg; respiratory rate, 16 breaths per
abdomen w ithout guarding. minute. On examination, you notice an ill-appearing
and somnolent young man. He has strong distal
1. Which of the following tests is most likely to confinn
pulses and his capillary refill Ia normal. He has no
the probable cause of this patient•s condition?
focal neurologic deficits, but mild nuchal rigidity is
a. Urinalysis
present. He has a b lanching, macular rash on his
b. Right lower•quadrant ultrasound
distal extremities, which is notably absent from his
c. Bimanual pelVIc examination head and trunk.
d. Pregnancy test
e. Stool culture 1. Which of the following would be the least im-
portant to include in your initial management of
2. You perform the remainder of your evaluation and
this patient?
confirm the diagnosis of PID. What Is the most
L Establish IV access.
likely organism responsible for the pattent's Illness?
b. Obtain an immunization history.
a. HSV c. Perform a lumbar puncture.
b. Nelsserla gonorrhoeae
d. Perform a head CT.
c. Treponema pall/dum e. Start empiric antibiotics.
d. Trichomonas vaginaJis
e. Chlamydia trachomatis 2. You obtain some additional historical details from
f. Aand/orC the child's parents. They tell you that the boy was
g. B and/orD previously healthy. Recently, the family vacationed
II. B and/or E in North Carolina and had gone camping. When
asked about tick exposures, they do not recall any
3. As part of your evaluation, you recommend that specific bites, but they do remember seeing them
she undergo testing for other STis, including HIV.
on his clothing. Given this information, you become
Although nervous, she agrees to be tested. You
concerned about the potential for RMSF. Which
try to quell her fears over the testing process by
is the best choice of antimicrobial to specifically
providing her with counseling about HIV infection
cover the organism responsible for RMSF?
and the screening process for this infection. Which
a. Doxycycline
of the following statements about HIV testing or
b. Cefotaxlme
Infection is •false"?
a. An HIV screening test may be falsely negative c. Vancomycin
d. Gentamicin
in a patient with a recently acquired infection.
e. Acyclovir
b. ll'le recommended first-line H IV screening test
Is a combined antigen/antibody test. s. The child Is admitted to the hospital and his condi-
c. Most HIV Infections In children are acquired In tion gradually Improves while on broad-spectrum
the perinatal period. antibiotics. The following day, his CSF returns
d. An EUSA rapid HIV test will tell you if a perinatally positive for Neisseria meningitidiS. The parents tell
exposed newborn has acquired HIV infection. you that he has not been around anyone sick but
e. Transmission of HIV in a teenager is more that he shares a room at home with his 8-year-old
likely to occur through sexual contact than brother. You decide that chemoprophylaxis of the
IV drug use. family is warranted. What is the drug of choice to
use as prophylaxis for close contacts exposed to
VIGNmE4 invasive meningococcal infection?
It is July and you are working In the emergency a. Doxycycline
department. You evaluate a 13-year- old boy who b. Rifampin
presents with 2 days of fever and headache. He has c. AmoxiciUin-clavulanate
been vomiting today and, according to his parents, d. Nitrofurantoin
he has been lying around and complaining of feeling e. Amoxlclllln
ANSWERS
VIGNETTE 1 Question 1 of GAS Infection, such as glomerulonephritis, are

1.AnewerA: present. Bacteremia is rare in scarlet fever; therefore,
S. pyogenes, or GAS, is responsible for •strap throat• the yield of blood cultures is low. A blood culture
(streptococcal pharyngitis) and scarlet fever. Acute would not be Indicated In this case. A monospot
pharyngotonsillit is is the most common manifesta- test is used to assess for the diagnosis of mononu-
t ion of acute infection, followed by skin infections cleosis caused by EBV. Although it may be helpful
(impetigo or pyoderma). Both suppurative (periton- to distinguish strep pharyngitis from mononucleosis,
sillar and retropharyngeal abscesses, adenitis, otitis it would not be recommended in this case. Despite
media, and sinusitis) and nonsuppuratlve (rheumatic a negative rapid antigen test, GAS would be more
fever and glomerulonephrit is) complications may likely than EBV, given the patient's age and clinical
be seen following strep pharyngitis, particularly if presentation. Although the clinical presentation In
untreated. S. aga/actiae, or group B streptococci, this case is consistent with scarlet fever caused by
are a maJor cause of Invasive neonatal bacterial GAS, it can be difficult to distinguish streptococcal
infections such as meningitis, bacteremia, or pneu- pharyngitis Infection from viral pharyngitis or infectious
monia. S. pneumoniae (pneumococcus) is a major mononucleosis. Therefore, laboratory confirmation
cause of bacterial illness in children. Although its of GAS pharyngitis via culture was warranted, but
prevalence has decreased because of w idespread no additional testing Is required.
vaccination, It Is frequently responsible for otltls
media, sinusitis, community-acquired pneumonia, VIGNETTE 1 Question 3
and less commonly bact eremia or meningitis. 3. AnswerD:
Pneumococcus infection is extremely unlikely to Antibiotic use impacts the development of several
be associated with rash. S. aureus Is a ubiquitous potentially serious complications. However, it does
organism that is most frequently responsible for skin not affect a child's likelihood of developing post-
and soft tissue infections. It can cause a variety of streptococcal glomerulonephritis. This potential
invasive suppurative infections and toxin-mediated complication may occur following GAS pharyngitis
infections as wall, but not acute pharyngit is. Viridans or skin infection regardless of antibiotic administra-
group streptococci Is a group of non-A and non-B t ion. Families should be counseled on signs of this
st reptococcal bacteria t hat may cause a variety of complication (hematuria, edema, hypertension, etc.),
clinical infections in children. Most often, viridans as additional therapies may be needed if they occur.
group streptococci are associated with endocarditis Treatment of GAS pharyngitis reduces the likelihood
In children with congenital heart disease or artificial of the development of many poststreptococcal com-
heart valves. plications including suppurative sequelae (such as
retropharyngeal or peritonsillar abscess formation)
VIGNETTE 1 Question 2 and ARF. Treatment with oral penicillin, or a one-time
2.Answer E: IM dose of penicillin G, is highly effective and will also
Several rapid diagnostic tests are available for shorten the clinical course and reduce transmissibility.
practitioners and ara frequently Implemented in
the office setting. Although these tests have a high VIGNETTE 2 Queltlon 1
specificity (few false-positive results), their sensitivity 1.Answer8:
Is variable. These tests are also highly dependent Ptualnfluenza viruses (specifically types 1 and 2) are
on proper collection of the sample to accurately the most common viral pathogens causing laryngo-
identify infection. Thus, throat culture is used as the tracheitis or croup. Although many forms of croup are
gold standard for confirmation of the d iagnosis of mild and self-limited, there can be degrees of upper
streptococcal pharyngitis and should be obtained on airway obstruction that can cause respiratory distress
all children who have a negative rapid streptococcal and hypoxemia and benefit from intervention. Spe-
antigen test. This patient's sample was cultured for cifically hoarse, barky cough and Inspiratory strtdor
GAS and was reported as positive. An ASO titer may increase suspicion for croup over other cauaes of
be useful in the diagnosis of recent or past GAS respiratory distress in infants and young children such
Infections. However, It Is not commonly used In the as bronchiolitis (RSV being the most common cause),
acute setting and is often more helpful to confirm pertussis (whooping cough), and bacterial or atypical
recent infection in the setting of a negative throat pneumonias (S. pneumonise, M. pneumoniae). Children
culture, or when potential systemic complications with epiglottitis, which is uncommon and caused most
often historically by H. influfJIJZIJe type B, are at high risk a bronchodialator used for reactive airway disease/
for airway obstruction and are often toxic appearing, asthma exacerbations.
drooling, and hold themselves In a forward-leaning
•trtpod~ position to maintain their airway. VIGNETlE 3 Queslkln 1
1.AnswerC:
VIGNETTE 2 o-stlon 2 The most likely diagnosis in this case is PID. PID is
2.AnswerA: due to ascending infection of the female genital tract
In this patient with croup, the diagnosis is clinical. The and refers to infection of the uterus, fallopian tubes,
degree of respiratory distress and the presence of hy- or any portion of the female reproductive organs. It
poxemia are important, provide severity assessment, should be considered in any sexually active female with
and inform management. If the patient is hypoxemic, abdominal pain. A history of fever, vaginal discharge,
supplemental oxygen is beneficial and is supportive. dysuria, dyspareunia, irregular vaginal bleeding, and
Hypoxemia also can help clinicians assess response lower abdominal pain are all suggestive features,
to therapy and improvement. A chest x-ray is not many of which are present In this case. Bimanual
indicated unless pneumonia is considered. A neck pelvic examination Is necessary to confirm the diag-
x-ray may be Important If foreign body aspiration or nosis by detecting the presence of cervical motion
epiglottitis are considerations or If the patient Is not or uterine or adnexal tenderness. Pyelonephritis is
responding to therapy. A poeterlor-antertor radiograph an ascending urinary tract infection that involves the
may demonstrate subglottic narrowing, called the kidney. Common historical details suggestive of this
•steeple sign." Given the preceding rhinorrhea and type of infection include dysuria, fever, flank pain,
fever leading up to this presentation, and stridor with vomiting, abdominal or pelvic pain, or costovertebral
hoarae voice, a clinical diagnosis of croup should be angle tenderness. Diagnosis is suggested on the basis
made. Laboratory testing such as a CBC is of limited of history and UA. However, urinary tract infections,
diagnostic utility. In severe cases, it may help increase including pyelonephritis, can be confirmed only by
suspicion for primary or secondary bacterial infection, urine culture. In this scenario, pyelonephritis should
but is not necessary in most cases. B. pertussis PCR be considered and UA and urine culture should be
would be the diagnostic test of choice if pertussis performed. However, it is less likely than PID given the
or whooping cough was being considered. Children history. Appendicitis Is Inflammation of the appendix.
with pertussis do not typically have stridor or hoarse It Is frequently caused by obstruction of the appendix
voice, and Instead may have a prolonged cough and and will classically present as right lower-quadrant
In the paroxysmal stage have bouts of severe cough pain. Right lower-quadrant ultrasound is often the firat
with Inspiratory whoop after a coughing spell. These imaging test used to confirm this diagnosis because
children are typically afebrile. Infants may present it avoids the radiation exposure encountered in a CT
with respiratory distress, hypoxemia, and/or apnea. scan. Early in the disease process, abdominal pain
may be generalized or periumbilical. Although this
VIGNETTE 2 Q...Uon 3 etiology must be considered in any child presenting
3.Answer B: with lower abdominal pain, the history and exam
The recommended therapy for children with findings described would be more suggestive of
moderate-to-severe croup is dexamethasone and PID. Pregnancy must be considered in the workup
nebulized racemic epinephrine. The benefits of of any sexually active female presenting with ab-
these medications result from reduction In airway dominal pain. In practice, pregnancy testing should
Inflammation and spasm. They have been shown be performed on any female of chlld-beartng age
In trtals to Improve symptoms and reduce hospital presenting with abdominal pain, vaginal bleeding,
admissions. Given croup Is a viral Illness, antibiotics or any concerning pelvic or abdominal complaints.
such as azithromycin, ceftriaxone, and arnoxicillin Given her recent menses, pregnancy would be less
would not be therapeutic for this patient and thus are likely. Acute gastroenteritis (AGE) may be due to a
not indicated. Azithromycin is the antibiotic therapy number of bacterial, viral, or parasitic agents. Stool
of choice for both M. pneumoniae and 8. pertussis. culture is used to identify bacterial agents responsible
High-dose amoxicillin is the first-line treatment for for AGE. A history of diarrhea is the key historical
AOM, sinusitis, and bacterial pneumonia treated as detail and is absent in this case. AGE may also be
outpatient with oral therapy. These infections share associated w ith vomiting or abdominal pain, but
common likely pathogens including S. pneumoniae these are less commonly seen. Some causes of AGE
and nontypeable H. influenzae. Ceftriaxone is indi- may be associated with crampy abdominal pain, but
cated in a patient w ith complicated pneumonia with a constant and severe abdominal pain would be rare.
history of frequent amoxlcllllnlamplclllln use and who Given the history provided, acute gastroenteritis
perhaps failed first-line therapy. Inhaled albuterol Is would be unlikely.
VIGNETTE 3 Question 2 is commonly referred to as the ''window period• and

2.Answer H: may be anywhere from 6 weeks to several months,
PID is usually a polymicrobial Infection. c. ttacho- depending on the type of screening test used. The
matis and N. gonorrhoeae are the most commonly combination antigen/antibody assay Is followed by a
isolated organisms from testing associated w ith this H IV-1/HIV-2 antibody differentiation immunoassay, to
infection. N. gonorrhoeae can cause a number of confirm the result and determine if the patient is Infected
genital tract infections, including vaginitis, urethritis, with HIV-1, HIV-2, or both viruaea. Appi'W'imately90%
cervicitis, or salpingitis. C. trachomatis is the most of HIV transmissions in children occur in the perinatal
common reportable STI in the United States, with period. There is a high risk of transmission of HIV to
prevalence ranging from 2% to 20% among adoles- a fetus or newborn baby by Infected mothers who
cent females, and would be the most likely organism are untreated. With treatment of the mother, this risk
responsible for the patient's infection among those is greatly reduced. However, perinatal infection still
listed. Any patient with PID should be treated for far outnumbers those cases in which HIV is acquired
both gonococcal and chlamydlal Infections while through sexual contact, IV drug use, or exposure to
awaiting test results because colnfectlon Is common. contaminated body fluids by other means. For an infant
Human papillomavirua (HPV) infections are the most bom to a mother with HIV, an Initial antibody test will be
common STis of any type, but are not reportable positive and reflect maternal antibody. Thus, an ELISA
and do not cause PID. HSV can be transmitted will not accurately reflect the HIV status of the Infant.
through sexual contact. Genital infections may be To assess HIV Infection In an Infant, HIV RNA PCR Is
characterized by vesicular lesions but often times go the test of choice. A positive result at birth indicates
unnoticed. Although HSV can cause painful genital Infection acquired in utero. Testing should be repeated
lesions, it is not responsible for PID. T. pallidum is at specified time points over the first 4 to 8 months of
the organism responsible for syphilis. Although all life. Adolescents have the most rapidly increasing rate
sexually active adolescents should be screened for of H IV infection in the United States, but still represent
syphilis, especially those with other STis, it does a minority of total cases. For teenagers, the most likely
not cause PID. Primary disease is characterized by route of exposure is through unprotected sexual con-
painless ulcers (chancres) at the site of inoculation. tact with an HIV-positive individual. Although sharing
Secondary syphilis consists of a maculopapular rash, needles with an HIV-infected person would carry the
mucocutaneous lesions, and generalized symptoms single greatest risk for transmission, this practice Is
such as lymphadenopathy, fever, and malaise. Ter- relatively uncommon compared with exposure from
tiary syphilis occurs many years later, If untreated, sexual contact.
and involves gumma formation of the akin, bones,
and internal organs. T. vaginali:~ is responsible for VIGNETTE 4 QuMtlon 1
trichomoniasis and Is often asymptomatic. When 1.Answer D:
symptoms develop In females, vaginal discharge, On the basis of the described examination, the patient
itching, and Irritation are present It is the second has no focal deficits. His presentation (both history and
most common STI in the United States, and coin- physical examination) suggests an infectious process
fection with chlamydia! and gonoccocal infections rather than a traumatic one. As the patient has no focal
is common. neurologic deficits but does have a fever, it is unlikely
that he has enlarged ventricles or an intracranial
VIGNETTE 3 Question 3 bleed, two conditions that would be evident on head
3.Answer D: CT. Isolated meningitis Is associated with a normal
The original HIV screening test was an EUSA test In head CT. In the vignette, the child has evidence of
which a patient's serum Is combined wtth HIV anti- possible meningitis. Establishing IV access Is critical,
gens. If antibodies to HIV are present in the patient's both for administenng parenteral medications and
blood, they will combine with the antigens and yield for rehydration, which is likely to be necessary in this
a positive result upon analysis. This test has a high case based on the patient's history of vomiting and
sensitivity (few false negative results) and is, therefore, fever. Moreover, the patient's condition could change
a good screening test. Currently, a ''fourth-generation" quickly, so establishing IV access will be important.
antigen/antibody combination HIV-1/2 immunoassay is Asking the parents about the child's immunization
the preferred screening test. This combines antibody history is also essential. Given that meningitis is a
and antigen detection, which is better able to identify concern, knowing whether the child has received all
early infection compared with antibody alone, because age-appropriate vaccines will impact the likelihood
there is a period of time after the contraction of HIV, that certain organisms are responsible for his con-
before the development of detectable antibodies, when dition. Specifically, a 13-year-old child should have
a screening test will be falsely negative. This period received Immunizations against H. lnfluenzae type b,
S. pneumonlae, and N. menlnglt/dls groups A, C, Y, It provides good gram-negative and some gram-pos-
and W-135. Obtaining CSF for analysis Is crucial In Itive coverage as well. vancomycin Is typically used
the diagnosis of meningitis. Cell count and differential, In the setting of potential serious Infections where
protein, glucose, and culture are all necessary diag- gram-positive bacteria are suspected. It provides
nostic te6tS to perform In this case. In addition, given excellent gram-positive coverage and is 1he agent of
the time of year, viral PCR may be useful to confinn a choice for empiric treatment of methicillin-resistant
viral source of infection. Although it is not certain that S. awvus. Gentamicin offers broad gram-negative
the child's illn888 is due to a bacterial source, starting coverage. It is not an optimal antibiotic choice for1he
empiric antibiotics is imperative. Bacterial meningitis management of meningitis in children as it does not
is a life-threatening condition and antibiotics should penetrate the blood-brain barrier well in the absence of
not be withheld while awaiting test or culture results. inflammation and does not cover the likely pathogens
It is recommended that blood and CSF cultures be in this age group. Acyclovir is an antiviral that provides
obtained before starting antibiotics, if possible, to therapy for several viruses, including HSV. It is often
optimize their diagnostic yield. used empirically in the setting of meningitis because
HSV meningoencephalitis is a devastating illness with
VIGNETTE 4 Quasllon 2 worse outcomes when not treated promptly.
2. Answer A:
RMSF is cauaed by Rickettsia rickettsii, a bacterium VIGNETlE 4 QuasiiDII 3
carried by dog ticks. This illness classically presents 3.Answer B:
as fever, headache, and a centrally spreading rash. The Rifampin is the drug of choice for prophylaxis of all
rash initially begins as erythematous maculas, which close contacts. Two days of therapy is advised, with
develop into petechiae and purpura as the illness the dose depending on 1he Individual's age. Other
progresses. Doxycycline Is the drug of choice, even options for chemoprophylaxis include a single IM dose
for young children in whom this medication would of ceftriaxone or a single dose of ciprofloxacin for
oroinarily be contraindicated. If RMSF is suspected adults. Anyone who has had contact with the child's
on the basis of history, doxycycline should be given oral secretions or who lives in the same household
promptly. None of the other medications listed would as the child should be treated. Generally, health care
effectively treat RMSF. Although their use may be workers do not require prophylaxis unless they have
Indicated as part of empiric coverage for the above-de- had significant exposure to the child's respiratory
scribed child, these antibiotics would not be used to secretions. The other answers given In the question
specifically b9at this rickettsial illness. Cefotaxime is a would not provide adequate protection against the
third-generation cephalosporin and is generally a good development cf disease and 1herefore should not
choice for empiric coverage of suspected meningitis. be given.
Immunology, Allergy, and
Rheumatology
Megan L Curran and Katie S. Fine
IMMUNOLOGY and mycobacteria. Patients with SCID are highly

susceptible to opportunistic infections from organ·
The immune system, composed of specialized cells
isms such as fungi and Pneumocystis jiroveci. With
and molecules, is responsible for recognizing and
the recent recommendation in the United States
neutralizing foreign antigens. The innate immune
to vaccinate all children with the live, attenuated
system provides the initial, relatively nonspecific
rotavirus vaccine at 2 months of age, children with
response to an invading microorganism. Pre·formed
SCID may be at special risk for vaccine-associated
effectors and pathogen-associated molecular patterns
diarrhea. Vaccine· assodated mortality may be seen
provide the stimulus for inflammation. recruitment
and activation of effector cells, and ultimate clear-
in children with SCID in developing countries who
ance ofthe infectious agent. Two to 3 days following
still utilize the live poliovirus vaccine and bacille
Calmette-Guerin vaccine to prevent tuberculosis•
.foreign antigen exposure, the adaptive immune
With these children in mind, there has been a strong
system provides more specific pathogen recognition
initiative in the United States to develop a newborn
and more complex cellular interactions, resulting in
screening initiative for SCID, which is now in place
defense against infection and immunologic memory.
Immunodeficiency li}'lldromes increase mscepb.ollity
in almost all state screening labs. The incidence of
SCm in the United States is predicted to be 1:50,000
to infection, malignancy, and autoimmune disorders
to 1:100,000 children. It is significantly higher in
(Table 8·1). Table 8·2lists clinical criteria that should
populations with consanguineous families.
prompt an evaluation for immunodeficiency.
SCID represents a group of genetically derived
DISORDERS OFT-CELL IMMUNITY disorders ofT-cell deficiency. The most commonly
T -cells modulate most immune responses, providing identified gene that is defective in boys with scm is
recruitment of macrophages, assistance to B cells to the X-Unked gene,IL2RG, that encodes the common
make immunoglobulins, and direct killing ofinfected r·chain of several interleukin receptors, including
host cells and tumor cella. Therefore, they are the major interleukln·2 (IL-2). Boys with X·linked scm present
efrectors ofcell-mediatEd immunity, important in the in the first 6 months oflife with severe virallnfectf.ons,
defense against intracellular and opportunistic infections. bacterial infections, diarrhea, and failure to thrive.
T-cell-based immunodeficiency is a life·threatening A complete blood count reveals severe lymphopenia
emergency in the neonate, requiring rapid recogni- (adjusted for age), and enumeration ofT cells reveals
tion to institute life...saving therapies. Bone marrow nearly absent CD4 T cells. Girls may also present
transplantation is curative. Severe combined immu· with SCID, although the genes responsible include
nodeficlency (SCID) and hwnan immunodeficiency other proteins in the fl...2 receptor signaling pathway.
virus (HIV) infection represent congenital (SCID) and Children with DiGeorge syndrome may also be
acquired (HIV) T-cell immunodeficiencies diagnosed with T-cell immunodeficiency because
of a lack of thymus maturation. Occa.sionally, the
Clinical Manlfastatlons defect is so severe that they may present with SCID.
Hlstrxy Blld PtryslcaJ Examination It Is more common. however, for these children to
T -<:ell abnormalities predispose patients to infec- present in infancy with diseases unrelated to the
tions with intracellular pathogens, including viruses immune system (e.g., congenital heart disease,
143
!...........
!Dilcxdf:n ofhumoral
II I ' I .........
1'IIIU 1-1. Causes, Characteristics, and Evaluation of Immune CCmponent Deficiencies
La.............
• Impaired opiCIIlization • frequent. recurrent • Quantitative total
~immunity • Inability to 1yBel pyogenic infectiou Immunoglobulin levels:
aglutinate bacteria wU:h emacellular JgG, lgA. ancllgM
• Inability to neutralize encapsulated • Vaccination antibody
bactl!rial toxina organiama titma
• frequent bacterial
I otitis media, llinuaitis,
and pneumonia
I
infections
rn..,.,...olcell-modlal>d Inablllty ofT cells to • Frequent, recurrent • ALC and T-cell
~immunity direct lk:ell antibody infections with enumeration
synthesis to T.-cell~specific opportunisticflow, • Abnormal mitogen
antigena grade organisms and .atimulation response
viruses • DeJayed
• Increased inciderwe of hypersenaitivity skin
I autoimmune disorders telting
and malignancies
!Phagocytic clilordera: • Insufficient number of • Cellulitis, akin • Absolute neutrophil
iquantitative (neutropenia) ruru.trophila abiiCI!IIIea, furunculosis
• Stomatitis, gingivitis, •
count
Blood smear
exuniuation tor blam
I rectal inflamnurtion
• Pneumonia. sepsi.l • Antineutraphil
i
antibodies
Phogocyticdloo..- • Inability to kill • Increased tusceptibility • Nitroblue tetrazollum
j fund:ional (chronic irit:lwlellular bacteria to infectiont with tat
l granulomatous clileue) secondary to £allure
to generate oxygen
catalase--positive
bacteria and fungi
• DHR c onversion test
metabolitea such as the • Chronic lymphadenitis,

superoxide anion abscesses, granulomas,
I osteomyelitis,
granulomatous colitis
ii Phagocytic clilordera:
functional (leukocyte
• Inability of the
neutrophil to migrate
• Increased susceptibility • Plow cytometry for
to infections with CD18
! adhesion de6.ciency) to the aite of infection catalase--positive
bacteria and fungi
• Severe gingivitis,
! intestinal fistulas, poor
wound healing
IComplement disorders • Impaired opsonization • Recurrent bacterial • Total hemolytic
infections with complement (CHso)
encapsulated, • Assays of the cl.auical
extracellular orpnisms and alternative
• Increased susceptl'bility complement pathways
to meningococcal,
gonococcal disease
• Increased incidence of
autoimmune dlaeaae,
espedally SLE
i .Abbrelllallons: ALC, absolute lymphocyte oount: DHR, dlhydrorhodamlne reduction; SL.E, systemic lupus erythematcsus.
:ooouoo•••-•••••••••••••oouooono-oooooouooooooooo..oooooo.oo••••••••••·••••••••••••••••••••••nooooooOoOoOoOOOOOO-OOOOOO-OOOO•O-•••••••••••••••-••••••••••oooooooo ..ooooooooouoooouoooooooooooooooooooooouooooooooooooo•••••••••••••••••••••••• ••••••••••••••••••••••••"""'"'''''''O-ooO
Chapter 8 I Immunology, Allergy, and Rheumatology • 145
TilLE 8-2. Clinical CritBria for Evaluation at DISORDERS OF HUMORAL IMMUNITY

Immunodeficiency Syndromes B-cells produce antibodies, the primary effectors of
! Severe, peraiatent, or recurrent s!nopulmonary humoral immunity. Antibodies are a vital component
j infections ofthe immune system. particularly in defense against
IInfection by an unusuaJ.• or opportunistic pathosen
extracellular pathogens such as encapsulated bacteria.
A variety of antibodies activate complement. serve
j Family hiatory ofimmunodeficiency as opsonins, inhibit microbial adherence to mucous
IInfection at an unuaualll.te (e.g., brain or liver membranes, and neutralize various toxins and viruses.
Iablceu) As a group, antibody (humoral) deficiency syndromes
~ Failure to thrive, diarrhea, and lymphopenia in an are the most common immunodeficiency diseases
!infant encountered in pediatric practice.
j Orronic gingivitis Clinical Manifestations
! •including Aspergillus, S6178tla msrcescens, NocardJa species, HistDry and Physical Examination
i Burlcholderia cepacia, and vaccine-associated pathogens A history of recurrent infections with encapsulated
!. ~~~~-~--~!~!~.~~..~i-~~..~-~-~-~-~-~1.:............................... organisms, such as Haemophilus influenzae and
Streptococcus pneumoniae, and failure to respond
hypocalcemic tetany from thymic hypoplasia). Other to appropriate antibiotic therapy are suggestive of
structures and organs derived from the branchial a primary B-cell deficiency. In addition, there is
pouches during embryogenesis may be malformed often a history of frequent upper respiratory tract
as well, including the ears and face. The severity of infections beginning after 6 months of age (when
the immunodeficiency is extremely variable. Some maternal antibodies are lost), including otitis media,
children exhibit recurrent and life-threatening in- sinusitis, and pneumonia.
fections, whereas other children have intact thymic Dlffllnntlal Diagnosis
(and therefore immune) development. X-linked agammaglobulinemia {XLA; also termed
Diagnostic Evaluation Bruton tyrosine kinase de.fi.ciency or Bruton disease)
occurs in affected boys beginning around 6 months
Absolute lymphocyte counts (calculated by multi-
ofage, which correlates with the waning ofmaternal
plying the percentage of lymphocytes by the total
white blood cell [WBC] count) and T cells are gen- antibodies transferred across the placenta. These
patients do not produce antibodies and have virtually
erally decreased. T -cell function, measured by in
no mature B cells. In addition to their susceptibility
vitro mitogen stimulation and intradermal delayed
to encapsulated organisms, individuals with this
hypersensitivity testing, is absent or significantly
compromised. Antibody production is generally
disorder are prone to severe, often life-threatening,
enterovirus infections.
absent; however, this may not be appreciated during
the first 4 to 6 months when maternal antibodies are Common variable immunodeficiency (CVID) is
still present in the blood. No thymic shadow is seen an inherited disorder of hypogammaglobullnemia
(particularly IgG and IgA) with equal distribution
on chest x-ray in patients with DiGeorge syndrome.
between the genders. Onset may be in early childhood
Fluorescent in situ hybridization testing ofchromo-
with recurrent sinopulmonary infections or later
some 22 detects the 22q11.2 deletion.
onset (adolescence or even adulthood for unclear
Treatment reasons). Specific antibody formation to vaccines is
SCID is treated initially with immunoglobulin re- defective. In addition to sinopulmonary infections,
placement and aggressive identification and treatment the incidence oflymphoma and autoimmune disease
ofinfections. Children are rapidly referred for bone is increased in these patients.
marrow transplantation. which is curative. Future Selective IgA deficiency is the mildest and most
treatments for X-Un.ked SCID will certainly include common immunodeficienc y syndrome. IgA defi-
gene therapy as an alternative to bone marrow trans- ciency is diagnosed when the serum IgA. level is
plantation: however, this is avallable currently only less than 5 mg/dL, and serum levels of the other
in research trials. SCID due to DlGeorge syndrome antibody classes are normal. Patients react normally
has been successfully treated with both thymic and to viral infections but may be susceptible to bacterial
bone marrow transplantation. infections of the respiratory, gastrointestinal (GI),
HN is discussed in detail in Chapter 7. and urinary tracts. Some patients are asymptomatic.
Dlagnastlc Evaluation Specifically, the host's antibodies do not respond

Quantitative measurement of IgG, IgA, and IgM normally to carbohydrate antigens. Autoimmunity
levels is an important screening test for specific may be present. Survival to adulthood is rare because
deficiencies and for panhypopmmaglobulinemia. ofbleeding, infections, and associated malignancies.
In order to rule out othercauses of hypoproteinemia Therefore, bone marrow transplantation is recom-
as etiologies for low Immunoglobulins. another se- mended for young infants.
rum protein saeen such as albumin or transferrin Hyper-IgMsyndrome is a group of disorders that
should be ordered at the same time. Antibody titers have defects in both T-cell and humoral immunity.
generated against tetanus and diphtheria (protein The most common form is X-linked, because of a
antigens) and pneumococci and H. influenzae (car- mutation in the CD40L gene. The interaction between
bohydrate antigens) after immunization also assess CD40L on T cells and CD40 on B cells is necessary
B-cell function. for inununoglobulln class switching from IgM to
A unique scenario arises when considering the IgG, IgA, or IgE. Boys present in the first year of
etiology for hypogammaglobulinemia in yowtg infants. life with recurrent sinopulmonary infections and/
All serum immunoglobulin classes are present at or P. jiroveci pneumonia. Diagnosis is made due to
birth.. but most do not reach adult levels until early to the presence oflow IgG and lgA, with elevated lgM
middle childhood. Maternal IgG is actively transported and absent titers to chlldhood vaccines. Treatment
across the placenta and is protective throughout the is bone marrow transplantation.
first few months oflife. Over the first 6 to 8 weeks of
life, maternally derived lmmunoglobuliru; decrease DISORDERS OF PHAGOCYTIC IMMUNITY
and are replaced by the child's growing production. Phagocytes are responsible for removing particulate
Transient hypogammaglobulinemia of infancy is matter from the blood and tissues by ingesting and
a recognized disorder in which the acquisition of destroying microorganisms. These cells must be able
normal infant immunoglobulin levels is delayed. to adhere to the endothelium. move through the tis-
Although some of these patients are subsequently sues to their site of action, engulfthe harmful matter.
diagnosed with other primary immunodeficiencies, and kill it intracellularly. Phagocytic disorders are
the majority eventually develop normal immunoglob- due to an insufficient number of normal neutrophlls
ulin levels by 2 to 5 years of age and. in contrast to (neutropenia); to phagocytic cell dysfunction; or to
children with CVID, XLA, or SCID, they have intact the inability of the phagocytic cell to migrate to the
responses to vaccination and low (but not absent) site ofaction. Neutropenia may result from infection
inununoglobulin levels. Generally, these children do (particularly viruses), medication administration
not require immunoglobulin replacement and receive (penicillin, sulfonamides, anticonwlsants), circulating
only supportive care for typical childhood illnesses. antineutrophil antibodies, malignancy in the bone
marrow, or aplastic anemia. Chronic granulomatous
Treatment disease (CGD), the most common inherited disorder
The mainstays of therapy for XLA and CVID are of phagocytic immunity, occurs when neutrophils
appropriate antibiotic use and periodic gammaglob-
and monocytes are unable to kill certain organisms
ulin administration. Intravenous immunoglobulin
after ingesting them because ofa failure to generate
(MG) and/or subcutaneous gammaglobulin provides
superoxicle. Leukocyte adhaton deficiency (LAD) arises
antibody replacement and has revolutionized the when neutrophlls are trapped in the bloodstream and
treatment ofhumora.l immunodeficiency syndromes. are unable to migrate into the tissues because of a
defect in adhesion molecules necessary for binding
COMBINED IMMUNODEFICIENCY SYNDROMES of the leukocyte to endothelial cells.
Combined humoral and cell-mediated immunode-
ficiencies tend to be inherited and manifest a wide Clinical Manif8stations
range of clinical severity. Affected patients c:Usplay History IJIIf/ Pl1yBicaJ Examination
Increased susceptibility to both traditionallyWulen.t Patients with neutropenia generally do not experi-
and opportunistic infections or may present with ence serious or life-threatening infections unless the
autoimmunity. neutropenia is both~ (absolute neutrophil count
Wukott-Aidrich syndrome is an X-linked reces- [ANC] <0.5 X 10"'/J.LL) and chronic (lasting longer
sive disorder of (primarily) B-and (usually) T-cell than 2 to 3 months). Typical complaints include
Immunity, atopic dermatitis, and thrombocytopenia. gingivitis, skin infections, rectal inflammation. otitis
media, pneumonia, and sepsis. Patients are often in- those with infectious complications may respond to
fected with Staphylococcus t.IUNllU and gram-negative recombinant human granulocyte-colony stimulating
organisms. Of note, patients with neutropenia are factor injections. All patients with CGD should re-
unable to mount a sufficientinflammatory response, ceive prophylactic trimethoprim-sulfamethoxazole.
so typical signs of infection such as erythema, warmth, Agressive treatment of deep-seated bacterlal and
and swelling may be absent even in the presence of fungal infections Is aitical. Bone marrow transplan-
significant pathogen load. tation is frequendy recommended. and gene therapy
CGD is characterized by chronic or recurrent is a promisingarea of research. Treatment for LAD is
pyogenic infections caused by bacterial and fungal adequate treatment ofinfections and bone marrow
pathogens that produce catalase (S. aureru, Candida transplantation.
alblcam, Aspergillus) and by most gram-negative
enteric bacteria. Both X-Unked and autosomal in- DISORDERS OF COMPLEMENT IMMUNITY
heritance occur. Abscesses and granuloma formation Although quantitative deficiencies of virtually all
occur in the lymph nodes, liver, spleen, lungs, skin, complement components have been described. they
and GI tract. Failure to thrive. chronic diarrhea, and are far less common than the immunodeficiencies
persistent candidiasis ofthe mouth and diaper area are mentioned earlier. The primary mechanism ofdisease
common. Affected individuals are also at increased is impaired opsonlzation. Patients with complement
risk for opportunistic infections, disseminated viral disorders have increased susceptibility to bacterial
illnesses, and inflammatory bowel disease. infections and a higher incidence of rheumatologic
Children with LAD are msceptible to infections disease. In particular, deficiencies of the terminal
with the same microorganisms as those with CGD. complement components CS to C9 increase the
In contrast to CGD, patients with LAD have WBC likelihood of Ne~rla meningitidis infections. De-
counts that are 5 to 10 times normal and are unable ficiencies of the early forms of complement (Cl to
to form granulomas. Severe gingivitis, intestinal C4) are seen with increased frequency in patients
fistulas, and poor wound healing, such as delayed with systemic lupus erythematosus (SLE).
separation ofthe wnbllical cord, are significant clues
for the consideration of LAD.
ALLERGY
Diagnostic EValuaiiDn
An allergic reaction is an undesirable immune-mediated
Severe neutropenia il defined uan ANC <0.5 X lOS/~. response to an environmental stimulus. Allergies
Serial complete blood counts will reveal a leukoeryth-
have been implicated as a contributing factor in
roblastic response unless the condition is chronic.
anaphylaxis, asthma, allergic rhinitis, and atopic
Bone marrow examination is required ifmalignancy
dermatitis. Allergic reactions range from mild to
or aplastic anemia is a consideration.
life.-threatening and are never considered adaptive.
In CGD, the WBC count typically ranges between
The allergic triad of atopic disease consists of
10,000 and 20,000/J.ll with 60\16 to 80\16 polymorpho-
atopic dennatitis (eczema), allergic rhinitis, and
nuclear cells. Leukocyte chemotaxis is normal. The
asthma. Atopic children will frequently develop ec-
hallmark abnormality is the inability ofaffected cells
U11Ui, followed by allergic rhinitis, with the eventual
to produce an oxidative burst resulting in hydrogen
development of allergic asthma. This is known as
peroxide. The nitroblue tetrazolium test and the di-
the allergic march.
hydrorhodamine reduction (DHR) test are laboratory
studies performed to detect the inability to produce ATOPIC DERMATITIS
this reduction reaction.
Atopic dermatitis is a chronic, relapsing and remit-
The most common fonn of LAD results from a
ting inflammatory skin reaction to specific allergens,
genetic defect in CD18, which is the ~ portion of
including specific foods and environmental allergens.
LFAl andis necessary for tight adhesiDn between the
The most common allergens associated with eczema
neutrophil and the endothelial cell Leukocyte chemo-
include milk proteins, egg, fish, wheat, soy, dust mJte,
taxis is abnormaL Flow cytometry analysis of CD18
and animal dander. ln addition to immune alteratioii&,
expression on neutrophils will establish the diagnosis.
barrier dysfunction and microbial factors also play a
Trellbnent role in the pathogenesis ofatopic dermatitis. Eczema
Children with acute neutropenia need no special usually appears in infancy and affects upward of 10\16
treatment. Patients with chronic neutropenia and of the pediatric population. Genetic predilection is
the highest risk factoL About half of patients with months of pollination and is uncommon before 4
atopic dermatitis later develop allergic rhinitis and/or to 5 years of age. Tree pollens are common during
asthma. Early therapeutic intervention may prevent early spring, followed by grass pollens, which are
the progression of the allergic march. detected until the early summer. Ragweed season
starts in the late summer and persists until the first
Clinical Manifesbrtions frost. Perennial disease persists year round, usually in
The typical rash consists ofa pruritic, erythematous, response to household allergens (molds, dust mites).
weeping papulovesicular reaction that progresses to
scaling, hypertrophy, and lichenification. In infants Pathogeneela
younger than 2 years, the eruption involves the The offending allergen binds to IgE on mast ceUs in
extensor surfaces of the arms and legs, the wrists, the upper respiratory tract, with sobaequent release
the face, and the scalp; the diaper area is invariably of inflammatory mediators. This localized inflamma-
spared. Flexor areas predominate in older age groups, tion results in nasal congestion, rhinorrhea, and/or
as well as the neck, wrists, and ankles. The diagnosis postnasal drainage, sneezing, and occaslonallyitching.
of atopic dermatitis is primarily clinical, based on
Risk Factors
history, physical examination, and response to treat-
Atopy and genetic predisposition are the major risk
ment. The differential diagnosis includes contact
factors. Smoking in the home in the first year of life
dermatitis and psoriasis, a chronic nonallergi.c skin
also increases the likelihood of subsequent disease.
disorder (see Chapter 10).
Paradoxically, heavy exposure to animal dander early
TrHtment in lire may reduce the risk ofsubsequent atopic disease.
Eczema ls commonly referred to as ~e itch that Clinical Manifestations
rashes:' The goal of treatment is termination of the
History
itch- scratch-itch cycle. Patients should try to keep
Patients with allergic rhinltis are plagued with
their skin well-hydrated with lotions that do not contain
nasal congestion, profuse watery rhinorrhea, and
fragrances. Tight clothing and heat may precipitate
sneezing. Associated allergic conjunctivitis is com-
exacerbations and should be avoided. Moisturizers
mon. Unrelenting postnasal drip produces frequent
are the mainstay of treatment, followed by the use
coughing and/or throat clearing. Patients may also
of topical corticosteroids for areas ofinflammation.
complain of drowsiness because of recurrent brief
Pimecrolimus cream, an inhibitor ofT-cell activation,
awakenings at night. As a group, children with
has been approved for patients over 24 months ofage
untreated allergic rhinitis have been shown to have
who cannot tolerate topical steroids or have resistant
decreased school performance when compared
disease. Topical tacrolimos is another immunomodu-
with their peers.
lator that may be used in more severe cases. Recently
approved phosphodiesterase inhibitor (crisaborole) Physical Examination
and anti-11-4 and IL-13 cytoldne blocker (dupilumab) On examination, the nasal mucosa appeara boggy
mark an important addition of new therapies for and bluish. Two characteristic features of allergic
atopic dermatitis. Severe chronic eczema may be rhinitis are allergic shiners (dark circles that develop
complicated by bacterial superinfection. under the eyes secondary to venous congestion)
and the allergic salute (a constant upward wiping
AU.ERGIC RHINITIS motion with the hand that causes a horizontal crease
Allergic rhinitis is a type 1 hypersensitivity immune across the middle of the nose). Because of the severe
response (IgE mediated) to environmental allergens congestion, patients may become obligate mouth
including airborne pollens, animal dand~ dust mites, breathers, and a gaping mouth and palatal arching
and molds. Allergic rhinitis is the most frequent may be seen on physical examination. Chlldren with
cause ofchronic or recurrent clear rhinorrhea in the allergic rhinitis are also prone to recurrent sinusitis
pediatric population. Allergic rhinitis affects sleep, and otitis media with effusion.
cognition, performance, and quality of life.
omarenaal Diagnosis
Epidemiology Infectious rhinitis is much more common than
It is estimated that up to 4.0% ofchildren are affected allergic rhinitis in infants and toddlers and is often
by allergic rhinitis by the time they are 6 years ofage. mucopurulent. Sinusitis causes chronic rhinorrhea
Seasonal allergic rhinitis, or hay fever. ls limited to and postnasaldrip associated with facial tenderness,
cough, and/or headache. When a nasalforeign body ASTHMA

is present, the discharge is usually unilateral, thick, Astluna is discussed in detail in Chapter 6. A significant
and foul smelling. Other possible diagnoses include proportion ofasthma is allergic in nature. Allergens
vasomotor (idiopathic nonallergic) rhinitis, which frequently associated with asthma exacerbations
appears to be due to an exaggerated vascular response include mold, dust mites, and pet dander. Allergen
to irritants, and rhinitis medicamentosa, which results avoidance is the first step in effective treatment.
from an overuse of topical decongestants. Other therapies are discussed in Chapter 6.
URnCARIA AND ANGIOEDEMA
Usually, a careful history confirms the diagnosis.
Patients who do not respond favorably to a trial of Urticaria and angioedema are classic type 1 hyper-
second-generation (nomedating) antihistamines sensitivity reactions.llrticarla describes the typical
may require further workup. Elevated nasopharyn- raised edematous hives on the skin or mucous
geal eosinophil levels may support the diagnosis. membranes resulting from vascular dilation and
A serum radioallergosorbent test (RAST) may be increased permeability. The lesions i~ blanch,
used when skin testing cannot be performed, but and generally resolve within a few hours to days.
the sensitivity is 10% to 25% less than the preferred Angioedema is a similar process confined to the
direct skin testing for specific allergens. lower dermis and subcutaneous areas; the depth
results in a well-demarcated area ofswelling devoid
Treabnent of pruritus, erythema, or warmth. Although acute
The most effective treatment for any allergic condition urticaria and angioedema occur frequently in the
is allergen avoidance. Switching to air-conditioning pediatric population, chronic forms are rare.
in the summer (rather than keeping the windows
open) affords some protection to patients with pollen Clinical Manifastations
allergies. Limiting the amount of humidity in the The diqnosis is based on a detailed history of recent
home can decrease the presence of dust mites and exposures or changes in the patient's environment.
various fungi. Dust mite mattress and pillow covers The multiple allergens and conditio:na associated
as well as frequent washing and/or drying ofbedding with urticaria and angioedema include foods, medi-
on high heat help with limiting dust mite exposure. cations, insect stings, infections, and some systemic
EUminating animal dander and limiting exposure to illnesses. Clinical manifestations may be delayed as
cigarette smoke are also helpful. long as 48 hours after the initial encounter.
Pharmacotherapy is an important adjunct if Hereditary fonns ofangioedema exist but are not
avoidance is not possible. H 1-histamine blockers IgE mediated. Patients with hereditary angioedema
(oral or intranasal) are the mainstay of treatment. have an inherited Cl esterase inhibitor deficiency.
These nonsedating formulations are approved Greater than 50% of the time, the inciting trigger
for use in children older than 2 years. Intranasal remains a mystery. The angioedema is frequently
cromolyn is helpful as a preventive medication if asymmetric and is not accompanied by urticaria.
taken before the onset ofsymptoms. Nasal topical
steroids are very effective treatments with minimal Tr8abnent
side effects. Oralleuk.otriene receptor antagonists Treatment depends on severity, which ranges from
may be beneficial in some patients. Topical and mild to J.ife..threatening (Le., swelling around the
inhaled sympathomimetic& (the most popular airway). Subcutaneous epinephrine is the treatment
being pseudoephedrine) are useful for short-term of choice in emergency situatiom, followed by
therapy only and, if taken improperly, may result intravenous diphenhydramine and steroids. Oral
in severe rebound congestion. Allergy immuno- antihistamines, sympathomimetics, and occasionally
therapy (shots) is indicated and is very effective for oral steroids are appropriate in milder cases. Newer
the treatment of allergic rhinitis, allergic asthma, treatments for hereditary angioedema include Cl
and allergy to stinging insects. The child must be esterase replacement and kallikre:in inhibitors.
able to articulate symptoms of a reaction to the
FOOD ALLERGIES
immunotherapy before administration. Studies
have demonstrated that use of immunotherapy Pathogenesis
may prevent the development of further allergies Food allergy is an immune-mediated response to a
and subsequent atopic disease. spedfi.c food protein. It is important to distinguish
between food intolerance (an undesirable nonim- delay in the introduction of solid foods until after
munologic reaction) and true food hypersensitivity, age 4 to 6 months may prevent the development of
which is an 1gB-mediated immune response. Examples certain food allergies. Guidelines now recommend the
of nonimmunologic advene food reaction include introduction of ase-appropriate peanut-containing
caffeine-induced tachycardia and la.ctose intolerance. foods as early as 4 months for the prevention of
peanut allergy.
Epid8miulugy
Eighty percent of all food allergies present during
the first year of life. The overall prevalence of food RHEUMATOLOGY
allergies is also higher in children (5" to 896) than
The modern concept ofrheumatic disease encompasses
in adults (196 to 296). Relatively few foods are rep-
a large number ofautoimmune and autoinflammatory
resented; peanuts, eggs, m.Uk proteins, soy, wheat.
conditions. In autoimmune disorders, immune dys-
tree nuts, and fish account for over 9096 of reported
regulation ofself-tolerance by the adaptive immune
cases. Exclusive breastfeeding may delay presenta-
system results in the production of autoantibodies
tion unless the mother is ingesting the offending
and self-reactive T cells, leading to inflammation
proteins regularly. One-third of patients with atopic
and target organ damage. As a group, autoimmune
dermatitis and 1096 of those with asthma also have
disorders are not unconunon in pediatrics; examples
a food allergy.
include most juvenlle idiopathic arthritis (JIA), SLE,
Clinical Manlfasbrllons and juvenile dermatomyositis (JDM). In contrast,
Hiatory and PhysJcal Examination autoinflammatory disease develops when the innate
A detailed history, including daily records of intake immune system is abnormally stimulated. often
and symptoms, is essential for the diagnosis. True because of genetic predisposition. leading to the
food allergies can present with isolated cutaneous overproduction of inflammatory cyt:okines such as
reactions, Gl symptoms, respiratory symptoms, ll..-1, tumor necrosis factor alpha (TNF-a), and ll..-6.
and life-threatening anaphylaxis. Symptotru~ that Most autoinflammatory diseases are quite rare, with
develop during weaning are particularly suggestive the exceptioill!l ofsystemic JIA and Crohndisease. The
offood allergies. periodic fever syndromes (PFS) are considered to exist
within the group ofautoinflammatory disorders. The
Diagnostic Evaluation manifestations of rheumatic d.lsease in childhood are
Skin testing has a low positive predictive value; it is protean, and typical presenting signs and symptoms
more helpful for ruling out specific food proteins are often seen in nonrheumatic conditions as well
as causative lgE triggers. A RAST will identify Particularly common are comtitutionalaymptoms
IgE an.t:J.'bodies to specifi.c foods in the serum. The such as malaise, fatigue, weight Joss or poor weight
double-blind, placebo challenge-food challenge is the gain, and/or fever. Clinical manifestations and
current gold standard. Several foods are eliminated laboratory abnormalities associated with specific
from the patient's diet for a period before testing. Then disorders are noted in Table 8-3.
the foods are disguised and tested, alternating with
placebos, over several days. A challenge is considered JUVENILE IDIOPATHIC ARTHRinS
positive ifsigns and symptoms recur after ingestion.
Epid•miolugy
Such testing must be performed in a hospital setting,
JIA is the most common rheumatic disease in chil-
as anaphylaxis is a poJSible complication.
dren, with a prevalence of at least 1:1,000 children
Treatment in the United States. JlA is an umbrella term for
Treatment entails eliminating the offending food the clusification of chronic arthritis (>6 weeks)
from the diet. Patients and their caregivers should be occurring in individuals under 16 yean of age. Other
educated in the use ofan autoinjectable epinephrine causes of arthritis must be excluded before the di-
pen. For infants with severe, widespread allergies, agnosis ofJIA can be applied. In the past. childhood
elemental hypoallergenic formulas are avallable. arthritis was called '"juvenile rheumatoid arthritis• or
Cow milk, soy, egg, and wheat allergies are usually •;uvenile chronic arthritis• and classified acmrding
outgrown after avoidance of the offending food. Oral to slightly different criteria. Because the majority
challenges can be conducted safely to reintroduce of children with juvenile arthritis do not resemble
the food. However, peanut Oegum.e), nut, and fish adults with rheumatoid arthritis (RA) and not all
a11ergi.es usually persist. Breastfeeding coupled with children with arthritis have a chronic course, the
TIILI 8-3. Clinical Manifestations and Laboratory Findings of Rheumatic Disease

..fllllmpiDm •a lllllww-.:1......
Cllnlc6J llanll8ltillfDn
Dry~ dry mouth Sjijgnm syndrome
Oral/nasal ulcen SLE
Gruwlomatom with polyangiitis (formerly Wegener
granulomatosfs)
B~etcUseue
Cltest pain/pleurttil SLE

Syatemic JIA
Vasculitis
Arthritis Qoint swelling, morning stiffness) JIA
SLE
Vasculitis
Mwcle wealmeu }tMlnile dennatomyusitia
Skin tightening/thickening systemic sclerom
Linear scleroderma
Raynaud phenomenon SLE
systemic sderom
Vasculitis
Purpura Henoch-Scltonlein purpura
Small- and medium-vessel vuculitis
Malar rub SLE
Juvenile dermatomyolitia
Gottron papula (extensor aurface rub) Juvenile derma.tomyusltil
Nai1fold capillary chanpa SLE
Juvenile dermatomyusitia
Syatemic sderom
Vasculitis
Systemic JIA
Kawasaki disease
Markedly elevated ESR Systemic JIA
Kawasaki disease
Vasculitis
Thrombocytoaia Systemic JIA
Kawasaki disease (late stage)
Protelnurlalhema.turla SLE (lupus nephritis)
Small-veuel vuculitls
Henoch-Sclt6nlcln purpura
Sterile pyuria Kawaaald diteale
Elevated muscle-related enzymes }tMlnlle dermatomyositis
Juvenile polymyositis
SLE
Antinuclear antibody SLE and I'l!lab!d dilordera (IICleroderma, SjOgren
syndrome)
JIA (nonsyatmnic)
Anti-cW>NA, anti-Smith SLE
(contimled)
TABLE 8-3. Clinical Manifestations and Laboratory Rndlngs of RheumaUc Disease (continued)
i Antiphospholipid antibodies SLE
IAnti-.ONA Linear ac:leroderma
IRheumatoid factor Rheumatoid factor-positive polyarticular JIA
!Low complement C3, C4 SLE
~ AbbnMallons: dsDNA, double-atranded DNA; ESR, &fYihi'()Cj'te sedimentation rate; JIA, jlMit"'lle Idiopathic arthritis; SLE, ~lc
! lupus erythematosus; ssDNA. slngl•stranded DNA. ,
=•••••••-•oooooooouOOOOooooooooooooooo•oooooooooooooo oo_o,.oooooo.,.oooo-ooooooooo••••+••••••••••••••••••••••••••••~•••••••••••••••••••~••••••••••••••••••••••••••••••••••••••••••OoooOOOOooooooo. .o oooooooooooooooooo,.oooooooo.o ooooooooooooooooooo••••••••••••••••••••••••••••••••••••••
term JIA was imtituted. The most common subtype antinuclear antibody (ANA) test. The majority of
ofJIA is oligoarticul.ar (-45%), followed by polyartic- patients with oligoarticular JIA experience remission
ular (-25%), systemic (-10%), psoriatic (-5%), and after several years ofactive arthritis; late recurrences
enthesiti.s--related arthritis (ERA [ -10%]). can occur.
Chronic, nongranulomatous anterior uveitis (iri-
Pathogenesis
docyclitis) is detected in up to a third of patients with
The etiology of JIA is unclear, but genetic and
oligoarticular JIA. A positive ANA test is associated
environmental factors are likely both involved.
Certain human leukocyte antigen (HLA) types are
with the development of this condition. Chronic
anterior uveitis is typically asymptomatic but can
associated with an increased risk of disease. The
underlying pathophysiology in most forms ofchronic
be appreciated on slit lamp examination. Because of
the risk ofvisual impairment and blindness, routine
inflammatory arthritis is synovitis (inflammation
screening is indicated in JIA patients at risk for this
and hypertrophy of the synovium), a term that is
complication.
often used interchangeably with arthritis. TNF-a
Polyarticular JIA, the next most common sub-
is the major cytokine involved in the development
type, can be subdivided into rheumatoid factor
ofsynovitis/arthritis in JIA; therapeutic blockingof
(RF)-positi.ve and RF-negative disease. RF-posi.tive
TNF-a has dramatically improved the outcome of
many children with JIA.
JIA resembles adult RA, with erosive, symmetric
small (wrist, hand, fingers) and large joint arthritis
Clinical Manlfea1Btlans and rheumatoid nodules. RF-positive JlA typically has
History and PhysiCal Examination its onset in adolescence and takes a chronic course.
Arthritis is a clinical diagnosis defined as swelling RF-negative JIA usually presents in early childhood.
within a joint, increased warmth over the joint, may have both large and sm.all joint involvement, and
painful or limited movement of the joint, and/or carries a better prognosis than RF-positi.ve disease.
joint tenderness. Morning joint stiffness and stiffness Systemic JIA is quite distinct from the other JIA
after immobility lasting for more than 30 minutes subtypes, both in the clinical manifestations and
is a classic symptom of joint inflammation and is in the fact that systemic JlA is an autoin:flamma-
particularly common in JIA. Any synovial joint can tory disorder. Extra-articular manifestations are
be affected; often overlooked is the temporoman- prominent and often precede the onset of arthritis.
dibular joint. The presence of severe joint pain is Systemic JIA presents with intermittent high fevers
not characteristic of JlA and suggests an alternate that occur once or twice dally. with normal or below
diagnosis (infectious or reactive arthritis, mechanical normal temperatures in the interval. The patient
disorders). JIA subtypes are claasified by the number appears toxic and suffers from profound malaise
and location of joints involved. physical findings, during the fever episodes; a faint. evanescent, non-
associated diseases or family history, and sometimes pruritic salmon--colored rash is often present as well.
extra-articular manifestations (Table 8-4). Hepatosplenomegaly. lymphadenopathy, and signs
Oligoarti.cular JIA is the most common subtype. of serositis (pericarditis) may be noted on physical
The typical patient is a young girl 2 to 4 years of examination. The arthritis can involve both large
age. Large joints (knee, anJde) are most commonly and small joints and is often destructive. There is a
involved. Long-standing arthritis can result in joint marked acute phase reaction, including leukocyto-
contractures, muscle atrophy, and increased extremity sis, thrombocytosis, anemia, elevated erythrocyte
growth in the affected limb (leading to limb length sedimentation rate (ESR) and C-reactive protein
discrepancy). Up to 75% of patients have a positive (CRP), and elevated ferritin. Neither ANA nor Rf
1-
TilLE 1-4. Clinical Manifestations of JIA
i• .....
• Arthritia oC four or fewer joints
• Most commonly l.Jwolves knee. ankle,
..........
Early chllclh.oodo peW at 2-4 y
.......
F >>> M
wrilt, elbows
l Polyartluitb Subdivided according to the preaence of
rheumatoid factor
i Rheumatoid fac:toc • Arthritis offive or more joints Biphuic distribution; early peak F >> M
I neptive at 2-4 y and later peak at 6-12 y
i Rheumatoid factor • Most commonly distal symmetric Late childhood or adolescence F >> M
! positive arthritis
Rheumatoid nodules
!S}'deJDlc arthritis : Arthrit:IJ with or preceded by quotidian Throughout Childhood F=M
(claJiy) fever Cor at least 3 d. aa:ompanled
by one or more ofthe fu1lowmg:
Ij 1. Evanescent erythematous raah
2. Lymphadenopathy
3. Hepatomegaly and/or splenomegaly
4. SerOiitis
I • Mandatory exclusion of infection
and malignancy; arthritis may not be
present early in coune
• Arthritis can .i.avol.~ larse and lllllall
I jolnD
~--·
Arthritis and psoriasis or arthritis with Biphasic distn'butiono early peak F> M
at least two of the following: at 2-4 y and later peak at 9-11 y
L Dactylitis
2. Nail pitting or onycholysis
3. Psoriasis in first-degree relative
Large and sm.all joint arthritis
iEadleattb-related : Arthritis and enthesitis or arthritis or Late childhood or adolescence M >> F
! arthritll enthesitis with two of the following:
1. Sacroiliac joint tenderness or
J.nflammatory lumbosacral pain
2. HLA-827 antigen
3. Onset after age 6 y in males
4. Acute (aymptomatlc) anterior lr/eltls
I 5. Hiatory ofi-U.A-827-usoclated
~ d!seaae in a first-degree relative
i...................................................................................................................................................................................................................................................................................
:
Abbreviations: HLA, human leukocyte antigen; JIA, juvenile idiopathic arthritis. ~
~·············
is present. Macrophage activation syndrome is a at the site of tendon insertion) is often present in
potentially fatal hyperinflammatory complication the Achilles tendon, plantar fascia, patellar tendon
ofsystemic JIA, characterized by fevers, cytopenias, insertion. and anterior superior lliac spines. ERA is
and very elevated serum ferritin, among other clinical associated with HLA· B27 and occurs predominantly
and lab findings. in boys more than 6 years of age. Extra-articular
A common manifestation of ERA is spondyloar- manifestations include acute anterior uveitis, oolitis,
thritis, that is, i.ntlamm.ation of the axial skeleton and/or aortic insufficiency.
(sacroiliac joints, small intervertebral joints) and the Psoriatic arthritis is defined as arthritis in the
large weight-bearing joints of the lower extremities. setting of psoriasis (see Chapter 10) or arthritis in
In addition, entheldtis (inflammation and tenderness a patient with two of the following: a first·degree
relati.lle with psoriuis, dactylitis (sausage digit), and failure). With the institution of the biologic therapies,
nail pitting or onycholysis. Nail findings may be quite crippling arthritis has become wry rare.
subtle. Dactylitis, when present, is a pathognomonic
finding of psoriatic arthritis and is due to flexor SYSTEMIC LUPUS ERYTHEMATUSUS
tendon tenosynovitis. Epidemiology
Dlffanntlal Diagnosis SLE is a chronic autoimmune disease character-
The ditferentlal diagnosis ofJIA is extensive. Reactive ized by widespread inflammation that can affect
or postinfecti.ous arthritis (including acute rheumatic multiple organs. Pediatric SLE is usually diagnosed
fever), other systemic inflammatory conditions in late childhood or adolescence, but SLE may be
(inflammatory bowel diseue, connective tissue diagnosed well before puberty. When SLE presents
diseases, Henoch~Schonlein purpura [HSP], other before puberty, the male:female ratio is equal; after
forms of vasculitis), and infection (septic arthritis, puberty, SLE is far more common in females, Asians,
viral arthritis, Lyme disease) can present with bona African-Americans, and Hispanics have higher
fide arthritis. Malignancy (leukemia, neuroblastoma, incidences than Caucasians.
bone tumors), benign tumors, and musculoskeletal
Pathogenesis
trauma may mimic arthritis.
The pathophysiology ofSLE is complex, but a predom-
Diagnostic Evaluation inant factor is abnormal handling ofcell death leading
Laboratory assessment is used primarily to supplement to an increased exposure to self-nuclear components.
the clinical evaluation. Evidence ofa mild acute phase The result ofabnormal apoptosis is the generation of
reaction is typically present (except the impressive multiple autoantibodies, often directed against the
response in systemic JIA), but is nonspecific. ANA components of the cell nucleus (ANAs) that cause
is often p~ent (except in systemic JIA and ERA) immune complex disease and antibody-mediated
and is associated with an increued frequency of cellular cytotoxicity, with subsequent target organ
anterior uveitis. RF, an autoantibody directed against injury. The etiology ofSLE is multi&ctoriaL Individuals
a portion of the IgG molecule, is present onlyin -596 with deficiencies of early complement components
of patients with JIA, The presence of the m.A~B27 (Clq, C2, C4) are more prone to develop SLE. The
allele is useful for classification; howeveJt it should not early complement components are needed for normal
be considered a diagnostic test because it is p~ent apoptotic cell clearance.
in 7% to 84J6 ofthe healthy population. Synovial fluid
Dlffanntlal Diagnosis
analysis yields a WBC count of more than 2,000/mm9
Given its ability to affect so many organ systems,
with predominantly mononuclear cells.
SLE is considered a "great masquerader:"' Adding to
Treatment diagnostic uncertainty is the fact that overlapping
Theatment consists of medical management and conditions can result in a mixed clinical picture when
physical therapy. Single large joint arthritis is often the patient has features of two or more rheumatic
best managed with intra·articular corticosteroid diseases at the same time.
injection. When multiple inflamed joints are pres-
ent, a disease-modifying drug (e.g., methotrexate)
is frequently necessary. Biologic therapies designed HIBIDry and Physical Examination
The diagnosis ofSLE can be based on the American
to neutralize specific cytokines (such as TNF-a) or
provide receptor blockade, as in the case ofiL-1, 11~6, College of Rheumatology classification criteria
(Table 8-5). Fever; malaise, fatigue, and weight loss
or T.cell costimulati.on. have dramatically improved
the outcomes for children with JIA who have &il.ed are very common. Mucocutaneous .findings include
painless oral ulcers, malarrash, discoid lupus, alopecia.
more traditional therapies.
and photosensitivity. The arthritis in SLE is nonero-
Prognosis and Colqlllcallons sille but otherwise can mimic JIA. Pericarditis and!
The prognosis of JIA varies. Generally, the more or pleuritis OCCUI'II in up to 30~ ofpediatric patients.
joints involved in the first 6 months, the more likely Lupus nephritis, glomenxlonephritis precipitated
the disease course will be chronic. Complications by immune complex deposition. is one of the most
ofarthritis include bony erosions, deformities, and severe orpn manifestations ofSLE and is often pres.
growth disturbances (llrnb overgrowth, growth ent at diagnosis. Renal involvement is described as
TAIL! M. Systemic I.JJpus Erythematosus: ofSLE patients) and anti--dsDNA (present in 60% of
Classification Criteria SLE patients) are very specific for lupus. Circulating
anti-Ro and anti-La antibodies are associated with
Four of the followlng muat be present:
secondary SjOgren syndrome and in an SLE-affected
Malar rub mother may cause consenital heart block and neo-
Dillc:oid rub natal lupus in her fetus.
PbotosenJltMty Treatment
Oral ulcers Although SLE has hi.storicallybeen usodat.ed withhigh
Arthrltil morbidity and mortality, the prognosis and quality of
life are improving. Wrth appropriatE therapy. a majority
Serositis
of patients have good long-term survival and normal
Renal disorder (hematuria, proteinuria) function. Treatment depends on which organ sy&t£ms are
Neurologic disorder involved. General considerations includethe avoidance
Hematologic dlaorder (anemia, leukopenia, of sun exposure and the use of sunscreen to avoid an
thrombocytopenia) increase in aill. death; associatEd photosensitivity can
iAntinuclear antibody trigger not onlyskin rashes but also systemic SLE flares.
The antimalarial drug hydroxyd\loroquine is particularly
! Immunologic disorder (anti-Smith. anti-dai>NA, helpful in preventingdisease flares and intreating m.u~
~ antiphoaphollpid antibodies)
cocutaneous disease manifestations. Mild cases ofSLE
i Abbnwiation: dsDNA, clouble-s'trandad DNA
l:.....Dllta frOm Ama1cen Collaga or Rheumatology 1982, I'8Vi9ad 1997. with predominantly musculoskeletal involvement are
_ .........................................
............................................................................................
addressed with nonsteroidal anti-inflammatory dru.g.1l
class I (normal. light microscopy), class ll (mesangial (NSAIDs) or disease-modifying drugs if necessary.
proliferation), class ill (focal proliferative), class N Renal and CNS involvmtent require more aggressive
(diffuse proliferative), or class V (membranous). Renal treatment In severe cases, immunosuppressive therapy
failure is most common in class N lupus nephritis. is necessary. Dailyoral or intermittentintravenous pu1se
Central nervous system (CNS) lupus can present corticosteroid administration is often employed. In
severe target organ disease, drugs such as cyclophos-
with psychosis, depressioD; confusion. or seizures.
phamide, mymphenolatemofetil. or azathioprine may
Diagnostic Evaluation be ne<asary. Biologic therapies (e.g.. B-cell depletion)
Anemia, leukopenia (most commonlylymphopenia), may offer additional benefits to patients with SU:.
and thrombocytopenia are characteristic. The ESR is
often chronically elevated because of the polyclonal DERMATOMYOSmS
gamm.opathy ofSLE and will increase above baseline Epidemiologr
during a disease flare, but CRP is usually normal A JDM is a multisystem autoimmune disease predom~
rise in the CRP may indicate infection rather than inantly involving skin and skeletal muscles. The GI
SLE disease flare. A Coombs test is often positive tract is less commonly involved. JDM is rare, with an
and may be associated with a hemolytic anemia. annual incidence of -4:1,000,000. Girls are affected
Complement levels, including C3, C4, and CHso, more commonly than boys, with age at presentation
may be useful disease-activity markers with a de- typically between 5 and 10 years.
pressed level below baseline indicating active SLE
disease. The ANA is virtually always positive, but Pa1hogenesil
this finding alone is insufficient for diagnosis, and The primary disease process occurs in the small
the ANA is not a disease~activity marker. Antiphos-- blood vessels (vasculopathy) and is humoraHy me-
phollpld antibodies (lncludlns lupus anticoagulant dlated. Immune complex deposition. complement
and anticardiolipin antibodies) are associated with. activation, and infiltration with CD4lymphocytes
an increased risk of arterial and venous thrombo- in the musculature lead to subsequent capillary and
aea and Libman-Sacla endocarditis. More specific muscle injury. The etiology of JDM is unclear but
autoantibodies against nuclear components include likely includes genetic and environmental factors.
anti~Smith (Sm), anti~double~strandedDNA (dsDNA), HLA 88/DR3 and HLADQalphal'"0501 are associated
anti~ribonucleoprotein (RNP), anti~Ro (SSA). and with hJsher risk for disease. The condition seems
anti-La (SSB) antibodies. Anti-Sm (present in 30% to be associated with. viral illnesses in some cases.
Dlffarantlal Diagnosis Corticosteroid-sparing agents such as methotrexate

Polymyositis, an inflammatory muscular condition are often given from the onset of treatment. Import-
without skin findinp, has a Aimilar clinical presenta- ant second-line agents include MG, mycophenolate
tion but is less common in children. The pathologic mofetiL and cyclosporine. Hydro:xychloroquine is
features are distinct from those ofJDM; in polymyo- thought to be effective in treating the cutaneous
Ji.tis, CDS lymphocytes 1nfiltrate the muscle fascicles manifestations ofJDM. Physical therapy is essential
and. attack muscle fibers direcdy. and should be tailored to the individual patient on the
basis ofdisease activity and COW'Se. Early aggressive
Clinical Manlfas1atlo• therapywith a resultant reduction in muscle and skin
HlstDry and PhysJcBJ Examination inflammation within the first 6 months ofthe start
Because it predominantly affects the limb girdle of the disease may prevent subsequent development
musculature, JDM produces characteristic proxi- of calcinosis.
mal muscle weakness with relative sparing of distal
strength. Activities such as climbing stairs, doing Prognosis
sit-ups, and lifting the hands over the head become Patients with a limited (monocyclic) disease course
difficult. Patients often report a history of malaise, generally have a good long-term outcome; those with
fatigue, weight loss, and intermittent fevers. The a more chronic course may suffer from significant
muscle weakness is accompanied by the pathogno. disability, especially ifcalcinosis develops. Pulmonary
monic violaceous dermatitis of the eyelids (heliotrope disease, cardiac disease, and GI perforation, although
rash), hands, elbows, knees, and ankles. Gottron rare, are leading causes of death.
papules are characteristic lesions resembling scaly
erythematous papules on the extensor surfaces of OTHER CONNECTIVE nSSUE DISORDERS
the metacarpophalangeal and interphalangeal joints Other connective tissue disorders are quite rare in
of the fingers, the elbows, and the knees. Nailfold childhood. Presentations are similal; and clinical
capillary chant;es are common. The weakness may differentiation may be difficult.
advance to involve bulbar muscle groups used for Systemic sclerosis is characterized by fibrous
swallowing and phonation. Long-standing inflam- thickening of the skin (scleroderma), particularly
mation eventually may result in calcium deposits in involving the distal extremities and face, and fibrotic
the skin and muscle (calcinosis cutis), scarring, and disease ofinternal organs (Le., esophagus, intestinal
significant muscle atrophy. tract, heart, lungs, kidneys). Early clinical findings
Diagnostic Evaluation include Raynaud phenomenon. the triphasic discol-
The most striking laboratory abnormality is marked oration of the fingers and toes from white (ischemia)
elevation of serum creatine phosphokinase, an en- to purple (cyanosis) to red (reactive hyperemia), and
zyme released during muscle breakdown (as well as hand and foot edema, which later progresses to frank
other muscle enzymes such as aldolase, aspartate sclerodactyly. Mortality risk is related to the degree of
aminotransferase, and lactic dehydrogenase). von cardiopulmonary involvement (pulmonary fibrosis),
Willebrand factor is typically elevated.. presumably pulmonary arterial hypertension, and renal disease
secondary to active endothelial inflammation. Mag- (systemic hypertension, renal failure).
netic resonance index pennits good visualization Localized scleroderma (morphea) is ~rized
of muscle inflammation; electromyography is less by discrete areas oflinear streaks (linear morphea)
frequently employed. Definitive diagnosis rests on or patchy morphea. The affected skin initially ap-
characteristic muscle biopsy findings, including pears erythematous, later becoming indurated, with
perivucular inflammatory infiltrate, perifascicular thickening and hardening of the skin and underlying
atrophy, loss ofcapillaries, focal necrosis, and muscle soft tissues. Internal organ disease is very rare. Dis-
fiber regeneration. ability can result if the sclerodermatous lesions occur
over joints, involve the &ce, or are large enough to
ln!atment restrict growth.
Treatment oonsists of pharmacologic management Sjiigren syndrome is characterizedbythe lymphocytic
and. physical therapy. The major component of the infiltration of exocrine glands, most commonly the
medical regimen is corticosteroid therapy, either salivary and lacrimal glands, resulting in dry mouth
in the form of dally oral prednisone or intermittent (xerostomia) and dry eyes (3WOphthalmia). Affected
pulse (high-dose) methylprednisolone therapy. individuals may develop chewing and swallowing
difficulties and are at risk Cor severe dental caries. Fifteen percent of patients experience recurrence of
Insufficient tear production may lead to chronic their disease.
corneal abrasions and resultant corneal scarring. The diagnosis of Kawasaki disease rests on the
Anti-Ro (SSA) and anti~La (SSB) antibodies are of- presence of guidelines established by the American
ten detected. Secondary SJ6JN!n syndrome may be Heart Association in 2004 (Table 8·6). The sequential
a consequence of other connective tissue diseases. (rather than simultaneous) appearance of disease
manifestations may initially result in misdiagnosis. The
PRIMARY SYSTEMIC VASCUUnS disease progresses in phases. During the acu~ phase
Vasculitis is an in1lammatory process of the vessel (first l to 2 weeks), the typical diagnostic features are
wall with resultant ischemia and necrosis. Apart from accompanied by extreme irritability. Characteristic
IgA vasculitis (HSP) and Kawasaki disease, primary laboratory findings include leukocytosis, significantly
systemic wuculitidu of~ young are relatively rare. elevated ESR and CRP, elevated liver transaminases,
InIgA vasculitis, IgA-containing immune complexes and sterile pyuria. Defervescence marks transition
are found within vessel walls. The annual incidence to the subacuteplr.t:zM, lasting several weeks. Clinical
of lgA vasculitis is approximately 1:5,000, but is as findings subside, but significant thrombocytosis carries
high as 1:1,400 in chlldren 4 to 6 years of age. It is a high risk for the development of coronary artery
somewhat more common in boys. Kawasaki disease aneurysms; about 2596 of untreated patients develop
occurs in about 1:10,000 children annually in the this complication. Aneurysms constitute the most
United States, is more common in boys, and has a significant cause of morbidity and mortality because
peak age of onset between 2 and 3 years. of rupture or thrombosis. Current treatment recom-
mendations consist of MG (2 g!kg) and high-dose
Clinical Manifestations and Trlllltmant aspirin therapy (80 to 100 mg/kg/day) in four divided
IgA vasculitis typically presents with the symptoms doses during the acute stage, followed by low-dose
ofskin, joint, GI, and kidney disease. Incidence peaks aspirin therapy (3 to 5 mg/kg/day) until the end of
in the winter months, and the condition is often the convakscentphase (several months later). MG
preceded by an upper respiratory infection (most typically results in rapid and profound improvement,
commonly group A Streptococcus). The classic rash and administration significantly reduces the risk of
consists ofnonthrombocytopenic purpura localized formation ofcoronary artery aneurysms. Repeated
to dependent areas of the body (lower extremities, IVIG treatment may become necessary if fevers
buttocks). Distn'bution of the rash may be atypical recur or persist. Second-line treatment regimens
(primarily facial) in clilldren. less than 2 years of incorporate high-dose corticosteroids and possibly
age. Other common findings, particularly early in TNF inhibitors (infliximab). Anticoagulant therapy
the disease, consist of scrotal edema and extremity may be indicated in patients with documented cor-
swelling. When present, acute arthritis may be ex- onary aneurysms.
quisitely painful, even rendering a child immobile.
GI involvement il usually significant, including
colicky abdominal painJ vomiting, and upper and lAlLI I-I. Clinical Criteria for Diagnosis of
lower tract bleedins. Bowel wall thickening and Kawasaki Disease
intussusception can occur. Glomerulonephritis is j Fever persisting fur 5 d or more, together with four of !
present in up to 40% of patients. It is usually mild; 1the full.owins cl1n1cal c:riteria (by history or physlcal ~
however, up to 5% of children with HSP-associated 1examination): ~
glomerulonephritis will develop end-stage renal !1. Changes in extremities !
disease. The demonstration of IgA deposition in ~ • Acute (erythema of palms/soia. swelling of l
the vessel wall by direct immunofluorescence is 1 hancWfeet) l
pathognomonic. !&A vasculitis usually requJres only 1 • auon1c: (pertungual peeling of Bngersltoes>
supportive treatment. Spontaneous resolution oc- 12. Polymorphous exanthem
curs in the majority of patients in less than 4 weeks, 13. Bilai2ral bulbar conjunctival injection
although symptoms may persist for up to 12 weeks. 14. <ltanges in llpa and/or oral cavity (erythema,
Musculoskeletal pain responds to treatment with
NSAIDs. Systemic glucocorticoids are reserved
I cracked Ups; cUffu.ae injection of oral muco11a)
for severe GI manifestations and sign11icant renal j 5. Cervical lymphadenopathy>1.5 em (ua:ually

involvement (which may require cyclophosphamide). 1 unilateral)
: ...........................................-............. .........................................................................
~······._. :
PERIODIC FEVER SYNDROMES concentrated in Arabic, Turkish, and Armenian

The PFS are frequently included in the rheumatic people, non-Ashkenazi Jews, and other Mediterra-
disease category. Mapping of the human genome nean populations such as ltalians, Greeks, and Leb-
in the late 1990s has led to the ability to define the anese. FMF is an autosomal recessive disorder with
majority of PFS as Me ndelian genetic diseases of fevers that occur for 1 to 3 days every 4 to 8 weeks.
Other common clink:al features include peritonitis,
the innate immune system; thus, they are a subset
erysipelas-like rash, and oligoarthritis. FMF results
of the hereditary autoinflammatory disorders.
from a defect in the MEFV gene.
The genetically mutated proteins are linked to the
Tumor MC1'08ilfoetor rectptor-auociated periodic
pathways ofinflammation. apoptosis, and cytokine
&yndrome (TRAPS) is an autosomal dominant disorder
processing. Common to all PFS is fever that has an
seen worldwide, with fevers lasting 7 to 21 days and
abrupt onset and termination and is identical in its
occurring two to three times per year. Abdominal
presentation with each recurrence. The clinical onset pain, severe deep mu&cle aches with overlying ery~
ofPFS is typically in childhood or adolescence, and thema, conjunctivitis, periorbital edema, and large
patients are symptom free between attacks but may joint arthritis are hallmarks of TRAPS. Genetic
have subclinical inflammation. The WBC, CRP, and mutations are found in the gene that encodes for
ESR are significantly elevated with fever attack and the TNF receptor (TNFRSFlA).
may remain slightly elevated in between attacks. Periodic fever, aphthous stomatitis, pharyngitis,
Amyloidosis may result from chronic, untreated in- adenjtis syndrome (PFAPA) is a common fever syn-
flammation with any of the PFS. The PFS are distinct drome for which no genetic mutation hu been found.
in their clinical presentation. ethnicity, inheritance, Specific diagnostic criteria include (1) three or more
and genetic defects. Thus, clinical history with patient episodes of fever lasting no more than 5 days and
fever diary, family history, ethnicity, and physical occurring in regular intervals of 3 to 6 weeks with
examination are essential to assist in the diagnosis an early age ofonset (typically younger than 5 years);
of PFS. A differential diagnosis of recurrent fevers (2) tender cervical lymphadenopathy, pharyngitis, or
should include the broad categories of infection. aphthous ulcers; (3) exclusion ofcyclic neutropenia
neoplasm. andnoninfectlouslnfiammatory disorders. or other fever syndromes; {4) normal WBC, CRP,
Famlllal Medltm'alfeanfovu (FMF) is the most and ESR between attacks; and (5) normal growth
common PFS and can be seen worldwide but is and development.
• Patients with cell-mediated immune dysfunction • Severe neutropenia, defined as an ANC

are susceptible to autoimmune disorders, intra- <0.5 x 1o'IJ!L, may result from Infection, certain
cellular organisms, and opportunistic infections medications, circulating antlneutrophil antibodies,
from organisms such as P. jlroveci. malignancy, or bone marrow dysfunction. The
• Persistent hypocalcemic tetany and/or congenital typical signs of Infection (erythema, warmth,
heart diseaae, coupled with the absence of the swelling) are often absent In the presence of
thymic shadow and cell-mediated immunode- neutropenia.
ficiency, suggests chromO&ome 22q11 deletion • CGD is characterized by chronic or recul18nt
~.e., DIGeorge) syndrome. infections because of catalase-producing
• Hwnoral immunodeficiency predisposes patients to bacteria or fl.llQI. In pa1icular, patients develop
infection with encapsulated organisms. Conmon frequent skin infections and abscesses The
inte.,-;ions Include otitis media, pneumonia, and nitroblue tetrazollum test and the DHR test are
sinusitis. Quantitative lmnulOglobulin studies laboratory studies that are useful for detecting
and antlx>dy titers agahrt vaccine antigens CGD. Patients with CGD should receive daly
are abnormal In patients with humoral immune prophylactic trimethoprim-sulfamethoxazole
dysftn:tion. Gammaglobuln therapy (ntra\1r and periodic T-interferon.
nous or intramuscular) provides antibodies to • Allergic rhinitis may be seasonal or peren-
patients with humoral immunodeficiency. nial. Nonsedatlng H1 -hlstamlne blockers and
intranasal steroids are the mainstays of treat- • Dermatomyositis is an inflammatory disease

ment. Peanuts, eggs, milk, soy, wheat, and of the skin, strtated muscle, and occasionally
fish account for the overwhelming majority the Gl tract. Weakness begins in the proximal
of food allergies. extremity muscle groups and is accompanied
• The signs and symptoms of food allergy in by a characteristic violaceous dennatitis. Serum
infants include rash around the mouth, hives, creatine kinase levels are markedly elevated.
irritability, diarrhea, and failure to thrive. • HSP is characterized by abdominal pain, vomiting,
• JIA is characterized by chronic synovitis Gl bleeding, and palpable, nonthrombocytopenlc
and classified by the number and location of purpura over dependent regions.
joints involved, physical findings, associated • Kawasaki disease presents with high fever,
diseases or family history, and extra-articular lymphadenopathy, and mucocutaneous lesions.
manifestations. High-dose IVIG reduces the risk of coronary
• SLE consists of widespread connective tissue artery aneurysms in Kawasaki disease.
inflammation and vasculitis. The diagnosis of • PFAPA is a common disorder and is seen world-
SLE is clinical. Lupus nephritis is the most wide. FMF is also seen frequently in multiple but
common clinical manifestation, resulting in specific ethnic groups. The other PFS 8f8 rare, but
significant morbidity. Typical laboratory findings mapping of the human genome and increased
include falling complement levels, a positive familiarity by the medical community is increasing
ANA titer, and a positive double-stranded DNA the frequency of diagnosis. Amyloidosis is a serious
antibody titer. long-term complication of chronic Inflammation.
CLINICAL VIGNETTES
VIGNETTE 1 testing and the fact that your patient has her worst
symptoms in the summer. Which of the following
A 6-yaar-old girl presents to your pediatric office with
associations is incorrect?
a chief complaint of nasal congestion and chronic
L Tree pollens are common in the earty spring.
rhinorrhea. She has had constant nasal congestion
b. Dust mites are most common In the fall.
for over a year, but her symptoms have worsened
now that it is summer and the windows are open.
c. Ragweed season starts in the late summer
and persists until the first frost.
She has an unremitting postnasal drip and continu-
d. Molds are year-round allergens.
ally clears her throat. She is becoming increasingly
e. Grass pollens are most likely to produce sum-
drowsy because she awakens frequently at night.
mertime symptoms.
In addition, her snoring has increased. The physical
examination reveals very boggy nasal mucosa and 3. You have detenmlned that your patient has
clear mlnormea. You are consldertng a diagnosis of allergic rhinitis secondary to cat dander, dust
allergic rhinitis. mites, tree pollens, and grass pollens. You are
ready to discuss risk factors for allergic minitis
1. Which of the following examination findings would
as well as your treatment recommendations with
NOT support a diagnosis of allergic minitis?
the parents. Which of the following statements
L Eczema
potentially associated with allergic rhinitis edu-
b. Allergic shiners
cation is false?
c. Allergic salute L The fact that both parents suffer from allergic
d. Palatal arching
mlnltls does not affect their daughter's risk of
e. Urticaria for over 6 weeks
having allergic minitis.
2. You decide to refer your patient to an allergist b. Intranasal steroids are a very effective therapy
for direct skin testing for specific allergens. She with minimal side effects.
tests positive to several allergens. You attempt c. Dust mite exposure can be limited by frequent
to make a connection between the results of the washing and/or drying of bedding on high heat.
180 • BLUEPRINI'S Pediatrics
d. Allergen immunotherapy is an effective therapy L This patient is not at an increased risk for au-
for cat dander allergy. toimmune disorders or malignancies.
e. Nonsedatlng antihistamines are available and b. lhls patient's B cells are unable to produce
are the mainstay of treatment of allergic rhinitis. antibodies needed to help protect against
encapsulated organisms.
VIGNmE2 c. This patient's treatment should include replace-
A 15-yea~old male is referred to your immunology clinic ment therapy with MG.
because he is •always sick• with respiratory and Gl d. The onset of CVID is most common in late
infections. He did not have any infections during the adolescence and early adulthood.
first 6 months of his life. He attended day care from 1. The incidence of CVID is equal in males and
ages 1 to 5 with 15 other children and then started females.
kindergarten. During his attendance at day care, he
had the usual viral infections but no more than his VIGNETIE3
siblings or other day care attendees. Since the age A 3-year-old boy presents to your urgent care center
of 12, he has been frequently diagnosed with otitis with an 8-day history of high fevera, rash, red eyes,
media, sinusitis, tonsillitis, and lntermment diarrhea. persistent crying, refusal to walk, and decreased oral
Durtng the past year, he has been hospitalized twice intake. He goes to day care, so his mother thought
with pneumonia. The flrst lung Infection was caused by that he had "caught a virus" from another child. Upon
H. lnfluenzse B; the second was caused by S. pneu- arrival to urgent care, the nurse informs you that he
moniee. He is up to date on all of his immunizations has a fever of 104.5°F. On physical examination, he
including vaccination against HiB (fl. lnfluenzae B). In is difficult to console and appears uncomfortable. His
addition, he received the 7-valent Prevnar vaccination conjunctivae are ln)ected but without any drainage. He
at his 2-year and 5-year health maintenance visits. In has cracked, red lips and a red tongue. He has a few
the past 6 months, he has lost 5 lb. Recent studies enlarged, tender left cervical lymph nodes, wHh the
of his diarrheal stools demonstrated the protozoan largest lymph node meesurtng 2 em In diameter. His
parasite Giardia Iambiia. Physical examination reveals heart examination is nonnal except for tachycardia,
an underweight, pale-appearing teenage male. He and his lungs are clear to auscultation. His abdomen
has normal tonsils and normal lymph nodes but a is nontender, and you do not appreciate any organo-
mildly enlarged spleen. You are concerned about an megaly or masses. He has diffuse, tender swelling of
Immunodeficiency and decide to order some addi- the hands and feet and an irregular erythematous rash
tional studies. on his trunk and extremities. You are concerned that
1. Which of the following aspects of this patient's case he may have Kawasaki disease.
would NOT support limiting testing to diseases 1. You recall that lgA vasculitis (HSP) is another
affecting only the humoral system? systemic vasculitis that occurs in children and
a. No Infections durtng the ftrs1 6 months of life consider adding it to your differential diagnosis.
b. VIral Infections while at day care Which of the following statements is true?
c. Pneumonia with encapsulated pyogenic L Kawasaki disease and lgA vasculitis are equally
organisms common in the United States.
d. Infections with organisms against which he b. The peak ages for Kawasaki disease and lgA
has been previously immunized vasculitis are identical.
e. Frequent Gl infections including G. Iambiia c. lgA vasculitis is characterized by a persistent,
2. Which of the following tests is least likely to high fever.
give you Information about a patient's humoral d. The rash is similar in both conditions.
Immune system? e. Gllnvolvement In lgA vasculitis Is severe and
a. T and B lymphocyte subpopulatlons may lead to Intussusception.
b. Quantitative immunoglobulins OgG, lgA, lgM) 2. You decide to order some laboratory tests to
c. Delayed hypersensitivity skin testing evaluate your suspicion of Kawasaki disease.
d. Specific antibody testing for H. influenza& B Which of the following laboratory results would
1. Ability to produce antibodies following immu-
not support a diagnosis of Kawasaki disease?
nization with S. pneumoniae L Elevated WBC count
3. Your patient's test results connrm a diagnosis of b. Normal ESR
CVID. You prepare to discuss the results with the c. Elevated liver transamlnases
patient and his parents. Which of the following d. WBCs In the urine with a negative urine culture
statements is false? e. Elevated platelet count
3. You review this child's clinical findings and deter- reveals mild elevation of CRP and ESR. You formulate
mine that he meets the fever requirement (fever a differential diagnosis and consider ollgoartlcular JIA
for at least 5 days} and has all five of the clinical as a potential diagnosis.
criteria for Kawasaki disease: extremity changes
(swelling of the hands and feet), polymorphous 1. Which of the following characteristicsofthis case
exanthem, bilateral bulbar conjunctival injection, would be least compatible with a diagnosis of
Up/oral cavity changes (cracked, red lips and oligoarticular JIA?
L Absence of significant joint pain
strawberry tongue}, and cervical lymphadenop-
athy 1.5 em. All of his laboratory results are also b. Mild elevation of CRP and ESR
consistent with Kawasaki disease. You decide to c. Joint swelling for less than 6 weeks' duration
lnHiate treatment tor Kawasaki disease with IVIG d. Onset before age 16
at 2 g/kg and aspirin therapy. What major com- e. Arthritis involving four or fewer joints
plication of Kawasaki disease ara you attempting 2. Although this patient does not have overt evidence
to avoid with these therapies? of eye disease, you explain to the patient's mother
L Peeling of the skin of the fingers and toes
that an ophthalmologic slit lamp examination is
b. Glomerulonephritis necessary to rule out uveitis. Which of the fol-
c. Coronary artery aneurysm lowing laboratory tests would be most helpful in
d. Amyloidosis assessing this patient's risk for the development
e. None of the above of chronic anterior nongranulomatous uveitis?
L RF
VIGNETlE.
b. ANA
A mother brings her 3-year-old daughter to your office c. HL.A-827
for an evaluation of left knee swelling. The child's symp- d. Serum ferritin
toms began approximately 30 days ago with morning e. WBCcount
stiffness that Initially lasted 30 minutes. However, she
now limps all day. The review of symptoms is negative 3. Which of the following statements regarding
for fevers, rash, sore throat, pain, Gl symptoms, or physical examination findings in JIA is false?
recent infectious illnesses. The patient's vital signs ara L Long-standing arthritis can lead to 6mb length
within normal limits. Physical examination reveals a discrepancy.
well-appearing child with a swollen left knee and ankle. b. Patients with systemic JIA often have an ev-
The joints ara not erythematous but ara warm to the anescent salmon~colored rash.
touch, have a decreased range of motion, and ant tender c. Dactylit is is a common finding across JIA
to palpation. The child has a flexion contractura of the subtypes.
left knee and walks with a limp, but the remainder of d. Achilles tendon Insertion tenderness Is often
the examination is normal. A radiograph of the left knee prasent in patients with ERA.
demonstrates mild soft tissue swelling and effusion e. RF-positive patients have symmetric polyar-
without osseous abnormalities. Laboratory testing thritis of small joints.
ANSWERS
VIGNETlE 1 Question 1 in turn, is followed by asthma is known as the allergic

1.Answer E: march. Allergic shiners are dark circles that develop
Urticaria that lasts for more thane weeks is classified under the eyes secondary to venous congestion and
as "chronic urticaria" and is not an lgE-mediated pro- ara frwquently seen in children with allergic rhinitis.
cess. Urtlcar1a that develops Immediately following The allergic salute Is a horizontal crease across the
exposure to an allergen Is most 6kely lgE-mediated middle of the noee because of the constant upward
and may accompany allergic rhinitis. Urticaria for e wiping motion of the nose with the hand. The allergic
weeks is not associated with allergic rhinitis. Eczema salute is a hallmark of allergic rhinitis. Severa nasal
may prasent in infancy or earty childhood as the first congestion In patients with allergic mlnltls may lead
sign of atopic (allergic) tendencies/Illness. The pro- to obligate mouth breathing; palatal arching may be
grassion of eczema followed by allergic rhinitis which, seen on physical examination as a result.
VIGNETTE 1 Quesllan 2 until approximately 6 months of age. Thus, it is not

2.AnswerB: surprising that the patient did not have any Infections
Dust mites, pet dander, and molds are known as before 6 months of age. A deficiency in cellular or
perennial allergens; all generally produce year-round phagocytic immunity would likely lead to infections
symptoms. Of note, it is unusual to be allergic to pine before 6 months of age. Humoral immunity Is required
trees (I.e., Christmas trees); rather, the mold on the for protection against encapsulated organisms such
tree produces the allergic symptoms. Rinsing off the as H. influenzs.e BandS. pneumoniae. Antibodies
tree and letting it dry before putting it in the house produced in the humoral immune system serve
may prevent allergic symptoms. The other answers as opsonlns, activating complement to prepare
contain correct associations. Tree pollens are detected encapsulated organisms for killing. Patients with
in early spring; followed by grass pollens in lata sprtng deficiencies of the humoral Immune system lack
and summer; foDowed by ragweed in late summer these protective antibodies even if they have been
until the first frost. The patient's symptoms worsen In immunized against these organisms (as seen in this
the summer, when grass pollens are most prominent. patient). Isolated lgA deficiency is the most common
Having air-conditioning that would allow the windows immune deficiency, defined by a serum lgA level
to be kept closed would assist in limiting exposure to of less than 5 mg/dl. lgA deficiency is common
grass pollens. to all the humoral immune deficiencies. Frequent
Gl infections, including G. Iamblia, are common in
VIGNmE 1 Quesllan 3 patients with lgA deficiency.
3.Answerk
Parental history of allergic rhinitis is positively associ- VIGNETlE 2 Question 2
ated with the development of allergic rhinitis. Allergen 2. AnswerC:
avoidance is the most effective treatment. Dust mites Positive results on delayed hypersensitivity skin
need humans, moisture, and wannth for survival. testing to Candide and other infectious agents that
Hence, high concentrations of dust mites reside in mat- humans are commonly exposed to are a measure of
tresses and bedding. Dust mite covers for mattresses cell-mediated immunity. This test would be normal in
and pillows, and washing or drying bedding on high patients with a disorder affecting exclusively humoral
heat to destroy dust mites, are excellent avoidance immunity. Lymphocyte subpopulations are a useful
measures. It Is very dlfftcult for patients and families test when evaluating deficiencies of the humoral
to give up their pets. In addition, pet owners expose Immune system. Patients with XLA will have very low
others to animal dander from their clothing on a dally levels of B cells. Patients with CVID may have normal
basis. Thus, eliminating the pet from the home will not levels of B cells. Quantitative immunoglobulin testing
totally eliminate exposure. Allergen immunotherapy is required to confirm and help differentiate among
is an effective therapy and reasonable choice for this humoral immune deficiencies. Levels of immunoglob-
patient. Topical nasal steroids are safe and effective ulins may be only modestly decreased in CVID, but
in the treatment of allergic rhinitis if administered cor- affected patients lack antibodies to infectious agents
rectly. The nasal steroid opening should be directed that they have been Immunized against and cannot
away from the nasal septum and every effort should be produce antibodies following a vaccination. Studies
made not1o sniff following administration. Even topical tor these specific deficiencies are confirmatory tests
steroids may inhibit linear growth. Thus, frequent height for the diagnosis of CVID.
measurements should be obtained In patients using
Inhaled corticosteroids long term. There are a growing VI6NET1E 2 Quadan 3
number of nonsedatlng antihistamines for use In the 3.AnswerA:
treatment of allergic rhinitis. Many of these agents are Patients with CVID are at increased risk of developing
now available without prescription. autoimmune diseases such as autoimmune thyroiditis,
hemolytic anemia, autoimmune thrombocytopenia,
VIGNmE 2 Questlan 1 and pernicious anemia. In addition, CVID patients
1.Anawer8: have a 300-fold Increased risk of lymphoma and a
It is common for healthy children to have frequent SG-fold increued risk of gastric carcinoma. The on-
viral infections when exposed to other children with set of CVID may occur in early childhood but is most
similar illnesses. Serious viral infections are much common during adolescence or young adulthood. The
more common in children with deficiencies in cellular incidence is equally distributed between males and
immunity, as T cells are required to destroy viruses. females. Replacement therapy with IVIG is required
Before 6 months of age, infants are protected by to help protect against Infections with encapsulated
humoral Immunity from the mot her. lgG crosses organisms that may be llfe..threa1enlng In patients
the placenta from mother to child and Is protective wlthCVID.
VIGNETIE 3 Quesllan 1 VIGNETIE 4 Question 1

1.Answer E: 1.AnswerC:
lgA vasculitis is a systemic small vessel vasculitis The absence of significant joint pain is typical of JIA.
that affect& the skin, joints, kidneys, and Gl tract. The For unknown reasons, children with JIA do not com-
Gl tract involvement is prominent and may manifest plain of joint pain, even in the setting of obvious joint
with abdominal pain, vomiting, and Gl tract bleeding. swelling. Severe joint pain is a red flag that should alert
Bowel wall thickening occurs, w ith occasional sub- the clinician to consider alternate etiologies such as
sequent intussusception. The annual incidence of infection and malignancy. Oligoarthritis patients typ-
lgA vasculitis in the United States is 1:5,000, which ically have mild elevation of CAP and ESR; however,
is more common than Kawasaki disease (annual these tests can also be normal. A marKed acute phase
U.S. incidence ~ 1:1 0,000). The two vasculitides also reaction is atypical and should prompt workup for an
have slightly different peak ages, with HSP occurring alternate diagnosis such as infection. Diagnostic cri-
more commonly In children between ages 4 and 6, teria for JIA requl1'8 patients to have objective findings
and Kawasaki disease occurrtng more commonly In compatible with arthritis for at least 6 weeks' duration.
chlld1'8n 2 to 3 years of age. Persistent, high fever Is Alternative etiologies In the differential diagnosis that
a key disease manifestation of Kawasaki disease, cause arthritis, partlcularty reac1tve or postlnfectlous
but not lgA vasculitis. The classic rash associated arthritis, generally 1'9Solve within this time frame. The
with HSP is palpable purpura localized to dependent presence of a flexion contractul'8 indicates that this
areas of the body, such aa the lower extrgmities and patient has likely had arthritis for longer than there-
buttocks. In children less than 2 years of age, the rash ported 30 days, as this finding is more consistent with
may be atypical and involve the face. In contrast, the long-standing disease. Onset before age 16 years is
rash in Kawasaki disease Is more variable and is often required to bestow the diagnosis of JIA. The number
described as a polymorphic exanthem that involves of affected joints helps differentiate oligoarthritis from
the trunk and extremities. polyarthritis. Oligoarticular arthritis affects four or fewer
joints in the finrt 6 months of disease, whereas with
VIGNETIE 3 Quesllan 2 polyarticular JIA, five or more joints a111 affected. Large
2. Answer8: joints such as the knee and ankle are mo111 commonly
The ESR In Kawasaki disease Is significantly elevated, affected In ollgoarthrttls.
along with an elevated CAP. Elevated WBC count
(leukocytosis), elevated platelet count (thrombo- VIGNETIE 4 Question 2
cytosis), elevated liver transaminase&, and WBCs 2.Answer B:
in t he urine w ith a negative urine culture (sterile RF is an autoantibody directed against a portion
pyuria) are all characteristic laboratory findings for of the lgG molecule; it is not associated with an
Kawasaki disease. increased r isk of anterior uveitis. RF occurs in
-5% of JIA patients and, when present, is more
VIGNETTE 3 Quedon 3 common with polyarticular JIA. RF is considered
3.AnswerC: a poor prognostic Indicator regarding overall dis-
Approximately 25% of untreated Kawasaki disease ease severity and the likelihood of persistence into
patients develop coronary artery aneurysms. Throm- adulthood. ANA is detected in up to 75% of patients
bocytosis related to Kawasaki disease is associated with oligoarticular JIA. ANA-positive patients are at
with a high risk of subsequent aneurysms. Aneurysms Increased risk of developing uveitis, which occurs In
constitute the most significant cause of morbidity up to one-third of patients with this type of juvenile
and mortality, because of ruptul'8 or thrombosis. In arthritis. Because the uveitis Is often asymptomatic,
addition to IVIG, high-dose aspirin therapy In the patients who are ANA-positive require more frequent
acute stage and low-dose aspirin in the convalescent slit-lamp examinations to avoid the development of
phase constitute the Mstandard of care• treatment visual impairment and blindne88 that can occur with
rvgimen. Peeling of the skin of the fingers and toes untreated disease. HLA· B27 is associated with ERA
occurs during t he course of Kawasaki disease; and spondyloarthritis. Affected patients can have
however, it does not lead to major complications. anterior uveitis, but it is generaly acute rather than
Glomerulonephritis can be a serious comp6cation chronic, and these patients are often symptomatic,
of lgA vasculitis. It is present in up to 40% of lgA with red painful eyes. Other HLA types have been
vasculitis patients, and up to 5% of those patients associated with an increased risk of oligoarticular
will develop end-stage renal disease. Amyloidosis JIA, but not uveitis. Ferritin can be quite elevated in
is a major complication of several of the PFS, and patients with systemic JIA but is not associated with
it is related to chronic, untreated inflammation, but an Increased risk of Iridocyclitis. It Is not common for
not Kawasaki disease. patients w ith ollgoartlcular JIA to have a significantly
elevated ferritin. The WBC count is normal in patients not examined in the setting of a fever. Other physical
with ollgoartlcular JIA. examination findings In these patients can Include
toxic appearance, arthritis, hepatosplenomegaly, and
VIGNETTE 4 Q...tlan 3 serositis. Dactylitis Is not a common finding across JIA
3.Answer C: subtypes. Dactylitis, when present, is pathognomoniC
Long-standing arthritis can lead to limb length di~ tor psoriatic arthritis. This Is commonly referred to
ancy, with 1he affected limb longer than the unaffected. aa a "sausage digit," and it occurs because of flexor
The presence of joint inflammation leads to increased tendon tenosynovitis. The findings of nail pitting or
blood flow to the growth plates of the affected joint, onycholysis may be subtle in patients with psoriatic
which, in tum, leads to stimulation of bone growth. arthritis. Achilles tendon insertion tenderness is often
This is a common finding in untreated patients with present in patients with ERA. Enthesitis is inflamma-
oligoarticular arthritis affecting the knee. Other common tion and tenderness at the insertion site of tendons
physical examination findings in long-standing arthritis to bone. The common sites of tenderness in ERA
include joint contractures and muscle atrophy of the patients include the Achilles tendon, plantar fascia,
affected limb. Patients witt! systemic JIA often have patellar tendon, and anterior superior iliac spines.
an evanescent salmon-colored rash, particularly when RF-posltlve patients have symmetric polyarthritis of
febrtle. Rashes are not commonly found In other subtypes small joints. RF-posltlve JIA resembles adult RA with
ot arthritis. The rash of systemic J lA Is generally more a predominantly distal, syrnmetrtc arthr1tls of the small
prominent durtng fever episodes and can be missed It joints Including the fingers, wr1sts, and hands.
Neurology
Leon G. Epstein and Katie S. F11e
two streams, receptive and expressive. Receptive

NEURODEVELOPMENT language delay is more likely to be associated with
NORMAL DEVELOPMENT future intellectual disability than expressive language
Both intellectual and physical development in infants delay. Overall, language delay is the most commonly
and children occur in predictable, sequential manners. diagnosed form ofdevelopmental delay in preschool
Table 9-1 presents the typical progression of devel- children.
opmental milestones. Notable skills are subdivided Age-adjusted parameters are employed when
into gross motor, fine motor (Includes visual-motor), evaluating the developmental achievement offormer
language, soclal!emotional, and adaptive milestones. preterm infants. Until2 years of age, a child's chrono-
The two developmental screens most commonly logical age should take into account the gestational
employed by child psychologists are the Denver II age at birth. For example, at his or her 9-month
developmental screening test and the Clinical Adap- checkup, an infant born at 28 weeks' gestation should
tive Test/Clinical Linguistic and Auditory Milestone be able to perform akil.l.a typical for a 6-month-old.
Scale (CAT /CLAMS). The Denver ll evaluates chil-
dren birth to 6 years of age and divides streams of SPEECH AND lANGUAGE DELAY
development into gross motor, fine motor--adaptive, An individual's ability to speak impacts his or her
Jansuage, and personal- social. The CAT rates prob- capacity to communicate with others and develop
lem-solving/visual-motor ability and the CLAMS social relationships. Speech delay is the most com·
assesses language development between birth and mon developmental concern raised by parents. As
36 months of age. many as 15% of young children have some sort of
speechllanguage delay at one time or another during
DEVELOPMENTAL DELAY the preschool years. Persistent speech delay which
Sometimes development does not progress as ex- significantly interferes with communication suggests
pected. Developmental delay is diagnosed when aspeecManguage disorder. In most cases, there is no
performance lags significantly compared with underlying biologic abnormality (genetic syndrome,
average attainment in a given skill area. The devel- neuromuscular disease) associated with the disorder.
opmental quotient (DQ) reflects a child's present Language disorders result in the inability to un·
developmental achievement: DQ = (developmen- d.erstand or acquire the vocabulary, grammatical
tal age/chronological age) X 100. A DQ below 70 rules, or conversation patterns of language. Speuh
constitutes developmental delay. Developmental disorders involve difficulty producing the sounds and
dissociation refers to a substantial difference In the rhythms of speech. Phonetic disorders are problems
rates of development between two skill areas. An with articulation. Speech and phonetic disorders are
example of a developmental discrepancy between expressive disorders, whereas tan,uase disorders often
motor and language development would be a child affect both expressive and receptive language skills.
with isolated speech delay due to hearing impairment Dysfluency produces Interruptions In the How
whose gross motor development is normal. of speech. Developmental dystluency is observed
Language ls the but indicator offuture intellectual In many preschoolers, resolves by age 4. and is not
potential. Language development is divided into pathologic. True dysfluency (stutterlns), characterized
185
TDLE 11-1. Typical Developmental Miles1Dil8S

i.... ........ .... (VIIIal) llaiDr ' a·•
1Birth-
~ 1 mo
Raila head sUgbdy 1n
prone position n:r-
Follows with eyes to
: bands
Alerts/at:artlea to IOUDd Fixea on &c:e (at birth)
!,,',,, 2 mo Raises chest and head Regards object and Coos and vocallzes
otfbed 1n prone polit:ion f'oUowl through 180" arc; reciprocally
Social mille; recognizes
parent
briefly retains rattle
1,',,,_ 4 mo Lifb onto eJrteru1ed Reaches for objects with Orients to voice; laQihs lnitlata social
elbowa in prone pos!Uon; both bands together; and squeals interaction
steady head control with bats at objects; grabs and
~6mo =:~~oedowr =~::one

! support; rolls in both hand; transfers objects
.._. iemptiuoob~or
person as unfamiliar
!9
!,,,_
mo =~:ut mppo~ :~~~pap;
finger~feeds
crawla; pulls to at:aod
lmitatesspeecluouncls
(noiLipecific "'mama:'
Playa gesture games
\pat--a-cake·);
'"dada~); understands understands own name;
i "no" object pennanenc:e;
stranser anxiety
i,! 12 mo Cruiaes; st:ancls alone; Can voluntarily release Discrimina.tive uae of Imitates; comes when
"mama.• •dada." plua1-4 called; cooperates with
~~- :_ -·-- ==
tabs a few independent items
dressing
!,,, indrpendently ~~ball to aboYe; uaes jargon;

WKH:UliiUll respondl to one-ltep
· wrbal commands
I18mo ==he!~=.. ::,::.::;..~ =~!:;;:., Plays near (but not

with) other children
i
;!,_~mo ~:bal ~overldc!han¥.·d~~;:: ~~ ==~
UU"Uwa
jumpa with two feet off
,... spoon; copies a straight
line
U&el •1• and "me";~
of speech intel.l.lgible to
i36 mo :::cycle; broad Copies a circle =:8 word sentences; Knows age and gender;
l•r :_m_m« ~·~- 2?;;~ ~~

I.Sy ~- .....- :.:;-.;r""'-"" Aobwhat ....... ....., ::::~
"rules• and abides by
loy Rfdoubike w,......,. --- ::.rlehtfmmleft;

L..............................................................................................................................................................~~-~~~~-~.................................~..~..~~~-~........:
Chapter 9 I Neurology • 187
by signs of tension and struggle when speaking, sound teacher rating forms. The severity of intellectual dis-
repetition, or complete speech blockage, significantly ability is currently defined as mild, moderate, severe,
impedes the ability to communicate. or profound on the basis ofadaptive functioning. IQs,
Parental conoern is a good predictor of the need although still measured in diagnostic testing, are no
for further workup. As many young chlldren. are longer used to classify the severity of impairment.
uncomfortable speaking freely in front of strangers, The cause of mental disability 1s identified in only
a debliled history is often n.e<Jessary to characterize about half ofcases. Intellectual disability should come
the quantity and quality of the patient's speech. Any to the attention of the pediatrician when a child has
child with suspected Janguage delay should undergo exhibited delays in one or more areas and continues
a full audiology evaluation, followed by referral to a to fail developmental expectations past the age of
speech pathologist for further workup and treatment (if 5. Obvious dysmorphisms occasionally suggest a
indicated). The most oomm.on cause of mild-to-mod- specific disorder (e.g., trJsomy 21, Fragile X. or fetal
erate hearing lou in }'Owtg children is otitis media alcohol syndrome). Unles1 there is a specific suspected
with effusion. Most children with expressive language disorder, chromosomal microarray analysis is cur-
delay secondary to mJddle ear effusions will catch up rently the first-line test when suspecting a genetic
by preschool age. Early and intensive speech therapy cause. Identifying a genetic etiology is important in
often results in significant and sustained improvement determining a family's recurrence risk and aiding in
in oonunwlication sk1lls over time. prognosis. Neuroimaging may be considered as part
of the diagnostic evaluation. Comorbid conditions
GLOBAL DEVELOPMENTAL DELAY (cerebral palsy, behavioral disorders, seizures) are
Global developmental delay is a term reserved for not uncommon. Treatment is interdisciplinary,
children under age 5 who have failed to meet two supportive, and symptom-specific, with the goal of
or more of the expected developmental milestones maximizing adaptive functioning and quality oflife.
for age (language, gross motor. fine motor, and
adaptive). A detailed history to rule out exogenous AUTISM SPECTRUM DISORDERS
causes (intrauterine infections, perinatal injury, Autism spectrum disorders (ASD) are neurode-
environmental exposures. nutritional deficiencies) velopmental disorders characterized by persistent
and careful physical examination for dysmorphisms, impairment in reciprocal social communication and
neurocutaneous stigmata. mJcro- or macrocephaly, interactions a.s well as restricted, repetitive patterns
and abnormalities In tone, among other findings, of behavior, intere.sts, or activities. These features
should be pursued to identify potential etiologies. are present in early childhood and impair everyday
A significant proportion of these children may functioning. Pervasive developmental disorder and
subsequently be diagnosed with a genetic disorder, Asperger syndrome are now classified as ASD. The
but the etiology remains unclear in a large number reported prevalence of these conditions has been
of these patients. rising over the past decades and is now estimated
to be about 1 in 68 chndren in the United States.
It is unclear whether this is due to improved re-
porting. more inclusive criteria, or a higher rate of
INTEUECTUAL DISABILITY disease. ASD is more common in males. It is usually
Intellectual disablllty as defined in the Diagnostic diagnosed between 18 months and 3 years of age,
and Statistical Manual ofMental Disorders, Fifth although symptoms such as impaired attachment
Edition (DSM- V) is a disorder with onset during the and poor eye contact are often present from infancy.
developmental period that includes both intellectual Autism is currently thought to be a multifactorial
and adaptive functioning deficits in conceptual, disorder. Children with genetic conditions such as
sod.al. and practical domains. The most commonly Fragile X and tuberous sclerosis are known to be at
used intelligence quotient (IQ) tests in the pediatric an increased risk for ASD. Ongoing research 1s iden-
population are the Wechsler scales (preschool and tifying other genes IIS50Ciated with the development
school age, WPPSI and WISC) and the Stanford-Binet of ASD as well as possible environmental triggers
(school age). The Vmeland Adaptive Behavior Scale that could alter brain development. Long-term ep-
is used by psychologists to measure a child's adaptive idemiologic studies hat1e notfound any tUSociation
functioning on the buis of parent, caregiver. and between the measles, mumps, and rubella (MMR)
vaccine or thimerosal (a vaccine preservative) and and language training, social modeling, and family
the development ofautism. support. Pharmacologic intervention targets specific
symptoms such as anxiety. hyperactivity, and perse-
Clinical Manlfaslatlans verative behaviors. Early recognition and intervention
Children with autism spectrum disorder have sig- lead to better clinical outcomes in higher function-
nificant language and communication abnormalities ing children with ASD. The American Academy
(Table 9-2). They do not engage in meaningful social of Pediatrics recommends routine screening of all
interactions. They avoid eye contact, exhibit impaired children before 2 years of age. Common screening
reciprocity, lack understanding ofemotions, and do tools utilized by pediatricians include the Otildhood
not engage in pretend play. Affected children usually Autism Rating Scales and the Modified Checldist for
display atereotypic and/or repetitive behavior patrems Autism for Toddlers. The best prognostic indicators
and may have an attaclunent to or fascination with of future success include the extent of language de-
unusual objects. velopment present during the preschool years and
Per DSM-W criteria. Asperger syndrome was cognitive ability.
characterized by qualitative impairment in social
interactions resulting in difficulty forming relation- ATTENnON-DEFICrT/HYPERACTivnY
ships and relating to others as well as restricted, DISORDER
repetitive patterns of behavior, interests, and activ- Attention-deficit/hyperactivity disorder (ADHD)
ities, demonstrating intense interest in very specific is a neurodevelopmental disorder that interferes
topics (e.g., dJnosaurs, space, electronics). Although with functioning and/or development. Symptoms
controversial, DSM-V no longer recognizes Asperger are inconsistent with the developmental stage of the
syndrome as a separate entity, but as an autism child and manifested through maladaptive behav-
spectrum disorder instead. iors. Classic ADHD is more common in boys and
Management is usually diagnosed in elementary school. School
Treatment of ASD consists of intensive behavioral performance and peer relationships often suffer,
intervention (e.g., Applied Behavior Analysis or placing the child at risk for low self-esteem. In girls,
ABA therapy), sensory integration therapy, speech the ADHD predominantly inattentive subtype is more
common. ADIID symptoms persist into adulthood
in the majority of patients.
1III.E •2. Characteristics of Autism Spectrum
Disorders COnical Manif8statians
To be diagnosed with ADHD, a patient must meet
l Sodllllnletlcllon specifi.c criteria detailed in the DSM-V and summa-
!Umited eye contact and Caclal expresdon rized in Table 9-3. ADHD is defined by a persistent
~ Diftlculty developing peer relationJhi~ pattern ofimpairing levels ofinattention, disorgani-
IIndifference to social overlnrel zation. and/or hyperactivity-impulsivity. Symptoms
lLack of 1oclal reciprocity
must be present before age 12. persist for at least 6
months, and be observed consistently in multiple
I' Inflexibility environments (e.g., school and home). The signs of
j No engagement in pretend play ADHD may be minimized in settings that are novel,
~~ highly supervised, or narrowly focused on the patient.
j impaired reciprocal communication Thus, an affected child may not diaplay any behavion
i Laquap development deviant, rather than •imply typical of ADHD in the pediatrician's office.
! delayed Assessment
ADHD is a clinical diagnosis. Other causes such as
sleep disturbances as a potential cause ofinattention
should be ruled out. The initial assessment ofa child
with possible ADHD relies firmly on history obtained
!Repetitive, •elf-lll:imulatory behavior• (e.g., rocking, from parents and teachers. Age-appropriate rating
Ispiuning) scales (e.g., Conners Comprehensive Behavior Rating
i Preoccupation or fuclnation with a lingle object or Scales and the ADHD Rating Scale N for preschool
l subject ~
;ooooo.ooooooooooooo•·••••~•-•••n•••••~---- •oooooo•-••••••·•--•-••••-••-~-- chlldren and the Vanderbilt Assessment Scales for
TIILII-3. Diagnostic criteria fer Attention-DBficiV years of age with ADHD also have a learning disor-
Hyperactivity Disorder per DSM-V der. Oppositional defiant disorder is one of the most
common comorbid psycltiatric diagnosis; others may
lndlntlon {SIX orMoll at 1M Followlnfl)
include depression. anxiety, and conduct disorders.
Fails to pve dose attention to detaila or mab& Moreover, ADHD may coe:xist with neurologic
careleu miDba dJsorders such as epilepsy or Tourette syndrome.
Dlftlculty sustaining attention Pharmacologic intervention and behavior modi-
Does not seem to U.ten when spoken to directly fication in combination result in the best outcomes.
Does not foUow through on instructions and fails to Psychostimulants, including methylphenidate,
finish tub dextroamphetamine, .mJxed amphetamine salts, and
l.isd.examfetamine (inactive prodrug metabolized to
Dlftlculty organizing tub and actiYitte.
active form by the body) are available in immediate- and
Avoids, dislikes, or is reluctant to engage in tasks that extended-release formulations. All are designated as
require sustained mental effort controlled subiJtances. These drugs work by increasing
Loses thinp nec:esury for taw or activities the availability ofdopamine and norepinephrine. Side
Easily distracted by extraneouslltl.mull. effects include insomnia, elevated blood pressure,
Forgetful in dally actiYitiel nausea, and anorexia; rarely tics and dyskinesias
may develop. Nonstimulant options include atom-
IIJyptnclirity IIIJd lmpu/IMiy (Six Df Afore Dfthfl FDIIowitll}
oxetine (a highly specific norepinephrine reuptake
~ F'u:lgets with or taps hands or feet or squirms inhibitor), clonidine, and guan.faclne. The Food and
ILeaves seat in lituationa when remaining aeated is Drug A.drninistration requires '"blaclc box'" warning
1expected labels on both the stimulants and atomoxetine (risk
~ Runa about or cllmbs when Inappropriate of sudden cardiac death for the former; suicidal
IUnable to play or enpp in lei&uft activities quietly ideation for the latter). Depending on the patient's
degree of symptomatology, medication holidays on
l Often •on the go; acting u if•driven by a motor'" weekends and vacations may be considered.
ITalb eD:ellively
l Blurts out an an5We'r before a question has been CEREBRAL PALSY
1 completed According to an international executive committee,
IDifficulty waiting hJs or her turn cerebral palsy {CP) has been described as a group of
! Interrupti or intrudes on others permanent disorders of the development of move-
;,,,,,.,,,,,.,,,,,,..,.,,.,. ,,,.,,.,,,,,,.,, .,.,.,,,.,.,,..,,,.,~.,,,,,, ,,,,,,,noooooo ooooooooooooooo••••••• ••••••••••••••••••••n•••••••••=
ment and posture (causing activity limitation) that
are attributed to nonprogreS&ive disturbances that
occurred in the developing fetal or infant brain. The
school-age children) have been validated and are
motor component is often accompanied by sensory,
readUy available online. A complete physical exam-
perceptual, or cognitive dimubances. Approximately
ination should be performed. Child psychologists
one-third of cases develop after fu.ll-term birth
and psychiatrists employ more targeted testing to
following an apparently normal gestation. Modem
piclc up on inattention and lack of sustained focus.
case series have identified a single or mixed etiology
Management for the motor disability in at least 80% of cases of
The goal of therapy is to provide sustained symptom CP. Transient neonatal depression is not predictive
reduction throughout the day with an acceptable ofan eventual diagnosis ofCP. Excluding extremely
minimum of adverse effects. Children with ADHD premature or low-birth-weight infants, over 90% of
benefit from a multidisciplinary approach. Emotional infants with Apgar scores ofOto 3 at 5 minutes do not
support should be made available for the patient and develop CP. Infants with intrapartum hypoxia-ischemia
parents. A behavior management program must be who have normal neurologic examinations by 1 week
developed to assist both the parents and teachers of age have a good likelihood of normal outcome.
with positive reinforcement, structure, and discipline. Prenatal factors such as intrauterine infection,
Educational assessment should be considered for prematurity, placental hemorrhage, intrauterine
children with school underperformance. According growth retardation. and multiple gestations raise the
to data from the Centers for Disease Control and risk ofCP. Acquired postnatal causes ofCP include
Prevention (CDC), almost half of children 6 to 17 hemorrhagic or ischemic stroke, trauma, kernicterus
from severe hyperbilirubinemia, and infections of CP have an identifiable risk factor for brain insult
the central nervous system (CNS). (e.g., severe perinatal asphyxia. placental infarction,
maternal toxemia, extracorporeal membrane oxy-
Clinical Manifestations genation exposure). Cerebral dy&genesis, including
CP is classified by the pattern ofmotor impairments malformations of the cerebellum and brahtstem. can
and by the charactedstics ofmuscle tone. The most cause ataxic CP with hypotonia, truncal ataxia., and
common form is spastic CP, which is the consequence titubation (bobbing of the head and/or trunk). Hy-
ofinjury to the pyramidal motor tracts in the brain. potonic and ataxic CP often have genetic etiologies.
Spasticity is velocity-dependent increased muscle The American Academy of Neurology and the
resistance in response to passive stretch. Increased Practice Committee of the Child Neurology Soci-
tone in CP may have both spastic and dystonic fea- ety published a practice paramet2r addressing the
tures. Dystonia is sustained or intermittent muscle diagnostic assessment of the child with CP in 2004.
contraction generated by movement. Typically, it is The practice parameter suggests that the history
a posturing movement with a cooontraction of both and physical examination should be reviewed to
the extensors and flexors. CP is further classified exclude a progressive or degenerative brain disorder.
by which limbs are involved (Table 9-4). Recently, The child should be saeened fur associated conditions
classification systems based on function rather than including visual or hearing impairments, speech and
anatomic location have been introduced. Patients language delays, problem-solving deficits, and feeding
with CP may be initially hypotonic; increased tone and swallowing dysfunction. An electroencephalograph
develops over time, dependent on the severity of the (EEG) should be obtained ifthere is a hinory ofpossible
CNS injury. In infancy, delay in the disappearance of seizures. Neuroimaging with a magnetic resonance
primitive reflexes (such as the Moro or the asymmetric imaging (MRI) is recommended to discern an etiol-
tonic neck reflex) can be early indicators ofCP. The ogy (if possible) for the CP. If cerebral malformation
diagnosis of CP becomes more apparent over time is present, a genetic or metabolic evaluation should
when the child fails to meet gross motnr milestones. be considered. Evaluation for a hypercoagulable smte
Extrapyramidal or dyskinetic CP results from can be considered if a stroke is identified.
damage to the basal ganglia, which is involved in
DHhwanUaiD~gn~s
the regulation of muscle tone and coordination.
Affected patients exhibit involuntary choreoathe- Although CP is considered a nonprogressive disorder.
toid movements, dystonia, and postural ataxia, periods of rapid growth may transiently make the
in addition to hypertonic quadriparesis or spastic disorder appear progressive. Metabolic and genetic
diplegia. Kernicterus used to be a major cause of evaluation should be considered ifthe child has de-
extrapyramidal CP; however, improved management terioration or episodic decompensation, no etiology
of hyperbilirubinemia has decreased the incidence can be determined, or if there is a family history
of kernicterus. Most patients with extrapyramidal of childhood neurologic disorder. Progressive or
degenerative disorders that can be misdiagnosed as
CP include demyelinating disorders (metachromatic
TABLE....., Topographic Classification of Spastic leukodystrophy), Friedreich ataxia, ataxia-telangiec-
(PyramidaQ Cerebral Palsy tasia, dopamine sensitive dystonia (Segawa disease),
!Djplegia-bilateralleg spasticity and weakness. with and certain metabolic and mitochondrial disorders
! arms relatively spared. Often obserwd in preterm associated with spasticity.
i infants with PVL. Traabnant
! Q~p-allllmba lleVel'ely involved, uaually A multidisciplinary team approach, including a general
j lower mon! than upper. Oftm related to IMM!re PVl.,
pediatrician. physical and occupational therapists,
: aaphpia. or anbral clyageneaiL
nutritionist, speech-language therapist, orthope-
!Tetmpl~-Ullimbs severely invoiYed. usually dist, physiatrist or neurologist. and social support
l upper more than lower. Often related to severe PVl., services results in optimal function. Many systemic
!asphyxia. or cerebral dyagenesla. medicines (benzodiazepines, dantrolene sodium,
!H~-unllateral1D:volvement ofthe ann and tizanidlne) have been tried to reduce spasticity with
!leg. Usually due to a unllateral cortical Ie.lon such u variable success. Howevet; signi.fi.cant improvements
!more focal dysgeneafa or stroke. in motor function have been achieved by blocking
: Abbnmation: PVL, periventricular leukomalacia. j acetylcholine release at the neuromuscular level
: , , ,, " ' " " ' 000000000000000 0000000 • • • • • • • • • • • • • • • • • • • • •- • • •• • •• • • . , •- • • •• • • ••••••••••••••••••••••nooooonoooooo •••••••• oooooonoooooFoool
with botulinum A toxin (Botox) injections along Psychomotor retardation progresses to spasticity,
with stretching and/or serial casting to treat joint extensor posturing, seizures, and early death.
deformities. Intrathecal baclofun pumps can im- ktt syndrome is an X-linlced recessive disor-
prove spasticity with fewer central side effects, but der observed almost exclusively in girls; affected
the pumps can fail or get Infected. Many chlldren males succumb in utero. In the classlc form ofRett
ultimately require orthopedic surgery to correct syndrome, development is initially normal. Rapid
deformities and release cont:ractores. Dorsal nerve milestone regression begins in the second year of
rhizotomy has been used in selected cases to reduce life, with significant deceleration of head growth.
spasticity. This has become less frequent since the Repetitive hand wringing is the most characteristic
introduction of Botox injections. behavioral sign; other manifestations include seizures,
Children with CP may also suffer from intellectual ataxia, mental retardation. and autistic behavior. Life
disability, learning disability, and ADHD, among expectancy is appreciably shortened.
other comorbidities. These can occur individually Mitochondrial diJeues, which are caused by defects
or coexist. Up to 50% of patients with CP develop in either nuclear or mitochondrial DNA, can result
epilepsy. Hearing and visual impairments should be in energy failure at a cellular level. Individuals with
monitored and corrected ifpossible. If a child with mitochondrial disease can have poor growth, loss
CP is nonverbal or language Impaired. it is important of muscle coordination, muscle weakness, seizures,
to provide for alternate modes of communication visual disturbances, learning disabilities, stroke-like
including sign language, communication boards, symptoms as well as ophthalmologic, cardiologic,
and/or augmentative communication devices. Finally, and gaatroenterologic involvement. Phenotypes are
sleep disorden occur more commonly in children variable from patient to patient and so is prognosis.
with CP, requiring close monitoring ofsleep habits. Two of the most common and severe forms of mi-
tochondrial diseases, Leigh syndrome and Alpers
syndrome, often present in early childhood.
I:1 all ;t•1 •1 3H 3:13;f;i i''i:W •1 ~1·1 ;! t] 3;f.
Neural tissue degeneration can occur at any level
SEIZURES AND EPILEPSY
of the nervous system. from the brain cell bodies to
the peripheral nerves. Many degenerative diseases A seizure is a paroxysmal event that results from
are inherited; most are progressive and debilitating. abnormal neuronal excitability and synchrony.
Neurodegenerative disorders may be divided into Aberrant electrical activity disrupts normal brain
gray matter disorders and white matter disorders. function, leading to positive signs (motor, sensory,
Some inborn errors of metabolism, neurogenetic autonomic changes) and/or negative signs (loss of
syndromes, and mitochondrial diseases may also be awareness, inability to speak, loss of motor tone),
considered neurodegenerative disorders. depending on the cortical localization of the seizure.
Gray matt:udlsord!rs, which include Tay-Sachs, It is extremely Important to distinguish seizures from
Gaucher, and Niemann-Pick diseases, result from nonepileptic paroxysmal events mch as convulsive
lipid buildup in neuronal cell bodies. Hypotonia, syncope, breath-holding spells, rigors, movement
mental retardation, seizures, retinal degeneration, disorders, parasomnias, and psychogenic events.
and ataxia are common. These disorders, along A thorough history should help in differentiating
with the inborn errors of metabolism, are further these and guiding the correct diagnosis. The In-
discussed in Chapter 19. ternational League Against Epilepsy has defined
White matter disordttrs (leukodystrophies) are epilepsy as having at least two unprovoked seizures
inherited, progressive degenerative diaeases resulting more than 24 hours apart. one unprovoked seizure
from abnormally formed myelin. The anomalous with the probability of further seizure recurrence
formation impairs conduction and leads to rapid higher than 60%, or the diagnosis of an epilepsy
myelin breakdown. Leukodystrophies present with syndrome. In contrast, "provoked• or acute symp-
focal neurolog1c deficits, spasticity, visual disturbances tomatic seizures occur in the context of an acute
(optic atrophy/blindness), changes in personality, and brain insult (trauma, intoxication, infection, strolc:e,
cognitive decline. Adrenoleulrodystrophy, so named anoxia) and are not classified as epilepsy unless they
because of its frequent association with adrenal in- become recurrent following resolution of the acute
sufficiency, is an X..linked disorder characterized by illness. Some children develop epilepsy because of
areas of periventrk:ular white matter demyellnation. malformations of cortical development, speclfic
genetic etiologies such as Dravet syndrome due and an emergency plan in case of recurrent seizure
to SCNlA pathogenic mutation, or have specific is important. Serial seizures and seizures lasting
age-related genetic epilepsy syndromes such as more than 5 minutes can be treated with rectal
childhood absence epilepsy. Although the numbers diazepam. The child should be transported to the
are constantly changing because of new advances in emergency department by ambulance Ifthe seizure
genetic diagnoses, a significant number ofchildren continues after 5 minutes and/or does not resolve
with epilepsy remain without a known cause. following rectal diazepam administration. Febrile
.status epilepticus should be addressed aggressively
FEBRILE SEIZURES to prevent morbidity and mortality.
febrile seizures are typically brief (<5 minutes), The American Academy of Pediatrics has practi<Je
generalized sei%ures associated with fever. They parameters that address the evaluation offirst simple
occur in 2% to 5% of otherwise healthy children febrile seizure in neurologically healthy chlldren
aged 6 months to 6 years. Febrile seizures, even between 6 months and 5 years. In the history and
when recurrent, are not considered epilepsy. Febrile physical examination, it is important to rule out
seizures are divided into simple febrile seizures and CNS infections as potential causes for the seizure,
complex febrile seizures. Simple febrile seizures are considering that affected children less than 18 months
generalized, brief, and single (do not recur within old may not have meningismus on exam. It is also
24 hours). Complex febrile seizures are focal, pro- important to ask about possible ingestions (drugs or
longed (> 15 minutes), or repetitive (recur within toxins), a history mggestive of metabolic disorder,
24 hours). Approximately one-third of children or a derangement from unusual intake resulting in
present with complex febrile seizures and a subset fluid/electrolyte losses. Seizures are the presenting
of those will present with febrile status epllepticus sign in about 15CJ6 of children with meningitis, and
(>30 minutes). Febrile seizures luting greater than in about one-third ofthese children. meningeal signs
10 minutes are lilcely to continue on to febrile status and symptoms may be absent. The AAP guidelines
epilepticus; approximately halfof prolonged febrile recommend that lumbar puncture (LP) be strongly
seizures are focal and/or intermittent without recovery co~ after first simple febrile seizure in a child
between seizures. Prolonged febrile seizure is often leas than 12 months and ronsidered in the child be-
not recognized in the emergency department setting tween 12 and 18 months. LP should also be consid-
and is often ineffectively treated with anticonvulsant ered for children older than 18 months Ifthey have
medications. By definition, the diagnosis of febrile meningeal signs and in children who have recently
seizure e;&eludu children with intracranial infection received antibiotics because of concerns ofpartially
or a prior history of non.febrile seizure. Most febrile treated meningitis, which could mask some of the
seizures occur in the first 24 hours of an illness at physical exam findings. Blood glucose, basic serum
or around the onset of a feve.r and in children less electrolytes, calcium, phosphorus, magnesium, and
than 3 years of age. Often, there Is a strong family CBC are not routinely indicated but can be sent under
history of febrile seizures that can aid in diagnosis particular circwnstan<Jes. EEG and neuroimaging are
and reassurance. also not recommended in the evaluation of simple
About one-third ofchildren with febrile seizures febrile seizures.
will have a recurrence. Risk factors for recurrent Children with febrile seizu.res have an increased
febrile seizure include the following: (1) first febrile risk ofdeveloping epilepsy. Between 2% and 5% ofall
seizure befote age 1, (2) a family history of febrile chlldren with febrile seizures will go on to develop
seizures, and (3) a low-grade fever/short duration epilepsy. Three major risk factors increase the risk
offever at the time of the seizure. Children with all of late!: epilepsy: (1) complex febrile seizures, (2)
three risk factors or two febrile seizures have a 60% preexi.sting neurodevelopmental abnormality, and
to 70\16 recurrence rate. A lengthy febrile seizure (3) epilepsy in first--degree relatives. Additional risk
does not increase the risk of recurrence. but it does factors include a history offirst febrile seizure unde.r
Increase the rlsk that a recurrent febrile seizure will age 1, a short duration of fever before the seizure,
be prolonged. Daily antiseizure medication is not and multiple febrile seizures.
indicated in children with febrile seizures. Studies Although the risk ofdeveloping epilepsy in these
show that alternating acetaminophen and ibuprofen children is higher than that of the general population,
during a febrile illness may not prevent the seizure. it is important to note that over 90% ofchildren with
Education about seizure first aid. seizure precautions, febrile seizures do not develop epilepsy. OveralL
the morbidity and mortality associated with febrile regard to whether the movement subsided with gentle
seizures is extremely low. The risk of abnormal restraint, was stereotyped, or rhythmic rather than
neurodevelopment is no greater than the general tremulous. Focal features such as head or eye devia-
population. tion and auras such as epipstric sensation, dija vu,
or unusual smell should be noted. It is Important to
EPILEPSY ask lfany abnormal spells have occurred previously
Approximately 0.6CJii ofchildren Jess than 17 years of and whether the child had any recent illness, injury,
age have epilepsy in the United States. The incidence ingestion, neurologic changes/signs, or prior abnor-
for the total US population has been estimated to be malities ofdevelopment. The chiJd's past history and
1.2CJ1i, per most recent reports from the CDC. The family history often provide important supplemental
majority ofrecurrences after a first seizure occur within information. A1 the end of a thorough history, the
the first year, with recurrence risk ranging from 14% physician should be able to differentiate an epileptic
to as high as 65% according to observational studies seizure from a nonepileptic: paroxysmal event (such
described in the American Academy of Neurology as syncope or daydreaming) and should have an
practice parameters. By 2 years, the risk of recur- idea of the etiology (structural, infectious, genetic,
rence is between 30% and 50%. Some risk factors for metabolic, or unknown). Occasionally, the available
recurrence following a first unprovoked seizure In history is not sufJicient to make the determination
childhood include the following: (1) abnormal neu- of seizure versus noneplleptic paroxysmal spell. In
rodevelopment, (2) abnormal EEG, (3) prior febrile that case, the family should be educated in regard
seizures, (4) transient focal weakness (Todd paralysis), to the appearance ofseizures, as well as seizure :first
(5) first degree relative with epilepsy, or (6) seizure aid and precautions, and further evaluation will be
arising out of sleep. Healthy, typically developing necessary.
children whose initial seizure occurs while awake The comprehensive physical examination should
have the best prognosis for remaining seizure free. include vital signs, growth parameters, and the
After the first unprovoked seizure, generally the presence of neurocutaneous lesions, dysmorphic
child is observed off of daily medications, and the features, retinal abnormalities, signs of infection,
parents are provided with an emergency action plan. cardiac abnormalities, orpnomegaly, and/or trauma.
The recurrence risk increases to 70% to 80CJii after a A full neurologic examination assesses mental status,
second or third unprovoked seizure, at which point cranial nerve function (Including vision), and evi~
most children are started on maintenance antiseizure dence ofany focal abnormalities oftone or strength.
medications. sensation, coordination, reflexes, or gait.
About 50CJii ofchildren with epilepsy outgrow their
seizures, particularly those with age-related epilepsy Diagnostic Evaluation
syndromes such as self~limited focal epilepsies Practice guidelines established by the American
or ch1ldhood absence epilepsy. Some adolescents Academy of Neurology, the Child Neurology Sod~
develop epilepsy because ofan age·related epilepsy ety, and the American Epilepsy Society recommend
syndrome Quvenile myoclonic epilepsy) or trawnatic a routine EEG as part of the diagnostic evaluation
brain injury. The probable etiology and prognosis of following a first nonfebrile seizure. An EEG can
a seizure vary with the child's age, a family history of provide supplementary information to support a
epilepsy, a history of preexisting neurodevelopmental diagnosis of epilepsy. An abnormal EEG permits
disability, identified epilepsy syndrome, and the acute classification of the epilepsy as focal or generalized
symptomatic cause for the seizure. and may suggest a specific epilepsy syndrome (such
as the 3-Hz spik~and~wave pattern typically seen in
Clinical Manlfastatlans children with absence epilepsy). However, the EEG
History and Physical Examination data should be evaluated in light of the child's his-
The diagnosis of a seizure and ultimately ofepilepsy tory. A normal EEG does not rule out the diagnosis
Is based prlmarlly on history. Questions should In~ of epilepsy. Simi1arly, a child who has noneplleptic
clude what the child was doing and feeling before paroxysmal events may have an abnormal EEG and
and during the event, how the event evolved over not necessarily a diagnosis ofepilepsy.
time, how long the event lasted, and how the child H a focal structural etiology is suspected. neu-
behaved following the event. Attempts should be rologic examination is abnormal, development is
made to differentiate the abnormal movements in abnormal and/or etiology is unknown. and imaging is
necessary, brain MRI is the preferred modality. MRI TilLE M. International League Against Epilepsy
can demonstrate an abnormality (such as cortical 2017 Ssizure Classification
dysgenesis) in about 2006 ofcases of new-onset seizure.
Emergent neuroimaging should be considered if a ! GllntJtlllziJd Onltlf Stlzunls
chlld is not returning to basellne within hours, has !Motor
i
a postictal focal deficit, or has signs or symptoms 1 Tonic-clonic
concerning for increased intracranial pressure. Brain
MRl may not be necessary ifthe clinical history and
I Clonic
/I :::nk-at
:2::-~
EEG are consistent with certain genetic epilepsy
syndromes (such as childhood absence epilepsy). LP
should be considered in any child with persistently
altered mental status or meningeal signs and in
young infants less than 6 months of age. Ifincreased c.Uc
intracranial pressure is suspected or ifthe child has
focal neurologic signs, imaging should precede the I Epileptic apuma
LP. Toxicology screening is warranted if there is a i Nonmotor (absence)
question of Ingestion ofdrugs or toxins. Other labo-
ratory tests should be ordered on an indlvidual basis
if the child has vomiting, diarrhea, dehydration. or
1:
failure to return to baseline alertness.
Ii :m:clonia
cmst (Willi,.,.,.
Fot:M (Jf,_red,.,.,..,..,
CLASSIFICAnON OF SEIZURES AIID
EPILEPSY SYNDROMES j Motor onset
Table 9~5 delineates the International Classification I Automatisms
of Epileptic Seizures.
Focal seizures are those in which the first clinical
and elect:rographic changes occur in a localized area of
I::
I Epileptic 1p1WD11
the brain. The signs and symptoms ofa focal seizure
I~
are specific to the focus, and may be moto11 sensory,
autonomic, or higher cortical psychic symptoms.
Focal seizures are further categorized by whether
or not awareness is impaired
IN~_t_______
• Motor seizures may manifest as focal automa~
tisms, hyperkinetic, focal rhythmic twitching (the
jacksonian marchD progression of convulsions
to involve one side of the body as the seizure
spreads through the cortex); involuntary move-
ment (turning of the eyes, head. and/or trunk); I Seosory
or vocalization or arrest of speech. IIJnknown On8tJf
• Nonmotor seizures may include the foJlowi.ng
symptoms:
• autonomic-epigastric ..rising• sensation,
vomiting, sweating, pupillary changes, or
IM":m.-
i Epileptic lpiWDI
piloerection j Nonmotor
• behavioral arrest : Behavior arrest
• cognitive-aphasia. apraxia. neglect, di.ja vu, i •~v~y focal salzuru oould secondary generalize to bilateral i
jamais vu, illusions, or hallucinations !IDnlo-donlc seizure. i
• emotional-fear or joy
• sensory-tingling, numbness, unpleasant
odor or taste, vertigo, ftuh.ing lights, auditory
1. ~~~;.;~::.~-~-~::~::.:.~: :.:.~~-- _j .
symptoms
During focal seizures with impaired awareness, wave complexes. In a child with untreated absence
the child may have repetitive semipurpo.seful move- epilepsy, 3 to 5 minutes of hyperventilation will often
ments (automatism&) such as picking at the clothes, precipitate a typical absence seizure.
oral-buccal movements (chewing. swallowing), or Atonic seizures consist ofabrupt loss of postural
more complex motor movements such as kicking tone in the neck ("head drop") or the entire body
or flailing of the arms. Children with frontal lobe (•drop seizure'") whJch can cause injury to the child.
seizures may have bilateral motor movements, be- Myoclonic seizures are quick jerks similar to those
come combative, or have awakenings from sleep. It experienced by normal subjects while in light sleep.
is important to understand that any focal seizure Every child with epilepsy should be clinically
can evolve into secondary generalized seizures and evaluated to determine if he or she has one of the
should not lead to an erroneous diagnosis of gen- recognized childhood epilepsy syndromes. Oilldhood
eralized epilepsy. epilepsy syndromes are diagnosed on the basis of the
Generalized seizures are those in which the age ofonset, seizure types, and EEG appearance. Their
clinical and electrographic changes at seizure onset diagnosis has important prognostic, therapeutic, and
are bilateral and widespread in both hemispheres. genetic implications.
Consciousness is impaired from the onset. Individuals
have no recollection ofthe event and a preceding aura Dlffarantlal Diagnosis
is not typically described. Seizures may be nonmo- Neonates can have unusual movements or apneic
tor or nonconvulsive (such as absence seizures) or spells that are more often than not nonepileptic.
motor with bilateral isolated tonic, isolated clonic, Conversely, encephalopathic neonates may develop
tonic-clonic, atonic or myoclonic movements. subclinical seizures that can be detected only with
In a generalized tonic-clonic (GTC) seizure, the continuous EEG monitoring. Continuous EEG
tonic phase consists of sustained flexor or extensor monitoring is used for guiding therapy in neonates
contraction followed by the clonic phase (rhythmic, with encephalopathy or ongoing potential for sei-
symmetric, generalized contractions of the face and zures. Apneic spells associated with bradycardia are
an four extremities). Often, the patient exhales and typically reapiratory rather than epileptic in nature.
remains in exhalation during the tonic phase of a Young children (particularly toddlers) can have
GTC, with breathing commencing in a grunting or pallid or cyanotic breath~holding spells precipitated
irregular fashion during the clonic phase. Bowel or by a sudden pain or upset, followed by a cry and
bladder incontinence may occur. The child may bite color change. The child holds his or her breath in
the side of the tongue or buccal mucosa and can be exhalation and may then lose conscioumess briefly,
injured when falling to the floor. An aura or warning associated with full body stiffening or transient clonic
prior to the onset of the GTC implies a focal onset movements. Ifthe history is typical for breath~holding
with rapid secondary generalization. Similarly, a spells, potential evaluations beyond thorough history
postictal transient hemiparesis (Todd paralysis) and examination lnclude an ECG to rule out cardiac
implies focal seizure onset. The postictal phase is syncope and assessment for iron deficiency anemia.
typically characterized by unresponsiveness and Treating iron deficiency anemia when present can
flaccid muscle tone. The child should have gradual lead to a reduction in the occurrence of spells.
improvement in the level ofconsciousness over the In pediatric patients, syncope is often misdiag-
followtns 10 to 30 minutes. nosed as a seizure. Patients often describe the spell
Absence seizures begin between ases 4and 9 and occurring after prolonged standing or kneeling, after
consist of brief episodes of staring associated with standing up, in the setting of dehydration, sudden
altered consciousness. The typical duration is 5 to pain, or seeing blood. Preceding the fall, there may
10 seconds. Often. the staring is accompanied by be associated pallor, lightheadedness, visual changes
subtle clonic activity in the face or arms or simple ("vision coning down to black"). and muflled hearing.
automatisms (such as eye blinking, chewing, or per- The loss ofconsciousness is briet particularly ifthe
severative motor activity). Absence seizures startand child remains lying down; transient stiffening or
stop abruptly and have no postictal phase. Although clonic movements at the end ofsyncope (convulsive
brief, abserwe seizures can occur multiple times per syncope) is common and reflects transient decreased
day and interfere with learning and socialization. blood flow to the brain. Convulsive syncope is not
In a typical absence seizure, the EEG shows abrupt considered an epileptic seizure. Following common
onset and offset of3 Hz generalized spike-and-slow vasovagal syncope, a child should have little if any
confusion/mental status change. Findings sugges- seizure care, use of eme~:gency medication (such as
tive of potentially life-threatening cardiac syncope rectal valium), and how/when to access local emer-
include syncope during exercise, a family history gency medical services. The choice of antiepileptic
of deafness, or a family history of sudden death in treatment is based on risk~benefit and can be patient
ch1ldren or young people. dependent. When possible, identifying seizure type
Essential tremor, sputmlS nutans, tics, and none- and epilepsy syndrome helps predict which anticon~
pileptic myoclonus are various movement disorders vulsants may be molt benefi.clal (Table 9~6).
that may mimic seizures. Easential tremor may begin With medication, approximately SO% to 7QCJ& of
in infancy or childhood and typically involve the patients become seizure free. Another 10% to 3()CJ(,
chin. head. neck, and/or hands; it usually does not have significant reductions in seizure frequency and/
Interfere with normal fun.ctlons. Spasmus nutans is or Intensity. There has been a dramatic increase in
a clinical triad that presents In infancy consisting of the number of medications available for the man·
head nodding, torticolli5 and rapid, small-amplitude agement of seizures. Some of the newer agents have
nystagmus without alteration of consciowmess. A a better toxicity profile. Conventional antiseizure
child with spasmus nutans should have MRI of the medications require careful monitoring of serum
brain to rule out a tumor. Nonepileptic myoclonus levels, whereas most newer drugs do not require
is a sudden, involuntary jerk·like motion similar routine monitoring {Table 9·7).
to a startle response. NonepUeptic myoclonus can For children with focal epilepsy, cm::arbazepine
occur in normal circumstances, such as light sleep, should be considered for initial monotherapy on
or represent a movement disorder such as that seen the basis ofcurrent evidence regarding efficacy and
in opsoclonus myoclonus ataxia syndrome (OMS). tolerability. However, considering all factors (cost,
OMS is a rare autoimmune disorder that presents in effectiveness, side effect profile), carbamazepine,
early childhood with irritability, myoclonus, ataxia, valprolc acid. topiramate, and levetiracetam are all
and •dancing eye movements: defined as opsocla. reasonable choices to treat focal seizures. Ethosux·
nus. Often times, OMS represents a paraneoplastic imide is considered first line for the treatment of
diaorder because of neuroblastoma, which should childhood absence epilepsy, although valproic acid
always be ruled out. and lamotrigine have also been proven to be effica-
Tourette syndrome co.nsilts of motor and vocal tic& cious. for other generalized epilepsies, valproic acid.
(sudden. involuntary behaviors that are repetitive and leveti.racetam, topiramate, and lamot:ripte are good
stereotyped) that persist for more than a year. Common choices. Carbamazepine and axcarbazepine should
comorbid conditions include obsessive.o(X)mpulsive be avoided in genetic generalized epilepsy as they
tendencies and ADHD. Children can also have less may cause an increase in seizure frequency. It is
frequent tics ofone type or the other. Iftics become also important to note that although ethosuximide
disruptive and interfere with social or educational is very efficacious in treating absence seizures, it is
functioning, cognitive behavioral therapy or medi· ineffective for other generalized types of seizures.
cations (such as clonidine) may be beneficial. In most patients, it is reasonable to consider
Other conditions that are confused with seizures weaning off of antiseizure medication after the
include benign paroxysmal vertigo, temper tan- child has been seizure free for 2 years. In patients
trums, and night terrors. Psychogenic nonepileptic with particular epilepsy syndromes such as juvenile
seizures (PNES) should be suspected in the patient myoclonic epilepsy, the seizures are usually life~long,
with implausible findings {e.g., alert and responsive so medlcati.ons are generally not withdrawn. Recom·
during GTC movements). Continuous video EEG mendations to start and stop anticonvulsant& must
monitoring can be helpful to discern epileptic ver- be tailored to the individual patient, with decisions
sus nonepileptic spella. The treatment of PNES is made by the physician together with the patient
multidisciplinary, involving psychiatry. counseling, and family.
and social support. Itis not uncommon for a patient For patients with drug~resi.stant epilepsy (those
to have both epUeptic and nonepllepti.c seizures. who have failed two or more appropriately chosen
and adequately dosed antiseizure medications), addi-
Traatmant tional interventions are available. A comprehensive
Effective treatment ofepilepsy combines education epilepsy surgery evaluation may be indicated for some
and medication management Both the child and the focal epilepsies in which resection may be curative.
parents should become knowledgeable about acute The risks and benefits of such a procedure need to
TABLE H. Characteristics of Epilepsy Syndromes and Antiepileptic Drugs
Fht·Una n.tmant or Altarnlllllll Rrst-Una oa.r OptloM w
SaiZift...,.. EplaPIJ Stn*O• Cl..la.l Fulu,_ aiDica (ManotharlpJ) Traalnad .AIQimclln11B'Ipy
Focal seizures With or without Onset: Any age Oxcarbazepine Levetiracet:am Zonisarnide
impaired awareness Carbamazepine Lamotrigine Felbamate
Topiramate Brivaracetam
Lacosamide
Duration: Minutes
Aura, staring, automatisms, focal
tonic-clonic activity, postictal
confusion
EEG: Localized abnormalities
Benign epilepsy with Onset: 3-13 y Majority of children do Oxcarbazepine Lamotrigine
centrotemporal spikes, not require antiepileptic Carbamazepine Levetiracet:am
Rolandic epilepsy therapy
Duration: 1-2 min
Wakes from sleep, paresthesias one
side of the mouth, ipsilateral facial
twitching, drooling.
EEG: Unilateral or bilateral
centrotemporal spikes
superimposed on a normal
background
Generalized Idiopathic/generalized Onset: Any age Valproic acid (preferred Zonisamide {myoclonic Clobazam
seizures genetic epilepsy in boys only) seizures present) Ketogenic diet
Lamotrigine Levetiracet:am
Topiramate
Duration: Variable
Generalized tonic-clonic,
myoclonic
EEG: Generalized spike wave,
polyspike discharges
I~ (continued)
..
1at TABLE H. Characteristics of Epilepsy Syndromes and Antiepileptic Drugs (continued)
.........,... EpiiPIJ._.._
Childhood and juvenile
CI~ICIII Fulun11
Onset: 4-16 y (varies with
Fht-Une n.tnlent at
Dlalce (Manatherlpy)
Ethosuximide (absence
Altmllllln Flnlt-Une
nubnlnt
Diller OpllaM t.
Ad)lmclln IIB'Ipy
May worsen seizures:
absence epilepsy syndrome) only) Carbamazepine,
Valproic acid oxcarbazepine,
Lamotrigine phenobarbital,
phenytoin, tiagabine,
vigabatrin
Duration: 5-30 s up to 100 times
a day
No aura; abrupt onset, staring,
motor arrest, automatisms, no
postictal confusion.
EEG: 2-3 Hz spike wave complexes
Juvenile myoclonic Onset: 7-20 y (varies with seizure Valproic acid Clobazam
epilepsy type) Lamotrigine Ketogenic diet
Levetiracetam
Duration: Variable depending on May worsen seizures:
seizure type Carbamazepine,
gabapentin,
oxcarbazepine,
phenytoin, tiagabine,
vigabatrin
Absence, myoclonic (early
morning}, and generalized
tonic-clonic
EEG: Bilateral spike wave and
polyspike and wave discharges
3.5-6Hz
Lennox-Gastaut Onset: 3-Sy Valproic acid Lamotrigine Clobazam, rufinamide,
syndrome Topiramate laoosamide, felbamate
Vagal nerve stimulator
and ketogenic diet
Duration: Variable depending on
seizure type
Atypical absence, atonic (drop),
myoclonic, generalized tonic-
clonic, tonic
Intellectual disability
EEG: Slow spike wave complexes
1.5-2.5Hz I
~=illcl
Other seizure Infantile spasms Onset: <1 y Adrenocorticotropic Oral prednisolone
types hormone
Vigabatrin (tuberous I
sclerosis)
Duration: Brief, cluster Consider vitamin B6 trial. I
Flexor or extensor movements that
generally occur in clusters, head
drops
High-risk populations include
tuberous sclerosis, Down syndrome
and history of severe hypoxic I
ischemic encephalopathy
EEG: Hypsarrhythmia, burst
suppression, slow spike wave,
decrement
Neonatal seizures Onset: <3mo Phenobarbital Fosphenytoin Vitamin B6 and/or folinic ~
Levetiracetam acid trials i
Duration: Variable ______________________T<_o_p_iram

---a-te------------------------------1
Apnea, tonic, multifocal clonic,
focal clonic, myoclonic
l Benzodiueplnes (dJazepam.
llorazepam. donazepun)
.
TABLE ~7. Side Effects of COmmonly Used Antiseizure Medications
:···....... .... ~
Somnolence, ataJda, clysartbria. respiratory depreuiou. tachyphylaxis
~ Brlvaracetam Somnolence, fatigue

1 Carbamazepine Diplopia, D8111ea, and vomiting, atm.. leukopenia, thrombocytopenia
IClobazam Lethargy, fatigue, irritability
!Ethosuximide Rub. anorexia, leukopenia. aplastic anemia
i,,, Felbamate Decreased appetite. weight loss, nausea, in5omnia (aleepleuneu), headache,
aplastic llllemia, hepatic failure
IGabapentln Somnolence, dizziness, ataxia, fatigue
1Lacosamide Dizziness, headache, diplopia, nausea, prolonged PR interwl
l Lamotrigine Diz.zinels, ataxia, blurred or double viaion, Dllll.lea, vomiting, rub (including
i Levetiracetam ~===~.mood change&, gastrointestinal upset

IOxcarbazepine Somnolence, hyponatremia, rash
j Perampanel Somnolence, dizziness, headache, blurred viaion, aggreuion, hostility
i Phenobarbital Hyperactivity, Jedation, oystagmUJ, ataJda
!,_! Phenytoin Rub. nystagmus, ataxia, drug-induced lupus, gingival hyperplaaia, anemia,
leukopenia. polyneuropathy
I R.ufinamide Leth~ dizziness. ataxia. beadac:be, Jhortmed QT intenal
I Topiramate !=~~~ confuaion, headache, ataxia, weight loa, hyperthermia,
l,_ Valprolc add Hepatotoxicity, nausea and vomiliDg, abdominal pain, weJght pin. anemia,
leukopenia. thrombocytopenia
!. ~~-~~. . . . . . . . . . . . . . . . . . ... . . . . . . . ~~--~~~~.~~~. ~~~~. ~~--~~!~.................................................................,
be explored carefully with the patient and family. seizures. It is a condition that can have long-term
Another option is the ketogenic diet. Inducing ketosis consequences including neuronal death. neuronal
through a high~fat to carbohydrate and protein ratio injury. and alteration ofneuronal nd:worla, depending
diet may help control or reduce symptoms in some on the type and duration ofthe seizure. Generally, it
children. The vagal nerve stimulator. approved by is thought that a seizure is likely to be prolonged and
the Food and Drug Administration in 1997, has also lead to SE after 5 minutes and can cause long-term
proven quite beneficlal for some refractory patients. consequences after 30 minutes or more. Therefore,
any convulsive seizure lasting more than 5 minutes
EMERGENCY MANAGEMENT OF should be treated with emergency medication. For
STAnJS EPILEPTICUS (SE) out-of-hospital use, rectal diazepam (Diaatat) and
In 2015, the ILAE and the Comm.iasion on Classi- intranasal midazolam (Versed) are effective and
fication and Terminology and the Commission on safe in the setting of prolonged seizures. Ar. with
Epidemiology published new definition and clas- any other pediatric emergency, airway, breathing,
sification guidelines for status epilepticus. Status and circulation should be evaluated first and ad-
epilepticus is now t:lefirud as tz condition ruulting dressed u necessary. Intravenous, intranasal, or
either from the foilure of the meclumisms rupon- rectal short-acting benzodiazepines (lorazepam.
sible for seizllre termination or from the initiation midazolam, or diazepam) often stop the seizure.
of mechAnisms that lead to abnormally prolonged For a prolonged seizure not responsive to rescue
ben.zodiazepines, fosphenytoin and/or phenobarbi- history of present illness, and physical examination
tal loading doses are usually administered to break often suggest the etiology. Encephalopathy secondary
the seizure as well as prevent recurrence. After a to a systemic process such as ele<:trolyte imbalance,
short-acting ben.zodiazepine medication is used, a infection. or liver failure is characterized by fluctu-
longer--actins medication is necessary in treating ating mental status (Iethargy,irritabillty, confusion,
status epilepticus. The physician should stay at the dJsorientation) and nonlocalizlng neurologic manifes-
bedside and continue to escalate medications until tations such as myoclonus, tremors, and temperature
the seizures stop, preferably within 20 minutes. After instability. In contrast, levels of comciowmeu are
prolonged convulsive status epilepticus has resolved, abnormal but fairly stable when encephalopathy
individuals are at risk for nonconvulsive stabls epilep- results from structural lesions in the brain (tumor,
ticus, which can be subtle and easily missed. When abscess, hemorrhage), and focal neurologic signs
seizures end, patients typically close their eyes and are more common. Recent or concurrent febrile
may fall asleep, but ifeyes remain open or deviated illness could suggest infectious or postinfectious
and the child remains unresponsive, nonconvulsive encephalitis. Focal findings (hemiparesis, ataxia,
status epilepticus should be suspected. Patients with cranial nerve defects) and focal seizures are more
refractory status may require drug-induced comas common with herpes simplex (HSV) encephalitis
(pentobarbital or midazolam drips) as well as contin- than other viral etiologies. A subacute onset of
uous EEG monitoring to adjust and evaluate ongoing psychiatric symptoms or delirium associated with
management. Prognosis after status epilepticus is sleep disturbance, seizures, abnormal movements,
related to the underlying etiology for the prolonged and autonomic dysfunction suggests an autoim-
seizure. If a child has preexisting epilepsy, anticon- mune limbic encephalitis often associated with
wlsant levels are drawn. The child who is febrile antibodies to the N~methyl-o-aspartate receptor.
and toxic-appearing or has new repetitive seizures Reye syndrome, a rare mitochondrial disorder
and altered mental status warrants an evaluation characterized by acute-onset encephalopathy and
for CNS inkction or autoimmune encephalopathy degenerative liver disease, may follow a viral illness,
(including LP). A head computed tomography especially when aapirin has been administered. Signa
(CT) should be obtained prior to LP in a child with and symptoms include severe vomiting, delirium.
focal seizures, postictal focal deficits, or any signs stupor, hypoglycemia, and elevated transaminase
or symptoms of increased intracranial pressure. and ammonia levels. Metabolic disorders typically
Targeted or comprehensive toxicology screening is present with recurrent episodes of mental status
undertaken if there is any concern about ingestion. changes that clear when the acute process is cor-
Historic features consistent with metabolic disorder rected. A careful history may suggest environmental
(unexplained encephalopathy, deterioration during exposures or drug use. Particular areas of interest
illness, unusual odors) or unexplained acidosis or on examination include vital signs, liver size, pupil
coma sh.ould trigger metabolic evaluation including and funduscopic assessment, and neurologic findinp
glucose, lactate, pyruvate, ammonia, carnltine levels, (cranial nerves, reflexes, strength, sensation, and
acylcarnitine profile, serum amino acids, and urine cerebellar function).
organic acids.
DIAGNOSTIC EVALUAnON
Blood tests evaluate for electrolyte abnormalities,
ENCEPHALOPATHY uremia, hypoglycemia, acidemia, and hyperam-
Any disruption Jn blood flow, perfusion, oxygen, monemia. The WBC count is elevated in the presence
energy substrates, removal of metabolic waste, of infection. Urine and blood should be sent for
and electrolyte balance could lead to generalized toxicology screening. An emergent head CT scan
cerebral dysfunction with alteration in the level of is indicated in patients with evidence of increased
consciousness, which is known as encephalopathy. intracranial pressure or focal neurologic signs. ALP
is appropriate when meningitis or encephalitis is
CLINICAL MANIFESTATIONS suspected and increased intracranial pressure is not
The differential diagnosis ofpediatric encephalopathy, considered a risk for braJn herniation. Cerebrospi-
or deterioration in mental status due to generalized nal fluid (CSF) should be sent for a molecular viral
cerebral dysfunction, is extensive (Table 9-8). Fortu- panel and for the presence of paraneoplastic and
nately, the age of the patient, past medical history, autoantibodies. HSV encephalitis is characterized
TABLE W. Causes of Encephalopathy in Children

i /nfectlon Mefllllali: DiMnJerl
I.a:..'::!"':::..-:::..~ • Aminoacidopathies
• Organic acidopathiea
• Dilorden ofcarbohydrate m.etaboliam
! • Infections that may present with an altered leftl
ofconsciousness include menlngitia, encephalitis, • Disonien «fatty add oxidation
post:lnfectious encephal.omyelitis, brain abiceM, Mitot:hondri8l DiiDfflflts
' and subdural empyema. • Alpers syndrome
!• Sepm can produce generalized cerebral • Leigh syndrome
depression 1D the ab1e0ce of central nervow
• Reye syndrome
I}'Btem involvement.
IJisonlet3 ofthe Liver
! • Infection with Shlplla species occasionally
j presents with Isolated encephalopathy. • Hepatic encephalopathy
llnctullldlntrll:lllllll,.,.. Rensl Diii!B!Je

• Hypertensive encephalopathy
!• Trauma/abuse
'
!• Hydroc:Jephalw
• Kidney failure/uremia
Pulmonlty,.,.
!• Neoplamc infiltration or brain tumor
• Acute, chronic hypoxia
!• Arteriovenous malformation, embollam. moke
I/nftii/Onl(rctl QI/Jplllr20) GMioi!WCUAirl1lfiiiiN
• Cardiovucular failure/ahockfcompromiaed
!Ber:tro/Jfe traii*Jca perfusion
~• Hyponatremia
!• Hypematrem1a I EDdocttJoplllhy
1· Hypoglycemia
!• Hypocalcemia i • Diabetic ketoaddoals
~ • }{yperc:aklemJa !• Adrenal imufficiency
j• Hypomagnesemia l• Haahimoto encephalopathy
i /nrr.a.m.J Shuntlnfedlon IIMfuncfiDn I~ fJisonllrs
!.......................................................
:
Seizures Prd:l1ll Phatl _.. .............................................................................
, ~···· L~. . . ~.~~.~~.~~~. . . . . . . ..... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..
by temporal lobe seizures and interictal temporal HEADACHES

epileptiform discharges superimposed on a diffuse
slow wave pattern on EEG, as well as temporal lobe PATHOGENESIS
signal changes or edema on MRL Headaches are a common complaint in the pediatric
population. It is important to determine early in
TREATMEflJ the evaluation whether the headaches are primary
Specific identification of the underlying disorder is (benign headaches not associated with underlying
critical to resolving the encephalopathy and preserving neuropathology, including tension-type headaches
brain function. Treatment depends on the cause and and migraine headaches) or secondary (pathologic,
whether increased intracranial pressure is present. with the pain typically generated secondary to in-
Patients with severe disease require intubation and creased brtracranial pressure).
close lntta.cranial pressure monitoring in a pediatric Benign tension-type headaches are oftenassociated
ICU. Antloiotics are added in cases of bacterial in- with psychological stress or fatigue. Theyare typi.cally
fection; high-dose IV acyclovir is recommended for described as generalized, constant. and band-like in
patients with suspected HSV. Metabolic disorders distribution. They tend to occur in the afternoons
are discussed in Chapter 19. Ingestions are discussed and are often worse on weekdays and better on
In Chapter 20. weekends and over the summer break from school.
Most respond to over~the--counter analgesics, removal abnormalities raise the concern ofa structural lesion
of the inciting stressor. and rest. Affected patients causing headaches. Headaches accompanied by
who take analgeaics more than three to four times worsening focal neurologic deficits warrant emergent
a week are at risk for the development of chronic. evaluation for an intracranial source.
analgesic overuse headaches (rebound). Frequent
tension-type headaches can also be associated with Physical Examination
clinical depression. The physical examination includes an assessment
Migraine headachu are hypothesized to result from of growth parameters. vital signs (including blood
sudden progressive depolarization ofa hyperexcitable pressure), and structures of the head (sinuses,
cerebral cortex (•spreading cortical depression"). teeth). The funduscopic examination permits the
They are characterized by recurrent attacks ofsevere, detection of papilledema (swelling of the optic
throbbing, typically frontal or frontotemporal pain that disc) in cases of increased intracranial pressure;
lasts for several hours. Photophobia, phonophobia, CN VI palsy may also be present. VlSion acuity
nausea, and vomiting may also be present. In about should be documented Carotid bruits, which
one-third of patients, the headaches are preceded may be audible in patients with arteriovenous
by an aura, which is usually visual (e.g., scotomas). malformations (AVMs), should be ruled out. A
Symptoms resolve with sleep. Migraines are classified thorough neurologic examination is of paramount
as compllcated when they are accompanied and/ importance and includes mental status, cranial
or followed by transient neurologic deficits such as nerve function, strength, sensation, deep tendon
weakness/paralysis, sensory lollS, difficulty speaking, reflexes, gait, and coordination.
or alterationa in vision or mental status. Patients who
DiAGNOSTIC EVALUADON
suffer from migraine headaches are asymptomatic
and have normal neurologic examinations between Neither CT nor MRI of the head is indicated in the
episodes of pain. A positive family history ofmigraine patient with nonprogressive recurring headaches and
headaches is common. a normal neurologic examination. Neuroimaglng is
indicated in the setting ofany ofthe following: recent
CLINICAL MANIFESTATIONS onset of severe, debilitating headaches; hea.dache5
History that are increasing in severity and/or frequency;
A comprehensive headaclle history should include headaches in the setting of seizures or a history of
the description of acute versus chronic symptoms, neurodevelopmental impairment; and headaches
onset, progression, severity, location, duration, and accompanied by neurologic signs (i.e., papilledema,
timing of headaches. Response to medication and strabismus, unilateral weakness or sensory loss,
alleviating/exacerbating factors are important factors. dysarthria, ataxia, or changes in mental status,
Any associated weakness, visual disturbances, or cognition [decline in grades], affect, or behavior).
sensory changes should be reported. Questions about Such signs typical1y manifest within 6 months of
stress levels, recent life changes, and precipitating the onset of headaches in patients with underlying
factors (foods, menstruation, exercise) may assist neuropathology. Although structural lesions large
in the diagnosis. Asking the patient or caregiver to enough to result in symptomatic increased intra~
keep a headache diary can identify possible triggers, cranial pressure are almost always visible on head
including fatisue, sleep deprivation, fasting. caffeine, CT, MRI provides additional detail which may be
menstruation, and stress. beneficial in patients with abnormal CT scans or
Headaches that wake the patient from sleep or suspected posterior fossa lesions.
occur primarily in the mornings are suspicious for
increased intracranial pressure. These headaches DIFFERENTIAL DiAGNOSIS
are usually made worse by lying flat or increasing Primary pseudotumor cerebri syndrome or idio-
venous pressure by bending, sneezing, or straining. pathic intracranial hypertension is a benign but
Nausea and vomiting are not uncommon, partirul.arly important cause of headaches that typically occurs
on wakening, and are concerning in the patient who in overweight adolescent females, or in associa~
has no associated complaints of abdominal pain or tion with thyroid disease or in the use of certain
diarrhea. Pathologic headaches usually increase in medications (specific acne medications containing
both severity and frequency over time. Associated retinoic acid and some antibiotics).It is thought to
personallty changes, gait disturbances, and vision be caused by impaired CSF resorption. Although
the examination is positive for papilledema, the

increased intracranial pressure is accompanied by
I~13 II §~~lttt; l!§~~t•1;!;!1C!H[t(ij;le1 3ifW
normal neuroimaging. A LP is typically diagnostic Stroke refers to a sudden interruption of cerebral
(elevated opening pressure) and therapeutic. An. blood flow resulting in transient or permanent
opening pressure greater than 28 em H 2 0 should focal neurologic deficits. Although stroke is rare in
be considered abnormal when accompanied by children when compared with adults, it has been
the signs and symptoms of increased pressure. increasingly recognized over the years. About half
Acetazolamide, which decreases CSF production, of the children presenting with an acute stroke will
i.s the treatment of choice. Refractory cases may have an identified risk factor such as the following:
result in visual deficits and require serial LPs or
• Cardiac disease (congenital heart disease,
neurosurgical shunting. Intracranial hypertension
endocarditis)
is typically self-limited and resolves without com-
• Vascular disease (arteriovenous malformation,
plication. Weight lou for overweight individuals
aneurysm. moya moya)
is also recommended.
• Hematologic disorders (sickle cell disease and
TREATMENT coagulopathy)
• Infection (complications of meningitis or encephalitis)
Tension-type headaches respond to nonprescription
• Metabolic disease (most commonly homocystinuria)
analgesics and rest. Stress management techniques,
• Trauma (arterial dissection)
massage, and biofeedback training may also be bene-
ficial. Mental health counseling may be beneficial in Ischemic and hemorrhagic strokes occur more
patients with suspected social or emotional stressors. commonly in the perinatal period when compared
Ifthe child or adolescent has an underlying anxiety with older children. Neonates often present with
disorder. this should also be managed with the help seizures, and focal deficits may be more d.ifficult to
ofa child psychologist or psychiatrist. identify at presentation. Most strokes in children
Management of the migraine patient begins occur in the cerebral hemispheres, presenting with
with reassurance that the headache is not due to hemipU'esis, visual field defects, and/or aphasia.
underlying neuropathology. N onpharmacologic Brainstem and cerebellar strokes are less common. The
interventions (e.g., biofeedback, acupuncture, neurologic ma.nifatations correlate with the location
cognitive therapy, vitamin and herbal supplements) of the ischemia. Magnetic resonance angiography
are often very beneficial for controlling migraine can evaluate vessel abnormalities leading to stroke,
headaches. Patients should be instructed to eat and MRI with diffusion-weighted images can detect
regular meals, avoid fatigue, dehydration, and early strokes (<24 hours). Additional laboratory tests
sleep deprivation. Over-the-counter medications that may prove helpful include coagulation studies,
(ibuprofen, naproxen) work well as first-choice CBC and cultures, connective tissue/vasculitis pro-
abortive agents; intranasal or oral sumatriptan (as files (ESR, C3, C4, ANA), and workups to rule out
well as other triptan medications) u-e reserved lipid and metabolic abnormalities. Depending on
for older children with headaches that are severe the etiology, anticoagulation (low·molecular·weight
or unresponsive to over-the-counter medications. heparin, warfarin) or antiplatelet therapy (aspirin)
Subcutaneous sumatriptan is inappropriate for is helpful to prevent recurrences. Large clots may
children. Prophylaxis (daily medication) should be require surgical evacuation.
considered ifheadaches are frequent and disabling An AVM is an abnormal collection of U'teries
or interfering with daily functions (such as school and veins. Occasionally, a cranial bruit is present
attendance). Cyproheptadine may provide some on physical examination. More commonly, how·
benefit in young children. Anticonvulsant&, anti- eVf!r, AVMs present in a previously asymptomatic
depressants, and P-blockers have been prescribed individual with the sudden or insidious onset of
with vu-iable success. The Childhood and Ado- headache, vomiting, nuchal rigidity, prog.ressive
lescent Migraine Prevention Study, a randomized hemiparesis, diplopia, ataxia. and focal or general-
prospective double·blinded trial. recently showed ized seizures. Arteriography permits determination
that amitriptyline and topiramate, two of the most of the site of the abnormality and feeding veuels.
commonly prescribed preventive medications, are Surgical removal, embolization, or radiotherapy is
no more effective than placebo in preventing mi- necessary to prevent recurrent ischemic or hem-
graine headaches in adolescent patients. orrhagic stroke.
Thrombosis can occur at both arterial and vtmaus complete in children, although some patients expe-
sites. Conditions that prediapose to thrombosis rience permanent lingering disability. Intravenous
include sickle cell hemoglobinopathy, coagulation immune globulin shortens the duration and severity
disorders, congenitalheart disease, cardiac procedures, of the illness. Miller- Fisher syndrome is a variant
arrhythmias, endocarditis, and trauma. Traumatic of GBS that results in ophthalmoplegia, decreased
brain or neck inJury can cause arterial dissection, reflexes, and ataxia.
which is a common cause of thrombus formation 7lck paralysis resembles GBS, although ocular
and ischemic stroke. Acute CNS infections, sy&temic palsies and pupillary abnormalitie11 are common
inflammation, anemia, and dehydration can predispose additional findings. Certain ticks in the Appalachian
to cerebral venous sinus thrombosis, which results and Rocky Mountains are capable of producing a
in nonspedfi.c clinical findings Including headache, neurotoxin that blocks acetylcholine release. The
seizures, signs of increased intracranial pressure, patient recovers completely once the tick is removed
and focal neurologic deficits. Some CNS infections from the skin.
such as tuberculous meningitis and varicella virus Acute transverse myelitis is an inflammatory
may result in vasculopathy, which can also lead to disorder of the spinal cord resulting in acute motor
ischemic strokes acutely or later on after recovery. and sensory deficits as well as bowel and bladder
dysfunction. It can present as a result of a postin-
fectious process or autoimmune disorders such as
WEAKNESS multiple sclerosis or neuromyelitis optica. However,
Abnormalities leading to weakneu, paralysis, or both many times a cause is not identified Back pain may
may occur at any level- from the motor cortex and precede weakness and sensory deficits. When con-
pyramidal tracts to the anterior horn celL periph- sidering this diagnosis, it is extremely important to
eral nerve, neuromuscular junction. and muscle. rule out spinal cord compression, spinal cord tumors,
Differential diagnosis is, therefore, broad and will ischemia, and hemorrhage. Direct injury to the cord
depend greatly on the time course ofsymptoms and from blunt trauma also needs to be ruled out from
localization within the neuroaxis. the patient's history. Patients are treated with immu-
notherapy includingN steroids and plasmapheresis,
DIFFERENT1AL DIAGNOSIS and prognosis is variable.
Gutllaln- Barre syndro~ (GBS), also known as Mya:sthenla gmvts (MG) is a chronic autoimmune
acute inBammatory demyelinating polyneuropathy, disorder ofthe neuromuscular junction. Autoantibodies
and tra11SVU'Se myelitis are two of the most common bind to the postsynaptic acetylcholine receptor and
causes of acute weakness in childhood. GBS is an block transmission. The rate of receptor breakdown
acute~onset, progressive, ucending weakness caused also increases, so fewer receptors are present. The
by autoimmune·mediated injury to the myelin sheaths principal symptoms are easy fatigability and weak-
of nerve roots and peripheral nerves. More than half ness that are exacerbated by sustained activity and
ofcases develop 7 to 21 days after an acute respiratory improve with rest. Juvenlle MG typically presents in
or gastrointestinal viral illness. Both sensory and au- late childhood or adolescence; the onset may be rapid
tonomic dysfunction can develop. Initial symptoms or insidious, and symptoms wax and wane aver time.
include numbness of the distal extremities, back or Almost half of patients experience ocular muscle
leg pain, followed by progressive (usually) ascending involvement, resultins in ptosis and/or diplopia.
weakness. Deep tendon reflexes can be diminished Bulbar weakness leads to dysarthria and difficulty
or absent. Severity varies from mild weakness to swallowing. Historically, the classic supportive study
progressive involvement of the trunk and cranial is a positive tensilon test, (used in adults but not
nerves. Respiratory muscle involvement may neces- in children): intravenous anticholinesterase (edro-
sitate mechanical ventilation. Significantly elevated phonium chloride) results in a transient increase in
CSF protein level and/or nerve root enhancement muscle (particularly ocular) strength by blocking
on MRI support the diagnosis of GBS. Motor nerve the breakdown ofacetylcholine in the synaptic cleft.
conduction studies will be abnormal and demonstrate Repetitive nerve stimulation studies demonstrate a
evidence of demyelination usually several weeks after decremental response following repeated stimulation.
initial presentation. Symptoms may progress for up Acetylcholine receptor antibodies are measurable in
to 4 weeks, with resolution typically beginning ap- the serum in some but not all patients. MG may go
proximately 4 weeks thereafter. Recovery is usually into complete or partial remission after several years;
however, most patients continue to experience peri- An antisense oligonucleotide intrathecal therapy
odic exacerbatiollll throughout adulthood, Frequent (Nusinersen/Spinraza) modulates alternate splicing
dosing of an anticholinesterase (pyridostigmine) in the ancillary SMN2 gene to produce the full-length
improves symptoms. Corticosteroids and other im- protein. This therapy markedly reduces morbidity
mune suppressants are prescribed for maintenance and mortality, because of respiratory fallure, in SMA.
therapy and acute exacerbations. Thymectomy reaults If combined with newborn screening to allow for
in significant improvement in many patients with treatment in the presymptomatic stage, this new
MG, presumably because the thymus is thought to gene therapy may potentially cure this previously
sellllitize the lymphocytes producing the offending lethal disorder. Diagnostic testing for SMA consists
antibodies. of specific gene testing.
Duchenne-type muscular dystrophy (DMD), an Thmors that compress the spinal cord result in
X-Unked recessive disease of muscle tissue, is the weakness and paralys!J below the lesion and constitute
most common muscular dystrophy and occurs pre- a surgical emergency. Cervical spinal cord injuries
dominantly in boys. Serum creatinine kinase (CK) produce sudden-onset paresthesia& and paralysis.
levels are drastically elevated. The disease presents Environmental toxin exposure may induce acquired
in early childhood with motor delay. Weakness is neuropathies or myopathies. For example, infants
greatest in the proximal muscle groups, so the patient In certain endemic areas (or those fed honey) may
has difficulty with standing and climbing resulting be exposed to Clostridium botulinum spores and
in the Gowers' sign, when a child has to climb up his develop progressive flaccid paralysis from the elab-
own thighs to stand up from a sitting or squatting orated toxin, which irreversibly blocks the release
position. Hypertrophied calves are also evident of acetylcholine at the motor endplate.
on exam. As the disease progresses, ambulation is
lost, the muscles atrophy, and contractures develop. DIAGNOSIS AND TBEATMENT
Cardiac and cognitive abnormalities often present as Diagnostic workup is tailored by a comprehensive
well. Treatment is mostly supportive; glucocorticoids history and physical examination. Patients with
(prednisone and defla.zacort) are approved to be asymmetric weakness or signs of increased intra-
started before there has been substantial decline to cranial pressure should undergo neuroimaging to
improve function. As discussed in recent diagnostic rule out mass effect and hydrocephalus. Findings
and therapeutic guidelines for DMD published In localized to a particular level of the spinal cord
Lancet Neurology, there are emerging therapies and warrant evaluation (including spinal MRI) for cord
clinical trials targeting the dystrophin gene mutation compression or injury. An urgent neurosurgical
via exon skipping and other forms of gene therapy. consultation is advised if cord compression is sus-
Most children become wheelchair bound early in the pected clinically. A LP is helpful when infection is
second decade, with death in adolescence or early suspected. Supportive treatment may be required
adulthood from respirator y failure or cardiomyopa- in most cases, but more definitive treatments, 1f
thy. Multidisciplinary care should include nutrition, available, are disease-specific.
rehabilitation, physical therapy, orthopedics, cardi-
ology, and oftentimes pulmonology.
ATAXIA
Spinal muscle atrophy (SMA) is an inherited
disorder involving degeneration of the anterior Ataxia is the inabilityto coordinate purposeful move-
hom cells and cranlal nerve motor nuclei The most ment and control balance. Conditions that affect the
severe form, SMA type 1 (Werdnig-Hoffmann cerebellum, connected sensory/motor pathways, and
disease), becomes evident in early infancy with the inner ear are likely to cause ataxia in children.
generalized hypotonia and weakness. SMA type 2 The moat common causes in the pediatric popu-
presents between 6 and 12 months ofage. The child's lation are infectious labyrinthitis, acute cerebellar
most advanced motor function is sitting. In SMA ataxia. and drug iJlSestion (e.g., sedatives). Meta-
type 3, wa1kJns is achieved but lost as the dJsease bolic derangements, hydrocephalus, head trauma,
progresses. Cognitive abilities are unaffected in all and cerebellar hemorrhages or tumors may also
types of SMA. SMA is now known to be due to a cause ataxia. Chronic ataxia may be secondary to
loss of function mutation in the SMNl gene which a genetic disorder or brain malformation involving
codes for the survival motor neuron (SMN) protein. the cerebellum.
DIFFERENTlAL DIAGNOSIS so the family history may be positive for neurologic

VII'81 infection of the labyrinthine structures can illnesses.
cause an acute ataxia which is often associated with 'The examination includes evaluation of mental
horizontal nystagmus. Acute cerebellar ataxia is status, cranial nerves, muscle tone and strength.
usually a clinical spectrum from relatively minor deep tendon reflexes, and cerebellar findings (ap·
abnormalities (dysmetria or subtle difficulties with pendicular vs. truncal) including gait. Abnormal
coordination) tD inability txJ walk or stand. It occurs gait may be a manifestation of weakness (reduced
most commonly between the ages of2 and 7 and often reflexe11 and muscle strength) rather than imbal-
follows a viral illness. The patient appears otherwise ance. The examiner should note the presence of
well, with no changes in the level of consciousness nystagmus and/or signs of increased intracranial
or mental status. Headache and nuchal rigidity are pressure (bradycardia, hypertension, papilledema,
absent, and the CSF is sterile. The prognosis ofacute meningismus, positional, and/or progressive head·
cerebellar ataxia, which involves only the trunk, aches). If the child is old enough and cooperative,
limbs, and mild nystagmus, is quite good, with the tests such as heel-to-knee, finger-to-nose, and rapid
return of normal coordination within a fuw days tD alternating movement help evaluate cerebellar
weeks. This benign disease should be distinguished function. The Romberg test evaluates function of
from acute arebellitis, in which an acute infection the peripheral nerves and posterior columns. With
causes inflammation of the cerebellum that can rap- the patient standing balanced with feet together,
idly progress txJ increased intracranial pressure and the Romberg sign is present (abnormal) ifthe child
herniation ifnot identified appropriately. As discussed cannot maintain balance when he or she closes the
in a prior section, cues associated with opsoclonus, eyes. It is usually positive in sensory ataxias, but not
myoclonus, and irritability require evaluation for OMS in primary cerebellar ataxias.
and neuroblastoma. In addition, ataxia that is slowly
DIAGNOSTIC EVALUADON
progressive with or without cranial nerve deficits or
associated signs ofincreased intracranial pressure is Toxicology screens should be considered in ambu-
more likely to be caused by an infratentorial tumor. latory patients or patients with suspected abuse.
Chronic ataxias typically have a genetic basis Neuroimaging permits assessment for cerebellar
such as ataxia-telangiectluia or Friedreidt awia. pathology (tumo~ inflammation. abscess, hemot'--
Ataxia·telangiectasia is an autosomal recessive neu· rhage, cerebellitis). CT of the head should always
rodegenerative disorder that presents in childhood precede LP in patients with ataxia, but brain MRI is
and progresses to wheelchair dependence. The preferred to best evaluate pathology in the posterior
ataxia is associated with extensive telangiectasias fossa. LP permits analyais for abnormalities noted in
and immunodeficiency. The genetic defect is located acute or postinfectious processes and paraneoplastic
on chromosome 11. Friedreich ataxia presents later syndromes. Chronic or recurrent ataxia warrants
in childhood with progressive ataxia, sensory losses, metabollc and genetic workup.
weakness, and muscle wasting. Skeletal deformities
(scoliosis) invariably follow. Most patients die of PHAKOMATOSES
cardiomyopathy-related heart disease before 30 years
of age. Inheritance iJ autosomal recessive, linked to Phakomatoses are neurocutaneous diseases char--
a defect on chromosome 9. acterized by lesions in the nervous system. skin.
and eyes. Two autosomal dominant conditions are
CLINICAL MANIFESTATIONS encountered in children: neurofibromatosis and
History and Physical Examlnatlun tuberous sclerosis. Sturge- Weber syndrome is a vas-
The history should include detalls regarding disease cular neurocutaneous syndrome that is traditionally
onset (acute vs. chronic) and progression (slow vs. included in the phakomatoses.
rapid). Associated symptoms may include fever,
headache, vomiting, vertigo, photophobia, and NEUROFIBROMATOSIS
altered mental status. Recent precipitating events Neurofibromatosis types 1 (von Recklinghausen
{seizures, infections, head trauma) and exposures disease) and 2 (bilateral acoustic neuromas) are the
(medications, heavy metaJs, solvents, gases) should most common variants in children. Neurofibroma-
be documented. Some ataxias have a genetic basis, tosis type 1 is a clinical diagnosis based in part on
TUI.E W. Diagnosis of Neurofibromatosis Type 1 ofthese proteins are involved in tumor suppression
through the mTOR pathway.
!Two or more ofthe following must be present to Disease severity varies greatly. Typical skin lesions
!meet diagnostic criteria:
: include aah~leajspots (flat, hypopigmented macules),
ll. Six or more cafe.-au~lait apota, >5 mm in size in shagreen patches (areas ofabnormal sld.n thickening),
j children and > 15 mm in pcmpubertal individuals sebaceous adenomas, and ungual fibromas. Ash-leaf
! 2. Axillary or inguinal .freckling spots are the earliest manifestation and are best de-
!3. Two or more Lisch nodules (hamartomas) in the tected by Wood lamp examination. Neuroimaging
;iris demonstrates the distinctive periventricular kno~like
! 4. Two or more neurofibromas or one or more areas oflocalized swelling. or tubers. Subependymal
1 plexiform neurofibroma nodules and giant cell astrocytomas may also be
present. Intellectual disability and seizures (including
! 5. A diltlnctl.ve oueous lesion. mch u aphenol.d
in&ntile spasms) are common. Tumors also have a
1 d)'lplaala
predilection for the kidney, heart (particularly cardiac
! 6. Optic gliomas
rhabdomyomas), and retina. Treatment consists of
17. Affected firJrt..degree relative hued on the antiepileptic therapy and surgical removal of related
;..........P.:!E!~J...~~~-············-·······························....................................J
1. .
tumors when 1ndicated. mTOR inhibitnrs such as
siroli.mu.s and everoli.mu.s have now been successfully
used for the management ofsubependymal giant cell
the presence of six or more ~au·lait spots of a astrocytomas, renal angiomyolipomaa and topically,
specific size (Table 9·9). A 1arge gene on chromosome for dermatoJosic findings such as facial angiofibromas.
17 coding for neurofibromin has a high spontaneous
mutation rate, Patients with neurofibromatosis type STURGE-WEBER SYNDROME
1 are at an increased risk for optic pathway gliomas Sturge-Weber syndrome is a neurocutaneous disorder
and other low-grade gliomas in the CNS. They characterized by vascular malformations of the brain
typically require evaluation and treatment for glia. (leptomeningeal angiomatosis), eyes, and skin. A
mas,leamlng disorders, renovascular hypertension. port~wine stain (nevus flammeus or facial angioma)
scoliosis, and occasionally seizures. Routine vision over the area innervated by the first division of the
screening is critical Neurofibroma5 can occur in the trfseminal nerve should alert the primary physician
skin or peripheral nerves and can cause pain as well to pursue further evaluation. Most affected children
as motor and 5ensory impainnents and may require develop intellectual disability, seizures, hemiparesis,
surgical resection; however, most will recur. and visual impairment, with approximately a third
Bilateral acoustic neuromas are the hallmark of of them developing glaucoma. The syndrome results
neurofibromatosis type 2. Complications include from a sporadic mutation in the GNAQ gene, which
hearing loss and vesb.'bular disorientation. Brain MRI was recently discovered. Tunable (pulsed) dye laser
demonstrates bilateral eighth cranial nerve masses. therapy fades the port-wine stain but does not ad·
Neurofibromas, meningiomas, schwannomas, and dress the underlying neurologic dysfunction. Lesions
astrocytomas are also associated with type 2 neura. should be treated early in life to optimize cosmetic
fibromatosis. Cataracts and retinal hamartomas are outcome. The severity and frequency of the seizures
not uncommon. Surgical debulking is appropriate is associated with subsequent developmental delay
when hearing impairment becomes pronounced. and may ultimately require surgical intervention
Cochlear implants have restored hearing in some (hemispherectomy). About 10" of children with
patients. The genetic abnormality occurs on chro- a unilateral port-wine stain over the dermatome
mosome 22, which produces a protein called merlin. innervated by CN V1 will be affected with Sturge-
Weber syndrome; this percentage is higher if the
TUBEROUS SCLEROSIS lesion is bilateral.
Thberous sclerosis, like neurofibromatosis, is a
progressive autosomal dominant neurocutaneous
disordel:. although sporadic cases are more common
NEURALTUBEDEFECTS
than inherited ones. TSCl and TSC2 genes have Failure of neural tube closure during the third and
been identified in chromosomes 9q34 and 16p13 and fourth weeks ofgestation results in a group ofrelated
encode for hamartin and tuberin, respectively. Both disorders tenned neural tube defects. Maternal
malnutrition, drug exposure (e.g., valproic acid), dysfunction, foot deformities, and increasing motor
maternal hyperthennia, congenital infections, ra- deficits. Spina bifi.da defects have a high incidence
diation. and genetic factors are all associated with ofinfectious complications, cortical malformations,
an increased risk of neural tube defects. There is a and Chiari type II malformation (dysgenesis and
3'.1(, to 4'.1(, risk of a second affected child being born downward displacement of the lower brainstem and
to parents who already have one child with a neural cerebellum that often results in hydrocephalus and
tube defect. Because failure of closure results in at times stridor, apnea, and dysphagia).
persistent leakage of ~fetoprotein into the amniotic
fluid, the maternal senun ~fetoprotein level at 16 TREATMENT
to 18 weeks' gestation is an excellent screening tool Planned cesarean section delivery prior to the onset
for identifying hfsh·risk pregnancies. The incidence of labor results in improved outcomes and overall
of neural tube defects Is decreased in infants whose motor function. Early closure of repairable back
mothers receive at least 400 mg/day of folic acid lesions and prophylactic antibiotics until closure
supplementation prior to conception and during the reduce the risk ofinfection. 'The majority ofinfants
early weeks of pregnancy. The overall incidence of with myelomeningocele dewlap hydrocephalus within
neural tube defects is declining worldwide because the first month of life. Early ventriculoperitoneal
of improved maternal nutrition and widespread (VP) shunt placement, even for mild hydrocephalus,
prenatal diagnosis. In some circumstances such appears to improve intellectual outcome. Infants
as anencephaly, mothers may undergo subsequent with severe cyanotic episodes, apnea, stridor, and
elective tennination of the pregnancy. dysphagia from ClUari type U malformations ben-
efit from early cervical decompression. Meticulous
CLINICAL MANIFESTATIONS attention to urodynamics, anticholinergic medica-
Abnormalities may occur anywhere along the CNS; tion. and clean intermittent catheterization result
the higher the lesion, the more severe the sequelae. in urinary continence for the majority of patients
Neonate. with anencephaly are bom with large skull and reduce the risk of urinary tract complications,
defects and virtually no cortex. Brainstem function the major cause of death after the first year of life.
is marginally inblct. Many are stillborn; others die Surgical release of rethe.red spinal cord can prevent
within days of birth. Encephalocele& are protrusions of deterioration of motor and sphincter dysfunction
cranial contents through a bony skull defect, umally in and may partially reverse acquired deficits. Fetal
the occipital region. Affected patients manifest some surgery is associated with measurable preservation
form of intellectual disability, seizures, and motor of motor and sensory function.
deficits. Hydrocephalus is a frequent complication.
Spina biflda includes a variety of conditions HYDROCEPHALUS
characterized by IU'lural tube defects with incomplete
fusion of the vertebral arches. Myelomeningoceles PATHOGENESIS
are protruding sacs of neural and meningeal tis- Hydrocephalus is the pathologic enlargement of
sues, whereas mJJningoceles contain meninges only. the ventricles that occurs when CSF production
Both are most common in the lumbosacral region. outpaces absorption. usually secondary to outflow
Bowel and bladder sphincter dysfunction is the obstruction. In obstructive or noncommunicating
rule, and sensorimotor loss exists below the lesion. hydrocephalus, the block exists somewhere within
In spina bifida occulta., the bony vertebral lesion the ventricular aystem, and the ventricles proximal
occurs without herniation of any spinal contents. to the obatruction are selectively enlarged. The most
Birthmarks, dimples, subcutaneous masses, or hairy common cause is aqueductal stenosis, but other
tufts at the base of the back suggest an underlying causes include Chiari type U malformations., arach-
defect. When identified in infancy, patients should noid cyst, Dandy-Walker malformation. intrauterine
undergo spinal ultrasound or spine MRI to rule out infection. and intraventricular hemorrhage. Acquired
occult dysraphism. Although the infant may initially noncommunicating hydrocephalus in older children
appear neurologically intact, the caudal end of the is most often due to posterior fossa neoplasms and
cord is affixed or tethered to the distal spine. AB aqueductal stenosis or gliosis.
the vertebral column grows throughout childhood, In contrast, all ventricles are proportionately
the tethered distal spinal cord develops traction enlarged in nonobst:ructive or communicating hymo.
injury, resulting in gait disturbance, sphincter cephalus, which occurs when CSF absorption at the
arachnoid villi is impaired secondary to meningitis, not be attempted in the presence of asymmetric or
subarachnoid hemorrhage, or leukemia. Rarely, obstructive causes ofincreased intracranial pressure
communicating hydrocephalus is due to excessive because of the risk of herniation of the brain across
CSf production from a choroid plexus papilloma. the tentorium or throush the foramen magnum.
CLINICAL MANIFESTATIONS TREAtMENT
History and Physical Examination Patients with hydrocephalus are at risk for develop-
The clinical manifestations of hydrocephalus de- mental delay, visual impairment, motor disturbances
pend on the rate ofonset and whether the fontanels and, in severe cases of obstructive hydrocephalus,
are still open. An inappropriate increase in head death. Ifthe underlying etiology cannot be corrected,
circumference or bulging anterior fontanel may be surgical diversion with a VP shunt reduces intracranial
the only indication in infants; poor feeding, irrita- pressure and relieves the symptoms. An endoscopic
bility, lethargy, downward deviation of the eyes (the third ventriculostomy is a surgical alternative to VP
"setting swt• sign), spasticity in the legs, apnea, and shunt when CSF obstruction occurs at or distal to
bradycardia often provide additional clues that the the cerebral aqueduct This type ofventriculostomy
infant has increased intracranial pressure. In older may occasionally close because of gliosis, but this
patients with acute COW'Ses, the signs are relatively intervention avoids the risks of mechanical hilure
clear and include morning headaches that improve and infection present with the VP shunt.
after upright positioning or vomiting, irritability Indwelling shunts can be complicated by mechanical
and/or lethargy, papilledema, and diplopia because failure of the device, problems due to overshunting
of CN VI palsy. Spasticity, clonus, and hyperreflexia or undershunting, and infection. Staphylococcus
most prominent in the legs are additional neuro- epidermidi& is the most frequently isolated pathogen.
logic signs of hydrocephalus. The Cushing triad, Systemic and lntraventrJcular antibiotics are always
consisting of hypertension, bradycardia, and slow administered. Shunt removal is almost always indi-
irregular respirations, is a late and ominous sign of cated. The programmable valve is a technological
increased intracranial pressure implying imminent advance in shunts that permits external adj118tm.ent
risk of brain herniation. to optimize ventricular pressure and helps avoid
over- or undershunting.
DIFFERENTIAL DIAGNOSIS
Conditions that lead to increased intracranial pressure
ABNORMAL HEAD SHAPES
without hydrocephalus include acute intraventricu-
lar hemorrhage, diffuse brain edema (secondary to Microcephaly is defined as a head circumference
traumatic brain injury, hypoxic ischemic enceph- that is greater than two standard deviations below
alopathy, large ischemic stroke or encephalitis), mean head size for age. Microcephaly may be con-
cerebral venous sinus thrombosis, abscesses, and genital. as a result of genetic conditions (e.g., trisomy
many tumors, all of which are easily differentiated 21, Angelman syndrome, GLUT 1 deficiency, Rett
by CT or MRI. Additionally, children may have large syndrome) or acquired from congenital or perinatal
head circumferences because of m.egalencephaly insults (maternal drug ingestions, congenital TORCH
without hydrocephalus or benign famillal macro- infections, insufficient placental blood flow, or hypoxic
cephaly. Other causes of ventricul.omegaly such as ischemic inJury). Affected children often demonstrate
brain volume loss should also be considered in the both cognitive and motor delay; associated seizure
differential of hydrocephalus. disorders are not uncommon. *Microcephaly" which
matches weight and length percentiles in an infant
DIAGNOS11C EVALUATION without congenital anomalies may be normal and is
Neuroimaging (CT or MRI) is an important adjunct often referred to as relative microcephaly.
in the evaluation of hydrocephalus. Anatomic mal- Macrocephaly, in contrast. refers to a head cir-
formations, ventric ular size, and source ofobstruc- cumference greater than two standard deviations
tion are clearly delineated. A head ultrasound may above the mean. Macrocephaly may be fami1ia1;
be sufficient in the infant. In children who have a however, cranioskeletal dyspluiu, storage diseases,
VP shunt, rapid sequence MRI can assess ventric- and hydrocephalus should be explored as possible
ular size without exposing the child to cumulative causes, particularly ifthe growth rate crosses multiple
radiation over time. If a LP is indicated, it should percentile lines over time.
Positionalplagiocephaly mers to benign flattening Craniosynostosis a the premature fusion of one

of the back ofthe head caused by infants placed to sleep or more cranial sutures. It may be idiopathic, part of
exclusivcly on their backs, without enough tummy a syndrome, or associated with poor brain growth.
time. A variant results when an infant preferentially Bone growth continue& alons the open suture lines.
lies with the head turned toward one side. This could resulting in an abnormally shaped head. As an
cause tlattening of the parleto-ocdpital area accom- example, if early obliteration of the sagittal suture
panied by prominence of the .forehead on the same occurs (most common), the child will develop a
side. Hypotonia and torticollis should be ruled out in long head and a narrow face (scaphocephaly). In
those instances, but most cases require no interven- contrast, premature closure of the coronal suture
tion beyond counseling the parents to encourage the results in a very wide face with a short, almost
child to lie with the head tilted tn the opposite side box-like, skull. Surgical intervention consists of
(by moving a mobile or colorful object to that side). reopening the sutures and retarding their subse-
If there is a cosmetic concern. a soft plastic helmet quent fusion and often involves care by a plastic
fitted by a plastic surgeon may be successful in gently surgeon in conjunction with a neurosurgeon. Most
molding the back of the head into a more acceptable defects are repaired before 12 months of age for
shape when instituted prior to 9 months of age. cosmetic reasons.
KEY POINTS
• Until2 years of age, a child's chronological age • Phannacologic Interventions for ADHD include
should be adjusted for gestational age at bi'th stmulants, the prodrug lladexam18tamine, and
When assessing developmental achievement nonstimulants such as atomoxetine.
• The Wechsler preschool scale is used to assess • CP is a static disorder of movement and postlR
IQ in preschoolers. resulting from a fixed lesion of the brain. If a
• Language Is the best Indicator of intellectual child with CP exhibits progresaive deterioration,
potential. an alternate clagnoals should be sought
• Any child with a suspected speech or language • Febrile seizures are typically brief, generalized
disorder should be referred for a full hearing seizures with fever which occur in up to 5% of
evaluation. otherwise healthy children aged 6 months to 6
years. About a third of children with a history of
• Dysftuency may be developmental between febrile seizure will have recurrent febrile seizures.
3 and 4 years of age. Dysfluency which is ac- Febrile seizures, even when recurrent, an~ not
companied by tension, struggle, and/or total considered epilepsy. Children with a history of
word blockage or severely limits communi- febrile seizure are at slightly greater risk than
cation should be considered true dysfluency their peers to develop epilepsy later in life.
(stuttering), neceasitatlng referral to a speech
therapist. • The context of the chlld'a age, past medical and
family histories, and any prior unusual spells
• Autism spectrum disorder represents a contin- an~ important In the differentiation of a seizure
uum of chronic, nonprogresslve developmental from a noneplleptlc event. The diagnosis of a
disabilities Involving Impairments in social seizin Is based prlmarly on the detaled history.
interaction, communication, and behavior.
• When evaluating a patient with headaches, it is
Asperger Is now considered one of the autism
important to determine whether the headaches
spectrum disorders.
are primary (tension or migraine headaches) or
• Any association of autism with administration of secondary (pathologic) In etiology. Clinical man-
the MMR vaccine and/or thimerosal has been ifestations that should prompt consideration of
definitively dlsproven. pathologic headaches Include symptom focalltyj
• The predominant elements of ADHD are in- frontal or occipital location; debilitating episodes
attentlveneas, hyperactivity, and impulsivity. of pain; increasing frequency and/or severity;
headaches and vomiting upon awakening; and screen fer neural tube defects. The incidence
neurologic signs. of neural tube defects Is decreased In Infants
• Abnormalities leading to weakness, paralysis, whose mothers receive folic acid supplemen-
or beth, may occur at any level within the neu- tation before conception and in the early weeks
roaxis, from the motor cortex and pyramidal of pregnancy.
tracts to the anterior horn cell, peripheral nerve, • Clinical manifestations of hydrocephalus in-
neuromuscular junction, and muscle. GBS is an clude inappropriately large head circumference,
acut~onset, progressive, ascending weakness bulging fontanel, and poor feeding On Infants);
caused by autoimmune-mediated demyelinating irritability and/or lethargy; morning headaches
polyneuropathy. MG is a chronic autoimmune and vomiting; papilledema and diplopia; and
disorder that affects the neuromuscular junc- hyperreflexia of the lower limbs. A LP is contra-
tion. DMD Is an X-llnked recessive disease Indicated If herniation of the brain Is a concern.
that causes progressive muscular weakness • Positional plagiocephaly is the benign flattening
in which the Gower's sign is often a diagnostic of the back of the head often seen In Infants
clue on physical examination. placed to sleep exclusively on their backs. It
• The most common causes of acute ataxia in the should be distinguished from craniosynosto-
pediatric population are infectious labyrinthitis, sis. Most cases of plagiocephaly require no
acute cerebellar ataxia, and toxic Ingestion. Intervention beyond counseling the parents
• An elevated maternal serum a-fetoprotein level to encourage "tummy time" when the baby is
at 16 to 18 weeks' gestation Is an excellent awake and under direct supervisor.
CLINICAL VIGNETTES
VIGNETTE1 L Focal epilepsy

b. Lennox-Gastaut syndrome
A mother brings her 6-year-old boy to your office with
c. Juvenile myoclonic epilepsy
a chief complaint ot •staring spells~ over the last 6
d. Childhood absence epilepsy
months. The episodes have been noted by both parents
and the patient's teacher. Events last 10 to 20 seconds,
e. Transient Ischemic events
during which he stares blankly and is not responsive. 3. Which of the following represents the most ap-
There Is no clear eye or head deviation. Occasionally, propriate Initial therapy for this patient, given his
the spells will be associated with lip licking and eye diagnosis?
fluttering. The spells have a definite end, after which L Ethosuximide
he quickly returns to baseline and resumes his activ- b. Carbamazepine
Ity. The boy Is unaware of the episodes. Hals a good c. L.orazepam
student and there has been no noticeable decline In d. Phenytoin
his schoolwork. There is no family history of aeizuree. e. Fosphenytoin
The vital signs and physical examination are normal.
VIGNETTE2
1. Which of the following is the next best step in the
During a routine health maintenance visit, the mother
evaluation of this patient?
of a 3-year-old male expreesea concern regarding his
L CT of the brain
development. The patient spoke his first words at 12
b. EEG
months of age and was speaking in two-word phrases
c. MRI of the brain
by age 24 months. He was using a pincer grasp at 12
d. Admission for inpatient video EEG monitoring
months of age and can currently draw a circle. Review
e. Referral tor full psychoeducational testing
of gross motor milestones reveals that he walked at
2. The EEG reveals 3-Hz symmetric and synchronous 18 months of age, but has had difficulty keeping up
spike-and-wave activity. This result is most con- with his peers when running. He is slow to stand from
sistent with a diagnosis of which ot the following a seated position. Your examlnadon reveals prominent
conditions? calves, intact upper and lower extremity reflexes, and
normal sensation. The patient demonstrates a toe-toe Upper and lower reflexes are Intact. She walks with
galt with mild lordosis. He uses his hands to "climb a wlde-ba&ed galt and falls after three to four steps.
up" his legs when moving from sitting on the floor to
standing. 1. Your initial diagnostic evaluation would include
which of the following?
1. This patient's history and physical examination 1. Urine drug screen
findings are most consistent with which of the II. CT of the brain
following? c. l.J.Jmbar puncture
L Gross motor delay d. Urgent EEG
b. Global developmental daley t. (a) and {b)
c. Isolated delays In speech and fine motor skills f. All of the above
d. Isolated delay In ftne motor skills
2. CT of the head and laboratory studies are unre-
t. No developmental delays
vealing. She is admitted to the hospital for further
2. Which of the following represents the best initial evaluation and monitoring. Which of the following
step in the management of this patient? would be the most appropriate next step in the
L Serum laboratory testing evaluation, given that the above mentioned studies
b. MRI of the brain are negative?
c. Referral for pedlatrtc-speclftc physical therapy L MAl brain
d. Referral to a specialist In genetics b. Toxicology consult
t. Electromyography c. Neurology consult
d. Urine vanillylmandelic acid {VMA) and homo-
3. lhe child's serum CK level is significantly elevated
vanillic acid (HVA)
at 20,000 UIL (normal 22 to 198 UIL). A CK level
elevated to this degree Is virtually diagnostic of
e. Skeletal survey
which of the following condmons? 3. MRI of the brain and ur1ne studies are negative.
L Cerebral palsy Her galt neither Improves nor worsens over the
b. Spinal muscular atrophy course of hospitalization. Which of the following
c. Muacular dystrophy is the most likely diagnosis?
d. Multiple sclerosis a. GBS
t. Adrenoleukodystrophy b. Neuroblastoma
c. Pontine glioma
4. The patient has a 6-month-old brother. Which
d. Acute cerebellar ataxia
of the following represents his chance of being
t. Friedreich's ataxia
similarly affected?
L 25%
VIGNE'I"'E 4
b. 50%
A 14-year-old female is evaluated in your office for
c. 75%
d. His risk is the same as for the general population.
a 2-waak history of headaches. The headaches are
bilateral, frontal, and throbbing In nature. They persist
e. lhe brother is affected with the same condition. throughout the day without alleviating factors. She denies
VIGNET1E3 waking up with a headache and reports no nausea or
vomiting. She does report mild photosensitivity and
A 2-year-old female Is seen in the emergency depart-
blurred vision. There is no hiStory of photophobia. She
ment for gait changes over the last day or so. lhree
reports no recent Illnesses or traumas. She recently
weeks prior she had a cold with upper respiratory
started a new acne medication and takes an oral con-
symptoms, which resolved. Shels otherwise healthy
traceptive for dysmenorrhea. On physical examination,
and has normal development. There Is no history of
her weight is 150 lb (68 kg). Visual acuity is 20/1 00 in
trauma. The parents note that she appears "off bal-
the right eye and 20/40 in the left. Bilateral papilledema
ance• and falls easily. These symptoms have been
is noted. Extraocular movements are intact, with no
present since she woke up from a nap yesterday.
facial asymmetry or apparent hearing loss. Palatal lift
No abnormal eye movements have bean observed.
is symmetric and the tongue is midline. The remainder
On physical examination, all vital signs including
of the neurologic examination is normal.
temperature are within normal limits. She is alert and
shows appropriate social interactions. She has clear 1. Which of the following factors in this patient's
tympanic membranes, no skin findings, and a benign history and physical examination is a known risk
abdomen without organomegaly or masses. Pupils factor for pseudotumor cerebri?
are round and reactive, extraocular movements are L Weight
intact, there is no nystagmus, and she has a strong cry. b. Gander
When reaching for a toy, she often misses her target. c. Retinoid-containing acne medication
194 • BWEPAINTS Pedlatr1cs
d. Contraceptive use 3. The head CT is normal, and the lumbar puncture

e. (a), (b), and (c) opening pressure Is significantly elevated. Which of
f. All of the above the following can be effective in the management
of pseudotumor cerebri?
2. You strongly suspect pseudotumor cerebri.
L Amitriptyline
Which of the following tests will further support
b. Ibuprofen
this diagnosis?
c. Sumatrtptan
L CT of the brain
d. Acetazolamide
b. l.JJmbar puncture with opening pressure
e. Lamotrigine
c. VIsual-evoked responses
d. (a) and (b) only
e. All of the above
ANSWERS
VIGNETTE 1 Quullon 1 The patient is not responsive to •outside" stimulation

1.AnswerB: during the event but does not lose postural tone.
When episodes are suspected to be epileptic based on Subtle eye fluttering or automatism& may be noted
the clinical history and physical examination, the best during some episodes. Events are brief, lasting less
diagnostic study for possibly confirming and classifying than 30 seconds, and can occur as frequently as
seizures is the EEG. Sleep deprivation (sleep-deplived 100 times a day. Typical absence seizures are not
EEG), hyperventilation, and photic stimulation often associated with underlying brain anomalies. Epileptic
provoke abnormal electrical activity aiding in diagnosing syndromes differ in clinical presentation and by EEG.
the epileptic syndrome. A normal EEG does not rule Focal seizures present with localizedlfocal abnormal,
out a seizure disorder as the cause of the observable involuntary activity that may be motor, somatosensory,
episodes unless they occur while the EEG Is recording or autonomic In manifestation. Individuals may have
and cerebral activity remains unchanged (e.g., PNES). focal seizures with or without impaired awareness.
In more complicated cases, continuous video EEG The epileptic activity originates in the same area of
monitoring can be utilized to capture and characterize the brain each time but may spread, resulting in a
an event. Video EEG monitoring is also useful in cases secondary GTC seizure. Lennox-Gastaut syndrome
of suspected mallngerlng/Munchausen syndrome or Is character1zed by multiple seizure types, Including a
when nonepileptic spells represent reflux, tics, or other combination of atypical absence, generalized tonic-
seizure look-alikes. Neuroimaging (CT and MRI) is clonic, atonic, or tonic events. The EEG in Lennox-
indicated in most focal epilepsies and/or when trauma Gastaut syndrome is described as less than 2.5 Hz
Is suspected. Psychoeducatlonal testing, Including IQ slow spike and wave. Juvenile myoclonic epilepsy Is
and achievement testing, is recommended when a associated with generalized 4 to 6-Hz polyspike and
child is experiencing a decline in school performance. wave complexes on EEG. The syndrome takes its name
A psychological and ADH 0 evaluation, audiology and from the characteristic Involuntary myoclonic "jerks~
vision examinations, and measurements of adaptive of the upper limbs. Transient ischemic events are rare
behavior may help elucidate source(s) of academic In young children, but would be Important to rule out
difficulties and formulate a plan to encourage success if the events were not associated with demonstrable
in learning. epileptic discharges in EEG.
VIGNETtE 1 Question 2 VIGNETtE 1 Question 3

2. AnswerD: 3. AnswerA:
The EEG findings described are classic for absence Ethosuximide is the drug of choice for patients with
seizures. If the patient is old enough to cooperate, childhood absence epilepsy; in fact, this is currently
voluntary hyperventilation over several minutes may its sole indication. L.amotrigine or valproic acid are
provoke an episode dur1ng testing or durtng the clinic second-line agents for patients with excessive side
visit. Childhood absence epilepsy can present in chil- effects or poor seizure control. Intravenous lorazepam
dren that are 4 to 10 years of age and are otherwise is a very important drug for acutely aborting seizures in
typically developing. Seizures have an abrupt onset hospitalized patients; rectal diazepam serves the same
and offset and there Is no associated postictal phase. purpose for home use. Phenytoin and fosphenytoln
(a prodrug of phenytoin) are utilized In the emergency degradation of anterior horn cells. Patients vary in pnr
room In the treatment of status eplleptlcus. Carba- sentation from profound hypotonia (Wen:tnig-Hoffman)
mazeplnels contraindicated In this patient as It may In Infancy to the ability to walk with onset In late ado-
potentiate his seizures. lescencelyoung adulthood. Typically, the examination
is significant for tongue fasciculations, proximal greater
VIGNETTE 2 Quedon 1 than distal weakneaa, and areflexia. Multiple aclerosis
1. AnswerA; is an autoimmune demyelinating disorder of the brain
Walking is a gross motor skill that is typically acquired and spinal cord. Onset is later in life and more common
by 15 months of age, with a population average of in females, with waxing and waning of symptoms. Ad-
about age 12 months. Eighteen months demonstrates renoleukodystrophy is X-linked and occurs primarily in
a clear delay. This delay would have been picked up at boys; this peroxisomal disorder is a neurodegenerative
the 15- or 18-month health maintenance visits, either condition that alfects the white maHer of the brain.
through direct observation by the medical provider or
through developmental screening. AHaining the mature VIGNETTE 2 Question 4
pincer grasp by 12 months of age implies that his fine 4.Answer B:
motor skills are progressing appropriately. His language This genetic disease Is Inherited In an X-linked reces-
skills, as descr1bed, are typical. Because only one sive pattern. Fifty percent of females are earners and
stream of development Is delayed, this Is considered are not affected. Males are at a 50% risk of lnherttlng
Isolated gross motor ra1tler than global delay. the abnormal gene.
VIGNETTE 2 Quedon 2 VIGNETTE 3 Quastlctn 1

2.Answerk 1.AnswerE:
Given the patient's motor delays and weakness on The initial evaluation in this patient would include a
exam, initial serum laboratorytesting, in particular serum urine drug screen followed by a CT scan, or brain MRI
CK levels, will be most sensitive and specific for the if possible. Toddlers in general are at an increased
suspected diagnosis. An MRI of the brain should be risk for ingestions. Reviewing medications available
normal in this patient, but would be a consideration in a in the home may yield the answer, often with the help
child with global developmental delays or upper motor of the poison control center. Stat neuroimaging would
neuron signs on examination. Although not the best be indicated to rule out any posterior hemorrhage or
initial step, a referral to physical therapy is imperative evidence of cerebellar stroke. If a posteriorfossa tumor
for this patient to optimize his motor function, teach Is a consideration, It would be bes1 visualized by an
range-of-motion exercises, and promote stretching to MRI of the brain. An EEG would be considered If the
Improve his toe-toe galt. A genetics referral may be a patient had altered mental status in conjunction with
consideration in the future if a hereditary muscle disease gait changes or if the symptoms were intermittent.
is apparent on examination and by initial testing. An Areflexia or weakness noted on examination would
EMG would be helpful in further disceming the cause necessitate a lumbar puncture to assess for an ele-
of the patient's weakness if he had fatigable weakness, vated protein Indicative of Guillain-Barre Syndrome
bulbar weakness, or Joss of reflexes on exam. or its ataxic variant, Miller-Fisher.
VIGNETTE 2 Quesdon 3 VIGNETTE 3 QuiSIIDn 2

3.AnswerC: 2.Answerk
The most common muscular dystrophy is DMD. In The most common pediatric CNS tumors occur In
boys with DMD, the CK level can be elevated up to 20 the posterior fossa. Initial signs and symptoms might
times nonnal. DMD is an X-linked recessive disorder include cranial nerve palsies, ataxia, headache ~n
that rasutts from an absence of dystrophin. Weakness craased intracranial pressure), or seizures. The best
begins in the proximal muscle groups; the calf muscles imaging modality to visualize the posterior fossa would
appear hyper1rophlecl, and the child rises from a sitting be an MRI ot the brain. Ruling out a tumor would
position by leaning on the calves and using the arms take precedence over consultations. Urtne VMA and
to "climb" up the legs (Gowers' sign). Becker muscular HVA are metabolltee In the urtne that are elevated In
dystrophy haa similar clinical manifestations because cases of neuroblastoma. In addition, a paraneoplastlc
of abnormalities in the dystrophin protein, but the on- syndrome can be associated with neuroblastoma that
aet is later (adoleaoence), and the dieeaae is generally includes ataxia as well as dancing eyes (opsoclonus/
milder. CP is a nonprograssive disorder of movement myoclonus). A skeletal survey would be indicated if
and posture resulting from a static brain lesion acquired there was radiographic evidence of subdural bleeds
in the fetal or perinatal period. Spinal muscular atrophy of varying ages on CT, raising suspicion for nonacci-
is an inherited disorder that results in the progressive dental trauma.

3.Answer 0: 2.Answer B:
On the basis of the patient's history of a recent (most In pseudotumor cerebr1, the lumbar puncture is both
likely) viral infection, her age, lack of temperaturu eleva- diagnostic and therapeutic. Obtaining an elevated
tion, normal mental status, negative studies, and lack of opening pressure (>28 em H20) during the lumbar
deterionrtion, the most likely diagnosis is acute cerebellar puncture confirms the diagnosis. Removing spinal
ataxia. In 1he great majority ofcases, coordination returns fluid with a large volume t ap reduces the increased
to baseline (nonnal) within a few days to weeks. GBS intracranial pressure, and the headache usually
involves p1'0918SSive ascending weakness with loss improves significantly. However, with papilledema
af reflexes. Neuroblastomas most commonly present and other signs and symptoms of increased intra-
with an abdominal mass with or without an associated cranial pressure pntsent, neuroimaging is indicated
paraneoplastlc syndrome which has a mora subacute before the lumbar puncture (to rule out conditions
onset of symptoms wHh ataxia. A pontine glioma Is an that could potentiate herniation of the bralnstem
aggressive bralnstem tumor. Presentatton ranges from during the procedunt). VIsual-evoked potentials are
the signs and symptoms of hydrocephalus to lower used to evaluate visual Impairment In patients with
extremity weakness/pain/numbness and cranial nerve multiple sclerosis.
deficits. Adrenoleukodystrophy is a disorder invoMng
the white matter of the brain. Friedreich's ataxia pres- VIGNETTE 4 Quasllan 3
ents in older children/adolescents with a more insidious 3.Answer 0:
onset of incoordination accompanied by nystagmus, Serial lumbar punctures can be employed to alleviate
weakness, and other neurologic signs. the headaches. Acetazolamide is a pharmacologic
agent that decreases CSF production at the choroid
VIGNB'TE 4 QU81tian1 plexus. Ibuprofen is often effective as first line in young
1.Answer F: patients with benign tension or migraine headaches.
Pseudotumor cerebri is mora common in overweight Sumatriptan often relieves migraine headaches in older
girls. Additionally, retinoid-containing acne medications childntn and adolescents. Amitriptyline is a tricyclic
and contraceptives place them at risk for developing antidep1'9SS8nt commonly used as a preventive medi-
Idiopathic Intracranial hypertension. Other potential cation In children with frequent migraines. Lamotrlglne
associations Include medications such as tetracycline, Is an anticonvulsant that does not affect the symptoms
lupus, Addison disease, and hypoparathyroidism. of pseudotumor cerebrl.
Dermatology
Lacey L. Kruse, Anne W. Lucky, and Bradley S. Marino
(YZV), a herpesvirus. It is usually a mild, self-limited

SKIN MANIFESTATIONS OF
disease in immunocompetent children. Severity can
VIRAL INFECTIONS
range from a few lesions and a low-grade fever to
Hand, foot, and mouth disease (HFMD) is an acute hundreds oflesions and a temperature up to 105"F
infectious exanthem, most commonly affecting (40.6"C). Fatal disseminated disease may occur in
children 1 to 4 years of age. HFMD is predominantly immunocompromised children or in neonates
caused by Coxsackie A viruses, but can also be caused whose mothers develop the infection within 1 week
by Coxsackie B, echoviru.ses, and enterovirus 71. of delivery. Adolescents and adults often have more
Typically, there is a prodrome of fever, anorexia, and severe clinical courses. After an incubation period
oral pain, followed by crops of ulcers on the tongue of 10 to 21 days, there is a prodrome consisting of
and oral mucosa and a vesicular rash on the hands, mild fever, malaise, anorexia, and occasionally a scar-
feet, and occasionally the buttocks and thighs. The latiniform or morbilliform rash. The characteristic
individual vesicles often have a •football" shape with pruritic rash occurs the following day, appearing first
surrounding erythema. In recent years, epidemics of on the trunk and then spreading peripherally. The
atypical HFMD have become more common; affected rash begins as red papules that develop rapidly into
patients present with extensive, diffuse vesicular clear vesicles that are approximately 1 to 2 mm in
eruptions. Diagnosis of HFMD is made by history diameter (the so-called "dewdrop on a rose petalj.
and examination; treatment is supportive. The vesicles then become cloudy, rupture, and form
Gianotti-Crolti syndrome, also called papular crusts (Fig. 10-1). The lesions occur in widely scat-
acrofkrmtstitil of childhood, is a typically asymp- tered •crops: so several stages are usually present at
tomatic, erythematous, papular eruption occurring the same time. Vesicles often are present on mucous
in children aged 1 to 6 years. Upper respiratory membranes as welL Patients are infectious from
symptoms, lymphadenopathy, and fever may precede 24 ho\ll'lil before the appearance of the rash until all
the eruption, which is symmetrically distributed on
the face and extensor surfaces of the arms, legs, and
buttocks; Gianotti-Crosti typically strikingly spares
the trunk {Appx. Fig. A-1). Papules may coalesce
into larger edematous plaques or become purpu-
ric. Several viruses have been associated with this
syndrome, with hepatitis B infection being the most
common trigger in Europe, and Epstein-Barr virus
(EBV) most common in the United States. Associ-
ation with hepatitis 8 is rare in the United States.
Other triggers include cytomegalovirus, Coxsackie,
adenovirus, respiratory syncytial virus, parvovirus,
rotavirus, and vaccinations. Treatment is supportive,
although resolution may take up to 8 weeks.
Varicella (chkk.enpox) is a highly contagious disease FIGURE 1t-1. Ruptured, crusted vesicles from varicella.
caused by primary infection with varicella-zoster virus .~'!!.~~-~--~~~-~~--~-~!.:.Anne W. Ll!ci<Y:L. . . .-····----
197
the lesions are crusted, which usually occurs 1 week higher. After primary infection, VZV retreats to
after the onset of the rash. the dorsal root ganglia; as a result, it follows a der-
The most common complication of varicella is matomal distribution when reactivated. Although
secondary bacterial infection. usually with Staph- herpes zoster occurs in children. it is uncommon
ylococcus aureus or group A Streptococcus (GAS). in healthy children <10 years of age. An attack of
This typically presents u a secondary fever or with zoster begins with pain and/or pruritus along the
localized signs of skin infection. Other complica- affected sensory nerve and is accompanied byfever
tions include encephalitis, pneumonitis, arthritis, and malaise. A vesicular eruption then appears in
myocarditis, nephritis, and hepatitis. Progressive crops confined to the dermatomal distribution.
varicella with systemic involvement may occur in lfpical ofall herpesvirus infections, the lesions are
immunocompromised c:hil.dren and is associated with grouped vesicles on an erythematous base (Appx.
a 2096 mortality rate. Immunization with varicella Fig. A-2). The eruption lasts 1 to 4 weeks, with
vaccine has significantly reduced the frequency of pain persisting for weeks or months (postherpetic
this infection in the United States. neuralgia). Other complications from herpes zoster
Primary varicella is a clinical diagnosis. In include encephalopathy, aseptic meningitis, Guillain-
unclear cases, VZV infection can be confirmed Barr~ syndrome, pneumonitis, thrombocytopenic
by virologic or serologic laboratory evaluations. purpura, cellulitis, and arthritis.
VZV polymerase chain reaction testing or direct Herpes zoster can be quite painful, and narcotics
fluorescent antibody is typically preferred be- are sometimes needed Systemic administration of
cause of the rapidity and specificity; these should antivirals, such as acyclovir, may be considered for
be performed on epithelial cells swabbed from use in immunocompromised patients, patients older
the base of a lesion. Viral culture is specific in than 12 yean, children with chronic diseue, and those
confirming herpesvirus infections, but takes up who have received systemic steroids for any reason.
to 1 week. Other confirmatory methods include MolllliCWD contqionm is a cutaneous viral
Tzanck smears, looking for multinucleated giant infection cauaed by a poxvirus and is very common
cells (which confirm herpesvirus infection but are in childhood. Itis manifested by small, flesh-<nlored,
not specific for VZV), and serologic assays ofVZV pearly. umbilicated, dome--shaped papules. The pap-
immunoglobulin (Ig)M and IgG. ules may occur anywhere, but are most common in
Treatment ofvaricella is supportive and ln.dudes moist areas such as the axilla.e, buttocks, and groin
antipyretics and daily bathing to reduce the risk of region (Fig. 10-2). The papules spread via touching,
secondary bacterial infection. In some patients, auto-inoculation, and scratching. Lesions typically
ibuprofen has been associated with an increased risk resolve spontaneously over 1 to 2 years, though
of streptococcal cellulitis when given in the setting families often request treatment sooner. Treatment
of primary varicella. In addition. Reye syndrome is options include expectant management, curettage,
a rare complication seen in patients with primary cryosurgery with liquid nitrogen. cantharidin (an
varicella taking aspirin. Oral antihlstamin.es for pru- extract from the blister beetle that causes blistering
ritus are safe to uae. Immunocompromised children of the epidermis), oral cimetidine, and imiquimod
who are exposed to VZV are given varicella-zoster cream.
immune globulin within 96 hours of the exposure Verrucae, commonly known as wam. are caused
and observed closely. Administration ofthe varicella by the human papWomavirus. There are four com-
vaccine within 72 hours ofexposure may prevent or mon types including verruca vulgaris (common
lessen disease severity. Systemic antiviral medications wart) (Fig. 10-3), verruca plantaris (plantar wart),
such as acyclovir, valacyclovir, or famciclovir are not verruca plana (flat wart), and condyloma accuminata
indicated for children with uncomplicated primary (genital warts).
varicella, but may be adm.inistered in children with Treatment ofwarts in the pediatric population is
varicella pneumonia or encephalitis and immuno- based on the type and location of the wart and in-
compromised patients. cludes topical sal1cyllc add, cryosurgery,lmiquimod
Hupes zoster (shingles) represents a reactiva- cream. oral cimetidine, oral zinc sulfate, injected
tion ofVZV infection and occms predominantly in immunotherapies such as intralesional Candida
adults who previously have had variceUa and have antigen. and squarlc acid dibutylester. Patients may
circulating antibodies. Howevet; ifvaricella occurs require multiple treatments, especially in the case
early in life, the risk for shingles in childhood is of recalcitrant warts.
Chapter 10 I Dennatology • 199
the seasonal epidemiology and the clinical course

of the disease. The rash has a distinct morphology
that typically begins with a herald patch, a 2 to 10
em oval salmon- pink plaque on the trunk, neck,
or extremities (Appx. Fig. A-3). This is followed
by several smaller lesions often distributed in a
•Christmas tree pattern'" over the trunk and upper
extremities that develop over days to weeks. The
lesions often have peripheral scaling. which may
cause the condition to be confused with tinea cor-
poris. Some patients develop lesions with a more
papular appearance, especially younger children
and African-Americans. The rash .i5 typically as-
ymptomatic and fades spontaneously over 4 to 12
weeks. If the eruption is pruritic, topical steroids
or oral antihistamines can be prescribed. Sunlight
has been shown to hasten resolution of the lesions.
Unllateral thoracic exanthem (asymmetric
periflexural exanthem of childhood) is a rash with
varying morphologies that occurs in children ages
1 to 5 years. The eruption characteristically begins
on one side of the trunk, then spreads centripetally,
and may become generalized. The rash is seen more
commonly ln the winter and spring months and may
follow symptoms of low-grade fever; lymphadenop-
athy, and respiratory or gastrointestinal complaints.
R&URE 10-2. Molluscum on the face. Note how the A viral etiology has been presumed, although no
lesions have central umbilication. Omage courtesy of specific virus has been implicated. Often confused
-~:-~-~-~-'!:!.:. ~?.~J..................................................................- ................,_ with contact dermatitis, the lesions vary from ery-
thematous macules or papules with a surrounding
halo to morbilliform, eczematous, scarlatiniform,
or reticulate configurations that may spread to the
opposite side from initial involvement (Fig. 10-4).
Pruritus is common and can be treated in the same
manner as pityriasis rosea- assoclated pruritus.
Lesions resolve over 6 to 8 weeks without treatment
and may desquamate or leave postinflammatory
pigmentary changes.
SKIN MANIFESTATIONS OF
BACTERIAL INFECTIONS
Bacterial infections of the sldn are common, and in
FIGURE 10-3. Verruca w lgarls on the dorsal surface of most cases they are the result ofgroup A !!-hemolytic
the dig~-:.9~~~-~-.?.~..~~~-~~--~:.~~~-~· ~~~~>.9__...... Streptococcus or S. aureus infection.
Bullous impeUgo, which is caused by a
toxin-producing strain of S. aureus, begins as red
PRESUMED VIRAL EXANTHEMS macules that progress to bullous (fluid-filled) erup-
Pityri.ud ro11ea is an acute, self-limited exanthem tions on an erythematous base (as seen on Appx. Fig.
of unknown etiology. A viral etiology has been A-4). These lesions range from a few millimeters
suggested based on the presence of prodromal to a few centimeters in diameter. After the bullae
symptoms of malaise and pharyngitis, as well as rupture, a clear, thin. varnish-like coatingforms over
is considered (often a first~generation cephalospo~

rin such as cephalexin, with coverage against both
Staphylococcus and GAS). In settings where methi-
cillin-resistantS. aumu (MRSA) is suspected, agents
such as clindamydn or tri.methoprlm-sulfamethox-
azole may be more appropriate. The caretaker can
remove any honey~colored crusts with twice-daily
warm compresses.
Stapbylo<:oa:al tc:alded ald.n syndrome (SSSS),
caused by exfoliative toxin-producing isolates of S.
aureus, is most common in infancy and rarely occurs
beyond 5 years of age. Onset is abrupt, with diffuse
erythema, marked skin tenderness, irritability, and
fever. Within 12 to 24 hours of onset, superficial
flaccid bullae develop and then rupture almost
immediately, leaving a beefy red. weeping surface
(Appx. Fig. A-6). Although widespread areas may be
affected, accentuation is seen on periorlftcial areas
of the face, as well a.s flexural areas around the neck,
axillae, and inguinal creases. Exfoliation i.s caused
by a staphylococcal toxin and may affect most of
the body. There is usually a positive Nikolsky sign
(separation of the epidermis after light rubbing).
S. aureus can be isolated from the initial focus of
infection, which is often the periorificial areas of the
face, but the primary infection is often difficult to
FIGURE 10-t. Erythematous reticulated plaques 'Nith identify. The diffuse exfoliation and bullae contain
central clearing and scattered erythematous papules sterile fluid, as the eruption is toxin~mediated.
involving the right trunk and periflaxural region following Mild to moderate cases of SSSS are treated with
a viral upper respiratory infection. The unilateral thoracic an oral antistaphylococcal medication. Children
exanthem lesions subsequently desquamated before with severe infection should be treated as though
resolving completely over several weeks. Qmage they have a second-degree burn, with meticulous
~-~-~-~-~~-g~--~~-~--~:...~-~~~:1............................................................... fluid management and intravenous oxacillin or
clindamycin.
Folliculltll is an infection of the shaft of the hair
the denuded area. S. aureus can be cultured from the follicle, usually with S. aureus. Superficial folliculitis
vesicle fluid Bullous impetigo lesions can be mistaken is common and easily treated. The buttocks and
for cigarette burns, raising the suspicion for abuse. the lower legs in girls who shave are frequent sites
Nonbulloua impetiso, which is caused by both of infection. Deep forms of this infection include
group A p~hemolytic streptococci and S. aureus, furuncles (boils) and carbuncles. Furuncles begin as
begins as papules that progress to vesicles and then superficial folliculitis and are most frequently found
to pustules measuring approximately 5 mm in di- in areas of hair-bearing skin that are subject to fric-
ameter with a thin erythematous rim. The pustules tion and maceration. especially the scalp, buttocks,
rupture, leaving a honey-colored thin exudate that and axillae. Carbuncles are collections offuruncles.
then forms a crust over a shallow ulcerated base Superficial folliculitis responds to aggressive
(Appx. Fig. A~S). Local lymphadenopathyis common hygiene with antiseptic cleansers and topical anti.bi~
with. streptococcal impetigo. Fever is uncommon. otl.cs (mupirocln or clindamydn). Folliculitis ofthe
The causative organism can usually be isolated from male beard is unusually recal.ci.trant and requires an
the lesions. oral antistaphylococcal drug. Simple furunculosis is
Limited nonbullous impetigo can be treated with treated with moist heat. Larger and deeper furuncles,
topical antibiotics such as mupirocin ointment. H which are becoming increasingly more common
the lesions are bullous or widespread. oral therapy in the community (particularly with the spread of
MRSA), may need to be incised and drained. There IAILE 10.1. COmmon Tinea Infections and
is debate regarding oral antloiotic therapy following Their Treatments
incision and drainage. Rarely, folliculitis can be caused
by PseudomoNU aeuroginosa in the specific setting !•...... 'hftrrt
of bathing in contaminated hot tubs. These lesions i 'linea capitia Oral gri1eofuMn. ~8 wk
are self-limited when the exposure is discontinued. i (scalp) Selenium sulfide shampoo to kill
spores; does not endicate lnfectl.on
SUPERFICIAL RJNGAL INFECTIONS
Essentially, two fungal species cause the most common
IIT'mea corporis
(body)
Topical antifungals (e.g.,
clotrimazole) for at least 4 wk; oral
griseofulvin if refractory
superficial. infections: Trichophyton and Mtaosporum. 1Tinea cruria Same as tinea corporis
Trichophyton tonsurans is the most common cause l (genitocrural)
of tinea capitU in the United States. Microsporum j "jock itch•
canis is also common and is spread from animals, j Tinea pedia Same as tinea corporis, plus proper
especially .kittens and puppies. On the scalp, tinea
capitis manifests as patches of scaling and hair loss,
!. ~:~~.:~:~--~-~~. . . ~~-~~~~.... . . . . . . . . . . ... . . . . . . . . . . . . . ..
broken ofi' hairs lcn.own as "black dots" (Fig. 10-5),
and boggy, pustular masses known as kerions. The by superficial tan or hypopigmented oval scaly
latter can be associated with pain, itching, a diffuse patches on the neck, upper part of the back, chest,
morbillifonn eruption. and lymphadenopathy. On the and upper arms. Dark-skinned individuals tend to
skin of the body, tinea corporis frequently manifests have hypopigm.ented lesions during the summer
as annular plaques with peripheral scaling, giving the when uninfected skin tans from sunlight exposure.
appearance of rings (hence the name .,ring-worm"). However, inc:Uvidual patients may demonstrate both
Ttnea pedis, usually an infection with Trichophyton dark- and light-colored lesions at the same time (hence
rubnun, classically presents as scaling in a "moccasin" the name versicolor). Treatment options include
distribution and frequently also involves the inter- selenium sulfide shampoo, topical antifungals. or
digital spaces of the toes. Tinea cruris, also caused systemic antifungals for widespread or recalcitrant
by T. rubrum, presents with erythema, scaling, and cases. Recurrence in the summertime is common.
maceration in inguinal creases. Most superficial Diaper rash may result from atopic dermatitis,
skin infections can be treated with topical antifun- primary irritant dermatitis, or primary or secondary
gal agents. However, systemic antifungal drugs are Candida albicans infection. Eighty percent ofdiaper
necessary to eradicate dermatophyte infections of rashes lasting more than 4 days are colonized with
the nails or hair. Table 10-1 presents tinea infections Candida. Fiery red papular lesions with peripheral
and their treatments. papules, pustules, and scales in the skin folds and
Tinea (pityriasis) venic:olor is caused by infection satellite lesions are typical for candida! c:Uaper rash.
with the yeastMalasse%iafutfur and is characterized Barrier creams along with topical antifungals (such
as an azole cream or nystatin ointment) are the
first-line treatments of choice. Recalcitrant diaper
rash may indicate more severe problems such as
Langerhans cell histiocytosis or metabolic disorders
like zinc deficiency.
ACNE VULGARIS
Acne valpril is a very common, self-limited, multi-
factorial disorder of the pilosebaceous unit. Lesions
may begin as early as 7 years ofage. Development of
acne between ages 1 and 7 years is rare and warrants
workup for endocrine abnormalities. The prevalence
of acne increases steadily throughout adolescence
and then decreases in adulthood. Although girls
FIGURE 1D-5. Tinea capitis causing characteristic "black often develop acne at a younger age than boys, se-
~-~::...~~P.~.:.9..~~~-~-.?.~~-~-~-~.P.~--~~~--~:..~.~~:L..... vere disease affects boys 10 times more frequently
because ofhigher androgen levels. In fact, 15'311 of all pattern to flares associated with the menstrual cycle.
teenage boys have severe acne (Fig. 10-6). In girls, polycystic ovary syndrome is a common
The pathogenesis of acne includes multiple fac- underlying factor. Rarely, Cushing disease or any
tors such as androgen stimulation ofthe sebaceous other condition that results in androgen excess can
glands, follicular plugging, prollferation ofPropion- predispose to acne. Poor hygiene and dietary choices
ibacterlum acnes, and Inflammatory changes. There are not risk factors for acne.
is a predilection for the sebaceous follicle-rich areas Treatment should be individualized depending
of the face, chest, and back. Closed comedones on the patient's gender and the severity, type, and
(whiteheads) and open comedones (blackheads) distribution oflesions. Mild acne has a lower risk of
are noninflammatory and nonscarring. Pustules, scarring and generally responds to topical therapy.
papules, and nodules (formerly called cysts) are First-line therapy typically consists ofa topical retinoid
inflammatory and carry the potential for scarring. and, for those with inflammatory acne, also topical
Atrophic and hypertrophic scars or keloids may antibiotics and benzoyl peroxide. Benzoyl peroxide
occur. At puberty, there is androgen-dependent works by decreasing the colonization of P. acnea.
sebaceous follicle stimulation, leading to increased Topical retinoids (e.g., tretinoin, adapalene, and
sebum production. Female patients with severe acne tazarotene) have strong anticomedogenic activity,
often have high levels of circulating androgens. with side effects including dryness, burning, and
Risk factors include famlly history and puberty. photosensitivity. Topical antibiotics (clindamycin and
It is important to obtain a good medical history erythromycin) can decrease colonization ofP. acnes,
and a thorough physical examination. Age ofonset, but their sole use for acne treatment promotes bac-
distribution, morphology. and severity of lesions terial resistance. When used in combination with
should be recorded. A full menstrual history should topical or oral antibiotic therapy, benzoyl peroxide
be taken to determine whether there is a hormonal can prevent bacterial resistance. Newer topical
therapies include reti.noids combined with benzoyl
peroxide or topical antibiotics.
There is growing bacterial resistance to antibiotic
therapy for acne, and oral antibiotics should be used
only in severely affected patients or those who do not
respond to conventional topical therapy. Systemic
antibiotics for acne include tetracycline, doxycycline,
minocycline, and erythromycin. In females, oral
contraceptives may also be helpful by suppressing
androgen production and are now approved for
acne therapy. Oral isotretinoin is very effective for
acne, but because ofits teratogenicity and side-effect
profile, strict monitoring is required. See Figure 10.7
for a guide to acne therapy.
PSORIASIS
PsoriuU is a common but often undiagnosed child-
hood disease, with 1096 ofcases beginning before 10
years ofage and 35'311 before 20 years ofage. There is
often a positive family history, and specific human
leukocyte antigen inheritance is part of the mode
of transmission.
This papulosquamous eruption consists of ery-
thematous papules that coalesce to form dry plaques
with sharply demarcated borders and silvery scales.
The scales tend to build up into layers, and their
removal may result in pinpoint bleeding (Auspitz
FIGURE Ut·&. Typical inflammatory acne lesions. Qmage sign). Psoriasis often appears at sites of traUDUlj this
~.~.~.~..~~.g~..~.~~..~:..~.~~~J.............................................................. is .known as the Koebner phenomenon. It is usually
FIGURE 11-1. Therapy for mild, moderate,

and severe acne. BP, benzoyl peroxide;
OC, oral contracentive.
•••••••••••••••••••••••o•o•••oo ooOOOooooooooor.:::,,,,,, ,,,,,,_ ,,,,,,,,,,,.,,ooooooooooooOoooooooooouooooooo ,.,..,
Guide to Aone
IIIII
A. Cc>...tonll: Low
llocllr.-
A Co......:lan..: TopiCIII
.....
A CanedoiWI:Toplclll
IINI"Qih topical r.ano1c1. ..tlnald. r.anold.
B. lnftammaiiDry or mlud: B. lnlllrnmMDIY or mbltd: a. lnftammiiiDry: II' poor
BP with or without Sllne u for mild. t1 fHPCIMe ID cnl
IDpiCIII .tll'yomycln or poor NIPOIIM, llld lhort antllll011c or oc
cllnciiiJTIVCin plls a t.m cn1 antlbllltlc canllcllr,........ ID
l'dnold. (Ina-, daley, or dlnnd!IQGIII tor oral
minacrcline). ilotrwlincin.
C. In tam.lu, oanllldw cnl
-*-PIIv. plllll.
symmetric, with plaques appearing over the knees, ERYTHEMA MULnFORME

elbows, scalp, and periocular and genital areas. The Erythema multiforme (EM) is an acute, self-limited,
nails often demonstrate punctate stippling or pitting, hypersensitivity reaction. The most frequent etiologic
distal detachment ofthe nail plate (onydwlysis), and agents include viral infections such as herpesvirus,
accumulation of subungual debris. Examination of adenovirus, and EBV.
the palms and soles reveals scaling and fissuring.
Psoriatic arthritis also affects about 10% ofchildren Clinical Manlfastatlons
with psoriasis. Other comorbidities include obesity, The hallmark of EM is the target lesion. which con-
hyperlipidemia, and depression. The differential sUt:s of three distinct zones: an erythematous annular
diagnosis for psoriasis often includes atopic derma- rim, a zone of clearing, and a central erythematous
titis; however, atopic dermatitis is more pruritic and or violaceous lesion. These targetoid lesions are
concentrated In flexural creases, whereas psoriasis is symmetrically distributed and are most common on
typically less pruritic and favors extensor surfaces. the hands, feet, and extensor surfaces. Annular urti-
Psoriatic scalp lesi.ona may be confused with sebor- caria is often mlstaken for EM, but the lesions ofEM
rheic dermatitis or tinea capitis. evolve over days, not hours and are fixed (vs. annular
Psoriasis is characterized by remissions and urticaria, in which individual lesions resolve within
exacerbations. Group A (}--hemolytic streptococcal 12 to 24 hours). Urticariallesiona are common on
infection Is a common trigger for psoriasis In a ge- the trunk and tend to have edematous, erythematous
netically susceptible individual. The most important borders with central clearins; in contrast, lesions in EM
aspect of treating psoriasis is to educate the patient tend to occur on the extremities and develop dusky,
and family that the diseue is chronic and recurrent. necrotic centers. Burning and itching are common
Though there is no~ psoriasis can be controlled in EM lesiona. Systemic manifestations include fever,
with conscientious therapy. Topical steroids are the malaise, and myalgias. The most common cause of
mainstay oftherapy. Topical vitamin D cream or oint- recurrent EM in children is herpes simplex virus
ment and tar can also be helpful adjuncts to therapy. type L For uncomplicated EM. symptomatic treat-
For more severe cases, natural sunlight or ultraviolet ment and reassurance are all that are necessary. Oral
B (UVB) light is useful, and immunosuppressives antihistamines, moist compre11es, and oatmeal baths
(such as methotrexate) and biologic therapies like are helpful The lesions resolve over a 1- to 3-week
etanercept are considerations. period, with some hyperpigmentation.
STEVENS-JOHNSON SYNDROME AND

HYPERSENSITIVITY AND TOXIC EPIDERMAL NECROLYSIS
ALLERGIC REACTIONS
Steveru-Johnlon syndrome (SJS) and toxic epider--
Atopic dermatitisJ urticaria, and angioedema are mal necrolyais (TEN) are severe hypersensitivity
discussed in Chapter 8. reactions, most commonly triggered by drugs.
Clinical Manltas1atlans AU.ERGIC DRUG REACTIONS

Epidermal detachment of 1006 or less is consid- Allergic reactions to drugs typically present as urti-
ered SJS, 1006 to 30% is SJS/ TEN overlap, and carial or morbilliform exanthems that develop within
greater than 30% is TEN. SJS/TEN begins with a 1 to 2 weeks of starting a new medication. The risk
prodrome for 1 to 14 days offever, malaise. myal- of an allergic drug reaction may be increased ifthe
gias, arthralgias, arthritis, headache, emesis, and patient bu a concurrent viral illness, similar to patients
diarrhea. This Is followed by the sudden onset of with mononucleosis treated with amoxicillin. The
high fever, erythematous and purpuric macules eruption clears after the inciting agent is removed,
with dusky centers, inflammatory bullae of two or but may take several days to weeks. Following the
more mucous membranes (oral mucosa, lips, bulbar acute eruption. many patients tend to desquamate.
conjunctiva, and anogenital area; Appx. fig. A-7), Treabnent is based on symptoms. The decision to
and detachment of the epidermis causing denuda- discontinue the medication is based on the risks and
tion (positive Nikolsky sign). In the most severe benefits of the need for treatment in the primary
cases, involvement of most of the gastrointestinal, illness versus possible alternative medications.
respiratory, or genitourinary tracts may be seen.
Untreated, SJS has a mortality rate ofapproximately
1096. TEN in children is rare, but is associated with HYPERPIGMENTED LESIONS
a 3006 mortality rate. With the incidence of melanoma increasing, it is very
The most common causes of SJS include drugs important to identify suspicious lesions and under-
such as nonsteroidal anti-inflammatory drugs, stand risk factors. Children with fair skin, excessive
penicillin&, sulfonamides, and many antiepileptic sun exposure, and multiple nevi are at increased risk
medications and rarely immunintions. Mycoplasma for both melanoma and norunelanoma skin cancer
is the most common infectious trigger of SJS in such as basal cell and squamous cell carcinomas.
children, and Mycoplasma-induced SJS tends to be Congenital nevi are usually larger than acquired
less severe. The pathogenesis of SJS/ TEN appears nevi and can vary considerably in color and shape.
to be related to upregulated expression of fas They tend to get darker. thicker. and more hairy with
ligand in the epidermis, a mediator of apoptosis. time, although giant nevi often will become lighter.
Systemic complications include elevated liver Congenital nevi are classified based on their size.
enzymes, renal failure, and fluid and electrolyte Large or giant nevi are >20 em in greatest diameter
imbalance. Sepsis and shock are frequent causes (Fig.10-8); small nevi are < 1.5 em; and medium nevi
of death. are in betweeiL Congenital nevi have an increased
lifetime risk of developing melanoma, and this risk
Tntatment is stratified based on the size of the nevus. The exact
Treatment of the patient with SJS includes hospital- risk of melanoma is controversial; however, the risk
ization with barrier isolation, fluid and electrolyte in small and medium lesions appears to be low. The
support, treatment ofsecondary infections of the skin, lifetime risk of melanoma in a giant nevus is estimated
and meticulous skin care. For oral mucosal lesions,
mouthwashes with viscous lidocaine, diphenhydr-
amine, and Maalox (aluminum hydroxide, magnesium
hydroxide) are comforting. Because corneal ulceration,
keratitis, uveitis, and panophthalmitis are possible,
an ophthalmology consultation is recommended.
Children with TEN are treated as though they had
a full~body second-degree burn. Fluid therapy and
reverse barrier isolation are critical to survival; many
patients are treated in an intensive care or bum center
unit. Intravenous Ig has been used with some success
in several series of patients with TEN, presumably
because of its effects of binding or modulating the
effect of Fas ligand. Other therapies with anecdotal
success include systemic corticosteroids, cyclospo- F16URE 10·1. Giant congenital nevus on the back.
rine, and plasmapheresis. ~!:!:1.~~--~~~~--~~..~~:..~.~-~..~:..~~~~L.........................................
Chapter 10 I Oennatology • 205
to be between 5% and 15%. This risk is highest in

INFANTILE HEMANGIOMAS
the first 5 years of life. Giant congenital nevi, par-
ticularly those on the head or overlying the spine, Infantile hemaugiomas are vascular tumors that are
also portent a risk of neurocutaneous melanosis, a common in infancy, noted in 1% to 2% of neonates.
prollferation of nevus cells within the central nervous They are more common in females, Caucasians, and
system (CNS). This risk is particularly increased in premature infants. They are classified as superficial,
patients with multiple associated satellite nevi and deep, or mixed and are typically not present at
can be evaluated by magnetic resonance imaging birth. Superficial hemangiomas are bright red and
(MRl) of the brain and spinal cord. noncomp.ressible, whereas deep hemangiomas are
Many children develop acquired nevi during subcutaneous and compressible, and often have a
infanc y and childhood, reaching a maximum num- bluish hue and superficial telangiectasias. Mixed
ber in early adulthood. Patients with more than 15 lesions have characteristics of both superficial
common acquired moles may have an increased risk and deep hemangiomas (Appx. Fig. A-8). Infantile
for melanoma in the future. Nevi can be assessed by hemangiomas can be found in any location but are
using the ABCDE rules: watching for Asymmetry, commonly seen on the head and neck. Hemangiomas
irregular Borders, variations in Color, Diameter must be distinguished from more aggressive vascular
> 6 nun. and Evolution of the nevus. Nevi that tumors, such as hemangioendotheliomas, and from
change rapidly or exhibit atypical features may need vascular malformations, which may involve capillar-
to be excised. ies, veins, arteries, lymphatics, or combinations of
A Spitz (spindle and epithelioid cell) nevus is a these. Vascular malformations are present at birth,
smooth pink to brown to jet blaclc dome-shaped pap- exhibit little to no growth in infancy, and do not
ule. The management ofSpitz nevi is controversial resolve without therapy.
Although Spitz nevi are benign. they can clinlcally The evolution of infantile hemangiomas is
and histologically mimic melanoma, particularly generally predictable. They appear during the first
amelanotic melanoma, which is more common in month of life, maintain a period ofgrowth over the
children. Some experts therefore recommend excision, next several months to a year, and then begin to
whereas others prefer watchful waiting. When these slowly involute. Involution is marked by decreasing
lesions are excised. they should be excised completely size and change in color from a bright to duller red
and reviewed by an experienced pathologist who or purple to gray. Involution may take many years;
is familiar with Spitz nevi. Incompletely excised however, m ost lesions typically resolve by 10 years
lesions often recur. of age. There may be residual textural change in the
Halo nevi are moles that have developed a 1 to skin o r superficial telangiectasias.
10 mm halo of depigmentation. This represents an The most common complication of hemangi-
immune reaction against the nevus cells. Halo nevi omas is ulceration, which occurs in 5% to 10% of
may completely regress, leaving a white macule hemangiomas. This complication typically OCCW'S
that eventually fills in. They are generally benign in in the proliferative phase and is more common on
children. but may be associated with the presence the lips, neck, and diaper area. Ulceration is painful,
of vitiligo or melanoma at another site. often bJeeds, and has risk of secondary infection
and scarring.
PREVENTION Many hemangiomas do not require treatment.
A large amount ofchildhood sun exposure and frequent Lesions requiring active intervention are those that
sunburns are associated with increased risk for the pose life-threatening or functional risks. Large heman-
development of nevi and skin cancer. Sun protection giomas may cause heart failure; lesions involving the
with a sunblock having a sun protection factor of30 airway may cause obstruction; periocular lesions are
or more against UVB as well as protection against mandatory to treat to prevent astigmatism or blind-
ultraviolet A (UVA) light is recommended. Many ness; facial lesions may produce severe disfigurement
sunscreens now contain physical sun-blockers such or interfere with eating; genital and perianal lesions
as titanium dioxide or zinc oxide that provide UV may ulcerate and cause significant pain; lumbosacral
scatter rather than absorption. Reapplying sunscreen lesions may indicate underlying spinal abnormalities
frequently during exposure, avoiding long periods of (SACRAL syndrome); facial segmental hemangiomas
sun exposure in midday, and sun-protective clothing maybe assodated with CNS, cardiovascular, eye, and
are equally important for adequate protection. sternal anomalies (PHACE syndrome); and multiple
(>5) lesions may be associated with liver and other treatments for infantile hemangiomas include topical
internal hemangiomas. ~-blockers, local or systemic corticosteroids, laser, or
In the past decade, oral propranolol has become excision where indicated. Laser treatment can also
the treatment of choice for medically complicated be useful in addressing ulceration and improving
hemangiomas. Side effects of propranolol include the appearance offibrofatty residua after involution,
hypotension. bradycardia, and hypoglycemia. Other if desired.
KEY POINTS
• Children with chickenpox are contagious from • Psoriasis occurs at sites of trauma (Koebner-
24 hours before the onset of rash until all lesions lzatlon) and Is much less pruritic than atopic
have crusted over. dermatitis.
• S, auf9US and group A P-hemolytic Strepto- • EM is most commonly caused by herpes simplex
coccus cause most bacterial skin Infections. virus type I.
• T. tonsurans is the most common cause oftinea • Nevi should be followed for asymme1ry, irregular
capitis In the United States. borders, variations In color, diameter > 6 mm,
• Acne is best treated with combination therapy, and evolution.
and choice of therapy depends on the type • Sun protection against UVB and lNA light is
of acne. recommended to prevent melanoma as well
• Benzoyl peroxide can prevent antibiotic resis- as nonmelanoma skin cancer.
tance when treating acne. • Infantile hemangiomas are vascular tumors
• Psoriasis can be treated but not cured and is that appear in the first month of life, grow for
characterized by remissions and exacerbations several months, then spontaneously involute.
that may be precipitated by streptococcal
infections.
CLINICAL VIGNETTES
VIGNETIE1
3. Which of the following is the best treatment for
A healthy 4-year-old presents with fever, malaise, and
this eruption?
a new-onset pruritic erythematous papulovesicular
L Oral acyclovir
eruption involving the trunk, face, and extremities
b. Ibuprofen
(Fig. 10-1).
c. Aspirin
1. Which of the following is the most likely diagnosis d. Administration of immune globulin
in this patient? e. Supportive therapy
L Herpes zoster
b. Pityriasis roaea VIGNETIE2
c. Rubella A 5-month-old white female presents to your clinic
d. Primary varicella with a 8 mm bright red papule on her neck. The
e. Molluscum contagiosum family is highly concerned as the •bump~ was not
present at birth and continues to grow slowly.
2. What is the incubation period for the eruption
There is no bleeding, and the child appears to be
described In Question 1?
asymptomatic.
L 10to21 days
b. 3 to 10 days 1. Which of the following is the most appropriate
c. 21 to 28 days next step in the evaluation of this patient?
d. 3 to 4 months L Referral to surgery for excision
t. 24 to 96 hours b. Referral to oncology for evaluation of a malignancy
Chapter 10 I Dermatology • 207
c. Reassurance that this is a nevus. It will stop 3. Which of the following is the best treatment for
growing by 12 to 18 months of age, then slowly this eruption?
regress over several years. L Toplcall<etoconazole cream
d. Reassurance that this is a hemangioma. tt will b. Selenium sulfide lotion
stop growing by 12 to 18 months of age, then c. Oral griseofulvin
slowly ragAM~s over several years. d. Observation
e. Biopsy for definitive diagnosis e. Oral doxycycline
2. What would be the most appropriate next step in VIGNET1E4
the management of this patient if the nodule was
A 15-year-old male presents with a 9-month history of
located In the gluteal cleft?
several nonprurltlc well-defined, round, sliver scaling,
L Anticipatory guidance and support
erythematous papules, and plaques on his elbows,
b. MAl of the spine
knees, and scalp. He has an uncle with similar skin
c. Oral prednisone findings. You make the diagnosis of psoriasis.
d. Surgical excision
e. Oral propranolol 1. Infection with which of the following bacterial
agents is most likely to trigger psoriasis?
VIGNE'ITE3 L S. auraus
A 3-year-old African-American boy presents with a few b. Klebsiella pneumoniee
focal areas of asymptomatic scalp alopecia associated c. Haemophi/us lnfluenzae
with mild scale and black dots. The lesions have been d. GAS (Streptococcus pyogenes)
present for several weeks. He also has shotty posterior e. Bartonella hense/ae
cervical lymphadenopathy.
2. Psoriasis often appears at sites of physical,
1. Which of the following is the most likely cause of mechanical, or thermal trauma. This tendency is
this scalp eruption? known as which of the following?
L T. tonsurans L Auspitz sign
b. M. canis b. Koebner phenomenon
c.T.rubrum c. Nikolsky sign
d. C. alb/cans d. Herald sign
e. Epidermophyton flocc08Um e. Onycholysis algn
2. Which of the following Is the most likely compli- 3. Children with psoriasis are at highest risk for which
cation of this eruption? of the following comorbidities?
L Osteomyelitis L Asthma
b. Meningitis b. Food allergy
c. Kerion c. Obesity
d. Cellulitis d. Skin Infection
e. Progressive secondary alopecia e. Hypothyroidism
ANSWERS
1.Answer D: not be associated with systemic symptoms such as
The Image depicts the classic eruption seen In primary fever. Pityriasis rosea often Involves the trunk and
varicella, or chickenpox. Varicella occurs in a centrifugal flexural regions and begins with a single, larger lesion
manner, with lesions starting on the head and trunk known as the herald patch. The individual lesions of
and spreading to the extremities. The papulovesicles pityriasis rosea are ovoid, pink to violaceous patches
seen In varicella are often described as •dewdrops on or thin plaques with a cellarette of scale. Rubella may
a rose petal." The individual lesions should be present present in newborns as violaceous papules and nodules
in all stages including erythematous papules, papu- r'blueberry muffin• rash) or as enumerable erythema-
loveslcles, and crusted papules. Fever and malaise tous macules and papules coalescing on the face and
are common prodromal symptoms. trunk. Molluscum is a pearty, translucent, umbilicated
Herpes zoster usually occurs In a dermatomal papule most commonly found In moist areas such as
distribution (unless disseminated) and may or may the axillae, groin, and buttocks.
VIGNB'TE 1 Question 2 VIGNETTE 2 Question 2

2. Answer A: 2.Answer B:
The incubation pertod for varicella is 10 to 21 days. Infantile hemangiomas located In the lumbosacral r9gion
The virus is spruad via airborne droplet& and colo- may be associated with spinal dysraphism including
nizes the respiratory tract. The virus then replicates tethered cord, myelomeningocele, lipoma, and other
in the regional lymph nodes over the next 2 to 4 days. spinal abnormalities. MRI to evaluate the spinal canal
foDowed by spread to the reticuloendothelial system is essential for early diagnosis and management to
over 4 to 6 days, resulting in a primary viremia. A sec- avoid serious complications at a later age. Therefore,
ondary viremia develops over the next week, with the anticipatory guidance and support would be inapp~
virus spreading to viscera and skin, at which time the priate. The other 1reatment options listed should be
classic skin lesions develop. Patients are contagious deferred until the imaging study confirms or rules out
from 24 hours before the rash until all lesions crust associated anomalies of the spine.
over, which usually takes place within 5 to 7 days. The
other choices do not fit the time period for Incubation VIGNETTE 3 Quasllan 1
of vartcella. 1. Answer A:
Tinea capitis can be Identified by one or several patches
VIGNB'TE 1 Question 3 of scalp alopecia that are often associated with scale,
3.AnswerE: crust, and black dots. The black dots represent broken
Treatment of varicella Is based on several factors. hair shafts that occur when dermatophytes weaken
Most uncomplicated cases of varicella are treated the shaft and allow breakage. T. tonsul8fls accounts
with supportive therapy that may include antipyret- for more than 90% of tinea capitis infections in the
ics, daily "oatmeal• baths, and oral antihistamines United States. M. canis is the most common cause
for pruritus. Ibuprofen may be associated with an of tinea capitis wortdwide. T. rubrum does not cause
increased risk of streptococcal cellulitis in the setting tinea capitis; however, it Is the most common cause
of primary varicella. Aspirin should be avoided to of tinea corporis and tinea pedis. E. floccosum causes
prevent the rare complication of Reye syndrome. tinea pedis. C. a/bicans does not cause tinea capitis.
Oral acyclovir should be considered for patients at
risk for or with more severe disease Including ado- VIGNETTE 3 Question 2
lescents, those with chronic medical conditions, or 2.AnswerC:
those who arelmmunocompromlsed. Varicella-zoster A kerion Is a severe Inflammatory reac1ton presenting
immune globulin should be given within 96 hours as a boggy, pustular, alopecic eruption at the site of
to susceptible individuals (those who have not had tinea capitis because of an aggreesive host immune
primary varicella or Immunization and are at high response toward the dermatophyte. Kerions require
risk for serious disease or are pregnant) exposed systemic therapy with oral antifungal agents; oral
to varicella. prednisone is also administered to decrease inflam-
mation. None of the other choices occur with tinea
VIGNmE 2 QUI8tion 1 capitis, although a secondary bacterial folliculitis can
1.Answer D: develop and requires antibiotic therapy.
Infantile hemangiomas are common benign cutaneous
vascular tumors (rather than nevi) seen in infancy with VIGNETTE 3 Question 3
a predictable growth pattern of proliferation for 6 to 3.AnswerC:
12 months, followed by a slow regression over several Dermatophytes Invade the hair follicle In tinea capHis;
yean~. Therefore, the best answer Is reassurance that therefore, systemic antifungal therapy Is required for
this Is a hemangioma that will stop growing by 12 to penetration of the hair follicle. Oral griseofulvin Is the
18 months and regress over several ye81'8. The his- only syatemic antifungal agent listed and is the most
tory and clinical examination support the diagnosis; commonly used antifungal to treat tinea capitis in
therefore, a biopsy is not required. All uncomplicated children. Griseofulvin is Food and Drug Administration
hemangioma involving a low-risk site does not require approved for tinea capitis in children, has an excellent
any further treatment. High-risk sites include the face safety record, and is well tolerated. Most cases of
(especially lesions that obscure vision by enlarging the tinea capitis require 4 to 8 weeks of oral therapy. The
skin or lids around the eye}, genital and lumbosacral medicine must be taken with or directly following a
regions; options for these patients include surgery, meal and is best absorbed with fatty foods. Topical
laser, or systemic therapy. Oncology referral would ketoconazole cream will not penetrate the hair follicle.
be inappropriate as this is a benign lesion that can Selenium sulfide lotion can be used as an adjunctive to
ba followed clinically by the primary physician or a systemic antifungal therapy to decrease shedding of
dermatologist. viable spores but Is not a primary treatment. Antibiotics
Chapter 10 I Dermatology • 209
ara not indicated tor tinea capitis, and observation from a psoriasis plaque. The Nikolsky sign refers to
would not be appmprtate. separation of the superficial layers of the epidermis
with light pressure, a finding seen In SSSS. A herald
VIGNET'IE 4 Qu..aan 1 patch Is the first, and often largest, charactertstlc le-
1.Answer 0: sion seen in pityriasis roses. There is no "herald Sign.•
GAS (S. pyogenes) is the most likely bacteria to trigger Onycholysis refe111 to aeparation of the distal nail plata
peoriaais. GAS can induce guttate paoriaaia or cause a from the nail bed, a common finding in psoriatic nail
flare of existing psoriasis. Psoriasis may be triggered by disease. There is no "onycholysis sign."
any stress on the Immune system including illness and
psychological stress. GAS is the most likely bacteria VIGNETlE 4 QuMtlon 3
to trigger/worsen psoriasis. 3.AnswerC:
Obesity is the most common comcrbidity in both children
VIGNETTE 4 QuestiOn 2 and adults with psoriasis. Children with psoriasis are
2.Answer B: also at risk of hypertipidemla, hypertension, diabetes,
Psoriasis developing at sites of trauma is an isomor- and early cardiovascular disease. Asthma and food
phic response known as the Koebner phenomenon. allergy are comorbldltles associated with atopic der-
It Is often related to minor trauma or sunburn. The matitis, not psortasls. Skin superinfection In psoriasis
mechanism for this reactton Is not known. TheAuspltz Is uncommon, as oompared to atopic dermatitis that
sign refers to pinpoint bleeding when scale Is removed Is frequently superlnfected durtng disease nares.
cardiology
Michael R. c.r, Philip T. Thrush, R. Gregory Webster, and
Bradley S. Marino
of these patients. Children may acquire functional

INTRODUCTION
heart disease (e.g., myocarditis or cardiomyopathy},
The field of pediatric cardiology has experienced arrhythmia, or, more rarely, structural heart disease
a remarkable evolution over the past half century (e.g., endocarditis).
because of advances in diagnostic techniques,
interventional cardiac catheterization and cardiac
HEART MURMURS
surgical procedures, pediatric anesthesia, neonatal
medicine, and cardiac intensive care medicine. Heart murmurs are very common in children, with
Functional heart murmurs are very common in some reports suggesting up to 90% of children having
childhood and do not signify disease. The incidence a murmur at some point. Functional (•innocent")
of structural congenital heart disease (OID) is ap- heart murmurs are thought to be the result of
proximately 8 in 1,000 live births. Critical congenital normal. physiologic flow turbulence. Each of these
heart disease (CCHD), requiring cardiac surgery or murmurs has specific characteristics that generally
an interventional cardiac catheterization procedure allow it to be confidently diagnosed by an adequate
in the neonatal period, occurs in approximately 25416 physical examination alone {Table 11- l}.lt is equally
...,..........
T.IILE 11-1. Functional Heart Munnurs
!Munn• ,...,,lllllln Cl••twllllcl .__ !

i Peripheral Neonate (birth Medium-pitched systolic ejection 1\J.rbulence of flow where the main I
!§;·~ ::~) ~~~~~ ~;;; I

· the left lower sternal border and ventricle '
L~hum ~2::::::= Thrn~t8owm~J...W~~~ ~

9-7y
I
!
==~=:.:=
=:':!.oction""""""
CW>tld b - :;..~~-=
3-ll y heud but
....,lo<venocava_.
1D the
'
1
·',,,,,_
,
IPulmonary flow 6 y to Systulic ejection IDUJ'IDUI' best heard Thrbulmce ofOow where the main I
1 murmur adolacence at the left upper sternal border pu1mooary art:ery CDI1IIII!dB to the rigbt j
L.. . . . . . . . . . . . ... . .. . . .. . . .... . . . . . ... . . ... . . ... . . ... . . ... . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ... . ~.~~-~-~~--~2......!
-
210
Chapter 11 I Cardiology • 211
IAILE 11·2. COncerning Signs on cardiac however, it rarely has a primary cardiac origin.
Examination Children who have syndromes associated with heart
disease (e.g., Turner, Down, Wtlli.ams, Noonan, and
Heaves, thrillJ, or other aboormal or increaled DiGeorge/velocardiofacial) are at a higher risk for
preconiial activity
a pathologic murmur. The family hUtory .should
Brachiofemoral delay and/or decreaaed femoral include questions regarding syncope, sudden car-
pulse. c:Uac death (including details as available), sudden
Abnormal ftm or secx~nd heart sound (abnormal unexplained death (drownings, single-occupancy
splitting) motor vehicle accidents, falls, deaths during sleep),
Extra heart sounds cardiovascular events (heart attacks or stroke be-
Gallop rhythms (S., S., or aummation pllop) fore 50 years of age), connective tissue disorders
' (Marfan syndrome), hyperlipidemia, arrhythmia,
Ejection click
pacemaker/implantable cardioverter-deflbrillator
Opening map (lCD) placement, valvular disease, cardiomyopathy,
Pericardial rub ' andCHD.
Murmurs (pathologic in quality) '
, • Very loud or harsh In quality Physical Examination
i • Doea not chanp in int.enaity relative to patient The physical examination includes a compari-
L........~.~-~~-~ -~~-~-~~~~-~~..~.!~~.............1 son of the child's weight and height to normal
values for age and gender, as well as to previous
measurements on an appropriate growth curve.
important to recognize the signs and symptoms of Careful attention should be given to vital signs,
potentially pathologic murmurs, in order to facilitate including heart rate (Table l l -3), reapiratory rate,
rapid diqnosis and possible intervention (Table 11-2). and blood pressure. The examiner should assess
for cyanosis and digital clubbing (indicating a
CLINICAL MANIFESTATIONS right-to-left shunt), as well as signs of congestive
History heart failure (hepatomegaly or edema). Pulses should
Infants with significant heart disease may have a be palpated in both upper and lower extremities
history of difficulty feeding, tachypnea, irritabil- and compared. The examiner should inspect and
ity, diaphoresis, cyanosis, and/or failure to thrive. palpate the chest for placement of the apical im-
Symptoms in older patients may include shortness pulse and any heaves or thrills. Auscultation allows
of breath, dyspnea on exertion, exercise intoler- detection and characterization of heart sounds
ance, palpitations, paroxysmal nocturnal dyspnea, (normal and extra) and murmurs. Murmurs may
orthopnea, and syncope. Chest pain is a frequent be systolic, diastolic, or continuous and should be
complaint in older children and adolescents; graded according to their intensity.
TABLE 11-3. Age-Related Heart Rates
,...............
,.
! 2-12nt 1-IJ ~ur 12-1IJ
i Minimum heart rate (bpm) 82± 17 75 ± 11 61 ± 9 51± 5 47±6
j Mean heart rate (bpm) 147± 12 135 ± 10 107 ± 12 87± 8 81±9
! MaxiDwm heart rate (bpm) 213 ± 17 204± 13 180 ± 14 165 ± 17 164± 19
!Maximum RR interval 0.87 ± 0.1 1.00 ± 0.2 1.20 ± 0.2 1.36± 0.2 1.45 ± 0.2
~ All values are derived tom 24-hour rhythm monilcrs h the ambulatory setting. values are expressed as mean ± standard deviation.
j The o~inal reference alao provides values tor hospitalized patients. !,
!Abbreviations: bpm, beats per mlrute; IT"IIIUnum RR Interval, the longest Interval, l"l""lea$Ured In seconds, between two consecutiiJe
!QRS complexes. !
! Adapted from Messin MM, Bourguignon! A, Gerard P.. Study of cardiBc rate and rhythm patterns in ambulatory and hospit81ized children. !
!...............................................................................................................................................................................................
Cardiology. 2005;103:174-1 79.
-.........................................................................-.....................::
DIAGNGSnC EVALUATION Cyanosis is one of the most common presentations

Pulse oximetry assesses oxygen saturation in the of CHD in the newborn (Table 11-5). Pulmonary
blood. The chest radiograph evaluates heart size and disorders may lead to cyanosis as a result ofprimary
pulmonary vascularity. The heart size should be less tuns disease, airway obstruction. or extrinsic com-
than 5()1)6 ofthe chest diameter in children above age 1 pression of the Juns.Neurologic causes ofcyanosis
year. A prominent thymic shadow maymimlccarcflo.. include central nervous system dysfunction and
megalyin neonates andin&nts. Pulmonaryvascularity respiratory neuromuscular dysfunction.
is usually increased in lesions with large left-to-right
shunts (e.g., ventricular septal defuct [VSD], patent CLINICAL MANIFESTATIONS
ductus arteriosus [PDA]), and may be diminished in History and Physical Examination
lesions such as tetralogy of Fallot (TOF). All patients A complete birth history that includes maternal his-
with suspected pathologic murmurs shouldundergo an tory; prenatal, perinatal, and postnatal complications;
electrocardiogram (ECG) and eclwcardiogram (ECHO). history of labor and delivery and neonatal course
should be obtained. The exact timing of when the
TREATMENT child developed cyanosis is critical, as certain forms
The treatment of heart disease may be medical, of CHD present at birth, whereas others may take
surgical. interventional (cardiac catheterization), or as long as 1 month to become evident.
a combination of these, depending on the specific The initial physical examination should focus
abnormality. on the vital signs and the cardiac and respiratory
examinations, assessing for evidence of right, left,
or biventricular congestive heart failure and respi-
EVALUATION OF THE CYANOTIC ratory distress. Blue or dusky mucous membranes
NEONATE are consistent with central cyanosis. Rales, stridor.
Cyanosis is a physical sign characterized by a bluish grunting, flaring, and retractions should be evalu-
tinge of the mucoua membranes, sldn, and nail beds. ated on pulmonary examination. On cardiovascular
Cyanosis results from hypoxemia (decreased arte- examination, the precordial impulse is palpated.
rial oxygen saturation). Cyanosis does not become and the clinician should evaluate for systolic or
clinically evident until the absolute concentration of diastolic murmurs, the intensity of S1, ~ splitting
deoxygenated hemoglobin is at least 3.5 g!dL. Factors abnormalities, and the presence of an s3 or s4 gallop,
that influence the degree ofC}'Ulosis include the total ejection click, opening snap, or rub. Examination
hemoglobin concentration (related to the hematocrit) of the extremities should focw on the strength
and factors that affect the ~ dissociation curve (pH. and symmetry of the pulses in the upper and lower
P~ temperature, and ratio of adult to fetal hemo- extremities, evidence ofedema, and cyanosis ofthe
globin). Cyanosis will be evident sooner and can be nail beds. Hepatosplenomegaly may be consistent
more pronounced under the following conditions: with right ventricular or biventricular heart failure.
• high hemoglobin concentration (polycythemia) DIAGNOSTIC EVALUATION

• decreased pH (acidosis)
The goal of the initial evaluation of the cyanotic ne-
• increased Pcol
onate is to determine whether the cyanosis is cardiac
• increased temperature
or noncardiac in origin. Preductal and postductal
• increased ratio of adult to fetal hemoglobin
oxygen saturation and four-extremity blood pressures
Cyanosis should not be confused with acrocyanosis should be documented. An .ECG, chest radiograph,
(blueness of the distal extremities only). Acrocya- and hyperoxia test should be performed.
nosis is caused by peripheral vuoconstri.ction and Preductal (right upper extremity) and postductal
is a common finding during the first 24 to 48 hours (lower extremity) oxygen saturation measurements
of life, although children outside of the newborn permitevaluation for dijfuential cyanosis and reverse
period can also manifest this finding. differential cyanosis. When the preductal saturation is
higher than the postductal measurement, differential
DIFFEREN11AL DIAGNOSIS cyanosis exists. Possible diagnoses associated with
Cyanosis inthe newborn may be cardiac, pulmonary, differential cyanosis include persistent pulmonary
neurologic, or hematologic In origin (Table 11-4). hypertension of the newborn (PPHN; see Chapter 2)
It is important to investigate all possible etiologies. and left ventricular outflow tract obstructive lesions
UILE 11-4. Differential Diagnosis of Cyanosis in the Neonate

Clnl. .
Dlldill--ilulqmdDJt mi#inglesiou
Truncua arteriosua
........ ~~.
Pa:siateart pu]monary hypertenaion of the newborn

Airway ob&trllction
Total anomalous pulmonary venous return <lt.oanal atresia
D-tranapolition of the great arteries Vocal cord paralym
l.aJotu with ductlll-tkpMrklttprllmonf117 bloodflow Laryngotracheomalacla
Tetralogy of Fallot with pulmonary atresia" E:ctrinsic compt'U6ion of1M lungs
Critical puhnonic stenolil Pneumothorax
Tricuspid valve atresia" with normally related great Chylothorax
arteri~
Hemothorax
; Pulmonic valve atresia with intact ventricular septum Nearolopc
!Laloru wlth ducttll-tlqtmtknt &y&temlc bloodflow CNS dysjiutction
: Hypoplastic left heart syndrome Drug-induced depreuion of respiratory drive
!Interrupted aortic arch Postasphyxial cerebral dysfunction
!Critical coarctation ofthe aorta Central apnea
! Critical aortic stenosiJ kspinltory MIII'OmMKfiW dysfunction
i Tricuspid valve atresia with transposition of the great Spinal mi.Uicular atrophy
! arten~
:
Infant botulism
I PuJmona..,. Neonatal myasthenia gravis
!Primluy lwrgtllJetu8 HeJMtolop
!Relpiratory diBtrea syndrome Methemoglobinemia
j Meconium aspiration Polycythemia
!•A patent d.Jctus arteriosus may mprow mixing, especially with an intact ventricular septum.
! bMost rams.
: onooooooooooooooo"'''''''"'" ' ' '' ' '' ' '' " ' " " " "' ' " "" " " " " " " " " " "" ' " ' ' ' ' "' ' ' ' ' '' ' ' '' '' ' '' ' ' ' - ' '' ' ''''"' ' '' ' ' ' ' ' ' ' '' ''''""'''''''' ' ' '' n " ooooooooooooooooooooooooo"'"'''"'''''''' ' " " "" " '''" ' ' "' " ' "' """" '""'' " " ' "' ' "' ' ''''"u"' ' " ' '" " ' '" " ' ' ' ' " ' ' '" :
such as interrupted aortic arch (IAA), critical coarc- lower than the postductal saturation. and reverse
tation of the aorta, and critical aortic stenosis. This differential cyanosis exists. In the absence ofa mea-
phenomenon occurs when deoxygenated blood from surement error, this can only occur in the presence of
the pulmonary circulation enters the descending aorta transposition of the great arteries (TGA) with either
through a PDA, decreasing the postductal oxygen PPHN or coarctation of the aorta/IAA. In this situ-
saturation. More rarely, the preductal saturation is ation, highly oxygenated blood from the pulmonary
circulation enters the descending aorta through a
T.ULE 11-1. Most Common Congenital Heart Disease PDA, increasing the postductal oxygen saturation.
Leading tD Cyanosis in the Newborn Four--extremity blood pressure measurements that
show a systoUc blood pressure In the upper extrem-
1ThtrUogy of FaDot
ities greater than 10 mm Hg higher than that in the
j Tranapoaltion of the great veuell lower extremities are consistent with coarctation
~ Trh:ulpid atresia of the aorta or other lesions with ductal-dependent
j Pulmonary atresia with intact ventricular septum systemic blood flow with a restrictive ductus arte-
iTruncuJ arWiosua riosus. Practicallyspeaking, measurement ofa right
upper extremity blood pressure and one In either
! Total anomalous pulmonary venous connection leg should be sufficient and may introduce less
!..~~~-~-~-~~-~~. . . . .... . . . . . . . . . . . . . . . . . . . . . . . . . . . ! measurement error. The ECG evaluates the heart
rate, rhythm, axis, intervals, forces (atrial dilation. mixing of pulmonary and systemic venous return or
ventricular dilation/hypertrophy), and repolarization abnormalities in intracardiac flow. They present with
(abnormal Q-wave pattern. srrr wave abnormalities, variable degrees ofcyanosis because ofintracardiac
and corrected QT interval). mixing or a paucity of intracardiac mixing.
In the absence of rapid access to ech.ocardiog-
raphy, a hyperoxia test should be carried out in all lRUNCUS ARIERIOSUS
neonates with a resting pulse oximetry reading less Tmncus arteriosus (Appx. Fig. A-9) is a rare form of
than 85\11). The hyperoxia test con&ist:s of obtaining cyanotic CHD that coMists of a single arterial vessel
a baseline right radial (preduct:al) arterial blood gas arising from the base of the heart, which gives rise
(ABG) measurement with the child breathing room to the coronary, systemic, and pulmonary arteries.
air (FI~ = 0.21) and then repealing the measure- The number of valve leaflets varies from two to six.
ment with the chlld inspiring as close to 100% oxygen and the valve may be insufficient, stenotic, or both.
(FI~ = 1.00) 85 possible. Pao2. should be measured A VSD is almost always present. There is complete
directly via arterial puncture. Pulse oximetry mea- mixing ofsystemic and pulmonary venous blood in
surements are not appropriate for interpretation of the truncal vessel. A less common form is associated
the hyperoxia test. A Pa~ greater than 250 mm Hg with IAA. This lesion, along with other conotruncal
on 100% oxygen essentially rules out fixed right-to-left anomalies (TOF, IAA, certain forms ofVSD, isolated
shunting in cardiac disease. Such patients are more arch anomalies, and vascular rings), is frequently
likely to have a puhnonary etiology for their cyanosis. associated with 22qll microdeletion (i.e., DiGeorge
A Pa~ less than 50 to 100 m.m Hg on 100% oxygen syndrome).
is very suggestive of a cardiac lesion.
Clinical Mantre&latlon&
The combined results ofthe tests desaibed earlier
The clinical manifestations of truncus arteriosus
will typically point the cliniclan in the right direction
vary depending on the amount of pulmonary blood
85 to the source of the cyanosis and. in some cases,
flow. At birth. a nonspecific murmur and minimal
may also suggest a specific diagnosis. If a cardiac
symptoms may be present, because oflimitation of
caw~e is deemed likely, an ECHO and cardiology
pulmonary blood flow by the typical elevated neonatal
consultation should be obtained.
pulmonary vascular resistance (PVR). Congestive
TREATMENT heart failure/pulmonary overcireulation develops in
a matter of weeks as the PVR falls and pulmonary
Cyanotic infants require immediate assessment of
blood flow increases at the expense ofsystemic blood
the ABCs (Chapter 20) and stabilization. Prosta-
flow. This is typically manifested by tachypnea and
glandin E1 (PGE1) administration, via continuous
poor weight gain. On cardJac examination, a systolic
intravenous infusion, should be started in any un-
ejection murmur is heard at the left sternal border,
stable infant with a strong suspicion of CCHD. In
and there is usually a loud ejection click and a single
newborns with mixing lesions or defects that have
second heart sound (~). Pulse pressure is widened
ductal-dependent pulmonary or systemic blood
and bounding arterial pulses are palpated. A chest
flow, PG~ acts to maintain patency of the ductus
radiograph reveals mild cardiomegaly, increased
arteriosus until definitive surgical treatment can be
pulmonary vascularity, and occasionally a right
accomplished. Rarely, the patient with CHD may
aortic arch (30% of the time). Seventy percent of
become progressively more unstable after the insti-
children with truncus arteriosus have biventricular
tution ofPGE1 therapy, indicating a defect that has
hypertrophy on ECG. Hypocalcemia and absence of
obstructed pulmonary venous flow (e.g., obstructive
the thymic shadow (on chest radiograph) may occur
total anomalous venous return).
if the patient has DiGeorge syndrome.
Traabnant
CYANOTIC CONGENITAL HEART Surgical repair is performed in the neonatal period.
DISEASE: DUCTAL-INDEPENDENT This involves closing the VSD, separation of the
MIXING LESIONS pulmonary arteries from the truncal vessel (using
The following lesions typically do not depend on a the truncal valve and vessel as the neoaortic valve
PDA to provide either adequate systemic or pulmo- and neoaorta), and placing a conduit between the
nary blood flow. They represent forms ofCHD where right ventricle (RV) and the pulmonary arteries to
there is either significant, obligatory intracardiac pnwmeprumonarybloodflow.
D·TRANSPOSITION OF THE GREAT ARTERIES ECG generally reveals right-axis deviation and right
I>-transposition of the great arteries (D~TGA) (Appx. ventricular hypertrophy.
Fig. A-10) accounts for 5% of CHD and is the most Treatment
common form ofcyanotic CHD presenting in the fust PG~ administration is generally necessary to increase
24 hours oflife. There is a 3:1 male predominance. aorta (deoxygenated) to pulmonaryartery (oxygenated)
In this defect, the aorta arises anteriorly from the shunting through the ductus arteriosus, which may
morphologic RV, and the pulmonary artery arises further improve mixing. A balloon atrial septostomy
posteriorly from the left ventricle (LV). This config- (Rashkind procedure) may need to be performed
uration puts the pulmonary and systemic circuits to enlarge the PFO and thereby increase atrial level
in parallel rather than in series; the systemic circuit mixing, which is the key to optimal intracardiac
(deoxysenated blood) is recirculated through the body, mixing and improvement in systemic saturations
whereas the pulmonary circuit (oxygenated blood) in the presence of restriction to flow at the atrial
recirculates through the lungs. Unlike ductal-depen- septal level The arterial switch procedure, which
dent lesions, an adequate~sized patent foramen ovale restores the LV as the systemic ventricle, is usually
(PFO) is required to allow mixing ofthe systemic and performed during the first week of life.
pulmonary circulations and is necessary for survival,
rather than pure patency ofthe ductus arteriosus. The TOTALANOMALOUSPUUMONARYVENOUS
three basic variants are D-TGA with intact ventricular CONNECTION
septum (60%), D-TGA with VSD (30%), and D-TGA
Total anomalous pulmonary venous connection
with VSD and pulmonic stenosis (1096).
(TAPVC) (Appx. Fig. A~ll) is a rare lesion (1% to
Clinical Manifestations 2% ofCHDs) in which the pulmonary veins are not
Cyanosis is present from birth, with the degree of connected to the left atrium. The pulmonary veins
desaturation dependent on the amount of mixing come to a confluence behind the left atrium, which
across the PFO. The infant is often tachypneic, but then drains anomalously into the right atrium either
wilhout respiratory distress. On cardiac examination. directly or indirectly through other systemic venous
a loud, single S1 is apprec iated. A systolic murmur pathways.
indicates the presence of a VSD and/or pulmonic
stenosis. The chest radiograph usually reveals mild Thue a~fow varlant6:
cardiomegaly and increased pulmonary vascular
• Supracardiac (50% of cases): Blood d.ralns via a
markings. An "egg-shaped silhouette" is charac-
vertical vein into the innominate vein or directly
teristic and results from the anterior aorta being
into the superior vena cava.
superimposed on the posterior pulmonary artery,
• Cardiac (ZOCJ(, of cases): Blood drains into the
thereby narrowing the mediastinum (Fig.ll-1). The
coronary sinus or directly into the right atrium.
• Infradiaphrapnatlc: (20% ofcases): Blood drains
via a vertical vein into the portal or hepatic veins.
• Mixed (10% ofcases): Blood returns to the heart
via a combination of the routes described earlier.
TAPVC can occur with or without obstruction.

Pulmonary venous flow is obstructed when the
anomalous vein enters a vessel at an acute angle
or courses between or through other mediastinal
or infradiaphragmatic structures. The presence or
absence ofobstruction determines whether there is
pulmonary venous hypertension and severe cyanosis
(obstruction) or increased pulmonary blood flow
and mild cyanosis (no obstruction). Because there
is no pulmonary venous return to the left side ofthe
heart, shunting of blood from right to left (through
FIGURE 11-1. Chest x-r8P/ of transposition of the great an atrial septal defect [ASD] or PFO) is necessary
~~!~:..Q.~.~.~~..~.~~.~..~r..q~·...~E~.!!:o/...~~~!~:1..................... for blood flow to the systemic vascular bed.
Clinical Manltas1atlans CYANOTIC CONGENITAL HEART

The clinical presentation varies greatly depend- DISEASE: LESIONS WITH
ing on the pathway of pulmonary venous return DUCTAL-DEPENDENT PULMONARY
and whether it is obstructed. The infant without BLOOD FLOW
obstruction may present with mild cyanosis at
birth and progressive congestive heart failure The following lesions typically depend on patency of
because of excessive pulmonary blood flow. An the dactus arteriosus to provide adequate pulmonary
active precordium will be present with a right blood flow, but are quite variable in their anatomy
ventricular heave, a wide and fixed split ~ with and physiology. All present with cyanosis because of
a loud pulmonary component, and a systolic a paucity of pulmonary flow, but generallymaintain
ejection murmur at the left upper sternal border. systemic perfusion.
On chest radiograph, cardiomegaly is noted with
increased pulmonary vascularity. The heart often TRICUSPID ATRESIA
has the characteristic contour ofa •snowman,• seen Tricuspid atresia (Appx. Fig. A~l2) is a rare defect
when the pulmonary veins drain via a vertical vein (<1% of CHD) that is characterized by complete
into the innominate vein and ultimately the right atresia of the tricuspid valve. This lesion leads to
superior vena cava, although this is often a later severe hypoplasia or absence of the RV. Tricuspid
finding. On ECG, right-axis deviation and right atresia can be divided into two types: tricuspid atre-
ventricular hypertrophy are seen. sia with normally related great arteries (NRGA) or
Infants with pulmonary venous obstruction tricuspid atresia with TGA. Ninety percent ofcases
display marked cyanosis and respiratory distress. of tricuspid atresia have an associated VSD. In this
A loud, single (or narrowly split) S:z is heard on anatomy, the systemic venous return is shunted
cardiac examination. and tachypnea with respira- from the right atriwn to the left atrium through the
tory distress may be present. The chest radiograph PFO or an ASD. The left atrium and LV handle both
generally shows normal heart size with markedly systemic and pulmonary venous return. Oxygenated
increased pulmonaryva.scular markings and diffuse and deoxygenated blood is mixed in the left atrium.
pulmonary edema. Right ventricular hypertrophy The VSD allows blood to pass from the LV to the
is seen on ECG. These infants are often initially right ventricular outflow chamber and pulmonary
misdiagnosed as severe PPHN or severe primary arteries. The vast majority of patients with tricuspid
lung disease. Of note, supra.cardiac total anomalous atresia with NRGA have pulmonary stenosis. The
pulmonary venous return (TAPVR.) can present with amount of pulmonary blood flow (and therefore the
reverse differential cyanosis because of the highly degree ofcyanosis) in these patients is dependent on
oxygenated pulmonary venous return coursing from the size of the VSD and the degree of the pulmonary
the superior vena cava, across the tricuspid valve, and stenosis. The larger the VSD and the lesser degree
then across the PDA to the lower extremity systemic of pulmonary stenosis leads to increased pulmonary
circulation. On rare occasions, the diagnosis ofinf- blood flow and higher saturations. Alternatively, the
racardiac TAPVR is suspected when a consistently smaller the VSD and the greater degree of pulmo-
elevated Pa0:1 is found on a venous blood gas analysis nary stenosis leads to decreased pulmonary blood
from an umbilical venous line (because of the highly flow and lower saturations. In occasional patients,
oxygenated pulmonary venous return entering the pulmonary stenosis is mild, pulmonary blood flow
inferior vena cava). is adequate, and cyanosis is minimal, but when
pulmonary stenosis is signi.6.cant, cyanosis may be
Treabnent severe. The latter patients may depend on patency
Corrective surgery is performed emergently in the of the ductus arteriosus to provide sufficient pul-
newborn period if pulmonary venous obstruction monary blood flow. Patients with tricuspid atresia
is present and is one of the few cardiac lesions with pulmonary atresia will by definition have ductal
where this approach is required. If the anomalous dependent pulmonary blood flow.
pulmonary veins are unobstructed (more common In 30% ofcues, transposition ofthe great vessels is
in the supracardiac or cardiac subtypes), repair also present, which results in blood passingfrom the
is elective and typically takes place during early LV through the VSD to the right ventricular outflow
infancy and often in the neonatal period around to the ascending aorta. Tricuspid atresia with TGA
the time of d.iainosis. is often associated with coarctation ofthe aorta and/
or aortic arch hypoplasia. Unlike tricuspid atresia maintain consistent and adequate pulmonary blood
with NRGA, which has ductal-dependent pulmonary flow. The modifted BTS is a Gore-Tex tube placed
blood flow, tricuspid atresia with TGA may have between the subclavian artery and the pulmonary
ductal-dependentsystemic blood flow. The variable artery. Some centers are now utilizing ductal stent-
anatomy of tricuspid atresia, as described earlier. can ing to maintain pulmonary blood flow instead of
manifest as different physiologic states, and this is performing a modified BTS. Ifthe pulmonary blood
very important in the management of this defect. flow is adequate, surgery will not be required during
the neonatal period. These infants are often described
Clinical ManlfestaUon& as having balanced circulations, suggesting adequate,
The clinical features of tricuspid atresia are dependent but not excessive pulmonary blood flow and normal
on the degree of pulmonary stenosis present. Most systemic blood flow. Rarely, infants with increased
commonly, neonates will have significant pulmonary pulmonary blood .flow may require banding of the
stenosis or even pulmonary atresia. These infants pulmonary artery to restrict flow. Regardless of the
present with progressive cyanosis during the first 2 neonatal course, all infants with tricuspid atresia will
weeks of Ufe. Ifpulmonary atresia is present, severe undergo further surgeries to separate the pulmonary
cyanosis is noted when the ductus arterioms becomes and systemic circulations. In infancy, a cavopulmo-
restrictive. Less commonly, infants may have minimal nary anastomosis (anastomosis of the superior vena
or no pulmonary stenosis. These infants may have cava to the pulmonary artery, called a hemi-Fontan
normal or even increased pulmonary blood flow or bidirectional Glenn shunt) is performed to pro-
and may have no card1ac symptoms or symptoms vide stable pulmonary blood flow. A final surgery is
ofcongestive heart failure. On cardiac examination, performed at 2 to 5 ~ars ofage. Th.is procedure, the
abnormalities include the holosystolic murmur ofa Fontan procedure, redirects the inferior vena cava
VSD at the left lower sternal border, a systolic ejec- and hepatic vein fiow into the pulmonary circulation.
tion murmur across the pulmonary valve (because A child with tricuspid atresia with TGA should
ofincreased flow across the valve). and possibly the have PGE1 started to maintain ductal patency and
continuous munnur of a PDA. On ECG, there is sy.temic blood flow. Surgical management fur tri-
left-axis deviation (one of the few lesions where this cuspid atresia with TGA depends on the degree of
finding is common), right atrial enlargement, and left arch obstruction. Patients with hemodynamically
ventricular hypertrophy. Findings on chest radiograph significant arch obstruction will require a more
include normal heart size and variable degrees of extensive surgery with reconstruction of the aortic
pulmonary vascularity, depending on the presence, arch and placement of a reliable source ofpulmonary
absence, or variable degree of pulmonary stenosis. blood flow, generally in the Corm ofa modified BTS.
Neonates with tricuspid atresia and TGA also pres- Similar to patients with tricuspid atresia and NRGA,
ent with cyanosis and possibly poor feeding. Ifsevere these patients will proceed down a single-ventricle
arch hypoplasia or coarctation of the aorta is present, palliation pathway with a cavopulmonary anasto-
the patient may present with shock after closure of mosis, followed by Fontan completion.
the ductus arteriosus. Clinical severitydepends on1he
degree ofarch obstruction. The chest radiograph may TET1W.OGY OF FALLOT
reveal cardiomegaly and increased pulmonary vascular
TOF (Appx. Fig. A-13) is the most common CHD
markings as the PVR 6ills and the child's pulmonary
(10%) presenting in childhood. Fifteen percent ofall
blood.tlowinc:reues, resulting in congestive heartfailure.
patients with TOF have 22qll microdeletion; 50% of
Treatment patients with 22qll microdeletion have TOF. The four
Treatment of tricuspid atresia is determined by the components ofTOF include an anterior malalignment
specific anatomy and physiology, which as noted VSD, which results in valvar and subvalvar pulmonary
earlier, is variable and dependent on the amount of valve stenosis, rlshtventricular hypertrophy, and an
pulmonary blood flow and the presence or absence "overriding" larJe a.scendingaorbl (Fig.ll-2). Infants
of an aortic arch abnormality. A child with tricuspid with TOF are cyanotic becaUJe ofrightJtoJlef't shunting
atresia with NRGA and restriction to pulmonary blood across the VSD. The degree of right ventricular out-
flow should have PGE1 started to maintain ductal flow obstruction determines the timing and severity
patency. Surgical management for tricuspid atresia of the cyanosis. In neonates, blood shunted from
with decreased pulmonary blood flow may involve the aorta to the pulmonary artery through the PDA
placing a modified Blalock-Taussig shunt (BTS) to provides additional pulmonary blood flow. Infants
chest x-ray. The ECG reveals right·axis deviation

and right ventricular hypertrophy.
Traabnant
The treatment of"Tet spells" is aimed at dimini.shing
right-to-left shunting by increasing systemic vascu-
lar resistance, decreasing PVR, and/or increasing
preload. The older child who has "Tet spells'" may
squat to increase their venous return and improve
their systemic perfusion. In the infant, initial mea-
sures include calming the patient. holding the child
in a knee-chest position (which increases systemic
vascular resistance and preload), and the adminis-
tration of supplemental oxygen and morphine sui·
fate to diminish the agitation and hyperpnea, in an
FIGURE 11-2. Echocardiogram of tetralogy of Fallot. attempt to minimize oxygen consumption. If these
Characteristic features Include right ventricular
hypertrophy (A); ventricular septal defect (VSD) (B); measures are not successful. volume expansion and
overriding aorta (C); right ventricular outflow tract vasoconstrictors may be given to increase systemic
obstruction (not vlsualtzed In this Image) (D). Omage blood pressure and systemic vascular resistance and
~~-~~-~..~!.g~...~.~~-~~~!~~.1............................................................. thereby "shunt" more blood through the restrictive
right ventricular outflow tract and improve oxygen
with severe obstruction to right ventricular outflow saturation. In addition, ~blockers may be given to
and ductal-dependent pulmonary blood flow, present decrease infundibular spasm and improve cardiac
within hours of birth with severe cyanosis. Cyanosis filling by increasing diastolic fi11:ing, and sodium
may not develop In children with mild obstruction bicarbonate may be given to reduce acidosis and
until later in infancy. Some children with TOF have decrease PVR. In most institutions, elective surgical
an adequate amount of pulmonary blood flow and repair is performed during the first 3 to 6 months
normal saturations and are often referred to a.s "'pink" of life, but urgent surgery is indicated ifa hypercy-
tets. Aasociated lesions include additional VSDs, right anotic episode ("Tet spell'") occurs. Neonate5 with
aortic arch. left anterior descending (LAD) coronary TOF with critical pulmonary valve stenosis are
artery from the rljht coronary artery coursing across generally repaired at presentation. In some cases of
the rightventrlcular outflow tract, and aortopulmo- TOF with associated anomalies (such as multiple
nary collateral arteries. VSDs, LAD coronary artery from the right coronary
artery coursing across the right ventricular outflow
Clinical Manlresta11ons
tract, or pulmonary atresia) or based on institutional
Infants may be asymptomatic or present with cya-
preference, a modified BTS may be placed during the
nosis and tachypnea of varying severity. They may
neonatal period prior to definitive repair. generally
have characteristic periodic episodes of cyanosis,
around 6 months of Ufe.
rapid and deep breathing, and agitation known as
hypercyanotic or "Tet" spells. These are thought to
be caused by an increase In right ventricular outflow EBSTEIN ANOMALY
tract obstruction, which leads to increased right-to-left Ebstein anomaly (Appx. Fig. A-14) is a rare form
shunting across the VSD. Such spells may last minutes of CHD in which the septal leaflet of the tricuspid
to hours and may resolve spontaneously or lead to valve is displaced inferiorly into the right ventricular
progressive hypoxia, metabolic acidosis, and death. cavity and the anterior leaflet of the tricuspid valve
On cardiac examination, a right ventricular heave is redundant and sall-llke. This results in a portion
may be palpable, and a loud systolic ejection mur- of the RV being incorporated into the right atrium.
mur is heard in the left upper sternal border. The Functional hypoplasia of the RV results, as well as
heart size is generally normal on chest radiograph, tricuspid regurgitation. In severe cases of Ebstein
with decreased pulmonary vascular markings. The anomaly, antegrade pulmonary blood flow from the
right ventricular hypertrophy will lead to upturning RV is limited by the severe tricuspid regurgitation
of the apex on chest x-ray ("boot-shaped• heart). so that the maJority of the pulmonary blood flow
Twenty·five percent of children with TOF have a comes from the PDA. A PFO is present in 8096 of
right-sided aortic arch, which also may be noted on neonates with the anomaly, with resultant right·to·left
shunt at the atrial level. The right atrium is mas-

sively dilated. which may result in atrial tachycardia.
Wolff-Parkinson- White (WPW) syndrome ocCUl'S in
approximately 20CJ6 of patients with Ebstein anomaly.
Ebstein anomaly can be associated with maternal The following lesions typically depend on patency of
lithium use. the ductus arteriosus to provide adequate systemic
blood flow. All present with signs and symptoms of
Clinical Manifestations inadequate systemic perfusion and can be mistaken
Neonates with severe disease present with cyanosis for other disease processes, such as sepsis. Cyanosis
and congestive heart failure in the first few days of is often present because of intracardiac mixing,
life. The cardiac examination reveals a widely fixed systemic venous deaaturation, pulmonary venous
split~ and a gallop rhythm. A blowing holosystolic desaturation, or a combination of the three.
murmur is heard at the left lower sternal border
consistent with tricuspid regurgitation. This is one of HYPOPLASTIC LEFr HEART SYNDROME
the few lesions that present with an audible murmur Hypoplastic left heart syndrome (HLHS) (Appx.
noted immediately after birth. Chest radiograph Fig. A-15) is the second most common congenital
shows marked cardiomegaly (often referred to as a cardiac lesion presenting in the first week of life
~to--wall heart) with notable right atrial enlarge- and the most common cause of death from CHD
ment and decreased pulmonary vascular markings in the first month of life. In this syndrome, there is
(Fig.ll-3). Characteristic ECG findings include right hypoplasia of the Lv; aortic valve stenosis or atresia,
bundle branch block with right atrial enlargement. mitral valve stenosis or atresia, and hypoplasia of the
The presence of an accessory pathway/WPW is ascending aorta and aortic arch. These lesions severely
indicated by a delta wave and a short PR interval. reduce or completely eliminate blood flow through
Children with milder forms of the disease may the left side ofthe heart. Oxygenated blood from the
present later in childhood with fatigue. exercise pulmonary veins is shunted left to right through an
intolerance, palpitations, and/or mild cyanosis with ASD. Right ventricular cardiac output (which is a
clubbing. mixofsystemic and pulmonary venous return) goes
Treillment to the pulmonary arteries and through the ductus
Severely cyanotic newborns require PGEt infusion arteriosus to the descending aorta. Systemic blood
to maintain pulmonary blood flow through the flow is completely ductal dependent, and perfusion
PDA. In general, attempts are made to avoid early to the head/upper extremitieJ as well as coronary
surgical intervention. Some infants progress down artery perfusion is retrograde when aortic atresia or
a single-ventricle palliation pathway. Surgery on critical aortic stenosis is present.
the abnormal tricuspid valve is difficult, but, in ex- Clinical Manifas1ations
perienced hands can lead to very acceptable results As the ductus arteriosus closes, neonates with HLHS
when performed outside ofinfancy. Patients with the will have severely diminished systemic blood flow
most severe forms of Ebstein anomaly may require and rapidly present in shock, with signs of poor
heart transplantation. systemic perfusion, tachycardia, and tachypnea. A
right ventricular heave may be present. A single S2
will be present and possibly a continuous murmur
consistent with flow through the closing PDA.
The chest radiograph reveals pulmonary edema
and progressive cardiac enlargement. The ECG
is consistent with right ventricular hypertrophy,
and there is poor R wave progression acroJS the
precordial leads.
Treatment
PGE1 should be initiated u soon as possible to main-
tain ductal patency because ofthe ductal~dependent
systemic blood flow. Only a palliative procedure
FIGURE 11-3. Chest x-ray of Ebstain anomaly. (Image is available, as there is no corrective surgery for
~-~-~--~!. 1?.~. ~.~~-~.!t...~.~~!~.~:.L........................................................... this lesion. The stage I (or Norwood) palliation is
220 • BWEPRINTS Pedlatrtcs
performed in the first week oflife. The stage I pro- I palliation by any of the methods described earlier
cedure involves anastomosis of the pulmonary artery and are awaiting their second surgery (interstage)
and aorta with aortic arch reconstruction to provide live with extremely tenuous cardiac physiology and
Wl.Obstructed systemic blood flow, enlargement of are at high risk for decompensation and even death.
the atrial communication with atrial septectomy, and
placement of a modified BTS or right ventricular to INimRU~D AORTIC ARCH
pulmonary artery conduit to provide a stable source IAA is essentially an extreme form ofcoarctation of
of pulmonary blood tlow. The second-stage proce- the aorta. {fig.ll-4). There are three types ofl.AA:
dure, a cavopulmonary anastomosis (bidirectional
Glenn procedure or Hemi-Fontan) is performed at • Type A is interruption beyond the left subclavian
3 to 6 months of age. A modified Fontan comple- artery.
tion procedure is generally performed between 2 • Type B is interruption between the left subclavian
and 5 years of age and is the last stage of palliation, and left common carotid arteries.
effuctivcly separating the pulmonary and systemic • Type Cis interruption between the left common
circulations. Some centers do not perform the stage carotid and the right brachiocephalic artery.
I surgical palliati.on and use a combined catheter and Systemic blood flow depends on patency of the
surgical-based approach ("hybrid technique•), limiting ductus arteriosus, which shunts blood from the
pulmonary blood flow through surgical placement of pulmonary artery to the descending aorta. IAA is
bilateral pulmonary artery bands, enlarging the ASD often associated with a 22qll microdeletion.
with catheter-based balloon dilation and/or stenting,
and catheter-based stenting of the ductus arteriosus Clinical Manlfestllltlons
to maintain systemic blood flow. In these patients, Neonates with IAA have ductal-dependent systemic
surgical aortic arch reconstruction is performed at blood flow and present with circulatory collapse as
the time of the second stage of palliation. From a the ductus closes. The clinical presentation is similar
clinical standpoint, infanbl who have undergone stage to that of mHS afrer the ductus arteriosus closes.
Aortic arch interruption

Restrictive ductus arteriosus
-~......._-+--Posterior malalignment
wntricular septal defect
RGURE 11-4. 1nterrupted aortic arch with restrictive patent ductus arteriosus. Typical anatomic findings include atresia of
a segment of 1he aortic arch between the left subclavian artery and the left common carotid (the most common type of
Interrupted aortic arch-"type B'l {a); posterior malallgnment of the Infundibular septum resulting In a large wntrlcular
~~~. ~~..~.~. .~.~~. ~~.~~.~. ~~. ~).~.-~. ~~P.!~. ~~.i.~..~....~~.~.~.~..!~.~~..~..P.~~~J~t........... ...... . . . .-.. .
Of note, severe coarctation of the aorta presents in Clinical Manlfaslatlons

a similar fashion to IAA with ductal closure. ASDs are usually asymptomatic, although exercise
intolerance may be noted in older children, In chil-
Traabnant dren with underlying pulmonary disease, moderate
PG£1 therapy should begin immediately to maintain to large ASDs can be more symptomatic. Paradoxical
symnuc blood flow via right-to-left ahunti.ng at thePDA. embollsm, leading to a stroke. may occur. Supraven-
Surgical treabnent involves an extended end-tcrend tricular tachycardia (SVT) from atrial enlargement
anastomosis of the interrupted aortic segments. may also occur. On examination, a right ventricular
heave is often present. A systolic ejection murmur in
ACYANOTIC CONGENITAL HEART the pulmonic (left upper sternal border) area and a
DISEASE mid-diastolic rumble in the lower right sternal border
reflect the increased flow across the pulmonary and
Acyanotic cardiac defects are anatomically and tricuspid valves, respectively. S1 is loud. and S1 is
physiologically diverse. Those that result in increased widely split on both inspiration and expiration ("fixed•
pulmonary bloodflow (left-to-right shunts) include splitting). The chest radiograph reveals a normal to
ASD, VSD, PDA, and atrioventricular septal defects mildly enlarged cardiothoracic ratio (because the RV
(AVSD or AV canal defects). Acyanotic lesions that is an anterior structure and not profiled well on an
result in pulmonary venous hypemnslon include anteroposterior chest x-ray) and more impressive
coarctation ofthe aorta and aortic valve stenosis. The enlargement of the main pulmonary artery with
acyanotic lesion that results in normal or decreased some degree of increased pulmonary vascularity.
pulmonary bloodflow is pulmonary valve .stenosis. The ECG often shows right ventricular enlargement
In general. left-to-right shunting lesions can be with an rSR' pattern. Right-axis deviation is seen in
divided into two types, pre- and post-tricuspid, secundum defects, whereas primum defects have
which assist in determining the cardiac response to characteristic extreme le.ft~axis deviation.
the shunt. The prototypical pre-tricuspid shunt is an
ASD, which leads to right atrial and right ventricu- Treatment
lar dilation. Both VSD and PDA are post-tricuspid Spontaneous closure ofsmall secundum ASDs (the
shunts and lead to dilation of the left atria and LV. most common type) often occurs in the first several
Combination ofthese lesions, as seen in AVSD, leads years oflife. In both symptomatic and asymptomatic
to right- and left-sided dilation. children with suitable secundumASDs, transcatheter
device cloaure may be undertaken after 2 years of
ATBIAL SEPTAL DEFECTS age. Less commonly, younger chUdren can undergo
ASDs account for 8% ofCliD and have a 2:1 female- transcatheter device closure. Moderate- to large-size
to-male predominance. There are three types of ASDs: secundum ASDs that have not spontaneously closed
and are not candidates for device closure must be
• Ostium secundum defects, seen in the midportion addressed surgically. Ostium primum and sinus ve-
of the atrial septum nosus ASDs will not close spontaneously and must
• Ostium primum defects, located in the lower be addressed surgically. Surgical closure involves
portion of the atrial septum pericardial patch or suture closure.
• Sinus venosus defects, found at the junction of
the right atrium and the superior or inferior vena
cava, usually associated with anomalous drainage VENTBICULAR SEPTAL DEFECTS
of the right pulmonary veins The VSD is the most common congenital heart
derect, accounting for 25% of all congenital heart
The degree of atrial shunting depends on the size
defects. The five types of VSDs are as follows (as
of the ASD and the relative compliance of the atria.
seen in Fig. 11-5):
whidlis directly relatr.d to theventrk:ularco~ in
diastole. Because rlght\'mtricu!ardiastolic compliamE • Muscular
is usually ~ater than left ventricular diastolic com- • Inlet
pliance, and therefore ri8ht atrial pressure is less than • Doubly committed juxta-arterial (outlet)
left atrial pressure, left..to-right shunting occurs at the • Perim.embranous (conoventricular)
atrial leveL resulting in right atrial and right ventricular • Malallgnment (which are typically a variant of
enlargement and increased pulmonary blood flow. perimembranous/conoventricular)
FIGURE 11-li. (A) Verrtrlct.dar septum viewed from the right ventricular side is made of four components;/, inlet
component extends from the tricuspid annulus to attachments of tricuspid valve; T, trabecular septum extends from
inlet out to apex and up to smooth-walled outlet; 0, outlet septum or infundibular septum, which extends up to the
pulmonary valve and membranous septum. (B) Anatomic position of defects: a, outlet defect; b, papillary muscle of
the conus; c, perimembranous defect; d, marginal muscular defects; e, central muscular defects; f, inlet defect; g,
apical muscular defects. (From Allen HD, Gutgesell HP, Clark EB, et al. Moss and Adams Hea!t Disease in Infants,
~~!..~~-~~~~~.!..~.~-~-=--~-~!!~~.f?.~!~!.f~.:..~.P.f?.!~c~..~!!!!~~-~--~-!Y.!!~.~~.:. ?.29..~.:L. ..................... . .............................. . -..
Muscular and perimem.branous VSDs are the and PVR and systemic vascular resistance (SVR)
most common types. Muscular VSDs occur in the determine shunt flow. When the PVR is less than
muscular portion of the septum and may be single or the SVR, which is typical outside the immediate
multiple, located in the posterior, apical, or anterior newborn period, the shunt flow is from left to right.
portions ofthe septum. Inlet VSDs are typically seen In this case, the amount of LV and left atrial dilation
in AVSD/AV canal-type defects, but can also be seen is directly proportional to the &ize of the left-to-right
in isolation and occur in the inlet portion of the sep- shunt. Right ventricular hypertrophy occurs when
tum beneath the septal leaflet of the tricuspid valve. PVR increases. Ifleft untreated, the large VSD may
Doubly committlld juxta--arterial VSDs are positioned result in elevated pulmonary arterial pressures and
in the outflow tract of the RV beneath the aortic and may lead to pulmonary vascular obstructive disease,
pulmonary valves. Perimembranous VSDs occurs in pulmonary hypertension, and Eisenmenger syndrome.
the membranous portion of the ventricular septum. In such cases, the VSD shunt reverses and becomes
Malalignm.ent VSDs result from malalisnment ofthe right to left when the PVR exceeds the SVR.
infundibular septum and are typically membranous
in nature, but can also involve portions of the mus- Clinical Manlf8staUon&
cular septum. Anterior malalignment results in TOF Oinica1 symptoms are related to the size ofthe shunt
(because of crowding of the RV outflow tract), and and the PVR. A small shunt produces no symptoms,
posterior mal.alignment results in subaortic stenosis whereas a large shunt gives rise to signs of pulmonary
(because of crowding of the subaortic area) and is overcirculation (congestive heart failure) and failure
often associated with aortic valve stenosis and aortic to thrive when the PVR is low. The smaller the defect,
arch hypoplasia or interruption. the louder the murmur. Small VSD murmurs are harsh
When the VSD is small, shunt flow is left to right and systolic, with short to medium in duration, heard
from the high-pressure LV to the lower pressure RV. best at the mid-to-lower left sternal border. Larger
Small shunts result in relatively normal pulmonary VSDs demonstrate a long systolic murmur (often
blood flow. A VSD is considered large when the described as holosystolic or pansystolic) at the left
dimension is greater than the aortic valve annulus. sternal border and can have a more ejection quallty
Large VSDs allow LV and RV pressures to equilibrate, at the upper sternal border because ofincreased flow
across the pulmonary valve. They also demonstrate subaortic stenosis, and double-chambered RV. In
a diastolic murmur (or rumble) over the mitral area these cases, the defect may require closure, despite
because ofthe increased flow across the mitral valve. the small size. Similarly, doubly committed VSDs
As the PVR increases in patients with nonrestrictive have a high risk for the development of aortic cusp
VSDs, shunting from left-to-right decreases, the mur- prolapse and aortic itLiufficiency, necessitating surgical
mur shortens, and the pulmonary (late) component closure, despite a small anatomic defect. Muscular
of~ increases in intensity. El.senm.enger syndrome VSDs are the most likely to close spontaneously.
results in a right ventricular heave, short systolic The treatment for large VSDs, with .significant left-
ejection murmur, diast:ollc murmur of pulmonary to-right shunting and variable levels ofcongestive
valve insufllciency, and a loud. single~. heart failure/pulmonary overcirculatlon, is surgical
Chest radiographs and ECGs in .small VSDs are closure before pulmonary vascular changes become
normal. Moderate·size VSDs may show mild cardio· irreversible. Surgical intervention usually involves
megaly and slightly increased pulmonaryvascularity patch closure. In some cases, transcatheter device
on chest radiograph with a prominence ofthe main placement in the interventricular septum may be
pulmonary artery segment. Large left..to--right shunts used for muscular VSD closure. Congestive heart
result in cardiomegaly, increased pulmonary vascu- failure may be treated with diuretics, and systemic
larity, and enlargement of the left atrium and LV. The afterload reduction with an angiotensin-converting
ECG is consistent with left atriaL leftventric• or enzyme (ACE) inhibitor. Growth failure may be
biventricular hypertrophy. Right ventricular hyper- improved with increased caloric density of feeds
trophy predominates when PVR is high. and even nasogastric enteral feeds to optimize
caloric intake.
Treabnent
Most small VSDs close without intervention (40% by COMMON ATRIOVENTRICULAR CANAL DEFECT
3 years, 75% by 10 years) and those that do not and The common AV canal defect or AVSD (Fig. 11-6)
are of no hemodynamic significance do not require results from deficiency of the endocardial cushions
intervention. Perimembranous defects can be asso- and results in an ostium primumASD andinletVSD
ciated with the development of aortic insufficiency, with lack ofseptation ofthe mitral and tricuspid valves
Primum atrial -
septal defect
-Inlet ventricular
septal defect
Sir
val
RGURE 11-&. Complete common atrioventricular canal. Typical anatomic findings Include large atrial and ventricular
septal defects of the endocardial cushion type; single atrioventricular valve; left-to-right shunting, which is noted at
~~~--~~-~--~~--~~.~~!~. ~.~. ~-~-~.P.~.!~.~-~~--~!~. ~!.~~~~~--~-~. ~-~-~D.~--~~..~~~-~-~!.J?.!~~.:..............................................
(common atrioventricular valve [CAVY]). The various obstruction and residualleft~sided AV 'VllM disease.
forma ofAV canal defects account for 5% ofall CHDs Infants with a large VSD oomponent should be repaired
and are most commonly seen in children with Down by 6 months to decrease the risk of pulmonary artery
syndrome. In an incomplete AV canal defect. the hypertension and pulmonary vascuJar obstructive
CAVYleafletsattach dlrectly to the top ofthe m.uscular disea5e. The ASD and VSD portions are closed, and
portion of the ventrirular septum. As a result. there the CAVV is divided into left and .rigbt sides. Suture
is no communication beneath the AV valves ~en closure of the cleft leaflets of the septated left-sided
the RV and LV (i.e., no VSD). The communication at AV inflow is performed to make the LV inflow as
the atrial level is an ostium primum ASD. The mitral competent as possible. Complete heart block occurs
valve has a •cleft," and there may be some degree of in 5% ofpatients undergoing repair, and residualleft-
mitral regurgitation. In complete common AV canaL sidedAV valve disease (inJuftidency, stenosis, or both)
there is a CAVY that is not attached to the nwscular is not WlCOnunon.
ventricular septum. Ar. a result, there is a large inlet
VSD located between the CAVV and the top of the PATENT DUCTUS ARTERIOSUS
muscular ventricular septum. In this defect, there is a Persistent patency of the ductus arteriosus accounts
left-to-right shunting at the ostium prirnum ASD and for 10% ofCJID. The incidence of PDA is higher in
1nl.etVSD. Because of the increase in pulmonary blood premature neonates. The ductus arteriosus connects
flow from both a large pre- and post-tricuspid shunt, the underside of the aorta and the left pulmonary
pulmonary hypertension and pulmonary vascular artery just distal to the takeoff of the left subclavian
disease may develop aver time. In untreated cases, artery from the aorta (Fig. 11-7). The direction of
Eisenmenger syndrome may develop. blood flow through a PDA depends on the relative
resistances in the pulmonary and systemic circuits. In
Clinical Manifestations the nonrestrictive (large) PDA, a left-to-right shunt
The clinical manifestations and treabnent ofincomplete is present as long as the ~mic vascular resistance
common AV canal are the same as those described is greater than the PVR. IfPVR rises above systemic
for an ASD. There may be a blowing systolic mur- vascular resistance, a right-to-left shunt develops.
mur heard best at the left lower sternal border and
apex, consistent with mitral regurgitation through
the mitral valve cleft.
In oomplete commonAV canal defects, the degree
of congestive heart failure/pulmonary overcircula-
tion depends on the magnitude of the left-to-right
shunting and the amount of CAVV regurgitatioiL If
shunting or valve regurgitation is significant, symp-
toms are seen early in infancy, typically tachypnea,
dyspnea, and failure to thrive. On examination, the
precordium is hyperdynamic, a blowing holosystolic
murmur is heard at the left lower sternal border, and
S2 is widely split and fixed. Cardiac enlargement and
increased pulmonary vascularity are visible on the
chest radiograph. The ECG reveals a superior axis,
characteristic of a canal defect, along with biatrial
and biventricular enlargement.
Treatment
Prior to surgical repabo congestive heart failure is
typ1callytreated with cliUl'el:ks. An ACEinhibitor can
FIGURE 11·7. Patent ductus arteriosus. The ductal
be added for persistmt symptoms. The symptnmatic arteriosus connects the underside of the aorta to the
patientwith completeCAWis generally repaired during takeoff of the left pulmonary artery. When pulmonary
infancy. The asymptomatic child with incomplete canal vascular resistance falls, blood ftows from left to
without pulmonary hypertension mayundergo elective right from aorta to pulmonary artery. (From Pillitteri A.
repair within the first few years oflife. These patients Matemal and Child Nvrsing, 4th ed. Philadelphia, PA:
are at long-term risk for left ventricular outflow tract !::!E'.!?.!.~.~..YY.!!.~i·~-~..~..~-i-~~-~-~~..~-g-~:L...............................................
Clinical Mantfastatlons More than half ofinfants with coarctationwill have

Symptoms are related to the size of the defect and no symptoms in infancy. Neonates with critical
the direction of flow, the latter of which is directly coarctation have ductal-dependent systemic blood
related to the SVR and PVR. A small PDA causes no flow and may present with circulatory collapse as
symptoms or abnormalities on chest radiograph or the ductus closes, similar to HLHS and IAA. On
ECG. A large PDA with left·to·right shunting may examination, the femoral pulses are often weak and
result in congestive heart failure/pulmonary overclr- delayed, or even absent, and there is upper extrem-
culation and failure to thrive. Bounding pulses may ity hypertension. On cardiac examination, there is
be palpable because of the increased pulse pressure. a nonspecific ejection murmur at the heart apex.
A continuous murmur begins after ~ peaks at ~ There can be murmur in the subscapular area. If
and trails off during diastole. The chest radiograph the coarctation is associated with a bicuspid aortic
of a patient with a large PDA shows cardiomegaly, valve, an apical ejection click will be heard. The chest
increased pulmonary vascularity, and left atrial and radiograph and ECG are normal in mild lesions. In
ventricular enlargement. The ECG shows left ventric- patients with more severe obstruction, the chest
ular or biventricular hypertrophy. IfPVR rises above radiograph may reveal an enlarged aortic knob and
systemic resistance (pulmonary hypertension), flow cardiomegaly. Right ventricular hypertrophy is seen
at the PDA reverses, and cyanosis is noted. ECG and in the neonatal ECG; left ventricular hypertrophy is
chest radiograph findings become more consistent more common in the older patient.
with right atrial dilation, right ventricular dilation/
hypertrophy, and a decrease in the prominence of Treatment
In neonates with criticalcoarctation of the aorta, the
the peripheral pulmonary vascularity.
child's systemic blood flow is ductal dependent, and
Treatment PGE1 should be started prior to surgical intervention.
Indomethacin decreases PGE1 levels and is often Treatment may be surgical, with end-to-end anasto-
effective in closing the ductus in the premature mosis or patch aortoplasty, or intervention.al. with
neonate, but is associated with risk of renal insuf- balloon dilation angioplasty with or without stent
ficiency. Recently, oral acetaminophen has been placement. T'lllling and type oftherapy depend on age
used as an alternative treatment strategy. A PDA at diagnosis, severity of illness, and related defects.
usually closes in term infants in the first month of Restenosis at the .surgical repair site is not uncommon,
Ufe. Children with Down syndrome are at higher especially in neonates. Persistent hypertension after
risk for continued patency. If the ductus remains intervention in the older child may require f}-blocker
patent, coil embolization or device closure in the therapy, and all children who undergo coarctation
cardiac catheterization laboratory or surgical ligation repair are at risk for hypertension during their lives.
may be performed. There is significant controversy
and institutional variability in the treatment of both AORnC STENOSIS
neonates and children with a PDA. In aortic stenosis, the valvular tissue is thickened. is
rigid. and domes in systole. Commonly, the valve is
COARCTAnON OF TltE AORTA bicuspid rather than tricuspid and. often, the annular
Coarctation of the aorta (Appx. Fig. A-16) accounts dimension is hypoplastic. The increased pressure
for 8% of congenital heart defects and has a male- generated in the LV, as it attempts to direct blood
to-female predominance of 2:1. When coarctation flow across a stenotic valve, results in left ventricular
of the aorta occurs in a female, Thrner syndrome hypertrophy and. over time, decreased compliance
must be considered. The obstruction (narrowing) is and ventricular performance.
usually located in the descending aorta at or near the
insertion site ofthe ductus arteriosus, but the entire Clinical ManifasiBtions
aortic arch can be hypoplastic. Coarctation results in The degree of symptoms is related to the severity
of the stenosis and the level of ventricular function.
obstruction to blood flow (between the proximal and
Infants with minimal stenosis are asymptomatic.
distal aorta) and increased left ventricular afterload.
The neonate with critical aortic stenosis hu duc-
Clinical Manifestations tal-dependent systemic blood flow and may present
The degree of narrowing determines clinical sever- with circulatory collapse if the ductus closes. The
ity. Infants may be asymptomatic or present with cardiac examination is characterized by a harsh
irritability, difficulty feedJng, and f.illure to thrive. systolic ejection murmur heard at the right upper
sternal border that is preceded by an ejection click. occurs with time because ofincreased right ventricular
In severe aortic stenosis, a thrill may be palpable. afterload. In critical P"lmonic mnosis, a decrease
The more pronounced the stenosis, the louder the in the compliance of the RV increases right atrial
murmur. However. ifventricular function is highly pressure and may open the foramen ovale, producing
compromised, only a soft murmur may be appre- a right-to-left shunt.
ciated. The chest radiograph shows cardiomegaly.
Pulmonary edema may be noted in cases with ven- Clinical Manlfaslatlons
tricular dysfunction. Left ventricular hypertrophy Most patients are asymptomatic. Severe pulmonary
is seen on the ECG. In some cases, a strain pattern stenosis may cause dy~pnea on exertion and angina.
of ST depression and inverted T waves consistent Right-sided congestive heart failure is rare, except
with ischemia may be notl!d. in infants with critical pulmonic stenosis who may
have ductal-dependent pulmonary blood flow.
Tntatment Chara.cteristically, the ejection click of pulmonic
In neonares with critical aortic srenosis, sysremlc stenosis varies with inspiration, and a harsh systolic
blood flow is ductal dependent and PGE1 should be ejection murmur is heard at the left upper sternal
started and the patient stabilized prior to surgical or border. In severe srenosis, a thrill and right ventric-
catheter-based intervention. Ifintervention is required. ular heave are palpable. On chest radiograph, heart
relief of the aortic valve narrowing is usually best size and pulmonary vascularity are normal, but the
accomplished by balloon valvuloplasty. Intervention pulmonary artery segment may be enlarged. The
does not creare a normal valve and regurgitation and degree of right ventricular hypertrophy and right-
restenosis is common. These may progress over time axis deviation present on ECG correlates with the
with requirement for aortic valvuloplasty or aortic degree of srenosis.
valve replacement with a mechanical, homograft.
or autograft valve (Ross procedure). Traatmant
In neonares with critical pulmonary stenosis, the
PULMONIC STENOSIS child's pulmonary blood .Bow is ductal dependent,
Pulmonic valve stenosis accounts for 5~ to 8~ of and PGE1 should be starred prior to surgical or
CHD. In many instances, the valve is only mildly catherer-based inte~ntion. Catheter-based inrer-
abnormal and quite functional. In other cases, the vention is performed most commonly, typically with
valve is dysplastic with only a small central opening, excellent short- and long-term results.
and there is often postsrenotic dilation of the main Table 11-61ists the findings for the 10 most com-
pulmonary artery. Right ventricular hypertrophy mon congenital heart lesions.
TAILE 11-1. Andings for the 10 Most Common Congenital Heart Lesions
i........ PrlllllltiiM ECI Rldloiii'Qh
1 Atrial septal defect Murmur Fixed split ~ MildRVH :!:CE, 1'PBF
IVentricular septal defect Murmw;CHF Holosystolic murmur LVH. RVH :!:CE, 1'PBF
! Patent ductuJ arteriosus Mumwr,±CHF Continuous murmur LVH, ±RVH ±CE, 1'PBF
IAV canal defect Mumwr,±CHF Holosystolic murmur *Superior" axis :!:CE, 1'PBF
j Puhnonlc steDOiiJ Murmur, ±cyanosis Click, SEM .RVH :!: CE, NL, or .J.PBF
j Thtralogy of Fallot Murmur, ±cyanosis SEM RVH :!:CE,.J.PBF
!Aortic ltl!l1oail Munnur, ±OfF Click, SEM LVH :!:CE, NL, PBF
!Coarctation ofthe aorta Hypertlmsion .J.Femoral pulses LVH :!: CE, NL, PBF
l Transposition «the
! great arteria
l Single ventricle
Cyanosis
(Variable)
Marked cyanosis
Loud~
(Variable)
RVH
(Variable)
:::MfpBF i
i Abbnwiations: CE. cardiac anlargarnant; CHF, congestille heart failure; LYH.Iaft ventrio..llar hypertrophy; NL. normal; PBF, pulmonary blood !
! flow; RVH, ~ght vent~cular hypartrophy; SEM. systolic ejection murmur. i
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Chapter 11 I Cardiology • rD
ACQUIRED STRUCTURAL HEART BE include intravenous drug abuse, an indwelling

DISEASE central venoWI catheter, and/or prior cardiac sur-
gery. In '.UXJ7, the American Heart Association's
RHEUMATIC HEART DISEASE Endocarditis Committee, together with national and
Acute rheumatic fever causes cardit:ia in 50% to 80% international experts on 8£, extensively reviewed pub·
of patients. Rheumatic heart disease results from llshed studies in order to determine whether dental,
single or multiple episodes ofacute rheumatic fever. gastrointestinal, or genitourinary tract procedures
Mitral regurgitation is the most common valvular are possible catllles of BE. These experts determined
residual lesion of acute rheumatic carditis. Aortic that there is no conclusive evidence that links dental,
insufficiency may also occur, with or without mitral gastrointestinal, or genitourinary tract procedures
regurgitation. Late-stage disease may progress to with the development ofBE. The practice ofgiving
mitral and/or aortic stenosis. Patients with severe patients antibiotics prior txJ a dental procedure Js no
valvularinvolvement manifest signs and symptoms of longer recommended except for patients with the
chronic congestive heart failure. Chapter 7 discusses highest risk ofadverse outcomes resulting from BE:
acute rheumatic fever in more detaiL
• Prosthetic cardiac valve
KAWASAKI DISEASE • Previous endocarditis
• CJID only in the following categories:
Cardiac effects may include pericarditis, myocarditis,
• Unrepaired cyanotic CHD, including those
and coronary arteritis. It is the development ofcoronary
with palliative shunts and conduits
artery an.eurysms, with their potential for occlusion.
• Completely repaired CHD with prosthetic
howevelf that makes the disease life-threatening.
material or device, whether placed by surgery
Coronary artery aneurysms develop during the sub-
or catheter intervention, during the first 6
acute phase (11th to 25th day) in approximately 25%
months after the procedure (Prophylaxis is
of cases but regress in most patients. Early therapy
recommended because endothell.alization of
with intravenous immunoglobulin decreases the
prosthetic material is thought to occur within
incidence of coronary artery aneurysms to less than
6 months of the procedure.)
10%. High·dose aspirin therapy given during the acute
• Repaired CHD with residual defects at the
inflammatDry period lessens the likelihood ofaneurysm
site or adjacent to the site of a prosthetic
development. Low.dose aspirin is continued for6to 8 patch or prosthetic device (which inhibits
weeks (or indefinitelyiftheaneurysmsdo not resolve). endotheJialization)
Some children with large to giantaneurysms require
• Cardiac tnuuplantation recipients with cardiac
chronic dual antipJatelet therapy or even anticoagula-
valvular disease
tion. An ECHO is used txJ assess ventricular function
and detect and follow coronary artery aneurysms. It is important to remember that the change in
Evidence of myocardial ischemia acutely or during recommendations regarding antibiotic prophylaxis
provocative testing warrants a cardiac catheterization was based on the effectiveness of this modality to
or alternative cardiac imaging (speciftcally myocardial reduce endocarditis and should not be misinterpreted
perfusion imaging), and in some cases may require that children with unrepaired and repaired forms of
coronary artery bypass surgery. Chapter 8 offers a CJID that do not meet criteria for prophylaxis are
thorough dbicusrdon of Kawasaki disease. not at risk for endocarditis.
In children, alpha-hemolytic streptococci (Strep-
ENDOCARDinS toooCCIU virid4ru) and Staphylococcus tlliT'eiU are the
Pathogenesis most common etiologic agents. In the pastS. viridans
Bacterial endocarditis (BE) is a microbial infection accounted for the majority of cases of endocarditis
of the endocardium. Although it may occur on nor- in ch.ildren., but recent data suggest that Staphylo--
mal valves, BE is more likely to occur where there cocci spp are more common than Streptococci spp.
is turbulent flow because of congenitally abnormal S. a~us appears to be more common in children
valves, valves damaged by rheumatic fever, acquired without CHD, whereas Streptococci spp were more
valvular lesions (mitral valve prolapse), and prosthetic common in children with OID. When the infection
replacement valves. Additionally, certain forms of is a complication of cardiac surgery, Staphylocoacus
unrepalred structural heart disease (VSD and PDA) epidumidis and fungi should be consldered.Entero-
may increase the risk. Factors that may precipitate coccal spp infections are rarer in children than in
adults. Gram~negative organisms are also rare, causing reactions. The true incidence of myocarditis is un~
approximately 5% ofcues ofendocarditis in children known as many mild cases go undiagnosed.
and are more likely in neonate&. immunocompromised
Clinical Mantrasta11ans
patients, and intravenous drug abusers.
The clinical manifestations of myocarditis can
Clinical Manifestations range from very mild to severe and can present
Fever is the most common finding in children with as a mixed picture with pericarditis, often termed
BE. Often, a new or ch.anging murmur Is auscultated perimyocarditis. Sudden. severe onset of myocar-
and typically consistent with AV valve or semilunar ditis with severe dysfunction is termed fulminant
valve regurgitation. Children with endocarditis myocarditis. H myocardial damage is mild, patients
usually display nonspecific symptoms, including may be asymptomatic; the diagnosis may be made
chest pain, dyspnea, arthralgia, myalgia, headache, by finding ST- and T-wave changes on an ECG
and malaise. Embolic phenomena such as hematuria done for an unrelated reason or the episode may go
and strokes may occur. Other embolic phenomena undiagnosed. Severe myocardial damage presents
(Roth spots, splinter hemorrhages, petechiae, Osler with fulminmt congestive heart failure and arrhyth-
nodes, and Janeway lesions) are relatively rare in mia. Elucidation of a viral prodrome is helpful, and
children with BE. common symptoms include fever; dyspnea, fatigue,
and abdominal pain. Tachycardia, evidence of hep-
Diagnostic Evaluation atomegaly, regurgitant murmurs related to tricuspid
Typical laboratory findings include elevation in white and/or mitral regurgitation, and S, gallop may be
blood count, erythrocyte sedimentation rate, and appreciated on examination. The ECG often reveals
~reactive protein. Anemia is common. Hematuria
ST-segment depression, T~wave inversion, and low
may be seen on urinalysis. Multiple blood cultures voltage. Arrhythmias and conduction defects may
increase the probability of identifying the causative also be present. Heart size on cheat radiograph varies
pathogen. A transthoracic and/or transesophageal from normal in fulminant myocarditis to markedly
ECHO is used to identifyvegetations and/or thrombi enlarged. The ECHO typically reveals ventricles
in the heart. ECGs should be monitored on a serial that are dilated with decreased systolic function.
basis to detectAV conduction abnormalities. Co~ Pericardial effusion is common. Vtral etiology should
plete heart block can occur with severe endocarditis. be investigated by polymerase chain reaction from
TrHtment the throat, stool, and blood. Cardiac MRl can also
Medical management is variable and dependent on define the degree of myocardial dysfunction as well
the organism and specific patient characteristics as characteristic contrast enhancement patterns
(native valve, CHD, or prosthetic material) but consistent with myocarditis. Endomyocardial biopsy
generally consists of 6 to 8 weeks of intravenous may be indicated to confirm diagnosis, but clinical
antibiotics directed against the isolated pathogen. history, examination, laboratory evaluation, and cardiac
Surgery is indicated for endocarditis when medical MRI are usually sufficient to confirm the diagnosis.
treatment is unsuccessful. refractory congestive heart
Trel'bllent
failure exists, serious embolic complications occur, Therapy for patients with viral myocarditis is sup-
myocardial abscesses develop, or there is refractory portive to maintain perfusion and oxygen dellvery.
infection of a prosthetic valve. Ventricular arrhythmias, conduction abnormalities,
and congestive heart failure are treated as indicated
FUNCTIONAL HEART DISEASE Intravenous immunoglobulin is often given to those
with decreased function despite limited data, to min-
MYOCARDinS imize further damage to the myocardium. Patients
Most cases of myocarditis in the developed world with fulminant myocarditis often require aggressive
result from viral infection of the myocardium, pre- support including mechanical drculatorysupport, but
dominantly adenovirus, parvovirus B19, coxsackie the patients have a good prognosis of recovery. For
A and B, echovirus, and human herpes virus 6. It all patients with myocarditis, the majority (-2/3) will
is unclear whether the myocardial damage results have complete myocardial recovery. although this may
from direct viral invasion or an autoimmune anti- take several years. The degree of myocardial recovery
body response. However, myocarditis can also be is variable, and for those who do not fully recover.
the result of bacterial or fungal infections, systemic some will require chronic enteral heart failure treat-
autoimmune diseases, or hypersensitivity or toxic ment and others may require heart transplantation.
CORONARY ARTERY DISEASE diuretics, an ACE inhibitor, and a fl-blocker. If the

Although coronary artery disease is rare in childhood, child presents in cardiogenic shock, medical therapy
the atheroJclerotic process appears to begin early in with inotropes (e.g., milrinone) and positive pressure
life. Evidenre indicates that progression ofatheroscle- ventilation (decrease left ventricular afterload and
rotic lesions is influenced by genetic factors (familial wall stress) are attempted, and if not successful at
hypercholesterolemia) and lifestyle (cigarette smoldng. achieving adequate oxygen delivery and end organ
inactivity, high-cholesterol diet, high-saturated-fat support, the child may require mechanical circulatory
diet). Certain diseases place children at increased support. Extracorporeal membrane oxygenation or
risk for hypercholesterolemia (e.g., JOme storage and a ventricular assist device may be used as either a
metabolic diseases, renal failure, diabetes, hepatitis, bridge to myocardJal recovery or cardiac transplan-
systemiclupus erythematosus). Because many lifetime tation. Antiarrhythmic medications or placement
habits are formed d1lling childhood, the opportunity ofiCD is reserved for treatment of potentially fatal
exists for prevention of coronary artery disease. ventricular arrhythmias. In addition, family history
should be assessed and screening (either genetic or
DILATED CARDIOMYOPATHY ech.ocardiographic) of first-degree relatives is war-
Dllated cardiomyopathy (DCM) is the most common ranted when a familial/genetic cause is identified or
cardiomyopathy encountered in children and is char- cannot be ruled out by another etiology.
acterized by ventrlcular dilation and myocardial dys-
function. Idiopathic DCM is the most common etiology, HYPERmOPHIC CARDIOMYOPATHY
although it is difficult to exclude a prior undiagnosed Formerly known as idiopathic hypertrophic subaortic
episode of myocarditis or familial/genetic cause de- stenosis or hypertrophic obstructive cardiomyopathy,
spite negative testing given the clinical yield ofcurrent hypertrophic cardiomyopathy (HCM) is a disorder
genetic testing panels. DCM can also be associated in which the left ventricular myocardium (usually
with neuromuscular disease (e.g., dystrophinopathy) asymmetrically involving the interventricular sep-
or drug toxicity (e.g., anthracyclines). In 25'16 to 484J' tum) is significantly thiclcened. resulting in variable
ofcases ofDCM, thereis genetic abnonnalityleading degrees ofleft ventricular outflow tract obstruction.
to cytos1cdet:al or sarcomeric protein abnormalities. The thiclcened stiff LV has compromised diastolic
Clinical Manifestations function and usually preserved or hyperdynamic
Signs and symptoms are related to the degree of systolic function. Abnormal motion of the mitral
myocardial dysfunction. Symptoms can include valve results in mitral insufficiency. In 30% to 65% of
anorexia, feeding intolerance, abdominal pain. em- cases of HCM, there is genetic abnormality leading
esis, dyspnea, orthopnea, and paroxysmal nocturnal to sarcomeric protein abnormalities. The inheritance
dyspnea. The cardiac examination reveals tachycardia is autosomal dominant with incomplete penetrance.
(compensatory) with an Sa gallop and often a murmur
consistent with mitral regurgitation. As heart failure
Most cases are asymptomatic and discovered as a
worsens, dependent edema. a right ventricular heave,
result ofevaluation ofa heart murmur. When present
and pulsus altemans (beat-to-beat variability in pulse
(generally in adolescence), symptoms include dyspnea
magnitude) may be noted. The heart is enlarged on
on exertion, (ex.ertional) chest pain, and syncope. The
chest radiograph, often accompanied by pulmonary
initial symptom ofHCM can be sudden cardiac death
edema. The ECG is notable for tachycardia, broaden-
because of arrhytlunia during exertion in otherwise
ing of the QRS complexes, and nonspecific ST-and
healthy, asymptomatic individuals. A systolic ejection
T-wave iachemic changes. Ventricular dilation and
murmur at the left lower sternal border and/or apex
function ia evaluated by ECHO. Cardiac MRI with
delayed enhancement may be used to evaluate for
may be accompanied bythe soft, holosystolic murmur
the presence of fibrosis. of mitral regurgitation and an ~ gallop. There may
be a left ventricular heave and the point ofmaximal
Traatmant impulse may be displaced. The chest radiograph
Initial treatment ofa child presenting with symptomatic shows nonnal vascularity and mild left ventricular
heart failure includes diuretics (to reduce preload), enlargement. The ECG illustrates left-axis deviation.
vasodilators (decrease afterload), and if necessary left ventricular hypertrophy, and possible ST- and
inotropes (increase contractility). Many chlldren with T-wave changes consistent with ischemia or strain.
mild-to-moderate dysfunction can be managed as The ECHO is diagnostic and is able to determine
an outpatient on oral medications, most commonly degree of thickness and outflow tract obstruction.
nutment
TilLE 11-7. Factors That Influence Arrhythmia Risk
Therapy is centered on preventing fatal ventricnlar
arrhythmias and decreasing outflow obstruction HHtt 1/kJck (Wirylng r/tlgrlll)
by improving left ventricular filling via slowing the Fetal heart block secondary to maternallupw
intrinsic heart rate. Medications that reduce the risk erythematoiUI
ofarrhythmia and decrease chronotropy and lnotropy Ischemic heart disease
include calcium channel blockers and P-adren.ergi.c
Cardiomyopathy
blocking agents. Life-threatening ventriculac arrhythmia
risk is stratified based on several factors, including Cardiac tumors, cysts, and other mechanical
ventricular septal thickness, presence ofventricular disruption
arrhythmias, syncope, cardiac MRI findings (assess-- Hereditary neuromuscular disease and rheumatologic
ment of myocardialfibrosis), and exercise stress test disorders
(assessment for inducible arrhythmia, exertional Elevated vapl. tone (usually transient and typically
ischemia, and progressive obstruction). lCD may be benign)
warranted for either primary prevention (based on Infectioua (myocarditis, Lyme dileue, Chagu
risk stratification) or secondary prevention after prior ! diseue. and others)
successfully resuscitated sudden cardiac death. The
avoidance ofcompetitive sports is essential because ! Increased intracranial pressure .
sudden death during exertion is a sigrillicant risk (4% IIatrogenic heart block (typically from cardiac surgery, !
to 6~ ofaffected patients a year). In addition, family ~ cathetedzation, or secondary to medications) ~
historyshould be assessed and screening (either ge- IIdiopathic heart bloclt (may be lnherl~d, progreMive, I
netic or echocardiographic) offirst-degree relatives is 1or lntennlttent) i
warranted when a familial/genetic cause is identified
or cannot be ruled out by another etiology.
ITtt:hylntJythmlll i
i Cardiomyopathy !
ARRHYTHMIAS
!Friedreich ataxia (atrial tachycardia or fibrillation) !
IMuscular dystrophies (Duchenne, periodic I
The heart's normal electrical pattern is sinus rhythm
with intact AV conduction. The sinus node sets the
iparalym) i
! Glycosen storaw: disease (Pompe disease) !
overall heart rate, with input from the autonomic system
(sympathetic and parasympathetic tone) andintrinsic l Collagen vucular diJeases (rheumatic carclitfa, I
~ symmic lupua erythematosus, periarteritfa noclosa,
1
conditions (volwne status ofthe heart and each person's ~ dermatomyositis)
intrinsic heart rate). Normal heart rates vary and the
diagnosis of an abnormal heart rate should be made !Eodoaine dilorders (e.pedally hyperkalemia,
after considering the age of the patient (Table 11-3).
i adrenal dysfunction, hyper-- or hypothyrold!Jm)
Abnormal rhythms are typically classified as iKawasaki disease
those that are too fast (tachyarrhyt:luniu) and those ! Drug toxicity, chemotherapeutic agents
that are too slow (bradyarrhythmias). In children,
pathologic tachyarrhythmias are more common than
IBlunt thoraclc trauma (commotio cordls)
pathologic bradyarrhythmias. !PrDitJnt/IJd orAllnDnnll RflptJIItiDIIII
Although the most common arrhythmias in j Long QT syndrome, Brugada syndrome,
pediatrics occur in structurally normal hearts, the i arrhydunogenic right ventricular cardiomyopathy,
concerningarrhythmias often occur in CHD, genetic i catecholaminergic polymorphic ventricular
heart disease, or acquired heart disease. Pediatrician.& !tachycardJa. drug effects
caring for children with one of these underlying ICongtn/tM Hfltlrt ms...
heart abnormalities should be particularly alert for !Some form.~ of congenital heart dlaeue pred.lapose
compJaints of palpitations or syncope. Electrolyte i patients to 1upraventricular arrhythmiaa (e.g., Ebstein
abnormalities, especially in serum levels of potassium, i anomaly, atrial septal defects, and those defects
calcium, and magnesium, may predispose patients to l that require complex atrial surgery); ventricular
arrhythmias. In addition, a new or unusual arrhythmia !arrhythmi.u (e.g., aortic valve cliseue, pulmonary
should raise a concern of drug toxicity, poisoning, 1valve disease, coronary artery anomalies); and heart
or an acquired systemic disorder. Table 11-7 lists ! bloclc (because of the underlying malformation or the i
etiologies predisposing children to arrhythmias. L~~~~.~~. ~.~~~~.~?..:. . . . . . .... . . . . . -.. . . .1
TACHYARRHYTHMIAS that is wider than the QRS in normal sinus rhytlun.

Abnormally fast heart rhythms may be cawed by a Ventricular arrhythmias create a wide QRS on the
reentrant circuit or an automatic arrhythmia. In a ECG because the electrical impulse does not track
reentrant circuit. an abnormal path ofcardiac muscle down the AV node and does not follow the normal
traps an electrical impulae in a circular pattern. The conduction system. In some patients, an underlying
leading edge of the electrical wave chases the trailing conduction disorder (e.g., a bundle branch block) can
edge in a monotxJnous loop, foll.owingthetrackofthe cause the QRS morphology in normal sinus rhythm
circuit. Each circuit ini.tiat5 a signal to the adjaamt to be wide, thus making supraventricular arrhythmias
myocardium and triggers a C::OrreJPOnding heartbeat. appear to be wide complex arrhythmias. However,
Reentrant arrhythmias may cause serious, J..ire.-threaten~ usually wide complex rhytluns (with a QRS duration
ingarrhythmias (e.g., ventricular tachycardia). In other > 120 m.s) should be assumed to be a ventricular ar-
cases, such as in reentrant SVT, the tachycardia can be rhythmia and treated as potentially life-threatening
symptomatic and annoying, butis rarelylife..threatening. until proven otherwise. Figure 11-8 illustrates several
Automatic arrhythmias are due to abnormally fast typical arrhythmia tracings, including ventricular
impulse formation. In automatic arrhythmias, a small tachycardia and ventricular fibrillation.
group of cells initiate a heartbeat that is too fast for Differential Diagnosis
the body's physiologic needs. Examples ofatrial au~
matid.ty are ectopic atrial tachycardia and multifocal • Ventricular tachycardia: Usually in the setting of
atrial tachycardia. Finally, some arrhythmias include congenital or acquired heart disease. Can occur
features of both reentrant circuits and automaticity. in drug ingestion, in genetic heart disease, or in
Atrial.fibrillation and -ventricular fibrillation are the most the setting of cardiomyopathy.
common examples of these more chaotic arrhythmias. • Ventricular fibrillation: Termln.al rhythm that
Regardless ofthe type ofarrhythmia. the appearance develops after hypoxia, ischemia, or high-voltage
of the ECG is a good first step in directing clinical electrical injury; predisposing !acton include CJID,
management. Table 11-8 illustrates one classification cardiomyopathy, and genetic heart diseue, includ-
system for pediatric blchyarrhythmias, based on the ing long QT syndrome and Brugada syndrome.
appearance of the QRS complex. • Arrhythmias auociat«l with an acceuory connec-
tion: An accessory connection creates a bypass
Wide Complex Tachycardia tract that electrically connects the atriwn and
Narrow complex arrhythmias usually have a QRS ~icle outside the AV node and can cause several
morphology identical to that of normal sinus rhythm. wide complex arrhythmias (see Narrow Complex
Wlde complex arrhythrniaa have a QRS morphology Tachycardia: .Accessory Connections on page 233).
TilLE 11-1. categorization of Tachyarrhythmias

...._ CampiBAn.,lwlllll ....... Camp. . Anlql 7
------ - - - -
i Automatic Ventricular tachycardia Sinus tachycardia

i Ectopic atrial tachycardia
lh-
Multlfocal atrial tachycardia
Junctional ectopic tachycardia
Antidromic AV reciprocating tachycardia• Atrial flutter
Scar~mediated ventricular tachycardia AV nodal reentrant tachycardia
Fallclcular ventricular tachycardia Orthodromic AV reciprocating tachycardia•
Torsade de polntes Permanent form of Junctional reciprocating
1-.
;
!
Ventricular fibrillation
Atrial Bbrillat1on with ftlltricular preexcitation•
j Tachyantlythmlaa In the "n~ complex" column may present with a wide CIRS canplex In the presence or bundle branc:t\ block,
tacltycardia•
Atrial fibrillation
i In the setting or alactrolyte abnormallllee r:x at hJstl heart ratee Q.e., with aberrated QRS complexes). Arrhythmlaa that depend on an
~ accessory AV comectlon are marked with an asterisk (•). Common and llfe-thl9atenlng forms or arrhy1hmla are addl9888d In the text.
i: AbbnMatlon: AV, atrkMintrlcular. c
~ For an introduction to other arrhythmias in the table, see Walsh EP, SaU JP, Triedman JK. Caroiac Anflythmias in ChikJren Bnd 'rbung j
i Adults with Congenit8J He6rl Dl688se. Philadelphia, PA: Uppincott Williams & Wilki'ls, 2001 .
.........................................................................................................................................................................................................-..............................................................................-.......i:
• Rate-rela~d bundle branch block (aberrancy): In

Sinus tachycardia
some cases, an SVT will occur at a rate that is too
fast for all the parts of the ventricle to conduct
Orthodromic
reentrant Although this is a benign finding. it cannot be
tachycardia assumed to be causing wide complex tachycardia
until other causes have been excluded.
Atrial flutter Treatmtlllt

WJ..de complex tachycardia should be treated as ifthe
Atrial fibrillation patient has ventricular tachycardia. If the patient is
hypotensive or unrespoMive, start basic life support
and cardiopulmonary resuscitation. Pediatric Advanced
Ventricular Life Support should be instituted as soon as possible.
tachycardia
High-quality cardiopuhnonary resuscitation and
Ventricular cardioversion or defibrillation must occur as early
fibrillation as possible in the treatment course. In most cases
FIGURE 11-l lllustration of tachycardia morphologies. of wide complex tachycardia, expert consultation
P-waves are difficult to appreciate in orthodromic is recommended after emergency resuscitation.
ventricular tachycardia because they may be subsumed Figure 11-9 outlines pathways for the management
into the QRS complex. By contrast, P-waves during of wide complex tachycardia.
atrial flutter may be more obvious because they occur Patients with nonnal blood pressure, intact mental
at a higher frequency than QRS complexes. In atrial status, and no other signs of cardiopulmonary in~
fibrillation, the QRS complexes occur at irregular
stability can undergo a more thorough evaluation.
intervals and the baseline tracing is interrupted by
frequent P-waves of changing morphologies and Diagnosis is usually enhanced by obtaining a 12-lead
intervals. P, electrical inscription of atrial contraction ECG during tachycardia and a suatained rhythm strip.
~e P-~~). ____..._._____.........-·-·-·-·- These tools can help differentiate ifa tachycardia is
Ventricular Tachycardia
• 3 or more beats
• Wide QRS (>0.08 eecond)
• AV dleeoclalon
• Rille: 150-300/mlnute
I
[ 1
Hemodynamically St!llble
I Hemodynamically Unstable
Hypotenelve
I
1 ~
Expert conaullation
Detl!lnnine cauae
IGo to Pediatric PuleeleM Arrest
Management .Aigoriltlm
I
T
AmloclllrOM: 5 mgo1<g IV
or
Procaln.mlda: 15 mg'kg IV
"Do not roultlely administer
amiOdarone and procainamide
together
T
Synchronized cardown~lon:
O.IH JJkg (If not effective,
lncreue to 2 Jlkg)
sustained or intermittent, identify the relationship reversed and it goes backward up the AV node, it
of the atrial signal and the ventricular signal, and is called antidromic reentrant tachycardia (ART).
determine the pattern of the wide QRS. Both ORT and ART are amenable to termination
by adenosine, but a patient in ART will have a wide
Narrow Complex TachyCardia
complex arrhythmia because the AV node is not
Narrow complex tachycardias conduct to the ven-
depolarizing the ventricles normally. Therefore, care
tricle using the normal cardiac conduction system.
must be taken to exclude a ventricular tachycardia
Usually the QRS will appear identical to the QRS in
prior to attempting intervention in ART. Once ORT
sinus rhythm. Typically narrow complex tachycardias
or ART is terminated, those children whose accessory
are well-tolerated by the patient. A 12-lead ECG can
connections can conduct from the atrium to the
often differentiate between an automatic tachycardia
ventricle may have ventricular preexdtation on their
and a reentrant tachycardia. Automatic tachyardias
ECGinsinusrhythm(Fig.ll-10). Thecombination
tend to gradually accelerate and decelerate in rate
of ventricular preexcitation and tachyarrhythmias
("warm up and cool down•), tend to have a P-wave
is called WPW syndrome. Ventricular preexcitation
80 to 120 ms before the QRS, and do not terminate
can occur without a tachyarrhythmia and all patients
with vagal maneuvers or AV nodal blocking agents
with ventricular preexcitati.on should be referred
(such as adenosine). The most common pathologic
to a cardiologist for further risk stratification. They
tachycardias in normal children are reentrant. These
are at risk for SVT and may have a very small risk
SVTs tend to have abrupt onset and offset, have a
of sudden death.
P-wave that follows the QRS instead of preceding
it, and responds abruptly to vagal maneuvers or AV T181ltmsnt
nodal blocking agents. Patients with hemodynamically unstable narrow
complex tachycardia should undergo prompt syn-
Dllfrlnlntlal Diagnosis chronized cardioversion. Synchronizing the electrical
• Sinus tachycardia: Often secondaryto fever. stress, impulse with the QRS complex decreases the risk
dehydration, hyperthyroidism, heart failure, and of the cardioversion therapy inadvertently inducing
anemia. ventricular fibrillation. When performed with the
• Reentrant supraventricular taChycardia: Most electrodes in the correct place and with the correct
cases result from an accessory connection be-- energy, cardioversion almost always terminates re-
tween the atrium and ventricle (notably WPW entrant tachycardia. If it is ineffective, then a rapid
syndrome) or an abnormal AV node (AV nodal reconsideration of the differential diagnosis should
reentrant tachycardia). occur. with special attention paid to the poasibility of
• Atrial.flutter: Most often occurs in normal neo- sinus tachycardia and another disease that requires
nates or in older children after cardiac .surgery. an immediate intervention (e.g., sepsis, volume loss,
• Atrial.fibrillation: Most often seen with left atrial drug intoxication).
enlargement due to structural heart disease, ven- In reentrant naiTOW complex tachycardia, vagal
tricular preexcltation, or cardiomyopathy. maneuvers (such as ice to face and carotid maasage)
enhance vagal tone to slow conduction In the AV node
Accessory Connections and often result in termination of the arrhythmia. If
An important subgroup ofSVTs occurs in children vagal maneuvers are ineffective, adenosine may be
whose hearts have an accessory connection. In normal given to block the AV node and break the reentrant
hearts, the AV node is the only electrical connection SVT. Reentrant SVT, whose circuit involves the AV
between the atrium and the ventricle. In hearts with node (especially ORT and atrioventricuJar nodal reen-
an accessory connection, a small pathway of con- try tachycardia [AVNRT]), is likely to break with the
ducting tissue crosses the AV valves, without going administration ofadenosine. Adenosine is unlikely to
through the AV node. These pathways may conduct tenninate a narrow complex tachycardia that results
from atrium to ventricle, from ventricle to atrium. or from Increased automaticity or a reentrant mechanism
in both directions. They cause a circuit that usually that does not involve the AV node (sinus tachycardia,
goes through the AV node, through the ventricle, ectopic atrial tachycardia, junctional ectopic tachy-
through the accessory pathway and back through cardia, atrial flutteJ; or atrial fibrillation). A rhythm
the atrium to the AV node again. When this circuit strip should be run during administrationofadenosine
goes down the AV node. it is called orthodromic because even if the arrhythmJa does not terminate,
reentrant tachycardia (ORT). When the circuit is adenosine may reveal a diagnostic clue. Adenosine
FIGURE 11-1D.. Ventricular preexcitation. In all12 leads, the PR interval is short and there is little or no iso919ctric
period between the end of the P-wave and the start of the QRS complex. Lead I shows an immediate and gradual
upslope belween the P-wave and the QRS complex. lhis pattern is often called a "delta wave• because of
~~~~9.-~-~~E..~~~P..~--~-~~..9.~..~-~-e!~:........................... . . . . ....... ....... . . . . . . . . . . . . . . .. . . .. . . ............. ............................. ................................ ........................
carries a very small risk ofventricular fibrillation and

it should be administered with a defibrillator avail- Sinus bradycardia
able. If adenosine returns the child to normal sinus
rhythm, pharmacotherapy may decrease the risk of
recurrence in the long run. <ltoices include digoxin,
P-blockers, andcaldum channel blocker. ~Blockers
Arst-degree IW block ~ ~ ~ ': ++ P
should be especially considered ifthe baseline ECG

after conversion of tachycardia reveals WPW syn- Second-degree
drome (short PR interval and delta wave). Digoxin and AV block
calcium channel blockers may increase conduction
across an accessory pathway and increase the small
risk ofsudden death because ofventricular fibrillation.
2:1/Wblock
Many patients with reentrant SVT prefer permanent
elimination of the arrhythmia to pharmacotherapy.
Catheter-based ablation ofan arrhythmia substrate is R R R R
a safe, effective procedure in the modern era. ~~~~ F'J_~ ': 1!.
Complete (third-degree) ---v-r--;--"''r-
Atrial flutter usually requires electrical or phar- AVblock
macologic cardioversion to restore sinus rhythm. FIGURE 11·11. 111ustratlon of bradycardia morphologies.
Postconversion pharmacotherapy may include digoxin, In first-degree a1rloventr1cular f.AV) block. the PR Interval
P-bloclcers, amiodarone, flecainide, or sot:aloL Ifatrial Is prolonged, but there Is always a 1:1 relationship
fibrillation is present and the patient is unstable, between atria and the ventricles. In second-degree
heart block, P-waves are regular, but Intermittently,
cardioversion is indicated. If the patient is stable,
the Impulse Is not conducted to the ventricle. When
the duration ofatrial fibrillation should be assessed. the AV node blocks, no QRS deflection occurs. If the
Ifsymptoms are of unknown duration or have been PR interval prolongs with each beat before the drop
present for 2 da)'5 or more, evaluation for intra-atrial {shown here), it is called Type I second-degree heart
clots or sustained anticoagulation is required prior block, or Wencksbach conduction. In 2:1 AV block,
to cardioversion and expert consultation is required. the impulses are only conducted to the ventricle half
of the time. Other ratios are possible as well {3: 1, 4:1,
BRADYARRHY11tMIAS etc.). In complete heart block, there is no electrical
relationship between the atria and the ventricles. P,
Bradyarrhythmlas may result from depressed auto- electrical inscription of atrial contraction (the P-wave);
maticity at the sinus node (sinus node dysfunction) or A, electrical inscription of the ventricular contraction
conduction bloclc before the ventricle is depolarized !~.~-.9.~--~~.P.!~L............. ..... ........... . .. ........................... . .......................
(AV bloclc). Bradyarrhythmias that may result from
sinus node dysfunction include sinus bradycardia,
rhythm) may occur. Patients with sinus bradycardia
junctional bradycardia, ectopic atrial bradycardia,
can usually increase their heart rate appropriately
and sinus pauses. Bradyarrhythrnias that may result
from AV block include first-degree heart block, sec- when stimulated.
First-degree heart block results from slowing of AV
ond-degree heart bloclc, and third-degree (complete)
conduction at the level of the AV node. First-degree
heart block.
heart block is associated with increased vagal tone;
Differential Diagnosis medication administration (digoxin and P-bloclcer);
Figure 11-11 shows the rhythm strips ofvarious bra- infectious etiologies (viral myocarditis, Lyme disease);
dycardias. Sinus bradycardia is caused by a decreased hypothel'lllia; electrolyte abnormalities (hypo-/hy-
rate of impulse generation at the sinus node. It may perkalemia, hypo-/hypercalcemia, and hypomagne-
be associated with increased vagal tone, hypoxia, semia); CHD; rheumatic fever; and cardiomyopathy.
central nervous system disorders with increased First-degree AV block is characterized on ECG by PR
intracranial pressure, hypothyroidism, hyperkalemia, interval prolongation for age and rate. Otherwise,
hypothermia, drug intoxication (digoxin, fl.-blockers, the rhythm is regular. originates in the sinus node,
calcium channel blockers), and prior atrial surgery. and has a normal QRS morphology.
It is also a normal finding in healthy athletes. When Second-degree heart block refers to episodic inter-
sinus bradycardia becomes too slow, sinus pauses ruption ofAV nodal conduction. Some P-waves are
or escape rhyt)un.s (ectopic atrial rhythm, junc- followed by QRS complexes; others are not, In healthy,
tional rhythm, or a slow idioventricular ventricular asymptomatic children, gradual PR prolongation
and occasional dropped beats are common during AV canal defect, or maternal lupus erythematosus
deep sleep because of high vagal tone. Daytime or (particularly anti-Ro antibodies). Other causes in-
symptomatic second-degree heart block is unusual clude open heart surgery (especially after large VSD
and requires further evaluation. closure), cardiomyopathy, or Lyme disease. Fetuses
Third-degree heart block exists when no atrial or newborns with congenital complete heart block
impulses are conducted to the ventricles. The atrial may present with hydrops fetalis.
rhythm and rate are normal for the patient's age,
and the ventricular rate is slowed markedly (40 to Trea1ment
55 beats per minute [bpm]). The QRS is of normal Figure ll-12 shows one management algorithm for
duration if an escape rhythm arises from the spe- bradycardia. Typically, no intervention is necessary
cialized ventricular conduction system (Junctional for bradycardia ifcardiac output is maintained and
rhythm). However, if an escape rhythm arises from the patient is asymptomatic.
the distal His bundle or Purkinje fibers, the QRS In asymptomatic patients with chronic first-de-
interval is prolonged (ldioventricular rhythm). gree heart block, usually no therapy is needed.
Congenital complete AV block can be an isolated Progressive or symptomatic first-degree heart block
abnormality or can be associated with I....TGA, requires further evaluation. Second-degree heart
Bradycardia with a pulse
fl*1ephrlne
0.01 rriQikg
R&plll -v 3-!5 mlnutaa Trelt
Hypertenelve Clllll
HydraiiD!e
l..abetalal
l\llropru~~lde
FIGURE 11-12.. Pediatric bradycardia management algorithm. ABC, airway, breathing, circulation; CPR,
~.~.~.i.~.P.~!!n~n.~..~.~~~~~.~.~..~.9.~..~~~.~~~~..~.~.~.~.:........................................................................ . ............ ....... ................................................._..
block limited to time of elevated vagal tone (such unstable, transcutaneous or transvenous pacing can
as when the patient is deeply asleep) is not usually be performed acutely. Permanent t:ransvenous or
pathologic. However, any other type ofsecond-degree epicardial pacemaker placement can be performed as
heart block requires further evaluation, especially if soon as practicaL Asymptomatic third-degree heart
it is symptomatic to prevent progression to higher block still requires additional evaluation because
degree heart block or elimination of the external some patients will progress to symptomatic brady-
factors (such as medications or infections) that may cardia and complete heart block is associated with
cause AV block. In rare cases, a pacemaker may be a small risk of sudden death events. Symptomatic
indicated for second-degree heart block if reliable third-degree heart block or complete heart block
AV conduction cannot be ensured. associated with higher-risk features (ectopy, wide
Complete heart block always requires further evalu- complex escape rhythms, or other heart disease) is
ation. Ifthe chlld with heart block is hemodynamically typically managed with permanent pacing.
KEY POINTS
• Cardiac munnurs are very common in children device, and cardiac transplantation recipients
of all ages and do not signify disease, but need with cardiac valvular disease. According to the
to be evaluated In the context of other signs 2007 BE prophylaxis guidelines, these patients
and symptoms. warrant dental prophylaxis.
• The absolute concentration of deoxygenated • Most cases of myocarditis In North America
hemoglobin determiles the presence of cyanosis. result from viral Infection of the myocardU11.
• Cyanosla In the newborn/neonate may be • Dilated or congestive cardiomyopathy is
awdlac, pulmonary, neurologic, or hematologic cNncterized by myocardial dysfunction and
In origin. FolloWing stabilization of a cym'lOtlc ventricular dlation; It Is uaually lclopathic.
Infant, the goal of the preliminary workup (chest • HCM may present as sudden death during
radiograph, ECG, hyperoxia test, and ECHO) physical exertion In an asymptomatic, otherwise
is to determine whether the lesion is cardiac ~Y individual.
or noncardlac In origin. • Therapy for HOM Is centered on preventing
• Comparison of preductal to postductal measure- fatal ventricular arrhythmias and Improving
ments of oxygen saturation allows the clinician left ventricular filling by slowing the Intrinsic
to evaluate for differential cyanosis, which can heart rate. Medications that reduce the risk
help narrow the differential diagnosis. of arrhythmia and decrease chronotropy and
• Cyanotic heart disease can be classified into inotropy include calcium channel blockers and
ductal Independent and ductal dependent, p-adrenerglc blocking agents.
with the latter being subcategorized Into • Normal heart rates vary by age. Tachycarcllc
ductal-dependent systemic blood flow and and bradycardlc rates should be compared to
ductal-dependent pulmonary blood flow. nonnal values for age.
• PGE1 therapy should be started in all unstable • The most common reason for narrow complex
Infants with suspected ductal-dependent CHD, tachycardias Is sinus tachycardia. Treatment of
even before definitive diagnosis. sinus tachycardia should Include an effort to
Identify extracaralac causes, Including Intravas-
• Patients with the highest risk of adverse out-
cular volume status, peripheral blood pressLn,
comes resulting from BE include those with fevers, pain, autonomic status, and hematocrit
prosthetic c.-dlac valves, previous endocaRitis,
unrapand cyw'lOtlc CHD Including those with • Narrow complex tachycardias tend to be well
palliative shunts and conduits, completely re- tolerated acutely, whereas wide complex tachy-
paired CHO with prosthetic material or a device cardias often result In hemodynamic instability
within 8 months of the procedure, repaired CHD and are considered a medical emergency.
with residual defects at the site or adjacent • Symptoms are the key feature in datennining
to the site of a prosthetic patch or prosthetic whether bradycardia requires treatment.
238 • BWEPRINTS Pedlatr1cs
CLINICAL VIGNETTES
VIGNETTE 1 for placement of bilateral ear t ubes as a toddler. He

A 7-day~ld male infant preeenta to the ED with leth- has had normal growth and development and his
argy and grunting respirations. He was born at term parents report that he is very active, easily keeping
after a normal pregnancy to a 34-yeer-old mother up with peers. He has had no recent illnesses. His
after an uncomplicated spontaneous vaginal delivery. mother reports that he was playing in the house that
His parents state that he has not eaten well over the morning, when he suddenly came to her complaining
last day and has been increasingly sleepy. HiB urine that his chest Mfelt funny, like butterflies.• She felt his
output has been normal until today. On examination, chest and reports that his heart feh like it was "beating
he appears pale and mottled with tachypnea and mild fast." On examination, he is a well-developed child
retractions. He Is lethargic but responds appropriately who is anxious but appears well. He is afebrile and
to painful stimuli. His heart rate is 170 and respiratory Is breathing comfortably. You are unable to count his
rate 80. His lungs are clear to auscultation bilaterally. heart rate by palpating his pulse so you connect him
You are able to palpate a strong right brachial pulse to a monitor, which demonstrates that his heart rate is
but cannot palpate femoral pulses. Capillary raflllln 220 and regular with a narrow complex. Blood pressure
the legs Is very prolonged. Is 75/50 and respiratory rate Ia 24.
1. Which ofthe following Ia the most likely diagnosis? 1. Which of the following is the most likely diagnosis?
a. Neonatal sepsis L Sinus tachycardia
b. Dehydration b. Ventricular tachycardia
c. Coarctation of the aorta c. svr
d. Congenital adrenal hyperplasia d. Complete heart block
e. TGA e. Atrial fibrillation
2. The Infant Ia endotracheally Intubated and Intrave- 2. You suspect that he has SVT. Which of the follow-
nous access is obtained. Which of the following is Ing tests Is most likely to aid with the diagnosis?
the most important diagnostic test to perform next? a. ECG
L Blood culture b. ECHO
b. ECHO c. Chest x-ray
c. Chest x-ray d. Telemetry
d. CT of chest e. Cardiac catheterization
1. 21-Hydroxylase level 3. The ECG confirms a narrow complex tachycardia
3. Which of the following treatments should be with a regular rhythm and a fixed rate of 220 bpm.
initiated next? P-waves are not diacemable. You ask the patient
L Normal saline bolus to try various vagal maneuvers (placing thumb in
b. Hydrocortisone mouth and blowing, standing on head) without
c. Nitroprusside infusion Improvement. Which of the following Is the next
d. Epinephrine infusion most appropriate therapy?
e. PGE1 infusion L ~-Blocker
b. Amiodarone
4. PGE1 infusion is begun intravenously and the c. Digoxin
patient is stabilized. As you monitor the patient, d. Adenosine
which of the following Is a common side effect
e. Transcutaneous pacing
of treatment with PGE1 infusion?
L Drymouth 4. While placing an IV, the patient becomes unstable,
b. Apnea with thready pulses. You are no longer able to
c. Hypotension obtain a blood pressure. He becomes uncon-
d. Vomiting scious. Which of the following is the next most
•• Rash appropriate therapy?
L Amiodarone
VIGNET1E2 b. Transcutaneous pacing
A 5-year-old previously heanhy boy presents to the c. Epinephrine
emergency department with complaints of uchest d. ~-Blocker
feeling funny." His medical history is significant only e. Synchronized cardioversion
VIGNETIE3 VIGNETIE4
A 1-year-old male arrives in t he ED with a 4-day A 1-day-old male infant is in the mother's delivery room
history of vomiting and abdominal pain. His mother and becomes increasingly cyanotic with agitation. The
states that he has had low-grade fevers, decreased physician is called and on examination he finds a com-
appetite, and has been breathing "fast and hard." fortably tachypneic, well-perfused but dusky newborn.
On examination, he is cool with delayed capHiary Ther9 is no murmur auscultated but he detects a loud
refill. He is alert and interactive. His heart rate is singleS:!. His lungs are c lear to auscultation bilaterally.
150 bpm and respirat ory rate 60 rpm. On abdominal He has easily palpable, strong brachial and femoral
examination, his liver edge is 4 em below the right pulses. He is taken back t o the nursery and is placed
subcostal margin. On cardiac auscultation, he has on telemetry with a continuous pulse oximeter. His heart
occasional irmgularity and a gallop but no murmur is rate is 160 bpm and his saturation is 75% in the right
heara. He has mild subcostal retractions w ith coarse upper extr9mity and 85% in the left lower extr9mity.
lung sounds throughout.
1. Which o1 the following is the most likely diagnosis?
1. Which of the following is the most likely diagnosis? L Neonatal sepsis
L Pneumonia b. Coarctation of the aorta
b. Viral gastroenteritis c. Obstructed TAPVR
c. Aortic valve stenosis d. TGA
d. DCM e. Anemia
e. Dehydration 2. The infant is transferred to an intensive care unit,
2. A chest x-ray is obtained which reveals a large and an ECHO is done, which confirms the diagnosis
heart with mild pulmonary edema. The vital signs of TGA. As the ECHO Is being done, the child is
remain stable and the child is neurologically becoming more cyanotic. Which o1 the following
appropriate. Which of the following is the most pharmacologic Intervention could be attempted
important diagnostic test to perform next? to improve the saturations?
a. Blood culture L Epinephrine infusion
b. ECHO II. PGE1 infusion
c. Complete blood count with differential c. Tylenol
d. CT of chest d. Hydrocortisone
.. B-type natriuretic pepdde .. Antibiotics
3. A bedside ECHO demonstrates severe systolic 3. The PGE1 is started and the child continues to
dysfunction with moderate mitral regurgitation. have oxygen saturations in the 50% to 60% range.
The child Is breathing quickly but has a stable The baby is becoming hypotensive and volume is
blood pressure, perfusion appears adequate, and being given. Which o1 the following lnterventlonal
he Is Interacting appropriately. What Is the Initial procedures should be attempted quickly?
class of drugs to be prescribed? a. Arterial switch procedure
a. Diuretics b. Norwood procedure
b. ACE inhibitors c. Atrial septostomy
c. Anticoagulation d. Pulmonary valve dilation
d. Phenylephrine e. Chesttube
e. Narcotics
4. What surgical Intervention Is required to correct
•· The toddler Is transferred to the Intensive care this circulation?
unit, and there he becomes extremely tachy- a. Arterial switch procedure
cardic and starts t o act very agitated. His blood b. Norwood procedure
preesure is high but his perfusion is poor. What c. Bidir9ctional Glenn operation
is the appropriate therapy for this patient who d. BTshunt
is now showing progressive evidence of poor .. Fontan operation
cardiac output including c hanges in neurologic
status? VIGNET1E5
a. Phenylephrine A term newborn male is transferred to the neonatal
b. ~-Blocker intensive care unit at 12 hours of life after a nurse
c. Benzodiazepine noted perioral cyanosis during breastfeeding. The
d. Intubation infant has mild t achypnea, with a respiratory rate
e. Narcotic of 65 breaths per m inute, a heart rate of 155 bpm,
2AO • BLUEPRINTS Pediabics
a normal upper extremity BP for age, and a right at 3 Umin with no change in the saturations. All
upper arm saturation of 80%. On examination, there of the following are potential options to improve
Is mild cyanosis, no retractions or grunting, a IIWI the saturations except:
harsher systolic eJection munnur at the left upper a. Nonnal saline bolus
sternal border, no hepatomegaly, and 2+ pulses in b. Morphine sulfate IV
the upper and lower extremities with a capillary refill c. Knee to chest poeition
of 2 seconds. d. Make attempts to calm the patient
1. What is the next best management option to aid
e. Change to a non- rebreather at 10 Limin to
maximize 0 2 delivery
In the diagnosis?
a. Chest radiograph VIGNETTE&
b. Venous blood gas
A 10-week-old ex-full-term female presents for d~
c. Complete blood count creased feeding. She is bottle fed and was taking
d. ECG
2 to 3 oz per feed over 16 to 20 minutes without
e. Blood glucose difficulty until a week ago, at which point she began
2. The chest radiograph raveals a nonnal cardiac taking only 1 oz at a time, but over 20 minutes and
size and decreased pulmonary vascular marl<lngs. with several breaks. Her mother describes that she
What Is the most likely diagnosis? seems to breathe faster with feeds and sweats on
a. Complete AV septal detect her forehead. She has not had any fevers or viral
b. TAPVR respiratory symptoms. On examination, she is overall
c. Critical aortic stenosis comfortable, but tachypneic without Increased work of
d. TOF breathing. Her heart rate Is 145 bpm and 0 2 saturations
e. HLHS are 99%. Weight gain since the prior visit has been
minimal at 5 glday. Examination reveals a harsh IIINI
3. Cardiology Is consulted, but an ECHO cannot be
systolic murmur, a hyperdynamic precordium, and a
obtained for over an hour. The decision Is made
liver edge 3 em below the costal margin with strong
to proceed with a hyperoxia test. An initial ABG brachial and femoral pulses.
obtained from the right radial artery demonstrates
a P~ of 45 mm Hg. After administration of 1. Based on 1tle history and physical examination,
100% Fl02 via an oxygen hood, a repeat ABG what is the most likely diagnosis?
from the right radial artery demonstrates a PBO:! L ASD
of 62 mm Hg. This is most consistent with which b. VSD
ofthe following? c. Coarctation of the aorta
1. PPHN d.TOF
b. Pneumothorax e. Pulmonary stenosis
c. Congenital diaphragmatic hemla 2. Chest radiograph performed as part of the evalu-
d. Slgnlftcant Intrapulmonary shunting
ation demonstrates cardiomegaly and increased
e. lntracardlac shunting pulmonary vascular markings. These findings
4. Based on the results, what is the next most ap- can be seen with all of the following fonns of
propriate step in the management of this infant? CHD except for:
1. Start PGE, L Large PDA
b. Initiate supplemental oxygen via nasal cannula b. Moderate to large VSD
c. Endotracheal Intubation and mechanical c. Moderate aortic stenosis
ventilation d. Complete AV septal defect
d. Nonnal saline bolus e. Truncus artertosus
.. Empiric antibiotics
3. Echocardiography performed during a cardiology
5. Echocardiography reveals TOF with moderate visit demonstrates a large perimembranous VSD
right ventricular outflow tract obstruction. Given with lett-sided heart dilation, no significant valve
the size of the pulmonary valve, PGE is able to be abnonnalities, and normal cardiac function. The
weaned off on day of life 3 with stable saturations best option to ameliorate symptoms is:
In the 90% to 92% range on room air. Repeat a. Change feeding frequency to fiV8ry 90 minutes
echocardlography 2 days after discontinuation of formula
of PGE conflnns PDA c losure. You are called b. Start digoxin
to the bedside because of acute desaturation c. Start Lasix
to the 70% range asaociated with agitation and d. Refer for immediate surgical closure
tachypnea. The nurse has placed a nasal cannula e. Start solid feeding early to improve caloric intake
._ The next patient In clinic Is a 6-month-old male a. Most small muscular VSDs will close spon-
with a known small muscular VSD diagnosed In taneously over the first several years of
the neonatal period as part of an evaluation for age.
a murmur. Hia weight and height are at the 60th b. All VSDs lead to clinical symptoms at some
percentile for age and he takes 4 to 6 oz per feed point during childhood.
as well as some solids. His heart rate, 1'88piratory c. VSD is one ofthe most common forma of CHD.
rate, blood pl'88sure, and saturations are normal. d. Some small VSDs may require surgical in-
On examination, there is a short, high-pitched tervention if they are located near the aortic
systolic munnur along the left sternal border. valve and there is the development of aortic
Otherwise, his examination is normal. His mother regurgitation.
is very concerned about his cardiac diagnosis. All t. Children with small VSDs are unrestricted in
of the following are t11.1e except: their physical activity.
ANSWERS
VIGNETtE 1 QuestiOn 1 allowing for further management. The ECHO may

1.AnswerC: demonstrate narrowing In the aorta, the presence
Coarctation of the aorta accounts for 8% of congenital or absence of the ductus arteriosus, the ventricular
heart defects and has a male-to-female predominance function and geometry, and presence of any associated
of 2:1. The narrowing Is usually located In the descend- lesions, such as bicuspid aortic valve.
Ing aorta at the Insertion site of the ductus artertosus A chest x-ray may demonstrate cardiomegaly but is
and results In obstruction to blood flow and Increased typically nondlagnostlc. A chest CT will provide diag-
LV aftertoad. The degree of narrowing determines the nosis, but Is not necessary In this scenario. Although
clinical severity. A neonate with a critical coarctation a blood cuHure may be indicated in this child, it will
(one where the narrowing is so severe that the ductus not provide immediate diagnosis.
arteriosus is necessary to supply systemic blood flow) A bedside ECHO demonstrates asevere juxtaductal
may present as in this vignette, with evidence of shock coarctation of t he aorta with a tiny ductus arteriosus,
as the ductus arteriosus closes. On examination, decreased left ventricular function, and a bicuspid
pulses distal to the coarctation will be weak or absent aortic valve.
but preductal pulses (right radial) may be preserved.
Late-onset neonatal sepsis may pr88ent similarly, VIGNETtE 1 Question 3
with nonspecific signs such as poor feeding, lethargy, !.Answer E:
and tachypnea and can progress to shock. Dehydration The goal of early therapy In this scenario Is reopening
may also occur commonly In this age group, because of the ductus arteriosus, which will restore perfusion
of Insufficient Intake, and can result In hypovolemic distal to the coarctation. The ductus arteriosus Is sen-
shock. Congenital adrenal hyperplasia Is most com- sitive to prostaglandin. PGE1 infusion has a very short
monly a result of 21-hydroxylase deficiency. Males half-life so must be given as a continuous intravenous
born with this defect have no genital abnormalities infusion. In a stable infant, typical starting doses are
and may present with poor feeding, failure to thrive, 0.02 to 0.05 IJg/kgfmin but in a patient in shock with
dehydration, and shock. Although physical examination a tiny or closed ductus, doses up to 0.1 IJQ/kg/min
findings may be similar and nonspecific in all of these may be necessary.
scenarios, there should be no discrepancy between A normal saline bolus may be indicated in this child,
upper W"td lower extremity pulses. TGA is a common who has been eating poor1y and may have a degree
congenital heart defect in which the aorta arises from of intravascular volume depletion. However, a fluid
the RV and pulmonary artery from the LV so that the bolus will not restore distal perfusion because it will
circuits are in parallel rather thW'l in series. Infants with have no effect on the ductus arteriosus. Similarly, with
TGA typically present at birth with cyanosis, rather decreased left ventricular function, epinephrine infusion
than shock. may also be Indicated. Eplnephrtne Is an excellent
Inotropic agent but at higher doses Is associated with
VIGNETtE 1 Queatlan 2 Increased systemic vascular resistance, which may
2.Answer B: be detrimental to a failing ventricle. It w ill also not
The diagnosis of coarctation of the aorta is made with improve distal perfusion because that relies entirely
ECHO, which can be done rapidly and at the bedside, on patency of the ductus arteriosus. Nitroprusside
2A2 • BLUEPRINTS Pediabics
is a vasodilaling agent that is used for hypertension relationship. Rarely, the QRS may be wide, because
and for heart failure, to decrease systemic afterload. of transient, rate-limited bundle branch block or In
AHhough the child In this scenario has heart failure, the setting of an unusual reentry tachycardia called
the Increased afterload Is due to a •ftxed~ obstruction antidromic SVT. ECHO Is useful for evaluating cardiac
~.e., the coarctation) so administration of a vasodilator anatomy and function and may demonstrate 1hat
in this setting is contraindicated. Last, hydrcoortiaone there is tachycardia but will not be diagnostic. Chest
is used in infanta with glucocorticoid or mineralooorti- x-ray and cardiac catheterization are not indicated
coid deficiency but would have no role in 1his setting. in this scenario. Telemetry may be useful but simple
monitoring will not allow measurement of intervals or
VIGNmE 1 Q..Uon 4 assessment of multiple leads.
4.Answer B:
The most concerning side effect of prostaglandin VIGNETTE 2 Question 3
therapy is apnea, which occurs commonly with the 3.AnswerD:
institution of therapy and is dose dependent. Infants Rapid administration of adenosine causes transient
who are not intubated and ventilated prior to the start block of the AV node and will result in prompt ter-
of prostaglandin Infusion necessitate close monitoring mination of most forms of SVT (those Involving the
and often require Intubation. For this reason, when AV node In the circuit). Adenosine must be delivered
transferring a newborn on a prostaglandin Infusion to via rapid IV push because the half-lite Is extremely
a tertiary hospital, many centers will prophylactically short. A P-blocker or digoxin may be prescribed for
intubate a newborn prior to the transfer. long-term treatment/prevention of SVT but is unlikely
Prostaglandin may cauae systemic vasodilation, to terminate an acute tachycardia. Amiodarone is an
but signifiCant hypotension Is uncommon. The other antiarrhythmic that may be useful for incessant SVT
side effects may be reported with many drugs, but in but should only be given under the supervision of a
general prostaglandin infusion is well tolerated. cardiologist. Transcutaneous pacing is not indicated.
VIGNmE 2 Q...Uon1 VIGNETTE 2 Qu88tian 4

1.Answer C: 4. Answer E:
SVT is 1he most common pathologic tachycardia that Patients with unstable hemodynamics and SVT should
occurs in pediatric patients. Collectively, the term su- undergo Immediate synchronized cardloverslon (0.5 to
praventrfcu/ar tachycardia encompasses all tachycan::lla 1 Jlkg) without delay. Amlodarone, ~blocker therapy,
that originates above 1he ventricle. The characteristic and transcutaneous pacing may have a role In stable
features Include abrupt onset and termination, fixed Incessant SVT. Epinephrine Is an Inotropic agent that
cycle length, normal QRS complexes, and usually is used for resuscitation and ventricular dysfunction.
lack of discernible P-waves. In pediatric patients, two
mechanisms, atrioventricular reentry tachycardia and VIGNETTE 3 Question 1
AVNRT, predominate. 1.AnswerD:
Sinus tachycardia occurs frequently in all ages and Cardiomyopathies are diseases of the heart muscle,
is the most common form of tachycardia. In this patient characterized by abnormal findings of chamber size
with absence of accompanying causes (such as fever), and wall thickness or functional abnormalities. Car-
a heart rate above 200 points to a possible pathologic diomyopathies can be either primary (confined to
mechanism. Ventricular tachycardia is uncommon in heart muscle) or secondary (myocardial damage as
the pediatric patient. The hallmark feature is a wide a result of a systemic illness). The annual incidence
QRS complex tachycardia. Although most ventricular of all case of pediatric cardiomyopathy is between
tachycardias are unstable, a rare patient will present 1.13 and 1.24 cases per 100,000 children. The most
wHh a stable ventricular tachycardia. Complete heart common cartllomyopsthy In children Is DCM, which
block occurs when conduction does not occur across Is characterized by left ventricular systolic dysfunction
the AV node. This leads to bradycardia, typically with an increase in left ventricular size. Mitral regur-
with a junctional or ventricular escape rhythm. Atrial gitation and ventricular arrhythmias can develop and
fibrillation can lead to tachycardia when there is rapid be present at initial presentation.
ventricular conduction. This arrhythmia, which is very DCMs can present with signs and symptoms of
uncommon in the pediatric population, is associated congestive heart failure- tachycardia. diaphoresis,
with an irregular rhythm. breathlessness, abdominal pain, and pallor. Young
children often present with abdominal pain, vomiting,
VIGNmE 2 Question 2 and anorexia because of mesenteric ischemia. On
2.AnswerA: examination, these patients may have sinus tachy-
The diagnosis of SVT is made by ECG. The ECG will cardia with or without ectopy, a gallop rhythm, jugular
demonstrate a tachycardia with normal QRS duration. venous distension, hepatomegaly, and a murmur that
When P-waves are evident, there is usually a 1:1 AV is consistent with mitral regurgitation.
Pneumonia can pi'8S8nt similarly, with vomiting would not be appropriate. Although anticoagulation
and Increased work of breathing, and If the Infection will be important, eventually it is not the first class of
Is severe and leeds to bacteremia the patient can drugs to use.
present In septic shock. If the Infection leads to lack In decompensated heart failure, the systemic
of oral Intake and fever leads to Insensible fluid loss, vascular resistance is elevated and initially the blood
the child could be dehydrated. The child in the above pressure will be maintained even if the overall cardiac
case has hepatomegaly out of proportion to symptoms output is poor. Further increasing the systemic vascular
and signs consistent with infection. The child also resistance will increase the afterload on the heart and
has a gallop rhythm and irregular heartbeat because lead to further decompensation.
of ventricular ectopy, which is inconsistent with viral Eventually, after initial resuscitation, the goal will
gastroenteritis or bacterial pneumonia. be to optimize outpatient heart-failure management
A child with aortic valve stenosis would not present with an ACE inhibitor and a P-blocker. In addition, the
to the emergency department in shock. Aortic valve patient will require anticoagulation to prevent thrombus
disease is usually detected on a routine examination formation in the dilated LV.
when a care provider hears a systolic ejection murmur
and click. It would not account for the many signs and VIGNETIE 3 Question 4
symptoms of congestive heart failure that are present 4.Answer 0:
on this child's examination. Intubation and positive pressure ventilation will decrease
the arterload and wall stress on the left side of the
VIGNETIE 3 Quedon 2 heart. It will now be safe to sedate the child in order
2.Answer B: to decrease oxygen demand and allow for optimiza-
The diagnosis of cardiomyopathy is dependent on tion of the child's cardiac output. Intubation in these
patient history, physical examination, and echocar- children is not without risk and should be performed
diographic features of DCM. The ECHO should be in a controlled manner with appropriate personnel
confirmatory and done quickly to assess the severity and resuscitation drugs close by. If perfusion does
of the ventricular dilation and systolic dysfunction, not increase with the initiation of positive pressure
but should not interrupt close surveillance and rapid ventilation or the child becomes hypotensive, further
initiation of additional therapy. On ECHO, the ventricular therapy is warranted.
size will be measured, the ejection fraction calculated, If the blood pressure Is adequate but perfusion Is
and the presence and severtty of mitral regurgitation poor, modulation of aftertoad should be attempted
determined. Patients presenting In this degree offallure with vasodilator therapy such as mllrtnone, which
often develop cardlogenlc shock quickly after amval will provide Inotropic support and vasodilation, or
and require rapid escalation of therapy. They are also with nitroprusside. In children with heart failure and
at risk of lif~threatening arrhythmias. hypotension associated with hypoperfusion, contin-
ACT of the chest would show a large heart but would uous intravenous epinephrine should be considered.
not be able to estimate the severity of the dysfunction. Although sedation (benzodiazepines and narcotics)
It would not be safe to place this child in aCT scanner may decrease the oxygen demand and calm an agi-
until he is supported and well compensated. tated child, in patients with heart failure it may blunt
The laboratory tests listed may be done to guide the catecholamine surge that is required to maintain
future therapy but are not necessary for initial diag- cardiac output and lead to a rapid decline and car-
nosis or management. A B-type nabiuretic peptide diogenic shock.
may help differentiate between myocardial disease Increasing afterload with phenylephrine, with
and pneumonia, but it Is not the sole test necessary no additional inotropic support, will lead to further
to diagnose a cardiomyopathy. deterioration.
VIGNETIE 3 Quatlan 3 VIGNETIE 4 Question 1

3. Answer A:. t.AnswerD:
Therapy of DCM is mainly directed at treatment of D-TGA accounts tor 5% to 84)6 of congenital heart
heart failure-related symptoms and prevention of defects and is the most common fonn of cyanotic
disease-related complications. Treatment of decom- CHD presenting in the first 24 hours of life. In this de-
pensated heart failure is focused on diuresis with fect, the aorta arises anteriorty from the morphologic
loop and thiazide diuretics for volume overload and RV and the pulmonary artery arises posteriorly from
afterload reduction. In addition, given the degree of the lY.. The pulmonary and systemic circulations are
dysfunction, initiation of vasodilatoryfmotropic support therefore in parallel rather than series; the systemic
with IV milrinone would also be reasonable if the blood circuit (deoxygenated blood) is recirculated through the
pressure supports this. body, whereas the pulmonary circuit (oxygenated blood)
This child's examination is concerning enough recirculates through the lungs. Associated lesions occur
that starting an oral regimen with an ACE inhibitor in one-third of infants, with VSD baing most common.
Only 25% of patients with 0 -TGA are diagnosed in intra-atrial communication is achieved, the child
utero by ultrasound; most present after delivery with should have Improved hemodynamics and often ttle
cyanosis. In the absence of apparent lung disease, PGE1 Infusion can be discontinued. Once the atrial
cyanotic neonates usually have CHO. Children with communication Is adequate, the child should be able
TGA will usually present with •comfortabletachypnea." to wah safely tor the corrective surgical Intervention.
On examination, these newboms will have a loud,
single 5t but most often do not have a munnur. Their VIGNETlE 4 Question 4
oxygen saturations can range depending on the size 4.Answerk
of the intracardiac shunt. This patient has reverse After preoperative stabilization, arterial switch p~
differential cyanosis. This phenomenon is only seen cedure is typically performed in the first week of life.
in patients with TGA with pulmonary hypertension or The arterial switch operation establishes sequential
an aortic coarctation. c irculations with concordant atrioventricular and
Neonatal sepsis will not present with comfortable ventriculoarterial connections. Concurrent closure of
tachypnea. Children with sepsis may be cyanotic intracardiac shunts (ASO or VSO) as well as ligation of
and tachypneic but will be working hard to breathe. the ductus arteriosus is pelformed. Surgery for 0-TGA
Obstructed TAPVR presents with cyanosis, but these generally occurs within the ftrst week of life. In term
children will also have evidence of difficulty In breath- Infants, regardless of coronary artery pattern, mortality
Ing because of pulmonary edema from the venous rates remain low for the arterial switch procedure (1.1%
obstruction. to 6% In most centers).
Coarctation of the aorta also makes up 5% to 8% The Norwood operation is the first-stage palliative
of all CHO. This illness usually presents later in the operation that is perfonned tor infants with HLHS.
newborn period after the ductus arteriosus closes. The first operation consists of three components: an
These newborns do not present with cyanosis but aortic arch reconstruction, atrial septectomy, and the
usually with feeding intolerance. institution of a stable source (BTS or right ventricle to
pulmonary artery conduit) of pulmonary blood flow.
VIGNmE 4 Q...Uan 2 At 3 to 6 months of age, the child will undergo a bidi-
2.Answer B: rectional Glenn or hemi-Fontan operation, a superior
The goal of starting a PGE, infusion is to reopen the vena cava to pulmonary artery anastomosis. At 2 to 4
ductus arteriosus, which will Increase pulmonary blood years of age, the child wnl have a Fontan procedure,
ftow and Improve the oxygen saturations. The ductus an Inferior vena cava to pulmonary artery anastomosis,
arteriosus Is sensitive to prostaglandin. The Initiation thereby completing their single-ventricle palliation.
of PGE1 can be quick and Is relatively safe. The side
effects of PGE1 include apnea, fever, and systemic VIGNETlE 5 Question 1
vasodilation. Occasionally, a child will need to be 1.AnswerA.
intubated for frequent and/or persistent apneic events. In the evaluation of a neonate with cyanosis, deter-
Epinephrine may increase cardiac output and may mination of the degree of compromise is of utmost
slightly improve oxygen saturations but not as reliably importance. In this case, the infant is cyanotic and
as reopening the ductus arteriosus. tachypneic, but not in acute respiratory distress and
with intact systemic perfusion. A chest radiograph is a
VIGNmE 4 Q...Uan 3 readily available and reproducible test, which provides
3.Answer C: a significant amount of information about both the
The definitive treatment of 0 -TGA is surgical but other cardiac and pulmonary systems.
management (pharmacologic and interventionaO may From a cardiac perspective, evaluation of the cardio-
be necessary urgently after delivery because of hypox- thoraclc ratio (which should be < 50%) and the qualitative
emia. This urgent, postdellvery treatment Is directed amount of pulmonary blood ftow Is extremely useful.
toward the establishment of adequate tissue oxygen A paucity of pulmonary vascular markings suggests
delivery, whiCh Ia achieved via the mixing of the sys- an inadequate amount of pulmonary blood flow and
temic and pulmonary circulations, thereby allowing points toward the possibility of a ductal-dependent
oxygenated blood to raach the systemic circulation. pulmonary lesion. Increased pulmonary vascular
The most important component to allow for adequate markings in the early neonatal period could suggest
mixing is a large ASO. If the atrial communication is obstruction to pulmonary venous return or significant
small, it must be enlarged to allow for adequate oxy- left-sided obstruction to blood flow. It would be very
genation. Ar1 atrial balloon septostomy can be done unusual to have significant pulmonary overcirculation
at the bedside with echocardiographic guidance, or it in the first several days of life. Primary pulmonary ab-
can be done in the cardiac catheterization laboratory nonnalities such as meconium aspiration, congenital
with the guidance of ftuoroscopy. Once an adequate pneumonia, or pneumothorax are readily diagnosed
by chest radiograph. Alternative diagnoses such as lesion such as congenital diaphragmatic hernia have
congenital diaphragmatic hemla can also be detected. a reasonable degree of normal lung tissue, allowing
In the presence of a normal heart rate for age, an for an increase in Pao2 w ith hyperoxygenatlon.
ECG Is unlikely to provide substantial data to help
with the diagnosis of cyanosis, although it is often VIGNETlE 5 Quasllan 4
obtained as part of a more detailed evaluation for 4.AnawerA.
CHD. A blood glucose and complete blood count In the aetting of a cyanotic neonate with tachypnea
may be useful, but do not generally point toward a without respiratory distress or decompensation, intact
diagnosis. Of note, polycythemia generally makes systemic perfusion, and a hyperoxia test that did not
cyanosis more apparent, but in this case, the pulse lead to a significant increase in PaD:!. a variant of
oximetry is diagnostic of desaturation. Lastly, a VBG ductal-dependent pulmonary blood flow CHD should
can be very useful in determining acid/base status be highly suspected. As such, PGE should be initi-
and significant hypercarbia, but unlike an ABG does ated until a more definitive evaluation of the anatomy
not provide a P~. {echocardiography) can be performed.
Increasing inspired oxygen will not significantly im-
VIGNETTE 5 Question 2 prove saturation In the presence of a fixed lntracardlac
2.Answer D. shunt. Aggressive airway control In the absence of
The results of this chest radiograph point toward a respiratory distress Is not Indicated. However, apnea
cardiac lesion with decreased pulmonary blood flow. Is a known side effect of PGE and practitioners need
The most likely diagnosis is TOF with significant right to be able to control an airway in any infant where PGE
ventricular outflow tract obstruction. A left-to-right is initiated. Volume resuscitation with normal saline is
shunting lesion such as a complete AVSD would gen- indicated if there is a ooncern for intravascular volume
erally lead to an increased amount of pulmonary blood depletion or hypoperfusion, but is unlikely to improve
flow, but only after the PVR decreased, which would be pulmonary b lood flow to a significant degree in this
unusual in a child of this age. The chest radiograph at case. Infection should be high on the differential in any
this age would more commonly be normal, unless there infant with symptoms of tachypnea and cyanosis and
was significant AV valve regurgitation in utero, which is often empirically initiated in neonates with suspected
could lead to cardiomegaly. TAPVR, which is generally cardiac disease while the evaluation is ongoing, but
obstructive to some degree, would be expected to in this case, the data point to the need to establish
demonstrated Increased Interstitial markings. Even In ductal patency first.
the absence of obstruction, the pulmonary vasculabJre
would not be decreased. Both crttlcal aortic stenosis VIGNETTE 5 Quastlan 5
and HLHS would not present with preserved systemic 5.Anawer E.
perfusion, as in this case, and there is generally in- In some instances, neonates with TOF who are started
creased pulmonary markings from either pulmonary on PGE because of initial desaturation can improve
venous congestion or early overcirculation. their total pulmonary blood flow as the PVR decreases.
If the right ventricular outflow tract is of reasonable
VIGNETTE 5 Quedon 3 size, PGE can be stopped.
3.Answer E: However, children with TOF are at risk for hyper-
In larger, tertiary care centers, access to pediatric cyanotic or ~ret• spells. It is vital that these spells be
echocardiography may be readily available, but at recognized and acted on promptly, to avoid circulatory
other centers, this may not be the case. A hyperoxia compromise. The initial interventions include calming
test can be utilized to determine if cyanosis is related the Infant and positioning in the knee to chest position,
to Intrapulmonary or lntracardlac shunting. Failure to both of which are easily accomplished. Increasing
significantly Increase the Pao2 on an ABG after Inspiring Intravascular volume with a normal saline bolus can
a high o.z concentration suggests a fixed lntracardlac Improve rtght ventrtcular filling and pulmonary blood
shunt. The Pao2 often increases in the presence of flow, but obviously requires IV access. Morphine can
significant intrapulmonary shunting. In some cases, also be used, but also requires IV access, and as with
the increase in Pa~ is equivocal, especially in the any medication that can lead to sedation, practitioners
prusence of severe lung disease. must have the ability to maintain an airway. Although
Many children with PPHN have a PDA. leading to providing some additional oxygen can improve respira-
differential cyanosis, which is why obtaining a pre- tory efficiency, the desaturation is caused by increased
ductal ABG is important, as this usually represents intracardiac shunting and decreased pulmonary blood
the best estimate of the pulmonary venous return. flow, so increasing 0 2 delivery to the lungs is unlikely
Other primary pulmonary disease processes such to improve saturations and may delay the other ma-
as a pneumothorax and a thoracic space-occupying neuvers to improve pulmonary blood flow.
VIGNB'TE 8 Quesllan1 VIGNETTE 8 Question 3

1.Answer8: 3.AnswerC:
The infant in this case has classic signs and symptoms There are multiple approaches to the symptom-
of pulmonary overcirculation. The history of normal atic treatment of pulmonary overcirculation from
feeding and growth that begins to change over time a moderate to large VSD. Typicaly, initiation of a
with the development of respiratory symptoms with diuretic can improve t he respiratory rate and lead to
feeds is due to the progressive increase in pulmonary a decrease in caloric expenditure. In an infant of this
blood flow as the PVR falls over the first several post- age with these relatively new symptoms, it would be
natal weeks t o months. This fall in PVR is variable, most reasonable to attempt some form of medical
with some infants demonstrating symptoms in the first management. Most infant s with a moderate to large
several weeks of life, whereas others may not have symptomatic VSD require surgical repair at 4 to 6
significant symptoms for the first 4 to 6 months of life. months of life. For children with significant symp-
The murmur on examination, comfortable tachypnea, toms of overclrculatlon with poor growth and lack of
and hepatomegaly also point toward a cardiac etiology symptom control with medical management, ear1y
for the change In feeding and growth. A moderate to surgical Intervention can be considered. Increasing
large VSD would be the most likely etiology for the feeding frequency could theoretically increase caloric
symptoms and physical examination findings. ASDs intake, but feeding also leads to caloric expenditure
generally do not present in infancy with a degree of and the infant may not be interested in feeding at
pulmonary cvercirculation that leads to symptoms. This shorter intervals. Digoxin was used in the past for
is based on the total flow across the defect, which is pulmonary overcirculation, but is rarely used today.
less than a VSD because of the pressure difference ACE inhibitors are often added to diuretics for bet-
between the left and right atria, when compared to the ter symptom control. Starting solids in a child of
pressure difference between the LV and RV. Symptomatic this age may not be possible because of oromotor
coarctation can present with tachypnea because of left tone, and typically the caloric density of solid intake
atrial hypertension, but more often prasents outside even with typical amounts in early infancy does not
of the neonatal period wtth an abnormal physical ex- provide significant caloric supplementation. Rice
amination, either hypertension or decreased femoral cereal can be added to formula or expressed breast
p ulses. TOF and pulmonary stenosis (PS), both lesions milk to Increase caloric density, but t he Increase In
that can result In decreased pulmonary blood flow, viscosity may not be t olerated.
would not be expected to present w ith t achypnea
and hepatomegaly. Additionally, growth is generally VIGNETTE 6 Quedan •
preserved because of the lack of significant respiratory 4.AnswerB:
symptoms and the appropriate use of calories. VSDs are one of the moat common forms of CHD.
Small VSDa generally do not lead to any symptoms
VIGNmE 8 Q...Uan 2 and the vast majority will close spontaneously. In
2.Answer c. the event that they do not close, they rarely require
Cardiac lesions that lead to either a significant amount intervention. Moderate to larger size defects can
of pre- or post-tricuspid shunting demonstrate increased get smaller over time, but much of this depends on
pulmonary vascular martclngs and cardiomegaly on their location, with muscular and perimembranous
chest radiograph. An ASD is a classic pre-tricuspid defects being much more likely to decrease in size
shunt, as Is partial anomalous pulmonary venous when compared to Inlet and doubly committed
return. A VSD Is a classic post-tr1cuspld shunt, as Is type defects. Small per1membranous and especially
a PDA A complete AVSD has components of both a doubly committed defects can lead to aortic valve
pre- and post-tr1cuspld shunt (because of the ASD regurgnatlon secondary to prolapse of one of the
and VSD). Symptomatic aortic stenosis may present aortic valve cusps into the defect. Even though the
with some degree of cardiomegaly, but the total pul- VSD may be small and of little hemodynamic sig-
monary b lood flow is normal. Instead, there may be nificance, the defect will generally require surgical
increased interstitial martcings because of left atrial closure to preserve the long-term function of the
hypertension as a result of elevated left ventricular aortic valve. Similarly, perimembranous VSDs can
filling prasures. This is a d ifferent finding on chest be associated with t he development of subaortic
radiograph compared to the "fl~ and diffuse nature stenosis and double-chambered RV, both of which
of pulmonary overcirculation. Truncus arteriosus leads may require surgical int ervention. The VSD will be
to a significant increase in pulmonary blood flow as the closed at the same time. Children w ith small, hemo-
PVR falls because of the direct connection between dynamically insignificant VSDs have no restrictions
the aorta and the pulmonary arteries. on their physical activity.
Hematology
Jane A. Rivas, Christina M. Barriteau, Sherif M. Badawy,
and Bradley S. Marino
This chapter reviews the common, nonmalignant Figure 12-1 outlines the common causes of ane-
blood disorders of children. It is divided into four mia in children.
main sections: (1) anemia, (2) disorders of white
blood cells (WBCs), (3) disorders of hemostasis, GUIDING THE ANEMIA DIFFERENTIAL
and (4) l::rarulfusion and blood products. This is not Anemia can be the result ofa oombination of two or
an exhaumve review of all blood disorders; rather it more of three basic mechanisms. The oombination
focuses on the commonly encountered hematologic of a focused history, physical examination, complete
issues (normal and abnormal) and diseases seen in blood count (CBC) (which includes a mean corpuscular
infants, children. and adolescents. Some conditions volume), reticulocyre count, and peripheral blood
span multiple pathophysiologic categories, but are smear is usually sufficient to accurately diagnose the
discussed in only one section of this chapter. most oommon forms ofanemia without the need for
further expensive and unnecessary tests.
ANEMIA History
Anemia is defined as a hemoglobin (Hb) concentration Taking a good history is key through the differential
that is two or more standard deviations below the diagnosis proceu. A.ddng about birth hiatory, dietary
mean value for age and sex, resulting in a Hb oon- history, prior episodes of overt bleeding, a patient's
centration that is too low to deliver enough oxygen race, ancestry, and family history, a good review of
to meet cellular metabolic demands. systems, and a history of medicatioDB can all guide
Hb concentrations vary by age, sex, and race. the differential diagnosis for a patient's anemia.
The normal Hb concentration is relatively high in • Birth History: Prematurity, low birth weight,
newborns but declines with age, reaching a nadir hemorrhagic obstetrical or perinatal compllca-
known as phpiologic anemia ofinfancy. This nadir tions, and any possible twin-twin, fetomaternaL
occurs at 6 to 8 weeks of age in premature infants
or fetoplacental transfusion.
and 2 to 3 months of age in term infants. The Hb
• Dietary History: It is critical to obtain a dietary
concentration rises gradually throughout childhood, history with attention to excessive consumption of
reaching adult values after puberty. Males have higher cow's milk or prolonged exclusive breastfeedlng,
Hb values than females, particularly after puberty both of which may cause lron-defi.dency anemia.
and the start of menarche. African American8 have It is also important to ask about pica, which is a
slightly lower Hbvaluea compared with Caucasians. neurobehavioral manifestation of Iron deficiency
Anemia may occur in isolation or as part of a with patients craving for and eating substances not
broader pathophysiologic state. Anemia can also normally eaten. Pica can lead to lead poisoning if
be multifactorial, especially in patients with chronic there is lead In the child's environment.
health conditions. It can be understood through
• Bleeding: Ask about overt bleeding from any site.
three basic mechanisms: Including the gastrointestinal (GI) tract (melena,
1. Decreased red cell production hematochezia), genitourinary tract (hematuria,
2. Increased red cell destruction (hemolysis) menorrhagia), and other mucocutaneous sites
3. Blood loss or sequestration (epistaxis, oral bleeding).
247
Common TypM fJf Alanla by llechanlem and MCV
Microcytic
• Iron Deficiency
• Thalassemia Blood Laa/
• Anemia at Sequmrstlon • Abnormal Hemoglobin • VItamin B12
Inflammation • Acute Blood L.oss • Sickle Cell Dlaeaae Deficiency
• Lead Poisoning • SpleniC Sequestration • Unstable Hemoglobin • Folate Dellclency
• Slderoblastlc • ABC Enzyme Disorders
Anemia • G6PD Deficiency
O.cnuecl RBC Nonmeg~loblallc
Production • Pyruvate Kinase Deficiency
• RBC Membrane Disorder • Aplutic Anemia
• Anemia of • Heradllary Spnerocy1D81al • Malignant Bone
mnammalion Elliptocytosis Marrow Infiltration
• Transient • Myelosuppressive
Erythroblastopenia Extrlrwlc ~CI8 Drugs
of Childhood • Dlamond-Biackfan
• Chronic Renal
• Immune Hemolytic Anemia Anemia
• Autoimmune • Fanconl Anemia
Dl88888
• Neonatal Allolmmune • Hypothyroidism
• Malignant Bone
• Mlcroanglopathlc Hemolytic
Marrow lnfiHration
Anemia
• Viral Associated • Hemolytic Uremic syndrome
1\'analent Aplastic
• Thrombotic
Crisis
Thrombocytopenic Purpura
• Mygloauppn~eaiYB
Drug&
• Dlsaamlnated Intravascular
Coagulation
• Pan»tysmal Nocturnal
Hemoglobinuria
FIGURE 12-1. The most common forms of anemia are organized on the basis of their mechanism and mean
cell volume.
oooooooooooooooooooo o " "' ' " ' " ' ' " " " ' ' ' ' ' ' ' ' '''uoooooooooooooooooooo ooooooooooooooooooOo00000060000" ' " " ' '' '" " ' " " ' W . ' " """''''''uoooooooooooooooooouooooooooooooo ooo•" " "" ' '" ' " ' ' " " ' ' ' " ' ' ' ' ' ' ' ' ' ' ''''''uoooo.oooooooooooooooooooooooooo-oooooooooooo,.ooooooooooooooooooooooo
• Race, Ancestry, Family History: Mediterranean. abnormalities of the thumb and forearm are as-
East Asian, African descent, or family history of sociated with some of the bone marrow failure
splenectomy or cholecystectomy may suggest an (BMF) syndromes.
inherited hemolytic anemia. • Vitals: Tachycardia and postural changes in heart
• Review of Systems: Poor weight gain should rate and blood pressure are seen with acute blood
prompt consideration of a systemic disease or loss, but compensation to chronic anemia may
malabsorption. A history of recurrent acute or lessen some of these findings.
chronic inflammation. such as rheumatoid arthri- • Skin: The skin ofseverely anemic children, espe-
tis or inflammatory bowel disease, may suggest cially those with light to medium complexions, may
anemia of chronic disease. appear ycllowish (sallow), and this is important
• Medications: Can cause either decreased red cell and easy to differentiate from jaundice. Jaundice
production or hemolysis. One should also inquire .is a different hue and is also visible in the sclera
about fever, bone pain. weight loss, bruising, jaun- (scleral icterus). Petechiae, purpura, and ecchy-
dice, fatigue, rash, and cough that might suggest mosis indicate low platelet coWlt, which in the
other systemic causes ofanemia. presence of anemia could indicate bone marrow
infiltration or failure.
Phplcal EXam • Cardiac: A flow murmur may be heard in moderate
A careful examination can reveal the presence and
to severe anemia.
the severity of anemia by the degree of pallor (skin,
• Abdomen: Hepatomegaly and/or splenomegaly
conjunctivae. mucosae) and loss of palmar crease
can be a sign ofleukemia or inherited hemolytic
pigmentation. The examiner should seek clues of
anemias.
spedfic causes of anemia: • Lymph Nodes: Lymphadenopathy can point to
• General Appearance: Maxillary hyperplasia and leukemia or chronic inflammation.
frontal bossing can indicate hemolytic anemia
and ineffective erythropoiesis. Short stature, Table 1~ llists physical finc:Unp that suggest a
abnormal facies, cafe·au-lait macules, and bony specific cause of anemia.
Chapter 12 I Hematology • 249
j....,.,.._
TilLE 12-1. Significance of Physical Findings in Ute Evaluation af Anemia
l'llfllaiRIIII.. ....._... ..n...__ tc-ata.nll)
ISlin Hyperpigmentation
CIU-au-lait nw:ules
Fanconi anemia, clylkeratosil congenita
Fanconi anemia
Jaundice Hemolysia
Petech1ae, purpura Bone marrow 1nftltration. autoimmune hemolyais with
I autnbmnune tbrombocytopen. bemolyt:lc uremlc
syndrome
!Head Frontal boulDg Thalassemia major. lliclde cell anemia
i Maxillary hyperplasia Thalassemia major, sickle cell anemia
IiEyes Microcephaly
Microphthalmia
Fanconi anemia
Fanconi anemia
IMou~
Retinopathy Sickle cell disease
Gl.osaitla Brz deflclency
Oeftllp Diamond Blackfan anemia
Hyperpigmentation Peut:z-Jeghers syndrome (GI blood loss)
Telangiectasia O&ler-Weber-Rendu syru:irome (GI blood lots)
Ii Leulcoplalda Dyskeratosis congenita
!Oust Shield chst (widespread nipples) Diamond BJaclcf'wn anemia

Mumwr Prosthetic valve bem.olyala
~
Sidde cell disease, thal..uaemia, immune hemolytic anemia,
~~-
Splenomegaly
hereditary spherocytosis,~ lymphoma. Epstein-
Barr virus, portal hypertenalon
Hepatomegaly Sidde cell disease, leukemia, lymphoma
1 Extremities Absent thwnbl Fanconi anemia

Absent radii Thrombocytopeoia~ablent radius syndrome
I Trlphalangeal thumb Diamond-Blackfan anemia
Spoon nan. (koUonychla) Iron deB.clency (extremely rare phylical finding In clilldren)
I Dystrophic nails Dyskeratosis congenital
i;.................................................................................................................................................................................................................................................................................................
Abbreviation: Gl, gastrolnte611nal.
:
Diagnostic Evaluation The second most important laboratory clue to

Initial laboratory tests needed to evaluate anemia the cause of anemia is RBC size, measured as the
include a CBC (including red cell indices), differen- mean cell volume (MCV).
tial WBC count, reticulocyte count, and peripheral • Individual types of anemia may be macrocytic
blood smear. (high MCV), normocytic (nonnal MCV), or
One of the most important laboratory clues to microcytic (low MCV).
the ca111e ofanemia is the reticulocyte count, which • One must take care to interpret the MCV on the
provides evidence about the mechanism ofanemia: basis of age, sex, and race.
• The bone marrow responds to hemolysis by Examination of the peripheral blood smear is
increasing red cell production, releasing into a1so critical for the diagnosis of anemia (Figs. 12-2
the circulation immature red blood cells (RBCs) and 12-3), as it provides morphologic clues about
called reticulocyte& (reticulocytosis). the red cells, white cells, and platelets that the CBC
• Decreased RBC production results in a reticulo- does not. Figure 12-1 outlines the most common
cyte count that is too low for the degree ofanemia causes of anemia and classlfies them according to
(reticulocytopenia). mechanism of anemia and RBC size.
• A direct antiglobulin test (OAT) demonstrates the

presence ofimmunoglobulins on the RBC surface
and is diagnostic of immune hemolytic anemia.
• A gluoose--6~phosphate dehydrogenase (G6PD)
assay should be considered in African American
and Mediterranean individuals with hemolytic
anemia, although it can be falsely negative during
acute hem.olyBis and should be perfunned 4 tD 6
months later.
• Hb separation techniques (Hb electrophoresis,
isoelectric focusing [IEF], and high·pressure liquid
chromatography [HPLC]) are used to diagnose
hemoglobinopathies or inherited Hb disorders
(e.g., thalassemia and siclde cell anemia).
FIGURE 1!-2. Peripheral blood smear. Generally nonnal
red blood cells are shown with biconcave disc • Newborn screening procedures to identify infants
morphology. Also shown are a monocyte (top nucleated born with significant hemoglobinopathies, such
ceiQ, lymphocyte (bottom left nucleated ceiQ, and as sickle cell disease (SCD) and severe forms of
neutrophil (bottom right nucleated ceiQ. The platelets thalassemia, are CWTently in place in every state
are nonnal in size and shape, but they appear to be in the United States.
~!!~.~-~--~~-~..!~..~~~~..!~..~-~-~-~..Y.!~:....................................... • Serum iron concentration, total iron-binding ca-
pacity (TIBC), iron saturation percent, and serum
There are many other available tests that can ferritin levels are needed to confirm a diagnosis
clarify or establish the diagnosis when initial testing of iron deficiency.
is insufficient. Examples include the following: • Positive heme tests of stool or gastric contents
indicate GI bleeding.
• Inhemolysis, serwn lactate dehydrogenase (LDH) • The erythrocyte sedimentation rate {ESR) ~
and indirect bilirubin are elevated, haptoglobin is generally elevated in anemia of inflammation,
decreased, and urine analysis will show urobilinogen.
FIGURE 1!-3. Examples of normal and abnormal red blood cell {ABC) morphology. {A) Normal RBCs. {B) Elllptocytes.
(C) Spherocytes. (D) SChlstocytes. (E) Hypochromic microcytic RBCs. (F) HowelhJolly bodies and acanthocytes.
.(9.~~~..~~..~-~-~!...~.~~!.·...~.9..!..!?..~.!?.~~-~-~-~-~..~!.~~~~!.~.~..~~..~..~~-~~-~..~.:..~~!~..9.~!!.~.~-~.:~..~~P..~.1..~.9.~.!~~:.L..
but it can also be &lsely elevated in patients with Iron-deficiency anemia can occur as early as
severe anemia. 3 months of age in the premature infant who has
• In children, a macrocytic anemia is most worrisome inadequate iron stores at birth. It can occur in the
for a syndrome of BMF or infiltration, so a bone infant or toddler who receives a diet exclusively
marrow examination is often needed, especially in composed of cow's mille, low-iron formula, or
the presence ofleucopenia, neutropenia, throm- breast milk (without iron supplementation after
bocytopenia, or other related clinical stigmata. 6 months). Nutritional iron deficiency can also
• Serum vitamin ~ 31 RBC folate levels and meth- occur during adolescence when rapid growth may
ylmalonic acid (MMA) may also be measured to coincide with a diet with suboptimal iron content.
assess for megaloblastic anemia, although dietary lb.is is a particular problem in adolescent females
d.eficlendes of these nutrients are uncommon in because of menstrual iron loss, especlally those with
children in developed countries. heavy menstrual bleeding. Iron-deficiency anemia
in adolescent males is rare, and an evaluation for
Treabnent occult blood loss Is wually warranted to rule out
Treatment depends on the underlying cause of the inflammatory bowel disease.
anemia. Specific conditions and their treatment are Prenatal iron loss can occur from fetomatemal
discussed in the following paragraphs. transfusion or from twin-to-twin transfusion. Perinatal
bleeding may result from fetoplacental transfusion or
obstetric complications such as placental abruption
MICROCYTIC ANEMIAS (LOW MCV) or placenta previa.
Hypochromic microcytic RBCs result from impaired Postnatal blood loss may be overt (bloody stools
synthesis of the heme or globin components ofHb or traumatic hemorrhage) or occult, as with anom-
or both. Inadequate heme synthesis may be the alies of the GI tract (e.g., juvenile polyps, Meckel
result of iron deficiency, recurrent or chronic in- diverticulum), inflammatory bowel disease, parasitic
flammation, sideroblartic states, copper deficiency, infestations, and idiopathic pulmonary hemosider-
or lead poisollin8. Decreased globin synthesis is the osis. Malabsorption of iron is uncommon, but can
hallmark of thalassemia. Iron-deficiency anemia, occur in certain disease states (e.g., celiac disease)
the thalassemia syndromes, and anemia ofinflam- or as an inborn error (e.g., iron-refractory iron-de-
mation are the most common causes of microcytic ficiency anemia).
hypochromic anemias.
Clinical Manlf881atlons
IRON-DEFICIENCY ANEMIA The typical presentations ofiron-deficiency anemia
Iron deficiency, the most common cause ofanemia in children are as follows:
during childhood, is usually seen between 6 and 24 • Asymptomatic incidental presentation during
months ofage but is not uncommon during adoles- routine workup or for unrelated medical issue
cence. Iron deficiency may be caused by the following: • Symptomatic iron-deficiency anemia
• Inadequate dietary intake of iron; • Behavioral abnormalities, like pica
• Decreased iron .stores at birth; The degree at which the anemia develops will
• Blood loss; or also impact the presentation of the conditions. Al-
• Malabsorption of iron. though mJld iron-deficiency anemia Is most often
Nutritional iron deficiency develops when rapid asymptomatic, with moderate iron deficiency (Hb
growth and an expandi111 blood volume put excessive concentration approximately 6 to 8 gldL), the child
demands on iron stores. Dietary risk factors include may have the following:
extended exclusive breastfeeding (more than 6 • Reduced appetite
months) without iron supplementation, consumption • Irritability
oflow-iron formula preparations, early institution of • Fatigue
low-iron solids, excessive cow milk intake, and the • Reduced exercise tolerance
absence ofiron supplements in high-risk situations • Inablllty to focus or concentrate
(e.g., prematurity). The iron present in breast milk
is much more bioavailable than the iron In cow's Physical examination shows skin and mucous
milk, but it 1s stlll insufficient to provide enough membrane pallor, tachycardia, and a systolic ejection
iron beyond 6 months of age. murmur along the left sternal bordeL The child with
severe anemia (Hb < 3 gldL) may show signs of TAILE 12-2. Classical Laboratory Findings fur
congestive heart failure, which include the following: Common causes of a Mild Microcytic
Anemia
• Tachycardia han ......_.. ....... ..
~gallop
•
• Cardiomegaly
I..... IIIIIDIInaJ' .....- ...........-.
• Hepatomegaly IRDW t Normal Normal
• Distended neck veins IMCV .1- .1- Normal or .1-
• Ral.es IRBCcount .1- t !
Children with slowly progressive. chronic anemia
may be remarkably hemodynamically compensated.
!HbA2 .1- ~ t * Normal
Glossitis, angular stomatitis, and koilonychia (spoon
nails) are umally never seen in children with isolated
IHb F Normal ~ ftrmal Normal
iron-deficiency anemia in developed countries, but !Serum iron .1- Normal .1-
as part of more generalized malnutrition in devel-
oping countries.
1TIBC t Normal Normal or!
Expected lab values in iron-deficiency anemia ! Ferritin .1- Normal t
are as follows: !-when the result of a test differs between a-thalassemia and
!P,.1halassemla, the resUt Is preceded by an "a:"or ·~·.
• LowHb !AtlblMatials: t, illCI8BSIId; ,!.., decr8ued; Hb A, harroglctlin Ae; Hb
i F, hen'llglcOn F (faa): MCV. rTl8lll1 eel voli.r ne; RBC, r9d blood eel:
• LowMCV i:......................................................
RDVV, r9d ee1 disbtbution width; n BC. total ron-tlirdi'G cepadly.
_.................................. ....................................-............:
~
• LowRBC
• High red cell distribution width (RDW) month. However. iron therapy must continue (at a
• Lowferritin lower dose: 2 to 3 mglkg/day of elemental iron) for
• Low iron saturation percent 2 to 3 months after the Hb normalizes to replenish
• Low serum iron tissue iron stores and prevent recurrent iron deficiency.
• High TIBC Iftlu! Hb does not increase as suspected. consider-
It is important to note 1hat serum Iron level fluc- ations should include nonadherence to iron, incorrect
tuates over time and is usually affected by rea!nt iron do6e ofiron, an incorrect diagnosis ofiron deficiency,
intake (ie., hours or days). Serwn ferritin is the most or malabsorption ofiron. Iron supplements, tablets, or
important marker for iron stores and reflects iron status liquid can cause darkening of tlu! teeth, GI upset, and
over a longer time period (l e,. weeks or months).lron constipation, which could affect adherence. Th.e liquid
deficiencywithout anemia occurs earlier with some risk iron fomwl.ations are not palatablefor most children and
of cognitive impairment In growing child.ren, which cou1d benefitfrom beingfl.avomlto improve adherence.
lfleft untreated, can lead to iron.deficiency anemia. Transfusion of packed red blood cell (pRBC)
Bone marrow examination is not necessary to is reserved for those with symptomatic anemia in
confirm a diagnosis of iron deficiency. A response whom a rapid correction is needed and those with
to appropriate iron supplementation is the best di- impending or established high-output congestive
agnostic test for iron deficiency. Table 12-2lists the heart failure. Although infants and young ch11dren
laboratory :findings typical for the common causes can tolerate remarkable degrees ofanemia, especially
of microcytic anemia. ifthe decline in Hb is gradual, individuals with severe
anemia must be transfused very slowly in serial, small
Trealmant aliquots (2 to 5 mL/lcg) of pRBC transfusion to avoid
Mild-to-moderate iron-deficiency anemia without cardiac decompensation caused by volume overload
evidence of congestive heart failure is treated with 3
to 6 mtJki/day ofelemental iron by mouth in one or a- AND ~-THALASSEMIA
two divideddoses. Giving iron supplement with orange The thalassemias are hereditary anemias character-
juice or other sources ofvitamin C could improveiron ized by decreased or absent synthesis ofone or more
absorption. The reticulocyte count increases within globin subunits of the Hb molecule. a-Thalassemia is
2 to 3 days ofiron therapy, and the Hb increases at a classically caused by deletions ofone or more of the
rate of approximately 0.3 gldL/day after 4 to 5 days. four a-globin genes, leading to reduced synthesis of
The Hb concentration usually normalizes within a a-globin. P·Thalassemia is classically caused by point
mutations of the ~globin gene, leading to reduced UILE 1~ comparison of t11e Classical
(p+ mutations) or absent (JJ0 mutations) synthesis P-Thalassemia Syndromes
of JJ~globin. The result of decreased production of
either the a- or ~globin is an imbalance between I..... a•••,...
the normally matched production of both, the key !PIP Normal
pathophysiologyof thalassemia. This imbalance leads
to an excess of one globin type CP in ~thalassemia, a
IPIP 0
P-Thalauemia trait (minor)
in ~thalassemia) that may pair with its~ is unsta-

IPJP•
ble, precipitates, and damages the membrane inside
i p·t~· P-Thalauemia lntennedia
the developing erythroblast, resulting in ineffective i p•tlf

erythropoiesis and hemolysis. Roughly 7CJ6 of the !pot~o P-Thalauemia major (Cooley anemia)
world's populations are carriers of thalassemia. : Abbi'IIVIatlons: ~. I)-globin gena; ~0• null allele (ab98nt globin !
Thalassemias are classified by clinical severity. i production); ~·. 1'\olomorphlc allele (decreased globin production); !
ii .................................................................................
/,the distinction between the two chromosomes. !
............ .............................................i
• ThalassemiamajorJs a transfusion-dependent condition.

• Thalassemia minor is the asymptomatic trait state
• Homozygous a-thalassemia major occurs when
with only mild anemia. all four a-globin genes are deleted. Failure to
• Thalassemia lntermedia encompasses all the
produce any ~globin chains results in y-globin
conditions of intermediate severity between the tetramers (Hb Barts) and small amounts ofembry-
major and minor states.
onic Hbs. Hb Barts has a high affinity for oxygen
Tables 12--3 and 12--4 classify the common thai~ and does not release it to the tissue. The result
assemia syndromes. is severe anemia, tissue hypoxia, heart failure,
The number of deleted globin genes determines hepatosplenomegaly, generalized edema. and
the hematologic consequences of a:~thalueemia. death in utero because of hydrops fetalls. The cis
These deletions can be cis or trtiiU. Cis deletions deletion is most prevalent in Southeast Asians,
occur when two ~globin genes are deleted from and therefore, homozygosity for cil deletions is
one chromosome, more common in Southeast more common in this population.
Asians, whereas trans deletions signify a-globin gene • HbH disease (a-thakusemia intermedia)results
deletions on each of the two chromosomes, more from deletion of three ofthe four a-globin genes.
common in Blacks. Different races and ethnicities In normal infants, fetal Hb (which consists of
have varying rates of both cis and trans deletions of two a-globin chains and two y-globin chains)
a-globin genes in their population. predominates at birth, but declines thereafter
as ~globin production falls and is replaced by
TABLE 12-3. comparison of t11e Classical (}-globin production. In newborn infants with
........
a-Thalassemia Syndromes Hb H disease, the dearth ofa-globin leads to the
formation ofHb Barts (y-globin tetramer), which
accounts for 10')6 to 40')6 ofthe total Hb. Hb Barts
j . .....,.. llannlla. ..... a..t..... is usually identified with newborn screening.
! asx/rw. 4 Normal With the reduction of a-globin synthesis and
! asx/a.- 3 Sllent carrier state the increase in ~globin synthesis at birth, Hb
Barts diminishes and Hb H <P-globin tetramer)
! --lao
2 Thalassemia trait
(a.-thalassemia predominates after the first few months oflife. Hb
minor) H eventually accounts for 1006 to 40% of the total
!, a.-/a- 2
Hb, and normal Hb A accounts for approximately
~to 90')6 ofthe total Hb. This diagnosis is most
1 HbHdisease common in children with Southeast Asian ances-
~ --/a- (a.-thalassemia try. Affected individuals have moderate anemia.
intermedia) variable hepatnsplen.om.egaly, and the need for
~ -- 1-- 0 Hydrops feta1is (a.- intermittent pR.BC t:ransfusiom.
thalusemia major) • ~Thalauemia trait, also known as ~thalassemia
. .
! Abbreviations: a, a-globin gene; - , deleted a-globin gene; /, the ! minor, results from the deletion of two ~globin
! distinction between the two chromoaomes; HbH, hemoglobin H. !
••• ""'''""'""'"'"''' '' ' " ' ' " " ' ' ' '' ' "' " '' '' ' '" ' "" " " ' ' ' '' ' ' ' '' ' ' ' '' ' ' ' '' '' '' ' '' ' '' ' ' ' ' ' '' '' '' '' " nooooooonooooooooooooooooo4
genes. This defect manifests with mild anemia,
hypochromia, and microcytosis. The a-thalassemia

trait, present in 396 of African Americans and 196
to 596 ofthose ofMediterranean descent, is often
confused with mild iron deficiency. The Hb elec-
trophoresis may be normal in these children, or
show decreased Hb ~and the diagnosis is oftEn
one of exclusion. It can be confirmed by parental
or genetic studies.
• Those with deletion ofonly one a-globin gene are
called •sfie:nt carriers" fOr a-thaJassemla because they
have a nonnal or near-normal Hb concentration and
nonnal or near-normal RBC indices, The condition
canbe documented byquantitative measurement of
globin chain synthesis or by gene analysis. A carrier
can produce offspring. depending on the genotype
ofthe normal parent, who are also silent carriers or
have a-thalassemia trait or Hb H disease.
Silent carriers and a-thalassemia trait do not require
therapy. However, individuals with a-thalassemia FIGURE 12-4. Thalassemia patient with frontal bossing
from extramedullary hematopoiesis. (This image was
trait ofAsian descent should have genetic counseling
provided by the Department of Hematology at the Ann
before starting a family because of the increased
risk of having an offspring with four gene deletions, ~-~--~~~~---~.:. ~~~-~--q~~~~~~-~--~-~~-~!. ~!.g~!.~.~-~1. . . . ..
resulting in hydrops fetalis. Patients with a-thalas- ineffective hematopoiesis. Peripheral blood
semia lntermedia, or Hb H disease, may need chronic smear reveals hypochrom.i.a, severe microcytosis,
transfusions, or splenectomy. Children bom with anisocytosis, and poikilocytosis. Hb F accounts
hydrops £et:a1is or Bart hemoglobinopathy can be for 954)(, of Hb in the po/~0 genotype and lesser
kept alive with lifelong blood transfusions. A matched amounts in other genotypes (e.g., p0Jp+),
hematopoietic stem cell transplantation is curative. • Children with ~-thalassemia intennedia have moderate
Newborns with l'-thalauemia have normal microcytic anemia, variable hepatosplenomegaly,
blood counts, unlike those with a-thalassemia, be- and the possible need for intermittenttransfusions.
cause the fetus and newborn normally use fetal Hb. The clinical condition ofb:n depends on the child's
P-Thalassemia major results either from complete or ability to tolerate the level of anemia.
near-complete absence of P-globin synthesis (classi- • Children with 1'-thalassemia minor, also called
cally, the .1}0/P0 genotype). fi-Thalassemia intermedia 1'-thalassemia trait, have only mild microcytic
can occur with a wriety ofgenotypes in which there anemia. On blood smear, the hypochromia,
Is moderately diminished, but not absent, 1'-globln microcytosis, and anisocytosis are dispropor-
production (e.g., ~0tp+ or ~+Jp+ genotypes). The child tionately severe, given the mild degree ofanemia.
with 1'-thalassemia minor, the heterozygous form, Hb separation shows elevation ofthe Hb A2 level
has one normal P-globin gene and one abnormal and sometimes elevation of Hb F.
1'-globin gene (e.g., PIP.,. or j}/.1}0 genotypes).
Treatment of fi-thalassemia is dependent on the
• In ~thalassemia majot; severe anemia, organomegaly, severity ofthe anemia. Children with ~-thalassemia
and growth failure progressively develop during minor often do not require therapies, but it is recom-
the first year of life. If untreated. bone marrow mended that future genetic testing be done before
hyperplasia and extramedullary hematopoiesis having children. The treatment of P-thalassemia
produce characteristic features such as frontal intermedia is dependent on the severity of mutations
bossing (Fig. 12-4), maxillary hypertrophy with in the P-globln genes. These individuals may require
prominent cheekbones, and an overbite. Failure rare transfusions, or they may require more intensive
to thrive is prominent in this population. If un- therapies like those children with P-thalassemia
treated. death occurs within the first few years major. Patients with fi-thalassemia have increased
of life because of progressive congestive heart iron absorption and are at risk of iron overload,
failure. Despite severe anemia, there Is a relative even with rare transfusions. In P-thal.assemia major.
reticulocytopenla, reflecting the characteristic patients will require chronic pRBC transfusions.
Because of this, they are at an increased risk ofiron a transfusion ofpRBC as a temporizing measure, in
overload, exposure to multiple RBC antigens, and particular those with prolonged or critical illness.
potential exposure to blood-borne pathogens. Iron
chelation therapy is essential for all P-thalassemia SIDEROBLASTIC ANEMIA
patients with iron overload. Hematopoietic stem Sideroblastic anemias are a rare group of disorders
cell transplantation and gene therapy are curative caused by either inherited or acquired defects in
options in patients with ~thalassemia major. mitochondrial metabolism. This then leads to inef-
fective heme synthesis and erythropoiesis. Leftover
ANEMIA OF INFLAMMATION iron from unsuocessful heme production and eryth-
Anemia of inflammation, also called •anemia of ropoiesis is transferred to the bone marrow, where
chronic disease,• can result from chronic inflamma- it is deposited around the nucleus of erythroblasts,
tory diseases, such as inflammatory bowel disease, giving the appropriately named •rtnged sideroblasts:"
juvenile idiopathic arthritis, chronic infections, Along with inefficient heme production, iron is lost
and malignancy. It can re.sult in either microcytic and will result in microcytosis.
or normocytic anemia, with 25% of cases being Expected lab values in sideroblastic anemia:
microcytic. The cytokines produced in inflamma-
• Low Hb and hematocrit
tory states disrupt iron homeostasis and result in
iron stores accumulating in macrophages in bone
• LowMCV
• Concomitant evidence ofiron deficiency (ferritin,
marrow and reticuloendothelial systems. Cytokines
serum iron, TIBC, saturation percent)
will also inhibit bone marrow red cell production
• Abnormal bone marrow biopsy with ringed sid-
and differentiation, resulting in either microcytic or
eroblasts (Fig. 12-5)
normocytic anemia. Anemia ofinflammation can be
thought of as a functional state ofiron deficiency. A Treatment ofsideroblastic anemia is often multi-
modest decrease in the survival time of RBCs and disciplinary and not just hematologic based on the
a relatively limited erythropoietin response also cause of the anemia.
contribute to the anemia of inflammation.
Anemia of inflammation ia often milder than LEAD POISONING
typical iron-deficiency anemia. As a result, it may be Lead can cause microcytic anemia through two
incidentally fOund on labs. In chJldren without known mechanisms:
causes ofinflammation. further workup is indicated.
1. Altered iron utilization
Expected lab values in anemia of inflammation:
2. Enzyme inhibition in heme production
• Hb concentration approximately 8 to 10 g/dL
or lower
• LowMCV
• High ferritin, ESR, and C-reacti~ protein
• Low serum iron concentrations, transferrin, and
TIBC
• Bone marrow shows micronormoblastic hyper-
plasia, increase in iron storage, and decrease in
the number of iron-containing erythroblast&.
Treabnent should be directed at the cause of the
inflammation. The anemia will resolve spontaneously
when the underlying inflammatory condition resol~.
Therapy with iron supplements is unnecessary and
ineffective unleas oomorbid iron deficiency is clearly
documented. The test of choice for iron defiden.cy
in the setting ofanemia ofchronic disease is soluble FIGURE 12-5. Ringed sideroblasts seen on iron stain
transferrin receptor level, which would be high in in a patient with congenital sideroblastic anemia.
that situation. Ferritin level is not helpful in this case (This image was originally published in The American
because it ia an acute phase reactant and it will be Society of Hematology Image Bank. Calvo K. Ringed
falsely normal or high in these patients. Some chil- sideroblasts seen on iron stain. 2015; image 60067. C
dren with severe anemia ofinflammation may need !..~-~--~~~~--~-~~~--~--~~-~~~!-~¥.-2.... ........................................
The miaucytDsis that is most often seen with lead exact cause ofTEC is not known, although a number of
intmicaDonleada ID altered iron utilization. AE. a divalent viruses have been epidemiologically linked to TEC. AE.
metal. leadcan disrupt iron absorptionand utilization, the name implies, TEC is a self-limited anemia and is
thus interrupting heme production. Iron deficiency usuallyassociated withnonnal WBC and platelet counts.
causes a microcytic anemia and plea; plea can result
in iJ1Fstion of more lead. This inrerplay between iron
TEC occurs between 6 months and 6 years ofage, with
deficiency and lead can develop through an initial lead
exposure that can then compoundboth the iron defidency
a peak incidence around 2 years of age. The history
and physical examination are unremarkable except for
and lead intoxication. In addition. lead inWferes with
the gradual onset of pallor over the course of weeks
the synthesis of heme in patienb with lead poisoning.
or months. Often, this is imperceptible to parents
Expected lab values in lead intoxication:
who see the child every day. An outside observer.
• High lead levels such as a visiting grandparent, may be the first to
• Low Hb and hematocrit recognize the pallor. There is no organomegaly or
• LowMCV lymphadenopathy, and the child is otherwise welL
• Concomitant evidence ofiron deficiency (ferritin, The differential diagnosis of TEC includes Dia-
serum iron, TIBC, saturation percent) mond-Blackfan anemia (DBA), which is a constitu-
tional BMF syndrome. DBA usually presents before
Although lead can result in microcytosis, the main
6 months of age, produces a macrocytic anemia, and
hemalnlogic frature inleadintmdcationisbasophilic stip-
is often associated with physical anomalies, such as
plingseen on a peripheral bloodsmear. Leadintoxication
hypoplastic thenar eminence, triphalangeal thumb,
is best treated with the removal of potmtial sources of
and characteristic (Cathie) facies.
ingestion orleadeJCP(l8Ul'e, andin severecases cbelati.on.
Associated Labctni1Dry Value&
NORMOCYTIC ANEMIAS (NORMAL In the laboratory usessment ofTEC, the associated
MCV) WITH DECREASED RED CELL anemia iJ norma<:ytic.
PRODUCTION • Low Hb and hematocrit
Normocytic anemias with decreased red cell pro- • Low reticulocyte count in the active phase
duction have many causes. A common theme is • High reticulocyte count in the recovery phase
impaired or inadequate bone marrow response to • Normal platelet count and WBC count
anemia, as occurs with replacement of the marrow Bone marrow biopsy shows few erythroid pre-
by fibrosis, infiltration of the marrow by malignant cursors and normal myeloid and platelet precursors.
cells, or deficiency of erythropoietin (e.g., chronic
renal disease). The bone marrow may also fail be- Treatment
cause of toxic insults. Transient marrow failure states The Hb concentration is usually at ita nadir at the
include the following: time of diagnosis. Spontaneous recovery occurs
within 1 to 2 months ofdiagnosis. RBC transfusions
• Transient erythroblastopenia ofchildhood (TEC) are necessary only if the patient has symptomatic
• Human parvovirus-induced aplastic crisis (in severe anemia or evidence ofcongestive heart failure.
patients with hemolytic anemia)
• Drug side effects or toxicity (e.g., antiepileptics
and chemotherapeutic agents) NORMOCYTIC ANEMIAS (NORMAL
MCV) WITH INCREASED RED CELL
Anonnocytic anemia also occurs with acute blood PRODUCTION
loss, in which a compensatoryincrease in total blood
volume results in the anemia before the bone marrow HEMOLmC ANEMIA
has time to correct the deficit in red cell mass. The Normocytic anemias with increased red cell production
anemia of inflammalion. discussed earlier. is often are most commonly caused by hemolysis. Hemolysis
normocytic, especially early in the coune ofthe disease. is synonymous with increased RBC destruction and is
defined as a shortened red cell life span. The anemia
TRANSIENT ERY11tROBLASTOPENIA OF and consequent tissue hypoxemia is sensed by the
CHILDHOOD renal interstitium. which produces erythropoietin
TEC is an acquired pure red cell aplasia caused by tem- in compensation to augment erythropoiesis. The
porarysuppression ofbone marrow erythropoiesis. The result is a compensatory reticulocytosis.
Chapter 12 I Hematology • H7
Hemolytic anemias can be caued by defects r

intrirWc to the red cell (intra.corpuscular defects)
or factors extrinsic to the red cell (ex.tracorpuscular
insults), that is damage from within or damage from
without. In general, intrinsic defects are hereditary
and extrinsic defects are acquired.
• Intrinsic hemolysis can be caused by defects of
any of the three components of the red cell: the
membrane, cytosol (enzymes), and Hb. Intrinsic
membrane defects include hereditary spherocy-
tosis (HS), hereditary elliptocytosis, hereditary
•
stomatocytosis, and paroxysmal nocturnal he-
moglobinuria (PNH). PNH is the only intrinsic
defect that is not inherited. Intrinsic Hb defects
or hemoglobinopathies include siclde cell disor-
..
FIGURE 12-i. Hereditary spherocytosis with multiple
spherocyt:es. (This image was originally published in The
-
ders and thalassemia. Intrinsic enzyme defects American Society of Hematology Image Bank. Scordino
include glucose-6-phosphate deficiency (G6PD) T. Spherocytes-hereditary spherocytosis. ASH Image
and pyruvate kinase deficiency. Bank. 201 8; 00080308. e The American Society of
• Extrinsic hemolysis can be classified as immune -~~-~-~~.'!?.W.:.L. ......... . ....-·······-··· ··-···················-··············· · ···· · ·-···············
and nonJmmune. Inmttme hmwlyttc 1111emia refers
to hemolytic anemia caused by the deposition of
antibody, complement, or both on the surface of maaophages, and membrane fragments are removed
the red cell that leads to its damage and eventual with each passage of the red cell through the splenic
destruction. Nonimmune hemolytic anemias can circulation. This progressive loss of membrane pro-
be microangiopathic (disseminated intravascular duces spherocyte& and microspherocytes. The poor
coagulation [DIC], hemolytic uremic syndrome deformability and osmotic fragility of spherocyte&
[HUS], thrombotic thrombocytopenic purpura leads to their early destruction. Inheritance of HS
[TTP]), toxin related (snake venom, copper, and Js usually autosomal dominant, but 25% ofcases are
arsenic) due to intraerythrocytic parasites (malaria, caused by new mutations or are autosomal recessive.
babesiosis) or extensive burns. However, all spherocytosis is not necessarily caused
by HS. A nmnber of other conditions could also
The following is a di.scuasion of four common
produce spherocytes, such as immune hemolytic
types of hemolytic anemia in children. Three are
anemia, sepsis, bums, and toxins.
examples of intrinsic defects (HS, SCD, and G6PD
deficiency), and one is an example of an extrinsic Clinical Manifestations
insult (autoimmune hemolytic anemia [AIHA]). HS can easily be diagnosed with a good history (e.g.,
intermittent scleral icterus), family history (e.g.,
HEREDITARY SPHEROCYTOSIS anemia, cholellthiasis or splenectomy), and physical
HS refers to a group of related diseases caused examination (e.g., mild splenomegaly). However,
by a congenital, intrinsic defect in the membrane HS varies greatly in clinical severity across patients,
cytoskeleton of RBCs. This defect Js caused by a ranging from incidentally discovered. asymptomatic,
deficiency or dysfunction of one or more of the mild anemia to severe anemia with growth failure,
membrane-supporting proteins, spectrin, ankyrin, splenomegaly, and a requirement for chronic transfu-
band 3 protein, or protein 4.2, whose role is to sions in Infancy with a future need for splenectomy.
maintain the proper deformability and elasticity of Severe disease is uncommon, however, and HS is often
the erythrocyte, producing a spherocyte. diagnosed incidentally, when anemia is discovered
The defect in the cell membrane shortens the on a blood count obtained for another purpose, or
red cell life span causing hemolytic anemia, and when screening is done for a family history of ane-
produces the characteristic morphology, the sphero- mia. HS can also be discovered when investigating
cyte, after which the condition is named (Fig. 12-6). the cause of anemia or jaundice.
The hemoJysis occurs mainly in the extravascular Newborns may have exaggerated or prolonged
compartment and in the spleen. The membrane of neonatal jaundice {uru:onjugated hyperbilirubin-
HS red cells is recognized as abnormal by splenic emia) because of the hemolysis superimposed upon
physiologic jaundice, and roughly one-third may require recowry from the aplastic crisis, nucleated RBCs will
transfusion for symptomatic anemia during the first first appear in peripheral blood followed about 1 day
few months of life when hemotysi.s is superimposed later by a burst of reticulocytosis. Aplastic crisis dis-
upon physiologic anemia of infancy. The need for covered during the recovery phase may be mistaken
pRBC transfusion during the neonatal period does for a hyperhemolytic episode, also charac:terized by
not indicate that the child will ha~ ongoing severe increased anemia, in which the reticulocyte count is
anemia and need further transfu&ion therapy later in life. increased from baseline. It is wise to exclude immwte
Beyond the newborn period. the typical features of hemolytic anemia by a OAT.
HS include jaundice (especially scleral icterus), which Purther testing is usually not needed to confirm
may be intermittent, and variable splenomegaly. Pallor the diagnosis of HS, but if necessary, it should be
and fatigue occur depending on the degree ofanemia. done after 6 months of age. Osmotic fragility test-
Jaundice may be noticed only during febrlle or other ing is a test for spherocytes, not HS. Any cause of
inflammatory illnesses when the hemolytic rate may spherocytosis (listed earlier in this chapter) will give
increase. These episodes are called "hyperhemolytic" a positive osmotic fragility test. Osmotic gradient
episodes, marked by .increased anemia, pallor, and ektacytometry can also demonstrate defects in red
jaundice. These episodes usually resolve spontaneously cell water content or volume, but not differentiate
when the underlying illness abates, although pRBC the different causes of spherocytes. A newer test,
transfusion maybe needed in some severe cases. eosin-5-malelmide binding, has high sensitivity and
Some individuals have recurring hyperhemolytic specificity for HS and might .see increasing use when
episodes requiring transfusion. Infection with human the diagnosis of HS is unclear.
parvovirus causes the transient aplastic crisis with a
Traabnant
moderate to severe exacerbation of the underlying
The most important "treatment" for HS is expectant
anemia due to temporary suppression oferythropoi-
esis. The aplastic crisis resolves when neutralizing management-awareness of and watchful waiting
for possible complications (e.g., aplastic crisis and
antibody is formed 1 to 2 weeks following infection,
providing lifelong immunityand protection against hyperhemolytic crisis), promptly addressing them
ifthey arise (e.g., cholecystectomy for symptomatic
further parvovirus infection. Because of chronic
cholelithiasis), and ongoing education ofthe patient
hemolysis, and the increased flux of bilirubin
through the hepatobili.ary system, individuals with
and family about the disease.
HS may develop bilirubinate (pigment) gallstones • Folic acid supplementation is rarely needed and
later in life. These gallstones may be asymptomatic usually only for severe hemolytic anemia.
or cause typical signs and symptoms of cholecystitis • Episodic pRBC transfusions may be given for
or choledocholithiasis (e.g., jaundice and right upper symptomatic or life-threatening anemia during
quadrant abdominal pain). the transient aplastic crisis or "hyperhem.olytic•
episodes.
AsaociiiiBd LaboraiDry Values • The need for multiple or regularly scheduled
Laboratory studies in HS typically show the foll.owing: transfusions should prompt serious consideration
• Low Hb and hematocrit (mild or moderate) for splenectomy.
• NormalMCV Splenectomy can often •cure• the hemolytic
• HighMCHC anemia, although the underlying red cell defect
• High reticulocyte count remains. Splenectomy should be reserved for those
• Low reticulocyte count may indicate aplastic crisis patients with symptomatic hemolysis affecting
• High indirectbilirubin or indirect hyperbilirubinemia their quality of life (e.g., fatigue, growth failure,
• A conjugated hyperbilirubinemia may indicate the need for frequent transfusions). The risks of
cholelithiasis. splenectomy include a Jifelong, increased risk of
Failure to obtain a reticuJocyte count when eval- overwhelming sepsis with encapsulated organisms
uating for the cause of anemia is a common reason (especially, Streptococau pneumoniae), thrombosis
that HS and other hemolytic anemias may be missed. and, possibly, pulmonary hypertension. Splenectomy
During the parvovirus-related transient aplastic should be delayed, when possible, until after 5 years
crisis, the anemia will be more severe, and there will ofage, because the risk of sepsis is higher in the very
be an inappropriately low reticulocyte count. Upon young. Individuals who have a splenectomy need
appropriate immwtization before and after surgery The younger RBCs, including the reticulocytes
(against the pneumococcl18, meningococcus) and produced in response to hemolysis episode, have
at least several years of postsplenectomy prophy- sufficient enzyme activity to resist oxidative stress
lactic penicillin (if not lifelons). Given the lifelong and do not lyse.
risk of sepsis, asplenic individuals also need to seek Hemolysis is mostoommon in males who possess a
immediate medical attention for any high fever for single abnormal X chromosome. Heterozygous females
the remainder of their lives. who have skewed X chromosome inactivation may
become symptomatic, as may femaleA homozygous
GWCOSE-6-PHOSPHATE DEHYDROGENASE for the A - variant. One percent of African American
DEFICIENCY females are A- variant homozygous.
G6PD deficiency, the most common RBC enzyme Severe G6PD deficiency, as with the Mediterra-
defect, is an X-llnlced condition. The deficiency of nean variant, can result in hemolysis that destroys
this enzyme in the hexose monophosphate shunt most of the red cell ma.JS becaU5e even the young
pathway results in depletion of nicotinamide adenine red cells have inllllfficlent enzyme activity. Hemolysis
dinucleotide phosphate and the inability to regenerate may be life-threatening, and pRBC transfusion may
reduced glutathione, which is needed to protect the be needed. During hemolytic episodes, physical ex-
RBC from oxidative stress. amination reveals Jaundice and dark urine (caused
The most common forms of G6PD deficiency are by hemoglobinuria and high levels of urobilinogen).
the K and Mediterranean variants. Splenomegaly is not a feature of G6PD deficiency,
and those patients with tM. on exam should be
• The mutation that causes the A- variant, found in
reassessed for an alternative diagnosis.
approximately 109' ofAfrican Americans, produces
an enzyme with a shortened half-life of 13 days. Associated Laboratory Values
• The Mediterranean variant occurs predominantly During a hemolytic episode, laboratory tests reveal
in persons of Greek and Italian descent. This elevated indirect blllrubin and IDH and low hap-
enzyme is extremely unstable and has a half-life toglobin. Initially, the hemolysis may exceed the
of only several hours. ability of the bone marrow to compensate, so the
When the RBC experiences oxidative stress, exposed reticulocyte count may be lowfor the first 3 to 4 days.
sulfhydryl groups on 1he Hb are oxidized. leading to On peripheral blood smear, the red cells appear to
dissociation of heme and globin moieties, with the have "bites" taken out ofthem (blister cells) or have
denatured globin precipimtingas Heinz bodies, which an asymmetric distribution ofHb (eccentrocytes).
can be visualized by special stains. Damaged red cells Measuring enzyme activity makes the diagnosis
are rem<md from circulation by the reticuloendothelial of G6PD deficiency. G6PD levels may be normal in
system; severely damaged cellB may lyse intravascularly. the setting ofacute, severe hemolysis because most
Known chemical oxidants include the following: of the deficient cells have been destroyed (leaving
only the younger cells with sufficient enzyme ac-
• Sulfonamide& tivity). Repeating the test at a later time, usually 4
• Nitrofurantoin to 6 months, when the patient is in a steady-state
• Primaquine condition is important.
• Dimercaprol
• Naphthalene (moth balls). Treatment
Patients with G6PD deficiency associated with acute
Hemolysis may also be precipitated by infection,
severe hemolysis need to avoid drugs and chemicals
inflammation. and, with the Mediterranean variant,
that initiate hemolysis. Treatment is supportive,
ingestion of fava beans or broad beans.
including pRBC transfusion during significant car-
CUnkaiManHedaUans diovascnlar compromise and vigorous hydration and
The typical course of miJd G6PD deficiency (as with urine alkalinization to protect the kidneys against
the A- variant) is episodic stres~ or drug-induced damage from precipitated free Hb.
hemolytic anemia. Patients with the A- variant have
a limited degree of hemolysis that is restricted to the SICKLE CEl.L DISEASE
older RBC population with insufficient G6PD activity Sickle cell disease (SCD) is the name for a group of
(because of the shortened half-life of the enzyme}. recessive genetic disorders cau.ed bysickle-hemoglobin
(Hb S). The most common and severe form of SCD

is sickle cell anemia (Hb SS), the homozygous state
for the Hb S mutation (P~lu~Val: valine substituted
for glutamic acid in the p--globin chain). Other forms
of SCD result from compound heterozygous states
with Hb S and other abnormal Hbs, such as Hb C
(sickle-hemoglobin C disease). In the United States,
approximately 1 in 2,500 newborns and 1 in 350
African American newborn~ has SCD, and at least
100,000 individuals are affected in the United States.
Millions are affected worldwide, mainly in Africa.
Ganatlcs and Pathophysiology
The common forms ofSCD are listed in Table 12-5.
Sickle cell trait, which is not a disease, is included FIGURE 12-1. Sickled red blood cell in canter of figure.
for comparison. (This image was provided by the Department of
The two main pathophysiologic consequences of Hematology at 1he Ann and Robert H. Lurie Children's
polymerization of Hb SS, or sickling. are hemolysis .~.~!?.~.~ ..~..9.~.!~.?.:1...........................................................................................
and vasa-occlusion. The mean RBC life span in Hb
SS is dramatically shortened to 10 to 20 days from
the normal RBC life span of 120 days. The rate of
hemolysis in SCD mually exceeds the rate at which Table 12-6lists the usual hematologic findings in
new RBCs can be produced by the bone marrow. the common forms of SCD. To confirm a diagnosis
Sickle erythrocytes (Fig. 12-7) are also abnormally ofSCD. however. some analysis ofHb types must be
adhesive and have weakened tlexibility. Consequently, performed, so called Hb electrophoresis. Abnormal.
they can adhere to the endothelium ofblood vessels Hb must be identified using at least two methods
and block the flow of blood. nus microvascular because they can be difficult to differentiate. Con-
obstruction. called 'VUO-'occlmion.leads to ischemia temporary Hb .separation methods include IEF and
and infarction of tissues in different body parts. HPLC. DNA-based diagnostic methods, which are
increasingly available, and family testing may be
needed in occasional diagnostic challenges.
In the United States and some other countries, universal
It is important to know that •sickle prep" or "Sick-
newborn screening programs for hemoglobinopathies
ledex'" does not differentiate between SCD and sickle
now identify individuals with SCD shortly after birth.
cell trait. These tests only confirm the presence of
Such earlydiagnosis is key to preventing early mortality
Hb S, which is found in both SCD and the trait, so
from sepsis and acute splenic sequestration.
it is not helpful for the diagnosis of SCD because
Beyond the immediate newborn period, the lab-
there is no quantification of Hb S percent.
oratory evaluation ofsuspected SCD should include
Because patients with SCD have a chronic
the following: hemolytic anemia, they also have unconjugated
• CBC hyperbilirubinemia and variable elevations ofLDH
• Reticulocyte count and aspartate transaminase • After the first year of
• .Examination of the peripheral blood smear life, the peripheral blood smear in Hb SS and Hb
• Hb electrophoresis Sj}0 shows the following:
TABLE 12-1. Comparison of the Common Sickle Cell Diseases and Sickle Cell Trait
Hb SS ps ps Hb S
................
Severe
Hb S~0 ps f30 Hb S Severe
Hb sc ~ JJC Hb S. Hb c Mild-moderm
Hb s~· ps ~· Hb S. Hb A Mild
Hb AS p ps Hb A, Hb S Asymptomatic ~
;oooooooooooo•""'"'"""'"""'"'''''' ' ' ' ' ' ' '• •oooon ,.ooooo oooooooo oooooooooooooooooooooooo oooooooooooooooooooooooooooooooooOoooooOoooooooooooo<ooooo"oooooooooooooooo-oooooooooooooooooooooooo"o""'''''''' ' ' ' ' ' " ' ' " ' " ' ' ' ' ' ' ' """"" ' " " "" " ' " ''"""'""""••••••noooonoooooooo:
TABLE 12-8. Typical Laboratory Rndings in the Common Farms of Sickle Cell Disaase
!~ Sfdde
-cell anemia
lgii(IML)
6-9
...
Normal
........... (%) l
10-25
ii Slclde-~0-thalauemla
'
6-9 Deaeaeed 10-25
IS~in c disease 9-12 Normal 5-10
l Sickle-p•-thalauemia 10-12 Deaea&ed 2--10
L~~-~-~~.:..t.'!!?.Y.~..~.~-~~~-~!.~~!.: ........-·············································-··········································-·············..................................._...........................................................
• Sickled RBCs the painful episode is usually symptomatic with a

• Polychromasia combination offluids and analgesia, and sometimes
• Howell-Jolly bodies hospitalization is needed.
• Poikilocytes • Analgesia must be tailored to the degree ofpain and
• Target cells in patients with Hb SC and Hb Sf3° the patient. A combination oforal (PO) or inti.'IM!nous
Hawell-Jolly bodies are indicative ofhyposplenism. (IV) zwnsteroidalanti·inflammatory drugs (NSAIDs)
Patients with Hb sc and Hb sp+ usually do not haw (e.g., Ibuprofm) and oral or IVopioid analgesics (e.g.,
significant numbers ofirreversibly sickled RBCs, but IV Dilaudid or PO Oxycodone). titrated to effect.
they have instead a larger number of target ceUs. The will usually achieve adequate pain relief
MCV is nonnal in Hb SS and Hb SC, unless there is • Maintenance fluids, PO or IY, provide the ap-
a coinherltance ofa--thalassemia. The MCV is low in propriate level of hydration without the risk of
Hb Sp0 and Hb Sf3+. Leukocyte and platelet counts are overhydration with increased risk of pulmonary
usually moderatelyincreased in SCD in the absence of complications (e.g., acute chest syndrome).
infection because ofthe chronicinflammatory process. • Transfusion is not effective for uncomplicated
painful episodes.
Clinical Manifestations • Patients should be carefully monitored in the
At birth, newborns with Hb SS have normal birth hospital setting, emergency room or Inpatient,
weight and are not anemic. Anemia and reticulo- ifpain cannot be adequately controlled at home,
cytosis usually appear between 2 and 6 months of or ifthey are at increased of complications from
age. Along with the anemia come jaundice and a their vaso-occlusive cri8es.
cardiac flow murmur. Jaundice and flow murmurs
are expected findings that should not cause concern. Acute Chest Syndrome
Splenic infarction and hyposplenism may begin to Acute chest syndrome is a pneumonia-like illness
occur by 3 months of age, which make the spleen that is defined as the triad of fever. hypoxia, and a
poorly functioning or nonfunctional Therefore, it new infiltrate on chest x-ray (Flg.12-8). Acute chest
is necessary to start prophylactic penicillin before syndrome often starts as a small infiltrate in one
this time to prevent pneumococcal sepsis. Acute lobe, but it can progress rapidly to involve multiple
vas<rocclusive events are unusual before 6 months of lobes, resulting in respiratory distress that could be
age. The first painful event is often dactylitis, which severe enough to require intubation and ventilatory
is a painful swelling of the hands and feet. Dactylitis support. Acute chest syndrome is a leading cause
is rare beyond 3 years of age. of death in adolescents and adults. Management
includes the following:
Vaso-occlusiw: Crises
Intermittent episodes of pain are caused by acute • Oxygen supplementation for hypoxemia
vasa-occlusion, primarily In bones and bone mar- • Maintenance of adequate hydration without
row, with consequent ischemia and inflammation. overhydration
Infection, dehydration, exposure to the cold. asthma • Antibiotics (e.g., third-generation cephalosporin
exacerbationa, or strellllll may precipitate pain. Patients and azithromycin)
with SCD-related pain, even severe, typically have • Adequate but not excessive analgesia as needed
no accompanying physical signs, such as edema for pain control
or erythema (an exception to this is dactyU.tis in • Transfusions or exchange transfusions may be
in&nts and very young children). The treatment of needed for moderate and especially severe cases.
professionals is important to prevent a fatal outcome.

Aggressive hydration is usually needed for patients
with hypovolemic shock, and pRBC transfusion is
usually needed for symptomatic patients with severe
anemia. Antibiotics are also often needed to cover
possible seps.ls. Splenectomy should be considered
after the second episode of sequestration.
lnfrK:tJons
Chi1dren with SCD have a very high vulnerability to
sewre pnewn.oooccal sepsis because of the early loss
of splenic retiruJoendothelial function (functional
hyposplenism or asplenia) caused by the repeated
vaso-occlusive infarctions ofthe spleen. '!'he damaged,
enlarged spleen graduallybecomes small and fibrotic,
and it is rarely palpable after 5 years ofage. Therapeutic
FIGURE 12·1. Acute chest syndrome with a new infiltrate splenectomyfrom recurrent splenic sequestration can
seen on chest x-ray. {This image was originally published
also result inan increased. risk ofpneumooocx:al infection.
in U.S. National Ubrary of Medicine Openi Image Bank.
Grumbo RG. Acute chest syndrome. 2008; MPX1166_syn- Fatal pneumococcal sepsis is now rare in children
cpic41473. C U.S. National Ubrary of Medicine.) with SCD in the United States because of universal
newborn screening for hemoglobinopathies, prophy-
lactic penicillin, and the routine protein-conjugated
Splenic Stltlusstratlon pneumococcal vaccine. Patient& with SCD also have a
In chlldren less than 2 years ofage in whom splenic predilection for osteomyelitis. In particular, salmonella
auto-infarction is not yet complete, the spleen may species cause about half the cases ofosteomyelitis in
become acutely enlarged and engorged with blood SCD and staphylococci cause the other hal£
sequestered from the systemic circulation, which is
called "splenic sequestration:' In patients who main- Aplastic Crlsls
tain some degree ofsplenic function later in life, such During many viral infections and inflammatory states,
as Hb SC patients, splenic sequestration may occur erythropoiesis may be modestly reduced, resulting in
at an older age. Patients with splenic sequestration relative reticulocytopenia and transiently more severe
usuallypresent with severe anemia, hypovolemia, and anemia. Human parvovirus, however, temporarily
marked splenic enlargement. The recognition ofacute destroys early red cell precursors in. the bone marrow
splenic enlargement and the signs and symptoms of and causes a dramatic and potentially life-threatening
acutely severe anemia by both parents and health care anemia (Fig. 12-9A and B). This episode of severe
RGURE 12-1. Aplastic anemia

with low {A) and high (B)
power views of dysplastic
bone marrow. The reduced
cellularity of 1he obvious from
1he low-powered image.
When seen 1hrough high
power, the bone marrow can
be seen to be replaced with
~rimari~-~e~?.Y.!~.:...................... ._
anemia without appropriate reticulocytosis is called these are more lilrelym occur in adult patients. When a
the "aplastic crisis;" Transfusion of pRBC is the most result ofan immun.e respODJJe, the disease process may
important intervention for symptomatic or severe be alloim.rnune or autoimmune mediated.
anemia. Lifelong immunity against parvovirus pre-
• Alloimmu~ hemolytic a111m1ia results from an-
vents recurrent episodes.
tibodies produced by one indMdual against the
Stroke RBCs of another indMdual of the same species,
Children and adults with SCD may suffer overt such as hemolytic disease of the newborn caused
strokes, causing neurocognitive dysfunction and/or by maternal-fetal incompatibility for minor RBC
other neurologic deficits. In the palt decade, primary antigens (e.g., Kell).
stroke prevention strategies using annual transcranial • Isoimmune hemolytic anemia is a special case of
Doppler ultrasonography and chronic transfusion alloimmune hemolytic anemia caused by isohemag-
regimens have been quite effective at preventing glutinins, which are naturally occurring anb."bodies
overt strokes in children. Imaging of the brain and with specificity against the A orB antigens of the
cerebral vessels is important for any chlld presenting ABO blood group. lsoimmune hemolytic disease
with weakness or other signs or symptoms ofstroke of the newborn is caused by maternal- fetal ABO
or other possible neurologic deficits. Transfusion with incompatibility (see Chapter 13).
pRBC, oftentimes exchange transfusion, is indicated • In Autoimmune hemolytic anemia (AIHA), the
for acute stroke and prevention of recurrent stroke. patient produces autoantibodies against autol-
ogous (self) antigens on his or her own RBCs.
Chronic OlfiB/J Dysfunction and Damage
AIHAs can be idiopathic, postinfectious (e.g ••
In addition to early splenic dysfunction and involu-
Mycoplasma pneumoniae, Epstein- Barr virus
tion, other forms of progressive organ dysfunction
[EBV]), drug-induced (e.g., penicillin, quinidine,
or daJnase occur with increasing age in the kidneys,
a-methyldopa), or may be a feature of an under-
bones, eyes, lungs, heart, and liver.
lying autoimmune disease (e.g., systemic lupus
Treatment erythematosus) or malignancy (e.g., lymphoma).
There are three main disease-modifying treatments
that can reduce the overall severity of SCD or cure
The typical presentation of AIHA is a previously
it: hydroxyurea, chronic transfusions, and hemato-
healthy young child with the rapid onset of fatigue,
poietic stem cell transplantation.
pallo~ jaundice and dark urine (hemoglobinuria);
• Hydroxyurea increasesthe concentrationoffebdHb splenomegaly is seen in a minority of patients. De-
orHb F, which reduces sickling. Clinically, hydroxy- pending on the degree, there may be tachycardia, a
urea reduces seD-relatedcomplications (e.g., painful flow murmur, and even impending heart failure. A
episodes and acute chest syndrome) and mortality, presentation with mainly jaundice but mild or no
and improves quality ofllfe in patients with SCD. hemoglobinuria is most consistent with IsG·medl-
• Chronic, monthly transfusions are effective at pre- ated extravascular hemolysis, that is, warm AIHA.
venting molt complications ofSCD, but the most A presentation with marked hemoglobinuria and
common indications are primary and secondary mild or no jaundioe is consistent with IgM-mediated
stroke prophylaxis. Complications of transfusions intravascular hemolysis, which is cold agglutinin
include iron overload and alloimmunization. disease or cold AIJ·IA.
• Hematopoietic stem cell transplantation is a
Aslocieted Labondary Values
curative treatment option for SCD. However,
The binding of antibodies (with or without com-
the widespread use of transplantation in SCD
plement) to the RBC membrane causes immune
is limited by the lack of donor availability and
hemolytic anemia. In assessing for hemolysis, a
toxicities of the procedure.
CBC and peripheral smear will show the following:
• Gene therapy is another curative option for
patients' SCD, and research studies are ongoing. • Low Hb and hematocrit (mild to severe)
• High reticulocyte count or compensatory
AUTOIMMUNE HEMOLYTIC ANEMIA reticulocytosis
Immune hemolytic anemia is common in children and • Polychromasia
often an isolated phenomenon. Although it can be related • Varying degrees of spherocytosiJ
to autoimmune, malignant. orinflammatory oonditions, • Red cell agglutination
The antJ.oodies resporwole for the hemolytic ane- Macrocytic anemia with megaloblastic features,
mia can be identified by the OAT (previously called including the following:
the direct Coombs test), wbJch is the diagnostic test • Vitamin B12 and folate deficiency
for AIHAs. The antibodies that cause AIHAs may • Dmgs that iilt:erfEre with folate metabolism (e.g.,
be of the IgG or IgM classes. methotrexate. trimethoprim)
• IgG antibodies tend tD bewann-reactive {maximal • Metabolic disorders (e.g., orotic aciduria. meth-
activity at 37"C). They ue considered "incomplete" ylmalonic aciduria, Lesch-Nyb.an syndrome).
antibodies because they can fix early complement Macrocytic anemias without megaloblastic
components but cannot agglutinate RBCs or features result from bone marrow injury, including
activate the complement cascade in its entirety. the following:
IgG-mediated hemolysis occurs primarily in the
extravascular compartment because of the trap- • BMF syndromes (e.g., DBA, Fanooni anemia,
ping of antibody·coated. RBCs by macrophages myelodysplasia)
in the reticuloendothelial system, especially the • Idiopathic aplastic anemia
spleen. IgG antibodies are associated with idio- • Drug·induced anemias (e.g., azidothymidine,
pathic cases, underlying autoimmune diseases, valproic acid, carbamazepine)
lymphomas, and viral infections. • Chronic liver disease; and hypothyroidism.
• IgM antibodies are usually cold reactive (maximal
activity at ...4"C). They are called •complete" an- MEGALOBLASTIC MACROCYTIC ANEMIAS
tibodies because they can agglutinate RBCs and VItamin B11 Deficiency
activate the complement sequence through C9, Vitamin B12 is a coenzyme needed for the formation
causinglysis of RBCs. Hemolysis occurs primarily of 5-methyl-tet:r:ahydrofolate, which is essential for
in the intravascular compartment. IgM antibodies DNA synthesis. It is found in meat. fish, cheese, and
are associated with M . p~UumonitU, EBV, and eggs. VItamin Bu combines with intrinsic facto~< which
some transfusion reactions. is produced by gastric parietal cells, and absorbed in
the terminal ileum. Transcobalamin II then transports
Treatment vitamin B12 to the liver for srorage. The availability
Therapy for AlHA varies depending on the cause ofvitamin B12 is reduced by any condition that alters
and the clinical condition of the patient. In general, intrinsic factor production. interkrel with .intestinal
treatment is supportive, with the judicious use of absorption, or reduces transoobalamin II levels.
corticosteroids and pRBC transfusions for warm Dietary vitamin Bu defidency is rare in developed
AIHA. In individuals that require chronic steroid countries except in the breastfed infant whose mother
use, alternative therapies (rituximab, azathioprine, is a vegan with poor attention to dietary sources of
mycophenolate mofetil) or splenecromy can be used. vitamin B12• Another cause ofvitamin B12 deficiency
If considering a therapeutic transfusion, it is is selective or generalized malabsorption.
important to understand that autDantibodies react Disorders such as congenital pernicious anemia
with virtually all RBCs, making cross-matching (absent intrinsic facror), juvenlle pernicious anemia
difficult. In some severe chronic cases, splenectomy (autoimmune destruction of intrinsic factor), and
may be indicated. Cold agglutinin disease tends to be transcobalamin II deficiency result in vitamin B12
steroid nonresponsive, and plasmapheresis could be deficiency. Other causes include deal resection, small
effective. Also, keeping patients warm can prevent bowel bacterial overgrowth, and infection with the
some of the hemolysis. fish tapeworm DiphyUobothrium latum.
Clinical ManttsstBt/ons
~~~~~~a''';w~mruMilll
The effects ofvitamin B1a deficiency include glossi-
tis, diarrhea, and weight loss. Neurologic sequelae
include paresthesia, peripheral neuropathies, and.
Macrocytic anemias can be subclassified on the
in the most severe cases, dementia, ataxia, an.d!or
basis of the preseooe or absence of megaloblastic
posterior colwnn spinal degeneration.
features as a marker of ineffective DNA synthesis
within RBC preCUl'80rs. Not all macrocytic anemias Associatsd Laboratwy VBIU6B
are megaloblastic, but all megaloblastic anemias are Megaloblastic chanses on peripheral blood smear
macrocytic. include the following (Flg.l2-10):
JhJatmsnt
Treatment for molt forDUI of vitamin 8 12 deficiency,
with the exception of bacterial overgrowth and
fish tapeworm, is parenteral vitamin B11• The
erythropoietic response is rapid, with marrow
megaloblastic changes improving within hours,
reticulocytosis appearing by day 3 of therapy,
and anemia resolving within 1 to 2 months.
MMA level is a useful marker of deficiency and
response to vitamin B12 therapy, although vitamin
B11 level may fluctuate over time and be affected
by transcobalamin levels.
Falata D&nclency
Dietary folate is usually found in liver, green veg-
FI&URE 12-tD. The peripheral blood smear of an infant etables, cereals, and cheese. Dietary folate is then
with megaloblastic anemia caused by severe vitamin
8 12 deficiency was remarkable for the presence of
converted in the body to tetrahydrofolate, which is
macroovalocytes, mlcrocytes, basophilic stippling, required for DNA syntheais. Because folate stores
and rare hypersegmented neutrophils. (This image are relatively small, deficiency may develop within 1
was originally published in The American Society of month and anemia within 4 months ofdeprivation;
Hematology Image Bank. Shponka V. Proytcheva M. however, it is rare, given the abundance of folate in
Megaloblastic anemia caused by severe 812 deficiency dietary sources. Etiologies include the following:
in a breastfed infant. 2017; image 61 082-image 61082.
~.~~..~.~~~.~..~.~~!~..~..!:!~~~~~L...........__... . ..... • Inadequate dietary i.ntalce
• Impaired absorption of folate
• fucreaseddemandforfula~
• Abnormal folate metabolism
• OVBlocyt:osis
• Neutrophila with hypersegmented nuclei (more Chlldren at risk are infants who were fed goat milk,
than four per cell) evaporated milk, or heat-sterilized milk or formula;
• Nucleated RBCs each has inadequate folate content. Malabsorptive
• Basophilic stippling states of the jejunum, such as inflammatory bowel
• Howell-Jolly bodies disease and celiac sprue, can cause folate deficiency.
Increased demand. fur folate occurs with an increased
The hallmark of megaloblastic anemia is nucle- rate of RBC turnover (e.g.. hyperthyroidism, preg-
ar-to-cytoplasmic imbalance in RBC precursors (the nancy, chronic hemolysis, malignancy). Relative
nucleus matures or develops more slowly than the folate deficiency may develop if the diet does not
cytoplasm). The MCV is usually greater than 100
provide adequate folate to meet these needs. Certain
fL. Hemolysis also results in elevated levels ofserum anticonvulsant drugs (e.g., phenytoin, phenobarbital)
LDH, indirect bilirubin. and serum iron.
interfere with folate metabolism and may also cause
Laboratory tlndings include the following:
folate deficiency.
• Low serum and/or RBCs folate level
Cllntcsl Msn/fsstattons
• Normal serum vitamin B12 levels Patients are often asymptomatic, but could present
• High homocysteine with pallor, glossitis, malaise, anorexia.. and poor
• NormalMMA growth. Unlike vitamin 8 11 deficiency, neurologic
In severe cases, megaloblastic anemia may be disease is not associated with folate deficiency.
accompanied by leukopenia and thrombocytopenia.
AssociiJtsd l.siJoratDry ~ues
Diagnosis of vitamin 8 11deficiency is confinned by
Laboratory findinga include the following:
a high MMA level and subnormal serum level of
vitamin B12• The Schilling test is no longer avail- • Low serum and/or RBCs folate level
able clinically in the United States. Homocysteine • Normal serum vitamin B12 levels
is usually high in both vitamin 8 12 defi.dency and • High homocysteine
folate deficiency. • NormalMMA
2IIS • BLUEPRINTS Pediatrics
Megaloblastic changes on peripheral bloodsmear

and bone marrow aspirate are similar to those noted
with vitamin ~z deficiency.
Treatment
It is imperative not to misdiagnose Btz deficiency
as folate deficiency because treatment with folate
may result in hematologic improvement but with
progressive neurologic deterioration. Treatment
with 1 mg of folate given orally every day for 1 to
2 month. treats the anemia and replenishes body
stores. Oinical response is rapid. following a time
course similar to that of vitamin B12 replacement
therapy. Children with chronic hemolytic conditions FIGURE 12-11. A child with Blackfan-Diamond anemia
may require folate supplementation. and triphalangeal thumbs. (This image was originally
published in U.S. National Ubrary of Medicine Openi
NONMEGALOBLASTIC MACROCmC ANEMIAS Image Bank. Ahmed Z, McGuiness CN. Thumbs up! A
novel use of the acutrak screw fixation system for the
Dietary vitamin ~z and folate deficiency are rare in management of 11iphalangeaJ thumb. 201 0; Figura 3. 0
children in developed nations. So, the evaluation of .~.:~.:..~.~~~~~!...~::!.~.~~--~--~~!~!.~.~.:)........................................................
a child with macrocytosis should always include con-
sideration of nonmegaloblutic caURS. BMF disorders
may be congenital or acquired. and it is especially About 90% of caaes are diagnosed within the first
important to consider congenital disorden in children. year of life.
Prognosis and treatment depend upon the diagnosis. Laboratory findings include the following:
This section briefly discusses two congenital BMF
• High MCV or macrocytosis (mild)
syndromes (DBA, Fanconi anemia) and one acquired
• Low reticulocyte& or reticulocytopenia (mild)
BMF disease (idiopathic aplastic anemia).
• Low or very low RBC precuraors in bone marrow
Dlamond-Biacldan Anamla aspirate and biopsy
DBA is a congenital pure red cell aplasia. Both auto- • High Hb F on Hb electrophoresis
&omal dominant and recessive patterns are reported. • High adenosine deamina.se in RBCs.
Twenty-five percent of patients have a mutation in
lhlatmsnt
the riboaomal protein S19 gene (RPS19). Mutations
Two~thirds of patients respond to oral corticosteroids,
in several other ribosomal protein genes have been
oftentimes with a very low, "subphysiologic" dose,
described as well.
with an improvement in or resolution of anemia.
Clinical ManlfsstJit/ons Steroid responders may maintain their response
Twenty· five pereent ofpatients have associated congenital indefinitely or eventually lose the response. Those
anomalles that include short stature, web neck, cleft who do not respond to steroids, lose their response,
lip, shield chest, and triphalangeal thumb (F'J.g. 12-11). or have excessive steroid-related toxicity may re-
TEC is an important consideration in the differential quire chronic pRBC transfusions. Hematopoietic
diagnosis of DBA. Generally. DBA tends to present stem cen
transplantation is a curative option for
at a younser age than TEC and.Is usually macrocytic, some patients with good outcomes in the presence
unlike TEC. Children with DBA are at a high risk for of matched sibling donor. Care should be taken to
multilineage BMF and leukemia later in life. ensure that matched sibling donors are also tested
Because ofan attenuated phenotype, members of before transplant to ensure that they do not have
the same family with DBA can present with varying the condition with a milder phenotype.
degrees ofseverity. For this reason, it is important to
Fanconi Anemia
screen all family members. Pregnancy and puberty
Fanconi anemia is an autosomal receuive disorder
can both trigger presentation of symptoms in indi-
viduals that do not present in infancy. that results in pancytopenia secondary to BMF. One
form is X·Unked. Mutations in over a dozen known
Assoclatrld LaboraiiHy Va/UBS genes can cause Fanconi anemia. The disorder results
The anemia develops shortly after birth but is not from defective DNA repair mechanisms that lead to
usually detected until later, when symptoms develop. excesaive chromosomal breaks and recombinations.
These chromosomal anomalies are found in all cells or other agents that damage DNA. Hematologic
of the body, not just the hematopoietic stem cells, manifestatioM include the following:
although there may be somatic mosaicism. The mean • Low Hb, WBCs and platelets (progressive
age at onset of pancytopenia is 8 years.
pancytopenia)
Clinical ManifeBilllions • High MCVor macrocytosis, which is universal
Fanconi anemia is characteri7.ed by multiple physical even before the onset of anemia
congenital anomalies, hematologic abnormities, and • High Hb F on Hb electrophoresis
an inaeased risk of hematologic and nonhematologic
Most patients with Fanconi anemia will develop
malignancies in the future. Common signs include
some degree ofBMF and hypoplastic or aplastic ane-
the following:
mia by the age of10. Howev~ some may not develop
• Hyperpigmentation and cafe-au-Jait spots BMF and aplastic anemia until later In adulthood.
• Microcephaly
TtBatmsnt
• Microphthalmia
Patients frequently require pRBC transfusions for
• Short stature
symptomatic anemia. Some patients have hematologic
• Horseshoe or absent kidney
improvement with androgen therapy. Hematopoietic
• Absent thumbs (Flg.12-12)
stem cell transplantation is the treatment of choice
• Absent or hypoplastic radii
for progressive BMF ifan HLA-matched donor can
Approximately 1006 of children with Fanconi be found. Because ofFanconi anemia patients' DNA
anemia develop myelodysplastic syndrome (MDS) repair defect, the preparative (pretransplant) doses of
or acute myeloid leukemia (AML). Individuals with radiation and chemotherapy, both ofwhich damage
Fanconi anemia have a 500 times increue in the risk DNA, must be reduced from what is normally used
of developing AMI., with the average age of onset for patients without Fanconi anemia to prevent
for MDS or AML being late adolescence. severe morbidity and death.
Assot:IBtrHI LtJbtJnJtDry vatuss ldiapa1hic Aplastic Anemia
Diagnosis is confirmed by demonstrating increased Idiopathic aplastic anemia is an acquired failure of
chromosomal breakage with exposure to diepoxybutane the bone marrow or the hematopoietic stem cells
that leads to pancytopenia. The disorder may result
from exposure to the following:
• Chemicals (benzene, phenylbutazone)
• Drugs (chloramphenicol sulfonamides)
• Infectious agents (hepatitis virus)
• Ionizing radiation.
Most commonly, a specifi.c cause ofaplasia is not
identified, and therefore, it is termed "idiopathic
aplastic anemia~ Postinfectious (e.g., hepatitis virus)
and idiopathic forms ofaplastic anemia are caused by
autoimmune destruction of hematopoietic stem cells
and/or the microenvironment of the bone marrow.
Idiopathic aplastic anemia is usually severe but can
also be mild or moderate based on bone marrow
FIGURE 12-12. Twelve-year-old boy with Fanconl anemia. cellularity percent at the time of diagnosis.
The classic phenotypic features Include short stature, Clinical Manifestations
microcephaly, broad nasal base, eplcanthal folds, Patients with severe aplastic anemiausuallypresent with
micrognathia, caM au lalt spots (chin and left temple}, signs and symptoms of anemia (e.g., fatigue, pallor),
absent thumb left {after reconstructive surgery), and
thrombocytopenia (e.g., easy bruising, bleeding), and/
tr1phalangeal thumb left. (This Image was reproduced
from Bessler M, Mason PJ, Link DC, Wilson DB. or neutropenia (e.g., fevers, infections). The onset of
Chapter 8: lnhertted bone marrow failure syndromes sigM and symptomsisoftenlnsidiousand slow. Toxic
{Figure 8-2). In: Nathan DG, Oskl FA, eds. Hematology exposures (e.g., medications, chemicals, radiation) are
of Infancy and ChUdhood, 7th ed. Philadelphia, PA: WB rare causes ofapl..ast:ic anemiainthe United States, but
~~~!:!~.~).~~~.~~:~~.~~.!.1............................................................... a complete history could elicit any such expo5ures.
AssoclatrKJ LaboratDry Va/UBS neutrophils. An increase in the neutrophil count

In the setting ofaplastic anemia, the CBC will show is often seen in the presence ofinflammation and
the following: infuctions, especially bacterial but not exclusively.
• Band cells are the immature form of the circulating
• Low Hb, WBCs and platelets (progressive
neutrophll (not yet having distinct nuclear seg-
pancytopenia)
mentation). The tenns •teft siU£t- or "bandemla•
• High MCV or macrocytosis
refers specifically to an absolute increase in the
• Low reticulocyte counts or reticulocytopenia
number of bands, whether or not the total WBC
• Low bone marrow cellularity
count is increased.
Aplastic anemia is diagnosed by the combination • Monocyte& also function as phagocytes and
of peripheral pancytopenia and a hypocellular bone antigen-presenting cells.ln the presence of neutro-
marrow. penia, there is often a compensatory monocytosis.
• An increase in eosinophtls is often seen in allergic
Trsatmflflt
and atopic conditions as well as parasitic infections.
Without treatment (historically}, 8096 of patients
• Basophils are the least numerous ofthe leukocytes
die within 3 months of diagnosis from bleeding or
and may also be involved in allergic responses.
infection. Therapy is typically both supportive and
• Lymphocytes are a critical component of the
definitive or curative, depending on the severity of the
lnunune system, and are responsible for both
symptorm. The treatment ofchoice is hematopoietic humoral and cellular immune responses.
stem cell transplantation with an HLA-matched
sibllns donor. Second-Une therapy includes immu- When a chlld with a suspected WBC dysfunction
nosuppression with horse-derived anti-thymocyte is encountered, a thorough medical history including
globulin (hATG) and cyclosporine, or hematopoietic the past and family history should be obtained along
stem cell transplantation from a matched unrelated with a detailed physical examination. In particular, a
donor, for patients who do not have a matched sibling history of medications, toxins, or other environmental
donor. There is growing evidence to support the use of exposures, and the frequency and severity of prior
thrombopoietin agonilt or thrombopoietin mhnetics infections is absolutely critical. A family history of
in addition to hATG and cyclosporine in patients other similarly affected individuals with a history of
with idiopathic aplastic anemia. Iftransplantation is early childhood or in utero deaths and any delays in
considered, it is important to minimize transfusions umbilical cord separation should also be obtained.
to reduce exposure to potentially sensitizing blood Recurrent fevers and infections ofthe skin and mucous
products. Neutropenic patients are at risk for serious membranes (espedally of the perianal region and
bacterial infection and usually require antibiotics mouth) are particularly indicative ofWBC dysfunction
when they develop fever. or deficiency. Gingivitis and oral mucosal ulcerations
are common features of chronic neutropenia.
WBC disorders can be broadly classified into
abnormalities ofWBC number (leukopenia or low
WBC, or leukocytes, are the primary systemic defense WBC count; leukocytosis or elevated WBC count)
mechani&ms against infections. The total WBC count and WBC functlon (leukocyte function disorders).
and the differential count often provide valuable
clues for the diagnosis and treatment of a variety of DISORDERS OF LEUKOPENIA
conditions, hematologic and nonhematologic. Most
Leukopenia is generally defined as a total WBC count
often. an increase or decrease in WBC number is
of less than 4,000 cella/mm3; however, this number
transient or secondary to another condition. The
varies by age. Because leukopenia may be caused
leukocytes are broadly categorized as granulocytes
by suppression of one of more types ofWBCs, one
(neutrophils, eosinophils, and basophils), lympho-
must pay close attention to the differential count.
cytes, and mononuclear phagocytes (monocytes):
The most common causes ofleukopenia are transient
• Gnmulocytu are so named becawe of the presence responses to infections (bacterial or viral) or drugs.
of intracytoplasmic granules. In these cases, the mechanism ofleukopenia could be
• Neutrophils are the largest population of gran- variable, including antibody-mediated destruction.
ulocytes and are also referred to as segmented bone marrow suppression. or a shift into the tissue
neutrophils ("segs")- these are the mature form of or marginated compartments. Decreases in WBC
types, other than neutrophils, are much less com- and connective tissue disorders, GI disorders,
mon. A marked decrease in lymphocytes, especially and the idiopathic hypereosinophilic syndrome.
inyoung infants, should prompt further evaluation • ~mphocyt04u is seen in hypersensitivity reactions,
for an underlying immune disorder, such as severe some leukemias, and in infections, primarily viral
combined immunodeftdency. VIral infections and infections and pertussis.
corticosteroids can also cause lymphopenia. • Monocytosis is associated with autoimmune
NeutropeDia is arbitrarily defined as an abso- conditions, infections (EBV, fungal. protozoal.
lute neutrophil count (ANC) less than 1,500/mm3 rickettsial, tuberculosis), and pomplenectomy.
for individuals 1 year of age or older and less than • Neutrophilit1 is seen with bone marrow stimula-
1,000/mm8 when under 1 year ofage. African Amer- tion, chronic inflammation. infections, congen-
icans commonly have lower neutroplill. counts than ital disorders, medication side effects, reactive
Caucasians, with an ANC normaUy as low as 600 to elevations, and 1n splenectomy.
800, so called benign familial or ethnic neutropenia.
The workup and treatment of these disorders is
Thus, it is very important to consider the patient's
dependent OD the individual clinical picture and course.
race/ancestry when interpreting leukocyte counts.
Neutropenia can be caused by the following: DISORDERS OF LEUKOCYTE FUNCTION
• Bone marrow suppression or replacement These conditions are rare and may involve abnor-
• Autoimmune neutropenia malities in one or more of their normal physiologic
• Vl.l'al infections resulting in bone marrow suppression functions, which include motility and migration,
• Medications (chemotherapy agents) chemotaxis, and bacterial ingestion and killing.
• Nutritional deficiencies Nonspecific clues to the presence of leukocyte
• Genetic conditions (e.g., Shwachman-Diamond dysfunction include the following:
syndrome)
• Chronic leukocytosis (especially in the well state)
• Congenital disorders caUJing neutropenia (e.g.,
• Lack of pus formation
Glycogen storage disease. type lb)
• Delayed separation of the umbilical cord.
It resolves when a causative infection resolves or
In neutrophil dysfunction, specifica.lly, the pri-
the offending drug is discontinued. When neutropenia
mary evidence of a problem is infection. This will
is prolong~ severe, or accompanied by decreases
manifest as an infection with unusual organisms, in
in other cell types, then a bone marrow examination
atypical locations, or as infections that occur more
should be considered. Fever or infection in the setting
frequently or at unusual ages.
ofsevere neutropenia (ANC < 500/mm3) often war-
Neutrophil dysfunction disorders include chronic
rants parenteral antibiotic therapy and hospitalization.
granulomatous disease, neutrophil-specifu: granule
deficiency, or leukocyte adhesion deficiency. Flow cy-
DISORDERS OF LEUKOCYTOSIS tometry and molecular genetics will aid in a diagnosis.
An increase in the WBC coWlt above the normal Ifleukocyte dysfunction is suspected, a referral to a
range is called "leukocytosis" and is most often en- pediatric hematologist and a pediatric immunologist
countered in response to inflammation, infection, is warranted. Treatment of these disorders is often
allergy, or as a consequence of some malignancies. supportive or curative with hematopoietic stem cell
Leukocytosis is a normal physiologic finding in the transplantation. These and other immune disorders
newborn period, during stress, and in pregnancy. are discussed more fully in Chapter 8.
Leukocytosis is commonly seen in association
with bacterial and viral infections and in chronic DISORDERS OF HEMOSTASIS
inflammatory states. An increase Jn neutrophils or
Normal hemostasis requires the integrity and
lymphocytes is the most common cause for leu-
interaction of blood vessels, platelets, and soluble
kocytosis. Specific conditions are associated with
coagulation (..clotting•) factors. Platelets and the
elevations in the different cell lines:
vessel wall are the key participants in primary
• Basophilia can be seen in allergic reactions and hemostasis, which includes vasoconstriction and
in some leukemias. the formation of a platelet plug at the site of vessel
• Eosirwphilia can be associated with allergy and injury. The platelets that are activated at the site of
drug hypersensitivity. parasitic infestations, skin tissue injury, in combination with exposed tissue
factor, bring about the secondary hemostasis, which the history and physical exam are consistent with
involves the formation of a fibrin mesh from the easy bruising (bruises at the line of the seatbelt or
action of soluble coagu]ation factors on the surface areas of tight fitting clothing), further evaluation for
of platelets and other cells. bleeding disorders is warranted.
Bleeding can result from abnormalities in any
of these systems. Defects in primary hemostasis DISORDERS OF PLATELETS
typically cause bruising and mucocutaneous bleed-
Platelets are key participants in primary hemoatasis.
ing. In contrast, defects in secondary hemostasis
Plateletdisorders can be either quantitative or qual-
classically cause hemarthrosis and hematomas in
itative. Quantitative abnormalities are identified by
addition to bruising and mucocutaneous bleeding.
the platelet count, whereas qualitative disorders are
Figure 12--13 demonstrates the clinical and laboratory
detected by measures of platelet function.
steps in evaluating bleeding disorders. Disorders of
Thrombocytopenia, defined as a platelet count
platelets and of coagulation factors are discussed
below 150,000/mm3, is a common cause of abnor-
in the following paragraphs.
mal bleeding. A low platelet count can result from
In asseasing a child for po881ole bleeding disorders,
decreased production or Increased destruction of
bruising secondary to nonaccidental. trauma (NAT)
platelets. The adequacy of platelet production can be
must also be considered and ruled out. A careful
estimated, when necessary, by assessing the number
history and physical exam can help distinguish NAT
of megakaryocytes in the bone marrow. Figure 12~14
from an underlying disorder of hemostasis. Ifbruising
lists the common causes ofthrombocytopenia during
occurs in a nonmobile child~ is on areas less prone to
the neonataL infant, and childhood periods.
trauma {face~ ears, neck, upper arms~ trunk. hands,
genitalia, buttocks, and anterior and medial thighs),
displays patterned bruls1ng (a hand or belt buckle), DECREASED PLATEIEI' PRODUCnON
or the story does not match the injury, it should BMF states causing thrombocytopenia include dis-
raise concern for possible child abuse. However, if orders resulting in pancytopenia (Fanconi anemia,
Approach to a Bleeding Child
COII8:nt _ _....,
1
Hl.tary lrnmu,_-...o;o,
Low platelet oount_ _ _ _ __. •• Consumption

CBC, PTiaPTT, PFA, :t TT _ _ _ _ _ _.....;._:;.;.;....;_;.....;..;..;;... Hypersplenism
·~-~
1
p--
Platelet count normal
vWBpanel
Yes • vWD panel normal
--•? --~;;;...__.,...
PFA abn........ .. • Platelet morphology
-......;.=.:.::;;...-~"
..
•• Flow
Platelet aggr.gation
............
"'""" .. ,
e.... for
No!
Ye;.;s_ _ _ _ _ _,. • Function fibrinogen aseay
TT abnormal? _ _ _ _ _ _ _.....;.;
No! • Fibrinogen I~Wel
Ye;;:s;...._ _ _ _ _+
PT/aPTT .atnormal? _ _ _ _ _ _.....;.
.• Hepabaorb
• Mixing atudles
Specific tactor aaeaya • corraded
No
1 Yes
All•crwnlng normal? - - - - - - - . ; ; . . . _ - - - - - - + • FXIIIIwel
• :t liver Ulclion,DIC panel
FIGURE 12-13. In assessing a bleeding child, a good history and physical exam are important in determining the
initial steps in treatment and laboratory aasessment. aPTT, activated partial thromboplastin time; 010, disseminated
!.~-~-~~-!~~--?.·~-~9.~!~~-~~!..~~~~..P.!.~~--~~-~~-~--~-~~~;..~!...P.~.~-~-~~!~. .~.~-~!..I.!.·. ~.~-~-~~-i.~.Y~~:...........-.................................
lltramboc:ylopenl• by Age at PreM~~tmlon
Infant Cl'lllclhoocl
• Maternal Immune lltrombocytopenia • Viral Infections • Idiopathic Thrombocytopenic Purpura
Neonatal Alloimmune • Medications • Medications
• Thrombocytopenia • Sepsis • Hypersplenism (e.g., thalassemia,
• Sepsis • Disseminated lnlnMl8cular Gaucher Dtaaaae, Portal Hypertension)
• Dlaaamlnated lnlnlVaSCular Coagulation • Sapsla
Coagulation • ldlopalhlc thrombocytopenic • Dlaaemlnated lnti'IMlSCUiar
• Congenitallnfactiona Purpura Coagulation
• Inherited Thrombocytopenia • Malignancies (Leukemia, • Leukamia
(e.g., WISkott-Aidrich syndrome) Neuroblastoma) • Aplastic Anemia
• Thrombocytopenia-Absent Radius • lnheril8d Thrombocytopenia • Thrombotic Microangiopathies
Syndrome (e.g., Wlskoii-Aidrlch syndrome) (e.g., Hem~Uremlc Syndrome)
• eongannal Amegllkaryocyllc • Hemophagocytic Lymphohlsllocytoala
Thrombocytopenia • HIV Infection
-~~-~~~~-~-~.:~.~.!!!~..~~~..~r..~.~~~-~-~~!.~.~-~..~~~~..~-~..~-~-~..~~-~~..~~..~-~~..~-~..~~.P.~.~-~-~~~!~.~.:.......................................
idiopathic aplastic anemia, leukemia); congenital

amegakaryocytl.c thrombocytopenia; Wlskott-
Al.drich syndrome; and thrombocytopenia-absent
radius (TAR) syndrome.
TAR syndrome, also known as congenital mega-
karyocytic hypoplasia, is an autosomal recessive
disorder in which thrombocytopenia develops in
the first few months of life and typically resolves
spontaneously after 1 year of age. Absence of the
radii is pathognomonic and the thumbs are usually
present as is seen in Figure 12-15. Wudwtt-Aldrich
syndrome is an X-linked disorder characterized by
immunodeficiency, eczema, and microthrombocyto-
penla (the platelets are small and few). Hematopoietic
stem cell transplantation is potentially curative.
Examples of thrombocytopenia caused by bone
marrow suppression include the following:
• Chemotherapeutic agents
• Acquired viral infections (HIY, EBV, measles)
• Congenital infections, including toxoplasmosis,
syphilis, rubella, cytomegalovirus, and parvovi- FIGURE 12-15. Three-month-old girt with
rusB19 thrombocytopenia and upper extremity abnormality,
• Drugs (anticonvulsants, sulfonamides. quinidine, found to have absent radii on x-ray consistent with
quinine, and thiazide diuretics) thrombocytopenia-absent radii syndrome. (This image
was provided by the Department of Hematology at the
Acquired postnatal infections (with the exception
~~..~~..~~~..!j.:.. ~~-~~..9.~!.~~-~. ~-~!?..~..~!.~~-~~~.1
of HIV) and drug reactions usually cause transient
thrombocytopenia, whereas congenital infections
may produce prolonged suppression of bone marrow
can result from allolmmune or autobnmune antibod-
function with persistent thrombocytopenia.
ies. Alloimmune IgG antibodies are produced against
the fetal plateletswhen the Cet:a1 platelet crosses the
SHORTENED PLATELET SURVIVAL placenta and presents itself to the maternal immune
Shortened platelet survival occurs more often system. If there is an antigen on the fetal platelet
than thrombocytopenia caused by inadequate that does not exist on the maternal platelet, it is
production. Platelet destruction is most commonly recognized as foreign and antibodies are created
immune mediated. Thrombocytopenia in the newborn against the antigen. Maternal antiplatelet antibodies
then cross the placenta, causing destruction of the In TTP, there is a lack of the von Willebrand
fetal platelet. This disorder is known as •neonatal factor (vWF) cleaving protease (ADAMTS 13) with
alloimmune thrombocytopenia:' The maternal a resultant increase in the large multimeric forms
antiplatelet antibody does not produce maternal of vWF. These large multimers have an increased
thrombocytopenia. Autoimmune 1gG antibodies are affinity for platelets, which leads to their aggregation.
transferred to the fetus through the placenta when activation, and eventual removal (thrombocytope-
the mother has immune thrombocytopenia (ITP). nia). Other findings in TTP include MAHA, rever,
These matErnal autoantibodies cross the placenta and renal involvement. and neurologic findings. DIC is
attack the fetal platelets. In contrast to alloimmune discussed in more depth under section "Acquired
antibodies, autoimmune antibodies also result in Bleeding Disorders.n
maternal thrombocytopenia (unless the mother has
had a splenectomy). Platal&t Trapping
Depending on the platelet count, the presence Platelet trapping 1s seen 1n patients with hyper-
of bleeding, and certain risk factors, neonates with splenism or Kaposiform hemangioendotheliomas
alloimmune or autoimmune thrombocytopenia may (Kasabach-Merritt syndrome). Hypersplenism
be treated with corticosteroids and/or intravenous refers to the nonspecific trapping of blood cells in
immunoglobulin (MG) until the maternal antiplate- an engorged or enlarged spleen of any cause, which
let antibodies dissipate in fetal circulation. Washed is most commonly seen in SCD, thalassemia syn-
maternal platelets or antigen~matched platelets are dromes, Gaucher disease, and portal hypertension.
the best platelet product for neonatal alloimmune Two causes of thrombocytopenia with diminished
thrombocytopenia. A discussion of childhood ITP platelet survival in children are ITP and DIC.
appears later in this chaptEr. Heparin~induced throm~ Immune Tbrombaeylopanla
bocytopenia is another form of imm~mediated ITP, previously called idiopathic thrombocytopenic
thrombocytopenia, paradoxically associated with purpura, is a condition caused by autoimmune de-
thrombosis. struction of platelets, primarily by antiplatelet auto-
antibodies. Antibody-coated platelets are destroyed
Hemolytic ThrombocytOpenia in the reticuloendothelial system, especially the
Thrombocytopenia secondary to microangiopathic spleen.ITP may be primary (occurring in isolation)
hemolytic anemia (MAHA) results in decreased or secondary, as a feature of an underlying disease,
platelet survival via entrapment in the small such as infection or an autoimmune disordet.
vessels (as with the RBCs) and removal from the
circulation. Microangiopathic disorders include Clinical ManifestBiion!J
the following: ITP is usually a clinical diagnosis based upon a typ~
ical history, physical, and blood count: the abrupt
• HUS onset of bruising and isolated thrombocytopenia
• TTP (with large platelets but an otherwise normal blood
• DIC count) without any other explanation in an otherwise
HUS, characterized by a MAHA, renal cortical healthy child with no organomegaly or adenopathy.
injury, and thrombocytopenia, is a major cause of Children typically present 1 to 4 weeks after a febrile
acute renal failure in children. Verotoxin-producing or viral illness with the abrupt onset of petechiae
gram-negative organisms (such as Eschuichla coil and bruising (Fig. 12-16).
0157:H7) that bind to endothelial cells cause HUS. Sometimes, there is no clear antecedent illness.
Because of endothelial injury, there is localized Some children will also have overt bleeding from
clotting and platelet activation. MAHA results from the mucous membranes, such as epistaxis and oral
mechanical injury to red cells as they pass through bleeding. Severe bleeding, including internal and
the injured vascular bed with fibrin deposition across intracranial hemorrhage, is rare in children with ITP
the lumen, and thrombocytopenia results from and can occur spontaneously or after trauma. There
platelet adhesion to the damaged endothelium with should be no history offatigue, bone pains, weight
subsequent activation and removal. An estimated loss, or unexplained fevers. Physical examination
60% to SO% of patients with HUS transiently require shows evidence, if any, of mucocutaneous bleeding
dialysis. Most children survive the acute phase and (bruising and petechiae), but no splenomegaly.
recover normal renal function. hepatomeply, or lymphadenopathy.
months (chronic ITP). The progression to chronic

ITP does not necessarily mean that a child will
have lifelong ITP.
The therapeutic plan should be carefully indi-
vidualized, with primary attention to the presence
of overt bleeding, rather than an arbitrary platelet
count. Severe bleeding, although rare, may occur
despite treatment, so treatment does not necessarily
prevent severe bleeding. There are two main ther-
apeutic options:
1. Watchful waiting with education and reassurance
awaiting spontaneous resolution or
2. Pharmacotherapy to temporarily increase the
platelet count.
FIGURE 12-16. Petechiae present on 1he legs of an
individual with idiopathic thrombocytopenic purpura. Pharmacotherapy is best reserved for children with
(This Image was originally published in UpToDate. Post troublesome, recurrent, or serious overt bleeding: chil-
TW. Immune thrombocytopenia (ITP). UpToDate Image dren engaging in risky physical activities; or excessive
Bank. 2018; 76871. C UpToDate. Image appears with parental anxiety despite education and reassurance.
P..~~-~!.~..~.~-.'1.:~~~-~L..... . . . . . . . . ... . . ..... ..... . . . . . . . . . . . . .... . . . . Children with oral hemorrhagic bullae ('"wetpurpmaj
as well as adolescents and young adults may tend to
Associated I.JJIJDrtltDry Values bleed more than other children, so pharmacotherapy
For most cases, the diagnosis of ITP does not require may be indicated in these scenarios.
a bone marrow examination, extensive laboratory The three most common first-line agents for
testing, or the detection of antiplatelet antibodies ITP are corticosteroids, IVIG, and less commonly,
(which is a poor test for this purpose). Howevei; if anti-D immunoglobulin. All three temporarily in-
labs are done, the following can be seen: crease the platelet count, lasting for 1 to 3 weeks,
• Thrombocytopenia and oth.erwbe normal blood so recurrent treatments may be needed. Children
counts with chronic ITP and troublesome bleeding may
• Increased mean platelet volume, indicating large require other interventions, such as splenectomy or
platelets inununosuppressive agents (e.g., rituximab). Newer
• Peripheral smear will show thrombocytopenia thrombopoietin mimetics,like Romiplostim and
with the presence of characteristic large, young Eltrombopag, are being studied in children and can
platelets (when the platelet count is less than be used an alternative second- or third-line therapy.
about 20,000/mm3 ) Just as important as any pharmacotherapy is ed-
ucation of the patient and famlly about medications
Ifthere are atypical findings on the history, phys-- and activities to avoid.
ical examination, the CBC, or the peripheral blood
smear, then bone marrow examination is indicated • Antlplatelet medications, such as aspirin, should
to exclude leukemia and aplastic anemia. If neces- be avoided completely.
sary to perform, a bone marrow examination will • NSAIDs, like ibuprofen. have only weak antiplatelet
classically show megakaryocytic hyperplasia but effects in vivo, but are probably best to avoid as
normal myeloid and erythroid elements. well. Acetaminophen is safe to use in ITP.
• Children should not engage in contact sports
Treatment
or engage in excessive rough-housing. Prudent
Childhood ITP is typically a benign, self-limited
protective measures should also be taken, like
disease that does not cause severe bleeding. and
wearing a helmet when riding a bike, not .sleeping
resolves spontaneously within 6 months. Treatments
on the top bunk of a bunk bed, or avoidance of
to raise the platelet counts are only temporizing
climbing to high places with the potential to fall
measures that do not affect the time to sponta-
(monkey bars, tree houses).
neous remission or cure the underlying disease. A
minority of children will have thrombocytopenia Families should be educated about the signs and
that lasts longer than 6 (persistent ITP) or 12 symptoms ofsevere, especially internal, bleeding that
require immediate medical attention, such as severe treatment), and the severity ofeach disorder is deter 4
headache, wmiting, lethargy, or loss ofcollJicioumess. mined by the degree offactor deficiency. Hemophilia
is characterized by spontaneous or traumatic hemor-
Canganltal Dlsanlars af Plll'btlats
rhages, which can be subcutaneous, intramuscuhu; or
Congenital platelet disorders can lead to impair-
within joints (Uke hemarthrosis seen in Fig. 12-17).
ment of platelets quantitatively and qualitatively.
Ufe-threatening internal hemorrhage may follow
Similar to ITP, they can present with mucocutane-
trauma or surgery. Musculoskeletal bleeding is often
ous bleeding, easy bruising, palpable ecchymosis,
what distinguishes hemophilia from the mucocuta-
purpura, excessive bleeding foUowing surgical or
neous bleeding seen with von Willebrand disease
dental procedures, or bleeding .from trauma One
and in platelet disorders.
such disorder is Bernard-Soulier syndrome. It is an
autosomal recessive platelet function disorder that • In mild hemophilia (5% to 49% of normal factor
impairs platelet adhesion to von Willebrand factor levels), children typically require significant
(vWF). Laboratory assessment will typically show trawna to induce bleeding, and spontaneous
thrombocytopenia, prolonged platelet function h.em.oiThage does not occur. Mild hemophilia may
analp.er (PFA) closure times, and large platelets on go undiagnosed for many years and is sometimes
blood smear. Platelet secretion deficits or low platelet diagnosed in the setting of unexplained postop-
stores can result in storage pool deficiencies or Grey erative bleeding.
Platelet Syndrome. Glanzmann thrombasthenia is an • With moderate hemophilia (196 to 596 of normal
autosomal recessive qualitative platelet caused by an factor levels), individuals require moderate trauma
abnormal platelet glycoprotein receptor. Myelofibrosis to induce bleeding episodes but may also have
and splenomegaly may be seen in these conditions. infrequent (approximately yearly) spontaneous
Additional laboratory tests such as platelet flow hemorrhage.
cytometryor platelet aggregations studies can aid in • In severe hemophilia (<1% of normal factor lev-
the diagnosis of these conditions. Depending on the els), children may have frequent, spontaneous
severity of the condition. treatment can vary from bleeding (approximately monthly) and bleed with
observation to platelet or factor infusions. very minor trauma. Severe hemophilia manifests
during infancy.
INHERITED BLEEDING DISORDER
Coagulation disorders can be inherited or acquired.
The most common inherited defects are hemophilia
A and 8 and von Wdlebrand disease.
Hemaphllla A and B
Hemophilia A is an X-linked recessive disorder
caused by deficiency of factor VIll and occurs in 1
in 5,000 males. The lack offactor vm causes a delay
in the production of thrombin, which catalyzes the
formation ofthe primary fibrin clot by the conversion
of fibrinogen to fibrin, which is then stabilized by
the action of factor xm.
Hemophilia B is an X-linked bleeding disorder
resulting from a quantitative deficiency offactor IX.
It occurs in 1 in every 30,000 males. The decrease in
the available factor IX again impacts the production
of thrombin and causes an inability to form a stable
clot. All other clotting factors are coded on autoso-
mal chromosomes and are, therefore, inherited in FI&URE 12-n. Hemarthrosis in a child with hemophilia.
an autosomal fashion. {This image was originally published in U.S. National
Ubrary of Medicine Openi Image Bank.. Lobet S.
Clinicsl ManifestBtions Hermans C, Lambert C. Optimal management of
Hemophilia A and Bare indistinguishable clinicaUy hemophilic arthropathy and hematomas. 2014;
(excluding definitive laboratory testing and specific . . __
t1-ibm-~~Q!.:..~.Y..:.~..:...."':!.~!~~ ~~~.!1'-~.~~~-~~~~-~:L
In newborns with hemophilia, there may be depending on timing of treatment initiation, choice
intracranial bleeding from traumatic delivery or of factor or factor stimulator, and the frequency of
prolonged bleeding after circumcision; otherwise, treatments.
bleec:ling complications are uncommon in the first The mainstay of hemophilia treatment is factor
year oflife. Circwncl&lon should be deferred in boys replacement (intravenous infusion of the spedfic
with a family history of hemophilia until hematology deficient factor). Factor therapy may be given
workup is complete. •on-demand.'" given when bleeding occurs, or u
part ofan ongoing prophylactic regimen to prevent
AssociBtfld LBI1orattHy VIJIUIIS
bleeding or both. An important long-term goal of
In order to make an accurate diagnom, the laboratory therapy is to prevent crippling joint damage caused
evaluation must be interpreted in a clinical context. by recurrent hemart:hrosis (hemophilic arthropathy).
• aPTT (activated partial thromboplastin time) Recombinant factors VIn and IX are now the treatment
will be prolonged and prothrombin time (PT) is offirst choice. Recombinant factors with prolonged
normal in both forms of hemophilia. half-life are currently being studied in children and
• In hemophilia A, factor VIII coagulant activity will eventually decrease the frequency oftreatment.
is low.
• For mild-to-moderate bleeding episodes, such
• In hemophilia 8, factor IX coagulant activity Is low. as hemarthrosis, a single infusion to increase the
• Genetic testing for hemophilia can identify the factor level to at least 40% is appropriate.
pathogenic mutation in the gene encoding factor
• Sometimes repeat doses are given, with the fre-
VIll or factor IX. quency depending on the half-life of the factor
It is important to distinguish hemophilia A and B (VIll: 8 to 12 hours, IX: 18 to 24 hours).
from other types of bleeding conditions on the basis • For life-threatening bleeding, maintaining the
of clinical assessment of their bleeding and via the factor level at 804Jfi to l()()IJ(, is necessary.
appropriate laboratory tests. Table 12-7 compares
Demwpreuin uetate (DDAVP) is a synthetic
hemophilla A, hemophilla B, and von Willebrand
vasopressin analogue that releases factor VIII from
disease.
endothelial cells. When administered, it may triple
lhJatmflllt or quadruple the initial factor VIII level ofa patient
The treatment and management of children with with mild or moderate hemophilla A but has no effect
hemophilia should be directed toward both treatment on factor IX levels. If adequate hemostatic levels of
and prevention of bleeds via factor replacement. factor VIII can be achieved with DDAVP, it can be
Based on a patient's presentation, therapies can vary the initial treatment ofbleeding for mild-to-moderate
YULE 12-7, COmparison of the Classical Features of Hemophilia A, Hemophilia B, and von Willebrand Disease
!.; C..ac:llliilllllu •'nlll 11--IIII.A ,_ Wllllnnll D l -
i Inheritance X-11nk.ed. Autosomal dominant or recelllive !
i Factor deficiency Factor VIII Factor IX von Wlllebrand factor (± 2 VIII def.) I
i meecUns al.te(s) Muscle, joint, surgical. Muscle, joint, surglcal Mucous membranes, skiD. surgicaL ~
: ~~a) :
I PT Normal Normal Normal

l aPTT Prolongoed Prolonged Prolonged or normal
I Factor vm Low Normal Low or normal
i Factor IX Normal Low Normal
I vWF antigen Normal Normal Low"
l vWF adivity Normal Normal !.ow-
lPlatelet function Normal Normal Low
i •Dtffer8nt foons of von Wlllebrand dl99988 may dacrae.se the antigen alone, actMty alone, or both.
!..~.~.~-~-~-~-:..~..P.~.~~!.~.~-~~-~:..~~-~-~--~~~-~~-~!~~!.~.~i-~-~:..~..~--~~~~-~~..~-~:........................................................................................
hemophilia A. BecaU.Ile DDAVP is an antidiuretic • Easy bruising

hormone analogue, hemophiliacs who frequently • Epistaxis
use DDAVP should be monitored for hyponatremia • Gingival bleeding
caused by water retention. • Menorrhagia
Mild acute bleedingepisodes can be treated in the • Other m.ucocutaneOU.Il bleed.Jng
home once the patient has attained the approprlate
In severe von Willebrand disease, there may be a
age and the parents have learned how to administer
marked. secondary .factor vm deficiency (because
recombinant factor VDl or IX or DDAVP. Bleeding
there is minimal or no vWF to carry and protect factor
associated with surgery, trauma, or dental extraction
VITI from clearance), and the patient will also have
can be anticipated, and excessive bleeding can be
manifestations similar to hemophilia (hemarthrosis,
prevented with appropriate replacement therapy.
hematomas). Approximately 85% of patients with
Aminocaproic acid (Amicar), an inhibitor of fibri-
von Willebrand disease have classic type 1 disease,
nolysis, may help treat oral bleeding after a dental
which results in mild-to-moderate deficiency ofvWF.
procedure. It is generally given before and after the
Many individuals with mild reductions in vWF levels
procedure.
have no bleeding at all.
The In08t significant complication of therapy today
is the formation ofinhibitors, which are neutralizing Assoc/atsd l.abonltlJry VaiUtiS
IgG antibodies directed against factor VITI or IX. Laboratory testing includes measurement of the vWF
These inhibitors prevent infused factor replacement antigen (vWF:Ag), which is the amount of protein
from working. Clinically signiticant inhibitors occur whether functional or not, and the vWF activity,
in 10% of patients with factor VITI deficiency and 1% which is measured functionally by the ristocetin
with factor IX deficiency. The treatment ofbleeding cofactor assay (vWF:RCoF). Analysis of vWF mul-
patients with an inhibitor is difficult. timer pattern is required for a specific diagnosis.
• For low-titer inhibitors, options include contin- Other t:e5ts may be abnormal.
uous factor vm infusions or administration of • Bleeding time may be prolonged.
porclne factor VIII. • Partial thromboplastin time (PTT) may be pro-
• For high-titer inluoitors, it is usually necessary to longed ifthere is a sufficient, secondarydeficiency
administer a product that bypasses the inhibitor, of factor VIIL
such as recombinant factor VIla or an activated • PFA-100 measures the time taken for blood, drawn
prothrombin complex concentrate. through a fine capillary, to block a membrane
Frequent U.lle of high doaes of prothrombin com- coated with collagen and epinephrine or collagen
plex concentrates, and especially of the activated and adenosine diphosphate. This is referred to
products, increases the risk of thrombosis, which has as the closure time and is measured in seconds
resulted in fatal myocardial infarction and stroke In and is abnormally prolonged in von Willebrand
adults. Induction ofimmune tolerance with continual disease. Anemia, thrombocytopenia, antiplatelet
antigen (factor) exposure can eradicate inluoitors. medications, and improper specimen collection
and!or handling (e.g., "tubing" the sample to the
von Wlllebrand Disease lab) will also falsely prolong the closure time.
von Willebrand disease is caused by deficiency of Therefore, a prolonged PFA-100 is not specific
vWF, an adhesive protein that connects suben- for von Willebrand disease.
dothelial collagen to activated platelets. vWF also • Genetic sequencing of the von Willebrand gene
binds circulating factor VIIL protecting it from may identify pathogenic mutations but is not
rapid clearance from the circulation. von Willebrand necessary for diagnosis.
disease is classified on the basis of whether vWF
is quantitatively reduced but not absent (type 1), Table 12-7 compares the findinp In classic von
qualitatively abnormal (type 2), or absent (type 3). Wdlebrand disease with those in hemophilia A and B.
Clinical Manifeststions 1l'Batmsnt

vWF is necessary to anchor platelets to the injured Intervention involves treatment of active bleeding
vessel wall, so the clinical manifestations of von (e.g., epistaxis) and prmmtion ofbleeding in high-risk
Wlllebrand disease are similar to those of throm- situations (e.g., preoperatively and/or during sur-
bocytopenia, including the following: gery). DDAVP, which stimulates the release ofvWF
from endothelial cdls, is the treabnent ofchoice for Assoclatsd l..abonltoty 'Values
bleeding episodes in most patients with type 1 von The diagnosis of DIC is a clinical one bolstered by
Willebran.d disease. Patients with type 3 disease (who laboratory evidence:
have no vWF to release), or with severe bleeding not
• Thrombocytopenia
responding to DDAVP, can be treated with a virally • Prolonged PT and PTT
attenuated vWF·containlng concentrate (Humate P). • Elevated fibrin split products and D-dimer
Cryoprecipitate should not be used, because it is
• Low fibrinogen and factor V and VIII
not virally attenuated. Hepatitis B vaccine should be
• Peripheral blood smear reveals schistocytes,
given before exposure to plasma-derived products. in.dicaq mlcroangiopathic disease
As in all bleeding disorders, medications that alter
platelet function. such as aspirin. should be avoided. Tl8atmllllt
The treatment ofDIC Is supportive. The disorder that
ACQUIRED BLEEDING DISORDERS caused DIC must be treated, and hypoxia, acidosis,
Acquired bleeding disorders usually result from and perfusion abnormalities need to be corrected.
underlying disease processes. Liver disease result- If bleeding persists, the child should be treated
ing in impaired synthetic production, chronic renal with platelets and fresh~frozen plasma (FFP), which
disease causing abnormal platelet function, intesti- replaces depleted clotting factors. Heparin may be
nal malabsorption and chronic antibiotic therapy useful in the presence ofslgniftcant arterial or venous
resulting in vitamin K deficiency, and consumptive thrombotic disease unless sites of life·threatening
coagulopathies causing DIC can all result in a lack bleeding coexist.
of hemostasis. It is important to consider these po-
VItamin K O&nclency
tential complications when treating the underlying
Coagulation factors (factors II, VII, IX, and X) and
disease of a patient.
antithrombotic factors (protein C and proteinS) are
DlSBIIIIIInatad Intravascular Coagulation synthesized in the liver and depend on vitamin K for
DIC is a consumptive coagulopathythat results when their activity. The factors must undergo a.-carboxy
intravascular activation ofcoagulation (mediated by glutamation to become active, whJch is catalyzed by
increased thrombin generation) leads to unregulated a vitamin K-dependent enzyme. When vitamin K is
thrombosis and secondary fibrinolysis or inhibited deficient, coagulation is impaired. Vtta:min K defi-
fibrinolysis (mediated by plasmin). Endothelial in- ciency often OCCUI'S because of the following factors:
jury, release of thromboplastic procoasulant factors
• Malabsorption, especially with cystic fibrosis, and
into the circulatf.on, and impairment of clearance of
with antibiotic-induced suppression ofintestinal
activated clotting factors directly activate and amplify
bacteria that produce vitamin K
the coagulation cascade. Intravascular activation of
• Overdose ofwarfarin, a drug that interferes with
the coagulation cascade leads to fibrin deposition
vitamin K metabollam., causes severe defid.ency
in the small blood vessels, tissue ischemia, release
of vitamin K-dependent :&.ctors
of tissue thromboplastin, consumption of clotting
• Maternal use ofwarfarin or anticonvulsant ther·
factors, and activation of the fibrinolytic system.
apy (phenobarbital, phenytoin) may also result in
Coagulation elements, especially platelets, fibrinogen,
vitamin K deficiency in the newborn.
and clotting factors II, V, and VIII, are consumed, as
are the anticoagulant proteins, especially antithrom- The most common disorder resulting from vitamin
bin, protein C, and plasminogen. Platelets are also K deficiency is hemorrhagic disease of the newborn,
activated and removed from circulation. Acute and which occurs in neonates who do not receive intra~
chronic conditioDJ associated with DIC include sepsis, muscular vitamin K at birth. This is becomins an
bums, trauma, asphyxia. malignancy, and cirrhosis. increasing concern because of parental refusal of
vitamin K administration triggered by personal beliefs.
Clinical Man/f8Stat1Dn
The bleeding diathesis may be di1ruse, with bleed- Cllnk:sl MBnlfBstatlons
ing from venipuncture sites and around indwelling Although most newborn infants are born with
catheters. GI and pulmonary bleeding can be severe, reduced levels ofvitamin K-dependent factors, only
and hematuria is common. Thrombotic lesions can a few develop hemorrhagic complications. Because
affect the exttemities, sldn, kidneys, and brain. Both breast milk is a poor source of vitamin K, breastfed
ischemic and hemorrhagic strokes can occur. infants who do not receive prophylactic vitamin
K on the .first day of life are at the highest risk for a mixture ofcoagulation factors II, VII, IX, and X, is
hemorrhagic dbease of the newborn. Peak incidence indicated fur severe bleeding along with vitamin K.
is at 2 to 10 days oflife. The disorder is marked by
DVTand PE
• Generalized ecchymoses
Venous thrombosis is rare in childhood. but the
• GI hemorrhage
incidence is rapidly rising with advances in supportive
• Bleeding from the circumcision site and umbil-
and intensive care (especially the use ofindwelling
ical stump
venous catheters), epidemic obesity, and the increasing
Affected neonates are also at risk for intracranial use of oral contraceptives.
hemorrhage.
• The estimated risk for thrombosis in children
Associated Labor8tDry Values in the general population is 0.07 per 10,000 and
Becausefactorsofthe extrinsic (VII), intrinsic (IX), about 5.3 per 10,000 in hospitalized children.
and common pathways (II, X) are affected, the fol- • The rate ofvenous thrombosis in children is only
lowing laboratory results can occur: one-tenth of that in adults.
• Thrombosis in infants and teenagers accounts
• Prolonged PT (most sensitive to vitamin K
for 7096 of the cases seen in children.
deficiency)
• Prolonged PTT (may occur to some degree in Venous thrombosis develops under conditions of
healthy newborns) slow blood tlow, an injured vascular endothelium,
• Decreased factor VII level and a hypercoagulable state. In older children,
unilateral acute limb swelling, with pain and dis-
The coagulopathy seen with hemorrhagic disease
coloration, and distended superficial veins should
may be confused with liver disease or DIC, both of
make one suspect a deep vein thrombosis. In other
which have a prolonged PT and decreased factor VII
cases, unilateral acute limb swelling is the only sign
level. Table 12-8 di1l'erentiates vitamin K defici.ency,
and one must have a high index of suspicion in
liver disease, and DIC by laboratory data.
patients with risk factors. Childhood thrombosis
Treatmllllt is umally multifactorial and is precipitated by the
The recommended preventive dose ofvitamin K for concurrence of multiple risk factors. The various
newborns is 1 mg given intramuscularly within a few risk factors for childhood venous thromboembolism
hours ofbirth. Thill is routine standard ofcare in the are listed in Table 12-9.
nursery. Nutritional disorders and malabsorptive A potentially life-threatening complication of
states respond to parenteral administration ofvitamin venous thrombosis is pulmonary embolism, which
.K. PO vitamin K may be used ifabsorption is intact, occurs when a thrombus or other substance (i.e., fat,
although IV vitamin K has quicker onset of action. air, bone marrow) enters and obstructs the puhnonary
FFP or prothrombin complex concentrate, which is arterial circulation. Pulmonary embolism may lead
to significant ventilation-perfusion mismatch and
TABLE 12-1. Differentiation ofV11amin KDeficiency,

Liver Disease, and DIC TIILI1 M. common Risk Factors for Venous
Thromboembolism in Children
iLIIIarlfllrJ'IIIt u. ...... DIC !• Indwelling venoWI catheters
! Prothrombin t t j • Estrogen-containing oral contraceptives
Itime t • Congenital heart diaeue
~ • Surgery, trauma. immobility, paresis
iPlatelets nl nltoJ. J. i • InheritEd thrombophiliu
IFibrinogen nl nltoJ. J. ~ • Antiphospholipid antibodies
IFactor VI1I nl nlto1' J. j•
~
Obesity
Uftl;~ftncy
IFactorVII J. J. nltoJ.. ~ •
• .l'f'U"U&U4U.I.
Cancer therapy (asparaginase)

l FactorY nl J.. J. ~ • Inflammatory bowel disease
j Abbnwiations: nl, normal; t , in018888d; J., dacraased; DIC, i • Nephrotic syndrome
!;..........................................................................................................................................
dill!18minated intTavalcular coagulation.
; !..~------~~~. . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .:
respiratory distress. The lung parenchyma affected • It is more important to base the need for transfu-
by the emboliam can undergo necrosis leading to sion on an assessment of the patient rather than an
pulmonary infarction. arbitrary Hb concentration. Chronicity ofanemia,
A long-term complication of venous thrombosis active bleeding, underlyins cardiopulmonary disease.
is the postthrombotlc syndrome, characterized by and other incllvidual factors induenc:e the decision
chronic swelling. paln, skin changes, and promi- to transfuse independentof the Hb concentration.
nent veins. • One unit of pRBC from a routine blood donation
An1icoapla1ion with various forms of hep- varies between 250 and 350 mL, so it is import-
arin (unfractionated or standard heparin, low- ant to calculate and consider ordering a specific
molecular-weight heparin) or with vitamin K volume of pRBC (rather than a specific number
antagonists such as warfarin are used as standard of unit of pRBC), especially for younger children.
therapy for the treatment ofvenous thrombosis and • The adminiJtration of10 to 15mLikg ofpRBC usually
pulmonary embolism. In specific cases, thrombolytic raises the Hb level by 2 to 3 gldL. This wlwne can
therapy with tissue plasminogen activator may be .safely be administered aver 3 to 4 hours except in
indicated to dissolve the thrombus; rarely, surgical severely anemic patients (Hb< 5 gldL) or those at
embolectomy is performed. Newer oral therapies risk for transfusion~associated circulatoryoverload
such as Rlvarox.aban, a factor Xa inhibitor, are not (TACO), where the rate of transfusion should be
yet approved for use in children less than 18 years much alower (1 mL pRBC/lcg/hour is safe).
of age, but studies are ongoing
Platfllst transfusions
• Indicated to prevent or stop bleeding in patients
TRANSRJSIONS AND BLOOD with thrombocytopenia or platelet function
PRODUCTS disorders.
Blood products should be transfused only when • Like pRBC transfusions, there is no "universal"
strict clinical and laboratory criteria are met. In all transfusion trigger for platelet transfusions, as
patients, and particularly in children, efforts should be bleeding risk and response to transfusion depends
made to avoid unnecessary blood product exposUI'el. on the patient and the disease.
Acute or chronic blood loss, and iatrogenic blood • Platelet transfusions are usually not indicated
loss in chronically hospitalized patients is a common in patients with ITP, Irrespective of the platelet
cause for appropriate transfusions. In both oncology count, except with life-threatening hemorrhage
patients with chronic transfusion-dependence and when given concomitantly with (after) other
in premature infants, anemia necessitating blood treatments like steroids and IVIG.
products can be more predictable and can be based FrBsh-FIDztln Plasma
on specific transfusion protocols.
The types of blood produc:U available and how • Indicated for replacement ofmissing coagulation
they are prepared have specific clinical indications factors (when the specific factor concentrate is
as well as rls.ks/bene:fits. For this reason, blood unavailable) or for plasma exchange.
products should be transfused only when strict
Cryoprsc/pltatfl
clinical and laboratory criteria are met. pRBC and
platelets are the most commonly transfused blood • A rich source ofcoagulation factors VIII and XIIL
products. Transfu&lon ofIJl'aDulocytes, whole blood, fibrinogen, and vWF, and is commonly used for
FFP, and cryoprecipitate may be warranted in special replacement offibrinogen in severely ill patients.
circumstances. • Cryoprecipitate should not be taed for hemophilia,
von Wdlebrand disease, or other blood disorders
pRBC TtBnsfusJons where safe, pathogen~free or pathogen-inactivated
• pRBC transfusion is indicated for symptomatic products are available.
or severe anemia.
Gnmulocyte Infusions
• pRBC transfusions increase the oxygen-carrying
capacity in anemic patients and help ensure ade- • These are rarely used and have been mainly utilized
quate tissue oxygenation. for patients with prolonged. severe neutropenia
• Transfusions can also be used to decrease the and life-threatening sepsis unresponsive to other
proportion of abnormal Hbs,like Hb S. therapies.
Whole 8/ood 'Thlnsluslons United States. A very small number of cases of

new variant Creutzfeldt-Jakob disease have been
• These are rarely used. except during exchange
transmitted by blood transfusion.
transfusions in neonates and in autologous blood
• Thnufusion-assoclated act& lung Injury (TRALI)
transfusions.
can be a serious, life-threatening complication
of transfusion characterized by noncardiogenic
TRANSFUSION RISKS pulmonary edema. The pulmonaryinjury results
Blood product tranafuaioru are usociated with sig- from the interaction ofneutrophlls and transfused
nificant risks and complications, although current antibodies (anti-HLA and antihuman neutrophJl
monitoring and testing procedures have reduced the antigens), their deposition in, and damage to, the
1ncidence ofmany. These risks must always be consid- pulmonary vascular bed
ered when making a decision to transfuse a patient. • TACO can result in pulmonary edema when the
The benefits of transfusion should outweigh these blood product is transfused at a rare greater than
risks. In the setting of an acute transfusion reaction, the cardiopulmonary system can handle. TACO
the transfusion should be stopped immediately, and may occur, for example, when a severely but
the reaction symptoms treated alons with evaluation chronically anemic individual (who has a normal
of the given product. The most common transfusion or high total blood volume in compensation) is
reactions are summarized in the following paragraphs. given a "normal" transfusion volume (e.g., 11 to
15 mL!kg over 3 to 4 hours).
Acute Transfu&lun Reactions
Matabollc Disturbances
• Febrile reactions are common. This results
from leukocytes present in pRBC and platelet • Hypothumia can occur ifproducts are not warmed
transfusions. They can be preventl!d by the use during large or exchange transfusions. This is
ofleukocyte filters or leukocyte-depleted blood particularly true in small children and infants.
products. Ifthey occur, the transfusion should be • Citrate toxicity results when patients are unable
paused. a blood bank transfusion workup should to toleratl! the amount of citrate used in blood
be started, and antipyretics administered. products for anticoagulation. Children with
• Allergic reactions are caused by protein antigens liver failure o r dysfunction cannot metabolize
1n the transfused product and occur in 1% to 2% citrate, putting them at risk for hypocalcemia and
of pRBC. Pruritus, rash, and urticaria, typically hypomagnesemia. This can then lead to cardiac
begin minutes after the infusion is started. Some- depression or wagulopathies.
times, severe allergic or anaphylactic reactions • Potassium tr»dcity can occur because stored RBCs
occur. The transfusion should be stopped, and leak potassium, which is increased with irradiation.
antihistamines should be administered. Cortico- The longer a blood product has been stored, the
steroids may be needed IgA-deficient individuals higher the risk of hyperkalemia. This is avoided
who have had anaphylactic reactions to blood by using a fresh product.
products require IgA-reduced products (e.g.,
Delayed or Lang-tann COmplications of
washed RBCa, IgA-deficient plasma).
TransfUsions
• Acute hemolytic tmn.sfusion reactiom are most
commonly caused by clerical errors resulting in • Iron overload (transfusional hemochromatosis)
the administration of the wrong (incompatible) occurs in chronically transfused patients be-
Wlit to the wrong patient. These reactions are cause the body has no mechanism to increase
characterized by a sudden onset of fever, chills, the elimination of iron. Iron chelation therapy
tachycardia, tachypnea, and vomiting with severe may be needed, depending on the iron burden.
hemolym that may result in multiorgan failure, to prevent organ injury and death.
shock, and DIC. • Alloimmunization can occur in multiply trans-
• Infections, sped.ftcally bacterial, can a1so be fused individuals who develop antibodies against
transmitted by transfusion, especially of platelet alloantigens on RBCs, WBCs, or platelets. Allo-
products, which are stored at room temperature. immunization may hinder the ability to find an
Transfusion-t:ranJmitted parasitic disease (malaria. appropriate blood product for a patient.
babesiosis) should be considered in the appropriate • Delayed he11Wlytic transfusion reactions can
clinical circumstances but are uncommon in the result in red cell alloantibodies that cause delayed.
posttransfusion hemolysis (3 to 14 days after of donors and testing of products. The current
traJUlfusion). estimated rUk of transmission ofHIV infection
• Treursfiuion-aasociat«:l grtfft-versw-host disease is about 1 in 2 million. that of hepatitis C virus
(TA-GVHD) occurs when immunocompetent is 1 in 2 million. and that of hepatitis B virus is
lymphocytes (which are normal passengers in 1 in 200,000. Other viruses, like cytomegalovi-
pRBC and platelet products, even fo11owing leu- rus (CMV) and EBV, can also be transmitted.
kofiltration) engraft in a recipient whose immune Transmission of Zi.ka virus through platelet
system cannot reject them. This is a very rare but transfusiollll has been reported abroad but not
fatal complication. IrracUation of blood products in the United States. Zika testing is standard for
can prevent this complication, and it is indk:ated most U.S. blood banks. VJ.ral infections must be
forimmunocompromlsed individuals and neonates. confirmed with seroconversion or isolation of
• Infections, namely &erious viral infections, are now a specific genomic variety that can be traced
extremely rare because of the intensive screening back to a donor.
KEY POINTS
• Anemia has three main causes: decreased red and othervuo-occluslve events, increased risk
cell production, Increased red cell destruction of bacterial infection, and chronic, progressive
(hemolysis), and blood loss or sequestration. organ damage.
• The mean corpuacularvoloole and the reticulocyte • G6PD deficiency Ia the most common RBC
count are the moat helpful WatfS to approach enzyme detect. It Ia X-Inked, and the severity
and classify the dlretential diagnosis of anemia. depends on the mutation.
• The most common hypochromic microcytic • Macrocytic anemias can be subclassified
anemias antiron-deficiency anemia, the thalas- on the basis of the presence or absence of
semia syndromes, and anerria of inflammation. megaloblastosls, a marker of ineffective DNA
• TEC is a normocytic anemia caused by bone synthesis within a RBC precursor. Not all
marrow suppression and occurs between 6 macrocytic anemias are megaloblastic, but all
months and 3 years of age. megaloblastic anemias are macrocytic.
• Normocytic anemias with increased red cell • Megaloblastic, macrocytic anemias reflect
production Oncreaaed reticulocytes) are most ineffective DNA synthesis and can result from
commonly caused by hemolysis. vitamin 8 12 or folate deficiency, drugs that in-
terfere with folate metabolism, and some rare
• Hemolytic anemias are caused by extrinsic
metabolic disorders.
factors and Intrinsic defects. In general, extrin-
sic factors are acquired, and intrinsic defects • Macrocytic anemias without megaloblastic
are hereditary. Extrinsic factors may be im- changes result from BMF and Include BMF
mune or nonlmmune. Intrinsic defects include syndromes (Diamond-Biackfan syndrome,
membrane defects, hemoglobinopathies, and Fanconi anemia, Idiopathic aplastic anemia,
enzymopathles. myelodysplasia), drug-Induced anemias, chronic
liver disease, and hypothyroidism.
• HS is caused by an intrinsic membrane defect
in the major supporting proteins of the ABC • Platelet disorders can be either quantitative or
membrane. qualitative. Platelets are an important compo-
nent of primary hemostasis, and either type of
• Sickle cell disease Is a group o1 related disorders defect can cause mucocutaneous bleeding.
resulting from an abnonnal P-globin chm in
the Hb molecule O.e., Hb S, ~~~Val), which, • Thrombocytopenia Is the most common cause
upon deoxygenation, allows the polymerization of abnormal bleedng In children. Thrombocy-
of Hb into insoluble rods that distort the RBC topenia caused by shortened platelet survival,
and damage lt. The clinical manifestations of which is much more common than thrombo-
SCD Include chronic hemolytic anemia, pain cytopenia caused by Inadequate production,
is caused by alloantibodies, autoantibodies, Life-threatening internal hemorrhage may follow

and microangiopathic states. trauma or surgery. Severity depends upon the
• ITP results mainly from autoimmune antibody level of factor In plasma.
formation against platelets. Childhood ITP is • von Willebrand disease is caused by a deficiency
typically a benign, self-limited disease that of vWF, an adhesive protein that connects sub-
infrequently causes severe bleeding and often endothelial collagen to activated platelets and
requires no pharmacotherapy at all. also binds to circulating factor VIII, protecting
• DIC results from severe illness, causing the it from rapid clearance. It is characterized by
activation of both coagulation (thrombin) and mucocutaneous bleeding, epistaxis, gingival
fibrinolysis (plasmin). bleeding, cutaneous bruising, and menorrhagia.
• Deficiencies of coagulation factors (disorders • The most common disorder resulting from
of secondary hemostasis) are characterized vitamin K deficiency is hemorrhagic disease of
by spontaneous or Induced Internal or external the newborn, which occurs in neonates who
bleeding, such as hemarthrosis and hematomas. do not receive vitamin K at birth.
In contrast, defects in primary hemostasis (e.g., • The transfusion of blood products should be
platelet disorders) cause mucocutaneous bleeding. based on patient-specific indications and not
• Hemophilia A results from a deficiency of factor on universal, arbitrary transfusion triggers for
VIII, and hemophilia B results from a lack of Hb concentration or platelet count.
factor IX. Both types of hemophilia are X-llnked • The many potential complications of transfusion
and characterized by spontaneous or traumatic of blood products along with the expected
hemorrhages, which can be subcutaneous, magnitude of the benefits should be carefully
intramuscular, or within joints (hemarthrosis). considered before transfusion.
CLINICAL VIGNETTES
VIGNETTE1 a. TEC
An 18-month-old child who was born at term is now b. Iron-deficiency anemia
brought to you, his pediatrician, by his mother because c. Lead intoxication
she is concerned that he has become increasingly initable d. Severe aplastic anemia
and tired over the past few weeks. He is drinking well, e. Leukemia
mainly milk, and his urine has been light yellow. You
notice that the child is markedly pale and that he has 3. What is the most likely cause of this patient's
no jaundice, adenopathy, or organomegaly. You obtain anemia?
a blood count in your office that shows the following: a. Early introduction of cow's milk
a. WBC 7,500/mm3 b. Consumption of goat's milk
b. Hgb 6.5 g/dl c. Occult Gl blood loss
c. MCV59 fl. d. Inadequate iron endowment at birth
d. RDW17.2% e. Hereditary malabsorption of iron
a. Platelets 525,000/mm3
4. You do not transfuse the child; rather you treat
f. Retlculocytes 1.6%
him with an oral preparation of ferrous sulfate,
1. What is the cause of the anemia? dosed at 6 mg elemental iron/kg/day. You have
a. Increased destruction (hemolysis) him return In 1 week for a blood count. Assuming
b. Decreased production the diagnosis is correct, you prescribed the right
c. Acute blood loss dose of Iron, the parents administered the Iron
d. Sequestration appropriately, and the child does not have mal-
2. Given that you now know the child has anemia absorption, which of the following blood counts
because of the above-mentioned reason, what is represents the expected response after 1 week
the most likely diagnosis? of iron therapy?
sickle cell trait on preconception testing. The father

Hp(glclL) MCV(tL) Reticaloc:ytu (96)
was tested for sickle cell trait preconception, and he
a. 6.5 59 1.6 did not have it.
••c:. 6.6
7.6
60
64
3
4.5
1. Assuming that the results of the sickle trait testing
were oorrect and that the father without sickle cell
trait is, indeed, the biological father, w hat type of
.
II. 11.3
11.5
70
75
2.5
1.5
hematologic abnonmality could the father have
that could explain the occurrence of SCD in his
child?
L G6PD deficiency
VIGNETTE2 b. a-Thalassemia trait
A 4-month-old baby boy, born at tenn without com- c. !}-Thalassemia trait
plications, Is referred to you for an abnonnal newborn d. Hereditary elliptocytosis
screening test for hemoglobinopathies. The Hb pattern t. Hgb G Philadelphia trait
reported from the first week of lite Is "F, N but the 2. By conflnmatory testing, you determine that the
newborn screening lab also reports a trace amount mother In question Indeed has only sickle call trait
of Hb Barts.
and the father has only !}"'-thalassemia trait. What
1. What is the significance of Hb Barts on newborn Is the probability for each of their subsequent
screening? pregnanciee that the child will have a form of SCD?
L The baby has a fonn of a-thalassemia. L <1%
b. The baby has a fonn of P-thalassemla. b. 25%
c. The baby has a fonn of ~thalassemia. c. 50%
d. The baby has a fonn of g.~-thalassemia. d. 75%
e. The baby has a form of HPFH (hereditary •. 100%
persistence of fetal Hb).
3. When this child turns 1 year of age, you
2. You choose to obtain an Hgb electrophoresis at obtain a CBC. Which of the following blood
4 months of age. The results show the~ counts would be most consistent with 8ickle-P"'-
of Hb A (8996) and Hb F (11 %), but no Hb Barts. thalassemia (SJi1?
What does the disappearance of Hb Barts indicate?
L Laboratory error
b. This baby had a transient, neonatal form of
H&b (&/elL) MCV(tL) Jleticaloc:yta (IJt,)
thalassemia. a. 7.5 78 15
c. The Hb F production has increased since birth. b. 7.4 64 18
d. An expected developmental phenomenon
e. 10.3 79 4
e. Nonpaternity
d. 10.1 62 3.5
a. Assume that this child is African American and e. 11.1 75 1.5
has no Asian ancestry. You determine that he has
a two-gene deletion a-thalassemia (a-thalassemia
trait). From which parent or parents did he almost VIGNETIE4
certainly inherit his a-gene deletions? You are caring for a young child undergoing inten-
L Two deleted genes from the mother sive chemotherapy for AML. She has expected
b. Two deleted genes from the father chemotherapy-related myelosuppression, her Hgb
c. One deletion each from the mother and the father concentration is 6.5 gldl. and she is symptomatic of
d. Two deletions each from the mother and the the anemia. You decided that she needs a transfusion
father of pRBC. You choose to inradiate the blood product
e. One deletion from etther parent and one new before transfusing it.
mutation
1. What complication of transfusion is prevented
VIGNETIE3 by irradiation?
A family presents to you with a newborn baby who L Alloimmunization
was recently identified by newborn screening to have b. Febrile transfusion reaction
a form of SCD. The parents are upset because they c.TRAU
were told by their obstetrician that they could not d. TA-GVHD
have a baby with SCD because only the mother had t. Viral transmission
2. You also choose to leukofiHer Oeuko-deplete or a. 7.0 g/dl

leuko-reduce) the blood to prevent alloimmuni- b. 8.5 g/dl
zatlon, transmission of CMV. and which of the c. 10.0 gldl
following complications of transfusion? d. 11.5 gldl
a. Acute hemolytic transfUsion reactions •• 13.0 gfdl
b. Febrile transfusion rMCtlons 4. Your patient begins to bleed from her nose and
c. Allergic ruactiona mouth. Her platelet count is 8,000/mnr, so you
d. Malaria decide to give her a lransfusion of platelets. Which
e. TACO of the following complications of transfusion is
much more common with platelets than pRBC?
3. You transfuse 10 ml.lkg of pRBC over 4 hours. The a. Transmission of bacteria
next day you obtain a CBC. Which posttransfusion b. TACO
Hgb concentration represents a typical response c. Transfusional hemochromatosis
to this volume of pRBC (assume no hemolysis or d. TA-GVHD
ongoing losses of blood)? e. Delayed hemolytic transfusion reaction
ANSWERS
VIGNmE 1 Q...Uan 1 VIGNETTE 1 Qul8tion 3

1.AnswerB: 3. Answer A:.
The normal range for the reticulocyte count is 0.5% to This history gives us a clue that the child is consum-
1.5%, but this nonnal range assumes a nonnal Hgb Ing too much milk, but fUrther specific questioning
concentration. Here, the rwtlcutocyte count Is far too low will be needed to detennlne when cow's milk was
for the degree ofanemia. So, the mechanism of anemia Introduced and the amount consumed (frequency and
is decreased production (Inadequate bone marrow re- volume). This is the most likely diagnosis, however,
sponse). Hemolysis, acute blood loss, and sequestration even though it is a preventable cause of anemia.
will cause a oompenB&tory reticulocytosis, which this Occult Gl blood 1088 is a possibility, but dietary iron
child does not have. A compensatory reticulocytosis deficiency would be more common. The child was
takes 12 to 24 hours to appear; so it may be lacking born at tenn, so he very likely had a normal endow-
(temporarily) when a patient presents immediately after ment of iron at birth (you should also ask about birth
the onset of hemolysis, blood loss, or sequestration. The weight to be complete). Hereditary malabsorption of
child in this case has been symptomatic for weeks, so iron is rare. Consumption of goat's milk Onstead of
this scenario is excluded. Hemolysis would also cause formula) classically leads to folate deficiency, with or
jaundice, dark urine, or both depending on the cause without iron deficiency, which would be macrocytic
(site) of hemolysis. This child has neither. He also does not {isolated folate deficiency) or normocytic (combined
have splenomegaly, so splenic sequestration Is excluded. Iron and folate deficiency), unlike the marked micro-
cytosis In 1hls case.
VIGNmE 1 Question 2
2.AnswerB: VIGNETTE 1 Question •
Iron-deficiency anemia is consistent with the history, •.AnswerC:
physical examination, all the measurements provided The reticulocyte response occurs first, 3 to 4 days
by the CBC (including the microcytosis, increased after starting appropriate iron therapy. The Hgb
ROW, and thrombocytosis), and the inadequate re- concentration then increases by about 1 gldl in a
ticulocyte response (inadequate iron to make new week's time. So the correct answer is C, showing
RBCs). TEC, severe aplastic anemia, and leukemia both a reticulocytosis and an increase in the Hb
cause normocytic or macrocytic anemias, not the concentration by about 1 gldl. Answer A shows no
marked microcytosis seen in this case. Isolated lead response, Inconsistent with the premises ofthe ques-
intoxication causes marked basophilic stippfmg but tion. Answer B shows only a reticulocytosis, although
not a marked microcytic anemia. The pica that some- the Hgb concentration should be higher after 1 week.
times accompanies iron-deficiency anemia may lead Answers D and E are consistent with several weeks
to secondary lead exposure, but the lead exposure of iron therapy (the Hgb concentration is too high for
does not causa the anemia. only 1 week of iron therapy).
VIGNETIE 2 Quesllan 1 sickle-p0-thalassemia (Hgb S~~- A negative test for the

1.AnswerA: presence of (Hgb S) does not exclude the presence of
Newborns make a predominance offetal Hgb (Hb F) and otherabnonnal hemoglobins or thalassemia trait. G6PD
a Ieeser amount of adult Hgb (Hb A), giving the normal deficiency and hereditary elliptocytosis, both common
•F. A" pattern on newborn screening (the predominant among African Americans, do not interact with sickle
Hb is always reported first. so that •f. A" means F >A). cell trait to produce a form of SCD. ~Thalassemia trait
Hgb F is composed of two rx and two 'Y chains (a.nz). and Hgb G Philadelphia trait are both abnormalities
When there is a relative deficiency ofa-chains because of the a-globin locus, but the colnherltance of Hgb S
of rx-thalassemia, then the relative excess of unpaired with certain other ~~globin abnormalities Is required to
..,-chains self-associate to fcnn Hgb Barts, a tetramer produce forms of sickle disease. Among the possible
of -,.chains fy~. The presence of Hgb Barts indicates answers, only ~-thalassemia trait is an abnormality of
the pl'888nce of a-thalassemia (the a-globin genes are the .fJ-globin. So, the child in question has a form of
linked toge1her on chromosome16). All the other choices aickhrP-thalassernia.
are abnormalities of the p-globln locus (the y-, &-, and
13-globln genes are all linked together on chromosome 11). VIGNETlE 3 QuMIIon 2
2.Answer B:
VIGNETIE 2 Quesllan 2 This is straightforward Mendelian inheritance. If one
2.Answer D: parent has S trait (AS) and the other has p+-thalassemia
Fetal Hgb production progressively decreases after trait (Ap'), then offspring have a 25% chance of having
birth and approaches the normal adult values of ap- nonmal hemoglobin (M), a 50% chance of having
proximately 1.596 to 2.596 by about 6 months of age trait (either AS or Ap+), and a 25% chance of having
in hematologically normal infants. Hb F production slckle-p+-thalassemia (Sp').
declines with age because y-chains synthesis declines.
Because y-chains synthesis declines with age, so will VIGNETIE 3 Question 3
the formation of Hgb Barts, a tetramer of y-chains (y.J. 3. AnswerD:
Therefore, the disappearance of Hb Barts as the baby Sickle-p+-thalassemia (SP1 typically produces a mild
ages is an expected developmental phenomenon. Trace hemolytic anemia (Hgb, 10 to 12 g/dL; reticulocytes, 296
amounts of Hb Barts can be detected by high~nsitiv to 5%) that is microcytic (MCV :s70 for a 1-year-old}.
lty techniques In older childran with one- or two-gene The anemia is too severe in choices A and B, and there
deletion ~thalassemia, but It Is not usually detected by is no microcytosis in choices A, C, and E.
Hgb electrophor&Sis outside of earty Infancy. y-lhalas-
semla, not a-thalassemia, Is a transient, neonatal form VIGNETlE 4 QuMIIon 1
of thalassemia. 1.Answer D:
Irradiation prevents only one complication: TA-GVHD.
VIGNETIE 2 Quaatlan 3 TA-GVHD occurs when immunocompetent lymphocytes
3.AnswerC: (which are normal passengers in pRBC and platelet
Two-gene deletion a-thal888emia (a-thalassemia trait) products, even following leukofiltration) engraft in a
can occur when two a-globin genes are deleted on the recipient whose Immune system cannot reJect them.
same chromosome, in cis(- - /a.ciJ, or when they are lhls Is a very rare but fatal complication. Irradiation
deleted on opposite chromosomes, in tnlns(a-/a-). of blood products can prevent this complication by
Among individuals of African ancestry, a-thalassemia damaging passenger leukocytes, so that they cannot
trait nearly always occurs in tnlns (rx-/a-), so this divide, and it is indicated for lmmunocompromised
child must have received one a-gene deletion from individuals and neonates.
the mother and the other from the father. In contrast,
individuals of Asian ancestry with m-thalassemia trait VIGNETIE 4 Question 2
may catTY both deletions in cis (- -/cui) or in ttans 2.Answer B:
(a- /a- ), so It Is possible to lnherHtwo deleted genes Febrile transfusion reactions are most commonly
from one parent In this scenario. caused by the recipient's immune response to pas-
senger leukocytes, and leukofittration is an effective
VIGNETIE 3 Quesllan 1 way to 111duce the f111quency of febrile transfusion
1. AnswerC: reactions. The other complications are not mediated
Even when only one parent has sickle cell trait, a couple by passenger leukocytes (and so are not reduced by
can still produce children with SCD. They cannot have leukoflltratlon). Hemolytic transfusion reactions are
a child with sickle cell anemia, which is homozygosity caused by host antibody formation against donor
for Hgb S, but they can have children with compound RBCs. Allergic reactions a111 mediated by transfused
heterozygous forms of SCD, such as sickle-hemoglobin plasma proteins. Malaria Is an intraerythrocyte parasite
C disease (Hgb SC), sickle-~..-thalassemia (Hgb sp+), or (and also cell free). TACO is mediated by the volume
2.88 • BLUEPRINTS Pediabics
of the transfused product, given faster than the body what product your blood bank uses to know how
can physiologically tolerate. much blood to give your patient.
VIGNETTE 4 Q...tlan 3 VIGNETlE 4 Questlan 4

3.Answer B: 4. Answer A:
A transfusion of 10 ml.lkg of pRBC will increase the Platelet products are stored at room temperature ~n
Hgb concentration by about 2 gldl, 80 only answer contrast, pRBC are refrigerated during storage), 80
B is correct. The posttransfusion increment depends bacterial contamination and growth is more common
on the volume of the transfusion and t he hematocrit with platelets. TACO can occur from any transfused
of the transfused product. The hematocrit of the product, as it is determined by volume. Transfusional
transfused product Is determined by the hemato- hemochromatosis is a complication of pRBC trans-
crit of the donor (male higher than female) and the fusion, specifically. TA-GVHD can occur with either
anticoagulant/preservative solution that is used. pRBC or platelet products (when the recipient is
Modern additive solutions produce a pRBC product immunocompromiaed and the product has not been
with an Hct of approximately 55%. Older, but still irradiated). Delayed hemolytic transfusion reactions
used, anticoagulant/preservatives such as CPDA-1 occur as a consequence of sensitization to transfused
(citrate-phosphate-dextrose-adenine) have a higher RBC antigens and the production of antibodies against
Hct (approximately 65%), so It Is Important to know the transfused RBC antigens.
Oncology
Aroop Kar, Rudy Allen, and Bradley S. Marino
.Every year, over 15,000 patients under the age of20 cancer survivors (and their caregivers) are aware of
years are diagnosed with cancer in the United States. their history of cancer and the therapies given to
Approximately two~thirds occur below the age of them, so that they are empowered to be advocates
15. The most common types of cancers in children for their own health as they grow older.
under the age of 15 are leukemias, followed by brain The following sections describe the more common
tumors. In the older adolescent group, lymphomas cancers in children and adolescents,
(mostly Hodgkin lymphoma), brain tumors, leu.k.emias,
and genn cell tumors predominate.
Common therapeutic modalities for treating child-
LEUKEMIA
hood cancer include IIRll'gery, radiation, chemotherapy, The leukemias account for the greatest percentage
hematopoietic stem cell transplantation, and biologic of cases of childhood malignancies (approximately
agents. The most commonly used chemotherapeutic 30~). There are approximately 5,000 new cases of
agents are listed in Table 13-1. leukemia diagnosed under the age of 20 every year
Although childhood cancer represents a small in the United States.
number of childhood diseases, it accounts for a
substantial number of deaths in children. It is the PATHOGENESIS
second most common cause of death below the age Leukemia resulu from malignant transformation
of 15, behind only accidents. In older adolescents, and clonal expansion of hematopoietic cells at
cancer is the fourth-leading cause of death, behind an early stage of differentiation, resulting in the
accidents, suicide, and homicide. Overall, tremen- uncontrolled prollferation of leukemic cells called
dous progress has been made, with cure rates now "'blasts:' Leukemias are classified on the basis ofcell
nearing 90%. Howewr, the adolescent and young morphology into lymphoblastic leukemias (derived
adult population has not seen this same increase from lymphoid lineage) and myeloid leukemias (de-
in survival rates. This has led to an emerging field rived from granulocyte, monocyte, erythrocyte, or
in oncology: adolescent and young adult oncology. platelet lineage). Acute leukemias constitute 97% of
Research efforts are increa5ingly focusing on this all childhood leukemias and are subdivided into acute
population. lymphoblastic /erkmia (All) and acute myeloid (or
A direct result of the progress in treating child- myelogenous) leukemia (AML). If untreated, they
hood cancers is a surge in the number of childhood are rapidly fatal within weeks to a few months of
cancer survivors. Issues relating to survivorship are diagnosis, but with treatment, they are often curable,
now being appreciated and need to be acknowledged with ALL having a better prognosis than that of
in pediatric and general practices. The number of AML. Chronic leukemias make up only 3% of child-
dedicated survivorship clinics with multidisciplinary hood leukemias, the majority of which are chronic
teams that have particular expertise in issues faced by myelogenous leukemia (CML) seen in adolescents.
survivors is on the rise. Still. primary care physicians Unlike patients with acute leukemias, CML can be
need to be aware that long-term complications of indolent and patients may survive without treatment
cancer therapies exist and that appropriate lifelong for months to years. If left untreated, the chronic
follow-up is needed. It is also important that childhood leukemias may undergo an acute transformation
287
TABLE 13·1. Usting of Common ChemotharapeuticAgants and ThairToxicities

i= .....
!AJkyiMJnfAgt1IIIJ
: Cydopbo.phamide Alkylation: c:roeHiDkiDg
IIfosfamide Hemorrhagic cystitiJ; reoal toxicity; ototoxicity; fertlllty
j Cisplatinum Platinatioo: cross~linking Ototoxicity; renal toxicity; deJa~ nausea
i Antimelaboliltl
!Methotreute Interferes with folate metabolism Mucositis; hepatic and renal toxicity; neurotoxicity
1Mercaptopurine Blocks purine synthesl& Mucolitis; hepatic toxicity
IThioguanine Blocks purine synthesis Muc:osl.til; hepatic toxlclty
j Cytarabine Inhibits DNA polymerase Mucositis; flu·like syndrome; ocular toxi.dty
: AntlllJmorAntlblorlc
j Doxorubicin Int:e.n:alatio.n; DNA strand breaks Mucosltis; cardiac toxicity
!Plant PfoductJ
1.,, Vuu:riatine Mitotic inhibitor; blocb SIADH; neurotoxicity-footdrop, conatlpation
microtubule polymerization
! Etopo&icle DNA rtrand break Mucositis; infusion reactioos; secondary leukemias
IAsparaginue Asparagine depletion Coagulopathy; pancreatitis; anaphylaxis
ICorticollteroida Receptor--mediated lympholysia
Increased appetite; hypertenai.on; hyperglycemia;
! myopathy; avucular necrosil; cataracts
j Atlbrellladon: SIADH, syndrome a! Inappropriate anddlur&tlc hcrmona secretion.
! Chemotherapy: A brief llstlr"Q of commonly used dlemotheropeutlc agents and their toxlcllles. To a greater or lesser extent, the
!following common tmdcllles are seen wl1h most chemotherapy: nausea, alopecia, myelosuppression, and mmunosuppresslon. In
; addition, infertility and &eeond malignancies are a concern foiiDVIIing chemotherapy.
~ Adapted from Pizzo PA, Poplack 00, ed&. Principle& and Practloe of P9dtatrlc Onoo.bfw, 51h ed. Phnadetphla, PA: Upplnoott Wiliams &
i Wlldns; 2006. ,
~oooo•oooo..•oooooo•oooooo•ooooooooooooooooooooo••••• •·••"''''''''''''''''''''''''''''''''''''nooooooooooonoooooo•••••••-••••••••••••••••~••-•••••••••••••••••••-••ooooooooooooo•ooooooooooooo•oo"""""''''''''-"""''"""""""'''''''"'''''''''''''~"'''''''nooo-•-•••••••
that requires immediate therapy to survive. Because precursor B-cell ALL. Mature B-cell ALL, or Burkitt
CML is so rare in children. a discussion ofthe chronic leukemia. which accounts for 2% to 31)6 of cases,
leukemias is beyond the scope of this review text. is treated like Burkitt lymphoma with a favorable
The following discussion focuses on ALL and AML outoome expected.
in childhood and adolescence. AML has historically been classified into eight
subtypes on the buis of morphology using the
CLASSIFICAnON French-American-British classification system!
ALL is classified byboth morphologic and immuno. MO to M7. MO is undifferentiated myeloblastic
logic methods. Morphologic classification is based leukemia, Ml is myeloblastic leukemia with min-
on the appearance of the lymphoblasts under the imal differentiation, M2 is myeloblastic leukemia
microscope. Immunologic classification is based on with differentiation, M3 is promyelocyti.c leukemia,
immunophenotype, which is described by surface M4 is myelomonocytic leukemia, M5 is monocytic
antigen expression as measured by flow cytometric leukemia, M6 is erythroblastic leukemia, and M7
analysis, considered to be the most definitive method is megabryoblastic leukemia. However. the World
ofclassification. The most frequent childhood ALL Health Organization has reclassified AML on the basis
immunophenotype, precursor B-cellALL, accounts ofclinical and molecular features, including whether
for about 804J6 ofcues. It is associated with a good the AML is due to prior radiation or chemotherapy,
prognosis overall. T· ceU ALL accounts for about 15% the presence of trisomy 21, the presence of several
to 2006 ofchildhood ALL. Outoomes forT-cell ALL other recurrent chromosomal abnormalities, or the
have improved significantly over the past several presence of dysplasia. The prognosis for AML is
years, largely because of treatment modifications, dependent on both subtype and risk factors. Patients
and are now comparable to the outcomes of some with acute promyelocyti.c AML and young trisomy
Chapter 13 I Oncology • 289
21 patients with acute megakaryoblasticAML have in adolescence, remaining less common than ALL
a good prognosis, as do patients with other favorable at all ages under 20 years but then exceeding ALL
risk factors. Risk factors will be discussed later in throughout the rest of adulthood.
this chapter. Syndromes with an increased risk for leukemia
in general include trisomy 21, Fanconi anemia,
EPIDE.MIOLOGY AND RISK FACTORS Shwachman-Dlamond syndrome, Diamond-Black&n
Table 13~2 compares the general characteristics ofALL anemia, severe congenital neutropenia, dyskeratosis
and AMI.. ALL, the most common pediatric cancei; congenita, Li-Fraumeni syndrome, Bloom syndrome,
acoounta for about 75% ofall cases ofchildhood acute ataxia~telangiectasia. X~linked agammaglobulinemia,
leukemia. ALL is somewhat more common in boys and severe combined immunodeficiency. Monozy-
than In girls and more common in white children than gotic twins have an increased risk ofleukemia ifone
in Afrlcan-Amel'ican children. The incidence of.AU twin develops ALL or AML during the first 6 years
peaks between 2 and 5 years of age. AMI. accounts oflife. Children who have undergone chemotherapy
for about 20% ofall cues ofpediatric acute leukemia. or radiation therapy for a first malignancy have an
However; the incidence ofAMI., in contrast to ALL, increased risk of developing a secondary leukemia
has a small peak below 2 years ofage and is increased (particularly AML) 1 to 10 years after treatment.
YULE 13-2. COmparison of the Clinical Presentation of All. and AML

1 ca........ ALL
l MlmJW Fa/Juri
1· Anemia (g/dL) Hb<7(43~) Hb<9(~)
!.~~penla Hb 7-11 (45%)
Hb> ll(m6)
Pit < 100,000 (7596)
WBC > 100,000 (20%)
1• Neatropenla (per mm') Pit < 20.000 (20%)

Pit 21.,000-99,000 {47%)
i Pit > 100,000 (25")

WBC < 10,000 (53%)
WBC 1().000-49,000 (309r>)
WBC > 50,000 (1796)
Fewr 6006
!MediaatinaliiUIIII 10% (mostly in T cell)
ICNS involvement 596 296
i Chloromas Common in M4. M5 subtype
I T..tlculor _ _, 296--596
Common in periorbital area
Rare
~ Disseminated intravascular c:oqulation Common {ap. in APML)
j Bone pain 2096
I Hepata.plenomeply sow.
IOther Leukemia cutis (1'"')
• Neonates
• Blueberry muffin spots
I
i AbbnNiellons: AU., eoute lymphocytic IGU<emla; AML, acute myalogenousleukemla; APML, eoute promyalocytlc leukemia; CNS,
Gingival hypertrophy (15%)
! central nervous system; Hb, hemoglobin: Pit, platelet; WBC, white blood eel.
i From Frank G, Shah SS, Cetallozzi M, at al, ads. The PhiiBdelphia Guide: lnpstieftt PediBttics. Maldan, MA: Blackwell; 2005:304. !
:.,.,,,.,.,,..,,,,,uooooo_,,,.,,,,,,,,,,,,,, ,,,,.,,.,,,,,,,,.,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,..,,.. ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,.,.,,,,,,,,..,,..,,.,.,.,,.,,,,,,.,.,,,,,,,,,,,,,.,.,,,,,.,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,_,,,,,_.,,,,,,,,,,,,,,,,,,,,,,,,,;
CLINICAL MANIFESTATIONS intravascular coagulation. Blood, urine, and viral

History and Physical Examination cultures may be obtained if infection is suspectEd.
Symptoms usually develop days to weeks before A chest radiograph is obtained to evaluate for
diagnosis. Nonspecific constitutional symptoms mediastinal mass. Ifa mediastinal mass is detected,
include lethargy, malaise, and anorexia. Children an echocardiogram may be considered to look for
may complain about bone pain or arthralgias caused possible cardiac dysfunction or cardiac effusion,
by leukemic expansion of the marrow cavity. Pro- and a chest computed tomography (CT) may be
gressive infiltration of bone marrow with leukemic obtained to evaluate airway compression. Because
cells may lead to fatigue and pallor from anemia, and ofthe potential for life-threatening cardiorespiratory
bleeding, bruising, or petechiae from thrombocyto- compromise from external compression ofthe mass
penia. The anemia is typically normochromic and againstvital structures, no sedation should be used in
normocytic. Decreased marrow production of red the patient with mediastinal mass until an anesthesia
blood cells leads to a low reticulocyte count. The consultation is acquired. A lumbar puncture (LP) is
white blood cell (WBC) count is low in a third of performed to evaluate for CNS disease. Ifthe patient
patients, normal in a third of patients, and high in a has significant thrombocytopenia or coagulation
third of patients. Many children have hepatospleno- abnormalities, these should be corrected before the
megaly and cervical lymphadenopathy at diagnosis. LP to prevent bleeding complications.
Extramedullary involvement may also be seen in the
central nervous system (CNS), skin. and testicles. TREAtMENT
CNS infiltration may cause neurologic signs and
The treatment strategy for both ALL and AML is
symptoms, such a.s headache, emesis, papilledema,
to stabiliz.e the patient at diagnosis, put the leuke-
and sixth cranial nerve palsy. Patients with AML mia in remission, and manage the complications
may develop a soft-tissue tumor called a chloroma of therapy. Managing leukemic complications at
in the spinal cord, brain.. or skin. presentation involves blood product transfusions,
DIFFERENTIAL DIAGNOSIS empirical treatment of potential infection with
intravenous (IV) antibiotics, prevention of the se-
The differential diagnosis ofleukemia includes aplastic
quelae of hyperviscosity, and correcting metabolic
anemia, idiopathic thrombocytopenic purpura, viral
abnormalities and renal insufficiency from tumor
infection (Epstein-Barr virus [EBV], parvovirus and
lysis syndrome. Neutropenia defined as an absolute
others), metastatic disease, bone marrow suppression neutrophil count (ANC) less than 500 cells/ mm9 (or
secondary to a drug or toxin. rheumatologic diseases
•tunctionai• neutropenia which is often presumed in
such u lupus or juvenile idiopathic arthritis, and
a patient with newly diagnosed leukemia despite a
hemophagocytic lymphohistiocytosis.
nonnal ANC) predisposes children to serious bacterial
DIAGNGSnC EVALUATION and fungal infections. The development offever in a
child with neutropenia warrants careful evaluation
A complete blood count (CBC) with manual differ- for bacteremia or sepsis and immediately initiating
ential and review of the blood smear to look for blast
empiric, broad·spectrum IV antibiotic therapy.
cells should be obtained in any child with suspected
leukemia. The peripheral blood can be sent for Acute Lymphocytic Laukamia 1barapy
flow cytometry to confirm and determine the type Patients with ALL are at risk for tumor lysis syndrome,
of leukemia. Bone marrow specimen .remains the a triad of metabolic abnormalities-hyperuricemia,
gold standard for diagnosis, even if peripheral blood hyperphospharemia, and hyperkalemia resulting from
has been used to type the leukemia. Bone marrow spontaneous or treatment-induced tumor cell death.
aspirate is sent for morphology, immunophenotype, This causes a rapid release ofintracellular contents
and cytogenetics (chromosome testing), which are into the circulation that can exceed the excretory
critical elements used to risk-stratify the leukemia capacity of the kidneys. Thmor lysis syndrome is
into a treatment group. A comprehensive metabolic more often seen in tumors with high growth rates
panel, lactate dehydrogenase (LDH), uric acid, calcium, such u T·cell ALL or Burkitt leukemia/lymphoma,
magnesium, and phosphorus are obtained to define and patients with mediastinal mass or high WBC
baseline values before chemotherapy and screen count, but should be anticipated in all cases of
for possible tumor lysis syndrome (discussed later). acute leukemia. Hyperkalemia can cause cardiac
Coagulation studies are sent to exclude disseminated arrhythmias. Initial IV fluids should never contain
potassium. Phosphate, especially at high serwn levels, than 5% of marrow cellJ, and the CBC values nor-
binds to calcium, resulting in precipitation of cal- malize. Induction therapy oCCUI'8 over 28 days with
cium phosphate in renal tubules, hypocalcemia. and vincristine, steroids, asparaginase, and intrathecal
tetany. Purines are processed into uric acid, which methotrexate. For high~risk patients, daunorubicin is
is released into the drculation. Hyperuricemia can added. More than 95% of patients with ALL achieve
result in precipitation of uric add in renal tubules remission after induction therapy. Fallure to achieve
and renal &ilure. Prevention and management of adequate response by the end of induction requires
tumor lysis syndrome includes vigol'OU8 hydration, intensification of therapy. However, even in patients
uric acid reduction with allopurinol or rasburicase, who achieve remission at the end of induction, it is
and potassium and phosphate reduction. The risk well known that additional therapy is necessary in
for tumor lysis is greatest during the first 3 days of order to continue treating occult disease and prevent
chemotherapy. relapse. The goals of the next phase, consolidation,
Hyperkulrocytosis is generally defined as a WBC are to kill additional leukemic cells with further
count of more than 100,000 cells/mm3, but clinically systemic therapy and to prevent leukemic relapse
significant hyperleukocytosis typically occurs with a within the CNS by giving intrathecal methotrexate.
WBC count of more than 300,000 to 500,000 cells/ Interim maintenance, which follows induction and
mm3 in ALL and more than 200,000 cells/mm3 in consolidation, is less intense and includes vincristine,
AML. In contrast to ALL, patients with AML and 6-mercaptopurlne, and methotrexate. The delayed
hyperleukocytosis are treated at a lower WBC count intensification course provides another round of
because AML blasts are larger and more adherent intense chemotherapy to induce a deeper remission.
than the blasts found in ALL. Hyperleukocytosis Maintenance therapy completes the therapeutic
can cause significant vascular stasis. Symptoms course and includes periodic intrathecal methotrex-
Include mental status changes, headache, blurry ate, vincristine and steroid therapy, as well as weekly
vision, dizziness, seizure, and dyspnea. "Without oral methotrexate and daily oral6-mercaptopurine.
therapy, hyperleukocytosis may cause hypoxemia The objective of maintenance therapy is to continue
and secondary acidosis or stroke from sludging in the remission achieved in the previous phases and
the lungs and CNS, respectively. The WBC count to provide additional cytoreduction to cure the
may be lowered using hyperhydration, hydroxyurea. leukemia. Patients with high~risk leukemia receive
or sometimes leukapheresls.lt is recommended that an additional Interim maintenance course before
the hemoglobin concentration be kept less than 10 entering maintenance therapy. They may also re-
g/dL to minimize viscosity (i.e., limit red blood cell ceive CNS-directed radiation therapy, but this is
transfusions), and that the platelet count be main- uncommon.
tained at more than 20,000/mm3 to minimize the Discontinuation of chemotherapy occurs when
risk of hemorrhage. the patient has remained in remission throughout
Large collections of malignant cells in the the prescribed course of maintenance therapy. The
mediastinum (mediastinal mass), common in T.cell total length of therapy is approximately 2.5 years
leukemia, can compress vital structures and cause for females and 3.5 yean for males. Leukemia can
tracheal compression or superior vena cava syndrome. recur during or after the completion of therapy. The
Superior vena cava syndrome is characterized by earlier the relapse, the worse the prognosis is (<36
distended neck veins; swelling of the face. neck, and months from diagnosis for bone marrow relapse, or
upper limbs; cyanosis; and conjunctival inJection. <18 months for CNS or testicular relapse). Isolated
The mass and the compressive symptoms it creates CNS relapses tend to have better outcomes.
usually resolve with chemotherapy. Patients with Factors associated with a worse prognosis in pa-
severe symptoms may warrant empiric steroid therapy tients with ALL include age greater than lOyears or
and/or emergent radiation therapy. less than 1 ~ar at cUasnosis, WBC count greater than
The ALL treatment regimen includes induction. 50,000/mm3 at diagnosis, failure to attain remission
consolidation, interim maintenance, delayed inten- by the end ofinduction therapy, and the presence of
sification, and maintenance phases of therapy. At the Philadelphia chromosome or hypoploidy in the
diagnosis, children with ALL undergo induction leukemia cells. Factors associated with a particularly
therapy, during which a maximum log kill of leu- good prognosis include trisomy 4 and 10, hyperdip-
kemic blasts occurs. Remission is achieved when loidy, or a TEL-AMLl (also known as ETV6-RUNX1)
leukemic blasts in the bone marrow decrease to less translocation (t(l2;21]) in the leukemia cells.
Acuta Myeloid Leukemia Tberapy Africa (•endemic•) is different than in developed

AML chemotherapy is shorter but more intensive countries (•sporadicj. Endemic Burkitt lymphoma
than that uaed for AU.. Induction therapy includes an usually presents as a rapidly expanding jaw lesion,
anthracycline, cytarabine, and etoposide. Although and 9596 of these tumors carry EBV genomes in their
9096 of patients with AML achieve remission with cells, whereas only 15% to 2096 of North. American
induction therapy, a fair number of patients relapse tumors are associated withEBV, and the presentation
within a year. Myelosuppression is severe, and good is more varied.
supportive care is essential. Between cycles of che-
motherapy, patients should be monitored closely for EPIDEMIOLOGY
signs ofinfection until they show signs of bone marrow Lymphomas are the third·most common m.a1ignancy
recovery. If remission can be achieved. patients are in childhood. after leukemias and brain tumors,
assigned a risk group on the basis of chromosomal and account for about 10% of childhood cancers.
alterations in the leukemic cells. Patients with However, altogether they are the most common
low-risk disease (including: inversion 16/t[16;16], malignancy presenting between the ages of 15 and
AMLl-ETO [also known as RUNXl-RUNXlTl] 19. There is a distinct geographic frequency of
translocation [t(8;21)], or trisomy 21 under the age NHL; in equatorial Africa, NHL accounts for 50%
of 4) are treated with chemotherapy alone. Patients of childhood cancer. In the United States, approxi-
with hJgh-risk disease (including therapy-related mately 60% of pediatric lymphomas are Nlfl.s; the
AML, myelodysplastic syndrome [MDS]-related remainder are Hodgkin lymphomas. NHL is more
AML, monosomy 5 or 7, a high allelic ratio ofFLT31 common in boys than in girls and has a median age
lTD, or a lack of remission) are treated with hema- of diagnosis of 10 years.
topoietic stem cell transplantation from a related or
unrelated donor after upfrontchemotherapy. Patients RISK FACTORS
who are neither hfsh ri&k nor low risk are considered Children with congenital immunodeficiency (e.g.,
intermediate risk, and treatment depends on their Wiskott-Aldrich syndrome, X-linked lymphopro-
response to therapy. liferative disease, severe combined immunode-
Acutepromyelocytic kukemi4 has a higher overall ficiency) and acquired immunodeficiency (e.g.,
survival rate (8096) than the other AML subtypes, AIDS, iatrogenic immunosuppression in organ
attributable to the efficacy of all-trans retinoic acid. and bone marrow transplant recipients) have an
Similarly, yoW18er patients with AML and trisomy increased incidence of NHL. Patients with Bloom
21 also have an excellent overall survival. Patients syndrome and ataxia-telangiectasia also have a
with secondary AML/myelodysplastic syndrome higher incidence ofNHL than the general pediatric
often have a poor response to therapy. population.
Table 13-2 compares the general characteristics
of ALL and AML. CLINICAL MANIFESTATIONS
T-celllymphoblastic lymphoma is most often
NON-HODGKIN LYMPHOMA associated with a mediastinal mass, whereas B-cell
lymphoblastic lymphoma tends to involve bone,
PATHOGENESIS isolated lymph nodes, and skin. Superior vena cava
Non-Hodgkin lymphomas (Nlll.s) are a heteroge- syndrome may be associated with any lymphoma
neous group ofdiseases characterized by a neoplastic presenting as a mediastinal mass. Burkitt lymphoma
proliferation ofimmature lymphoid cells. Unlike the often exhibits extremely rapid growth and can be
malignant lymphoid cells of ALL, the cells of NHL associated with tumor lysis syndrome even before
accumulate outside ofthe bone marrow. NHLs can be chemotherapy is started. The sporadic form of
divided into T- and B--cell categories. Histopathologic Burkitt lymphoma can present as an abdominal
subtypes in childhood NHL include lymphoblastic tumor associated with nausea, emesis, or intus-
(pre-T or pre-B cell), Burkitt lymphoma or diffuse susception. Other Burkitt locations may include
large 8--celllymphoma (mature B--cell), and anaplastic tonsils, bone marrow, and the CNS. The endemic
large cell lymphoma (T-cell). Other peripheral T-cell form of Burkitt lymphoma typically involves the
lymphomas come under the category of NHL but jaw, orbit, and/ or maxilla. Anaplastic large cell
are very uncommon in children. The presentation lymphoma is a slowly progressive disease with
and pathogenesis of Burkitt lymphoma in equatorial fever; weight loss is rare.
HODGKIN LYMPHOMA
The evaluation before therapy should include a
thorough history and physical examination with PATHOGENESIS
attention to the signs and symptoms that require a The cause ofHodgkin disease (liD) is unknown, and
more urgent evaluation including cough, dyspnea, a number ofstudies investigating potential etiologies
orthopnea, and chest pain. A CBC should be per- have shown that age, race/ethnicity, socioeconomic
formed to look for leukocytosis or leukopenia, status, and geographic distribution suggest a multi-
thrombocytopenia, and anemia. Ar. with acute leu- factorial etiology involving both environmental and
kemia, a comprehensive metabolic panel including genetic components. Patients who develop HD have
caJcium and phosphorus, in addition to uric acid and an increased incidence of immune dysregulation.
IDH. is used to evaluate for tumor lysis syndrome. There is increased risk in siblings and twins, and an
A chest radiograph should be performed to assess association with EBV, although the EBV genome is
for mediastinal mass before the sedation and biopsy not universally found in tumor tissue. In addition,
ofaccessible affected nodes, and an echocardiogram there is an increased risk of HD in patients with
may be considered. An anesthesia consultation is ataxia·telangiectasia and Wiskott·Aldrich and Bloom
requlred before the sedation of a patient with a syndromes.ln order from most to least common, the
mediastinal mass. An excisionallymph node biopsy four main histopathologic subtypes in pediatric HD
as well as bone marrow aspiration/biopsy sent for include nodular sclerosing, lymphocyte-rich. mixed
morphology, cell markers/immunophenotyping, cellularity, and lymphocyte depleted.
and cytogenetics should be performed to isolate
the type of lymphoma. An LP with cytology may EPIDEMIOLOGY
be performed to evaluate for CNS involvement. A HD accounts for 5,.; ofall cases of childhood cancer
CT scan of the neck, chest, abdomen, and pelvis before 15 years of age and 9% before 20 years of
helps assess the extent of disease. In addition, a age. Epidemiologic studies have identified three
positron emission tomography (PET) scan measures distinct forms of HD: a childhood form (younger
metabolic activity and is useful for evaluating the than 14 years), a young adult form (15 to 34 years
extent of disease and follow-up for residual disease of age), and an older adult form (55 to 74 years of
or recurrence. age). Its incidence has a bimodal distnoution, with
peaks occurring at 15 to 30 years of age and after
TREAtMENT the age of 50. It rarely occurs in children younger
ALL and lymphoblastic NHL therapy are patho- than 5 years. There is a slight male predominance in
logically similar but with a different distribution the childhood form ofHD, but it affects adolescent
of disease (marrow vs. nodal, respectively). Ac- males and females equally.
cordingly, lymphoblastic NHL is generally treated
with combination chemotherapy similar to that CLINICAL MANIFESTATIONS
used for ALL. History and Physical ExaminatiOn
Chemotherapy is the mainstay of treatment for The most common presentation is painless, rubbery,
Burkitt lymphoma unless the tumor is localized and cervical and/or supraclavicular lymphadenopathy.
complete surgical resection is po.uible. Therapy is Two·thlrds ofpatients also have mediastinal lymph-
given over a short period of time (4 to 6 months) adenopathy. which is more common in adolescent
using drup such as cyclophosphamide, vincristine. patients. Some patients have systemic symptoms
prednisone, methotrexate. doxorubldn, cytarablne, (B symptoms), which include unexplained fever,
and etoposide. Patients with CNS involvement have drenching night sweats, and an unintentional weight
a poorer prognosis. Potential tumor lysis syndrome loss of more than 1()1}6 over the preceding 6 months;
requires extremely careful management with in- these are correlated with worse prognosis. Other
creased hydration, frequent electrolyte observation presenting symptoms may include anorexia, fatigue,
and correction, allopurinoL and often rasburicase and pruritus.
for hyperuricemia. Patients with Burld.tt lymphoma
are at high risk ofdeveloping renal failure requiring DIFFEREN11AL DIAGNOSIS
dialysis from their tumor lysis syndrome. Anaplastic The differential diagnosis for HD includes other
large cell lymphoma is also treated with combination diseases that can result in lymphadenopathy with or
chemotherapy. without systemic symptoms. Reactive or inflammatory
nodes as a result of bacterial lymphadenitis, infectious TREATMENT

mononucleosis, tuberculosis, atypical mycobacterial Treatment depends on staging and response to
infection, cat-scratch disease, mv infection, histo- therapy (Table 13-3).
plasmosis, and toxoplasmosis should be considexed. Multiagent chemotherapy is given in a risk-adapted
Primary or metastatic malignant processes resulting and response·based manner. Involved field radiation
in cervical adenopathy or a mediastinal mass include therapy is used for patients with bulky disease or
leukemia. NHL, head/neck rhabdomyosarcoma, and with residual tumor after initial chemotherapy. The
germ cell tumors. most common agents used today are doxombicin,
bleomycin, vincristine, etoposide, prednisone, and
DIAGNGSnC EVALUATION
cyclophosphamide. Prognosis is highly favorable,
~ in NHL, evaluation for HD should include a with long-term survival varying from about 70% to
detailed history and ph'flical examination with more than 90% depencUng on the extent of disease
particular attention to cough, dyspnea, orthopnea, and response to therapy. Recurrent disease is often
chest pain. bleeding, bruising, jaundice, or pallor. responsive to therapy but can be difficult to cure
The physical examination should include a careful and may require high-dose chemotherapy followed
evaluation of all lymph node groups, including the by autologous stem cell rescue. There are many late
tonsils. Lymphadenopathy in the upper anterior and effects secondary to therapy, including secondary
posterior cervical chains tends to be more commonly mallgnan.t neoplasms (breast. thyroid, sarcomas);
associated with childhood infections, whereas nodes cardiac toxicity (anthracyclines and radiation therapy
in the supraclavicular area are highly suspicious [XRT)); pulmonary fibrosis (bleomycin); hypothy-
for malignancy. Lymph nodes that are more than 1 roidism (XRT); infertility (alkylating agents as afore-
em, matted, and nontender are ofgreatest concern. mentioned, peMc radiation); and mu.sculoskeletaV
EnJargement of the liver or spleen is consistent with growth (XRT). Because of the very high cure rate
more advanced disease. and the late effects of therapy, most recent study
IJnasingshould begin with a chest radfosraph before
any biopsy or procedure to determine the presence
and size of a mediastinal mass, and whether or not TUU: 13-3. Staging for Hodgkin lymphoma
~--
there is clinically significant mediastinal involve-
ment such as airway compromise or cardiovascular Dlfil....
compression. This may influence the way in which ~.!', I Invomment ofsingle lymph node
region or sinP extralymphatic site
the biopsy is performed and the type of anesthesia
!n Involvement of two or more lymph
required. A tissue biopsy is required to make the node regions on the same side of
diagnosis, preferably exciaionallymph node biopsy. diaphragm or localized involvement
The hallmark of diagnosis is the identification of of an ext:ralymphatic lite and one
Reed-Sternberg cells in tumor tissue, although this , or more lymph node regioDll on the
is not always present in liD. same side of the diaphragm
Recommended lab tests include a CBC, eryth-
rocyte sedimentation rate (ESR), and a chemistry
IIII Involvement of lymph node regions
panel including liver function tests. Eosinophilia

is seen in about 15% of patients, and a significant
1.,,, :!':vo':~'!~rC:::!;::
or loc:all.zed involvement of an
proportion of patients present with anemia. Global I!Xtralymphatic lib!
immune defects are common at diagnosis of HD,
and this immune dysregulation seen at diagnosis
iIV Dluemlnated involvement of one or
more extralymphatic organs with or
predisposes patients to opportunistic infections without lymph node involvement
during their treatment. Imaging studies include a !,_ "B" symptoiDI Fevet higher than 3rC Cot
CT scan of the neck, chest. abdomen. and pelvis. 3 consecutive days
~:::>,~
PET may identify skeletal disease at diagnosis and
is quite useful in following residual or recurrent
disease. Bone marrow aspiration/biopsy is often
indicated to assess for bone marrow involvement.
I
Bone scan is considered only for patients with l Thoae without B aymptoma have
bone pain. I atage (number) A diaeue .
;,,,,.,,,.,,,.,,,.,.,,.,,.,,,.,.,, .,,.,.,.,.,_,,u.,,.•._••••••" •••"•"'"''''''''''''''''''''''''''•••••••••••••••••••••••••••oo••oo••••
protocols aim to reduce therapy while maintaining examination. The Cushing triad (hypertension,
high cure rates, for instance by limiting XRT exposure bradycardia, and irregular respirations) is a late
in certain patients. finding of increased ICP. Other general symptoms
include developmental delay, behavioral changes,
k3 MI j ;#;\ ':1
3;i'l•1ifJtki j Mf,,IJ M•lif'J and failure to thrive.
Children with in.fratentorial tumors ofren. pres-
CNS tumors are the most common solid tumors in ent with deficits of balance or brainstem function
children and are second to leukemia in the overall (truncal ataxia, problems with coordination and
incidence of malignant diseases. In contrast to gait. and cranial ne.rve dysfunction). Because it can
adults, in whom supratentorial brain tumors are result from an increased ICP, a sixth nerve palsy is
more common, brain tumors In children are pre- not considered a localizins focal neurologic deficit,
dominantly infratentorial, involving the cerebellum whereas other cran1al nerve deficits, by definition,
and brainstem. Childhood brain tumors are differ- localize the lesion to the brainstem. Head tilt, as a
entiated further from those in adults in that they are compensation fur loss of binocular vision, is noted
most commonly low-grade astrocytomas or tumors with focal deficits of cranial nerves ill, IV, or VI,
of embryonal histology such as medulloblastomas, which cause extraocular muscle weakness. Nystag-
whereas most CNS tumors in adults are meningiomas mus is usually caused by cerebellovestlbular pathway
(benign tumors typically secondary to prior radia- lesions, but it may also be seen with a marked visual
tion), high-grade astrocytomas, or metastases from deficit (peripheral or cortical blindness).
non-CNS cancers. Children with CNS tumors have a Children with supratentorial tumors commonly
aign.ifu:antly better prognosis than adults overall The present either with signs ofincreased ICP or seizures.
cure rate for medulloblastoma, the most common Although most seizures are generalized, less dramatic
malignant brain tumor In children. exceeds 80% for episodes with incomplete loss of consciousness
those with standard risk. However, even histologically (complex partial seizures) and transient focal events
benign tumors may warrant treatment on the basis without loss of consciousness (partial seizures) are
ofsymptoms. Ependymomas, germcell tumors, and a1so seen. Personality changes, poor school perfor-
atypical teratoid rhabdoid tumor are other malignant mance, and changes in hand preference suggest a
neoplasms seen in the pediatric population. cortical lesion. Endocrine abnormalities including
D#ffuse intrtn.stc pontine gliomas (DIPGs) are precocious puberty and diabetes insipidus may be
diffuse astrocytomas involving the brainstem (pons) seen in pituitary and hypothalamic tumors. Babinski
and have an extremely poor prognosis. With rare reflex, hyperreflexia, spasticity, and loss ofdexterity
exceptions, most children succumb to DIPG in 6 occur with either brainstem or cortical tumors.
months to 2 years. Radiation therapy may stabilize
disease for a limited time, but chemotherapy has not DIFFERENTIAL DIAGNOSIS
altered the time course of survival. The differential di.asnosis Includes arteriovenous
malformation, aneurysm, brain abscess, parasitic
CLINICAL MANIFESTATIONS infestation, herpes simplex encephalitis, granulo-
The presenting signs and symptoms ofCNS tumors matous disease (tuberculosis, cryptococcal, sarcoid),
depend on the age of the child and location of the intracranial hemorrhage, pseudotumor cerebri,
tumor. Any CNS tumor may cause increased intra- primary cerebral lymphoma, vasculitis, and rarely
cranial pressure (ICP) by obstructing the flow of metastatic tumors.
cerebrospinal fluid (CSF). Symptoms ofincreased ICP
include headaches that interrupt sleep or occur in the DIAGNOSTIC EYALUAnON
early morning, vomiting, and lethargy. The headache CT and magnetic resonance imaging (MRI) are the
is usually present upon awakening, improves with imaging modalities used in diagnosing and localizing
standing, and worsens with coughing or straining. It tumors and other intracranial masses. A head CT
is intermittent but recurs with increasing frequency can be performed much faster than a brain MRI
and intensity overtime. Obstructive hydrocephalus and is safer in an unstable patient. A CT is useful
may produce macrocephaly if it occurs berore the as an initial screen and to assess for hydrocepha-
sutures have fused. Strabismus with diplopia can lus, hemorrhage, or calcification. MRI remains the
result from a sixth nerve palsy induced by increased gold standard for localization of brain tumors to
ICP. Papilledema may be detected on fundoscopic assist with surgical planning. MRI of the brain and
account for 70% of tumors, two-thirds of which

1'IIIU 1H. Approach to Treatment of Childhood
Central Nervous System Tumors arise from the adrenal medulla its~ and a third of
which arise from the retroperitoneal .sympathetic
ganglia. Thoracic masses, accounting for 20% of the
tumors, tend to arise from paraspinal ganglia in the
posterior mediastinum. Neuroblastomaof the neck
occurs in 5% ofcases and often involves the cervical
sympathetic ganglion.
EPIDEMIOLOGY
Neuroblastoma and other sympathetic nervous
system tumors account for approximately 8% of
all childhood cancers under the age of 15. It is the
most common solid tumor outside of the CNS under
the age of 15 , with approximately 650 new cases
diagnosed per year in North America. The median
age at diagnosis is 19 montlu; more than 50% of
children are diagnosed before 2 years of age, and
9096 are diagnosed before 5 years of age. There is a
slight male predominance. Neuroblastoma accounts
for 15% of the pediatric cancer-related deaths in the
United States every year.
RISK FACTORS
The etiology is unknown in most cases, and no
causal environmental factor has been isolated. No
spine is especially helpful in diagnosing tumors of prenatal or postnatal exposure to drugs, chemicals,
the posterior fossa and spinal cord. Examination of viruses, electromasnetl.c fields, or radiation has been
CSF cytology using LP is essential to determining strongly associated with an increased incidence of
the presence of metastasis in medulloblastoma and neuroblastoma. A family history of the disease can
germ cell tumors. be found in only 196 to 2% of cases. Neuroblastoma
has been reported in patients with some overgrowth
TREATMENT syndromes, Hirschsprung clfsease, congenital central
Treabnent of CNS tumors is best managed through hypoventilation syndrome (formerly known as Ondine's
a multidisciplinary approach, involving surgery, curse), pheochromocytoma, and neurofibromatosis
chemotherapy, and/or radiation depending on the type 1, suggesting the existence of a global disorder
pathology, tumor location, and age of the patient. of neural crest-derived cells.
Proton beam radiation has become more widely used
as it offers potential for leu exposure ofsurrounding CLINICAL MANIFESTATIONS
normal brain. Radiation therapy is generally with- The clinical manifestations are extremely variable
held or deferred for children less than 3 years ofage because of the widespread distribution of neural
because ofits profound adverse effect on neurocog- crest tissue and the length of the sympathetic chain.
ni~ development. Table 13-4 outlines the general
In addition. the biologic behavior is very diverse,
principles of treabnent of primary CNS tumors. from self-resolving asymptomatic disease in infants
less than 1 year of age to widely metastatic disease
NEUROBLASTOMA requiring myeloablative chemotherapy with autol-
ogous stem cell rescue.
PATHOGENESIS
Neuroblastoma is an embryonal malignancy of History and PhySical Examination
the postganglionic sympathetic nervous system. Abdominal tumors are hard, smooth. nontender
Neuroblastoma can be located in the abdomen, abdominal masses that are most: often palpated in
thoracic cavity, or head and neck. Abdominal tumors the flank and may displace the kidney anterolaterally
and inferiorly. Abdominal pain/distension and sys- ampli.6cation is important in assessing prognosis and
temic hypertension occur if the mass compresses determining treatment. Measurement of the urinary
the renal vasculature. Respiratory distress can be catecholamine& HVA and VMA, which are break-
seen in thoracic neuroblastoma tumon and large down products ofepinephrine and norepinephrine,
abdominal tumors in small children and infants. respectively, is abo useful for following response to
Sometimes the thoracic variant is asymptomatic, therapy and for detecting recurrence. Additional
and the tumor is discovered on chest radiograph modalities used for staging include bone marrow
obtained for an unrelated reason. Neuroblastoma biopsies, bone scan, metaiodobenzylguanidine
of the neck presents as a palpable tumor that may scintigraphy, and at times PET scan.
cause Horner syndrome (ipsilateral ptosis, miosis,
and anhidrosis) and heterochromia of the iris on TREATMENT
the affected side. Sometimes, thoracic or abdominal Treatment endorses a mult:imodal and multidisdplinary
tumors invade the epidural space posteriorly and approach and can involve surgery, chemotherapy, and
may compromise the spinal cord and result in back at times radiotherapy and/or biologic therapies. Several
pain and symptoms of cord compression. biologic variables have prognostic value and are used
The signs and symptoms vary according to the in addition to the International Neuroblastoma Staging
location of primary diJease and the degree of dis- System and/or the newer Inremational Neuroblastoma
semination. Metastatic extension occurs in lymphatic Risk Group Staging System for patients with ne~
and hematogenous patterns. Nonspecifi.c symptoms blastoma. These variables include age at diagnosis,
of metastatic disease include weight loss and fever. histopathology, DNA index of the tumor, and.MYCN
Speci1ic metastatic sequelae include bone marrow gene amplifi.cation. Depending on stage and biologic
infiltration, resulting in pancytopenia; cortical bone features, treatment can range from obaervation alone
pain, causing a limp; liver infiltration. resulting in for certain low-risk patients to multimodal therapy
hepatomegaly; periorbital infiltration, resulting utilizing surgery, conventional chemotherapy, high-
in proptosis and periorbital ecchymoses (raccoon dose chemotherapy with autologous stem cell rescue,
eyes); distant lymph node enlargement; and skin radiation, and biologic agents (cis-retinoic acid and
infiltration, causing palpable nontender subcutaneous immunotherapy) for high~risk patients. Chemother-
blWsh nodules in infants. Paraneoplastic effects, such apeutic agentsincludevincristine, cloxorublcln. ~
as watery diarrhea in patients with differentiated phosplwnide, carboplatin. cisplatin. arulmpotecan.
tumors that secrete vasoactive intestinal peptide or Stage MS tumors (age < 18 months, with metasta~
opsoclonus~myoclon~ataxia syndrome (chaotic eye ses confined to the skin, liver, and/or bone marrow)
movements, myoclonic jerking, and truncal ataxia), represent unique biology that either spontaneously
have been noted regresses or requires only minimal chemotherapy.
DIFFEREN11AL DIAGNOSIS
WILMS TUMOR
The differential diagnosis ofabdominal neuroblastoma
includes benign lesions such as adrenal hemorrhage, PATHOGENESIS
hydronephrosis, polycystic kidney disease. and sple- Wilms tumor is the most common renal tumor in
nomegaly, and malignant tumors such as renal cell children. It results from a neoplastic proliferation of
carcinoma, Wilins tumor, hepatoblastoma,leukemia, embryonal renal cells ofthe metanephros. The most
lymphoma, and rhabdomyosarcoma. often-citedgenetic anomalies in Wilins tumor involve
chromosomal loci llp13 (WTl) and llp15 (WT2).
Once a mass is confirmed by CT of the neck, chest, EPIDEMIOLOGY
abdomen, and pelvis, the diagnosis ofneuroblastoma
can be made by pathologic identification of tumor
Renal tumors account for 7"of all childhood can-
cers, with Wtlms tumor accounting for 9596 of these,
tissue or by the unequivocal presence of tumor cells foD.owed by clear cell sarcoma of the kidney and
on bone marrow aspirate combined with elevated rhabdoid tumor of the kidney. Renal cell carcinoma is
urinary catecholamines (homovanillic acid [HVA] uncommon in the pediatric population. The majority
and vanillylmandelic acid [VMA]), although these of renal tumors are unilateral, with only 5% to 10%
are not always elevated. Tissue biopsy for histology, being bilateral. They are predominantly diagnosed
DNA ploidy, and MYC-related oncogene (MYCN) in the first 5 years of life.
RISK FACTORS adjacent vessels (inferior vena cava), regional lymph

It is important to evaluate the patient for anomalies nodes, liver, and lungs. Bone scan and MRI of the
and syndromes associated with Wili:n.s tumor. As- head are indicated only for clear cell sarcoma or
sociated anomalies are seen in 1()116 ofWW:n.s tumor rhabdoid tumor of the kidney, respectively.
and include sporadic aniridia, hemihypertrophy,
TREAtMENT
cryptorchidism. hypospadias, and other genitouri-
nary (GU) anomalies. Associated syndromes include Treatment involves surgical removal of the lc.idney
Beclcwith-Wiedemann (hemihypertrophy, macro- (unilateral disease) if it can be safely done; otherwise
glossia, organomegaly, and omphalocele); Denys a biopsy can be performed or treatment can be ini-
Drash (nephropathy, male pseudohermaphroditism); tiated on the basis of radiographic appearance, and
WAGR (WJ.Ims tumor, aniridia. GU abnormalities, surgery may be done after chemotherapy. Surgery
and mental retardation); and Perlman syndrome also involves lymph node sampling. Chemotherapy
(unusual facies, macrosomia, organomegaly, renal and/or radiation are then prescribed depending on
hamartomas). the staging and pathology of the resected kidney.
Chemotherapy options range from a two-drug
CLINICAL MANIFESTATIONS treatment (vincristine and actinomycin) to a more
History and Physical Examination involved treatment. Radiation therapy tends to be
Most children (85%) are diagnosed after incidental reserved for those with unfavorable features and can
detection of an asymptomatic abdominal mass be used to treat metastatic sites.
by the child's parents while bathing or dressing Favorable prognostic factors include small tumor
the child, or by the pediatrician during a routine size, younger age at diagnosis, favorable histology,
physical examination. Abdominal pain or fever and no lymph node or extrarenal metastases or
may develop after hemorrhage into the tumor. capsular/vascular invasion. With modem therapies,
Other associated findings include microscopic or the 4-year overall survival of patients with favorable
gross hematuria (33") and hypertension (25%). histology Wilms tumor is over 85" even with met-
Hypertension occurs as a result ofeither renin se- astatic disease.
cretion by tumor cells or compression of the renal
vasculature by the tumor. Additionally, varicocele
can be present on physical examination if there BONE TUMORS
is spermatic vein cord compression of the tumor.
Primary malignant bone tumors account for 5% of
Acquired von Willebrand disease is present in up
to 8% of patients but is not routinely tested for as childhood cancers. Two forms predominate: Ewing
sarcoma and osteosarcoma.
it is typically asymptomatic.
DIFFERENTlAL DIAGNOSIS EWING SARCOMA

Paltlogenesis
The differential diagnosis ofWllms tumor includes Ewing sarcoma is an undifferentiated sarcoma that
benign lesions such as hydronephrosis, polycystic
arises primarily in bone and usually involves the
kidney disease, and splenomegaly, as well as malignant
translocation from chromosome 11 to chromosome
tumors 5UCh as renal cell carcinoma, neuroblastoma, 22, or t(ll;22), in affected cells. Ewing sarcoma is
lymphoma, rhabdomyosarcoma, and ovarian tumors.
thought to arise from a pluripotent neural crest cell of
DIAGNDSnC EVALUATION the parasympathetic nervous system. Other tumol'S
with the same or sim.Uar translocations occurring
Radiologic studies include abdominal ultrasound to
outside of bone are known as peripheral primitive
establish the presence of an intrarenal mass, assess
neuroectodermal tumors, and they are also members
the renal vuculature, and examine the contralateral
of the Ewing family of soft-tissue tumors.
kidney. An abdominal CT scan or MRI assesses the
degree of local extension and involvement of the Epidemiology
Inferior vena cava. A cr scan of the chest and abdo- Ewing sarcoma is seen primarily in adolescents
men is routinely performed to detect hematogenous and is more common in males than in females. It is
metastases, which are present at diagnosis in 1()116 significandy more common in Caucasians than in
to 15% of patients. 1he most common patterns of African Americans. Like osteosarcoma, it is more
spread include the renal capsule, extension through likely to occur in adolescents than in young children.
Clinical Mantfastatlons OSTEOSARCOMA

Pain and localized swelling at the site of the primary Pathogenesis
tumor are the most common presenting complaints. Osteosarcoma, also called •osteogenic sarcoma~ is
Unlike osteosarcoma, in which the long bones are a malignant tumor of the bone-producing me5en-
predominantly involved. flat and long bones are chymal stem cells. Osteosarcoma arises in either the
equally represented The most commonly Involved medullary cavity or the periosteum. The primary
sites are the pelvis (23%), femur (1896), and rib (13%). tumor is usually located at the metaphyseal portion
Other sites include the fibula, hwnerus, tibia, clavicle, of bones that are associated with maximum growth
and scapulae. In the long bones, Ewing sarcoma velocity, which include the distal femur, proximal
often begins midshaft, rather than at the ends as in tibia, and proximal humerus.
osteosarcoma. Systemic manifestations are more
common In children with metastases and include Epidemiology
fever. weight loss, and fatigue. Osteosarcoma iB seen mainly in adolescence, with a
male-to-female ratio of 2:1. Peak incidence occurs
Dlffllnntlal Diagnosis during the maximum growth velocity period in
The differential diagnosis for Ewing .sarcoma includes adolescents and young adults.
osteomyelitis, Langerhans cell histiocytosis, and
Clinical Manlfaslatlons
osteosarcoma. Metastasis to the bone by neuroblas-
Similar to Ewing sarcoma, pain and localized swelling
toma or rhabdomyosarcoma should be collBidered in
are the most common presenting complaints, but in
younger chUdre:n with a solitary bone lesion. contrast to Ewing sarcoma, systemic 1118I1ife5tations
Diagnostic Evaluation are rare. Because these tumors occur most frequently
Radiogaphs characteristically reveal a lytic bone lesion in adolescents, initial complaints may be attributed
with calcified periosteal elevation (onion skinniniJ to trauma. The most common tumor sites are the
and/or a soft-tissue mass. An MRI of the bony lesion long bones of the body including the distal femur
is needed to assess the extent. Bone scans and chest (40%), proximal tibia (2096), and proximal humerus
CTs are needed to assess for other metastatic sites, (10%). Metastases are present at diagnosis in 20% of
as well as PET scans. Bone marrow aspiration/biopsy cases, the majority of which are in the lungs. Gait
is needed to evaluate bone maiTOW involvement. disturbance and pathologic fractures may also be
A biopsy of the lesion confirms the diagnosis, along present.
with genetic studies looking for the t(11;22) which Diffwrantial Diagnosis
occurs in 85~ of patients. The differential diagnoses for osteosarcoma are
Trelltment simllar to those of Ewing sarcoma, and include
Treatment involves both systemic therapy (che- Ewing sarcoma, benign bone tumors, and chronic
motherapy) and local control therapy (radiation osteomyelitiA.
therapy or surgery). Chemotherapy is critical to both Diagnostic EValuation
reducing the size of the primary tumor and treating A lytic bone lesion with periosteal reaction is charac-
microscopic metastases, because almost all patients teristic on radiograph. The periosteal inflammation
with Ewing sarcoma have microscopic metastatic has the appearance ofa radialsunbuntthat results as
disease at the time of diagnosis. Specific agents in- the tumor breaks through the cortex and new bone
clude vincristine, doxorubldn. cyclophosphamide, spicules are produced. An MRI of the bony lesion is
ifosfamide, and etoposide. Local control generally needed to assess the extent. ACT scan of the chest
involves surgical removal of the primary tumor site is essential to detect pulmonary met:utues, which
with a limb-sparing procedure or rarely amputation appear as calcified nodules. In addition, a bone scan
if it iB located in an extremity. Lesions require the is needed to assess for other metastatic bony disease.
use of radiation therapy ifthe tumor is unresectable
and/or appropriate margins cannot be attained. Trelltment
The approximate 5-year survival rate for patients At diagnosis, 20% of patients have clinically detect-
with distal extremity nonmetastatic tumon is greater able metastatic disease, and most of the remaining
than 66~. Children with metastatic disease at diag- patients have microscopic metastatic disease. Man-
nosis have less favorable outcomes depending on agement of the primarytumor is surgical. either with
the extent of disease. limb-sparing surgery or amputation as necessary.
Unlike Ewing sarcoma, osteosarcoma is relatively serve as a red flag for further workup. In addition,
resistant to radiation therapy. The addition of both a parent or guardian may be the first to notice an
neoadjuvant (before surgery) and adjuvant (after abnormality in the child's eye (in photographs) and/
surgery) chemotherapy has raised the survival rate or vision that prompts further evaluation.
.substantially. Before chemotherapy, survival from The most important aspect of evaluation is the
osteosarcoma was 2096 with amputation alone. ophthalmologic examination. which should be per·
Currently, with aggressive chemotherapy, long·term formed by an experienced ophthalmologist. Both eyes
relapse-free survival is greater than 70'Jii. Specific need careful evaluation to determine the extent of
chemotherapeutic agents include cisplatin, doxoru- the tumor. Additional workup includes an MRI ofthe
bicin, and methotrexate, and sometimes the addition orbits and head to grossly assess involvement of the
of ifos&mide and etoposide. Aggressive treatment optic nerve and determine ifthere is involvement of
of metastatic disease is indicated because some pa- the pineal or parasellar sites (also known as trilateral
tients can be cured with. chemotherapy and surgical retinoblastoma). Bone scan and/or bone marrow
resection of an metastases. biopsies are obtained if there is a high suspicion
of systemic retinoblastoma involvement (high-risk
RETINOBLASTOMA features such as optic nerve involvement, choroidal
Pathogenesis invasion or extraorbltal spread, etc.).
Retinoblastoma (Appx. Fig. A·26) is the most common
intraocular ma.lignaru:y in children and is considered Treabnant
a malignant tumor of the embryonic neural retina. Treatment for retinoblastoma varies and can include
The majority of retinoblastoma is sporadic (60%), enucleation (eye removal), chemotherapy. local
but the remaining hereditary forms are transmit· therapies (laser, cryotherapy), radioplaques, and
ted u an autosomal trait with high but incomplete external beam radiation. Chemotherapy can be used
penetrance. The genetic mutation associated with. to help shrink the tumon, so that local therapies can
retinoblastoma is located at chromosome 13q14 at be more effectiw. Treatment is dependent on the
the RB1locus. extent of disease as graded by the Reese-Ellsworth.
dassification. .At times, upfront enucleation of the
Epidemiology involved eye (if unilateral) is needed if the local
Retinoblastoma accounts for approximately 3% therapies (laser or cryotherapy), with or without
of childhood cancers. It occurs in 1 out of 18,000 systemic chemotherapy, are unlikely to cure the
live births in the United States, with approximately eye. Enucleation is also performed in the setting of
300 new cases per yeR Two-thirds of cases occur bllateral disease if one eye is more involved than
before the age of2, and 95% occur before the age of the other and cannot be salvaged to preserve vision.
5. Vutually all bilateral disease (both eyes involved Subsequent therapy is then based on the pathology
with retinoblastoma) is hereditary, accounting for of the enucleated eye and whether the remaining
25% of cases and presenting in the first 2 years of eye is involved. It is important that a team approach
life. Sixty percent of cases are nonhereditary and involving the ophthalmologist, oncologist, and ra-
unilateral (one eye), and the remaining 15% are diation oncologist is used
hereditary and unilateral. Of note, a child born to a parent with bilateral
retinoblastoma or to a parent with unilateral reti.n~
Differential DiagnosiS blastoma with. a known genetic mutation should be
The differential is rather limited and includes con· screened by an ophthalmologist for retinoblastoma
genital cataract, medulloepithelioma, T(W)Cara canis at birth and at regular intervals until the child .is at
endophthalmitiB, persistent hyperplastic primary least 4 to 5 years old.
vitreous, and Coats disease. It is important that an
ophthalmologist with experience in retinoblastoma
be involved in the care of these patients. SOFT-TISSUE SARCOMAS
Diagnostic Evaluation PATHOGENESIS
Routine well~child checks and physical examinations Soft·tissue sarcomas (STS) are a very diverse group
can help detect retinoblastoma early. The presence of tumors. There are different types of STS that tend
of leukocoria (absence of a red reflex) is a finding to develop in diffurent age groups. In general, STS
often seen with retinoblastoma, and its presence can are divided into either rhabdomyosarcoma& (slightly
less than half) or no111'habdomyosarcomas. Rhab- Unfavorable sites include parameningeal, bladder,
domyosarcomas have been associated with certain prostate, and extremity. The most common sites for
familial syndromes, including neurofibromatosis and nonrhabdomyosan::oma sarcomas are the extremities,
Li-Fraumeni syndrome. Nonrhabdomyosarcomas trunlc/abdomen, and the head and neck.
are very heterogeneous, and their pathogenesis
and presentation are dependent on the histology. DIAGNOSTIC EVALUAnON
For example, malignant peripheral nerve sheath Radiologic evaluation includes appropriate imaging of
tumors are associated with neurofibromatosis type the primary site of the tumor and may include aCT
I, whereas some tumon such as malignant fibrous or MRI scan ofthe site to assess the extent ofdisease
histiocytoma or leiomyosarcoma are seen in fields and involvement of nearby structures. Additional
of radiation for a prior tumor. imaging for metastatic disease Includes CT of the
chest/abdomen and a bone scan. Further workup
EPIDEMIOLOGY involving bone marrow biopsies is dependent on the
STS make up approximately 713(, oftumors in children STS diagnosis and is required for rhabdomyosarcoma.
and adolescents, which represent approximately 700 For rhabdomyosarcoma, about 15% to 25% of newly
cases diagnosed every year in the United States. The diagnosed cases have distant metastases, with the
most common STS in children below the age of 10 lung being the most frequent site. Other sites include
is rhabdomyosarcoma. Rhabdomyosarcoma has two regional lymph nodes, bone, bone marrow, and liver.
major subtypes, embryonal (6006 to 70%) and alveolar
(20%). As. a child gets older, nonrhabdomyo.sarcomas TREATMENT
become more common. The nonrhabdomyosarcomas Treatment is quite variable depending on the diagnosis
encompass a number of different histologies such as and the stqing ofthe tumor. For rhabdomyosarcoma,
fibrosarcoma, maJJsnant fibrous histiocytoma, synovial treatment can use all three treatment modalities (sur-
sarcoma, and malignant peripheral nerve sheathtumor. gery, radiation, and chemotherapy). Complete surgical
Of notE, many ofthe STS have associated~ removal, ifpossible, is key with radiation for residual
somal abnormalities. Rhabdomyoarooma has been bulkdisease or microscopic tumor. Chemotherapy is
associated with the t(2;13) and t(1;13) translocations. used in virtually all cases to help with the reduction
Synovial sarcoma is associated with t(X;l8) translocation. of tumor size and eradication of metastases. The
duration and aggressiveness of the chemotherapy
DIFFERENT1AL DIAGNOSIS is dependent on multiple factors, includJng surgical
The difrerential diagnosis is quitE variable depending resection, histology, age at presentation, the site of
on the site of the primary tumor. Approximately34% disease, and the presence of metastases.
of rhabdomyosarcoma occurs in the head and neck, For nonrhabdomyosarcomas, treatment is depen-
23% in GU sites, and 17% in the extremities. Sites of dent on the histology, size of tumor; natural history
rhabdomyosarcoma associated with better prognosis of the tumor, and the presence of metastatic disease.
include the orbit, nonparam.enlngeal head/neck, GU Again, surgery, radiation, and chemotherapy all play
tract except bladder/prostate, and the biliary tract. important roles in the treatment.
KEY POINTS
• The leukemias account for the greatest per- immature lymphoid cells which, unlike the
centage of cases of chldhood malignancies. malignant lymphoid cells of All., BCCUTiulate
Leukemias are claaaifled on the basis of outside of the bone marrow.
leukemia cell morphology into lymphoblastic • Hodgkin lymphoma occurs mor8 commonly
leukemias or myeloid leukemias. ALL is the n adolescence and Is associated wtth a good
most common pediatric neoplasm overall and prognosis with modem therapies; however, late
Is generally associated wtth a good prosJlOSis effects of treatment .a common.
with modem therapies.
• CNS tumors .., the second most common
• NHL..s are a heterogeneous group of diseases pedia1ric mallgn.-.cy after leukemia, and the
characterized by neoplastic proliferation of most common solid tumors In children and
302 • BWEPRINTS Pedlatrtcs
adolescents. Brain tumors in children are commonly in adolescents, and often involves
predominantly lnfratentorlal, Involving the the pelVIs, femur, or rib.
cerebellum, mkl:lnlln, and brainstem. • Osteosarcoma Is a malignant tumor of the
• NBU"Oblastoma may occur in the abdomen, bone-producing cells of the mesenchyma and
thoracic cavity, or head and neck; it has a arises most often In the distal femur, proximal
widely variable presentation and biologic be- tbia, or proximal humerus during adolescence.
havior, ranging from spontaneous regression to • ~Is the mostconmon Intraocular
aggressive dissemination requiring multlmodal malignancy of chllc:h)od and may be either
therapy. sporadic or heredtt.y.
• Wilms tumor Is the most common renal tumor • Rhabdomyosarcoma Is the most common
In children, and therapy Involves surgery, che- pediatric STS and most commonly involves
motherapy, and sometimes radiation. the head and neck, GU tract, or extremities.
• Ewing sarcoma Ia an undifferentiated sarcoma
that arises primarily In bone, presents most
CLINICAL VIGNETTES
VIGNET1E1 3.. Plaleleta: 1 2,000/~tL

A 3-year-old boy is brought to the emergency de- 4.. ESR: 46 mmlh
partment (ED) for fever. According to his parents, 5.. Differential:
the fever ststed aboUt 1 week ago and has been as 10%
Neutrophils
high as 101.1°F. His fever has been accompalied by
increased fatigue. Hels less ilterested i1 playing with Lymphocytes 4296
his sister and his favorite toys. His parents report that Monocytes 5%
his appetite also seems to be decreased, but he has 1%
Eoslnophlls
not had any nausea or vomiting, nor has he lost any
weight. He was seen by his pediabician 3 days ago, Blasts 42%
who explained that he likely has a viral fever. When
This child is most likely to have which of the following?
he awoke from his nap today, he ntfused to walk on
1. AML
his own and Insisted on being carried. His pedlatrt-
cian referred him to the ED for further evaluation. You b. ALL
suspect that this child may have leukemia. c. CML
d. Chronic lymphoblastic leukemia
1. Which of the following physical examination e. NHL
findings would support this diagnosis?
L Hepatosplenomegaly 4. Which of the following would be considered a
11. Pallor poor prognostic Indicator for this patient?
.:. Bruising and petechiae L Hlsage
d. BandC b. His total WBC count
1. All of the above c. The presence of trisomies 4 and 10 in his
leukemia cells
2. Which of the following components of laboratory d. The presence of a TEUAML1 (ETV6-RUNX1)
tesmg is most likely to aid in your diagnosis? translocation in his leukemia cells
L CBC e. Refusal to ambulate
ra. Differential and peripheral blood smear
c. ESR VIGNETIE2
II.AandB A 14-year-old male haa a history of t rauma to his knee
e. All of the aboVe whHe playing football. The injury was initially traated
3.. The patient's CBC returns with the following values: conservatively with rest; however, pain has persisted,
1. WBC count: 64,000/mm' with swelling just above the knee 6 weeks later. The
2. Hemoglobin: 7.3 g/dL review of systems is otherwise negative.
1. Following a thorough history and physical ex- negative, as is the review of systems. She is on no
amination, which of the following is the most medications, and immunizations are up-to-date. She
appropr1ate next step? has an 18-month health maintenance visit scheduled
L Further obeervation, with the addition of icing with her pedlatr1clan In a week.
twice a day, compression, and elevation 1. Which of the following is the most appropriate
b. MRI next step in the evaluation of this patient?
c. Radiograph of the knee L Observation and evaluation at upcoming health
d. Referral to an orthopedic specialist maintenance visit
e. Referral to an oncology specialist b. Abdominal plain film
2. Which of the following represents the most likely c. MRI or CT of the abdomen
oncologic condition in this scenario? d. Abdominal sonography
L Leukemia a. Bone scan
b. Bone tumor (osteosarcoma or Ewing sarcoma) 2. An abdominal mass Is noted arising from or near
c. Metastasis from another site the kidney. Which two of the following are the most
d. Neuroblastoma likely oncologic causes of the mass?
a. Synovial sarcoma I. Neuroblastoma
3. Which of the following Imaging results Is most 11. Leukemia
characteristic of this condition? 111. Hodgkin lymphoma
L "Radial sunbursr pattern representing pertosteal lv. Wilms tumor
reaction and bone spicules v. Rhabdomyoearcoma
b. •Onion skin~ pattern of calcified periosteal L land II
elevation surrounding a lytic bone lesion b. landiV
c. Pathologic fracture just proximal to the tumor c. landV
d. Subluxation ofthe associated epiphyseal plate d. Ill and IV
e. Widening of the nearest joint space to more e.IVandV
t han the 95th percentile of typical findings 3. Biopsy ultimately reveals a diagnosis of neuro-
blastoma. Which of the following modalities may
VI6NET1E3 be used for treatment of this chDd?
An 18-month-old girl presents to the ED after the L Surgery
mother feels a ''lump in her belly'' during a bath. The b. Chemotherapy
child has been growing well with no acute Illnesses. c. Radiotherapy
She is eating and drinking with no emesis, and d. Autologous stem cell rescue
there is no history of trauma. Past medical history is e. All of the above
ANSWERS
count may be high, low, or normal. The differential and
VIGNETTE 1 Question 1 peripheral blood smear are also important because
1.Answer E: blasts, or circulating leukemia cells, are often seen in
Pallor, bruising, and petechiae are all common symp- the peripheral blood, especially on the blood smear.
toms of leukemia because the bone marrow cavity Is lhls profile Is consistent with a diagnosis of leukemia.
taken over by the leukemia cells, leaving It unable to ESR Is a nonspecific marker of Inflammation and Is
produce normal amounts of red blood cells and plate- not helpful In the diagnosis of leukemia.
leta. A1s the hemoglobin and platelet counts fall, the
symptoms of anemia (pallor) and thrombocytopenia VIGNETlE 1 Quastlan 3
(bruising and petechiae) become obvious. In addition, 3.Answer B:
hepatosplenomegaly is commonly seen because of 1he presence of leukocytosis, anemia. and thrombo-
leukemic infiltration. cytopenia with peripheral blasts is consistent with a
diagnosis of leukemia. Acute leukemias account for
VIGNETTE 1 Quesllan 2 97% of all childhood leukemias, with the remaining
2. AnswerD: 3% being chronic leukemias. The majority of acute
Leukemia typically presents with anemia (low hemo- leukemias are classified as ALL, with AML being lass
globin) and thrombocytopenia Oow platelets). The WBC common. ALL is more common in boys and has a peak
incidence between the ages of 2 and 5, whentaS AML •onion skin" appearance. Pathologic fractures may
does not peak until adolescence. Again, the ESR Is occur In the prasence of malignancy but typically
not helpful In the diagnosis of leukemia. Involve the tumor area. Epiphyseal plate subluxation
Is not associated with osteosarcoma, nor Is widening
VIGNETTE 1 .._..an 4 of the nearest joint space.
4.Answer 8:
Poor prognostic factors for ALL include a total WBC VIGNETlE 3 Question 1
count greater than 50,00Qimm3 , age less than 1 year 1.Answer D:
or greater than 10 years, and failure to enter remission Given the absence of radiation exposure, the rapidity
at the end of induction therapy. This patient's WBC with which the test can be obtained and interpreted,
count of 64,000/mm' places him at a higher risk for and the lack of side effects, an abdominal ultrasound
a poor outcome. The presence of trisomies 4 and 10 is the most appropriate Initial diagnostic study to
and/or a TELIAML1 (E'TV6-RUNX1) rearrangement assess an abdominal mass in a young child. Obser-
would be a favorable prognostic indicator, as would vation is inappropriate; although constipation can
the patient's age of 3 years. Refusal to ambulate is result in small"lumps• In the abdomen, the incidence
not correlated with prognosis. of serious Intra-abdominal pathology Is high enough,
and the rammcatlons potentially severe enough, that
VIGNETTE 2 Q.-tlan 1 observation alone Is not a viable option. A plain fllm
1.Answer C: may show the mass, but the overlay of other tissues
Plain films (radiographs) are quick and easy to ob- limits the detail and will not reveal fluid; if the mass
tain, with instant access to results. Radiographs are is present on examination, it is unlikely that a plain
the most appropriate initial radiographic modality to film would provide any additional information. MRI
assess persistent pain and swelling. If plain films are or CT is indicated if the ultrasound is concerning for
negative or unrevealing o.e., demonstrate the observed a pathologic lesion. Bone tumors do not present as
swelling but no associated abnormality), MAl should abdominal masses.
be considered. Although trauma is the most common
cause of limb pain in all ambulating ages, the differential VIGNETlE 3 Question 2
diagnosis includes oncologic etiologies. 2.AnswerB:
Neuroblastoma and Wilms tumor occur at this age and
VIGNETTE 2 Quesllan 2 present with an abdominal mass. Neuroblastoma Is
2.Answer 8: a tumor arising from the postganglionic sympathetic
Given the absence of systemic symptoms, Including nervous system. Most are found In the abdomen; of
fevers, weight loss, easy bruising and bleeding, and these, the majority initiate in the adrenal medulla. These
fatigue, which would support a manow infiHrative tumors tend to be firm, smooth, and nontender. Wilms
process, a bone tumor is the most likely oncologic tumor is a tumor of the kidney. Like neuroblastoma,
cause. Although trauma does not cause bone tu- the most common presentation is the presence of an
mors, affected patients often present with a history asymptomatic abdominal mass, often noticed inci-
of trauma at 1he site, presumably because trauma, dentally. Often, a parent or caretaker notes the mass.
especially mild trauma, is so common in children and Sometimes, an uHrasound will suggest a mass arising
adolescents. Leukemia tends to have more systemic from the kidney, but more precise imaging with CT
manifestations. Neuroblastoma is usually diagnosed or MRI will instead reveal involvement of the adrenal
at a much younger age. Metastasis from another site gland mora suggestive of neuroblastoma, and vice
is rare without other symptoms. Although synovial versa. Leukemia does not typically cause an abdom-
sarcoma may present this way, It Is far less common Inal mass. Hodgkin lymphoma typically presents In
than osteosarcoma or Ewing sarcoma. adolescence and Is diagnosed during an evaluation
tor persistent, rubbery cervical lymphadenopathy,
VIGNETTE 2 Q.-tlan 3 occasionally associated with fever, weight loss, and
3.AnswerA: fatigue. Rhabdomyosarcomas most often involve the
Both oateoearcoma and Ewing sarooma are more com- head and neck or GU regions or the extremities.
mon in adolescents than children, but osteosarcoma
is typically not associated with other symptoms such VIGNEnE 3 Question 3
as fever, weight loss, and fatigue. In addition, osteo- 3.Anawer E:
sarcoma usually involves the distal femur, proximal Treatment for neuroblastoma can range from observa-
tibia, or proximal humerus, whereas Ewing sarcoma tion alone for certain low-risk patients, to multimodal
tends to involve the pelvis, femur, or rib. The "radial therapy involving surgery, chemotherapy, high-dose
sunburst• pattern Is the typical radiographic finding chemotherapy with autologous stem oell rescue, and/
in osteosarcoma. Ewing sarcoma tends to have an or radiotherapy depending on the assigned risk group.
Gastroenterology
Joshua Daniel Prozialeck, Jeffrvy B. Brown, Saeed Mohammad,
Barry K. Wershil, and Bradley S. Marino
often owrlap with another, and none has a clearly

ABDOMINAL PAIN
distinct etiology. In addition to FGIDs,.functional
Abdominal pain is a common pediatric problem constipation is among the most common causes
encountered by primary care physicians and medi- of abdominal pain. Lactase deficiency may cauae
cal and surgicalsubspecialists. Chronic abdominal recurrent pain with exposure to milk sugar in dairy
pain is defined as at least three bouts of pain severe food. Inflammatory bowel disease (IBD), generally
enough to affect activities over a period of at least 3 cl.assified as either ulcerative colitis or Crohn disease,
months. Although the exact prevalence of chronic is a chronic condition often associated with diarrhea,
abdominal pain in children is not known, it appears anemia, and poor growth in which pain is a major
to account for 296 to 496 of all pediatric office visits; symptom. Celiac disefUe, an immune-mediated
approximately 1596 of middle school and high school disorder related to wheat gliadins, may present with
students experience weekly abdominal pain. In chil- abdominal pain, although anemia and poor growth
dren with typical symptoms and without objective without pain are also common manifestations. A
evidence ofan underlying organic disorder, chronic less frequent cause of intestinal inflammation is an
abdominal pain is most frequently functional. eosinophilic gastrointestinal disorder of the small
intestine or colon.
DIFFERENTIAL DIAGNOSIS Infectioua conditions (including bacterial and viral
Functional abdominal pain is now classified as a gastroenteritis) are common causes of acute abdominal
pain-related functional gastrointestinal disorder pain. Mesenteric lymphadenitis may cause persistent
{FGID}.It is a specific diagnosis that needs to be pain following an infection. Extrainteatinal infections
distinguished from anatomic, infectious, inflamma- may also cauae abdominal pain; these include group A
tory, or metabolic causes of abdominal pain. There streptococcal infections, urinary tract infections, and
is growing evidence to suggest that FGIDs may be lower lobe pneumonia&. Pelvic inflammatory disease
associated with visceral hyperalgesia, that is, a de- (PID) is an important consideration in adolescent
creased threshold for pain in response to changes in females. Infectious mononucleosis is one of several
intraluminal pressure. Functional abdominal pain may systemic infections that can cause abdominal pain.
be categorized as functional dyspepsia {discomfort Gallbladder diseases (including cholecystitis, cho-
in the upper abdomen), irritable bowel syndrome or ledocolithiasis and biliary colic), pancreatitis, gastritis,
IBS {pain associated with changes in stool consistency and peptic ulcer disease are less common in children
and defecation frequency), abdominal mignline (par-- but warrant consideration. eapeci.allywhen the pain is
oxysmal abdominal pain associated with anorexia, localized to the right upper quadrant or epigastrium
nausea, and/or vomiting), functional abdominal pain and is worsened by meals. Helicobacter pylori is a
(episodic pain not meeting criteria for other FGIDs), cause ofgastritis and ulcer disease. Abdominal pain
or functional abdominal pain syndrome (functional is a primary feature in Henoch-Schonlein purpura
pain with other somatic complaints and with some (HSP) but may also be seen in other vasculitides,
loss of function). Patients can also be diagnosed with including Kawuald disease, polyarteritis nodosa,
a combination of FGIDs. Although these entities and systemic lupus erythematosus. Pain can also
may have discrete definitions, the symptoms of one be a manifestation of sickle cell crisis.
305
Acute appendicitis is the most common sur- linear growth, gastrointestinal blood loss, significant
gical caWie of abdominal pain. lntus5Wiception is vomiting, chronic severe diarrhea, persistent right
an important pediatric disease that presents with upper or right lower quadrant pain, unexplained
intermittent but severe pain and may also manifest fever, and/or family history of IBD are generally
with striking lethargy. Incarcerated hernia, volvulus, an .indication to pursue further diqnostic testing.
bowel obstruction, and testicular torsion represent
surgical emergencies. Tn.uma can lead to significant Physical Examination
intra-abdominal injury and pain. One goal of the abdominal examination is to ascertain
Urologic obstruction at any level is an important whether the child has an abdominal process that re-
consideration. Ureteropelvic junction obstruction. quires surgical intervention. Watching the child walk,
hydronephrosis, and renal stones can cause signif- climb onto the examination table, and interact with
icant pain. Gynecologic causes are an important both parents and staff before formally examining the
part of the differential diagnosis in adolescent girls. child's abdomen helps one to gain an appreciation for
Pregnancy should alwa}'B be coru~idered, especially if the degree ofincapacitation or emotional overlay that
symptoms are consistent with an ectopic pregnancy. may be present. The abdomen should be inspected,
Dysmenorrhea, ovarian cysts, mittelschmerz, PID, auscultated, and palpated. Peritoneal signs include
cervicitis, endometriosis, and ovarian or adnexal rebound tenderness, guarding, psoas or obturator
torsion are all potential problems in this population. signs, and rigidity of the abdominal wall Right lower
Psychiatric causes ofabdominal pain are WlCOm- quadrant tenderness requires the consideration of
mon in children. True malingering is UDUllual, as are appendicitis. Rectal skin tags or fistulae may suggest
conversion disorders. However; many children do the diagnosis ofCrohn disease. Unless the diagnosis
experience abdominal pain in the setting of stress, is thought to be uncomplicated viral gastroenteritis,
especially in the context of schooL and abdominal a rectal examination is most often indicated to detect
pain also can be seen in children with depression. tenderness or hard stool and to obtain stool for occult
Although children with chronic abdominal pain and blood testing. Ifthe patient is an adolescent female,
their parents are more often anxious or depreoed, a pelvic examination is often indicated as part ofthe
the presence ofanxiety, depression. behavior prob- appropriate evaluation. Cervical motion tenderness
lems, or recent negative life events is not useful is consistent with PID.
in distinguishing between functional and organic The examination of children with functional
abdominal pain. Nonetheless, inquiry into recent abdominal pain is often devoid of positive physical
social changes in the family unit or at school may findings. Alarming signs on abdominal examination
provide great insight into the etiology of the pain. include localized tenderness in the right upper or
right lower quadrants, a localized fullness or mass
CLINICAL MANIFESTATIONS effect, hepatomegaly, splenomegaly, costovertebral
HlstDry angle tenderness, tenderness over the spine, and
The history should 1ocaJ.ize the pain and determine perianal abnormalities.
its quality, temporal characteristics, and exacerbating
and alleviating factors. With "inffammatory" pain, the DIAGNOSTIC EVALUATION
child tends to lie stilL whereas with •colicky" pain, The diagnostic test strategy is dictated by the history
the child cannot remain still. Colicky pain usually and findings on the physical examination. Surgical
results from obstruction of a hollow viscus. It is consultation should be sought ifthere is concern for
important to ascertain whether the child has had appendicitis, volvulus, testicular torsion. or other
previous abdominal surgery; with a history of pre- conditions requiring urgent surgery. A complete
vious laparotomy, small bowel obstruction becomes blood count with di.ffe.rentia]. serum electrolytes
more likely. Pain may be accompanied by anorexia. and chemistries, amylase, lipase, stool hemoccult
nausea, emesis, diarrhea. or constipation. Ifthe pain examination. urinalysis, and radiographic studies
wakes the chlld at night, an organic cau.se is more should be performed if there has been abdominal
Ulcely, but nighttime pain does not exclude functional trauma or ifan acute surgical condition is suspected.
disorders. Both bilious emesis and nonbilious emesis Blood type should be determined for possible
maybe seen in small bowel obstruction. The presence transfusion if bleeding is a pm~enting feature. An
of alarming symptoms or signs including, but not ultrasound. computed tomography (CT) scan, or
limited to, involuntary weight loss, deceleration of magnetic resonance imaging (MRI) may be useful
Chapter 14 I Gastroenterology • 307
when appendicitis is being considered. When Wl- frequently in children between 10 and 15 years ofage.
complicated viral gastroenteritis is the most likely Less than lQCJt. of patients are younger than 5 years.
cause and the child is well hydrated, no studies need
to be performed, but ifbacterial enterocolitis ia being CLINICAL MANIFESTATIONS
considered because of the presence of blood. travel Oassically, fever, emesis, anorexia, and diffuse
history, or Wcontacts, stool should be obtained for periumbilical pain develop. Subsequently, paln. and
culture. Group A streptococcal pharyngitis and PID abdominal tenderness localize to the right lower
require appropriate cultures. To diagnose a urinary quadrant as the parietal peritoneum becomes
tract infection, a urinalysis and urine culture should be inflamed. Guarding, rebound tenderness, and ob-
performed. Screening for celiac disease is performed turator and psoas signs are commonly found. The
with serologic screening studies. The most sensitive appendix tends to perforate approximately 36 hours
and specific tests include tissue tt'anJglutaminase IgA after pain begins. The incidence of perforation and
and endomysiallgA antibodies. Current confirmatory diffuse peritonitis is higher in children younger than
testing for celiac disease requires an upper endoscopy. 2 years, when diagnosis may be delayed. Atypical
Screening for IBD ia best performed by history and presentations are common in childhood. especially
physical examination, but a complete blood count with retrocecal appendicitis, which may present with
(CBq and erythrocyte sedlm.entation rate (ESR) or periumbilical pain and diarrhea. Retrocecal appen-
C-reacti.ve protein (CRP) may be helpful screening dicitis usually does not induce right lower quadrant
tools. Increasingly, focal calpmtectin is being used pain until after perforation. Bacterial enterocolitis
as a screening test for intestinal inflammation, caused by Campylobacter and Yersinia species may
especially when diarrhea is present, but this test is mimic appendicitis because both can result in right
neither perfectly sensitive nor specific for mD. Higher lower quadrant abdominal pain and tenderness.
specificity for IBD is achieved when the level is >250 Diagnosis ofappendicitis is established clinically by
Jlg/g. In many cases, especially when functional pain history and by physical examination, which should
is thought to be the cause of the pain, less diagnos- include a rectal examination to detect tenderness
tic testing may be more helpful than more testing. or a mass. A moderately elevated white blood cell
This will enable the focus to remain on appropriate count with a left shift is often seen in appendicitis.
treatment strategies. A plain film of the abdomen may demonstrate a
fecaljth. An inflamed appendix may be noted on
TREATMENT ultrasound or CT, which are imaging modallties
Treatment is directed at the underlying cause of the often used to evaluate patients with suspicion of
pain. Infections may require antimicrobial therapy. acute appendicitis.
Lactase deficiency and celiac disease improve with
specific dietary intervention. Constipation is well TREATMENT
treated with laxatives and a bowel rehabilitation plan. Laparotomy and appendectomy should be performed
Diagnostic trials ofhistamine-2 receptor antagonists before perforation. When appendicitis results in per-
or proton pump inhibitor therapy may be very helpful foration, the patient should be given broad~spectrum
when considering esophagitis, gastritis, duodenitis, antibiotics (e.g., ampicillin, gentamicin, metronidazole.
or nonulcer dyspepsia. Functional abdominal pain is or piperacillin/tazobactam monotherapy) to treat
best treated with a biopsych.osocial model. Medical peritonitis from intestinal flora. The mortality rate
treatment for FGIDs might include acid reduction rises significantly with perforation.
therapy for pain associated with dyspepsia. antispas-
modic agents, low dosages of tricyclic psychotropic
INTUSSUSCEPTION
agents, or nollltimulating laxatives or antidiarrheals.
Intussusception results from telescoping ofone part
of the intestine into another. Intussusception causes
APPENDICITIS impaired venous return, bowel edema, ischemia,
Appendicitis is the most common indication for necrosis, and perforation. It is one ofthe most com-
abdominal surgery in childhood. Appendicitis results mon causes of intestinal obsnuction in infancy. Most
from bacterial invasion of the appendix. which is more intussusceptions are ile ocolic; the ileum invaginates
likely when the lumen is obstructed by a fecalith, into the colon at the ileocecal valve. Previous viral or
parasite, or lymph node. Appendicitis occurs most bacterial enteritis may cause hypertrophy of the Peyer
patches or mesenteric nodes, which are hypothesized DIFFEREN11AL DIAGNOSIS

to act as the lead point in intussusception. A specific Table 14-llist:s the most common causes ofvomiting
lead point is identified in only 5% ofcases but should in infants and children.
be sought in neonates or in children older than 5
years. Recognizable lead points in intussusception
include Meckel diverticulwn, an intestinal polyp, TilLE 1._1. Differential Diagnosis of Vomiting in
lymphoma, or a foreign body. Intussusception has Children
also been associated with HSP; in this setting, it is lnf8ctloul
usually Ueo-ileal. It can be very difficult to distin-
Vual. gastroenteritis, e.g., Rotavinls and Norovinu
guish HSP complicated by intussusception from the
inflammatory abdominal pain seen in simple HSP. Bacterial enterocolitia/sep8ia
Hepatitis
CLINICAL MANIFESTATIONS Food poisoning
Violent episodes ofirritability, colicky pain. and emesis Pelvic J.nBammatory dlseue
are interspersed with relatively nonnal periods. Rectal
Peritonitis
bleeding occurs in 80% of patients but leu commonly
in the form of the classic "currant jelly" stools (stools Pharyngitis/toDJillitis
containing bright red blood and mucus). The degree of Pneumonia
lethargy shown by the child may be striking. A tubular Otitis medt.a
mass is palpable in approximately 80% of patients. A Urinary tract infection
plainabdominal film may showa paucity ofgas in the
right lower quadrant or evidence of obstruction with Metabolic
air fluid levels. An ultrasound examination is the gold Diabetic btoacidoaia
standard for diagnosing intussusception. A contrast Inborn erron of metabol.lam
enema or air enema, which often proves therapeutic Addisonian crisi.s/adrenal insufficiency
as well as diagnostic, demonstrates a characteristic
Reye syndrome
"coiled spring" appearance to the bowel.
OIIJtJr
TREATMENT Ureteropelvic junction obltrw:tion
Fluid resuscitation with normal saline or lactated Hepatic failure
Ringer solution is usually necessary. Hydrostatic Congest:m heart failare ex peri<:arditis
reduction with a contrast enema or pneumatic
Lead poisoning
reduction with an air enema is successful in 75% of
cases if performed in the first 48 hours. Peritoneal Munchausen syndrome and Munchauaen l)'lldrome
signs are an absolute contraindication to this proce- by proxy
dure. Laparotomy and direct reduction is indicated CeniJII Nervous Sysfsm
when reduction by enema is either unsuccessful or lncrealed intracranial pressure
contraindicated. The immediate recurrence rate is Ventricular--peritoneal shunt malfunction
approximately 15%. When a specific lead point is
MeniDgltls
identified. the recurrence rate is higher.
Encephalitis
Labyrinthitis
EMESIS
Migraine
Vomiting is one of the most common presenting Seizure
symptoms in pediatrics and can be caused by both
Th.mor
gastrointestinal (GI) and non-Gl pathologies. Compli-
cations ofsevere, persistent emesis include dehydration GynllciJJoiJic
and hypochloremic, hypokalemic metabolic alblosis. Pregnancy
Forceful emesis can result in a Mallory-Weiss tear ~Jnlint
of the esophagus at the gastroesophageal junction Gutroeloph.,.W reflux
or erosion of the gastric cardia; chronic emesis can
result in distal esophagitis. Cow's or eoy milk protein Intolerance
TilLE 14-1. Differential Diagnosis of Vomiting in
Children (continued) HlsiDry
In infants, the history should differentiate between
Bowel obatruction
b.'Ue vomiting (forceful expulsion ofgastric contents)
Duodenal atresia and effortless regurgitation ("spitting up"). The latter
Pyloric mnosil is often due to gastroesophageal reflux. Frequency.
Malrotatioo with or without volvulua- appearance (bloody or bilious), amount, and tim·
ing of emesis are important. Emesis shortly after
Incarceratecl hernia
reeding in the infant is probably gastroesophageal
lntu.aulception reflux. If the emesis is projectiJe and the child is 1
Mecbl diverticulwn with toraion to 3 months of age, pyloric stenosis must be con-
Hinchspruns diaeue sidered. Poor weight gain and emesis may indicate
~Child
pyloric stenosis or a metabolic disorder. Macrolide
antibiotics are known to cause emesis and diarrhea;
Appendicitis
chemotherapeutic agent& and some toxic ingestions
i Eosinophilic esophagitis/gutroenteritis cause emesis. Ifthe child has a ventriculo-peritoneal
i Pancreatitis shunt, vomiting may be a sign of shunt obstruction
I Hepatitis and increased intracranial pressure. Emesis with sei-
i Cholecystitis zure, headache, or both may indicate an ln.tracranial
process. Diarrhea, emesis, and fever are seen with
~ Cyclic vomiting syndrome gastroenteritis. Fever. abdominal pain, and emesis are
IB~ obstruc:tion typical for appendicitis, whereas bilious emesis and
I Malrotatioo with or without volvulua abdominal pain are seen with intestinal obstruction.
Emesis and syncope may result from pregnancy.
Intussusception Physical Examination
Mecbl dlverticulwn with torsion On physical examination, the initial assessment should
AdheUons
focus on the child's vital signs and hydration status.
Chapter 5 discusses signs and symptnms ofdehydra-
Superior maenteric: artery syndrome
tion. A bulging fontanelle (in infancy) or papilledema
Posttraumatic obstruction" implicates increased intracranial pressure as the
: RespinltDty cause ofthe emesis. Emesis is common in infectious
!Posttuslive emelil pharyngitis. The lung fields should be auscultated
for cracldes or an asymmetric examination to rule
I Reactive airway .syndrome out pnewnonia. Emesis and vaginal discharge in
i MtJtllutJonl the female adolescent warrant a pelvic examination
IChemotherapeutic agents to evaluate for PID. The abdominal examination
! Cancer chemotherapy should focus on bowel sounds and the presence of
IDisoxin and other can:Uac drugs distention, tenderness, or masses. Hypoactive bowel
sounds may indicate ileus or obstruction, whereas
IAntibiotics, e.g., erythromycin hyperactive bowel sounds suggest gastroenteritis.
!Theophylline Abdominal mass with emesis may indicate intuSSU5-
ICaustic agents ception or malignancy. Tenderness on examination is
! Ipecac suggestive ofappendicitis, pancreatitis, cholecyBtitis,
~ EmotkJniii/IJnWtnl peritonitis, or PID.
IPsydwpnic DIAGNOSTIC EVALUADON

l Bullmla Specific laboratory studies depend on the suspected
I Rumination cause. Appropriate cultures, a complete blood count,
i "Malrotation with or without volvulus Ia much more lkely In an and serum electrolytes may help determine the cause
i Infant than In a child. ofvomiting and the metabolic complications secondary
!bf:rom duodenal hematoma, ruptured vi9Cus.
:,,,,,._,,.,.,,,,,.,,.,,..,., ...,.,,.,,.,.,,._.,.,.,, ,.,,.,....,,,.,.,,,,,,,,,,,,.,,,,,,,,,,,,,uoooooooooooooooooooooooooooo•••••••••••••••ooi to vomiting. A chest radiograph will help rule out
pneumonia. Ifa surgical process within the abdomen waves may be seen. lntrasonography reveals the
is considered, upright and supine abdominal films hypertrophic pylorus. Upper GI study may .show
should be obtained, along with a complete blood. the classic •string sign!"
count and chemistry panel. Amylase and lipase are
elevated in pancreatitis. Ifvomiting is prolonged or 1REA1MENT
the patient Is slgnificantly dehydrated, electrolytes Initial treatment involves nasogastric tube place-
will help guide replacement therapy. Ammonia levd, ment to decompress the stomach and correction of
lactate, pyruvate, serum amino acids, and urine dehydration, alkalosia, and electrolyte abnormalities.
organic acids should be sent if metabolic disease is Pylorom}'Otomy should take place after the metabolic
suspected. Urinalysis and urine culture should be anomalies are corrected.
obtained to assess the degree of dehydration and
rule out urinary tract infection.
MALROTATION AND VOLWLUS
TREATMENT Malrotation occurs when the small intestines rotate
Ifthe cause appears to be a self-limited nonsurgical abnormally in utero, resulting in malposition in the
infectious process (viral gastroenteritis or bacterial abdomen and abnormal posterior fixation of the
enterocolitis), and if the patient Is not signlftcantly mesentery. When the intestine attaches improperly to
dehydrated, outpatient therapy is indicated. Oral the mesentery, it Is at risk for twisting on its vascular
rehydration therapy (ORT), discussed in Chapter 5, supply; the twisting phenomenon is called volvulus.
is recommended for dehydrated infants. For older This condition has ita most common presentation
children. fluids should be encouraged. with advance- in the newborn period and is a surgical emergency.
ment to a regular diet as tolerated. Children who
are severely dehydrated or are unable to effectively CLINICAL MANIFESTATIONS
hydrate themselves orally should be admitted to the The history almost always includes bilious emesis,
hospital. A surgical consultation should be obtained and, in older children, a history of past attacks
ifindicated. lfventricu1o-peritoneal shunt malfunc- of bilious emesis is occasionally elicited. Physical
tion is a possibility, the standard ofcare dictates that examination may reveal abdominal distention or
a CT of the head and a shunt series be obtained in shock. Blood-stained emesis or stool may be noted.
tandem with a neurosurgical consultation. Abdominal radiographs typically show gas in the
stomach. with a paucity of air in the intestine. An
upper GI series with small bowel follow-through
PYLORIC STENOSIS confirms the diagnosis by illustrating the abnormal
Pyloric stenosis is an important cause ofgastric outlet position of the ligament ofTreitz and the cecum. A
obstruction and vomiting in the first 2 to 3 months of positive stool test for blood may indicate significant
life. The most common age of presentation is 2 to 4 bowel ischemia. Unexplained lactic acidosis may be
weeks oflife, with an inddenoe oflin 500 infants. Male an important sign of intestinal ischemia.
inf'anb; are affected 4:1 over female infants, and pyloric
stenosis occurs more frequently in infants with a fiunily TREA1MENT
history ofthe condition. Current evidence suggests that Operative correction of the malrotation and the
erythromydn therapy may precipitate pyloric stenosis. volvulus should be undertaken as soon as possible
because bowel ischemia, metabollc acidosis, and
CLINICAL MANIFESTATIONS sepsis can progress quickly to death.
Projectile nonbilious vomiting is the cardinal reature
ofthe disorder. Physical findings vary with the sever-
GASTROESOPHAGEAL REFLUX
ityofthe obstruction. Dehydration and poor weight
gain are common when the diagnosis is delayed. Gtutroesophageal reflux (GER), defined as the passage
Hypokalemic, hypochloremic metabolic alkalosis ofgastriccontents into the esophagus, and GER dJsetue
with dehydration is seen secondary to persistent (GERD), defined as symptoms or complications of
emesis in the most severe cases. The classic finding GER, are common pediatric problems. Clinical man-
ofan olive-sized, muscular, mobile, nontender mass ifestations ofGERD in children include regurgitation.
in the epigastric area occurs in most cases but may poor weight gain, dysphagia. abdominal or substernal
be difficult to palpate. VIsible gastric peristaltic pain,. esophagitis, and respiratory disorders.
DIFFERENTIAL DIAGNOSIS such as Crohn disease and eosinophilic or infectious

If the infant is having forceful emesis, projectile esophagitis in older children. Eosinophilic esophagitis
vomiting, or retching, then aimple reflux is not the (EoE) does not respond to antacid therapy and may
most likely cause, and the differential diagnosis for be a cause of poorly responsive reflux symptoms. A
emesis should be broadened (see Table 14-1). In characteristic endoscopic appearana. with furrowing
the infant with recurrent regurgitation. a thorough and white exudate, and biopsy with>15 eosinophils
history and physical examination. with attention to per high-power field is diagnostic for EoE. A normal
warning signals, is generally sufficient to allow the appearance ofthe eaophagus during endoscopydoes
clinician to establish a diagnosis of uncomplicated not exclude GER. A trial of time-limited medical
GER (the "happy spitter•). therapy for GER is useful for determining if GER is
causing a specific symptom.
Hls1ory TREATMENT
The diagnosis ofGER is often clinical. based on typ- Diet and Ufestyle Changes
ical symptoms and the lack of signs and symptoms Esophageal pH monitoring has demonstrated that
of other disorders. Infants typically have effortless infants have significantly less GER when placed in the
regurgitation as opposed to retching and vomiting. prone position than in the supine position. However,
Adolescents are more likely to have typical heart- prone positioning is associated with a higher rate
burn than yoWlS children and i.n&.nts. Upper airway of sudden infant death syndrome (SIDS). In infants
symptoms may occur, although there are limited from birth to 6 months of age with GERD, the risk
data to link reflux to hoarseness, chronic cough, of SIDS generally outweighs the potential benefits
sinusitis, otitis media, and visible irritation of the of prone sleeping. In children older than 1 year, it is
larynx. Reflux is not a common cause ofirritability, Ukely that there is a benefit to left-side positioning
unexplained crying, or distress in otherwise healthy during sleep and elevation of the head of the bed.
infants, and treatment with histamine type-2 recep- There is evidence to support a l-to-2-week trial
tor antagonists or proton pump inhibitors will not of a hypoallergenic formula in formula-fed infants
improve these symptoms despite raising the gastric with regurgitation. Milk-thickening agents do not
pH. Most apparent life-threatening events (ALTE.s; improve reflux index scores by pH monitoring but
now called BRUEs for "brief resolved unexplained do decrease the number of episodes of vomiting.
eventsj are not related to GERD. Children and adolescents with GERD should avoid
identified food triggers. While these may be individ-
Physical EXamlna11on ualized on the basis of history, caffeine, spicy foods,
In most cases, the physical examination of the child and high-fat foods that delay gastric emptying may
with GER is normal In severe cases, infants present provoke symptoms. Obesity, exposure to tobacco
with poor weight gain or failure to thrive. smoke, and alcohol are also associated with GERD.
DIAGNOSTIC EVALUATION Medications

In most infants with vomiting, and in most older Histamine type-2 receptor antagonists (H2 RAs) pro-
children with regurgitation and heartburn, a history duce reliefofsymptoms and mucosal healing in older
and physical examination is sufficient to reliably children and adults. Proton pump inluoitors (PPis),
diagnose GER, recognize complications, and initiate the most effective add-suppressant medications, are
management. The upper gastrointestinal (Gn series superior to H2 RAs in relieving symptoms and healing
Is neither sensitive nor specific for the diagnosis of esophagitis in children and adults. Although a brief
GER, but impedance manometry with esophageal therapeutic trial may be indicated, in infants with
pH monitoring is useful to establish the presence of GER, it is not evident that treatment with either H2
abnormal add reflux, determine ifthere is a temporal RA or PPI therapy results in symptomatic improve-
association between add reflux and frequently occur- ment, and they may increase the risk of pneumonia
ring symptoms, and aaseaa the adequacy oftherapy in and some gastrointestinal infections. There are also
patients who do not respond to treatment with acid concerns for adverse effects acid-suppression ther-
suppression. Endoscopy with biopsy can assess the apy could have on the developing intestinal flora.
presence and severity ofesophagitis, strictures, and Therefore, chronic use of these medications is not
Barrett esophagus, as well as exclude other disorders recommended unless clearly indicated.
Surglcal111wapy
TMLE 14-2. Differential Diagnosis at Diarrtlaa in
Case series indicate that surgical therapy generally
Children
results in favorable outcomes, but this intervention
should be restricted to patients who fail medical ther- : Acuts Dl8trll6l
apy, have intractable pain, neurologic impairment, !lntBBtlnll/lnfedlons
recurrent bleeding. or aspiration. The potential risks, !Viral. e.g., rot:avlrul, norovirua, adenovirua,
benefits, and costs of successful prolonged medical iutrovirul
therapy versus fundoplication have not been well l Bacterial, e.g., Sh~Ua, Salmonella, Campylobacter,
studied in infants or children in various symptom ~ diarrheagenic.&chuichia coli (0157:H7,
presentations. ~ enteroaggregative, and others), Yersinia, Cloltridium
1tlljfidle, Vlbrio spp, e.g., V. clwlertze, poutbly
DIARRHEA
IAeromoNU spp, PlulomoNU spp
l Parultlc, e.g., Giardia, Ct"Jpwaporltlllml, Enttunoeba
Diarrhea is defined as an increase in the frequency ihi&tolytia
and the water content of stools. VU'al gastroenteri- ! Nonlnflct1oul
tis is the most common cause of acute diarrheal i! Intussusception
illness throughout the world. The complications
of acute diarrhea include dehydration, electrolyte
i Appendicitis
and acid- base disturbances, bacteremia and sepsis, ~ Osmotic diarrhea. Le., hyperconcentrated Infant
1fommla, medk:ations, disa<:cluuidue deftdenc:y
and malnutrition in chronic cases. Enteritis refers
to small bowel inflammation, whereas colitis refers
! (acute)
to large bowel inflammation. l Toxic ingestion: Iron. mercury, lead. fluoride
! ingestion
DIFFERENTIAL DIAGNOSIS IAntibiotics, chemotherapeutic agents
Table 14--21i.sts the most common causes ofdiarrhea : Chtt1nic DilnfleB
in the pediatric population in developed countries. : lmmunod6llcJtnc
CLINICAL MANIFESTATIONS i Acquired immunodeficiency
History l Congenital immunodeficiency
The history should ascertain whether the diarrhea ~ lnf8ctloul
i5 acute or chronic/recurrent and should establi5h
the frequency and appearance of the stools (bloody
i c. cftJi:ite
with mucous, or watery). Dietary indiscretions and

l Parultea, e.g., Gitutlt., CryptMporidlum
manipulations may result in diarrhea. Small infants i GaslrrJiniJ1stiMJ
have diarrhea when they are fed concentrated formula ICow's/fQy milk intolerance
and certain fruit juices; for example, apple and pear IUlcerative coUtis
may cause toddler's diarrhea. Weight loss or lack of i Crohn cllileue
weight gain in association with diarrhea indicates
more severe disease. Certain medications, especially
ILactase or sucrase defidency
antibiotics and chemotherapeutic agents, may cause !Irritable bowel syndrome
diarrhea. Vll'lll and bacterial gastroenteritis are both !Encopresis with overflow incontinence
highly contagious, and so sick contacts are likely.
Clostridium di.Jiicile infection was previously almost
IExceuive fruc:to.e or sorbitol intake
always associated with antibiotic therapy, especially in
i Pancreatic insufficiency, e.g., cystic fibrosis
hospitalized patients. However, community-acquired !Celiac disease
C. difficik infection without antecedent antibiotic !Neuroendocrine tumor
therapy is now recognized as common. Unfortunately, iAUQy
relapses of C. dijjicUe infection are common, occurring
in 1596 to 3~ of patients. Test ofcure i1 not indicated
IFood allergies
j Eoainophilic p.strointzstinal diJorders
but symptomatic illness within 14days of completion
of treatment is often indicative ofa recurrence and I IPWcu8tll
should be reinvestigated. Recurrence requires either !..!:.!~:~.~.~-.................... ............. . ...... . ... . . . .......:
retreatment or a change in therapeutic approach with reduce the likelihood of hospitalization when rotaviral
prolonged treatment (taper therapy), pulse therapy, illness oCCUl'S. When a child has mild-to-moderate
probiotics, intravenous immunoglobulin therapy, or diarrhea, continued use of the child's preferred, usual.
fecal microbiota transplantation. and age-appropriate diet should be encouraged to
prevent or llmlt dehydration. Regular diets are gen-
Physical Examination erally more effective than restricted and progressive
Chapter 5 discusses signs and symptoms of dehy- diets, and in numerous trials have consistently pro-
dration, which are critical in the evaluation of a duced a reduction in the duration of diarrhea. The
patient with diarrhea. An attempt should be made to historical BRAT diet (consisting of bananas, rice,
determine the degree of dehydration to guide ther- applesauce. and toast) is unnecessarily restrictive,
apy. The abdominal examination focuses on bowel but may be offered as part of the chlld's usual diet.
sounds and the presence ofdistention, tenderness, or Cear liquids are not recommended as a substitute
masses. Hypoactive bowel sounds point to intestinal for oral rehydration solutions (DRS) or regular diets
obstruction. Hyperactive sounds are consistent with in the prevention or therapy ofdehydration. The vast
gastroenteritis. Abdominal mass with diarrhea could majority of patients with mild-to-moderate AGE do
indicate intu.uusception or malignancy. not develop clinically important lactose intolerance
and do not need to be mllk restricted. In selected
DIAGNOSTIC EVALUATION patients with documented, persistent clinical lactose
When evaluating a child with diarrhea, inspecting intolerance, lactose-free formulas are recommended.
the stool is critical to evaluation and formulation of The vomiting child should be offered frequent small
a treatment plan. Ifthere is a history ofblood and/ feedings (every 10 to 60 minutes) of any tolerated
or mucous in the stooL if the child needs hospital- foods or ORS. Dehydration should be treated with
ization, or if the chlld 1s younger than 3 months of ORS, for a period of4 to 6 hours or until an adequate
age, bacterial cultures should be obtained. Rapid degree of rehydration is achieved. When the care
tests for rotavirus and norovirus are available; provider is unable to replace the estimated fluid
however, laboratory tests need not be routinely deficit and keep up with ongoing losses using oral
performed in children with signs and symptoms of feedings alone, or the child is severely dehydrated
acute gastroenteritis. Serum electrolytes are some- with an obtunded mental status, IV fluids or NG ORS
times useful in assessing children with moderate to should be given for a period of 4 to 6 hours or until
severe dehydration who require intravenous (N) adequate rehydration is achieved. It is appropriate
or nasogastric (NG) fluids. A normal bicarbonate to involve the family in the decision regarding the
concentration may be useful in ruling out or char- method offluid replacement. Refeeding of the usual
acterizing dehydration. For persistent diarrhea, the diet should be started at the earliest opportunity
diagnostic evaluation should proceed in a stepwise after an adequate degree of rehydration is achieved.
fashion. including a complete blood count and stool Following rehydration therapy in the chlld. with
tests for bacterial pathogens (including C. dq]icile mild-to-moderate dehydration. regular diets may be
and common parasitic pathogens, i.e., Giardia and supplemented with ORS containing at leut 45 mEq
Crypt:osporidium). Subsequent evaluation for chronic Na../L, and targeted to deliver 10 mL/kg for each
diarrhea may include tests for immunodeficiency, stool or emesis. It is important to reassess hydration
pancreatic insufficiency, celiac disease. and the like, status by phone or in the office when a chlld refuses
as approprJate. Persistent dJarrhea may complicate ORS. This can be a sign of severe lllness, or refusal
acute diarrhea in infants, especially when there is may indicate an absence ofsalt craving, and, as such,
preexisting undernutrition. resolution of dehydration. Antidiarrheal agents and
antiemetics are not recommended for the routine
TREATMENT management of children with AGE. Certain pro-
Acute gastroenteritis (AGE) 1s usually self-llmlted. biotics, in particular Lactobacillus GG, have been
However, the goals of treatment are primarily pre- shown to decrease the duration of rotaviral and
vention and/or management ofdehydration and sec- nonrotaviral diarrhea. Ondansetron may decrease
ondarily improvement ofsymptoms, the latter being vomiting and hospitalization rates in those patients
an appropriate concern of the family. Immunization who require IV or NG fluids. It is recommended that
with rotavirus vaccine is an important approach antimicrobial therapies be used only for selected
to llmlt severe diarrhea. prevent dehydration. and children with AGE who present with special risks or
evidence ofa serious bacterial infection. The infant overflow diarrhea resulting from leabge around the
with salmonellosis represents just such a special case. fecal mass, anal fissure, rectal bleeding, and urinary
If the stool culture is positive for salmonella and tract infection caused by extrinsic pressure on the
the infant is afebrile and does not appear toxic. the urethra. Encopruis, which is daytime or nighttime
infant can be reexamined and observed at home. If soiling by formed stools in children beyond the age
the stool culture is positive and the infant is febrile, of expected toilet trai.ning (3 to 5 years), is another
the infant's age determines therapy: complication ofconstipation. In older children, it is
important to ask specifically about soiling because
• The .infant younger than 3 months should be
such information may not be expressed because of
admitted to the hospital; a blood culture is ob-
embarrassment. These children are unable to sense
tained, and intravenous antibiotics started. A
the need to defecate because of stretching of the
lumbar puncture and urinalysis should also be
internal sphincter by the retained fecal mass. Non-
considered in this age group.
functional etiologies of constipation are delineated
• The infant older than 3 months should be admitted
in Table 14-3.
to the hospital; a blood culture should be sent, but
antibiotics may be withheld pending the results CLINICAL MANIFESTATIONS
of the blood culture.
• Any infant with a positive stool culture who looks
Abdominal pain caused by constipation is often
toxic or has a positive blood culture should be
diffuse and constant. The pain may be accompa-
admitted for intravenous antibiotics and evalu-
nied by nausea, but vomiting is unusual. Stools are
ation for pyelonephritis, meningitis, pneumonia,
hard. difficult to pass, and i..nfrequent. Discussion of
and osteomyelitis.
withholding behavior (•potty dancej can be helpful
Treatment for C. dljflctle involves enteral therapy in identifying functional etiologies of constipation.
with metronidazole or vancomycin. Vancomycin An organic cause of constipation (cystic fibrosis,
may be somewhat more effective but is much Hirschsprung disease) is more l.ikel.y in a patient who
more expensive. Fidaxomicin is another treatment did not pass meconium in the first 24 to 48 hours
option. Giardia lmnblia and Crypttnporidium are oflife. Fmdings that suggest concern for an organic
also common causes of persistent diarrhea and, if etiology of constipation include failure to grow,
found. treatment is available with metronidazole or pilonidal dimple covered with a tuft of hair., absent
nitazoxanide. anal wink, tight empty rectum in the presence ofa
palpable fecal mass, anteriorly displaced anus, and
decreased lower extremity tone or strength.
CONSTIPATION
Constipation is defined as the infrequent passage DIAGNOSTIC EVALUATION
ofhard stools. Constipated infants fail to empty the Most often no diagnostic studies are needed. Ifthe
colon completely with bowel movements and over diagnosis is unclear, a plain abdominal film can be
time stretch the smooth muscle of the colon, resulting helpful because a colon full offeces supports a diag-
in a functional Ueus. In contrast to constipation, ob- nosis ofconstipation. Thyroid studies, including free
stipation is the absence of bowel movements. Beyond T,. and thyroid-stimulating hormone (TSH) levels,
the neonatal period, the most common cause (90% are indicated if hypothyroidism is suspected. Ifhy-
to 95%) ofconstipation is voluntary withholding or pokalemia or hypocalcemia is a potential cause, an
"functional• constipation. Intentional withholding electrolyte and chemistry panel may be obtained. A
is often noted from the very beginning of toilet rectal mucosal biopsyis required to make the diagno.&is
training. A family history ofsimilar problems is often of Hirschsprung disease; anorectal manometry can
obtained. Stool retention may be caused by conflicts also be diagnostic. An elevated lead level implicates
in toilet trainiJ18 but is usually caused by pain on plumbism as the cause of constipation.
defecation, which creates a fear of defecation and
further retention. Voluntary withholding of stool 1REA1MENT
increases distention of the rectum. which decreases The general approach to the child with functional
rectal .sensation, necessitating an even greater fecal constipation includes the following steps: determine
mass to initiate the urge to defecate. Complications whether fecal impaction is present, treat the impaction
ofstool retention include impaction, abdominal pain, if present, initiate treatment with oral medication,
lactulose, and sorbitol seem to be equally efficacious,

TABLE 1W. Etiologies af Nonfunctional Constipation
the choice among these is based on safety, cost, the
~ Psyr:/laloflc child's preference, ease of adm.i.nistration, and the
~ • Dymmctional toilet training
practitioner's experience. A behavioral program of
1 • Sexual abuse
dally toilet sitting after meals and positive reinforce-
1~ ment is often helpful in structuring the approach
i• Low-ftber ciJet for the family.
1 • ~ flufdlntake
While dietary changes are anticipated by fam-
: llrtBstiMI ilies as part of the treatment plan, no randomized
1 • Jleua
controlled studies have demonstrated an effect on
!! • Hir&cluiprung diJeue
,..._,, __ _., __a•• stools of increasing intake of Bulds, nonabsorbable
l• ~UIAC IRii
carbohydrates, or dietary fiber in children. Forceful
i • Anal stenosis
!
j • Rectal abscess or fiuure implementation of diet is undesirable. The education
! • Stricture following necrotizing enterocolitis ofthe family and the demystification ofconstipation,
1• eollagen vucu1ar disease including an explanation of the pathogenesis ofcon-
i Dtugr Of lbKIM stipation, are important steps in treatment. Providing
j • Lead hope to a frustrated famlly is key. If fecal soiling is
j • Narcotica present, an important goal for both the child and
!• Phenothiazine~ the parent is to remove negative attributions. It is
i• Vincrlstine especially important for parents to understand that
: • Ant:ichol.l.nergica soiling from overflow incontinence is not a willful
~ lltJutumurlcull and defiant maneuver.
i • MeninJomyelocele
i• Tethered cord
j • Infant botulism HIRSCHSPRUNG DISEASE
j • AbRnt abclomlnall!Ulldes (prune belly Hirschaprung disease, or congenital aganglionic
i 1}'1\drome) megacolon, occurs in 1 in 5,000 children and re-
I• Pseudoobmuction sults from the failure of the ganglion cells of the
j .,.,.,. myenteric plexus to migrate down the developing
l• Hypokalemia colon. As a result, the abnormally innervated distal
l• Hypercalmmla colon remains tonically contracted and obstructs the
!Endoctfnf flow of feces. Hirschsprung disease is three times
! • Hypothyroidism more common among boys and accounts for 20%
! Othtr of cases of neonatal intestinal obstruction. In 75%
! • Cystic 8brom
:oooo••••oooooooooooooooooooooooooooooooOooooooooooooo~oooooooooooooooooooooooooooooooooooooooo OooooooooooooooooooonoooooooooooooooooooOooo:
of cases, the aganglionic segment is limited to the
rectosigmoid colon. whereas 15% extend beyond
the splenic flexure.
provide patient and family education and follow-up,
and adjust medications as necessary. Polyethylene CLINICAL MANIFESTATIONS
glycol (PEG) 3350 is efficacious for colonic clean out The diagnosis should be suspected in any infant who
in children. When daily medication is necessary in falls to pass meconlwn within the first 24 to 48 hours
the treatment ofconstipation, PEG 3350 also appears of life or who requires repeated. rectal simulation
to be superior to other osmotic agents in palatability to induce bowel movements. In the first month of
and acceptance by children. The goal is to achieve a life, the neonate develops evidence of obstruction
soft (mashed potato or pudding consistency) stool with poor feeding. bilious vomiting, and abdominal
on a daily or more frequent basis. Data in children distention. In some cases, particularly those with
under a year of age indicate that PEG 3350 is safe short segment (< 5 an) involvement. the diagnosis
and effective in this age group as well. There is ex- goes undetected into childhood. In the older child.
tensive experience with other therapies including failure to grow may be seen, as well as intermittent
magnesium hydroxide, and lactulose or sorbitol bouts of intestinal obstruction. enterocolitis with
Long-term studies show that these therapies are bloody diarrhea, and, occasionally, bowel perforation.
effective and safe. Because magnesium hydroxide, sepsis, and shock. Stool that is palpable throughout
the abdomen and an empty rectum on digital exam- in childhood can cause GI bleeding. Hematvnais
ination are m05t mggestive ofthe disease. Abdominal refers to the emesis of fresh or old blood from the
radiographs show distention of the proximal bowel GI tract. Fresh blood becomes chemically altered
and no gas or feces inthe rectum. Contrastenema may to a ground-coffee appearance within 5 minutes of
demonstralt! a transition zone between the narrowed exposure to gastric add. Henratoc1tezla is the passage
abnormal distal segment and the dllated normal of fresh (brJsht red) or dark maroon blood from the
proximal bowel. However, a normal contrast enema rectum. The source is usually the colon, although
does not rule out the diagnosis. Anal manometry upper GI tract bleeding that has a rapid transit time
demonstrates failure ofthe internal sphincter to relax can also result in hematochezia. Melena describes
with balloon distention of the rectum. Rectal biopsy shiny, jet-black. tarry stools that are positi~ for occult
reveals absence ofganglion cells, an abnormal pattern blood. It usually results from upper GI bleeding, and
of acetylcholinesterase staining, and hypertrophied the color and consistency results from the blood being
nerve trunks and is the diagnostic study of choice. chemically altered during passage through the gut.
TREATMENT DIFFERENTlAL DIAGNOSIS

Hirschsprung disease is often treated surgically in The differential diagnosis for GI bleeding is generally
two stages. The first stage involves the creation of divided into upper and lower GI tract etiologies.
a diverting colostomy with the bowel that contains Upper GI bleeding occurs at a site proximal to the
ganglion cells, thus permitting decompression of the ligament ofTreitz, whereas lower GI bleeding occurs
ganglion-containing bowel segment. In the second at a site distal to this ligament. Although hematemesis
stage, the aganglionic segment is remo~d and the from upper GI bleeding can be seen in critically ill
ganglionic segment is anastomosed to the rectum. children from esophagitis or gastritis, or in children
This procedure is often postponed until the infant with portal hypertension from esophageal varices,
is 12 months of age or delayed for 3 to 6 months most GI bleeciing in children is from the lower tract
when the disease has been diagnosed in an older and manifests as rectal bleeding. Table 14-41ists
child. The mortality rate for thiA disorder is low in the most common causes of rectal bleeding by age.
the absence of enterocolitis; major complications Minor bleeding presents as stool streaked with blood
include anal stenosis and incontinence. and is usually caused by an anal fissure or polyp.
Inflammatory diseases, such as IBD or Infectious
enterocolitis, result in diarrheal stool mixed with
GASTROINTESTINAL BLEEDING blood. In contrast, Meckel diverticulum typically
Gl bleeding may be acute or chronic, gross or results in a significant amount of bleeding without
microscopic, and may manifest as hematemesis, diarrhea. Table l~Slists the associated signs and
hematochezia, or melena. A plethora of disorders symptoms of the major causes of GI bleeding.
:
l
.......
TABLE 1H. Causes of Rectal Bleeding by Age of PaUent
ftfost frt:quent t:aUfiiJS

lnfant .. 2J 2 ' .. Pnlldlloll Pl_....lto......._
j Vitamin K detlciency Analtlaaure Infectious diarrhea Inlectloua diarrhea

! Ingested maternal blood Cow's!soy milk enterocolitis Polyp Polyp
: Cow'alsoymilk Infectious diarrhea Analfiuure 180
! enterocolitis
I Neaotizing enterocolitla lntllUuaception Meckel diverticulum HSP
!Hirschsprung diJeue Meckel diverticulum
!J..sa fl8qufnt c...
IVolvulus Duplication cyst mD Anal 6.aaure
! Duplication cyst Vucular malfonnation Vucular malformation Vascular malformation
I Upper Gl tract bleeding Upper GI tract bleeding with Upper Gl tract bleeding
rapid transit with rapid transit
Hemorrhoid
L~.~~-~-~-~-=.~.~~-~-~~~~~~~--~~-~--~-~~-~-~!!~..~.~-~-~-:..!.~.~~--~~-~~~-~..~!..~.~~:..................................................................J
TilLE 1W. Diagnosis of Gastrointestinal Bleeding

!• c- ...................
I Upper Meclicalion
Varices
Inges&n ofNSAIDI
Splenomegaly or evidmce of liver disease
i &ophaptia Dysphagia, vomiting, dJ-pepsia
1"- PUD
Fissure
Chronic polyps
Cow's!toy m1Jk
Eptgaltrlc pain. meal-relattd
Bright red blood on surface of the stool
Painless rectal bleeding on the surface of stool; may have some mUC1D admixed
mood mbred with stool; may have diarrhea, hypoalbwnJnemJa, and edema
enterocolitis
Meckel diverticulum Painless, often a large amount of blood
1 IBD Diarrhea, fever, abdominal pain, poor growth. associated aystemic signa and
symptoms
Bacterial colitis Diarrhea, abdominal pain, antecedent watery diarrhea, e.g., Escherichia coli
0157:H7 or antibiotic exposure, e.g., Clo&trldium di:flicik
! HSP Joint pain, abdominal pain. purpura
I lntwlluaception
1AbbnNtatlons: HSP, Henoch-5oh0nleln pupura: lBO, Inflammatory bowel disease; NSAID, nonsteroidal anti-Inflammatory drug:
1PUD, peptic ulcer disease. •••••••• - uooooo
!ooooooou~ooooooooo•~••"''"'''''''''""""''"''''"~"""' oooooooooooooooooooooooooooooooooooooooooou ooooouoooooo ooooou oooooo oooooooo o o ooao-ooo
l
• • • • • • - • • • •••••oo.U.oooooO.oOoooOOOOOOOO•" " " .,oooo.ooooooo,.ooooo ooooooooooo o o oooooo• oooooooooooo ooo o o ooooo oonoooooooo O
CLINICAL MANIFESTATIONS or clammy skin with pallor is suggestive of shock

HistDry or anemia. On abdominal examination, attention
It is important to define the onset and duration of should foClU on assessing for masses (e.g., in the right
bleeding, color (brJsht red vs. dark maroon vs. tarry lower quadrant; may be caused by Crohn disease or
black), rate (brisk vs. gradual), and type of bleeding intussusception), tenderness (e.g., in the epigastrium
(hematochezia, hemateme&is, melena. blood-streaked suggesting peptic ulcer disease), and splenomegaly or
stool). For upper GI bleeding, questions about forceful hepatosplenomegaly and caput medusae (suggesting
vomiting, ingestion of ulcerogenic drugs (sali.cylates, portal hypertension and risk ofvarices).
nonsteroidal anti-Inflammatory drugs, steroids), and Capillary refill (thenar eminence in neonates and
a history of liver disease or peptic ulcer disease are infants) &houl.d be assessed on the extremity examina-
helpful. For lower Gl tract bleeding, inquire about tion. On rectal examination. the clinician may assess
diarrhea, or constipation with large or hard stools for anal fissure, which is best seen by spreading the
and difficult or painful defecation. Emesis of red buttocks and everting the anal canal (most fissures
fluid may not be blood and can be due to vomiting are located at the 6-- and 12.-o'clock positions). It is
ofingested O.uids or foods (sugared children's drinks, also beneficial to perform a stool test for occult blood.
beets, red gelatin, acetaminophen elixir). Black stool feel for hard stool, and look for a dilated rectum in
is not always caused by blood in the stool; it can occur children with chronic constipation or anal fissure.
following ingestion ofiron, bismuth. or blackberries.
Physical Examination DIAGNOSTIC EVALUAnON
The immediate priority when examining a child with Unless the source of bleeding is clearlythe nasophar-
GI bleeding is to determine if hypovolemia exists ynx, an anal :fissure, or hemorrhoids, a complete blood
from an acute bleed. Vital signs should be examined count with differential and platelet oount and usually
for orthostatic changes or for evidence of shock coagulation studies should besent Hemodynamically
(tachycardia. tachypnea, hypotension). The earliest significant GI bleeding is a medical emergency and
sign of significant Gl bleeding is a raised resting requires careful monitoring, often in an intensive
heart rate. A fall in blood pressure is not seen until care unit with blood available fur transfusion. Gastric
at least 40136 of the intravascular volume is depleted. lavage can aid in diagnosis ofan upper GI bleed; how-
Dermatologic abnormalities such as petechiae ever, a negative lavage does not rule out a proximal
and purpura indicate coagulopathy, whereas cool bleeding source. A pediatric gastroenterologist should
be consulted for patients with significant bleeding. of the population and is located within 100 em of
A surgical consultation is often indicated, although the ileocecal valve in the small intestine. The peak
it is wtcommon to require surgery for an upper GI incidence of bleeding from the diverticulum is at 2
bleed in children. In the stable patient, a thorough years of age. Heterotopic tissue, usually gastric, is 10
history and physical examination with consideration times more common in symptomatic cases because of
of the age-related causes usually leads to diagnosis. acid secretion and ulceration of nearby ileal mucosa.
Gastric lavage is unnecessary in children with minor
or nonacute GI bleeding. The precise diagnosis is CLINICAL MANIFESTATIONS
often made by upper or lower endoscopy. which also The most common presentation of Meckel
allows for therapeutic intervention. Ifthere is bloody diverticulum is painless rectal bleeding. Eighty~five
diarrhea, stool should be sent for culture. Bloody di- percent of patients with Meckel diverticulum have
arrhea following several days of nonbloody diarrhea hematochezia, 10% develop intestinal obstruction
is commonly seen in i.nfecti.on with Escherichia coli from intussusception or volvulus, and 5% suffer
0157:H7, which in 10% to 15% of patients can lead from painful diverticulitis mimicking appendicitis.
to hemolytic uremic syndrome. In the hospitalized The diagnosis is made by performing a Meckel scan.
neonate with bloody stool, necrotizing enterocolitis The technetium.-99 pertechnetate scan, preceded by
must be considered, and an abdominal film and prepentagastrin stimulation or an H2 RA, identifies
evaluation for sepsis should be performed. When the ectopic acid-secreting cells that mediate the
swallowed maternal blood is suspected as the cause hemorrhage.
ofGI bleeding, the Apt red blood cell fragility test is
performed on the child's stool or emesis to differen- TREATMENT
tiate maternal blood from the blood of the neonate. Definitive treatment is surgical resection.
A Meckel diverticulum should be considered when
there is a large amowtt of painless rectal bleeding.
INFLAMMATORY BOWEL DISEASE
TREATMENT mn is a generic term for Crohn disease and ulcerative
The unstable child with severe bleeding or hypovolemia colitis, which are chronic inflammatory disorden of
is evaluated by primary and secondary physical exam the intestines. Ulcerative colitis produces diffuse,
surveys, per Chapter 20. A normal hemoglobin or confluent colonic ulceration and crypt abscuses
hematocrit does not rule out severe acute bleeding; limited to the mucosa. It involves the rectwn in
full hemodilution takes up to 12 hours in the acutely 95'36 of patients, with or without contiguous exten-
bleeding patient. Intravenous normal saline or Ringer sion higher in the colon. Ulcerative colitis does not
lactate at 20 mL!kg boluses should be given until the affect the small intestine. The pathology of Crohn
vital signs are sufficiently improved. Type 0-negative disease involves transmural inflammation often in a
whole blood should be reserved for the unstable discontinuous pattern, which results in skip lesions.
patient with acute bleeding that cannot be quickly Crohn disease may involve any part of the GI tract
brought under control The most common error in (mouth to anus). In pediatric patients, the process
management of the chlld with s~re GI bleeding is is ileocolonic in 40% of cases, involves the small
inadequate volume replacement. Hypotension is a intestine alone in approximately 30% of cases, and
late finding; fluid resuscitation should be governed is isolated to the colon in only 20'36 of cases. Crohn
by the level of tachycardia. The stable child without disease may result in transmural inflammation with
heavy bleeding or signs of hypovolemia should be fistula fonnation, perforation, or fibrostenotic disease
evaluated and treated according to the particular with stricture formation. Although the exact etiology
diagnosis. Three common causes of GI bleeding- of these disorders is not known, a combination of
Meckel diverticulum. ulcerative colitis, and Crohn genetic, immunologic, and environmental mech-
disease-are discussed in the following sections. anisms is implicated. Most pediatric patients are
adolescents, but both diseases are seen in infancy
and in preschool children.
MECKEL DIVERTICULUM
Meckel diverticuJ~ the vestigial remnant of the CLINICAL MANIFESTATIONS
omphalomesenteric du~ is the most common Crampy abdominal pain. diarrhea, and weight
anomaly of the GI tract. It is present in 2% to 3% loss are common manifestations in Crohn disease.
Although diarrhea is common, it is not universal In the evaluation ofsuspected lBO in the pediatric
Rectal bleeding is noted in only 3596 of cases of patient, a full colonoscopy with Ueoscopy is indi-
Crohn disease. Abdominal pain tends to be mo.re cated to evaluate all affected areas and to attempt to
severe in Crohn disease than in ulcerative colitis; it differentiate between Crohn disease and ulcerative
may be diffuse and is frequently worse in the right colitis. Due to the increased incidence of upper GI
lower quadrant. Perianal disease may produce skin tract disease in pediatric Crohn's compared with
tags, fissures, fistulae, or abscesses. Anorexia, poor adults, an upper endoscopy is often performed.
weight gain, and delayed growth occur in 4096 of Even with a full evaluation, it is sometimes difficult
patients. Most children with ulcerative colitis exhibit to differentiate ulcerative colitis from Crohn colitis
diarrhea (9396 to 9896) with blood (8396 to 95%) and in patients with isolated colonic disease, and thus a
mucous, abdominal pain, and tenesmus. Fifty-seven third type ofiBD exists: IBD-U (unclassified). VISu-
percent ofpatients present with moderate to severe alization of the mucosa in ulcerative colitis reveals
disease. Severe disease may be fulminant, with high diffuse, con.tl.uent ulceration, and easy bleeding. In
fever, abdominal tenderneu, distention, tachycardia, Crohn disease, deep ulcerations may be present, and
leuk.ocyto&is, hemorrhage, severe anemia, and more diseased areas may be more focal Upper GI study
than eight stools per day. Toxic megacolon and in· with small bowel follow-through in Crohn disease
testinal perforation are rare complications. often reveals ileal or proximal small bowel disease
Table 14-6 compares Crohn disease and ulcer- with segmental narrowing ofthe ileum (string sign)
ative colitis. Extraintestinal sequelae occur in both and longitudinal ulcers. A capsule endoscopy test or
diseases, may precede or accompany GI symptoms, magnetic resonance enterography can help identify
and include polyarticular arthritis, ankyl.osing small intestinal lesions in Crohn disease; these studies
spondylitis, primary sclerosing cholangitis, chronic are becoming the preferred means of small bowel
active hepatitis, sacroiliitis, pyoderma gangrenosum, imaging given that they are radiation sparing.
erythema nodosum, aphthous stomatitis, episcleritis, Anemia is common and usually associated with
recurrent iritis, and uveitis. Patients with Crohn iron deficiency. Megaloblastic anemia secondary to
disease are also at increased risk for nephrolithiasis folate and vitamin B12 deficiency may also be present.
secondary to fat malabsorption resulting in increased An elevation in the erythrocyte sedimentation rate
absorption of oxalate. and the CRP is common, but severe inflammation
can be present without significant elevation of
these inflammatory markers. Hypoalbuminemia
UILE 1M. Comparison of Crohn Disease and can be seen with malnutrition or a protein-losing
Ulcerative Colitis enteropathy in both ulcerative colitis and Crohn
disease. Serum aminotransferase levels are increased
!r.t~n Gnthn...._ Ulllidwcallls I if hepatic inflammation is a complicating feature.
i MalaiJe, fever, Conmwn So~s
Stool examination reveals blood and fecal leukocytes
! weight loss with a negative stool culture, and there is frequent
iRectal bleeding Sometimes Nearly always
1
elevation offecal calprotectin, which can be used to
!A~pUn Conmwn Common monitor disease activity.
!Abdominal mass Common Rare Physical examination, especially in Crohn disease,
may show short stature, low body mass index (BMI);
IPerianal diseue Common Rare
right lower quadrant tenderness, fullness, and/or
~ Deal involvement Common Rare (backwash mass; clubbing; pallor (if anemic); oral aphthous
ileitis)
ulcers; perianal disease (tag, fissure, ulceration,
I Sbidure Sometimes Not seen fistula, abscess); skin rashes; and arthritis.
!filtula Sometimes Not seen
ISkip ~eaona Common
The differential diagnosis ofiBD-Iike illness includes
! Tranmlural Common Not seen
bacterial or parasitic causes ofdiarrhea (C. difficile,
l inflammation E. coli 01S7:H7, Campylobacter jejuni, Yersinia
i Granulomu Somdimea Not seen enterocolitica, amebiasis), appendicitis, HSP, eo-
i Long-term. rWc of lncrealed Greatly sinophilic gastrointestinal disease, and radiation
i cancer increued enterocolitis.
iooooooOOOooooo•oooooooooooooooooo oooooo~oo•••-••••••,.•••••••••••••• •••••••,.•• ••ooooooouoooooooooooooo ooooooo"""""""""'"""'"'"":
lrHbnent Recurrence rates of up to 50% have been reported

Treatment of lBO is aimed at control of inflam- after segmental resection.
mation and mppression of the immune system.
5-Aminosalicylic compounds are a mainstay of
LIVER DISEASE
anti~inflammatory treabnent for ulcerative colitis,
but have a less clear role in Crohn disease. Antibiotics Hyperbilirubinemia and blliary atresia are discussed
have a role as anti-in£lammatory agents in Crohn in Chapter 2 and infectious hepatitis is reviewed in
disease. Aggressive nutritional support (including Chapter 7. In this section, we will review elevation
tube feeding) is important for growth but also has of aminotransferases. acute liver failure, Wilson
an anti-inflammatoryeffect and improves symptom disease. Alagille syndrome, and nonalcoholic fatty
control in Crohn disease. Corticosteroids have both liver disease.
anti-inflammatory and immunosuppressive effects,
and they remain a mainstay of early management. ELEVATION OF AMINOTRANSFERASES
Other immunomodulatory treatments including AST (aspartate aminotransferase) and ALT (alanine
mercaptopurine, azathioprine, and methotrexate aminotransferase) are released from dam.aged hepato-
are useful as steroid-sparing agents. Biologic therapy cyte&, indicating liver injury. ALT is more specific
with antitumor necrosis factor antibody (infliximab for liver disease because of its low concentration
and adalimumab) is increasingly used for moder- in other tissues. The degree of elevation of amlno-
ate and severe disease. Biologic use has expanded transferases may give a clue as to the etiology. The
to anti-integrin (vedolizumab) and anti-IL12/23 differential diagnosis of mild to moderately elevated
(ustekinumab) antibodies, currently approved for am.inot:ransferases ( <500) includes al-antitrypsin
patients 18 years and older. Because anorexia and deficiency, autoimmune hepatitis, chronic viral hep-
increased nutrient losses in the stool are common atitis (B, C, and D), hemochromatosis, medications
in children with IBD, adequate calories and protein and toxins, nonalcoholic fatty Uver disease (NA-
are essential. Oral supplements, nasogast:ric tube FLD), nonalcoholic steatohepatitis (NASH), Wllson
feedings, and, in some severe cases, central venous disease, celiac disease, and hyperthyroidism. More
byperalimentation are necessary. Vitamin and mineral dramatic elevation of aminotransferases (ALT and
supplementation, especially with iron, folate, and AST >500 UIL) suggests acute bile duct obstruction.
B1z• may be required. acute Budd-Oliari syndrome, acute viral hepatitis,
After 10 yean ofulcerative colitis, there is a cumu- autoimmune hepatitis, ischemic hepatitis (shoclc),
lative risk of 1% to 2CJ& per year for the development and medications/toxins. In alcohol-related liver in-
of carcinoma. Therefore, patients with ulcerative jury, there may also be very elevated tran.saminases.
colitis need an initial screening colonoscopy 8 to 10
years after the onset of ulcerative colitis symptoms ACUTE UVER FAILURE
and subsequent screening colonoscopies every Acute liver failure (ALF) is defined as biochemical
1 to 2 years. Studies have shown that patients with evidence of liver injury, without history of known
long-standing Crohn colitis are also at an increased chronic liver disease, and coagulopathy (lNR between
risk for development ofneoplasia. Surgery is eventu- 1.5 and 1.9 with mental status changes or INR >2
ally needed in 25% of patients with ulcerative colitis without mental status changes) not corrected by vi-
and 5096 to 7006 of children with Crohn disease. tamin K. A specific etiology is not identified in about
Surgery is indicated in ulcerative colitis when there 5096 of pediatric cases. Among identifiable causes,
is fulminant colitis with severe blood loss or toxic tmdns and medications including acetaminophen,
megacolon, intractable disease with a high-dosage anticonvulsants (phenytoin, carbama.zepine, and
steroid requirement, steroid toxicity, growth failure, valproic acid) and autoimmune hepatitis predom-
or colonic dysplasia. Because ulcerative colitis is re- inate. Other causes include mushroom poisoning,
stricted to the colon, colectomy is curative. Surgery recreational drugs (Ecstasy), and Wll.son disease.
is performed in Crohn disease when inflammation In children under 3 years of age, infections (herpes
is not controlled with medical therapy, or when simplex virus, enterovirus), metabolic conditions
hemorrhage, obstruction, perforation, or severe (galactosemia, hereditary fructose intolerance, ty-
fistula formation is present. In general, conservati~ rosinemia, urea cycle defects, fatty acid oxidation
management is warranted because removal of the defects). mitochondrial disorders, and neonatal
diseased bowel is not curative in Crohn disease. hemochromatosis/gestational alloimmune liver
disease may also result in ALF. Hemophagocytic quality of life may be an indication for liver trans~
lymphohistiocytosis (HLH) and acute leukemia plantation in severe cases. Cardiac murmurs occur
may also present with ALF. Hepatitis A and E are in 85% to 98% ofaffected individuals with the most
important causes of ALF in endemic areas. common abnormality being stenosis at some level
in the pulmonary arterlal system. Vertebral arch
WILSON DISEASE defects, the typical finding of butterfly vertebrae,
Wllson disease, also known as hepatolenticular and other minor slceletal defects can be seen. Mul~
degeneration, is a rare autosomal-recessive disease of tiple and recurrent bone fractures occur in up to
copper metabolism with a prevalence of 1:30,000. A 40% of patients. The most common ocular features
mutation in theATP7B gene, found on chromosome of AGS are hypertelorism and bilateral posterior
13, encodes for a P-type ATPase expressed mainly embryotoxon visible by indirect ophthalmoscopy.
in hepatocytes, which transports copper into bile During childhood, the facies are typically described
and incorporates it into ceruloplasmin. Absent or as triangular, with a broad forehead, deeply set eyes,
reduced function of this protein leads to decreased pointed chin, and a straight nose with a bulbOWI
hepatocellular excretion ofcopper into bile, resulting tip. Renal anomalies occur in 40% to 5096 of AGS
in copper accumulation in the liver and decreased patients, and renal involvement is now considered
ceruloplasmin. As liver copper levels increase, copper one of the major criteria for the diagnosis. Struc-
is released in the clrculation and deposits in other tural abnormalities include solitary kidney, ectopic
organs including brain, kidneys, and cornea. kidney, bifid renal pelvis, and multicysti.c or dys~
Wilson disease usually manifests as liver disease plastic kidneyB. Functional abnormalities include
in children and teenagers and as neuropsychiatric renal tubular acidosis, neonatal renal insufficiency,
illness in adults. It is a great imitator with diverse nephronophthisis, lipidosis of the glomeruli, and
presentations and must be considered in anyone with tubulointerstitial nephropathy. Vascular anomalies
chronic liver diseue as it may be fatal ifmissed. The in AGS involve the aorta, renal arteries, and cere-
diagnostic criteria include decreased ceruloplasmin, bral vessels; intracranial vessel aneurysms; internal
elevated ~hour urine copper, and Kayser-fleischer carotid artery aneurysms; and moyamoya disease,
rings. Dramatically increased hepatic copper is the which occurs in up to 9% of AGS patients. Growth
best evidence for Wilson disease. Treatment includes failure is multifactorial in etiology, including a genetic
chelatingagents (n~penicillamine, trientine, and tetra~ contribution. chronic cholestasis, Cat malabsorption,
thiomolybdate), zinc (which interferes with uptake congenital heart disease, and Umited oral intake. A
ofcopper and induces an endogenous chelator), and minority of AGS patients develop progressive liver
avoidance of food with hish copper content. disease leading to cirrhosis and portal hypertension.
although 25';16 ofAGS patients may eventually require
ALAGILLE SYNDROME liver transplantation.
Alagille syndrome (AGS), or arteriohepatic dyspltuia, Management
is an autosomal-dominant disorder caused by muta- Adequate nutrition is crucial, and a high-calorie diet
tions in the JAGl gene, which encodes a ligand in the with a high proportion of fat from medium~chain
Notch signallng pathway. The traditional diagnosis triglycerides is recommended in the neonatal period.
of AGS follows the guidelines of bile duct paucity Ursodeoxycholic acid is r ecommended to enhance
plus 3 of 5 clinical criteria including cholestasis, bile flow, and supplemental fat-soluble vitamins are
cardiac murmur or heart disease, skeletal anomalies, required to prevent deficiencies. Surgical biliary
ocular findings, and characteristic facial features. diversion may relieve pruritus and slow the progres-
JAGI and the Notch signaling pathway are crucial sion of the disease. Liver transplantation is indicated
for the development of the liver. bile ducts, heart, in patients with decompensated cirrhosis or failed
vasculature, kidneys, and other organs affected in diversion with incapacitating pruritus.
this multisptem disorder.
Clinical feetu1'81 NONALCOHOLIC FATIY LIVER DISEASE
The clinical features ofAGS include neonatal cholesta- AND STEATOHEPAMIS
.sis, hypercholesterolemia with the appearance of Nonalcoholic fatty liver disease (NAFLD) is the
cutaneous xanthomas, and malnutrition. Intractable most common cause of liver disease in childhood
pruritus leading to self-mutilation and diminished and adolescence. NAFLD includes .macrovesi.cular
fat accumulation within hepatocytes, without in- include elevated serum aminotransferase&, elevated
tlammation, whereas nonalcoholic steatohepatitis gamma-glutamyl transpeptid.aae (GGT) and alkaline
(NASH) includes fat accumulation associated with phosphatase, low high-density lipoprotein (HDL),
inflammation and/or evidence ofcellular injury. NA- and elevated fasting t:ris}ycerides. mtrasound and
FLD Is most commonly associated with. obesity as well MRI may be used for diagnosis. 'illtrasound is readily
as type 2 diabetes, hypertension, and dyslipidemla. available and inexpensive, but this technique is less
Other predisposing&ctors include male sex, Hispanic sensitive and cannot quantify the degree of hepatic
ethnicity, and Asian race (especially those ofChinese .steatosis, fibrosis, or inflammation. Liver histology
or Filipino descent). The pathophysiology ofNAFLD is helpful for definitive diagnosis.
is thought to be multifactorial. with hyperin.su.li.nemia.
Management
hepatic Insulin resistance, and carbohydrate-rich diet
The treatment goal is weight loss through lifestyle
important in development offatty llver.
modification, including diet change and increased
Clinical Features exercise. Although a 3% to 5% weight loss may de-
Clinically, most children are asymptomatic. Acan- crease hepatic steatosis, up to 10% may be necessary
thosis nigricans is found in > 50% of patients with to induce remission. Phannacologic treatments are
NAFLD. Laboratory findings that may indicate NAFLD still undergoing trials.
KEY POINTS
• The history and physical examination help to • Most children with uncomplicated viral gas--
determine whether abdominal pain is acute or troenteritis or bacterial enterocolitis can be
chronic/recurrent and whether a medical, sur- rehychted oraJy: antldlaiTheal medications are
gical, or nonorganlc disorder Is most lkely. In not Indicated In children with acute dlarThea.
the adoktscent female, genltola1nary pathology • Infants with diarrhea should be fed as close to
must be considered and a pelvic examination their normal diet as possible. Recovery is faster
should be performed. than if a restricted diet Is uaed.
• Appendicitis Ia the moat common surgical • Constipation resulting from organic causes may
Indication for abdominal pain In childhood. be caused by decreased pertstalsis, decreased
• Most intussusception results from invagination expulsion, and anatomic malformation.
of the ileum Into the colon through the ileocecal • Constipation is commonly associated with
valve, which results In periodic episodes of anal fissure In Infancy and voluntary withhold-
irritability, colicky pain, and emesis. ing or functional constipation In children and
• Most cases of emesis are caused by gastro- adolescents.
esophageal reflux, acute gastroenteritis, or • Hirschsprung disease should be suspected in
non-GI infectious disorders such as tonsillitis, any infant who fails to pass meconium within
otitis media, or urinary tract infection. However, the first 24 to 48 hours of life or who requires
intestinal obsln.lctlon, neurologic, metabolic, and repeated rectal stimulation to Induce bowel
drug-induced etiologies and nondigestive organ movements, or has poor feeding, bilious
dysfunction are Important causes not to miss. vomitWlg, and abdominal distention in the first
• Pyloric stenosis Is an Important cause of gas- month of life.
tric outlet obstruction and emesis in the first • The earliest sign of slgniftcant Gl bleeding is
2 months of life. a raised resting heart rate. A drop in blood
• In most m.rta and older chldren with emesis, presstn is not seen until at least 40% of the
rafklx, and heartl:>l6n, a history and physical ex- Intravascular voiLille Ia depleted. Hemody-
alii l8tion are sufficient to relablyd~ GERD, namically significant GI bleeding is a medical
recog~lze oomplcations, and initiate ma l8gemEll'1l emergency and requires careful monitoring,
• The most common cauae of di.mea in children often in an intensive care unit and blood avail-
is viral gas1roenterltla. able for transfusion.
• Meckel clllaticuUn, the moetcommon ~of • The pathology of Crohn disease Involves
the Gl tract, presents wlt1 pM1Iess rectal bleeding. transmural Inflammation In a discontinuous
• Ulcerative colitis produces diffuse superficial pattern, which results in skip lesions. Crohn
colonic ulceration and crypt abscesses. It disease may involve any part of the Gl tract
Involves the rectum in 95% of patients, with (mouth to anus).
or without contiguous extension higher in the • Therapy for IBD is aimed at achieving maximum
colon. Ulcerative colitis does not affect the symptom control with minimum aide etrects.
small Intestine.
CLINICAL VIGNETTES
VIGNE'ITE 1 VIGNET1E2
A 14-year-old girt presents to her primary care provider A 4-month-old gir1 presents to the hospital with a
with a 3-to-4-month history of abdominal pain. Sev- 2-day history of watery, nonbloody diantlea and fever.
eral mornings each week, the patient awakens with The infant was reported to have had 10 watery stools
epigastric and periumbilical pain, and she does not over the previous 24 hours. There was no history of
want to eat breakfast Eamg makes her pain worse, vomiting. Her birth hlslay was urveveallng, and she
and she does have some nausea. She does not have was fed exclusively on nilk-based formula from birth.
diarmea, constipation, or blood in her stool. She has One month ago, she weighed 5.5 kg. On the day of
not gained weight since her last visit 6 months ago. presentation, physical examination revealed an alert
On physical examination, she is a healthy-appearing, but Irritable and Ill-appearing Infant whh a weight of
Tanner Stage IV adolescent whose weight and height 818 5.1 kg, a temperature of 38.9°C, heart rate between
at the 50th percentile for age. Her abdomen Is soft but 170 and 190 beats per minute, respiratory rate be-
mildly tender throughout. There i8 no perianal disease, tween 40 and 80 breaths/min, and blood pressure of
and the stool in her rectum is hemoccult negative. 102155 mm Hg. The anterior fontanel is flat. The skin
1. You suspect that she has functional abdominal
was pale; she had dry lips and dry buccal muoosa,
reduced teara, and a capillary refill time of 3 seoonds.
pain (functional dyspepsia). Which of these tests
would be helpful to obtail to exclude other likely 1. Whk:h of the folloWing Is the most likely ettology
causes of her pain? of her Illness?
L ESR, CBC, anti-tissue transglutamlnase lgA L Salmonella
b. Upper gastrointestinal endoscopy b. Giardia
c. Breath test for H. pylori c. Rotavlrus
d. Upper Gl series (x-ray) d. c. difficile
1. RAST testing for food allergies 1. Pneumonia
2. Which of the following additional Items In the 2. What is the most appropriate treatment for this
history would support your suspicion of functional patient?
abdominal pain? L Intravenous or oral rehydration followed by a
L Unexplained fever clear lquld diet
~ Intermittent darrhea ~ Intravenous antibiotics
o. Family hiS1ory of lBO c. Oral rehydration and antidiarrheal medications
d. Weight loss d. Intravenous or oral hydration followed by a
e. Perianal disease cow's milk-based or soy milk diet
1. Oral rehydration and ondansetron
a Which of the following are appropriate options
for treatment? 3. Which of the following Is the most likely explanation
L Narcotic therapy for the pain for this persistent diarrhea?
b. PEG 3350 L Celiac disease
o. Food elimination diet b. Giardia
d. Emphasis on mamaining daily functioning c. Pancreatic insufficiency
despitepU1 11. Pos1vftl enteritis
e. Cholecystectomy • • Congenital diarrhea
VIGNETTE3 b. Repeating stool testing for C. difficile in 4 weeks

An otherwise healthy 14-year-old girl pl'&sents with 2 c. Repeattng stool testing for C. dlfflcll& only If
weeks of daily abdominal cramping, nausea, 1 to 2 her symptoms should r&turn
episodes of nonbilious emesis, and worsening malaise. d. Repeating stool testing for C. difficile following
She felt too unwell to attend school the past 2 days. any future antibiotic course
Low~rade fever to a max of 100°F has been recorded e. Testing family members for C. diffici/e
on several days. Though she noted a decl'&ased appe-
VIGNETTE.
tite, the1'9 has been no notable weight loss. Each of the
past 5 days, she notes 2 to 3 episodes of nonbloody An 11-year-old boy presents with a 3-month history
but •really nas~ diarrhea. She is a quiet, cooperative, of intermittent bloody diantlea and weight loss. He
nontoxic teen. VItal signs are normal with no orthostatic has perianal skin tags and fullness In the right lower
quadrant on examination. He has a microcytic anemia
changes noted. Her physical exam is normal except
and an elevated sedimentation rate. There is a family
for a diffusely tender abdomen more so on the right
history of ulcerative colitis in an uncle.
side with no rebound, guarding, or pain with jumping.
1. Which of the following is the most likely diagnosis?
1. Which diagnostic plan would best guide manage-
a. Ulcerative colitis
ment at this juncture?
b. Crohn disease
L CBC, ESR, fecal calprotectin
c. Infectious colitis
b. Stool for culture, ova and parasites (O&P), C.
d. C. difficile infection
diMclle tes11ng 1. Immunodeficiency syndrome
c. Serum electrolytes
d. Watchful waiting, 1'9View of bland diet 2. What is the most useful next step in the evaluation
e. Serum amylase, lipase, and liver panel of this patient?
L Upper Gl x-ray series
2. What Is the optimal treatment plan for this par- b. Fecal calprotectin
ticular patient? c. Upper endoscopy (esophagogastroduodenos-
L Oral metronidazole copy) and colonoscopy
b. IV metronidazole d. Abdominal ultrasound
c. Oral vancomycin e. Serologic IBD panel
d. IV vancomycin
e. Azithromycin for 5 days 3.. What is the most likely intervention in his future?
1. Varicella vaccine
3. Which of the following should be Included In b. Medication to reduce atreas
further surveillance? c. Endocrine referral for growth failure/growth
L Repeating stool testing for C. difficile at the hormone consideration
completion of her antibiotic course to docu- d. Restriction of milk
ment eradication e. Surgery
ANSWERS
VIGNETI'E 1 Question 1 common In children with functional abdominal pain

1.AnswerA: symptoms. Food allergies usually trigger symptoms
A series of relatively low~ost tests can exclude common temporally related to the time of food ingestion, that
causes of abdominal pain 1'9sulting from inflammation is, within 1 to 2 hours. Eosinophilic gastroenteritis,
(ESR, CBC), cellae disease (anti-tissue transglutaml- which Is not lgE mediated, Ia not likely to demonstrate
nase lgA}, gall bladder disease, or liver dlsea&e (serum positive RAST testing.
aminotransferase, alkaline phosphatase, and bilirubin),
and urinary tract disease (urinalysis). An ulcer is less VIGNETTE 1 Question 2
likely without a history of pain 1'91ieved by eating, and 2.Answer 8:
It Is more likely to cause acute and dally pain rather Diarrhea wlltlout blood, but sometimes wlltl mucus,
than intermittent pain lasting 3 to 4 months. Upper can be seen in functional gastrointestinal diaordenJ
gastrointestinal endoscopy is somewhat insensitive for (FGIDs). Although functional dyspepsia is distinct
ulcer disease. H. pylori infection is a cause of symptom- from irritable bowel syndrome, there is a great deal of
atic peptic ulcer disease and gastrttls but Is not more overlap In this spectrum of disorders. The pl'&sence of
alarm symptoms or signs suggests a higher possibility with increasing immunization against rotavirus, it is still
of organic disease and may justify the performance of a major cause of Illness, especially In unlmmunlzed
addmonal diagnostic tests. Alarm symptoms or signs patients. Salmonella Is much less common but In a
Include, but are not limited to, Involuntary welgh1 1oss, child this ill, it is reasonable to obtain a bacterial stool
deceleration of linear growth, gastrointestinal blood culture to exclude salmonellosis. Salmonella infection
loss, significant vomiting, chronic severe diarrhea, can but does not always have bloody diarrhea. The
persistent right upper or right lower quadrant pain, irritability of this child is a concern and could be due to
unexplained fever, and family history of lBO. A family dehydration (compensated shock) and acidosis. However,
history of lBO, especially in first~egree family members, the irritability seen with salmonellosis always raises a
increases the likelihood of lBO and, at a minimum, concern in a young infant for sepsis or meningitis. The
increases the concern on the part of the patient and flat fontanel and the child's mental status should be
family. While weight loss may occur in FGIDs, it is reassessed after hydration to ensure that the fontanel
unusual and minimal. Perianal disease is a hallmarK is not bulging and the irritability is improved. Giardia is
of lBO, and physical examination for abdominal pain less common in a child who is not ambulatory. It does
should therefore Include perianal inspection if not a not cause fever and usually does not cause this degree
rectal examination. All of the tests return normal, and of dehydration. C. dlfflc/Je Is uncommon as a cause
you continue the counseling you began at the first of diarrhea In children below 1 year of age and does
ofllce visit. not cause this degree of dehydration. Pneumonia can
cause fever and tachypnea and even be associated
VIGNETIE 1 Quedon 3 with mild diarrhea but not this degree of dehydration.
3.Answer D:
Improvement in symptoms will require cooperation VIGNETTE 2 QuHtlon 2
of the patient and family. Patients currently missing 2.AnswarD:
school should be encouraged to return to school. Oral rehydration is the mainstay of treatment to
School attendance is not part of the problem and in resolve the dehydration. This child is close to 10%
fact is part of the solution. Distraction from pain is a dehydrated. There has been a 400-g weight loss
useful strategy, and normal daily activities fulfill this since the last measured weight. Assuming the child
role. Use of acid-reducing medications may improve had continued to grow at t he 5oth percentile, she
pain even when not due to gastritis or ulcer disease, would weigh approximately 6.1 kg but Is actually 600
but the lowest effective dose should be used and the g less. Intravenous rehydration Is also appropriate If
medication discontinued If not effective. Low doses of the child refuses to drink or there Is concern about
antidepressant drugs, which Inhibit serotonin uptake decompensated shock. Most commonly, after a period
and facilitate endogenous endorphin release, may of rehydration, a normal diet can be resumed with
benefit children with pain predominant FGIDs. Bio- additional oral rehydration solution to compensate
feedback, hypnosis, and other cognitive behavioral for ongoing losses. Because this child is young and
treatments have been beneficial in many conditions the diarrhea severe, there is a higher chance that she
associated with chronic pain, including childhood will have temporary lactose intolerance and a soy
FGIDs. Narcotic therapy will simply create a second milk-based formula is also a reasonable option for a
problem, that is, dependency, and is better reserved short time, for example, 7 to 10 days. Probiotics may
for acute severe pain rather than chronic pain. PEG also shorten the course of the diarrheal illness. A clear
3350 is extremely helpful for constipation, but is not liquid diet will not provide adequate energy and will not
helpful for FGIDs without this symptom. A food elim- shorten the duration of diarrhea. Intravenous antibiot-
Ination diet Is difficult, and there Is no evidence that ics would be appropriate if this child appears septic,
It helps In FGIDs or evidence In this patient's history but antibiotics are not useful to treat viral diarrhea.
tor food allergy. This patient did not have evidence Antidiarrheal medications, for example, loperamlde
of gallstones; moreover, gallstones In the absence of may cause a sense of false security with decreased
specific signs and symptoms are rarely the cause of diarrhea due to pooling of Intestinal secretions In the
vague abdominal pain. A gallbladder emptying scan intestinal lumen, the so-called third spacing. They do
was not done, but this too, even when abnormal, has not decrease loss of fluid from the intravascular space.
poor predictive value for gallbladder pain. Loperamide is not indicated in this age group as it may
cross the blood- brain barrier with resultant lethargy
VIGNETlE 2 Quedon 1 and respiratory depression. Ondansetron is a useful
1.AnswerC: adjunct if vomiting Is present from uncomplicated
Rotavirus is the most common cause of severe diarrhea gastroenteritis. However, it has not been studied for
among infants and young children and is one of several this purpose in infants below 6 months of age. The
viruses that cause similar infections. Although the in- acute dehydration resolves with traatment, but the
cidence and severity of rotaviral illness is decreasing diarrhea persists for more than 14 days.

3.Answer D: 2.AnswerA:
Diarl'hea lasting morethan 14 days is considered to be c. difflci/e is now a fairly common infection seen
chronic or peraiatent. Postinfectious enteritis diarrhea may in community settings. Normal children who have
result from incomplete repair of the intestinal mucosa, had neither recent inpatient hospital stay nor anti-
a process that is normally complete in a week or less. biotic regimen are experiencing clinically significant
Use of probiotics and temporary removal of lactose from disease. More virulent strains may be contributing
the infant's diet can accelerate resolution. In developed to the increased incidence. In this patient who is
countries, severe, persistent dlarmea has become far tolerating oral fluids and solids, is nontoxic, and is
less common. Persistent diarmea is associated with otherwise healthy, oral metronidazole is the drug
undernutrition, both befora and after the illness. Shigella of choice. Oral vancomycin Is extremely effective;
and Cryptosporfdium infection are also risk factors, but however, its formidable cost and limited accessibility
persistent diarrhea can occur after acute viral gastro- on prescr1ptlon benefit plans encourage limiting usa
enter1tls. lmmunodeftclency Is a concern and should to more Ill patients and medically fragile children. IV
also be evaluated In an Infant with persistent diarrhea. therapy for C. dlfflcfle, which Is more Invasive and not
Celiac disease is not symptomatic until there has been as effective, is not preferred unless there is an ileus.
activation of the immune-mediated mechanism through Colonic concentrations of vancomycin are negligible
consumption of gluten, which should not be present following intravenous administration, and there is little
in cow's milk (or soy}-based formula. Giardia infection support for this therapeutic option. In the absence
can cause persistent diarrhea but is uncommon in an of diarrhea, stool levels of metronidazole after oral
infant who is not ambulatory. Pancreatic insufficiency intake are low because of absorption in the small
is most commonly due to cystic fibrosis and is pres- bowel. However, in the presence of diarrhea, stool
ent in 85% of patients with cystic fibrosis at birth. It concentrations are therapeutic. Azithromycin is not
does not present as an acute, febrile diarrheal illness an effective antibiotic for C. difficife. Fidaxomicin is
at 4 months of age that does not improve. Congenital a new oral antibiotic, which is effective. Our patient
diarrhea, for example, structural enterccyte disortlers recovers uneventfully with resolution of her cramping,
such as microvillus inclusion disease, congenital sodium nausea. and diarrhea over a few days.
or chloride diarrhea, or autoimmune diarrhea would
generally present w ith watery dlanhea and growth VIGNETTE 3 Quastlan 3
fallura befora 3 to 4 months of age. 3.AnswerC:
Recurrence of c. difficife infection typically develops 1 to 2
VIGNB'TE 3 Q...Uan1 weeka after stopping metronidazole or vancomycin, but
1.Answer B: can be delayed for up to 12 weeks. Recurrence rates
Stool culture and testing for O&P and C. difflcile is following treatment with metronidazole or vancomycin
most appropriate. The duration of symptoms ex- are similar at 15% to 30%. Indeed, recurrent disease
ceeds the allotted maximum of 10 to 14 days seen is so common that all patients should be forewarned
in a self-limited viral gastroenteritis. The presence of that this complication can occur after their course of
fever suggests an infectious and also, but less likely, therapy is complete, thereby facilitating prompt diag-
an inflammatory process. Although IBD can present nosis (retesting) and retrealment. Despite the risk of
with a similar symptom constellation, the duration is recurrent infection, test of cure is not recommended
usually longer and course more Indolent. Weight loss because there are no data that show persistent
Is often present. Should stool studies remain normal positive tests at the end of treatment put the patient
and symptoms persist, the screening labs In choice at greater risk for disease recurrence. Symptomatic
A are worthy of conslderatton. Electrolytes are help- patients should be retested but not asymptoma'llc
ful when the clinical picture warrants oral or IV fluid patients. Repeat testing following future antibiotic
to rehydrate or correct imbalances. Our patient had coul'8es is similarly not indicated, although minimizing
neither high output losses nor clinical concern for future antibiotic exposure is indicated. Risk factors
dehydration. Though acute pancreatitis and biliary for recurrent C. difflcile infection include a history of
d isease in this age could present with abdominal prior recurrence and use of additional antimicrobials.
pain, the location, presence of diarrhea, and fever Although good hand washing is always important,
speak against this. Stool testing was positive for the and nosocomial spread of C. difflcile is a major route
detection of toxin producing C. difficile by polymerase of infection, intrafamilal spread of C. diffici/e is low
chain reaction (PCR). Culture and ova, and parasite enough as to not warrant surveillance, anticipatory
testing were negative. treatment, or other interventions.
VIGNETTE 4 Question 1 would likely have a colonoscopy even with a normal

1.Answer B: fecal calprotectln. Abdominal ultrasound can be useful
The family history of lBO and the duration of symptoms for evaluation of an abdominal abscess or appendicitis
with weight loss are suggestive of lBO. Crohn diseaae but Is less useful for Identifying mucosal disease. Again,
is the most common lBO in children. The perianal skin a tissue diagnosis would still be lacking. Although a
tags and fullness in the right lower quadrant suggest 88l'Oiogic panel for lBO can be helpful, eapeciaUy to
transmural inflammation and ileitis, respectively, which add to the information which helps distinguish Crohn
are both associated with Crohn disease. Ulcerative colitis disease from ulcerative colitis, it is not a sensitive
would also have bloody diarmea but not skin tags and or specific way of screening a general population. A
less likelyfullness in the right lower quadrant. A family diagnosis of Crohn disease was made and treatment
history of ulcerative colitis raises concern for either initiated. The patient retums to the primary care phy-
Crohn disease or ulcerative colitis. Infectious colitis is sician for well child care while being followed by a
usually mora self-limited, except for C. dlfflclle Infection. pediatric gastroenterologist.
Although he should be tested for entertc pathogens
Including C. dlfflcl/8, there would still be a high degree VIGNETTE 4 Question 3
of suspicion for lBO if an Infection is present, suggesting 3.Answer E:
this infection might be a comorbidity or a presenting Children with Crohn disease are likely to have surgery
feature of the chronic Illness. When immunodeficiency In their future, to treat penetrating disease (fistulas,
syndromes present as colitis, this occurs in younger perforation) or strictures. In the ftrst 5 years of diagnosis,
children, that is, infantile (<2 years old) or very early about 50% of children will need surgery. Varicella tite111
onset (<10 years old) inflammatory bowel disease. should be checked at diagnosis. Moat children who
received a varicella vaccination on schedule will be
VIGNETTE 4 Question 2 immune. However, patients on steroids or other immu-
2.AnswerC: nosuppressive medications have a contraindication to
In the evaluation of suspected lBO in the pediatric live virus vaccination. Most patients with lBO are not
patient, a full colonoscopy with ileoscopy is indicated treated with stress relieving medication. There is no
to evaluate all affected areas and to attempt to differen- evidence that lBO is caused by stress. However, Uving
tiate between Crohn disease and ulcerative colitis. An with a chronic illness can be stressful, and stress can
upper endoscopy Is often performed to assess for any make a child wHh lBO feel less well or even contribute
microscopic Inflammation In the upper Gl tract. This to a flare-up. It Is Important to address normal as well
would be much more typical of Crohn disease. Only as special case stressors that may be affecting the
endoscopy and biopay can provide a tissue diagnosis, patient's ablltry to cope wtth chronic Illness. Growth
which ia the gold standard. Upper Gl study with small failure is not expected in children with adequately
bowel follow-through in Crohn disease often reveals treated lBO. In some patients with growth stunting,
ileal or proximal small bowel disease with segmental catch-up growth may be achieved with adequate sup-
narrowing of the ileum (string sign) and longitudinal pression of inflammation, nutritional supplementation,
ulcers. However, a tissue diagnosis would still be and, rarely and in addition, growth hormone therapy.
lacking. Fecal calprotectin is helpful to decide whether Lactase deficiency may occur transiently at the time
to perform an endoscopy In a patient with equivocal of diagnosis if there is extensive small bowel disease.
signs or symptoms or to follow a patient who has a Otherwise, lactose restriction is not needed as part of
diagnosis but may have mild symptoms. This patient routine management of lBO.
Endocrinology
Rachel B. Kadakia and Bradley S. Marino
OVERVIEW ('IYpe 1 diabetes) or a combination ofinsulin re~immce

and inadequate insulin production (Type 2 diabe-
The endocrine system is a system of glands, each tes). The cla.ssic symptoms of diabetes are polyuria
of which secretes a type of hormone directly into {frequent urination), polydipsia (excessive thirst),
the bloodstream to regulate the body. Hormones and polyphagia (increased hunger). Other forms of
are substances (chemical mediators) released from diabetes include gestational diabetes, neonabll dia~
endocrine tissue into the bloodstream, where they betes caused by genetic defects ofinsulin secretion,
travel to target tissue and generate a response. cystic fibrosis- related diabetes, medication~induced
The pituitary gland is considered the master diabetes {most commonly, steroid-induced), and
gland and signals other endocrine organs in a specific several forms of monogenic diabetes.
sequence referred to as an a~ds. The pituitary gland
is composed of anterior and poster ior portions. TYPE 1 DIABETES MELLinJS
The anterior pituitary, derived from Rathke pouch, Pathogenesis
secretes growth hormone (GH),Iuteinizing hormone Type 1 diabetes mellitus (TlDM) is characterized
(LH), follicle-stimulating hormone (FSH), prolactin, by autoimmune destruction of pancreatic ~cells,
thyroid~stimulating hormone, and adrenocorticotropic which produce and secrete insulin. TlDM accounts
hormone (ACTH). The posterior pituitary gland is for 5" of all diabetes cases diagnosed.
derived from neuroectoderm and consists of axons The overall incidence of TlDM is 2" to 3" per
from neurons with cell bodies in the periventricular year with a prevalence of 1/400 to 500 children in
nuclei of the hypothalamus. The posterior pituitary the United States. The peak age of onset is bimodal,
gland itself does not produce hormones. However, with the first peak occurring between ages 5 and 7
the posterior pituitary stores the hormones arginine and the second at the onset of puberty. However, the
vasopressin (AVP) and oxytocin. AVP and oxytocin disease may even be diagnosed in children under
are synthesized in the hypothalamus and transported 1 year old. Males and females are equally affected.
along these neurons to the posterior pituitary. The presence of anti-islet cell antibodies in 85% of
Hormones act by binding to specific receptors individuals with recent-onset DM and the increased
in the target organ. The production of hormones incidence ofother autoimmune diseases in children
is often regulated in a feedback loop. Hormones with TlDM suggest an autoimmune etiology. There
regulate various human functions, including growth is a 50% concordance rate among identical twins.
and development, reproduction, and regulation of Although the precise trigger of TlDM is unknown,
metabolism. Hormones are classified based on their genetic, autoimmune, and environmental factors
chemical composition (amine&, proteins, or steroids). have all been implicated.
The absence of insulin leads to impaired glucose
entry into cells. The body enters a catabolic state
DIABETES MELLITUS
and requires uae ofalternative fuel sources (fat, pro-
Diabetes mellitus (DM) is a group of metabolic dis~ tein) for energy via gluconeogenesis, lipolysis, and
eases in which a person has high blood sugar most proteolysis. Counter-regulatory hormones such as
commonly caused by either a deficiency of insulin epinephrine, cortisol. and GH are upregulated and
328
Chapter 15 I Endocrinology • 329
work to pzomote gluconeogenesis and glycogeno- Diagnostic Evaluation

lysis. Fatty acid oxidation OCCUl'S to produce ketone A random pluma glucose level greater than 200 mg!dL,
bodies, which se~ as an alternative source of fuel the presence of glucosuria and ketonuria, and an
for the body. elevated glycosylated hemoglobin (HbAJJ are con-
When the blood glucose concentration exceeds sistent with the diagnosis ofTlDM. In early diabetes,
180 mg/dL, the renal threshold for glucose reab- abnormallties may be seen on an oral glucose tolerance
sorption is exceeded, resulting in glycosuria. The test. A fasting blood glucose concentration greater
glycosuria then causes an osmotic diuresis with than 126 mg/dL and/or a 2-hour postprandial blood
increased urine output (polyuria). If insulin defi- glucose concentration after an oral glucose tolerance
ciency is severe, ketones are produced in significant test greater than 200 mgfdL are suggestive ofdiabetes.
quantities, the blood's native buffering capacity is Islet oell antibodies in the serum are found in 85116
overwhebned, and diabetic ketoacidosis (DKA) of new-onset Type 1 diabetics.
results with severe dehydration. acidosis, electrolyte The diagnosis of DKA is characterized by hy-
abnormalities, and potentially fatal consequences such perglycemia, ketonemia/ketonuria, and metabolic
as coma and death. In addition to DKA, the other acidosis (venous pH < 7 .25, serum bicarbonate
major complication seen in TlDM is hypoglycemia < 15 mEq/L). The response to metabolic acidosis
from insulin overdose, decreased caloric intake, or is a compensatory respiratory alkalosis and a drop
increased exercise without a concomltant ln.crease in serum PC02• Because of the hyperglycemla-me·
in calories. The only treatment for T1DM is insulin diated osmotic diuresis, dehydration occurs with
replacement. elevation of blood urea nitrogen. Total body stores
of phosphare and potassium are also depleted.
Clinical Manifestations However, even though total body potassium is low,
Hi811Jry IUld Physical Examination
laboratory evaluation can show low, normal, or even
A history of new-onset unintentional weight loss,
high levels of serum potassium depending on the
polydipsia, polyphagia, and polyuria suggests TlDM.
degree ofacidosis present. When acidosis is present,
When DKA is suspected in a chUd with known potassium moves from the intracellular space to the
TlDM, important historical information includes
extracellular space to maintain electroneutrality.
compliance with insulin therapy, the child's diet over
the previous day, and whether the chlld has been ill Treatment
and emotionally or phymcally stressed. DKA is a medical emergency and warrants rapid
The physical examination is generally normal in intervention. The immediate goals oftreatment are
TIDM unless DKA is present. The child with DKA reversal ofthe catabolic state through exogenous in-
appears acutely ill and suffers from moderate to sulin therapy and restoration offluid and electrolyte
profound dehydration. Symptoms include polyuria, balances. Initial fluid resuscitation consists ofadmin-
polydipsia, fatigue, respiratory distress, headache, istering normal saline or a lactated Ringer solution
nausea, emesis, and abdominal pain. The child's oflO mL/kg intravenous bolus. While the fluid bolus
mental status may vary from confused to comatose. is running, the total fluid deficit is calculated on the
On physical examination, tachycardia and hyperpnea basis of the amount ofdehydration. The fluid deficit
(Kussmaul respirations) are generally noted as well as should be replaced over a 48-hour period. The level
decreued capillary refill and skin turgor (dehydration). of hyperglycemia is assessed, and an insulin dl'ip is
There may be a fruity odor to the breath because of started at 0.1 Ulkglhr. The goa] is to decrease the
the ketosis. Intravascular volume depletion may be serum glucose by no more than 50 to 100 mgfdL/hr.
so marked that hypotension is present. Although A gluoose level that .falls too quickly oould precipitate
cerebral edema is uncommon, it frequently is fatal. cerebral edema. When serum glucose approaches
Altered mental status, unequal pupils, seizures, and/or 250 to 300 mgldL, dextrose should be added to
decorticate or decerebrate posturing indicate cerebral the fluids to avoid hypoglycemia. Hyperglycemia,
edema. Early identification and aggressive manage- acidosis, and ketone production will correct with
ment of increased intracranial pressure are pivotal insulin therapy. Until there is adequate insulin, the
to improve ou~ome. Symptoms of hypoglycemia or body will continue to produce ketones. Frequent
insulin toxidty are caused by catecholamlne release monitoring of blood glucose level, electrolytes, and
(trembling, diaphoresis, flushing, and tachycardia) add-base status is crucial.
and by cerebral glumpenia (.sleepiness, confusion, Children with new-onset diabetes who are not in
mood changes, seizures, and coma). DI<Aat diagnosis should be treated with subcutaneous
insulin. The starting dose ofinsulin is 0.5 to 1 U /kg/ risk for developing other autoimmune diseases, most
day depending on age and pubertal status. frequently Hashimoto thyroiditis and/or celiac dis-
Children with TlDM and their families require ease. These autoimmune diseases are .screened for
education on blood stucose monitoring. carbohydrate periodically in a patient with TlDM.
counting, and insulin administration. The treatment
approach is multidisciplinary and requires frequent TYPE 2 DIABETES MELLITUS
blood glucose monitoring, basal and prandial insulin Palllogenesls
replacement, psychological and social support, and 'I)pe 2 diabetes mellitus (T2DM) is a polygeniccondition
close medical follow-up. The patient learns how to that results from relative insulin resistance, insufficient
tailor insulin dosing based on the glucose level and insulin production. and jk:ell dysfunction. This insulin
the current meal. Most diabetics take insulin four to resistance initially causes a compensatory increase in
six times a day. The "basal-bolus'" method ofinsulin insulin secretion; h~ with time there is a progres·
administration is the most common and consists of sive decline in glucose-stimulatEd insulin .secretion.
a once daily basal insulin (glargine or le~mir) and
short-acting insulin (lispro or aspart) prior to car- Epidemiology
bohydrate consumption. This method allows for the T2DM now accounts for 10% to 40% of newly
most flexibility. Other insulin regiments include (1) diagnosed diabetes in adolescents. The increasing
a combination ofintermediate-acting insulin (NPH) incidence parallels the high prevalence of obesity.
and short-acting insulin (lispro or aspart), and (2) Most cases occW' during early adolescence, around
twice daily premixed insulin injections consisting of the onset of puberty. Prevalence is highest in Nati~
Americans (PIMA Indians), African Americans, and
70% to 75% intermediate-acting insulin and 25% to
30% short-acting insulin. Lastly, insulin pump therapy Hispanics but is seen in all ethnic groups. Genetic
susceptibility is important; however, environmental
can provide a continuous infusion of rapid-acting
insulin, and affords the ability to make the most factors, including obesity, physical inactivity, and
precise insulin dose adjustments. diet, play a major role.
Children with diabetes may require more insu- History and Physical Examination
lin during times of medical. surgical, or emotional Many patients are asymptomatic at presentation.
stress. If hyposlycemia occurs, a child may ingest a Others may have symptoms similar to those of
carbohydrate snack to increase the serum glucose TlDM. There is usually a positive &mily history. On
concentration. Ifthe chlld is vomiting, instant glucose physical examination, obesity is noted, with a body
or cake icing may be applied to the buccal mucosa mass index (BMI) usually greater than 30 kglm2•
to provide glucose. If the child is having a seizure, Often associated with T2DM is acanthosis nigricans,
intravenous glucose or intramuscular glucagon to a skin condition involving hyperpi8Jnentation and
release hepatic glucose stores should be given im- thickening of the sldn folds, found primarily on the
mediately. Glycosylated hemoglobin (HbA1J ~Is back of the neck and flexor areas.
should be monitored every 3 months to assess average
glycemic control. Traatmant
Ifmetabolic derangements are present or ifglyt:ated
Pragnolll hemoglobin is greater than 9%, insulin therapy is
The Diabetes Control and Complications Trial initiated. Metformin and biguanides are the only
demonstrated that intensi~ management and tight approved oral diabetic qenta used for the treatment
glycemic control reduces the risk ofdiabetes compli- ofT2DM in children older than 10 years. In addition
cations by50% to 75%. Complications from diabetes to medical therapy, lifestyle changes in diet and
include microvascular disease o£ the eye (retinopathy), exercise are particularly important.
kidney (nephropathy), and nerves (neuropathy). Mi-
crovucular disease is generally not obse~d until HYPOGLYCEMIA
the child has been insulin dependent for a minimum The definition of hypoglycemia is a plasma glucose
of 10 years. Accelerated large vessel atherosclerotic value ofless than 50 mg/dL or a whole blood glucose
disease may lead to myocardial infarction or stroke. level ofless than 60 mgldL.
Children with diabetes should ha~ annual screening
for complications, in.clu.ding urine collection for mi- Etiology
croalbuminuria, ophthalmologic examinations, and Hypoglycemia may result from (1) hyperinsulinism
fasting lipids. Patients with T lDM are at heightened (congenital, inaulinoma, exogenous administration of
insulin orinsulin-secretingagenb); (2) benign ketotic elevated from ~-cell hyperplasia, c.a using hypogly-
hypoglycemia (childhood, age 18 months to 5 years, cemia for hours to a fuw da}'B after delivery.
intolerance offasting states, ketonuria present); (3)
Traatmant
hormone deficiency (ACTH or GH deficiency); (4)
After the critical sample is obtained, administration
glycogen storage disease; (5) disorders of glucone-
of IV glucose is indicated, followed by continuous
ogenesis; and/or (6) defects in fatty acid oxidation.
IV infusion ofdextrose containing fluids. Long-term
Clinical Manifestation 11'Ulrul8ement will depend on the etiology of the
Features of hypoglycemia can be classified into two hypoglycemia.
categories. The first is activation of the autonomic
nervous system. causing a release of epinephrine. 1·1~i•1;1•13;fJ•1i'Uj•3;1;1 5dlli;,il•1:M
which manifests symptoms of sweating. shakiness,
tachycardia, and anxiety. The second is of neuro- NORMAL VASOPRESSIN REGULAnON
glycopenic origin, resulting in headaches, visual Arginine vasopreuin (AVP) is human antidiuretic
disturbances, lethargy, irritability, mental confusion, hormone. It is produced in the periventricular and
loss of consciousness, and/or coma. Infants may not supraoptic nuclei of the hypothalamus. AVP is
exhibit many symptoms of hypoglycemia. transported along neurons from these nuclei and
terminates in the posterior pituitary gland. An os-
Evaluation motic sensor is located near the supraoptic nuclei
During a hypoglycemic event the clrculating levels and detects changes in osmolality as amall as 1% to
ofcertain hormones and other biomarkers offuels 296. An increase in osmolality caused by dehydration
can useu the integrity of the metabolic and hor- triggers the release ofvasopressin, which then acts
monal systems. It is essential to obtain a "critical at V2 receptors in the collecting tubule of the kid-
sample• when the plasma glucose level is less than ney, causing translocation of aquaporin 2 channels
50 mgldL. The critical sample should include a (AQP2) and subsequent water reabsorption to occur.
confirmatory plasma glucose, serum bicarbonate, In addition to water reabsorption, vasopressin also
insulin, c-peptide, cortisol, GH, free fatty acids, plays a role in vasoconstriction and platelet aggre-
beta-hydroxybutyrate, acetoacetate, lactate, and gation by acting at V1 receptors.
ammonia. A comparison ofexpected normal values
to the critical sample is necessary to determine the DIABETES INSIPIDUS
etiology of hypoglycemia. In the fasting state of a There are two forms of diabetes insipidus. Central
normal individual, it would be expected for glycogen diabeta insipidus is due to loss of AVP from the
stores to be depleted and levels of gluconeogenic posterior pituitary. Nephrogenic ditlbetes insipidus
substrates, free fatty acids, and beta-hydroxybutyrate is due to impaired action of AVP at the level of
(the major ketone body) to rise significantly. GH the kidney. Central diabetes lnslpidw may also
and cortisol will be upregulated during a fast and occur after head trauma and in the setting of any
certainly elevated during a hypoglycemic event. hypothalamic- pituitary tumor or central nervous
Insulin levels should then decline to undetectable system (CNS) infection. Infiltrative diseases such as
levels (<2 U/mL). Total and free carnitine, acyl- Langerhans cell histiocytosis and sarcoidosis can also
carnitine profile, and serum amino acids should cause central diabetes insipidus. The most common
be collected in a nonfasting state to assess for an brain tumors in the pediatric population leading to
inborn error of metabolism. central diabetes insipidus are craniopharyngiomas or
Infants and children are more susceptible to CNS genninomas. Rarely, central diabetes insipidus
hypoglycemia than adults and cannot tolerate a occurs as an isolated idiopathic disorder.
prolonged fast. Thirty percent of normal infants who
undergo a 6-hour fast will have hypoglycemia. Other Clinical Manifestations
risk factors in the newborn period for hypoglycemia The child with diabetes insipidus has profound
include small for gestational age and stress (trauma, polydipsia and polyuria. Ifwater intake is inadequate,
asphyxia. sepsis, cold exposure).lnfants ofa diabetic severe dehydration and hypematremia occur. Ifthe
mother are also at risk for postnatal hypoglycemia. cause of the diabetes insipidus is a brain tumor
In these infants, intrauterine hyperglycemia leads to impinging on the pituitary gland, focal neurologic
resultant endogenous hyperinaulinemia. Postnatally, signs and visual abnormalities may be noted. Weight
glucose levels normalize, but insulin levels remain loss is also noted in children because profound water
intake occurs in pJace of food and other calorically Clinical Mantfaslatlons

rich sources of nutrition. In contrast, infants often Patients present with normovolemic hyponatremia;
experience weight gain as they are typically offered relatively concentrated urine; and normal renal,
calorically rich breut milk or formula to quench their thyroid. and adrenal function. Symptoms are related
thirstin place of water. Urine output may reach 5 to to the degree of hyponatremia and how rapidly the
10 L/day and Is dilute, with a low urine specific gravity hyponatremia progressed. A patient is unlikely to
and urine osmolality. Over time, serum sodium and have symptoms with a sodium of greater than 125
serum osmolality rise as a result of free water loss. mEq/L. Headache, nausea, lethargy, seizures, and
other CNS findings may occur when sodium falls
Diagnosis to less than 125 mEq/L.
The water-deprivation test is used to diagnose dia-
betes insipidus and must be performed in a hospital Management
setting because of a high risk of hypernatremic SIADH is a diagnosis of exclusion. Other causes of
dehydration without appropriate monitoring. The hyponatremia must be ruled out (hyperglycemia,
child is admitted and made NPO. Hourly serum increased serum lipids or protein, hypothyroidism,
sodium, plasma osmolality, urine osmolality, urine and adrenal insufficiency). A serum osmolality of
output, and vital signs are recorded. The diagnosis less than 280 mOsm/kg combined with urine os-
is established ifthe child demonstrates dilute urine molality of less than 200 mOsm and urine sodium
(urine osmolality < 300 mOsmlkg) in the setting of concentration greater than 20 mEq/L are consistent
hypertonicity (hypernatremia and plasma osmolality with SIADH. Patients are typically euvolemic. Most
> 295 mOsm/kg). Once diabetes insipidus is present, cases of SIADH are self-limited, and the mode of
a vasopressin injection is administered and urine os- management is fluid restriction. Demeclocycline,
molality i.s remeasured to assess for concentration. If which produces a reversible nephrogenic diabetes
the urine concentrates, the child has central diabetes insipidus, may also be utilized to treat SIADH.
insipidus.; ifthe urine does not concentrate, the child but only in chronic cases. Treatment for the acute
has nephrogmlc diabetes insipidus. symptomatic hyponatremia may be managed by
TnNdment the administration of hypertonic fluids. The goal is
Desmopressin acetate (DDAVP), an antidiuretic to raise the serum sodium level by 0.5 mEqlhr to a
hormone (ADH) analogue, is given intranasally, maximum of 12 mEq/L in the first 24 hours. Serum
subcutaneously, or orally to stimulate the lcidneys sodium should be monitored every 3 to 4 hours.
to retain water and reverse the polyuria, polydipsia,
and hypernatremia in central diabetes insipidus. SHORT STATURE
Chl.orothiazide is the most common treatment for
nephrogenic diabetes insipidus. Short stature or abnormal linear growth is a common
endocrinologic complaint. 1Wo normal variants of
SYNDROME OF INAPPROPRIATE SECRETlON short stature,fomilial (genetic) short stature and
OF ANnDIURETlC HORMONE constitutional delay, account for 80% of cases of
Syndrome of hyponatremia with inappropriate in- short stature. Pathologic causes also may result in
creased secretion of antidiuretic hormone (SIADH) short stature. Etiologies that result in proportion-
is observed in the presence of vasopressin and ate short stature are much more prevalent. Disor-
excessive water intake, resulting in an expansion of ders that result in disproportionate short stature
intravascular volume with a subsequent decrease predominantly affect the lons bones and include
in Na and serum osmolality. The syndrome is often rickets and achondroplasia. Disorders that cause
iatrogenic u a result of excessive IV fluids. SIADH proportionate short stature may result from either
may be identified in children with. encephalitis, a prenatal or postnatal insult to the growth process.
zneniJliitis, brain tumors, head trauma, pneumonia, Prenatal etiologies include intrauterine growth retar-
or psychiatric disease. Many drugs are also impli- dation. placentaldysfunction. intrauterine infections,
cated in SIADH, such as Usinopril. carbama:z.epine, teratogens, and chromosomal abnormalities. The
tricyclic antidepressants, and many anticancer drugs. most common chromosomal abnormalities that
Children with tuberculous meningitis and SIADH result in short stature are trisomy 21 and Turner
have a particularly poor prognosis, as do those with syndrome. Postnatal causes include malnutrition,
liver failure and SIADH. chronic systemic diseases, psychosocial deprivation,
drugs, and endocrine disorders. Common endocrine for age and pubertal status or if clinical suspicion is
defectB that :result in short stature include hypothy- high for GH deficiency.
roidism, GH deficiency, and glucocorticoid excess Some children who live in emotionally or phys-
and precocious puberty. Of note, with precocious ically abusive or neglectful environments develop
puberty there is initial acceleration ofgrowth; how- functional GH detldency due to psychosocial depri-
ever, final adult height is compromised, leaving the vation. These chlldren may have bizarre behaviors
individual with subsequent short stature compared that include food hoarding, pica, and encopresis,
to the genetic potentiaL u well as immature speech, disturbed sleep-wake
cycles, and an increased pain tolerance. Clinically,
DIFFEREN11Al. DIAGNOSIS they resemble children with primary GH deficiency,
Qilld:ren with familla1 short stature establish growth with marked retardation of bone age and pubertal
curves at or below the 5th percentile by 2 years of age. delay. H GH testing is done while the chlld remains
They are otherwise completely healthy, with normal in the hostile environment, there is a blunted GH
physical examinations. These children have bone response. GH therapy does not improve height in
ages that are concordant with chronologie age, and these children; when the child is :removed from the
puberty occurs at the expected time. Short stature deprived environment, GH testing reverts to normal.
is usually found in at least one parent, but height and catch-up growth is noted.
inheritance is complex, and the short ancestor may Primary hypothyroidism causes marked growth
be more distant. failure through diminished growth velocity and
Children with constitutional delay of growth skeletal maturation. Free thyroxine (free T 4 ),
develop at or below the 5th percentile with a nor- triiodothyronine thyroid-stimulating hormone
mal growth rate. 'This results in a curve parallel to (TSH), and thyroid antibodies should be measured
the 5th percentile. Puberty is signiJlcandy delayed, (even in the absence of symptoms) to rule out
which results in a delay in the bone age. However, any degree of hypothyroidism when evaluating
other laboratory testing is normal. Because these short stature.
children fail to enter puberty at the usual age, their CU&Iring dUe~Ue is a rare cause of short stature.
short stature and sexual immaturity are B.CC~entuated Hypercortisolism, from either exogenous steroid
when their peen enter puberty. family members are therapy or endogenous oversecretion. may have a
usually of average height, but there is often a history profound growth-suppression effect. Usually, other
of short stature in childhood and delayed puberty. stigmata of Cushing syndrome such as moon face,
The parents of children with constitutional delay buffalo hwnp, central obesity, purple striae, and
should be counseled that their child's growth is a hypertension are present if growth suppression has
normal variant and that the child will likely mature occurred. Chronic systemic diseases may result in
to the height expected for their family. short stature from lack of caloric absorption or in-
GH deficiency accounts for approximately 5% creased metabolic demands. Cyanotic heart disease,
of cases of short stature referred to endocrinolo- cystic fibrosis, poorly controlled diabetes, chronic
gists. Children with classic GH deficiency grow renal failure, human immunodeficiency (HIV) in-
at a diminished growth velocity (<5 cm/year) and fuction, and severe rheumatic illness can increase
have delayed skeletal maturation. A history of birth metabolic demands and dim.i.nish growth. Alterna-
asphyxia, neonatal hypoglycemia, or physical find- tively, intlammatory bowel disease, celiac disease,
ings of microphallus, cleft palate, or other midline and cystic fibrosis may reduce caloric absorption
defects are suggestive of pituitary dysfunction and and produce short stature.
increased likelihood of congenital GH deficiency. ~,.syndrome often rnan:irem as short stature
Acquired GH deficiency secondary to hypotha- and/or growth deceleration. Other clinical manifus-
lamic or pituitary tumor is usually associated with tations ofTurner syndrome may sometimes be subtle
other neurologic or visual impainnents. In an older and have a variable presentation amons patients.
child with more recent onset ofsubnormal growth. Given that the incldence ofTurner syndrome is 1 in
the index of suspicion for a tumor should be high. 2,500 females, gonadotropins and karyotype testing
Insulin-like growth factor~I (IGF-1) and its binding are indicated in the female adolescent with short
protein-3 (IGFBP-3) are used to screen for GH stature and delayed puberty. Elevated gonadotropins
deficiency. Formal GH testing with timed sampling (indicating primary ovarian failure) with a 45, XO
for GH is indicated if these screening tests are low karyotype is diagnostic.
Chronic administration of certain medications Most hormonal deficiencies causing short stature will
may result in poor growth. Long-term glucocorticoid result in a delayed bone age. An advanced bone age
therapy can impair growth. Stimulant medications likely indicates precocious puberty; a normal bone
such as methylphenidate (Ritaline) and dextroamphet- age, familial short stature; and a delayed bone age,
amine (Dexedrine) can lower appetite and lead to poor constitutional delay, hormone deficlendes, or chronic
linear growth secondary to an undernourished state. illness. Thyroid function tests must be completed
to evaluate for hypothyroidism. Urinalysis and renal
CLINICAL MANIFESTATIONS function testa are needed to rule out chronic renal
History disease. A complete blood count with differential
Important historical information includes the child's and an erythrocyte sedimentation rate may reveal
prenatal and birth history, the pattern of postnatal evidence of chronic systemic infection. The child's
growth, presence of chronic disease, long-term nutritional status may be enmlned through the
medication use, achievement of developmental serum albumin and total protein counts. Insulin-like
milestones, and growth and pubertal patterns of growth factor-1 {IGF- 1) and insulin-like growth
the patient's parents and siblings. Evaluating the factor binding protein-3 (IGF-BP3) are ordered to
child's growth charts is vitally important. A thorough screen for GH deficiency. Ifa chromosomal anomaly
feeding history, including what, how, and by whom is considered, obtaining a karyotype is necessary.
the child is fed. is also required. Magnetic resonance imaging (MRI) of the brain
Physical Examination should be considered ifserum testing documents GH
The majority ofphysl.cal examinations performed on deficiency or there are neurologic findings to justify
children with short stature are normal It is critical to the procedure. The MRI may identify a hypothalamic
plot the child's height and weight on the appropriate or pituitary process resulting in decreased central
growth curve for age. In addition, arm span and GH secretion. Other laboratory testing to consider
upper-to-lower-body segment ratio are measured ln.cludes tissue transglutamlnase antibodies (celiac
to check for pathologic disproportionate causes of disease), LH. FSH, estrogen or testosterone (to usess
shortstature. Midlln.e defectJ should also be noted. In puberty status), and prolactin (mild elevation could
young children. the head circumference should also suggest a disruption of the pituitary stalk).
be measured. In children with failure to thrive, weight
and height are diminished, and the head circumfurence TREATMENT
is often spared. When examining the child with short For most children with constitutional delay, reas-
stature, the physician may find dysmorphic features surance that the child's short stature is a normal
in a pattern suggestive of a particular syndrome. A variant suffices, In some select patients with no
skin exam should be performed and should look signs of puberty by 14 years of age, a 4- to 6-month
for signs of cyanosis indicating potential congenital treatment with the appropriate sex steroid (testos-
heart disease, violaceous striae as noted in Cushing terone or estrogen) may help to modestly increase
syndrome, and bruises and poor hygiene indicative stature and "jump-start" pubertal development for
of psychosocial deprivation. The thyroid is palpated psychological support until true pubertal devel-
to determine its size and its consistency and to assess opment begins. Children with GH deficiency are
for the presence of thyroid nodules. The lungs and managed with biosynthetic human GH adminis-
heart are examined to identify chronic cardiopuhno- tered by daily subcutaneous injection. Acceler-
nary disease. Abdominal tenderness or bloating may ated growth velocity on GH treatment results in
indicate inflammatory bowel or ailiac disease. Tanner catch-up growth in most children. GH therapy may
staging for both boys and girls must be documented be needed into adulthood because of its effects
to help differentiate among famillal short stature, con- on bone mass and lipid metabolism. Idiopathic
stitutional delay, and precociouJ puberty. A thorough short &tature (final adult height prediction below
neurologic and funduscopic examination may reveal the 3rd percentile) is considered an indication to
underlying CNS disease resulting in GH deficiency. treat with GH therapy. In addition, children who
were born small for gestational age and who failed
DIAGNGSnC EVALUATION to achieve catch-up growth by 2 years of age can
A boPU age {anteroposterior radiograph of the left wrist) benefit from GH use. Primary hypothyroidism is
assessment looks at the lndlvidual growth plates of the treated with levothyroxine. After several weeks
wrist and hand and is crucial in evaluating growth. of therapy, the growth velocity generally returns
to normal. Unlike GH therapy, levothyroxine Clinical Manlfaslatlons

therapy does not promote catch-up growth and Symptoms include fatigue, cold intolerance, lethargy,
may even accelerate the bone age. To manage the dry skin. hair loss, difficulty sleeping, and constipation.
short stature associated with Cushing disease. the Physical findings include slow linear growth. delayed
physician must identify and treat the underlying puberty, immature body proportions. edema. dry
etiology. Girls with short stature caused by Turner thin hair, dry skin, and delayed relaxation of deep
syndrome may receive GH to increase their final tendon reflexes.
adult height. Short stature caused by psychosocial
deprivation is treated by removing the child from Diagnostic Evaluidlon
Thyroid function tests reveal a depressed total T 4
the environment. Short stature caused by medir
serum concentration. Ifprimary hypothyroidism is
cations is reversed by discontinuing the offending
present, an elevated serum TSH concentration is
medication.
noted. If secondary hypothyroidism is present, the
TSH level may be low or inappropriately normal.
The detection of thyroid peroxidase antibodies or
THYROID DYSRJNCTION
thyroglobulin antibodies indicates an autoimmune
CONGENITAL HYPOTHYROIDISM basis for disease.
Congenital hypothyroitllsm (CH} is the most common Traatmant
endocrinopathy affecting newborns. Mandatory Patients with hypothyroidism require thyroid hor-
screening for CHis established in the United States mone replacement with levothyroxine. Both free
and allows the earliest possible treatment. CH is Tt and TSH should be monitored frequently at the
conaidered a medical emergency because delays in outset of therapy and yearly once normal values are
initiation of thyroid hormone treatment of weeks achieved. Hypothyroidism that persists untreated for
or months will result in developmental delays. The longer than 6 to 9 months results in linear growth
prevalence ofCHinthe United States is 1:4,000 live attenuation and may have a deleterious effect on
births. The most common cause of CH is thyroid final adult height.
dysgenesis (aplasia, hypoplasia, or ectopic tissue},
followed by dyahormonogenesis. The most common HYPERT1tYROIDISM
etiology ofdyshormonogenesis is abnormal or absent
In hyperthyroidism, T, levels are elevated and TSH
thyroid peroxidase function. leading to impaired
is suppressed. Most cases of hyperthyroidism in
organlfication of the tyrosine molecules.
children are caused by Graves disease. Other causes
Classically the TSH is elevated with a normal or
include a hyperfun.ctionins "hot" thyroid nodule or
low T•. There are two approaches to screening for
acute suppurative or viral thyroiditis. Graves disease,
CH. One is to measure the thyroid hormone level
an autoimmune disorder, is caused by circulating
(TJ, followed by pituitary TSH if the Tt levels are
thyroid-stimulating immunoglobulins that bind
low, and the second approach is to measure the TSH
to thyrotropin receptors on thyroid cells, causing
with a reflex T, if the TSH is high.
increased thyroid hormone production. Neonatal
Graves disease is most commonly caused by trans-
HYPOTHYROIDISM
placental passage of maternal thyroid-stimulating
The most common cause of juvenile or acquired immwwglobullns.
hypothyroidism is Hashimoto thyroiditis, a chronic
lymphocytic thyroiditis that results in autoimmune Clinical Manlfes1atlons
destruction of the thyroid gland. Other causes of Symptoms include weight loss despite a normal or
hypothyroidism include panhypopituitarism causing increased appetite, heat intolerance, emotional Jar
TSH deficiency, ectopic thyroid dysgenesis, admin- bility, restle881le&s, palpitations, excessive sweating,
istration ofantithyroid medications, and surgical or frequent loose stools, and poor sleep. There is often
radioactive iodine ablation for treatment of hyper- a change in behavior and deterioration of school
thyroidism. The incidence ofhypothyroidism in girls performance. Hyperthyroidism should be part of
is four times greater than in boyJ. There is often a an evaluation for attention deficit disorder because
family history autoimmune diseases. Most children there are many overlapping symptoms. On physical
present during adolescence; it is unusual to develop examination. the child may be flushed. fidgety, and
autoimmune thyroiditis before 5 years of age. warm, with proptosis, a hyperactive precordium.
resting tachycardia, and a widened pulse pressure. because of hyperthyroidism, antithyroid medications
The thyroid gland is generally enlarged, smooth, and beta blockers may be necessary.
firm (but not hard), and nontender, with a bruit on
auscultation of the gland. Often a fine tremor is noted. 111YROID NODULE
as well as brisk deep tendon reflexes. Acute-onset A single firm thyroid nodule is an ominous finding
tachycardia, hyperthermia, diaphoresis, fever, nausea, in the pediatric population. Unlike nodules in adults,
and vomiting indicate thyroid storm (malignant hy- the thyroid nodule in a child or adolescent is more
perthyroidism), which may be life threatening but is likely to be ma.Jisnant. Lack ofiodine concentration
rare in children. Infant s with neonatal Graves disease of a thyroid w l scan (cold nodule) increases the
tend to stare, are jittery and hyperactive, and have an likelihood of carcln.oma. Ultrasound evidence of a
.Increased appetite and poor weight gain. Tachycardia cyst is reauuring, but the solid component ofa cyst
is usually present, and thyrom.egaly may be palpable. should be considered for tine-needle aspiration.
The cardiovascular system is the most sensitive to The presence ofcalcification on ultrasound and the
elevated thyroxine levels, and these infants may have palpation of a lymph node suggest thyroid cancer,
evidence of congestive heart failure. most commonly papillary thyroid carcinoma. Most
recommend that thyroid nodules be surgically re-
Treatment
moved in the pediatric population.
The use ofantithyroid drugs (methimazole) to treat
Graves disease requires a prolonged period (usually PAINRJL THYROID GLAND
2 to 5 years) and close supervision by a physician.
Propylthiouracil (PTU) is no longer recommended in Subacute thyroiditis (viral infection) or suppuratrve
the pediatric population because of hepatic toxicity. thyroiditis (bacterial infection) can cause tenderness
of the thyroid gland. Both of these conditions are
Less than 6006 of patients will achieve permanent
remission with drug therapy alone. It may take associated with an elevation of the sedimentation
rate. Subacute thyroiditis causes hyperthyroidism
greater than 1 year for the TSH to recover from
following an initial viral illness resulting from release
suppression and normalize. A small percentage of
patients experience side effects to methimazole, of preformed thyroid hormone from the damaged
most commonly dermatologic (skin rash or hives) gland. The TSH may be normal or suppressed. The
second phase may include a return to a euthyroid
or agranulocytopenia. A beta blocker may be used
as an adjunctive treatment in the immediate post- state or culminate in hypothyroidism. Suppurative
diagnosis period to slow the heart rate and decrease thyroiditis may be accompanied by fever, URI
symptoms, and dysphagia. Bacterial infections are
the drive on the cardiovascular system while the
antithyroid medication reaches steady state. Once the treated with antibiotics, but the pain experienced in
T 4 is normalized, the patient can stop beta-blocker thyroiditis can be managed with anti-inflammatory
medications (ibuprofen, steroids).
therapy. Most physicians will delay the use of radio-
iodine ('.JuI) for the treatment ofthyrotoxicosis until
adolescence so as not to expose a child to radiation.
ADRENAL DYSFUNCTION
It is preferred in children to ablate the gland and
induce a hypothyroid state rather than underdose The adrenal gland is made up ofan outer cortex and an
and create a situation that would require repeat inner medulla. The cortex is derived from mesoderm
exposure to 131L Total or subtotal thyroidectomy and is made up of three zones, each responsible for
is an alternative therapy if the patient experiences the synthesis and secretion of specific steroid hor-
side effects to methimazole or is unable to achieve mones: the zona glomerulosa produces aldosterone,
remission with oral drug therapy alone. An expe- the zona fasciculata synthesizes cortisol, and the
rienced surgeon should perform this procedure to zona reticularis produces androgens. Cllolesterol is
decrease the complications. Surgical complications the precursor to all steroid production; a sequential
from a thyroidectomy include hypocalcemia from series ofenzymes leads to synthesis of aldosterone,
permanent or transient hypoparathyroidism and cortisol, and androgens. The production of cortisol
recurrent laryngeal nerve injury. Neonatal Graves is directed by pituitary ACTH, while aldosterone
disease generally resolves over the first several months is under the regulation of renin. Disease states can
oflife as maternal antibodies are cleared. Ifthe infant result in over- or underproduction ofadrenal steroid
is symptomatic or hemodynamically compromised hormones.
HYPOADRENOCORTICISM should be suspected ifthe corticotropin stimulation

Primary Adrenal Insufficiency test is abnormal (stimulated cortisol of <20 llg/dL).
Primary adrenal insufficiency may be congenital or
Traatmant
acquired and results in decreased cort::isol synthesis
and secretion. Depending on the disease process, Adrenal crisis is a life-threatening condition that
there may also be a decrease in aldosterone release. should be treated without delay. Correction ofelec-
In the newborn, primary adrenal insufficiency may trolyte abnormalities and dehydration is required
be caused by adrenal hypoplasia congenita, ACTH immediately with 5% dextrose in normal saline and
unresponsi~ness, adrenal hemorrhage, or ischemic
stress-dose intra~nous glucocorticoids. Long-term
management of primary adrenal insufficiency con-
infarction with sepsis (Waterhouse-Fredericbon
syndrome). In older children and adolescents, sists of maintenance doses of oral glucocorticoid&
autoimmune adrenal insufficiency (Addison disetUe) and mineralocorticoid&. The glucocorticoid dose is
is most common. It may occur alone or in association increased during times of acute metabolic stress to
with another autoimmune endocrinopathy such as avoid adrenal insufficiency.
Hashimoto thyroiditis or Type 1 DM. Thberculosis, CONGENITAL ADRENAL HYPERPLASIA
hemorrhage, fungal infection, neoplastic infiltra-
tion, and HIV infection may also cause destruction Congenital adrenal hyperplasia (CA.H) is a genetic
of the adrenal gland. Adrenoleukodystrophy is an condition in which there is underactivity or absence
X-linked recessive disorder oflong-chain fatty acid of a steroidogenic pathway enzyme. The clinical
metabolism that results in adrenal inrrufficiency and characteristics of CAH depend on where in the
progressive neurologic dysfunction. In contrast to pathway the enzyme deficiency lies. Figure 15-1 is
a schematic ofsteroidogenesis in the adrenal cortex.
primary adrenal insufficiency, secondary adrenal
21-Hy~liue deficiency accounts for ~of the
insufficiency is caused by an ACTH deficiency.
The most common cause of ACTH deficiency is cases of CAH. 21-hydroxylase deficiency is inher-
chronic steroid therapy, which results in suppression ited as an autosomal recessive trait and tends to
of pituitary ACTH. Congenital hypopituitarism or occur as either classic salt-wasting 21-hydroxylase
pituitary tumors (craniopharyngioma) also result in deficiency presenting in infancy or as virilizing
depressed pituitary ACTH secretion. 21-hydroxylase deficiency presenting anytime in
childhood. 21-Hydroxylase is needed to produce
Clinical ManlfaslaUons aldosterone and cortisol; its deficiency results in a
Symptoms ofadrenal insufficiency include weakness, buildup of the precursors ofaldosterone and corti-
nausea, vomiting, weight lou, headache, emotional soL Specl6cally,17-hydroxyprogesterone increases,
lability, and salt craving. Postural hypotension is which is then metabolized to dehydroepiandrosterone
common. Increased pigmentation ~r Joints and on (DHEA) and androstenedione, which are typically
scar tissue, lips, nipples, and the buccal mucosa is weak androgens. Androstenedione is then converted
observed in primary adrenal i.nsuffidency because of to testosterone. Both forms of21-hydroxylase defi-
increased ACTH secretion. Melanocyte-stimulating ciency result in decreased cortisol and aldosterone
hormone is a byproduct of the ACTH biosynthetic secretion. increased adrenocorticotropin hormone
pathway. The postural hypotension and salt craving (ACTH), and increased 17-hydroxyprogesterone.
are caused by a lack of aldosterone, leading to renal 11-~lase deficiency acoounts for 59(. ofCAH
sodiwn wasting. Adrenal crisis is a medical emergency and is also inherited as an autosomal rec:euive trait.
characterized by fever, vomiting, dehydration, and Similar to 21-hydroxylase deficiency, 11-hydroxylase
shock. It may be precipitated by intercurrent illness, deficiency impairs the production ofaldosterone and
trauma, or surgery. cortisoL ll·Hydroxylase Is responsible for the conversion
Electrolyte abnormalities associated with low of(l) 11-deoxyrortisol to cortisol, and (2) deoxycorti-
cortisol Include hyponatremia caused by inability to costerone to corticosterone in the aldosterone pathway.
excrete free water and hypoglycemia. Low aldosterone Deoxycorticosterone is a weak mineralocorticoid. but
production will also lead to hyponatremia (because in large quantities it has stronger activity. Children with
of the inability to reabsorb sodium), hyperkalemia, this condition typically present with hypertension and
and a metabolic acidosis. An elevated baseline ACTH cortisol deficiency in addition to hyperandrogenism
with a concurrent low cortisol level is consistent with because of shunting of the cortisol and aldosterone
primary adrenal Insufficiency. Adrenal insufficiency precursors down the androgen pathway.
Adrenal cortex Testis
CholecJteml
120,2~0
~ 17-0H- 17,21){)
A5 Pathway: 11" Pregnenolone ----+ 17«-Hydroxypregnenolone---+-
114 Pathway:
! at>HSD 17.0Hue
Prog88Wrone ----+ 17a-Hydroxyprogesterone ---+-
! Sb-HSD 17,21){) ..-------'L---,
! !
1+--..t
21-0Hue 21-0Haaa
!
11-Deoxycortioosterone
11·01-tuo !
11-Deoxycortisol
11-0Haae
Corticosterone
Cortisol
!18·0~
18-HydroxycorUcosterone
!
Aldosll!rone
MineralocortiCOid& Glucocorticoids Androgen&
~~~~~-15-.~.:.~--~~~!:1.~~!!~ ot..~eroidoger_l_!Sis in ~he adrenal oort~:········--····················-········································-················--··-············-
Clinical Manlfesbdlons and testosterone are also elevated, and renin and
In congenital 21-hydroxylase deficiency, 46, XX aldosterone levels are depressed.
infants are born with overvirilized ambiguous
genitalia. Oitoromegaly and Jabioscrotal fusion Treatment
may result in erroneous male sex assignment. Hydrocortisone therapy is used for cortisol replacement
There is normal ovarian development, and internal and reduces ACTH secretion and overproduction
genital structures are female. 46, XY infants born of androgens. Fludrocortisone, a synthetic miner-
with the defect have no genital ambiguity. UnJess alocorticoid, is administered to normalize sodium
identified by newborn screen, male infants may and potassium. Cortisol doses may range from 10 to
present with poor feeding, failure to thrive, leth- 20 mglm7'/day divided into three doses throughout
argy, dehydration, hypotension, hyponatremia, and the day. Fludrocortisone dosing is typically 0.05 to
hyperkalemia. Symptoms of emesis, salt wasting, 0.1 mg daily, although infants may require higher
dehydration, and shock develop in the first 2 to 4 dosing and even additional sodium supplements.
weeks oflife. Hyponatremia and hyperkalemia result Families require education on the administration
from lack of aldosterone, and hypoglycemia results of hydrocortisone "stress dosing:' They are asked
from decreased levels of cortisoL The diagnosis of to give larger doses of hydrocortisone during times
21-hydroxylase deficiency is made by documenting of physiologic stress (fever > 101•F, vomiting illness,
elevated serum levels of 17-hydroxyprogesterone trawna, surgical procedures). Depending on the
greater than 5,000 ng/dL (usually much higher}. In severity of the stress, a bolus of 50 to 100 mg/m2 is
11-hydroxylaae deficiency, there is overproduction given and then an additional 50 to 100 mg/m2/day
ofdeoxycorticosterone, which lw mineralocorticoid intravenously in three to four divided doses until
activity and results in hypernatremia, hypokalemia, clinically stable. Intramuscular (IM) hydrocortisone
and hypertension. Diagnosis is based on the mea- may be a.dm.inistered at home by the parent in the
surement of increased levels of 11-deoxycortisol vomiting child or child with mental status changes.
and deoxycorticosterone in the serum or their The linear growth and sexual development of
metabolites in the urine. Serum androstenedione children with 21-hydroxyla.se deficiency must be
monitored closely. Undertreatment, as indicated by suppress a pituitary source, but will not suppress
elevated 17-hydroxyprogesterone, androstenedione, an adrenal tumor. An MRI scan of the pituitary
and renin levels and by accelerated advancement of or CT scan of the adrenal glands is also helpful in
slceletal. maturity, leads to excessive growth. premature deterlllining the tumo.r location.
pubarche, and virllization of the child. Ultimately,
Treatment
undertreatment may lead to premature epiphyseal Both pituitary and adrenal tumors that cause Cushing
fusion and adult short stature. Overtreatment with
syndrome require surgical removal. Trans-sphenoidal
hydrocortisone suppresses growth and may cause microsurgery Is the most effective method ofpituitary
symptoms ofhypercortisolism. microaden.oma removal. Perioperative stress dosing
HYPERCORnSOLISM of glucocorticoids is needed to avoid adrenal insuf~
ficlency. Postoperatively, the patient may develop
Cushing Syndrome
a mineralocorticoid deficiency in addition to the
Cushing syndrome is a constellation of signs and
glucocorticoid deficiency.
symptoms that result from any form ofcortisol excess.
It is caused by either endogenous overproduction
of cortisol or excessive exogenous treatment with DISORDERS OF PUBERTY
pharmacologic doaes ofglucocorticoids. Endogenous PRECOCIOUS PUBERlY
causes fnclude Cushing disMse (pituitary overpro-
True precocious puberty is defined as secondary sex
duction of ACTH) and adrenal twnors. Cushing
characteristics presenting in girls before 8 years ofage
disease is the most common etiology of Cushing
and in boys before 9 years of age and may be either
syndrome in children older than 7 years. In most
gonadotropin-depmdmt or goMdotropin-independent.
instances, it is caused by a microadenoma of the
True central (gonadotropin-dependent) precocious
pituitary gland. resulting in ACTH oversecretion.
puberty is more common in girls than in boys. Preco-
which then stimulates cortisol production by the
cious puberty in girls is usually idiopathic, whereas in
adrenal glands. In infants and children younger than
7 years, cortisol~secreting adrenal tumors are most boys there is a greater incidence of CNS pathology.
Brain tumors causing gonadotropin-dependent pre-
common. Most adrenal tumors that cause Cushing
cocious puberty (GDPP) include gliomas, embryonic
syndrome are adenomas. Ectopic ACTH secretion
germ cell tumors, and hamartomas. Other causes
is a paran.eoplastic syndrome that may occur with
of GDPP include hydrocephalus, head injury, CNS
other mallgnancies; howeve~ this is exceedingly
infection, and congenital malfurmation. Gonado-
rare in children.
tropin-independent precocious puberty (GIPP) is
Clinical Manltes1atlons extremely rare but does occur in McCune-Albright
The classic signs and symptoms ofCushing syndrome syndrome (polyostotic fibrous dysplasia ofbone and
include slow linear growth with pubertal arrest, c~ au lait spots), .familial male-limited precocious
•moon• facies, central obesity, violaceous abdominal puberty (also known as familial testotoxicosis),
striae, acne, hirsutism, facial flushing, hyperpig- Leydig cell tumors, and ectopic human chorionic
mentation. hypertension, fatigue, muscle weakness, gonadotropin (HCG) production by neoplasms such
buffalo hump, and emotional and mental changes. as hepatic and pineal tumors. Benign premature
Some adrenal tumors also produce androgens and thelardre refers to isolated early breast development
cause virilization. Diagnostic testing should include that typically appears between ages12 to 2.4 months.
documentation of an increased 24-hour urine-free Premature thelarche is likely caused by small transient
cortisol collection and elevated midnight salivary bursts of estrogen from the prepubertal ovary or
cortisol test. If hypercortisolism is demonstrated. a from increased sensitivity to low levels of estrogen
low-dose dexamethasone suppression test is performed in the prepubertal female. Girls with this condition
to document the presence of Cushing syndrome. typically have a normal growth rate and bone age.
Dexamethasone is given in the late evening, and a Premature adrenarciu refers to the early appear-
cortisollevd is measured the next morning. Failure ance of pubic and/or axillary hair before 8 years of
of the dexamethasone to suppress the morning age in girls and 9 years of age in boys. This benign
cortisol level is consistent with Cushing syndrome. condition is caused by early maturation of adrenal
A prolonged hlsh-dose dexamethasone suppression androgen secretion. This is an isolated finding in
test is used to differentiate Cushing disease from children with a normal~ to slightly advanced growth
an adrenal tumor. High-dose dexamethasone will rate and bone age.
Clinical Manlfasta11ans sex characteristics at 14 years of age or the failure

In premature thelarche, gonadotropin and serum to complete genital growth 5 years from the onset of
estrogen levels are in the prepubertal range, and puberty. Constitutional delay ofgrowth and puberty
there is a normal linear growth rate and bone age, is the cause in 90% to 9596 ofcases. In these children.
unlike in true precocious puberty, in which one the bone age is delayed, growth is slow, and puberty
sees linear growth acceleration and bone age ad- simply appears late. There is usually a family history
vancement. In premature adrenarcl\e, the levels of of delayed puberty.
adrenal androgens are normal for pubertal stage but
DlffannUal Diagnosis
elevated for chronologie age. The chlld's bone age
Pubertal ddaycan be caused by primary gonadal fai1-
is usually slightly advanced. Children with prema-
ure (hypergonadotropic hypogonadism). Examples of
ture adrena.rche must be evaluated for other causes
this include 1\trner syndrome (45,X) or autoimmune
of increased androgen production, such as CAH,
ovarian failure (in girls} and Klinefelter syndrome
polycystic ovarian syndrome, or adrenal tumor. In
(47,XXY} in boys. Hypogonadotroplc hypogonadism
children with evidence ofsignificant androgen effect
is caused by hypothalamic/pituitary axis dysfunction.
(advanced bone age, growth acceleration), measure-
Examples include Kallmann syndrome, isolated go-
ment of adrenal steroids and androgens before and
nadotropic deficiency, hypothalamic and pituitary
after ACTH administration is used to identify those
tumors, hypopituitarism, and anorexia nervosa. Other
with CAH. The clinical manifestations of GDPP
endocrine disorders (e.g., hypothyroidism) may also
include premature development of secondary sexual
delay or advance puberty. Systemic, chronic diseases
characteristics and an accompanying growth spurt.
may delay puberty in both sexes.
Ifthe GDPP is secondary to pathology of the CNS.
focal neurologic signs can be present. Diagnosis is Clinical Manifestations
based on advanced bone age and pubertal levels The history and physical. examination should include
of gonadotropins (LH and FSH) and estrogen or an examination oflinear growth trends, the timing of
testosterone. A pubertal pattern ofelevated gonad- puberty in other family members, and an assessment
otropins after infusion of gonadotropin-releasing of the patient's current Tanner staging. Laboratory
hormone (GnRH) is indicative of GDPP. In GIPP, evaluation is helpful, including bone age, testoster·
gonadotropins are low, sex steroids (estrogen or one and estradiol levels, gonadotropins, FSH, LH,
testosterone) are high, and GnRH infusion has no prolactin, and thyroid function testing. Screening
effect on gonadotropin levels. for synemic disease may also be warranted.
TnHitment Treatment
Premature thelarche is a benign condition that does In the case of constitutional delay, a short course
not require any treatment. Premature adrenarche of sex steroids may be needed to initiate pubertal
that is not caused by CAH or a tumor is also a be- development. Psychosocial support is also import-
nign condition. GDPP is treated with Ions-acting ant. If permanent hypogonadism is determined to
GnRH agonists. GnRH agonists are administered be the etiology, sex steroid replacement is initiated
via quarterly or monthly injection (leuprolide) or as at the normal time of puberty and continued for
a subcutaneous implant (histrelin) replaced yearly. the patient's life.
GnRH analogues suppress gonadotropin release and
thereby decrease secondary sex characteristics, slow
DISORDERS OF CALCIUM
skeletal growth. and pl'el'ent the fu&ion oflons bone
epiphyseal plates. GIPP is managed by treating the Disorders of calcium and phosphorus metabolism
underlying disease process. result from abnormalities in the two major regula-
tors ofcalcium homeostasis: parathyroid hormone
PUBERTAL DBAY (PTH) and vitamin D. Total serum calcium is
Pubertal delay is characterized by a delay in the on- tightly regulated within a narrow range (normally
set of puberty or in the rate of progression through between 9 and 10.5 mg/dL). Calcium is bowtd to
normal sexual development. In females, this refers albumin. As a result, the total calcium may be low,
to the absence of secondary sex characteristics at whereas the ionized calcium is normal (1.1 to 1.4
13 years of age or the absence of menarche 3 years mmol!L). PTH is secreted by the parathyroid glands
from the onset of sexual development. In males, in response to low levels ofcalcium. PTH increases
pubertal delay denotes the absence of secondary serum calcium by releasing stored calcium from
bone, increasing renal retention of calcium, and Low serum cal.clum with low serum phosphorus
increasing the production of the active vitamin D is consistent with vitamin D deficiency. In vitamin
metabollU! (1·25(0H)2D). D deficiency, PTH levels are extremely elevated in
an attempt to normalize the serum calcium at the
HYPOCALCEMIA expense of bone resorption. resulting in excessive
Etiology renal phosphorus wasting.
Hypocalcemia may be the result of (1) inadequate
PTH secretion (hypoparathyroidism) or action Treatment
(pseudohypoparathyroidism), (2) vitamin D defi- The treatment of hypoparathyroidism is replace·
ciency or resistance, or (3) other disorders such as ment with oral calcium supplements and oral cal-
hypomagnesemia, hyperphosphatemia, hypoprotein- citriol, a synthetic version of 1.25 (OH)a vitamin D.
emia, and/or drug toxicity. There are congenital and Hypocalcemia as a result of vitamin D deficiency
famllial forms of hypoparathyroidism. Pseudohypa. should be treated with 25-0H vitamin D. Resistance
parathyroidiam is due to a PTH receptor mutation to vitamin 0 must be treated with oral calcium and
and creates a PTH-resistant state. Other causes of high doses of calcitrioL
hypoparathyroidism include autoimmune disease, HYPERCALCEMIA
surgical removal of the parathyroid glandJJ, DiGeorge
syndrome, and hypomagnesemia (magnesium is nee. Hypercalcemia is diagnoaed when calcium levels are
essary for adequate PTH secretion). Of note, many greater than 12 mgldL. Hypercalcemia may be due
cases ofhypoparathyroidiam are idiopathic in nature. to (1) hyperparathyroidism; (2) hypervitaminosis
D; (3) immobilization; (4) neoplasia; or (5) familial
VitaminD deficiency may be due to inadequate nutri-
hypocalciuric hypercalcemia. Hypercalcemia can also
tional intake. Higher riskindMduals include infants
be associated with Williams syndrome or multiple
who are exclusively breastfed. people with darker
endocrine neoplasia syndrome types 1 or 2a. which
skin pigmentation, use of medications that rapidly
are associated with hyperparathyroidism caused by
metabolize vitamin 0, and living in areas with limited
parathyroid hyperplasia.
sunlight exposure. Vitamin D requires enzymes in
the liver and kidney to convert the fat-soluble form COnical Manlfas1allons
of vitamin D to its most active form (calcitrio~ or Hypercalcemia may be asymptomatic or it may pres-
1,25 (OH)z vitamin D). In addition, there are vitamin ent with vomiting, lethargy, inability to concentrate,
D resistance syndromes in which hypocalcemia and depression, seizures, polyuria. and hypertension.
hypophosphatemia are seen despite elevated levels Patients may also present with renal calculi on ab-
of 1,25 (OH):z. Hypocalcemia may also be seen in dominal ultrasonography, pathologic fractures, or a
BartU!r syndrome, renal tubular acidosis, and as a short QT interval on electrocardiograph.
side effect of the administration of particular drugs
(furosemide, calcitonin, and antineoplastic agents). Treatment
Medical management ofsymptomatic hypercalcemia
Clinical Manifastations is hydration with intravenous sa.Une. Furosemide
A patient with hypocalcemia may present with may be given (1 mg!kg) in 6-- to 8-hour intervals;
carpopedal spasm (Trousseau sign), facial twitch- however, one must be careful of inducing dehydra-
ing (Chvostek sign), jitteriness, tetany, or seizures. tion. Bispho.sphonate infusions (pamidronate) have
Laryngospasm may cause shortness of breath or also been found to be useful to inhibit osteoclast
apnea. The electrocardiogram may reveal a prolonged function. A sestamibi parathyroid scan may be in-
corrected QT interval. Vitamin D deficiency often dicated to identify a surgically removable adenoma
presents with rachitic bone disease and poor growth of the parathyroid gland. Hypercalcemia caused by
parameters in children. The electrolyte pattern may vitamin D excess may be treated by glucomrticoids
identify and diagnose the defect of hypocalcemia. In or ketoconazole to suppress the renal activation of
hypoparathyroidism, the serum calcium is low, and 1-25(0H)2D.lt is equally important to identify the
serum phosphorus is elevated because of a lack of individual with familial hypocalciuric hyperca1.cemia,
renal stimuli by PTH to excrete phosphorus. This a benign condition, so that unnecessary aggressive
pattern is also seen in pseudohypoparathyroidism. management is avoided.
KEY POINTS
• DM i8 a chronic metabolic disorder character- Graves disease results from transplacental
ized by hyperglycemia and abnormal energy passage of maternal thyroid-stimulating
metabolism reaultilg from absent or dminished immunoglobulins.
insulin secretion or action at the ceiiUar level. • The most common cause of juvenile or acr
• T1 DM results from a lack of insulin production qued hypothyroidism Is Hashimoto thyroiditis,
by the jl-cells of the pancreas. Long-term which is an autolmmooe chronic lymphocytic
complications from T1 OM include microvas- thyroiditis that results In deatruction of the
cular disease (retinopathy, nephropathy, and thyroid gland. Hypothyroidism Ia treated with
neuropathy) and accelerated large vessel synthetic levothyroxlne.
atherosclerotic disease. • 21 -Hydroxylase deficiency accounts for 90% of
• The percentage of T2DM cases in children is the cases of CAH.In congenltal21 -hydroxylase
rising. deficiency, female Infants are born with am-
• The definition of hypoglycemia is a plasma glu- biguous genitalia, whereas male infants born
cose value of less than 50 mgldL. Hypoglycemia with the defect have no genital abnormalities.
may be the result of hyperinsulinemia, pituitary The diagnosis of this form of CAH is made by
disease (ACTH deficiency with or without GH documenting elevated levels of 17-hydroxy-
deficiency), glycogen storage disease, disor- progesterone in the serum.
del"8 of gluconeogenesis, or defects in fatty • Primary adrenal Insufficiency may be congenital
acid oxidation. or acquired and reaults In decreased cortisol
• In central diabetes lnq,ldus, there Is loss of and aldosterone secretion, whereas secondary
ADH secretion and an lnablity to concentra1e adr8nal insufftciency Ia caused by adrenocor-
the twine. This may occur after head trauma, ticotropin hormone (ACTH} deficiency and
with a brain tumor, or with CNS infection. manifests only with low cortisol.
• A low 88'\1'11 osmolality with inappropriately • CUshing syndrome Ia a constellation of symptoms
elevated urine osmolality and twine sodium are and signs that reeult from high cortisol levels and
consistent with SIADH. SIADH Is treated with is caused by either endogenous overproduction
fluid restr1ctlon. Hypertonic fluids may be ad- of cortisol or excessive exogenous treatment
ministered In acute symptomatic hyponatremia with pharmacologic doses of cortisol.
as long as the serum sodium is not corrected • True precocious puberty Is defined as sec-
too rapidly. ondary sex characteristics presenting before
• Eighty percent of cases of short stature result the age of 8 In girls and 9 In boys. Precocious
from normal variations In growth and develop- puberty may either be gonadotropin dependent
ment and are caused by either familial (genetic) or independent. The most common cause of
short stature or constitutional delay of growth pubertal delay Is constitutional delay.
and puberty. • Inadequate PTH secretion (hypoparathyroidism)
• Most cases of hyperthyroidism in children or action (pseudohypoparathyroidism) and
are caused by Graves disease, which is an vitamin D deficiency are likely causes of hypo-
autoimmune-Induced activation of the TSH calcemia in the pediatric patient. The treatment
receptor. Medical therapy for Graves disease of hypoparathyroidism Ia replacement with oral
consists of antithyroid medication. Neonatal calcium supplements and calcltr1ol.
CLINICAL VIGNETTES
VIGNETTE 1 VIGNET1E2
A 15-year-old previously healthy male began experi- A 121h-year-old girl presents with short stature (<3rd
encing fatigue and dizziness upon standing about 2 percentile) and growth failure. She has felt well, but
weeks ago. His appetite is poor. He has had no weight school records indicate that she has not grown in
gain over the past 6 months, and pubertal develop- height since age 8 years. She has had mild constipation
ment Is delayed. His father completed linear growth and cold intolerance. She is an •A• student in school.
by age 17 yeara, and his mother's age of menarche Her skln Is dry, and she has delayed relaxation of her
was 13 years. On physical examination, he appears deep tendon reflexes. You note diffuse homogeneous
thin, with weight at the 20th percentile and height at enlargement of 1he thyroid gland.
the 75th percentile. Blood pressure Is 90/60 mm Hg
supine, falling to 60140 mm Hg upon standing. Supine 1. Which set of thyroid function tests is most likely
pulse was 80 beats/min, increasing to 120 beats/min based on this patient's clinical findings?
standing. Clinically, he is well hydrated. He appears
to have a well-developed sun tan, noticeably different A I c D
from his parents, who are pale In complexion. The Serum T4 (j.lg/dL) 2.0 2.0 8.0 13.0
thyroid gland is mildly enlarged. Pubic hair and axillary Free T4 (ngldL) 0.6 0.6 3.2 5.2
hair are sparse, and testicular volume is 6 milliliters
bilaterally. His neurologic examination is normal. Ra- TSH(mU/mL) 75 1.5 2.5 0.1
diographs of the chest are normal. Bone age Is read 24-hour radioiodine uptake 3% SCJ' 15% 30'-"
as 13 years. Hematocrit is 30%. Serum thyroxine {T.c)
is 8.5 !Jg/dL. TSH was 2.9 JJ.U/ml (nonnal 0.3 to 5.0), Nonnal values T4 are 5 to 12 J.lg/dl, tree T4 are 1.1 to
FSH was 4.6 mU/ml (nonnal 5 to 30), prolactin was 4.0 ng/dl, and 24 hours radioactive Iodine uptake test
4.7 ng/ml (nonnal3to 24), and IGF-11evel was 252 (RAIU) Scan are 10% to 25%.
nglmL (normal152 to 540). Plasma cortisol at 8 AM
2. Which of ltle following Is the most likely underlying
was 2.9 IJg/dL.
cause of this patient's diagnosis?
1. What is the most likely diagnosis? L Iodine deficiency
L Primary adrenal insufficiency b. Autoimmune thyroiditis
b. Secondary adrenal insufficiency c. Functional nodule
c. Secondary hypoltlyroidism d. Multinodular goiter
d. ConstHutlonal delay of growth and puberty
e. Pituitary tumor VIGNET1E3
A 6-year-old female presents with a 6-month history
2. Which of the resuHs of further laboratory testing
of axillary and pubic hair development. In addition, the
would be most likely?
family has noticed an occasional acne lesion. There
L Serum sodium 132 mEqll. serum potassium
is no history of vaginal discharge or bleeding and no
6.8 mEqll.., serum bicarbonate 18 mEqll.... blood
breast tissue on physical examination. The parents
urea nitrogen 20 mgldl, ACTH 230 pmoVL
deny any known exogenous honnone exposure.
b. Serum sodium 130 mEqll. serum potassium
4.0 mEqll.., serum bicarbonate 27 mEqll.... blood 1. Which of the following does not support the
urea nitrogen 12 mgldl, ACTH 10 pmoVL diagnosis of premature adrenarche?
c. Serum sodium 145 mEqll. serum potassium a. Bone age of 7 years
4.2 mEqll.., serum bicarbonate 28 mEqll.... blood b. Growth velocity of 10 em/year
urea nitrogen 14 mgldl, ACTH 25 pmoVL c. Elevated DHEAS levels
d. Presence of body odor
3. What is the most likely pathology involving the
adrenal glands in this patient? 2. The patient's bone age is reported to be 10 years.
L Autoimmune destruction Upon review, the growth chart demonstrates
b. Tuberculosis that the height was fonnerly plotted at the 50th
c. L.ate-onset congenital adrenal hyperplasia percentile; over the course of 3 years, height is
d. Craniopharyngioma now at the 9oth percentile. Which of the following
fmdings would assist in the diagnosis of late-onset 1. What is the patient's Tanner stage?
21 -oH deficiency? a. Tanner 2 Breasts, Tanner 1 pubic hair
a. Hyponatremia b. Tanner 3 Breasts, Tanner 1 pubic hair
b. Hyperkalemia c. Tanner 2 Breasts, Tanner 0 pubic hair
c. Hypertension d. Tanner 3 Breasts, Tanner 2 pubic hair
d. Elevated 17-hydroxyprogesterone
2. What is the most likely diagnosis?
VIGNETTE4 L Hypothyroidism, with breast development occur-
A ~year-old girt developed increased thirst and poly- ring secondary ID van Wyk Grumbach syndrome
ur~a rather abruptly 2 weeks ago. She is constantly
b. Gonadotropin-independent precocious puberty
thirsty and becomes angry when fluids are not readily c. Gonadotropin-dependent precocious puberty
available. She has also begun wetting the bed after d. Benign premature thelarche
being dry for 2 years. 3. The patient is started on treatment with leuprolide
1. Which of the following represents the least likely injections. What isthe mechanism ofaction of this drug?
L Antagonist of the GnRH receptor on the
diagnosis in this child?
a. Diabetes mellitus pituitary gland
b. Diabetes insipidus b. GnRH agonist
c. Hyperthyroidism c. Estrogen receptor antagonist
d. Hypocalcemia d. L.H agonist
2. Initial screening tests include serum Na 150 VIGNETtE&
mEqll, K 4.5 mEqll, bicarbonate 28 mmoVL, Cl
110 mEq.IL, BUN 10 mgldl, Ca 9.5 mgldl. and 1. A 12-year~ boy presents to the emergency room
glucose 80 mgldl. Serum osmolality is measured with a seizure. Elactrolytes are obtained at 1he time
at 295 mOsmll. Osmolality of a first morning of the seizure and are notable for sodium 140 mEq/L
void of urine is 100 mOsmll.. What further tests n.
(135 to 145), potassium 4.1 mEqll (3.9 to 5. glucose
should be completed to confinm the diagnosis 76 mgfdl(70to 110)calcium 6.7 mgldl(8.8 to 10.8),
and detenmine possible causes? phosphorous 2.9 mgldl (3.0 to 4.8). What electrolyte
a. Repeat morning testing and renal unrasound abnormality Is 1he likely cause of his seizure?
b. Water-deprtvatlon teat and brain MRIIf respon- a. Phosphorous
sive to vasopressin b. Glucose
c. Oral glucose tolerance test and screening tor c. Sodium
autoimmune diseases d. Calcium
d. ACTH stimulation test and measurvment of He is stabilized and stops seizing. On further his-
free water excr9tion tory, his parents share that he is an extremely picky
~er and that his diet consists primarily of hot dogs,
VIGNmE&
ch1pa, carrota, and Frvnch fries. He has ice cream or
A 5-year-old girl presents for evaluation of breast de- yogurt very occasionally but does not eat any yogurt
velopment, noticed by her mother 2 months previously. or cheese. He has no history of fractures. He does not
She does not have any acne, axillary hair, or pubic hair: take any medications. Mom does take him outdoors to
Mom has noticed some whitish vaginal discharge on play a couple of days a week as the weather penmlls.
her underwear, but no blood. She denies headaches or You obtain further lab tests that show:
visual changes. Her height and weight had previously
been tracldng atthe 25th percentile until recentty, when 25 Hydroxy vitamin D, Total: 5.8 nglmL (30 to 119)
her height Increased to the 4oth percentile. On exam, 1,25 Dihydroxy vitamin D: 169 pglml (24 to 86)
she has firm breast tissue just under the areola bilaterally. Parathyroid hormone (PTH): 606 pglml {15 to 55)
There is no axillary hair or pubic hair: Hervaginal mucosa
appears pale pink in color. She has no birthmart<s or 2. What is the underlying cause of his low calcium?
rashes. The remainder of her exam is normal. a. Hypoparathyroidism
The patient's laboratory evaluation at 7 AM ruvealed b. High 1,25 dlhydroxy vnamln D
the following: (reference ranges noted for age) c. Low 25 hydroxy vitamin D
d. Lack of sunlight
LH 1.2 miU/mL (<0.4 miU/mL)
Estradiol 28 pglml (<18 pglmL) 3. What is the treatment for this patient's hypocaloemia?
L VItamin D, calcitriol, and calcium
TSH: 3.7 mU/ ml (0.5 to 4.3)
b. VItamin D and calcium
Free T4: 1.0 ngldl (0.9 to 1.6) c. Calcitnol alone
Bone Age: 7 years at the chronologie age of 5 years d. Daily multivitamin
ANSWERS
VIGNETTE 1 Question 1 autoimmune endocrine deficiencies. Other causes of

1.Answer B: primary adrenal insufficiency include tuberculosis or
The symptoms of fatigue, weight loss, and dizziness other granulomatous diseases, infiltrative diseases,
on standing are relatively nonspeclftc. However, the and adrenal hemorrhage. Brain tumors could result in
delayed puberty and bone age and the finding of pos- secondary adrenal Insufficiency from ACTH deficiency.
tural hypotension suggest adrenal insumciency. Primary late-onset congenital adrenal hyperplasia would pres-
(rather than secondary) insufficiency Is suggested by ent with early signs of androgen excess, linear growth
the hyperplgmentatlon and the effects of ACTH and Its acceleration, and bone age advancement, without the
melanocyte-stimulating activity. The enlargement of his salt wasting as seen in newborns.
thyroid gland may be due to risk of primary thyroiditis.
The clinical presentations of primary and secondary VIGNETTE 2 Question 1
insufficiency overlap EXCEPT for the finding of hyper- 1.AnswerA:
plgmentadon on physical examination. The presence of The patient's history and physical examination findings
high AC1li levels stimulates melanocyte activity; this suggest hypothyroidism. The most likely laboratory
is seen in primary adrenal insufficiency. The inability findings in uncomplicated primary hypothyroidism
to produce ACTH, as seen in hypopituitarism (either are represented in (A). TSH is elevated, and both T4
congenital or secondary to a brain tumor) would result and free T4 are low. The uptake of radioiodine by the
in ACTH deficiency and symptoms of adrenal insuf- thyroid at 24 hours (representing t he rate of iodination
ficiency. Although one may observe delayed puberty of thyroglobulin in the thyroid gland) is usually low. (8)
and bone age in an adolescent with hypothyroidism, is most consistent with secondary hypothyroidism
this patient's laboratory values are not suggestive of (pituitary TSH deficiency). (C) is reflective of a normal
secondary hypothyroidism. Secondary hypothyroid- subject. (D) 111presents a set of typical results in a
ism implies the pituitary's inability to respond to low subject whh hyperthyroidism (suppressed TSH and
thyroxine levels. The TSH may be mildly elevated or elevated total and free TJ.
normal in the setting of a low T4• Constitutional delay
of growth and puberty Is a diagnosis of exclusion. VIGNETTE 2 Question 2
Chronic illnesses that impair linear growth, delay 2.AnswerB:
the maturity of the bone, and delay puberty must be The most likely pathologic diagnosis in a spontaneously
excluded. Often, there is a famDy history of delayed hypothyroid patient with a goiter is autoimmune thy-
puberty In a parent roiditis. The diagnosis is confirmed in 80% to 90% of
cases by demonstrating elevated titers of antithyroid
VIGNETTE 1 Question 2 antibodiee in the patient's serum. Iodine deficiency
2.AnswerA: can result in a goiter; however, patients who consume
The most likely laboratory results would be those in diets that are not iodine deficient will not have this as
(A). Hyperkalemia would be expected because of a cause. Hypothyroidism caused by Iodine deficiency
mineralocorticoid deficiency, which occurs in primary Is rare In the United States (partly because of Iodized
adrenal insumciency but not usually in secondary adrenal table salt), unless the individual has emigrated from
insufficiency. Lack of mineralocorticoid predisposes another country. Functional thyroid nodule would pres-
to metabolic acidosis because of reduced hydrogen ent wtth thyroid fullness that is unilateral. Laboratory
lon excl'9tlon. The basellneACTH level would be high. tasting of affected patients demonstrates suppressed
The results shown in (B) are typical of secondary ad- TSH, from either overproduction of T4 by the nodule or
renal insufficiency because of pttuitary disease. Here ongoing recovery from a recent hyperthyroid phase.
there is no hyperl<alemia. The hyponatremia is due to Multinodular goiters are uncommon in the pediatric
retention of water rather than to renal sodium loss. population. Upon palpation, multiple discrete nodules
Baseline ACTH levels are low. The results shown in (C) can be palpated. Affected patients may have euthy-
are compatible with normal pituitary-adrenal function. roidism or hypothyroidism.
VIGNETTE 1 Question 3 VIGNETTE 3 Question 1

3. AnswerA: 1.Answer 8:
The majority of cases of spontaneous primary adrenal Premature adrenarche is the benign, self-limited ap-
insufficiency are due to autoimmune destruction of the pearance of secondary hair growth, body odor, and
adrenal glands, also known as Addison disease. This comedones that usuaOy occurs after age 6 years.
type of Insufficiency may occur In association with other lndMduals whh premature adrenarche grow at a
slightly elevated velocity. True pubertal growth rate is are met, a small dose of vasopressin is administered
typically 9 to 12 an/year, wherau prepubertal growth to determine whether the kidneys are responsive to
rate Is 5 to 8 em/year. Advancement of the bone age the hormone. If administration of vasopressin results
Is generally considered significant If the reading Is 2 In concentration of the ur1ne and serum sodium
years greater than the chronologie age. Many typical and osmolality improve, this confirms the diagnosis
individuals may have slightly advanced bone age reports of central Dl. Because central Dl is almost always
not BSSociated with pathology. Elevation of the weak cawed by a congenital defect or an acquired lesion
androgen DHEA (measured as serum DHEAS) occurs of the hypothalamic-pituitary region, a brain MRI is
earty in this condition. Gonadal stimulation (ovarian indicated. A repeat sample may not be diagnostic,
production of estrogen and testicular production of and 1here is no role for a renal ultrasound at this stage
testosterone) will progress normally in patients with in the evaluation. Furthermore, restricting fluids in a
premature adrenarche. pediatric patient wi1h possible Dl in the home setting
(for performance of labs the following morning) may
VIGNETTE 3 Q...tlon 2 provoke severe hemodynamic Instability. There is no
2.Answar 0: indication to perform an ORAL GLUCOSE TOLERANCE
The characteristic diagnostic finding in children with TEST In this patient without elevation of blood glucose
late-onset congenital adrenal hyperplasia is elevation or the presence of glucosuria. An ACTH stimulation
of 17-0H progesterone, the immediate precursor test will pennlt evaluation of cortisol secretion after
to the impaired enzyme 21-hydroxylase. Overt salt provocation. Cortisol deficiency may result In Impaired
wasting does not occur in late-onset 21-hydroxylase free water excretion, resulting in hyponatremia and
deficiency. Thus, 1he hyponatremia and hyperkalemia concentrated urine.
often observed in congenital CAH is not appreciated in
the late-onset form. The most common defect leading VIGNETTE 5 Que&tlan 1
to all forms of CAH is 21-hydroxylase deficiency, re- 1• .AnswerA:
sulting in relatively diminished cortisol and aldosterone The patient has Tanner 2 Breasts and Tanner 1 pubic
production and overproduction of androgens. The hair. Tanner staging can be described as outlined
second most common cause is a diminished effect below. Note that 1here is no such thing as Tanner 0
of the 11-hydroxylase enzyme. Interruption of this Bnlast&;
pathway leads to overproduction of precursors with
mineralocorticoid ettect.s and subsequent hypertension. Tanner Stage 1: Prepubertal
The 17-DH progesterone levels are usually markedly Tanner Stage 2: The preeence of a breast bud just under
elevated or will be elevated after stimulation with ACTH. the areola. There may be darkening of the areola
Tanner Stage 3: Further enlargement of breast tissue
VIGNETTE 4 Queslion 1 beyond the border of the areola
1. .Answer 0: Tanner Stage 4: Areola fonns a secondary mound
The kidney will begin to diurese once the blood sugar is above the breast
greater than 160 to 180 mgldl. Thus, the combination
of polyuria and polydipsia is a common presentation for Tanner Stage 5: Mature breast with smoothing of
diabetes at alleges. Diabetes Insipidus results when border between areola and rest of breast tissue
there Is Inadequate secretion of vasopressin, because Nipple (papilla) projects above areola
of Increased serum osmolality or diminished sensitivity PUbic Hair
to vasopre6Sin at the receptor level. In either setting, the
Tanner Stage 1: Prepubertal, no hair present
kidney will excrete free water regardless of hydration
level (i.e., even when the patient is dehydrated). Other Tanner Stage 2: Sparse growth of straight hair,
causes of polyuria are hyperthyroidism, hypokalemia sometimes can be curled
and hypercalcemia, ..d urinary tract infection. Several Tanner Stage 3: Coarse, curly hair spreading onto mons
medications can induce diabetes insipidus Oithium). Tanner Stage 4: Coarse, curly hair covering mons
but does not yet extend to thighs
VIGNETTE 4 a-lion 2
Tanner Stage 5: Coarse, curly hairs extending to thighs
2.Answer B:
This patient is very close to meeting the diagnostic PanlsiMale Genblla
criteria for diabetes insipidus (01; specifically, concen-
Tanner Stage 1: Prepubertal
trated serum Na 150 mEqll and/or serum Osm 300
mOsmll.} In the face of dilute urine {urine Osm < 600 Tanner Stage 2: Enlargement of scrotum and testes;
mOsm/L and/or urine apeclftc gravity < 1.005). This scrotal skin begins to thin
can at times be diagnosed by random sampling; If not, Tanner Stage 3: Enlargement of penis Oength first),
a water-<:leprivation test is warranted. Once Dl criteria continued growth of testicles
Tanner Stage 4: Increase In penile girth, scrotal skin Trousseau sign (carpopedal spasm), muscle cramping,
darkens, continued growth of testicles tetany, and larYngospasm.
Tanner Stage 5: Adult appearance of genitalia
VIGNETTE 8 QuMtlon 2
VIGNETTE 5 Qu88tlon 2 2. Answer: c.
2. Answer: c. This patient has vitamin D deficiency, likely because
The patient has an elevated LH and estradiol, making of insufficient dietary intake of vitamin D. Sunlight
gonadotropin-dependent precocious puberty the helps promote endogenous synthesis of vitamin D,
correct answer. Profound hypothyroidism with mark- and therefore individuals who have minimal sunlight
edly elevated TSH can cause breast development exposure or wear clothes that cover all their skin are
and/or ovarian cysts with vaginal bleeding because at rtsk for vitamin D deficiency. This patient likely has
of stimulation of the FSH receptor by high levels of some decreased expo8UJ8 to aun6ght based on history,
TSH (VanWyk Grumbach Syndrome). However, this but his primary issue is low nutritional vitamin D intake.
patient's thyroid function is normal. Furthermore, hy- Low vitamin D levels lead to inadequate absorption
pothyroidism is typically accompanied by a slowing of bott1 calcium and phosphorous. In response to the
of linear growth, not growth acceleration as seen in hypocalcemia, parathyroid hormone levels rtse appro-
this patient. Gonadotropin-independent precocious priately to help replenish serum calcium levels. FTH
puberty is characterized by elevated sex steroids with increases serum calcium by: (1) promoting conversion
suppressed gonadotropins. This is due to a peripheral of 25 hydroxy vitamin D to 1,25 dihydro.xy vitamin D
source of sex steroid production or exogenous expo- (the active form of vitamin D), (2) Bone 1'8S0rptlon,
sure to sex steroids. Benign premature thelarche is a (3) calcium reabsorption in the proximal tubule of
common cause of breast development in young girts; the kidney. Dietary sources of vitamin D include fatty
however, we would not expect to see pubertal levels of fishes (salmon, tuna, mackereO. beef liver, egg yolks.
gonadotropins and estradiol or a linear growth spurt. Fortified foods provide most of the vitamin Din the
diet through milk and some brands of yogurt. Other
VIGNETIE 5 Question 3 dairy products made from milk like cheese and ice
3. Answer: B. cream are usually not fortified.
Gonadotropin-dependent precocious puberty Is treated
with a GnRH agonist such as leuprolide or histrelin. VIGNETtE I Question 3
GnRH agonists downregulate LH and FSH release S. Answer: B.
because of diminished GnRH pulsatility. Leuprolide Treatment for vitamin D deficiency ia vitamin D supple-
is an intramuscular (IM) injection and is administered mentation. This patient also has low dietary intake of
monthly. There is also a long-acting formulation of calcium, so calcium needs to be replenished through
leuprolide that is administered every 3 months. Histrelin supplementation. VItamin DIs Initially given In high
is a subcutaneous implant that is replaced yearly. doses (e.g., 2,000 IU dally, although some recommend
a higher dose given weekly) until stores ara replenished
VIGNETtE I Question 1 (usually 2 to 3 months). Then the patient should be
1. Answer: D. maintained on daily supplementation of 400 to 600 IU
The patient has low calcium, which can precipitate dally. Calcltrtolls the synthetic version of active vitamin
seizures. Low sodium and low glucose can also cause D (1,25 dihydroxy vitamin D) and is not needed in this
seizures: however, this patient has normal levels of case because the patient's own PTH will promote
these electrolytes. Abnormalities In phosphorous do conversion of 25 hydroxy vitamin D to 1,25 dihydroxy
not typically cause seizures. Other signs and symp- vitamin D. A dally multivitamin typically contains only
toms of low calcium include twitching, prolonged QT 400 to 600 IU of vitamin D, which is not adequate t o
interval, arrhythmias, Chvostek sign (facial twitching), replenish vitamin 0 stores in this patient.
Orthopedics
John F. Sarwark, Vineeta Swaroop, and Katie S. Fine
INTRODUCTION
Early diagnosis of hip dislocation results in better
Pediatricians and family practitioners require a outcomes; therefore, examination of the newborn
basic knowledge oforthopedics, as musculoskeletal is critical Gluteal Cold asymmetry may accompany
complaints comprise a large percentage of office hip dislocation in the newborn; however, up to
visits in their patients. The timely evaluation and 7196 of normal infants have gluteal fold asymmetry,
management of congenital, developmental. traumatic, resulting in very low specificity for this sign. The
and infectious bone and joint conditiom in children Barlow and Ortolani provocative tests are most
can minimize complications and loss of function. helpful. With the inflmt's hip and knee each flexed
to 9<r, the examiner places the fingertips on the
DEVELOPMENTAL DISLOCATION greater trochanter, with the thumb web space over
OF THE HIP the knee and the thumb on the inner thigh. Gentle
pressure is applied to the flexed and adducted hip in
PATHOGENESIS a posterior direction during the Barlow maneuver,
Developmental hlp dysplasia (DDH) refers to a and a positive result occurs when there is a palpable
spectrum of pathologic anatomy of the hip joint clunk as the hip dislocates in a posterior-superior
that occurs in about 1 per 1,000 births. Dysplastic direction. This test can be immediately followed
hips at birth may be dislocated and irreducible, by the Ortolani maneuver (hip abduction with a
dislocated and reducible, reduced and dislocatable, resulting •c1unk• as the head relocates into the joint)
sublux.atable (loose but not dislocatable), or stable {Fig. 16·1). DDH may evolve over time, so children
with abnormal anatomy. DDH may develop In utero, should be screened at regular intervals until they are
during delivery, or, more rarely, during infancy and ambulatory. In examining an older infant (after 3 to
childhood. If a dislocation or severe subluxation (i.e., 4 months), hip dislocations become relatively fured,
femoral head not centered in the socket) persists, and a Galeazzi sign should be sought. By holding the
the acetabulum will not develop into a cup·like ankles with the knees bent and hips flexed 9<r, the
shape, and the head of the femur will move further examiner looks for any shortening of the (affected)
out of the socket. Once the ball is repositioned in thigh. Older patients may present with limited hip
the socket in an infant, the socket has the capacity abduction, a limp, and apparent shortening of the
to regain its cup·like shape. involved extremity.
Because most of the hip and pelvis aR not ossi·
EPIDEMIOLOGY .tied at birth, radiographs are not helpful unti14 to 6
DOH is most common in the newborn with breech months of age. lntrasound is more accurate fur the
presentation or a positive family history. Risk is detection of DOH from birth to about 4 months,
slightly increased in females and first--born children. although ultrasound screening is best delayed until
Association with other anomalies has been described, 4 to 6 weeks of age, when the rate of false positive
metatarsus adductus and congenital muscular tor· examinations is more acceptable. Routine ultrasound
ticollis being most common. screening of all infants is not recommended but
348
Chapter 18 I Orthopedics • 349
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'
. . ..
-~~-~~-~ ~-~.:.~.: ~~--~~>. ~~--~!~.~!. ~~~-~.:............................................... . ..................................................... . .. . . .... . ....................................
should be considered for babies with a family history

FOOT DEFORMITIES
of DOH and for those born in the breech position.
Flexl"ble foot deformities, such as flexible flatfoot. rarely
TREAtMENT predispose children to difficult walking, poor shoe fit.
When a positive finding. an abnormal•chmk,•limlted or pain. Almost any deformity of the foot that can be
hip abduction, or limb asymmetry is noted at the molded by the examiner's hands to an anatomically
newborn examination (or thereafter), the patient correct position requires minimal or no intervention.
should be refum:d for orthopedic consultation. Most Metatarsus adductus (in-toeing of the forefoot
dislocatable hips found on newborn examination without hindfoot abnormalities) is a common. benign
stabilizewithout intervention within the first 2 weeks condition caused by intrauterine positioning. When
oflife. Iftreatment is indicated in children younger compared with clubfoot, ankle motion is unrestricted.
than 6 months, a Pavlilc harness or other type of brace Mild metatanrus adductus is flexible, meaning the
that keeps the hip abducted and flexed is the best examine r can straighten out the foot deformity on
initial treatment. Closed reduction (manipu]ation of manual examination. In cases of severe metatarsus
the hip ball into the socket) and body casting (spica adductus, the forefoot is inflexible and cannot be
cast) is used in older patients. Cases that do not corrected into a normal position. Severe cases are
respond to conservative measures require surgical treated with serial bra.clng or casting starting at ages
reduction or further hip reconstruction. 6 to 12 months. Surgery is rarely indicated.
FIGURE Ui-2. Photographs demonstrating anterior (A) and posterior (B) views of talipes equinovarus. (Photographs
~.~.~.~..~~..~~..~r.!~~..~~:)........................................................................................................................................................ ..........................................................~..
Talipes equinovarus, or clubfoot, is a rare and The patient's age affects the differential diagnosis.
potentially debilitating deformity that can be Infection, inflammation, and neuromuscular diseases
described by the acronym CAVE-Cavus of the are common etiologies in children from 1 to 3 years
forefoot, Adduction of the forefoot, Varus of the ofage. From 3 to 10 years ofage, Legg-Calve-Perthes
hindfoot, and Equinus (plantarflexion) of the ankle disease, toxic synovitis of the hip, and juvenile id-
(Fig. 16-2). Dorsiflexion at the ankle is impo881'ble iopathic arthritis become more common. SUpped
in patients with clubfoot. Without treatment, the capitalfemoral epiphysis (SCFE) is a consideration
foot becomes progressively more deformed, and in pubertal patients.
calluses or ulcerations can develop when the child
developmentally begins to ambulate. Early Ponseti
TilLE 11-1. Differential Diagnosis of Limp by
casting intervention is essential for subsequent nor-
Disease catsgory
mal function and more normal development. Initial
treatment usually consists ofserial manipulation of ~ '1hltlma or OIIWUH
the foot with toe-to-groin casting; with appropriate j Fracture Muscular dystrophy
technique, over 95% of clubfeet can be corrected. ISoft-tissue injury Peripheral neuropathy
Long-term bracing is then used to avoid relapse.
Relapse, however, is common and is addressed with
ilnftN:tious NetJp/Mij
repeat casting and surgery. One in seven children ISeptic arthritis Bone tumors
with this condition also has other congenital malfor- !Osteomyelitis Leukemia
mations. All children with clubfoot should have an !Lyme arthritis Spinal cord tumors
examination ofactive toe ~M~~mtent (especially toe
dorsiflexion) to rule out neurologic causes ofclubfoot.
IDiskitis lletMitJiit;
!JnlflmnllfiDiy
! Transient synovitis
LIMP j Rheumatic dJseue Siclde cell dileue
Limp is among the most common musculoskeletal i Reactive arthritis Hemophllla
complaints prompting medical evaluation in children. I IJewlrJpmsniiiVAI:qujrtJd Olhsr
Pain, weakness, decreued range of motion, and
leg-length discrepancy may all disrupt normal gait.
! Developmental Appendlcltis
1c1ysp1u1a ofthe hip
DIFFEREN11AL DIAGNOSIS ! Awscular necrosis ~~lieinflammatory
The list ofconditions that present with limp is noted
(Table 16-1). Th.luma or minor injury is the most i Slipped capital femoral TeaticuJar torsion
common cause oflimp at any age. !..~~~~~~. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .;
Legg-Calvt-Pmhes disM.se is an avascular necrosis but may be hormonal (the condition is most common
(ischemic compromise) of the femoral head in chil- during puberty) in origin or related to excessive weight
dren. The etiology is unknown. Eventually (over -18 bearing (SCFE is more common in individuals with a
months to 2 years), the ischemic boneis resorbed and body mass index [BMI] > 90th percentile). It occurs
repaired. Legg-Calvi- Perthes disease occurs more slightly more often In males. Antecedent trauma is
often in males and younger children (4 to 8 years of not a contributingfactor. Although usually asymmet-
age). A painless or mlldly painful limp that develops ric at presentation. 25% to 33% of cases eventually
inAidiously is the most common presenting complaint progress to bilateral involvement. The typical patient
The pain maybe referred to the knee or thigh. clouding presents with increased BMI, a limp and pain, which
the diagnosis. Range of motion is limited. especially may be centered in the hip or groin or, less often. is
internal rotation and abduction. Initial radiographic referred to the knee. Limited hip internal rotation
studies may appear normal; subsequent Bhns demon- and outward rotation of the limb with hip flexion
strate epiphyseal radiolu.cen.cy (Fig. 16-3). A bone scan are present on examination. Radiographs with the
or magnetic resonance imaging (MRI) may be helpful child's hips in the frog-leg lateral position are the
to detect early changes caused by the blood supply. study of choice for noting epiphyseal displacement
Treatment involves containment of the softened (Fig. 16-4). Radiographs may show physeal. plate
femoral head within the acetabulum. preserving its widening, decreased epiphyseal height, and a Klein
spherical contour, and maintaining normal range of line (line drawn along the femoral neck) that does not
motion. Exercises, bracing, casting, or surgery may intersect the lateral epiphysis. The primary goal of
be prescribed; the best practices and treatment are treatment is stabilization and prevention offurther
not currently clear today. The amount and area of misalignment. Screw fixation is effective in the acute
ischemic damage atiect the prognosis. Severe sti11- setting. Chronic cases generally require osteotomy.
ness and subluxation of the femoral head out of the Long-term complications include avascular necrosis
hip socket are the most serious acute complications. and late degenerative changes similar to those seen
Long-term disability is related to healing of the fem- with osteoarthritis.
oralhead in a misshapen pattern (nonspherical}, and
CLINICAL MANIFESI'ATIONS
the subsequent dewlopment of arthritis in the fifth
decade oflife occurs for 50% of patients. History
SCFE is the gradual or acute separation of the The history should include questions about the
proximal femoral growth plate, with the femoral head onset, timing, and evolution of the limp. Pain may
slipping off the femoral neck and rotating into an be severe (fracture, i.nfection), constant, associated
inferior or posterior position. The cause is unknown with activity (injury), acute, or chronic. The absence
RGURE 1~3. Legg-Calv&-Perthes disease

of right hip. Nine-year-old boy with stiffness
in right hip who presented with complaint
of limp. Radiograph shows 50% collapse
with sclerosis of the right femoral head
when compared with his normal left
hip (opposite). (Courtesy of Cincinnati
Children's Hospital Medical Center,
-~~~~~~--~~-~-~!~~-~..9.~.~-~!.~.~:.L.........
FIGURE 11-4. Radiograph of a slipped

capital femoral epiphysis. Fourteen-year-
old adolescent male with complaint of
pain and limp In left thigh. Radiograph
shows about 30% slippage of the femoral
head off the femoral neck on the left
when compared With his normal right hlp.
(Courtesy of Cincinnati Children's Hospital
Medical Center, Department of Pediatric
9..~.~J?.~~.~.~.:L.......................................................................
ofpain suggests weakness or instability. Swelling and especially when a septic joint is considered. MRI is
stiffness over 6 weeks' duration are common in rheu- also extremely useful for the localized evaluation of
matologic disease. Toxic or transient synovitis often joints, cortical bone and marrow, cartilage, and soft
follows a recent viral illness. Any history ofbowcl or tissue. It may also be used to evaluate for abscesses
bladder incontinence suggests spinal involvement. (gadolinium-enhanced MRI) that may require sur-
gical debridement and drainage. The diagnosis of
Phyaical Examination septic arthritis (SA) is confirmed byaspiration of the
Observation of the child ambulatin3 is particularly affected joint for bacterial culture& and measurement
important because certain gait patterns are associ- ofWBC count. Patients with weakness should have
ated with specific disorders. Each joint should be serum creatinine kinase checked to evaluate for
examined for range of motion, swelling, warmth, muscular dystrophy or myopathy; electromyography
erythema, and tenderness. Fractures produce point and nerve conduction studies may also be helpful. If
tenderness and occasionally angulation. Neurologic the weakness is progressive and limited to the lower
evaluation includes deep tendon reflexes, strength. extremities, spinal cord or nerve compression must
and sensation. Extremities are assessed for adequate be ruled out with imaging studies (i.e., MRI).
perfusion and deformities. Muscle atrophy and fas-
ciculation may be present in neuromuscular disease. TREATMENT
Treatment for the condition is specific for that
DIAGNOSTIC EVALUATION disorder. Fractures and bone or joint infections are
All patients with Ji&nificant limp should have a phys- discussed in the following sections. For limp with no
ical examination to localize the area of tenderness associated fracture (occult injury), swelling (sprain
or stiffness, followed by radiographs of any area(s) or tear), or disability, rest, ice, compression, and pain
with positive findings. A blood teat with elevation control are indicated, as well as physical therapy in
ofthe sedimentation rate, C.reactive protein (CRP), some cases.
and white blood cells (WBCs) can suggest infection.
inflammatory arthritis, or occasionally malignancy.
COMMON FRACTURES IN CHILDREN
MRl is a preferred screening tool for poorlylocalized
limp or pain, with screening from the lumbar spine Children's bones are more flexible in comparison
to the feet as appropriate. Bone scan can occasionally with adults' and can bend, bow, or partially break.
be helpful. Ultrasound and computed tomography Incomplete "buclde" and greenstick fractures are
scan are most helpful when symptoms localize to a common in children compared with displaced
speclfic bone or joint. Sonography is useful to eval- fractures because of both this flexibility and the
uate for the presence (or absence) of joint effusion, presence of a thicker periosteal casing around
the bones. Because ligaments and tendons are over a growth plate is often a nondisplaced fracture
relatively stronger than bones and growth plates, even when x-rays are normal. Children's bones
fractures are much more common. than. sprai1f3 may bow or bend without any visible fracture after
before adolescence. It is reasonable to suspect that a trauma ("plastic deformation•). Stress fractures
any posHraumatlc bone or joint pain in children due to repetitive stress in athletes are frequently
is a fracture rather than a sprain, even ifthe lnitial invisible on initial radiographs. Pathologic fractures
radiographs are normal. result when underlying disease weakens the bone,
as may occur in osteogenesis imperfecta (01), be-
DIFFEREN11AL DIAGNOSIS nign tumors, malignancies, long-term steroid use,
Fractures can involve the growth plate, the weakest infection, endocrine disorders, and some inborn
portion of the chlld's skeletal system. Growth plate errors of metabolism.
fractures are categorized according to the Salter-Harris
classification (Fig. 16-5). It ia important to remember CLINICAL MANIFESTATIONS
that a small percentage of fractures are not visible History and Physical Examination
on the initial radiograph. only becoming apparent The hallmark of a fracture ia point tenderness over
2 to 3 weeks later on follow·up :films. Tenderness a bone. Localized sweWng, bruising, and angulation
CD
Type I Type II l'ype Ill
• May not be evident • Most common type of • May require open
on radiograph growth plate fracture reduction and fixation
• Excellent prognosis • Excellent prognosis • Fair to good prognosis
Type IV TypeV
• Usually requires open • Rarest type of growth
reduct.ion and fixation plate fracture
• High risk lor growth • Crush injury usually missed
disturbance unWsubsequentg~
failure occurs
• High risk for growth
disturbance
may be present. VISUal and functional comparison OSTEOMYELITIS

with the opposite (likely uninjured) aide is very
helpful. It is imperative that vascular perfusion and PATHOGENESIS
neurologic function (strength. sensation) be evaluated Bone infections require early evaluation. diagnosis,
In the area of and distal to the Injury. and aggreasive treatment to bring about a favorable
outcome. Acute hematogenous seeding is the usual
DIAGNDSnC EVALUATION source of origin; a prior minor trauma seems to in~
Radiographs should include anteroposterior (AP) crease susceptibility. The femur and the tibia account
and lateral views ofthe involved bone as well as the for two-thirds of cases. Infection usually begins in
joints immediately adjacent to the injury. Salter- the metaphysis, an area of relative blood Jtasis and
Harris types I and V may not be seen on these limited phagocytosis. Many neonates with bone
views; obllqu.e views or serial radiographs may be infection have an associated septic joint.
needed to confirm the diagnosis. Many childhood
fractures are radiographically invisible untill to 2 EPIDEMIOLOGY AND RISK FACTORS
weeks after injury, when the healing bone callus Incidence peaks in the neonatal period and again in
becomes visible. older children (9 to 11 years ofage), when osteomy-
elitis becomes more common in males. The predom-
TREATMENT inant organism in aU age groups is Staphylococcus
Most pediatric fractures can be adequately treated aureus. Methicillin~resistant S. aureus (MRSA) is
with cuts or splints (i.e., without surgery). Children encountered with increasing frequency. Group B
with severe limb pain after trauma should be splinted stteptococcl and Escherichia coli are important
even if x--rays are normal, in view of the likelihood pathogens in the neonate. Patients with sickle cell
of an "occult"' fracture. Fractures that are displaced disease are particularly susceptible to Salmonella
or malallgned often require manipulation in the osteomyelitis. Pseudomomu aeruginosa can cause
emergency room. Fractures through the growth foot osteomyelitis or SA after a puncture wound
plate require particular care because they may result through sneakers.
in crooked or shortened limbs. Open fractures that
break through the skin usually need antibiotics, op- DIFFERENT1AL DIAGNOSIS
erative washout, and debridement to minimize the Traumatic injury and malignant involvement ofthe
risk of infection. Femur fractures, elbow fractures, bone may present with similar symptoms. Range
and fractures that penetrate the joint often require of motion generally remains intact in patients with
surgical fixation with pins, plateJ, or rods. osteomyelitis as opposed to those with SA.
J>ill:!!if:#JwHI•ljj: lj i!!j•1 rjt:l:t;~ •* CLINICAL MANIFESTATIONS

"Nursemaid's elbow;" or mdial head&ubluxation, is a Infants present with a history offever and refusal to
common injury seen in young children. The history move the involved limb. Older patients also com~
is often remarkable for a sudden strong pulling of plain of localized bone pain and are often febrile.
the child's hand, resulting in rapid extension at the The physical examination may reveal soft-tissue
elbow. The child dangles the affected ann close to the swelling, limited range of motion. erythema, and
body with the elbow slightlytlexed and the forearm point tenderness. Rarely, sinus tracts drain purulent
pronated, often holding the wrist. Motion at the fluid to the &.kin surface.
elbow is limited and painful. Treatment consists of
extending the elbow and supinating the hand, then DIAGNOSTIC EVALUATION
fully flexing the elbow, which is often inadvertently The WBC count may be within the normal range.
performed by the radiology technician when they Approximately 50% to 60% of peripheral blood
take an AP radiograph of the elbow. A successful cultures are positive. Aspiration of the involved
reduction may be accompanied by a '"click• as the bone before antibiotics are started i& lce:y to the iden-
entrapped annular ligament pops back into place. tification ofthe causative organism. Identification
"Radial head subluxation• is a misnomer and is never permits sensitivity testing of the infecting organism,
apparent on a radiograph. Usually, the child begins which guides suc:cessful antimicrobial management.
to move the arm normally within minutes. Radiographs are initially normal but demonstrate
periosteal elevation or radiolucent necrotic areas in DIFFEREN11AL DIAGNOSIS

2 to 3 weeks. Bone .scans are positive within 24 to Osteomyelitis and inflammatory arthritis should be
72 hours. Gadolinium-enhanced MRI is very useful considered in the differential diagnosis. In addition,
to rule out subperiosteal or intraosseous abscess or many causes of reactive or postinfectious arthritis
necrotic bone, especlally in patients who have severe may present in a &imil.ar manner. Toxic synovitis of
symptoms or who are refractory to intravenous the hip is a frequent cause of hip pain and stiffness
antibiotics. Serum markers of inflammation are in children. It has not been definitively proven to be
usually elevated. An elevated CRP value is seen in an infectious condition, although it often follows a
9896 of cases and returns to normal within 7 days of viral illness. The hip is most commonly involved. In
effective treatment. The erythrocyte sedimentation contrast to SA, range of motion is minimally limited,
rate (ESR) 1.5 elevated in 90% of cases but requires the child is generally afebrile and will usually bear
longer (3 to 4 weeks) to return to normal. weight. the ESR is less than 40 mm/hr, and the WBC
count is leu than 12,000/mm3• Toxic synovitis resolves
TREATMENT without treatment (beyond oral anti~inflammatory
Treatment consists ofintravenous or high-dose oral medication) over 7 to 14 days.
antibiotics for 4 to 6 weeks. Initially, broad~spectrum
antlstaphylococcal agents (such as cefazolin, nafcll~ CLINICAL MANIFESTATIONS
lin, or oxacillin) are appropriate. Vancomycin may HI&1Dry and Physical Examination
be added if suspicion fur MRSA is high. Neonates SA presents as a painful joint, often accompanied
require coverage for group B streptococci and by fever. irritability, and refusal to bear weight. On
gram-negative bacilli. Patients with sickle cell should examination, range of motion is clearly limited. The
initially receive a third-generation cephalosporin for joint is tender and may be visibly swollen.
Salmo~Ua coverage. When the organism has been
recovered and sensitivities are available, therapy may DIAGNOSTIC EVALUAnON
be narrowed. Most patients do not require surgery The standard of care for evaluation of SA involves
unless they develop an absce88 or necrotic bone aspiration of the joint. The synovial .fluid yields a
(sequestrum). A severe joint infection can destroy WBC in excess of 25,000/mm3 and a pathologic
cartilage and cause arthritis. Growth arrest can rarely organism. The exception is N. gono"hoeae, which
occur if the growth plate is involved. is difficult to recover; blood, cervicaL rectaL and
nasopharyngeal cultures may be helpful
SEPTIC ARTHRITIS
TREATMENT
PATHOGENESIS Delay in treatment may result in permanent destruc-
SA (purulent infection ofthe joint space) is common tive changes and functional impairment. A septic hip
and potentially more debilitating than osteomyelitis. is an orthopedic surgical emergency. Intravenous
Pathogens are theorized to enter the joint during antibiotic therapy remains the treatment of choice;
episodes of bacteremia. conversion to oral therapy is appropriate when
sensitivities are known and symptoms substantially
EPIDEMIOLOGY improve. Ceftriaxone is an appropriate initial choice
The lnddence is hfshest in infants and young children. in the young child; a semisynthetic penicillin or (first-
Neonates may be illfected with group B Streptococau, or second-generation) cephalosporin is preferred in
E. coli, Streptococt:W pneumoniae, and S. aureus. older children because ofthe overwhelming presence
In infants older than 6 weeb and young children, of S. aureus arthritis in this age group. Vancomycin
the hip is the most common site. The knee is more is added in cases of suspected MRSA. Cefotaxime
frequently affected in older children. S. aureus is the is a better choice in the neonate. Antibiotic therapy
most li.lcely pathogen outside the neonatal period. can be specifically targeted to the pathogen when
Other bacteria with a predilection for Joints in younger culture results become available.
children includeKmgella. kingae and S. pneumoniae.
In older children, streptococci and gram-negative
OSGOOD-5CHLATIER DISEASE
bacteria are not uncommon. Neilseria gono"hoeae
must be consideredin the sexually active adolescent. Osgood- Schlatter disease is an overuse disorder
especlally if multiple Joints are involved. that involves swelling, pain, and tenderness over the
tibial tuberosity. It is caused by repetitive stress of low back prominence on one side of the spine versus
the distal insertion of the patellar tendon attachment the other. Patients with evidence of curvature on
to the growing proximal tibia. Osgood-Schlatter exam should rec:eive standing posteroanterior and
disease typically occurs between 10 and 15 years lateral thoracic/lumbar spine radiographs to allow
of age, during the adolescent growth spurt. Pain is angular measurement of the deformity.
worsened with kneeling, running, jumping, or squat-
ting but is relieved by rest. Radiographs may reveal lREAJMENT
irregularities of the tubercle ossification center and Treatment depends on the degree of curvature,
soft-tissue swelling. Most cases are mild and treated skeletal maturation, body habitus, and gender of
with activity modification and stretching exercises. the child. Premenarchal females are the most likely
Long-term morbidity is quite low; the disorder is to experience prosression of their curvature and
self-limited and almost always disappears when should be treated more aggressively. Curvatures
skeletal maturity is reached. less than 25" may be followed. More pronounced
deformity (25" to 40") in a child who is still growing
may benefit from external bracing until the growth
IDIOPATHIC SCOLIOSIS spurt is completed. Bracing does not reduce the
Idiopathic scoliosis is excessive lateral curvature of curve, but it can halt progression and is up to 85%
the spine found in otherwise healthy children with effective If used correctly. Unfortunately, compli-
normal bones, mWicles, and vertebral disks. The ance tends to be problematic. Curvature greater
cause is multifactorial, and heredity plays a role. than so· after the growth spurt may continue to
progress; such patients often have spinal fusion to
EPIDEMIOLOGY reduce the curve and stabilize the spine. Curves
Five percent of all children display some degree of greater than 90" are associated with clinically sig-
spinal deformity. Routine screening in primary care nificant decreased vital capacity and low functional
practice is important. Severe scoliosis requiring pulmonary reserve.
bracing or surgery occurs about seven times more
often in females than in males. Progression of
ACHONDROPLASIA
the curve is most rapid during the preadolescent
growth spurt. Achondroplasia is a skeletal dysplasia, a disorder
of physeal cartilage calclfication and remodeling.
DIFFERENTIAL DIAGNOSIS Inheritance is autosomal dominant. The physical
Occasionally, scoliosis may also be caused by neu- appearance is sa.ikingly characteristic: these patients
romuscular abnormalities, congenital deformities, are ofshort stature, with increased head circumference;
or miscellaneous causes. Kyphosis is an abnormal long bones are wide, short, and curved, and digits
rounding of the spine as seen from the side prorue are short and stubby. Kyphoscoliosis and lumbar
or sagittal aspect. Kyphosis is usually postural and lordosis may be quite pronounced. Heterozygote&
responds well to observation or physical therapy; in- have normal intelligence, sexual function, and life
flexible kyphosis may be associated with wedge-shaped expectancy. Homozygote& fare less well, given their
vertebral bodies (Scheuermann disease) and may increased susceptibility to pulmonary complications,
require bracing or corrective surgery. an abnormally small foramen magnum that predis-
poses to brain.stem compression early in life, and to
CLINICAL MANIFESTATIONS lower spinal stenosis that results in pain, numbness,
Idiopathic scoliosis is usually not associated with and disordered lower extremity neurologic function
back pain; such symptoms, ifpresent, warrant further in young adulthood.
investigation. The phyaical examination consists of
inspection and the forward bend test. First, the chlld
OSTEOGENESIS IMPERFECTA
is examined. from the rear while standing up. Shoulder
girdle and iliac crest areu are noted for asymmetry OI descnoes a group ofclosely related genetic disor-
and unequal height. Then, the Adams forward bending ders resulting in fragile, brittle bones. The common
test is performed. The child bends forward from the denominator in all variants is the abnormal synthesis
waist with the arms hanging freely. The examiner of type I collagen, which normally constitutes ap-
should examl.n.e the patient's back for a rib cage or proximately 90% of the bone matrix; type I collagen
TIILI1~2.
1.,....•••
......
Classification of Osteogenesis lmperfecta
.......... Grlliafldlc ............. ._,... •• ; lllnlfwtalla•

!'lfpel AutDiomal Frequent fm.durea from tbe Blue/gray ICleru; adult~
dominant neonatal period through oDIII!t &eniOriru!ural hearing
adolesam<Je"; MM!l'e bone loss (deafneu); abnormal
fragility; bow lep; joint dentition
I laxity; short stature
IType II Short, defonned limbs; Intrauterine growth Days
multiple in utero and retardation; stillbirth; blue/
neonatal fractures; severe gray sclerae
i
bone fragility
!1fpeiii Autosomal
receuive
Frequent fractures that heal
with deformation; severe
Normal or mildly blue/gray
sclerae
Generally
lhorten.ed
~~o!V
bone fragility; lower limb
deformitiell; short stature
Autosomal Increased susceptibility to Normal sclerae; increased Near normal
~ dominant fractures" risk for aortic dilation
is also dispersed in the teeth, ligaments, skin, ears, smceptibilityto fractures. mue sclerae are a charac-
and sclerae. The most severe form is type II. or teristic feature in some forms of the disease. Short
fetal 01, which results in multiple intrauterine and stature is not uncommon as a result of recurrent
birth fractures and is uniformly fatal in the perinatal fractures. Fractures associated with. 01 occasionally
period. Oinical severity depends on the subclass of raise the suspicion ofchild abuse. Patients with se·
01 (Table 16~2). Somevariantl came death early in vere disease may benefit from pamidronate therapy,
life; others present with only moderately increased which inhibits osteoclastic resorption.
KEY POINTS
• DOH may be demonstrated on physical exam- • The typical patient with Legg-Calv&-Perthes
ination by performing the Bartow and Ortolani disease is a young male child who presents
maneuve111 ~n newborns) and evaluating limb with a painless or moderately painful limp and
length and hlp adduction in infants older than knee pain.
3 months. DOH must be diagnosed and treated • The typical SCFE patient Is an adolescent or
early in life to obtain a favorable outcome. preadolescent male with a marked Increase In
• Plantar and dorsiflexion are normal in metatarsus BMI who presents with hlp or knee pain and
adductus, whereas In talipes equinovarus, the no history of trauma.
ankle and hindfoot are fixed in plantarflaxion. • Fractures through the growth plate may result
• Trauma Is the moat COITVllOn cause of limp in later growth defomllty or limb-length dis-
in all age groups. Radiographs are helpful crepancy. ~fractures categorized as
screening tools. Salter-Han1s type Ill or IV have the 5J881est risk
• When evaluating a complai1t of limp, evidence of of disruption of growth.
I"MUUiogic involvement (weakness, bowel, and/ • The peak incidence of osteomyelitis is binodal
or bladder Incontinence) necessitates aggressive (neonatal period and 9 to 11 years of age). Ar>
workup to rule out spinal cord compression. proximately half of blood cultures are negative.
so aspiration of the bone yields invaluable • Children with toxic synovitis have lower sed-
Information. Imentation rates and WBC counts than those
• S. aureus is the most common pathogen im- with SA. Generally, although the joint is tender,
plicated in osteomyelitis in a// age groups. It is children with toxic synovitis will bear weight.
also the most common pathogen in sickle cell • Scoliosis is more common in adolescent fe-
patients, who are also particularly susceptible males than in males. Idiopathic scoliosis does
to Salmonella. not result in back pain or fatigue.
• In cases of osteomyelitis, the MRI or bone • Bracing is recommended for scoliotic curves
scan is more sensitive than films early in the from 25° to 40° until the growth spurt is com-
disease process. plete. Bracing halts curve progression; it does
• The most common cause of SA in infants and not correct the curvature already there.
children isS. aureus. N. gonorrhoea& must be • Patients with 01 types I and II often have blu-
considered In the sexually active adolescent. Ish sclera. Type II 01 Is the most severe form,
resulting in intrauterine or perinatal death.
CLINICAL VIGNETTES
VIGNETIE1 VIGNETIE2
A male infant is born after full-term gestation to a primi- A healthy 22-year-old primigravida woman delivers
gravida mother and noted at birth to have bilateral foot a healthy, full-term female infant via Cesarean sec-
deformities. He does not have any other deformities in tion after it was discovered during labor that the
the extremities and Is able to move his feet and toes up infant was in breech position. On the first day of
and down. HIs feet are both In a posmon of adduction life, examination in the newborn nursery reveals no
and equinus (pointing inward and downward). apparent facial or musculoskeletal malformations,
but her presentation makes you suspicious she may
1. What are the deformities that describe a congen-
have developmental dysplasia of the hlp (DDH). A
ital clubfoot?
careful hip examination demonstrates that the left
L Abduction, eversion, planus, and neutral
hip is Ortolani positive.
hindfoot
b. Adduction, Inversion, neutral hlndfoot with 1. The risk factors that should raise your index of
normal dorsiflexion suspicion for DDH include all of the following
c. Abduction, inversion, neutral hindfoot with except:
normal dorsiflexion L Female gander
d. Cavus, adduction, varus, and equinus b. Breech presentation
1o Planus, abduction, valgus, and calcaneus c. Family history of DDH
2. What other deformities or systemic problems are d. Polydactyly of feet
commonly associated with clubfoot? e. First-born child
L None
2. The newborn hip examination is critical to
b. Congenital heart defects
Identify unstable, abnonnal hips and permit
c. Spinal dysraphism early treatment. The description of a hip exam-
d. Developmental hlp dysplasia
ination as Ortolani positive means which of the
e. Congenital constriction bands
following?
3. What is the best initial treatment for this patient? L The hlp Is loose (subluxatable) but Is nonnally
L Special orthopedic shoes located.
b. Physical therapy b. The hip is dislocated and irreducible.
c. Serial manipulations and casting c. The hip is normally located and dislocatable.
d. Early surgical correction d. The hip is dislocated and reducible.
e. Surgery at 1 year of age 1o The hlp clicks during examination.
a. Which of the following Is the best treatment for a d. Aspiration of the hip
dislocated, reducible hlp recognized In Infancy? e. AP pelvis radiograph
a. Observation
b. Abduction bracing (Pavlik harneea or hip ab- 3. The patient had blood cultures obtained in the
duction brace) emergency department and then went to the
c. Denis-Browne foot abduction splint radiology suite where a left hip aspirate was
d. Closed reduction and spica cast performed. Thrae milliliters of thick yellow fluid
e. Open reduction and spica cast wera aspira1ed. The initial gram stain was nega-
tive, cultures were started, and the WBC count of
._ What is the most significant long-term sequelae the ftuld was 90,000 cellslmm3 • What antibiotics
of properly treated DDH? should be started?
a. Umb-length inequality a. Penicillin
b. Weakness 11. First-generation cephalosporin
c. Early osteoarthritis c. Gentamicin
d. Stiffness d. Vancomycin
e. Scoliosis e. Second-generation cephalosporin
VI6NETTE3 4.. The patient was taken to the operating room and
A 3-year-old male presents with a 24-hour history of underwent incision, arthrotomy, and drainage of the
irritability, limping on his left leg, and fever of 102°F hip. What is the major concern if the diagnoai& and
by oral thermometer a1 home. He is now refusing to treatment ofSA of the hip is not carried out promptly?
bear weight on his left side. He has no chronic med- L Chronic osteomyelitis
Ical problems, was the product of a normal gestation b. Destruction of the hip joint (osteonecrosis}
and delivery, and has had normal developmental c. Dissemination of infection to knee and ankle
milestones. One week ago, he had a mild viral upper d. Development of bacterial pneumonia
respiratory lllnees, and he also had some bruising on a. Development of infection in opposite hip
his left leg after falling off some playground equip-
ment. On examination, he is supine on the table and VIGNETTE4
is irritable with any movement. His pulse and blood A 13-year-old female presents complaining of right knee
pressure are normal, and he does not appear in pain for 6 weeks. She is obese, with a BM I of 34 kglm2.
distress when he is at rest. Any movement of his left She denies any injury or recent illness or infection.
lower extremity causes him to cry out, and he holds She does not have pain at rest or at night. Her mother
his left hip in a position of flexion, extemal rotation, notes she has been limping. Her knee examination is
and slight abduction. Some laboratory studies were benign. She has no knee effusion and no tenderness,
orde~ by the emergency room physician and show and both knee and patellofemoral joints are normally
an eleva1ed WBC count with a normal hemoglobin. mobile. She walks with an antalgic gait on the right,
The thrae leading possible diagnoses for this pattent with limited time in stance phase on the affected side.
ara believed to be toxic synovitis, SA, and acute he-
1. The next focused examination should carefully
matogenous osteomyelitis (AHO).
assess which of the following?
1. Wha1 additional bloodwork will help narrow the L Spine
diagnostic possibilities? b. Hips
L Crea1inine phosphokinase c. Ankle
b. Erythrocyte sedimentation rate d. Foot
c. Alkaline phosphatase e. Contralateral knee
d. Serum calcium
'-The patient has very limited intemal rotation of
e. Albumin
the right hip when supine and has pain at the end
2.1n addition to a WBC count of 18,000/mm3, the of range-of-motion testing. She also has limited
patient's ESR was 90 mmlhr. Manipulation of the left internal rotation of the left hip in the supine position,
hip made the child very irritable, and any attempt but does not complain of pain. Flexion of the right
at passive internal rotation of the hip resulted in hip is possible only to goo and is accompanied by
extrame guarding by the patient and complaints obligatory external rotation of the hip as the thigh
of pain. What laboratory study Is deflnhlve for the flexes. Which of the following raprasents the best
diagnosis of SA of the left hlp? next step In the evaluation?
L C-1'88ctlve protein L Bloodwork to assess for an inflammatory
b. Ultrasound evaluation of the hip problem (CBC, ESR, CRP)
c. MRI imaging b. AP radiograph of the right hip
c. AP radiograph of the pelvis L Referral to an orthopedic surgeon within the

d. AP pelvis and frog lateral pelvis radiographs next week
t. MRI of the right hlp b. Elective referral to orthopedic surgeon
3. The patient was found to have bilateral SCFE on c. Crutches and physical therapy
d. Referral today to an orthopedic surgeon for
the radiographs, with the right side being slightly
surgical stabilization
more displaced. Which of the following is the best
t. MRI of the hips
Initial treatment for this patient?
ANSWERS
VIGNEilE 1 Question 1 when a clubfoot deformity is noted, although these

1.AnawerD: will be found rarely.
The four components of foot deformity In a congenital
clubfoot can be described by the acronym CAVE. VIGNEilE 1 Question 3
Cavusls a high arch of the foot with the first ray/great 3.AnswerC:
toe metatarsal in plantarflexion. Adduction is medial Serial manipulations and casting to hold the foot in
deviation of the forefoot, with the forefoot pointing the stretched position Is the standard treatment for
inward. Varus describes the position of the heel, with congenital clubfoot, and in the past decade a specific
the lnfer1or part of the heel pointing Inward. Equtnus method of manipulation and casting has been shown
describes the plantarflexion of the foot, with the toes to be superior to all other methods. This method was
and foot pointing downward. The key physical exam- developed by Ignacio Ponsetlfrom the Unlverstty of
ination finding in the newborn to diagnose clubfoot Iowa over five decades of studying clubfoot patients.
is that all of these deformities are present and the The patients are treated with toe-to-groin casts that
deformities are rigid. In particular, the foot cannot be are changed weekly, and when correctly applied, the
doralflexed to a neutral plantigrade position. In addi- deformity can be successfully corrected In over 95%
tion, the feet will typically have deep creases in the of patients. Seventy percent to 90% of patients will
middle of the foot medially and often a single deep have an Achilles tendon tenotomy at the completion
crease In the posterior heel. The small, fine multiple of casting to assist in treating the equinus component
transverse creases that are seen in normal infant teet of the deformity. Ponseti method casting should begin
are usually missing in clubfeet Clubfeet will not im- soon after the diagnosis of clubfoot is confirmed by
prove without treatment. Feet that are flexible and can physical examination, but It does not have to begin
be dorstftexed above neutral (such as most cases of immediately. Many studies and the experience of mul-
metatarsus adductus) are positional deformities that tiple practitioners have shown that clubfoot deformities
may improve without treatment. can be successfully corrected when treatment is begun
weeks and even months after birth.
VIGNETTE 1 Question 2
2.AnswerA: VIGNET'IE 2 Question 1
Congenital clubfoot is usually an isolated deformity 1. AnswerD:
found in otherwise healthy children. It is more common The major risk factors for DDH are female gender and
in boys and is bilateral in 50% of cases. Examination breech position. Other risk factors are family history
of the Infant with clubfoot should Include a careful of DOH and primigravida mother. DOH is believed to
neurologic examination to rule out a neurologic cause be multifactorial in etiology, with genetic predisposi-
of the foot deformities (make sure the infant can action and intrauterine positional factors playing a role.
tively dorsiflex and plantarflex the toes), and, as in all Musculoskeletal abnormalities in newborns can be
infants, a careful hip examination should be performed thought of as either production defects (abnormal
to assess for hlp Instability/DOH. Some authors have development of a part or parts leading to deformity) or
suggested that hip dysplasia ia more common in children packaging problems Ontrauterine pressure or constraints
with clubfeet, but larger and more recent studies have Imposed on a developing part result In deformity). In
refuted this. Up to one-third of children with congenital general, production abnormalities lead to progressive
constriction bands have a clubfoot, but these patients deformities if not treated after birth, and are commonly
make up an extremely small percentage of children treated with manipulations and casting or bracing or
who have clubfoot. The infant physical examination surgery. Packaging problems may Improve with growth
should include a careful search for constriction bands and time once outside the constraints of the uterus.
DOH is believed to be part production, part packaging, VIGNETTE 2 Question 4

as rat1ected by the risk factors. Female gender and 4. AnswerC:
family history relate to the possible production defect, A hip that develops in an abnormal position with the
and first-born child and breech presentation contribute femoral head not centered in the acetabulum (socket)
to packaging abnormalities. is at high risk for developing early osteoarthritis and
hip pain in adulthood.
2.Answer 0: VIGNETTE 3 Qu1511on 1
The newborn hip physical examination is an easential 1.Answer B:
skill to identify DOH in its earliest stages, when it can In patients presenting with possible musculoskeletal
be treated most successfully. The hip examination to sepsis, one of the most helpful laboratory tests is the
detect DOH is classically described as the Barlow and ESR. The ESR is nonspecific, but is usually very helpful
Ortolani maneuvers. The Barlow maneuver involves to rule out significant infection. It is an acute phase
first flexing the hip being tested to 90°; then 1he hip reactant, will be abnormally elevated in conditions
is actducted (knee across midline), and a gentle force associated with inflammation, and is usually greater
directed posteriorly Is applied to see If the hlp dis- than 40 mmlhr In children with SA and/or AHO. A
locates. The Ortolan! maneuver Involves taking the normal ESR Is reassuring, as It Is unusual to have SA
tested hlp from a position of goo fleXIon and maximum or AHO and have a normal ESR. The following criteria
abduction (knee away from midline) and lifting up on have been studied to differentiate SA from transient
the thigh/greater trochanter to see if the hip can be synovitis of the hip: (1) inability to bear weight on
felt to reduce. Thus, the Barlow test detects a hip that affected lower extremity, (2) history of fever, (3) WBC
is located and unstableldialocatable, and the Ortolani above 12,000/m~. and (4) ESRgreaterthan 40 mml
test detects a hip that is dislocated and reducible. hr. Patien1s with none of these criteria have almost
Because of confusion that can be created by describ- zero chance of having SA; those with one of four have
ing the physical examination tests by the Barlow or approximately a 5% chance; two of four a 40% chance;
Ortolani monickers, it may be better to describe the three of four a 75% chance; and four of four a 95%
hip by the findings of the examination, with five op- chance. The CRP is another test of inftammation and
tions: normal, stable examination; loosalsubluxatable is also frequently used to assess the risk of SA or AHO.
but not dislocatable hip (difficult to determine without It Is more time-sensitive than the ESR, because It will
extensive experience); reducedldlslocatable hip; become abnormal earlier In musculoskeletal sepsis,
dislocated/reducible hlp; and dislocated/Irreducible and will also return to normal earlier If the Infection
hlp (also can be difficult to detect). The sensation of Is being successfully treated. It Is thus more helpful
the femoral head sliding over the edge of the acetab- for monitoring the response to therapy for infections
ulum has been described as a •clunk" of dislocation of the musculoskeletal system. The complete blood
and a •clunk• of relocation-unfortunately, this has count is helpful to assess for the risk of SA, but it is
been mischaracterized by some as a hip "click.• Hip also useful to look at the hemoglobin. It is importantto
•clicks• are palpable brief sensations caused by either remember that many young patients with leukemia will
soft tissues impinging between the femoral head and present with complaints of musculoskeletal pain, and a
socket or tendons snapping around the hip, and do leukemic hlp effusion can mimic SA in its presentation.
not signify DOH. DOH in infancy is diagnosed by the Typically, these patients will be anemic, so a normal
examiner sensing instability of the femoral head, feeling hemoglobin is reassuring. The other blood laboratory
the head exit and reenter the socket. study that should be ordered in patients suspected of
musculoskeletal sepsis is a blood culture. Patients do
VIGNEnE 2 Question 3 not have to be febrile at the time the blood culture is
3.AnswerB: drawn, and In up to 50% of pattents with SA or AHO,
The safest and most effective way to reduce and stabilize the only culttn that returns positive Is the blood culture.
a dislocated hlp In an Infant with DOH Is with abduction
bracing, with the Pavlik harness being a commonly VIGNETTE 3 Question 2
employed device. Although some dislocated hips In 2.Answer 0:
Infanta may spontaneously reduce, the reliability of the The deftnttlve test for SA Is asplradon of the affected
hip stabilizing is unknown. Many orthopedic surgeons joint. The aspirate is sent for Gram stain and bacterial
may monitor a reduced, dislocatable hip (Barlow cultures as well as cell count analysis. Bacterial growth
positive) because many of these will stabilize as the from cultures or a WBC count of greater than 25,0001
hip matures and the influence of maternal hormones m~ with negative cultures is considered diagnostic of
recedes. Closed- and open-reduction techniques are SA. Aspiration of superficial joints can be accomplished
reserved for hips that fail to reduce with abduction without fluoroscopic/radiographic control, but for the hip
splinting. joint, the aspiration should be performed under fluoroscopic
control wilt1 an arthrogram ~nject radio-opaque dye into Hip pain is commonly referred to the knee in chil-
the joint) to conflnn that the hlp joint has been entered/ dren and adolescents; this referral can result in no
asplnd8d. The other tests are nonspecific. complaints of hlp pain In patients with serious hlp
pathology where timely diagnosis Is necessary to
VIGNETTE 3 Q...Uan 3 prevent significant complications. Thus, the examiner
3.AnswerB: should carefully examine the hips in every skeletally
The most likely organism in SA of the hip in a 3-year-old immature patient who presents complaining of
healthy child isS. aureus. The other likely organism is knee pain, especially when the knee examination
Streptococcus, with other organisms less likely. Before is unremarkable. Patients with hip pathology will
widespread Haemophilus lnfluenzse type B (Hib) immu- most frequently have pain w ith hip provocation by
nizations were instituted, Hib was commonly seen in this internal rotation, and will have increased hip/groin
age group. It is now rare and has been replaced by K. pain or weakness w ith active straight leg raising.
kingae as another common organism causing muscu- Radiographs of the hip are Indicated if the physical
loskeletal sepsis in children. All of these organisms are examination is abnormal.
typically susceptible to first-generation cephalosporins,
which are usually administered at much higher doses VIGNETTE 4 Question 2
for serious musculoskeletal Infections. The controversy 2.Answer D:
over the Initial choice of antlblodcs now Involves cover- The presentation of an obese adolescent with knee
age for community-acquired MRSA. The best plan for pain, limp, and painful and limited Internal rotation
empirical coverage likely involvee discussion with local of the Ipsilateral hlp strongly suggests the diagnosis
pediatric infectious diaease exper18 and assessment of SCFE. This is supported by the finding of oblig-
of the bacteriologic sensitivities of MRSA infections. atory external rotation of the hip with thigh flexion
In many communities, MRSA infections are commonly (Drennan sign), which usually signifies impingement
susceptible to clindamycin and trimethoprim-sulfa of the femoral neck on the anterior acetabulum. The
combinations, and many experts recommend adding diagnosis of SCFE is radiographic and can be made
one of these t o the initial antibiotic treatment with a at times on an anteroposterior view alone, but the
first-generation cephalosporin until culture111Sults return. frog lateral radiograph of the hip is t he most sensitive
In this case, the child is ill but not toxic or septic; use test. Thus, if SCFE is suspected, both lat eral and
of vancomycin in these settings may contribute to the frog-leg views should be ordered. As up to one-
development of vancomycin resistance. In the setting third of patients with SCFE have a silent slip on the
of systemic sepsis, vancomycin Is pnrferred to make contralateral hip, it is recommended that both hips
sure that MRSA Is covered. be Imaged.
VIGNETTE 3 Q...Uan 4 VIGNETTE 4 Question 3

4.AnswerB: 3.Answer D:
Failure to diagnose and treat SA of the hip can result Patients with SCFE who are able to weight-bear
in complete destruction of the hip, because bacterial are described as having stable slips. The standard
enzymes may cause lysis ofthe articular cartilage cells, treatment for stable SCFE ia surgical stabilization
and pressure from pus in the hip joint can limit blood of the slip with a single screw. The patient should
flow to the proximal femur and cause osteonecrosis/ be referred to an orthopedic surgeon on the day of
avascular necrosis. S. aureus infections are known diagnosis for evaluation and scheduling of surgery.
to occasionally be very aggressive and to cause There are many documented cases of stable SCFE
pennanent damage to the hlp joint. The major issues patients progressing to unstable SCFE (inability to
with destruction of the hip in a young child are the bear weight, increase in defonnity of the proximal
development of substantial limb-length d ifference over femur) while awaiting referral or surgery. Progression
time as the proximal femoral growth p late Is lost and from stable to unstable SCFE carries a substantial
with It 30% of the growth potential of the femur. With risk of complication, primarily osteonecrosis of the
loss of the femoral head, the hip will lose significant femoral epiphysis/head. The risk of osteonecrosis
biomechanical function, resulting in a permanent for st able SCFE treated with screw stabilization Is
6mp and abnonnal gait. Although the other options essentially zero and Increases to 201)6 t o 50% If
mentioned are posaible, they are not likely. the SCFE progresses to unstable. Osteonecrosis
can result in complete destruction of the proximal
VIGNETTE 4 Q...tlan 1 femur and hip, causing a pennanent limp and early
1.Anawer B: painful arthritis. Thus, patients diagnosed w ith SCFE
Skeletally immature patients who present w ith com- should be referred for orthopedic evaluation when
p la ints of knee pain frequently have hip pathology. the diagnosis is made.
Nephrology
Ren6 G. VanDeVoorde Ill and Katie S. Fine
INTRODUCTION
In renal agenesis, one or both kidneys fail to form.
The kidneys are the primary regulator of fluid and Bilateral renal agenesis is typically noted prenatally
electrolyte status in the body. They preserve equi- with marked oligohydramnios on ultrasound. This
librium by conserving or excreting electrolytes and results in Potter sequence (clubbed feet, cranial anom-
water. They also excrete waste products of metabolism, alies); affected infants are stillborn or die shortly after
such as urea, creatinine, and organic acids. These birth because of associated pulmonary hypoplasia.
dual functions are the primary means of maintain- Unilateral agenesis is usually an isolated defect but
ing the ionic, osmolar, and pH status of the body. may be associated with other abnormalities.
In addition. the kidneys contribute to other bodily In multicystic dyspla&tic kidney (MDK), the most
functions through the synthesis of erythropoietin, common renal cystic disease of childhood, the kidney
the production of vitamin D, and the regulation of consists of numerous noncommunicating, fluid~filled
blood pressure. Thus, the kidneys play a central cysts. Affected organs are nonfunctional, but the
role in the growth and development of children, condition is virtually always unilateral. MDK is a
placing them at risk when faced with anatomic or common cause of abdominal mass in the newborn
physiologic stressors to their function. Infants are (exceeded only by hydronephrosis from ureteropelvic
particularly susceptible because their kidneys are less junction obstruction). Diagnosis is confirmed by
effective in filtering plasma, regulating electrolytes, postnatal ultrasound (noncommunicating cysts) and
and concentrating urine. renogram (demonstrates lack offunction). Most cases
Renal abnormalities may be congenital (anatomic, undergo spontaneous involution. Follow-up imaging
cellular. or genetic) or acquired (infectious, inflam- with renal ultrasound is necessary until involution
matory, or traumatic). or surgical removal Nephrectomy is recommended
only when the kidney changes in size or appearance
(increased risk ofW.dms tumor), when the patient is
RENAL DYSPLASTIC AND persistently hypertensive, experiences pain, or has
CYSTIC DISEASES reCUITent infections of the involved side.
Renal dysplasia is a condition in which the renal pa- Polycystic kidney disease is an inherited disorder
renchymal tissue does not form correctly throughout. that occurs in two fonns: the autosomal recessive
Typically, both kidneys are affected. There may be and the autosomal dominant types. In the former,
areas of normal parenchyma Interspersed with areas of both kidneys appear enlarged but maintain their
fibrosis, immature development, or even other tissue sym.met:ric, reniform shape. The renal-collecting
{such as cartilage). Severity ranges from minbnal to tubules are dilated, producing small cysts that are
severe renal impairment, sometimes with. the devel- viSl'ble only u increased echogenicity on ultrasound
opment of isolated cysts or hypoplasia of the kidney. The condition is usually discovered prenatally (with.
The pre.s ence ofrenal dysplasia is associated with. an the advances in obstetric ultrasound) or during eval~
increased risk ofabnormal development elsewhere, uation of a palpable renal.m.us in an infant. Similar
particularly in the urinary collecting system, but also dilation is found in the hepatic bUe ducts, with varying
in conjunction with other syndromes. degrees ofperiportal fibrosis. In general. the lddneys
383
function poorly, and life expectancy is appreciably can sustain damage to the infected area of the renal
shortened. Severely affected infants may die within parenchyma, resulting in localized scarring, reduced
weeks without dialysis; leu affected infants su:ffi:r function, and hypertension. Common pathogens
from hypertension and an eventual decline in renal include Escherichia coli (801)(,), Proteus, and Kleb-
function during childhood. The autnsomal dom- siella species.
inant form of polycystic kidney disease is usually
not detected until adulthood. but may be diagnosed RISK FACTORS
earlier on ultruound for a positive family history, The most significant risk factor is thep~n~ ofan
hypertension, or hematuria. The cysts can be quite tUUJtomic orphysiologic IR'inary tract ablfl)rmality that
large and distort the normal shape of the kidney. predisposes to stasis ofurine, such as bladder outlet
Hypertension and renal .insufficiency develop over obstruction, vesicoureteral reflux. and dysfunctional
time, but do not always follow typical courses even voiding. These risk factors may be known from
within family cohorts. Early intervention to treat prenatal evaluations or may first become evident
hypertension or proteinuria is currendy indicated, with a UTI. Thus, a history of previous liTI is also
with transplant as a viable option when renal func- a significant risk factor.
tion diminishes. After the first year oflife (equal incidence), girls
have almost a 10-fold increased incidence over boys.
CLINICAL MANIFESTATIONS Although Wldrcumclsed male infants are more prone
The most prominent defect with renal dysplasia is to UTis, this risk diminishes after the first year of
inability to concentrate the urine. Dysplasia of the life and is not a sufficient indication for universal
renal tubules affects their ability to reabsorb fluids; routine circumcision.
affected patients have an obligate amount of urine
output that is unable tn change on the basis offluid DIFFEREN11Al. DIAGNOSIS
status. They may have frequent urination, difficulty The differential diagnosis for cystitis includes external
in attainingurinary continence, and be particularly genital irritation, meatal stenosis in the circumcised
susceptible to dehydration if they are unable to male, vulvovaginitis, vaginal foreign body, sexual
maintain volume status through impaired intake abuse, and pinworm infestation. Adenovirus can
(vomiting) or increased losses (diarrhea) of fluid. cause a self-limited hemorrhagic cystitis that does
Additionally, these children are at risk for poor not respond to antibiotics but may be mistaken for
growth ifthey have ln.creased losses ofelectrolytes, a UTI. In the adolescent, the possibility ofa sexually
especially sodium, in their urine. transmitted disease must be entertained. Posterior
urethralgia is a benign, self-limiting inflammation
DIAGNosnC EVALUATION of the posterior urethra in boys that may mimic a
The diagnosis is typically made by renal ultrasound, UTL for the febrile child, lower lobe pneumonia
with the kidneys appearing more hyperecholc often presents with fever, chills, and flank pain, a
than normal. These patients often do not present reminder that other sources of infection must also
with hypertension, but the diagnosis is sometimes be contemplated. Urolithiasis should be considered
stumbled upon during an evaluation for elevated in the patient presenting with dysuria, hematuria,
blood pressure if the serum creatinine is elevated. and flank pain.
Urine-specific gravity is often low, but the urine
sodium may be elevated in some patients. CLINICAL MANIFESTATIONS
In febrile infants, the urinary tract is the most com-
TREATMENT monsite of bacterial infection. Fever may be the only
Treatment for the specific disorders is discussed mani.festation of illness. However, infants may also
under "Differential Diagnosis!" present with other signs of systemic illness, such
as lethargy, vital sign instability, poor oral intake.
mottled appearance, and even jaunc:Uoe. The source
URINARY TRACT INFECTION ofinfection is almost always hematogenous seeding
Bacterial urinary tract infections {UTis) may be lim- of the kidneys, which explains the high rate of renal
ited to the bladder (cystiti.J) or may also involve the scarring observed in this gJOUp of patients. Also, a UTI
kidney (pyelonephritis). Children with pyelonephritis can be the first clinical suggestion ofan obstructive
Chapter 17 I Nephrology • 385
anomaly or vesicoureteral reflux in this age group. pyuria and bacteriuria are fairly specific for infection.
Ideally, the urine should be examined in all febrile However, the absence of these findings in the urine of
patients younger than 1 to 2 years. a high-risk patient, such as a febrile or ill-appearing
In older children, UTls more often result from an infant, does not rule out UTI; for instance, pyuria
ascent ofexterior fecal flora into the urinary tract. The is often absent in infants with pyelonephritis. Urine
signs and symptoms of cystitis are similar to those may be obtained by suprapubic tap (in neonates},
in adults and include low-grade fever, frequency, sterile catheterization of the bladder, or clean catch
urgency, d)'lluria, incontinence, abdominal pain, and in continent children; these are listed in their order
hematuria. In contrast, pyelonephritis presents with of increasing likelihood of contamination. Bagged
high fever, chills, nausea, vomiting, and flank pain. specimens are inadequate for evaluation of UTI.s.
Older chlldren are more likely to have an isolated A urine culture (results in 24 to 48 hours) and
infection of the bladder; upper tract involvement is dipstick urinalysis should be obtained in all febrile
suggested by elevation of the peripheral white blood infants without a definitive source ofinfection (and
cell (WBC) count, erythrocyte sedimentation rate, older patients with suspected U'l'U). Patients with
and C-reactive protein. positive dipstick results for leukocyte esterase (with
or without positive nitrites) should be treated for a
DIAGNOSTIC EVALUATION presumed UTI until culture results are available.
A positive urine culture is the gold standard for Susceptibility testing ls performed on any singular
diagnosis, although urine microscopy or dipstick bacteria isolated to ensure appropriate antibiotic
findings may suggest a UTI. The presence of nitrites treatment.
on urine dipstick .findings has a high specificity but The workup ofinitial confirmed UTis in children
a relatively low sensitivity for bacterial infection, is controversial and depends on the patient's age,
because not all bacteria produce nitrites. The absence severity of infection. and response to treatment.
of leukocyte esterase has a fairly high sensitivity. Figure 17-1 provides a suggested diagnostic algorithm
Additionally, urine microscopy findings of both for children with UTis. Current American Academy
UTI
Suspected pyelonephritis Suspected cystitis
I I
-----
< 5 yews of age? < 24 months of age?
I '-No
I--------
Yes Yes No
I
RUS RUS
I RUS
I
Initial UTI?
DMSA DMSA
VCUG Hydronephrosis?
I Yes
/ "- No
Yes
/ ~No No further workup
I I RUS
I I VCUG
VCUG Treatment
nonresponder
or
subsequent UTI
Yes
I \ No
VCUG
I No further workup
I
FIGURE 17-t. Suggested diagnostic algorithm for pediatric urinary tract infection. DMSA, technatium-99
dimercaptosuccinic acid renal scan; RUS, renal ultrasound; UTI, urinary tract infection; VCUG, voiding
~~~~-~~.:.....................................................................................................................................................................................................................................................
ofPediatrics guidelines recommend that all children TAILE 17-1. causes of Childhood Nephrotic
younger than 24 months undergo renal ultrasound Syndrome
to rule out hydronephrosis or structural lesions that
predispose to infection. Those with hydronephrosis and !Primary
those with normal ultrasound who do not respond to l • Minimal change diteue
appropriate antibiotic therapy within 48 hours should 1• "'--' _ _ _ ._I ..L.-~·I.....l---'-
n.IUII~u.aa~~-
also receive a voiding cyst:ouret:hrogram (VCUG). l• Membranoprollferative Jlomerulonepbrltia
In prompt responders with normal ultrasound&, the l• Membnnous nephropathy
VCUG is not mandatory. Other experts argue that
I Stt:f111f1My
all infected children younger than a certain age (6 to
12 months) receive a VCUG regardless of response
to treatment. It is IJkely that further studies will re-
1• ::!:) (hepatitil B, hepatitis C, HIV, malaria,
sult in more evidence--based recommendations. In i• Syatemic dilea~ea (ayatemk lupus erythematosls,

cases ofsUllpected pyelonephritis, a nuclear imaging Henoch-Schlmlmn purpura, IgA nephropathy)
study such as a dimercaptosuccinic acid (DMSA) i• Drugs (nonsteroidal anti-lnBammatory drugs,
is helpful to document areas of injury and possible i heroin)
scar formation. 1• Malignancies (lymphoma, leukemia)
TREATMENT ! • Genetic (Pinniah-type congenital nephrotic

Children with suspected cystitis should be treated with an i. . . . . ~~~!!..~.r.!:?.~--~~~L. . . . . . . . . . . . ... . . . .
appropriate oral antibiotic such as amoxidllin, ampicillin,
nitrofurantoin, or trimethoprim,sulfametho.xazole. If
the culture is negative, antibiotics may be discontfn, nations being idiopathic. Minimal change diuase
ued. A positive urine culture should prompt a 5- to (MCD) is by far the most common cause of primary
7-day coune with an appropriate oral antibiotic (on nephrotic ofidiopathic cases of pediatric nephrotic
the basia ofsensitivity results). syndrome; these are typically encountered in older
Nontoxic-appearing children with suspected pyel~ age groups.
nephritis should be treated with an onl cephalosporin
or intravenous (IV) ampldllln plus gentamicin or CLINICAL MANIFESTATIONS
a cephalosporin until culture results are avallable. Patients with early nephrotic syndrome appear quite
Patients who are toxic~appearing, unable to tolerate well, with a fairly insidious onset ofsymptoms. There
oral medications, or younger than 6 months must may be a history of nonspecific illness a few weeks
be admitted to the hospital for IV antibiotics and before the associated findings. Periorbital edema is
observation. Patients older than 6 months may be commonly the first abnormality noted; occasionally,
discharged on a culture--specific oral antibiotic to patients are treated for allergies because of their mild
finish the course of therapy provided their clinlcal initial presentations. This is followed by dependent
picture improves. Large defects on DMSA scan (lower-extremity) edema, weight gain. and general-
suggestive ofsevere pyelonephritis may benefit from ized edema (ascites, perineal edema). Anorexia and
a full course of IV antibiotics. diarrhea are variably present, often from intestinal
The prognosis fur patients with isolated cystitis is edema. Gross hematuria and hypertension are typ-
excellent; morbidity increases with recurrent infec- ically absent; these should raise suspicion of focal
tion. Most UTI·related complications are the result segmental glomerulosclerosis (FSGS), secondary
of pyelonephritis, including perinephric abscesses, etiologies, or glomerulonephritis.
renal scarring, and renal failure.
The hallmark of nephrotic syndrome is marked
NEPHROTIC SYNDROME proteinuria. Nephrotic,range proteinuria is usually
Nephrotic syndrome is a glomerular disorder char~ defined as proteinuria exceeding 1,000 mg/m2 /day
acterized by marked proteinuria. hypoalbuminemia, or a spot (random) urinary protein-creatinine ratio
hyperlipidemia, and edema. Its etiology may be exceeding 20. The proteinuria in childhood nephrotic
idiopathic (primary) or secondary (Table 17-1), with syndrome is relatively selective, consisting primar-
most cases (>90%) in chndren from Industrialized ily of albumin, with resultant hypoalbuminemia
(<2.5 g/dL). Hyperlipidemia, with elevated serum TREATMENT

cholesterol and triglyceride concentrations, is a Ifthe clinical presentation is consistent with uncompli~
consistent feature of nephrotic syndrome but does cated primary nephrotic syndrome, strict dietary salt
not always need to be confirmed. Hyperllpidemla restriction and oral steroid therapy are appropriate.
is usually transient, resulting from syndrome in Steroids result in prompt remission in most cases of
children. accounting for more than 80,_, ofall cases. MCD, often within 4 weeks. Nephrotic syndrome
Typical patients present between 2 and 6 years of that does not respond to oral steroids may require
age, with boys outnumbering girls 2:1. FSGS, mem- treatment with .stronger immunosuppressants, such
branoproliferative glomerulonephritis (MPGN), and as cyclophosphamide or calclneurin inhibitors. If
membranous nephropathy (MN) account for the symptoms do not resolve within 8 to 12 weeks, or if
remainder reduced lipoprotein catabolism as the the patient experiences frequent or severe relapses
associated lipases are lost in the urine. while on steroids, renal biopsy is indicated to confirm
Microscopic hematuria may be seen in 25% of the diagnosis and identify the histologic subtype.
patients with MCD, but more marked hematuria N albumin (followed by a diuretic) assists in
or the presence of casts on microscopy is indica- inducing temporary diuresis in the presence of in-
tive of other disorders. A renal panel will typically capacitating anasarca or edema-related respiratory
reveal mild hyponatremia (from total body fluid compromise. Albumin without diuretics would be
overload), hypocalcemia (secondary to the low al- indicated in patients presenting with hypotensive
bumin), and possibly a slight increase in creatinine shock; rapid expansion with colloid is needed in
(reduced intravascular oncotic pressure leading to these patients because of their low intravascular
renal hypoperfusion). In the patient complaining of oncotic pressures.
abdominal pain, a thorough examination for signs
of peritoneal involvement is necessary, especially if COMPLICATIONS
rever is present. Bacterial infections, particularly spontaneous
Renal biopsy is indicated for patient& outside the bacterial peritonitis, are frequent compllcations
typical age range for MCD, those with siJnificant renal of nephrotic syndrome. Patients in relapse are
insufficiency or casts in their urine, and those who at particular risk of infection from encapsulated
do not respond to steroids. Gross sections in MCD organisms, especially pneumococcus, because of
show few if any abnormalities (hence the name), loss of proteins that aid in phagocytosis of the
with the only consistent finding being effacement of capsule. The use of antibiotic prophylaxis during
epithelial foot processes demonstrated by electron periods of relapse is debatable and not proven
microscopy. FSGS is characterized by mesangial hy- to be cost-effective. Other serious complications
pertrophy offocal sections of the glomeruli. fibrosis, include thromboembolic events (from the loss of
and varying degrees of tubular atrophy. Increased antithrombotic proteins in the urine), persistent
mesangi.al cellularity and glomerular basement hyperlipidemia, and steroid toxicities (poor growth.
membrane thickening are found in diffuse MPGN. hypertension, Cushingoid appearance).
MN is characterized by diffuse thickening of the
capillary walls because of deposit formation. PROGNOSIS
The prognosis of MCD is excellent. Although up to
DIFFERENTlAL DIAGNOSIS 80% of patients relapse at least once (often triggered
Generalized edema may be present in hepatic, nu- by illness), very few develop any long-standing renal
tritional, cardiac, and other renal disorders. If the insufficiency. Those who do are often unresponsive
patient is edematous without low-serum albumin, to steroid therapy. Unfortunately, this includ.es most
then conditions with fluid and salt overload (heart patients with FSGS and diffuse MPGN, in whom
failure, renal failure, cirrhosis) should be considered. end-stage renal disease (ESRD) is common.
Ifhypoalbuminemia is present without proteinuria,
then intestinal losses of protein or hepatic failure
GLOMERULONEPHRITIS
may be more likely. Other conditions associated
with proteinuria include exercise, trauma, UTI, The term glomerulonephritis implies inflammation
dehydration, and acute tubular necrosis; however. within the glomerulus. Antigen-antibodycomplexes
none of these causes the degree of protein loss seen form or deposit in the subepithelial or subendothelial
in nephrotic syndrome. areas ofglomeruli. followed by immune mediators and
inflammatory injury. The major glomerulonephritic and hematologic d.i.Borders. Important laboratory
syndromes ofchildhood are listed in Table 17-2 with studies include urinalysis (possibly with urine cul-
their distinguishing characteristics discussed in the ture), urine microscopy, serum electrolytes with
following section. BUN and creatinine, complete blood count (CBC).
and coagulation studies.
CLINICAL MANIFESTATIONS The first step of the evaluation is confirmation
The initial presentation ofglomerulonephritis typically of blood in the urine by microscopy. Both hemoglo-
includes hematuria (overt or micro1100pic), protein- bin and myoglobin teat positive for blood on urine
uria, azotemia, oliguria, edema, and hypertension, dipstick; however, there are no red blood cells on
findings also referred to as nephritic syndrome. Red microscopic urine examination in the presence of
cell casts are invariably present; in fact, the urine is myoglobinuria. The presence of red blood cell casts
often described as "tea·colored• by parents. Protein- on urine microscopy conftnns the diagnosis of a
uria is present, but is umally much less prominent glomerulonephritis.
than in nephrotic syndrome. Glomerular filtration Ifglomerulonephritis iJ confirmed, the first test
is compromised by the inflammation, leading to should be an evaluation ofserum complement levels.
salt and water retention and circulatory overload, A low level of complement C3 is typical of acute
manifested by edema and hypertension. Decreased poststreptococcal glomerulonephritis, whereas a
filtration leads to increasing serum blood urea nitrogen persistently decreased level of C3 (and possibly
(BUN) and creatinine levels along with temporary C4) is highly suggestive of lupus or MPGN. Other
sodium and potassium dysregulation, Patients may tests that may assist if the patient iJ hypocomple-
complain of rn.alaise (likely from reduced clearance mentemic include an antistreptolysin 0 (ASO) titer,
of acid and uremic waste products) and fatigue anti-DNAse B titer, antinuclear antibody (ANA), and
(from fluid retention). Also, acute inflammation of anti-double stranded DNA antibody. Ifthe patient is
the kidneys may cause them to swell, resulting in normocomplementemic, an antinuclear cytoplasmic
flank pain from the st:retchi.ng of the renal capsule antibody (ANCA) may assist in detecting certain
in some patients. pauci-immune glomerulonephritides. However,
many of the nephritides are best diagnosed through
DIAGNGSnC EVALUATION a thorough history and physical examination along
Because there are several different glomerulone- with a diagnostic renal biopsy. Because each ofthese
phritides, each with its own distinctive features, the nephritides is diagnosed and treated differently, it is
initial evaluation should first focus on determining hereafter diBCWised separately.
whether nephritis iJ present or not. The differential AcuteJ106t8tl'eptococcalglomerulonephritis (APGN),
diagnosis of hematuria, the most prominent man- the most common glomerulonephritis in childhood,
ifestation of glomerulonephritis, includes other occurs sporadically in early school~age children
conditions (infection, trauma, stones, cystic disease) and is twice as common in males. Streptococcal
infections involving either the throat (pharyngitis)
or skin (impetigo) precede the clinical syndrome by
TABLE 17-2. Diseases tllat Present wtth NephrtUc 1 to 4 weeks. Although treating the streptococcal
Syndrome illness does not prevent APGN, obtaining a recent
j Acute poststreptococcal glomerulonephritis history of infection is important. Elevated ASO or
j Henoch-Sch6nlein purpura anti·DNAse B titers suggest recent infection. The
C3 component of the complement pathway is low
IImmunoglobulln A nephropathy and typically recovers in 6 to 8 weeks following the
IHemolytic urem~c syndrome omet of nephritis. Biopsies are not usually per-
1Synemk lupus erythanatoaul formed, because the renal involvement iJ typicaUy
IAlport syndrome transient, with complete recovery in a majority of
patients. Hypertension and edema are often the most
j Membranoproliferative glomerulooepluitia
significant sequelae and may be controlled through
j Paud-imlnune glomeruloaepbrltl.dea (Wegener's salt and fluid restriction, diuretics, and vasodilators.
!gnnul.omatosla, microscopic polyangiitis,
iGoodpastwe diseue) MPGN is an uncommon d.i.Border that has no
typical features outside of nephritis.lt is diagnosed
! Shmt nephritis i
:.,,. ...,.,.,,.,,.,,,,..,.,,, .,.,,., .,.,,., ,.,,,,,,.,,.,_ ,,,,, , ,,.,,_ ,,,,,,,,,,,,,, ,,,,,,, ,,,,,,,noooon'"o''''''''''"''''''''''''''''': by renal biopsy and should be suspected in older
patients with persistendy low C3levels after 6 to 8 basement membrane. All forrns demonstrate gener-
weeks. It is treated by high-dose steroids or other alized crescent formation in the glomeruli, thought
immunosuppressants with variable success, often to represent cellular destruction by macrophages
progressing to ESRD. Glomerulonephritis associ- with subsequent necrosis and fibrin deposition.
ated with systemic lupus erythematosus (SLE) is Fortunately, rapidly progressive glomerulonephritis
associated with decreased C3 and C4level.s; SLE is is rare in children. When present, it must be treated
further discussed in Chapter 8. immediately with strong immunosuppressants or
H~noch-Schonl~in pwrpUN (HSP) can present pheresis.
acutely with glomerulonephritis, often following AJport syndrome, or hereditary nephritis, is
symptoms ofinfection that are 1hought to be a trigger caused by mutations in the gene-encoding type
of the disorder. It is a systemic vasculltls character- N collagen that result ln an abnormal glomerular
ized by a purpuric rash often involving the lower basement membrane. Inheritance is X-Unked in
extremities and buttocks, crampy abdominal pain, the classic form of the disorder, although defec-
and arthritis. The C3 levels remain normal About tive genes encoding other glomerular basement
5096 of patients may have an elevated immunoglob- membrane components can cause similar disease.
ulin A (IgA) leveL although this is not diagnostic of Because type IV collagen is an important compo-
the disorder. Patients may be treated with steroids nent of the cochlea, Alport syndrome is associated
for severe arthritic or abdominal pain, although with sensorineural hearing loss. A family history
this does not necessarily alter the course of the ne- of renal failure or hearing loss, especially in males,
phritis. Most children with HSP nephritis recover should raise suspicion for the disease. The diagnosis
without intervention, but those with greater renal is usually confirmed through renal biopsy. which
involvement (characterized by significant proteinuria. reveals a characteristic splitting of the basement
hypertension, or elevation of creatinine) may require membranes, although early high-frequency hearing
prolonged courses ofimmunosuppressants such as loss and ophthalmologic features of the disease can
steroids, calci.neurin inhibitors, and antimetabolites. also assist in diagnosis. Patients inevitably progress
Two percent ofchildren with HSP develop long-term to ESRD over time, because there is litde to be done
renal impairment. to prevent progression. Significant progression of
.(fA nephropathy is the most common glomeru- renal disease typically occurs toward the end ofthe
lonephritis worldwide, with an increased prevalence second decade in most men and is often mirrored
in pan-Pacific Asian countries. Once thought to be by the degree of hearing loss.
a benign condition, it is now lrnown to slowly prog- Benign familial h~maturia, or thin membrane
ress to renal failure in 2596 of cases. Most patients disease, is a common cause of asymptomatic mi-
present with either asymptomatic gross hematuria croscopic and occasionally gross hematuria. Renal
occurring a few days after an upper respiratory function is normal, and biopsy, although unnecessary,
or gastrointestinal infection or with persistent reveals diffuse thinning of the glomerular base-
microscopic hematuria. However, some patients ment membrane on electron microscopy. Because
may present with fulminant nephritis. C3levels are transmission is autosomal dominant, asymptomatic
normal. The only method of confirmation is renal microscopic hematuria is usually found in other
biopsy, which demonstrates mesangial deposits of family members.
IgA in the glomeruli. Treatment varies from potent
immunosuppression (in those with rapid progression
HEMOLYTIC UREMIC SYNDROME
of disease or severe proteinuria), antiproteinuric
agents and antioxidants (in moderate disease), to Hemolytic uremic syndrome (HUS) is technically
no therapy in the majority of mild cases. not a glomerulonephritis, but presents with a similar
Rapidly progreuive glomerulonephritis is the nephritic picture. It is caused by endothelial injury
description given to a number ofacute glomerulop- of the renal vasculature with a subsequent cascade
athies that, for unknown reasons, deteriorate over a of mlcrothrombi formation and &hearing of eryth-
few weeks or months to renal &.ilure and even death. rocytes passing over the thrombi. A majority of
Many of these disorders are also systemic vasculitides cases are caused by a Shiga-like toxin produced by
and may have pulmonary involvement as well Some an enterohemorrhagic strain of E. coli (0157:H7),
of the pauci-immune glomerulonephritides have although atypical cases not associated with diarrhea
positive ANCA or antibodies against the glomerular also occur.
CLINICAL MANIFESTATIONS to ESRD. Those with atypical presentations often

Children with diarrhea-associated HUS often have have more significant disease sequelae, which may
an exposure to E. coli, either through undercooked recur, particularly if they have a genetic form of
meat or through an exposure to farm animal feces the disease.
(via water runoff or foods exposed to manure}.
Patients present with a prodromal diarrheal .illness RENAL TUBULAR ACIDOSIS
for 4to 7 days before the other manifestations of the
disorder. Diarrhea is often bloody and associated All forms of renal tubular acidosis (RTA) are
with significant abdominal pain. This is followOO. characterized by normal anion gap hyperchloremic
by pallor, jaundice, petechiae, and/or oliguria. Some metabolic acidosis, resulting from insufficient renal
patients are noted to be edematous from continued transport of bicarbonate or acidJ. The tubules are
fluid intake with declining urine output, such that the site of reabsorption and secretion. Most bi-
they may be hypertensive as well. carbonate filtered from the plasma is reabsorbed
in the proximal tubule, along with amino acids,
DIAGNOS11C EVALUATION glucose, sodium, potassium, calcium, phosphate,
HUS is characterized by the classic trio of microan- and water. In the distal tubule, the remainder of the
giopathic hemolytic anemia. thrombocytopenia, and bicarbonate is reabsorbed and hydrogen ions are
azotemia. The anemia and thrombocytopenia of the secreted into the tubular lumen. Defects in either
disease can be significant, with hemoglobin levels transport site compromise the kidney's ability to
dropping to less than 8 gldL and platelet counts maintain pH homeostasis.
often less than 100,000/~. Because red cells are
hemolyzed. lactate dehydrogenase levels are often CLINICAL MANIFESTATIONS
very elevated The blood smear demonstrates the Patients with RTA typically present with failure to
hallmark schistocytes of microangiopathic hemolysis. thrive during their infant or toddler years, although
Coagulation studies should be normal they may be older if the disorder was acquired
In patients with diarrhea, a stool culture fur E. late: in life. This stems from their chronic acidotic
coli 0157:H7 should be obtained to confirm typical state. which may also be associated with vomiting
HUS as well as for epidemiologic investigation, be- and anorexia. Polydipsia and polyuria with volume
cause this is a reportable disease to local and state contraction may also be seen. especially in proximal
health units. If the patient does not have associated RTA. Other presenting signs and symptoms may
diarrhea, an evaluation fur atypical HUS should be include findings of rickets or kidney stones.
carried out, because its treatment and prevention
is altogether different. DIAGNOSTIC EVALUATION
Any patientwith nongap metabolic acidosis of unclear
TREATMENT etiology warrants further workup to rule out RTA
Most therapies for HUS are supportive, because (Fig. 17-2). Patients with bicarbonate losses in the
there are no current treatments for the cascade of stool, primarily from diarrhea but also with other
events following endothelial injury. Transfusion fistula drainage, may also present with hyperchlo-
with packed red cells is needed in half of all pa- remic acidosis. Hypokalemia is seen in both distal
tients, generally provided ifthe serum hemoglobin (type 1) and proximal (type 2) RTA. whereas the
is less than 7 gldL or the patient is symptomatic. hyperkalemia oftype 4 RTA is secondary to a lack of
Platelet transfusions are usually uMecessary except aldosterone responsiveness in the collecting tubule.
in the face of active bleeding or for planned sur- Urine pH is typically elevated in distal and proximal
gical intervention ifthe platelet count is less than RTA; however. it may drop below 6 with proximal
20,000/.,U.. Fluid and electrolyte restriction is often RTA ifthe patient is acidotic enough. Another way
required when oliguria is present. Dialysis (either to discern between these two is by calculating a urine
peritoneal or hemodialysis) may be needed in up to anion gap (urine Na + K - Q). If the urine anion
251J1i of all patients. A majority of patients recover gap is positive, then ammonia production is likely
after the acute period, but there can be long-term impaired (as seen with a distal RTA).
sequelae to the kidneys. However, a percentage of Renal ultrasound may reveal nephrocalcinosis
patients never recover their function and progress with distal RTA. Most patients with proximal
Hyperchlol-* metabole Mlda.ls?

(low-serum pH; low-serum bicarbonate; nonnal anion gap)
!
Yes
!
Calculate urine anion gap
{Na• + K+}- Cl-
1
Positive (Cr < Na• + K"}

I
NoGIIosses
~ ~
Hypo-Jnormokalemia Hyperkalemia
(diarrhea, etc.)
~ ~
Urine pH > 5.5
~
Urine pH < 5.5
No exogenous Ct-
~ ~
saltadded
Urine pH < 5.5

~ Distal RTA (type 1) Distal RTA (type 4)
Proximal RTA (type 2}

~
FIGURE 17-2. Suggested diagnostic algo~thm for hyperchloremlc metabolic acidosis of unknown etiology. Gl,
gastrointestinal; RTA. renal tubular acidosis.
•••-·-•o•o.OOOOoooooooouoooooouoooooo._.._,,_,,...,,,,,,,,,,,,,,,--.,, , ,,,,,,, .,,,,,,, ,,,.,,.u..oooo ooooooou•••~•••••..._•••••••--•ooooooooooOo•-••••••••• ••••••-•••-••••••u•••••-••••••••••••••-•••••••••••••••••••••••••••ooooooooooooooouooooouooooouo
(type 2) RTA have it in conjunction with Fanconi

syndrome, a generalized disorder ofproximal tubule
a:
I :13Q: I;t•IH Itll•1 tj :! ;; if)! ~~i IUl•lifW
transport. Urinalysis may reveal mild sJucosuria Diabetes insipidus (Dl} i.8 a disorder in renal-concentrating
and proteinuria, whereas urine concentrations of ability, secondary to a lack of efficacy of arginine
potassium and phosphorus are elevated. Additionally, vasopressin (antidiuretic hormone) on aquaporin·
Fanconi syndrome has been associated with other mediated transport of water in the renal-collecting
dOOrders, including cystinosis, Wihon disease, and duct. It may be central or nephrogenic 1n origin. In
Lowe syndrome. central DI, the production or release of hormone is
insufficient (see Chapter 15). Nephrogenic DI (NDI)
TREAtMENT arises from end-organ resistance to the hormone,
Treatment consists of providing children with suffi- either from a receptor defect or !rom other pro-
cient amoWlts ofan alkalinizing agent (bicarbonate cesses that interfere with receptor action. NDI may
or citrate) to correct the acidosis completely and be congenital, with 90% of cases being X-linked, or
restore normal growth. Thiazide diuretics may be acquired. Acquired NDI has been associated with
administered in proximal RTA to increase proximal polycystic kidney disease, pyelonephritis, lithium
tubular reabsorption of bicarbonate. Hypokalemia toxicity, and sickle cell disease.
is treated concurrently when the alkali is coupled
with potassiwn as a salt. H RTA is associated with CLINICAL MANIFESTATIONS
an underlying condition, the primary disorder must Patients with NDI produce large amoWlts of very
be addressed. dilute urine regardless of their hydration status.
This polyuria necessitates exressive water intake diuretics or amiloride to decrease urinary sodium
(polydipsia) to compensate for these losses. Con- reabsorption. Prostaglandin synthesis inhibitors,
genital NDI typically rnanifusts in the first weeks like indomethacin. may have an additive effect on
of life with hypernatremic dehydration. because reducing water excretion.
such infants are unable to maintain sufficient fluid Children with NDI are at risk for poor growth
intake. Other features may include intermittent because their oral intake is predominantly fluid and
fever, irritability, vomiting, and poor growth. Inter~ may not be calorie~rich. The disease is l.ifelong but
estingly, associated pregnancies are not associated carries a good prognosis, provided that episodes of
with polyhydramnios, because the mechanisms hypematremic dehydration are minimized during
affecting urine concentration do not develop until the early years.
after delivery. Developmental delay may occur as a
result of frequent hypematremic seizures.
Some patients may not manifest symptoms until HYPERTENSION
they are stressed with illness. Older children may Normal blood pressure rises gradually as a child
present with polyuria, nocturnal enuresis (or sig- grows, reaching adult values during adolescence.
nificant nocturia), and constipation. Hypertension in the pediatric population is defined
as blood pressure greater than the 95th percentile for
DIAGNosnC EVALUATION age, gender. and height measured on three separate
Patients with DI are unable to concentrate their urine. occasions about 1 week apart. Essential (primary)
even with significant dehydration. Urine·specific hypertension is the most common form in adults.
gravity and osmolarity remain inappropriately low, Until recently, children were more likely to have sec-
whereas serum osmolarity is elevated. A urine os- ondary hyputmslon, usually related to renal disease.
molality below 500 mOsmlkg in a dehydrated child However, the increase in childhood obe&ityand high
should suggest DI; in fact, the urine osmolality is often sodium intake of the Westernized diet have led to a
below 200 mOsm/kg. Other causes of polyuria, such concurrent rise in pediatric essential hypertension,
as diabetes mellitus and renal salt wasting. can be which is being documented at increasingly earlier
ruled out by urine dipstick results for glucose, urine ages. Endocrine. vascular, and neurologic conditions
electrolytes, and decreased serum sodium levels. may also be auoclated with increased blood pressure
Differentiating central DI from NDI is not (Table 17~3). The younger the patient or the higher
possible on the basis of symptomatology alone, the blood pressure reading, the more likely the hy-
although the former more commonly follows head pertension is secondary in etiology.
trauma, meningitis, or is associated with midline
cranial anomalies. The DDAVP test can help dif- CLINICAL MANIFESTATIONS
ferentiate central from NDI, because NDI would Stable or slowly progressive hypertension is unlikely
not respond to the hormone; affected patients to cause symptoms; therefore, vigi.l.ance at health
would continue to have hypoosmolar urine. Water maintenance visits is needed. Family history is often
deprivation testing can also be considered to dif- positive for hypertension, stroke. or premature heart
ferentiate between Dl and psychogenic polydipsia, disease. Patients with secondary hypertension often
because patients with the former would become come to medical attention for complaints related to
hypernatremic over time. Perinatal testing to de- their un.derlying disease (e.g., growth Callure, edema).
tect arginine vasopressin receptor gene (AVPR2) Past medical history (including neonatal history of
mutations is now available. vascular catheters), recent medication use, and re-
view of systems for urinary tract symptoms provide
TREATMENT pertinent information.
Acute treatment consists of rehydrating the child, Severe hypertension or hypertension that has
replacing ongoing urinary losses, and correcting developed over a short period of time can cause
any electrolyte abnormalities. A low~sodium diet headache, dizziness, and vision changes. Hyperten-
(<0.7 m.Eq/lcg/day) is essential; maximal osmolal- sive encephalopathy is characterized by vomiting,
ity of the urine is fixed, so the amount of sodium ataxia, mental status changes, and seizures. Other
urinary excretion helps determine the obligate symptoms of hypertension may include epistaxis,
urine output. This should be coupled with thiazide chest pain, palpitations. and flushing.
TAILE 17-3. Differential Diagnosis of Pediatric DIAGNOSTIC EVALUATION

Hypertension Obtaining an accurate blood preuure reading is essen-
tial in the diagnosis of hypertension. The air bladder
IFlctlflous portion of the cuff should encircle the patient's arm
!• Anxiety ("white coat" hypertension) and be wide enough to cover 7596 of the upper limb. A
i
!• Inappropriate cuff size cuff that is too small will give a falsely elevated read-
!Pllnmy(EI ing; likewise, a cuff that is too large may yield lower
iRMII
~
pressure readings. Also, the patient should be calmly
seated for at least 1 to 2 minutes before measurement,
i • Glomerulonephrit
with the arm kept still and at heart level during the
i•
' Renal scarring from pyelonephritis meuurement
l•
: t""'-+1,. ~----
"7~~ Ifth1s measurement is elevated. then the remam-
!• Obstructive uropathy der of the physical examination should focus on
! evaluating for secondary causes of hypertension.
!• Renal trauma
I: • Renal tumor
At least once. the blood pressure should be taken
in all four extremities to exclude aortic coarctation.
j. Renal failure (acute or chronic) Particular attention should be given to the presence
Ii NeunJiogic
• Pain
of tachycardia (sympathetic stimulation), heart
munnur (as seen in coarctation), or gallop (heard
I·
i •
Iocreued inlraaanlal preuure
Traumatic brain injury
with significant fluid overload). Retinal examina-
tion should be performed to make sure there is
no papilledema to rule out intracranial causes of
!i • Malignant hyperthermia hypertension, especially in patients complaining of
===-
IDtup lllld Taxins headache. Poor growth. flank pain. a retroperitoneal
mass, large bladder, or abdominal bruit suggests a
renal or renovascular etiology. Obesity contributes
1: Calclneurin inhibitors
i •
to hypertension in a genetically predisposed patient.
Other secondary findings to consider include the
1. Cocaine and otheT street c1rup appearance ofCushingoid features and the presence
II Endoc:rfne
• Congenital adrenal hyperpluia
of thyromegal.y or nodules.
The initial laboratory evaluation should include
a CBC, serum electrolytes, BUN, creatinine, and
i • Cushing syndrome urinalysis. This is mainly to screen for any evidence
!' • Hyper- or hypothyroidism of renal disease, such as anemia, elevated creatinine,
i• Pheochromocytoma or proteinuria. The presence of hypernatremia
with hypokalemia may be associated with hyper-
l• Hyperaldosteronism
aldosteronism, whereas hypercalcemia may also
I. Hypercalcemia cause elevated blood pressure. Ultrasound of the
~~ kidneys permits assessment ofanatomy, whereas a
!
i • Renal artery stenosis Doppler ultrasound may show the renal vasculature
! but is rarely diagnostic of renal artery stenosis
i • Coarc:tation ofthe aorta
alone. Chest radiograph. electrocardiogram, and
!· Renal artery or vein thrombosla (including &om
echocardiogram to evaluate heart size and function
I! • umbilical cat:heb!n in newbonu)
Arteriovenous fistula
are often indicated, but more to evaluate for the
i presence of end-organ injury than the etiology of
! • Vuc:ulitia the hypertension. Other secondary tests to con-
! Ottlfr sider include thyroid function tests, serum renin
!• Chronic: lung disease (infants) and aldosterone, serum metanephrines, and urine
1. Acute intermittent porphyria
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catecholamines.
TREATMENT Acute renal failure (ARF) consists ofan abrupt reduction

The best treatment for essential hypertension is pre- in renal function. occurring over hours to days, with
ventive health care. High-salt diet, sedentarylikstyle. retention ofnitrogenous waste products such as BUN
cigarette use, alcohol or drug abuse. high-serum and creatinine (azotemia). Recently, the term •acute
chole&terollevels, and obesity compound the disorder kidney injury" (AKI) has been proposed to reflect
and Increase the morbidity and mortality. First-line a complex disorder that occurs In a wide variety of
treatment reCOD'I.IDendat:ions include decreasing daily settings, with clinical manifestations ranging from a
dietary sodium intake, decreased total caloric intake, minimal elevation in serum creatinine to anuric &ilure.
and increased cardi.ovucular activities. When these The mechanisms of AKI include prerenal. intrinsic.
measures fail after 3 to 6 months, either from patient or postrenal injury (Table 17-4). Prerenal injury is the
nonadherence or from nonefficacy, then pharmaco- functional response of a structurally normal kidney
logic therapy may be indicated. However, if patients to hypoperfusion. This is the most common fonn,
present with symptoms from their hypertension or accounting for about 55% of AKI, with hypovolemia
blood pressure readings that are greater than the 99th as the most common underlying mechanism. The
percentile. initial use ofantihype~ iswarranted decreasing glomerular filtration rate (GFR) produces
Secondaryhypertension responds to treatment of the oligwia (urine output < 400 rnL/m2/day) or anuria.
underlying disol.'der when possible. Antihypertensives Most patients recover completely from prerenallnjury
may be necessaryin the short term to address the blood unless it is unrecognized or inappropriately treated.
pressure elevation associated with the secondary cause. By contrast, intrinsic renal injury results from a
The choice of pharmacologic therapy is varied, structural or functional abnormality in the kidney
with several different cluses of agents available itself, accounting for about 4096 of AKI cases. The
in pediatric patients. Diuretics are often effective most common underlying mechanism is acute tu-
in patients with salt or fluid overload and may be bular necrosis (ATN), and the terms intrinsic ARF
used with a few minor side effects (increased risk of andATN are frequently used intexchangeably. ATN
dehydration). Calcium channel blockers are used in
all age groups with very little side effects, but may
not directly address the etiology of the hypertension. TAILI17-4. Causes of h:ute Kidney InJury
P-Blockers may be used for catecholamine-induced
hypertension, but are contraindicated in athletes
IPnwnal
Hypovolemia (dehydntion, Jhock, hemorrhase,
or patients with asthma. Angiotensin-converting
,! , •
nephrotic syndrome)
enzyme (AC.E) inhibitors are effective first-line
• Hypot:ension (decreued cardiac output, ahoc:k,
agents in children with renal disease (especially for
seplis, anaphylam)
unilateral renal artery stenosis) t~nd in adolescents
and athletes because of relatively few side effects • Renal vasoconltriction (nonsteroidal anti-
inflammatory drop, angiotenain-converting
and potentiallons-term benefits, but do require
enzyme lnhlbitora, hepa.totenal syndrome,
monitoring of renal function. a-Blockers may also renal artery stenosis, abdominal compartment
be effective for intra.cranial causes of hypertension. syndrome)
Additional vasodilators are available for pediatric
use, but often not as first-line agents. !lnt1fnslc
In patients with severe hypertension. rapid decreases
in blood pressure compromise organ perfusion. Hy-
i• ~:::,u:,= (prolonged prerenal
pertensive crisis Is an emergency and may be treated ·:',_• Acute glomerulonephritis (poltstreptococcal,
with sublingual nifedipine, IV labetalo], or IV drips membnnoprollferative, c:reiClelltic)
of nicardipine or nitroprusside. Hydralazine is also Acute interstitial nephritis (ldiopathi.c, antibiotics)
,.
1•
effective, espedally in neonates. Oose monitoring
in the intensive care setting is essential to prevent a
~m:) (hemolytic uremic
rapid drop in blood pressure.
!l'ollriiW
~ • Conpnibll (poaterior umbra~ valva,
ACUTE KIDNEY INJURY j ureteropelvic junction obstruction)
Renal failure is a potentially life-threatening con- : • Acquired (atones, clota, neuropnlc bladder,
dition. The incidence in children is increasing. : tumor)
••••••~••••••••••••••• •••••• ••••••••••••••n••••••••••••••••••••••••••••••oo.,ooooooooooooooo•••••••• ••••••••••••••••••••ooooo""''""''"'
is a poorly understood condition in which damaged abdominal or suprapubic masses. Other historical
tubules become obstructed with cellular debris. It and examination finclinp include those seen in the
may result from prolonged prerenal injury, sepsis, different glomerulonephritides.
the use ofnephrotoxic medications (such as amino-
glycosides, vmcomycln. and radiocontra.st media), DIAGNOSTIC EVALUAnON
or infection. Intrinsic renal injury can also occur in AI<I Is defined by an acute rise in creatlnlne, but Is
patients with glomerulonephritis, intersti.tial ne- also characterized by hyperblemia, azotemia, and
phritis, and renal vasculitis. Although HUS was the metabolic acidosis. Anemia is variably present Uri-
most common cause of intrinsic AKI a decade ago, nalysis fur hematuria, proteinuria, leukocytes, and the
the epidemiology has shifted in recent years, with presence of casts also provides useful information.
sepsis accounting for the majority of cases today. Red cell casts are typical ofacute glomerulonephritis,
lntrarenal conditions can present with oliguria or white cell casts are seen in interstitial nephritis or
anuria, although the urine output may also be normal pyelonephritis, and pigmented coarsely granular
when nephrotaxins are the cawe (nonoliguric renal casts indicate ATN. Urine and plasma urea nitrogen,
failure). Although many patients can recover from creatinine, osmolarity, and sodium can be used to
intrinsic renal injury, a significant number progress differentiate between prerenal and intrinsic injury
to chronic kidney disease. (Table 17-5). Urine culture is indicated if pyelone-
In postrenal injury, obstructive lesions at or below phritis is suspected.
the collecting ducts produce increased intrarenal Renal ultrasound is the .single best noninvasive
pressure and result in a rapidly declining GFR and radiographic teat for determining the site ofobstruc-
hydronephrosis. The lesions may be congenital (a tion in postrenal injury, as well as kidney size and
majority ofcases in pediatrics) or acquired. Patients shape and renal blood flow. It may also be useful to
with complete obstruction are anuric, whereas partial differentiate between acute and chronic kidney in-
obstructions may present with normal or increased jury, because kidneys are normal or enlargedlnAKI
urine output. and potentially shrunken in chronic kidney disease.
Renal nuclear acans can delineate renal perfusion
CLINICAL MANIFESTATIONS and functional differences. VCUG and Cfs may also
Oliguria Is one of the more frequently noted find- be indicated in certain cases as directed by initial
ings with AKI, although this may not be a feature imaging studies.
of interstitial nephritis or nephrotoxin-induced Renal biopsy Is indicated when the diagnosis
injury. Edema is usually evident but often insidious remains unclear or the extent of involvement is
in onset, first presenting with poorly fitting clothing unknown. Other laboratory tests for the different
or decreased energy levels. Findings of congestive glomerulonephritides may also be considered.
heart failure (respiratory difficulty, diffuse crackles
on lung examination, hepatomegaly) are very late TREATMENT
discoveries but require immediate intervention. Major complications of AKI may be metabolic
Other generalized symptoms may be nonspecific (hyperkalemia, hyponatremia, hypocalcemia, met-
and include malaise, fatigue, anorexia, and vom- abolic acidosis with high anion gap), cardiovascular
iting. Flank or abdominal pain may be seen with (hypertension, pulmonary edema, arrhythmias),
swelling of the kidneys or urinary tract, such as gastrointestinal (gastritis, bleeding), neurologic
from obstruction. (somnolence, seizures, coma), hematologic (anemia,
Most cases of AKI are diagnosed in hospitalized bleeding), and/ or infectious (increased suscepti-
patients, so their recent medical histories are known. bility to infections). These sequelae often need to
A history of recent dehydration. shock, cardiac sur- be treated directly while also addressing the cause
gery, or previous renal conditions may help clarify oftheAI<I.
the etiology. A complete list of recent medications Speclfic treatments for AK1 depend on the eti-
(including rad.iocontrast) is also very helpful in ology. Prerenal injury usually responds to prompt
diagnosing nephrotoxic medication injnry, espe- and vigorous correction of the renal hypoperfusion,
cially because most injury occurs with cumulative with either N fluid resuscitation or vasopressor use.
administrations of nephrotoxic drugs. Depending Postrenal injury often responds to correction ofthe
on the etiology, the physical examination may obstruction. either through placement ofa bypassing
reveal dehydration, cardiovascular instability, and catheter or through surgl.cal correction.
TilLE 17~. Typical Findings in Prerenal and Intrinsic Acute Kidney Injury
:......-.c•-- ..._.
1 MalfJ* Fflrt IIAnyAlnlmlflliM
iUrine-lpecificpvity >I.mo < 1.020
!Urine osmolaUty (mOsmlkg ~0) > 500 < 350
iUrine/plasma crealinine > 40 < 20
!Senun bloocl urea nitrogen /creatinine >20 < 15
~ Fractional exaetion of sodium (FENa) <1 >2
~.................................................................................................................................................................................................................................................................................................
;
FENa (%) ~ (lUIP)Na)I([UIPJC., X 100 1:
Once intrinsic AKI is established, treatment is described in renal dysplasia, resulting in polyuria,
largely supportive, consisting of appropriate fluid episodic unexplained dehydration, or salt craving.
management (careful replacement of insensible Other subjective complaints may include anorexia,
water loss and ongoing losses), correction of elec- nausea, malaise, lethargy, and reduced exercise
trolyte abnormalities, and dialysis (for fluid overload, tolerance-all from the gradual accumulation of
hyperkalemia, o r acidosis that is unresponsive to unfiltered toxins. Growth failure frequently prompts
medical therapies). Medications that undergo renal evaluation for renal disease in the outpatient setting.
clearance require dosing adjustments in AKI to avoid Riclcets may also be present. Other initial presen-
toxicity or further worsening of the renal injury. The tations include "isolated• hypertension or anemia.
underlying abnormality mullit be corrected to achieve With improvements in prenatal imaging, many
optimal resolution and to prevent recurrence; these abnor malities are noted before delivery.
treatments vary greatly depending on the primary
etiology. Examples inclu de immunosuppression DIAGNOSTIC EVALUATION
(immune-medJated disorders), antibiotics (pyelone- Patients with CKD demonstrate many of the same
phritis), removal of the offending agent (nephrotoxins laboratory abnormalities seen in AKI, including azo-
or interstitial nephritis), and occasionally watchful temia, acidosis, sodiwn bnbal.ance, and hyperblemia.
observation. The prognosis of AKI depends on the The diagnostic evaluations (urinalysis, CBC, renal
underlying etiology, the length of impairment, and panel, BUN, creatinine, calcium, and phosphorus) are
the severity of functional disturbance. also very similar. Urinalysis may show a low specific
gravity lf renal-concentrating ability has been lost,
whereas proteinuria may also be present. Anemia
CHRONIC KIDNEY DISEASE is usually more pronounced in CKD than in AKI,
Chronic kidney disease (CKD) implies that renal becaWie there is prolonged ceuation oferythropoi-
function has dropped below 3096 of normal over a etin production by the kidney combined with iron
longer period oftime, typically greater than 3 months. deficiency from impaired nutritional intake. Chronic
Function at 1096 or less than normal is defined as hypocalcemia leads to secondary hyperparathyroid-
ESRD. The most common causes of CKD in the ism (elevated intact parathyroid hormone levels),
pediatric population are congenital. most often due which may present with renal osteodystrophy on
to obstructive uropathy, followed by renal dysplasia skeletal radiographs. Hyperphosphatemia may aho
and other hereditary renal conditions. Some acquired be found in earlier stages of CKD. Renal ultrasound
glomerulopathic disorders, such as FSGS, are also may demonstrate changes in renal size (often small),
common causes in older children. density (often hyperechoic), and loss of corticomed-
uD.ary differentiation.
Unlike AIO, the different etiologies ofCKD typically TREAtMENT
do not produce oliguria except when it results from Treatment for CKD includes nutritional, pharma-
an acquired disorder or obstruction. Often, there cologic, and additional interventions to address the
may be an issue with renal-concentrating ability, as clinical manifestations ofthe disorder and hopefully
prevent rapid progression. Close monitoring ofclin- complications, like exit-site infections or peritonitit,
ical and laboratory status ill required Progression of are the most commonly reported problems, but can
CKD is beat avoided by controlling any associated usually be treated in the outpatient setting. Hemo-
hypertension while minimizin8 proteinuria through dialysis, performed at specialized pediatric dialysis
the use of ACE inhibitors and angiotensin receptor centers, provides close to l()l)f. of normal renal function
blockers. Protein restriction is controverslal. because but is time-consuming. Hemodialysis-associated
it lessens azotemia but can also adversely affect mortality is low, but complications of hemodialysis
growth and development. Sodium and fluid intake are not uncommon. They include bleeding (from
may need to be restr1cted. to control hypertension; the anticoagulation of the procedure), thrombosis
antihypertensive medication is often needed with. or infection of vascular access, and too rapid or little
advancing dlseue. fluid or electrolyte removal Acute dehydration may
Hyperblemia Js best avoided through di- occur with any treatment. Dysequilibrium syndrome,
etary potassium restriction or through the use of which occurs when the serum urea nitrogen level
potassium-binding resins, Uke Kayexalate. Acidosis drops too rapidly (resultins in cerebral edema), may
may require bicarbonate supplementation. Calcium be seen. more commonly with initial hemodialysis
supplementation and activated vitamin D are used treatments. Signs and symptoms ofdysequilibrium
to treat renal osteodystrophy, whereas phosphate syndrome include headache, nausea, vomiting, mental
binders and dietary restriction address hyperphos- statues changes, seizures, and coma.
phatemla. hon supplementation and recombinant Renal transplantation is the ultimate therapy for
erythropoietin address the anemia. Complete all children with ESRD, with few absolute contra-
catchup growth is unlikely, even when optimal ca- indications. The donated kidney may come from a
loric intake and normalization of metabolic param- related living or deceased donor. Living~related donor
eters occur; growth hormone may also be needed. transplants historically have better host and graft
Children with less than 10~ of nonnal renal function survival rates, although the differences are narrowing.
(creatinine>3 to 10 mgldL depending on size) require Children with CKD require complex and
either dialysis or renal transplant. Peritoneal dialysis. tiJne..amswnlng treatment and. as a consequence,
which can be performed at home, is the standard oftenexperience a reduction Inthe quality oflife and
for children requiring long-term dialysis. Infectious are predisposed to developmental and social delays.
KEY POINTS
• Infants with bilateral renal agenesis develop Potter typically responds to high-dose steroids within
sequence (clubbed feet, cranial anomalies) and 4weeks.
are typically stillborn or die shortly after birth • Glomerulonephritides are characterized by
because of associated pulmonary hypoplasia. hematuria, azotemia, oliguria, edema, and
• Ureteropelvic junction obstruction is the most hypertension. The prasence of red cell casts
common cause of hydronephrosis in childhood. on urine mlcroaoopy Is pathognomonic for
• Recurrent UTia are the most common presen- glomerulonephritis.
tation of veslcourateral reflux. • APGN Is the most common glomerulonephri-
• UTis are the most common bacterial infections tis In children. Its prognosis Is excellent, with
in febrle Infanta. The most significant risk factor normalization of C3 levels in 6 to 8 weeks and
for rectnent UTia ia the presence of a urinary resolution of clinical manifestations in 90%
tract abnormality that causes l.l'inary stasis, of cases.
cbstructjoo, reflux, or dy&Ulctional voiding. • HSP is a systemic vasculitis characterized
• Nephrotic syndrome Is characterized by severe by a purpur1c rash often Involving the lower
proteinuria, hypoabuminamia, hyperlipidemia, extremities and buttocks, crampy abdominal
and edema. MCD Ia the most common type pain, and arthritis. About 50% of patients may
of pediatric Idiopathic nephrotic syndrome; it have an elevated lgA level, although this is not
diagnostic of the disorder. C3 levels remain • Blood pressLn norms for children are related to
normal. age, gender, and height. Three blood pressure
• Alpert syndrome Is a fonn of hendtary neplvitis readings on separate occasions that are greater
associated with aenaomeural hearing loss. than the 95th percentile for age, height, and
gender constitute hypertension. The younger
• HUS is ctwacterized by the classic trio of mi-
the hypertensive child and the higher the blood
croangiopathic hemolytic anemia, thrombocy-
pressure, the mora likely that the etiology of the
topenia, and azotemia. A majortty of cases are
hypertension is secondary.
caused by a Shiga-llke tom produced by an
enterohemorrhagic strain of E. coli (0157:H7). • The causes of AKIInclude prerenal (55%), in-
trarenal (40%), or postrenal (5%). laboratory
• RTA is characterized by hyperchloremic meta-
findings include increasing levels of BUN and
bolic acidosis w ith a normal plasma anion gap.
creatinine, hyperkalemia, and metabolic acidosis.
The moat common type In childr11n is distal RTA
type 4 with hyperkalemia (from hypoaldostero- • The most common cauaes of CKD in the pe-
nism or pseudohypoaldosteronism), often seen diatric population are congenital, most often
with obstruction of the urinary tract. due to obstructive uropathy, followed by renal
dysplasia and other hereditary renal conditions.
• Dl is a disorder of urine concentration and can
Function at 10% or less than normal is defined
be central or nephrogenic. Clinical manifestations
include polyuria, polydipsia, and growth retar-
as ESRD.
dation. Therapy for NDIIncludes a low-sodium • Children with growth fallu111 should be screened
diet, thiazide diuretics, and indomethacin. tor renal disease.
CLINICAL VIGNETTES
VIGNET1E 1 Which of the following Is the most likely etiology

A 7-yeer-old boy presents to the emergency room tor of his symptoms?
gross hematuria of 1 day's duration. He also has had L SLE
decreased appetite and energy levels for the past 2 11. Poetstreptococcal glomerulonephritis (PSGN)
days. He has not had any fevers or vomiting, but had c. HSP nephritis
been ill about 3 weeki ago with 1 day of fever and d. lgA nephropathy
abdominal pain. On vital signs, he is afebrile with a a. HUS
heart rate of 82 beats per minute (bpm) and blood 3. ASO titer is also found to be elevated in this
pressure 120fl8 mm Hg. He has some eyelid swelling patient. Which of the following presents the best
and pretibial edema but an otherwise negative phys- therapy for this patient?
Ical examination. His urtne dipstick results show 4+ L Prednisone use (2 mg/kglday) for 4 to 6 weeks
blood and 2+ protein, but are negative for nitrite and II. Prompt antibiotic therapy to prevent disease
leukocyte esterase. Microscopic examination confirms progression
the presence of red cells in the urine, along with some c. Diuretic use for hypertension
red cell casts. Serum electrolytes ara within normal d. High-prctein diet for proteinuria
limits, but creatinine is slightly elevated at 0.7 mgldl. e. Prophylactic antibiotic use to prevent nephritis
1. Which of the following represents the most ap- recurrence
propriate next laboratory test? VIGNET1E2
L Serum cholesterol level
IL ANA A 5-year-old boy Is being evaluated In the clinic for
c. Serum lgA level several days of swelling. His mother first noted some
~ Complement level (C3) upper respiratory symptoms (rhinorrhea, nonproduc-
1. Serum and urine osmolarity
tive cough) about 2 weeks ago with no fevers. He
initially seemed to get better, but the swelling of his
2. lhe C3 level Is low at 22 mgldL (normal > 75), eyelids started 2 days ago, prompting her to give him
whereas a C4 level is nonnal at 25 mg/dl. CBC an antihistamine the past two evenings. The swell-
is notable for a slightly increased WBC count at ing has persisted and spread to his face, abdomen,
12,000/~L and a normal hemoglobin of 12.5 g/dl. and hands. The child hu a decreased appetite and
fatigue, but primarily complains of some abdominal cannot seem to gain weight. She was bom full-term
discomfort with no vomiting or diarrhea. His weight and was discharged home on day-of-life 2. She has not
Is 20.2 kg, heart rate Is 122 bpm, and blood pressure had any emergency room visits or hospital admissions
Is 85/52 mm Hg. He has notable swelling of his face, since then and has 1'808lved all of her 1'8C0mmended
eye6ds, and distal extremities. His lungs are clear. immunizations to date. She has no reported problems
The abdomen Is fairly distended. The remainder with recurrent fevera or diarrhea, but often has nonbloody,
of his physical examination is negative. Urinalysis nonbilious vomiting. She was formula fed and would
reveals trace blood with 4+ protein and pH 5, but is often require feedings every 2 to S hours including
otherwise negative. through the night, only being spaced out in frequency
by her parents' necessity at 8 months of age. Even
1. Which of the following laboratory results would
then she had occasional vomiting. She is now eating
be most unexpected?
solid foods, but has a limited appetite. She continues
L Serum sodium of 129 mEq/L
to have very good urine output, soaking through her
b. Serum bicarbonate of 12 mEq/L disposable diapers at times. In the office, she is a
c. Serum albumin of 1.8 gldl small toddler who is cruising about the examination
d. Serum calcium of 7.0 mgldL
room. Her height and weight ara both less than third
e. Serum creatinine of 0.6 mgldl percentile tor age; vtlal signs are stable. The rest of
2. Laboratory results return and Indeed show a her examination Is normal.
low-serum albumin at 1.7 g/dl and a calcium of
1. All ofthe following screening laboratory and radio-
7.9 mgldL, but otherwise normal electrolytes and
logic evaluations are potentially indicated, except:
creatinine. CBC results and C31evel are normal.
L Renal ultrasound
Which of the following is the most likely diagnosis?
b. VCUG
L MCD
II. HSP nephritis
c. Urtnalysls
d. Serum electrolytes, BUN, and creatinine
c. SLE e. Urtne and serum osmolartty
d. Interstitial nephritis
e. FSGS 2. The following results wera obtained from this
patient's samples:
1 The patient is started on prednisone 2 mglkg 1. Urinalysis: specific gravity 1.007, pH 7
daily along with an H2 blocker and mild diuretic. A
2. Trace glucose and pruteln; negative for blood,
week later, he presents in the office with fever and
leukocyte esterase (U:), or nltrtte
abdominal pain. He has not been eating because
3. Serum electrolytes: sodium 133 mEq/1.., potassium
he has felt nauseous, but has kept most of his
3.0 mEq/L, chloride 116 mEq/4 b icarbonate
medication down the past 2 days. He appears ill
14 mEq/L, BUN 8 mg/dl, creatinine 0.2 mgl
with a temperabJre of 102.3°F, a pulse of 142 bpm,
dl. glucose 108 mgldl
and BP 80/45 mm Hg. His weight is 22.2 kg. His
4. Serum osmolarity: 275 mOsm/L
abdomen Is distended and he flinches In pain with
5. Urine osmolarity: 800 mOsm/L
light palpation to each quadrant. You direct the
8. Renal ultrasound: Both kidneys are normal in
family to the local emergency department as you
length, shape, and position.
call to make certain treatment recommendations.
7. There is normal corticomedullary differentiation
Which of the following recommendations is most
without evidence of calcification. No hydrone-
appropriate?
phrosis is noted, and the bladder appears to
L Type and screen patient for expectant blood
have normal wall thickness.
transfusion. Which of the following Is the most likely diag-
b. Fluid-restrict the patient to less than 400 mU
nosis In this patient?
m2/day to prevent AKI.
L NDI
c. Place an IV for steroids.
b. Central Dl
d. Perform a right upper quadrant ultrasound for
c. Renal dysplasia
probable cholecystitis.
d. Diabetee mellitus
e. Place an IVfor antibiotics, including vancomycin
and a third-generation cephalosporin.
e. RTA
1 Which of the following Is the best next step In the
VIGNET1E3 evaluation of this patient?
A 14-month-old female presents to the oftlce with L Urtne electrolytes
concerns about poor growth. She had been seen in b. DDAVP stimulation test
another provider's office for all of her routine childhood c. Sterile urine catheterization
visits and was told that she was likely just "petite." d. Hemoglobin A,c level
The family's concern is that she drinks all day and just e. Serum lithium level
ANSWERS
VIGNETTE 1 Question 1 of albumin in his urine. The serum calcium is low be-
1.AnswerD: cause of the low-serum albumin; however; If adjusted
The patient has clinical and laboratory evidence of for the low-serum albumin, this value would be normal
glomerulonephritis, with the presence of red cell at 8.7 mgldl. Low oncotic pressure in the vascula'lure
casts on urine microscopy, mild hypertension, edema, results in fluid leakage into the interstitium, causing
and slightly elevated creatinine. The best next test total body fluid overload, a decnNISe in the serum
to order given this glomerulonephritic picture would sodium, and also decreased perfusion of the kidneys
be a C3 level to differentiate among the hypo- and and slight eleva'lion in creatinine. Nephrotic patients
normocomplementemic glomerulonephritides. Serum do not typically suffer from severe acidosis because
cholesterol may be considered if this patient had ne- most are able to appropriately acidify their urine.
phrotic syndrome, but his protelnur1a was not severe
(41 on dipstick). His edema is more likely from salt and VIGNET'IE 2 Question 2
fluid retention. Serum lgA levels are not diagnostic, 2.AnswerA:
even for lgA nephropathy. ANA may be considered as Most children who present with typical symptoms of
a follow-up test If the C3 level Is low. Urine osmolartty nephrotic syndrome have MCD. Symptoms that would
is not diagnostic for glomerulonephritis and would not be less typical for this diagnosis Include significant
be of value in furthering the investigation. hematuria ~ncluding gross hematuria), significant
hypertension, older age groups Qate adolescence),
VIGNETTE 1 Question 2 significantly increased creatinine level, and low C3
2.Answer B: levels. FSGS often presents with nephrotic syndrome,
PSGN is the most commonly acquired GN and typically but is more typical in older children. SLE may also
presents In early school-age children, 1 to 4 weeks present with nephrotic syndrome, but is typically seen
following a strep infection. It is associated wittl a low in older adolescent females. HSP nephritis often has
C31evel and posmve ASO test. SLE Is also associated other vasculitic findings (rash, abdominal pain, joint
with low C3 levels but may have low C4 as well. Also, Involvement), whereas Interstitial nephr1tls does not
SLE is Jess common in early school-age children and in present with nephrotic syndrome.
boys. HSP nephritis, JgA nephropathy, and typical HUS
ant not associated with low C3 levels. HSP often has VIGNETlE 2 Question 3
other vasculltlc findings, whereas HUS Is associated 3.Answer E:
with thrombocytopenia and hemolytic anemia. One of the more ser1ous complications of nephrotic
syndrome is spontaneous bacterial peritonitis. This
VIGNETTE 1 Question 3 patient has findings of bacterial peritonitis with fever,
3.Answer C: abdominal pain, and tenderness with palpation. Ne-
Diuretic use: The most common sequela of PSGN is phrotic patients are at increased risk of peritonitis from
hypertension, which is thought to be secondary to Streptococcus pneumonlae, In addition to gastrointes-
salt and fluid retention. Therefore, dietary salt and tinal flora. so antibiotic coverage should address both
fluid restriction or the use of diunttics may help with possibilities and include vancomycin. An ultrasound
the edema and hypertension. Antibiotic therapy may is indicated to confirm the presence of ascites (and in
be indicated if the patient has not been treated for his preparation for possible paracentesis), but should not
original (presumed) streptococcal infection, but more be restricted to the RUQ (cholecystitis). This patient
so to prevent rheumatic fever than disease progression. is also intravascularly depleted, w ith elevated heart
Even prompt trea'lment of streptococcal pharyngitis rate (although some of this may be from the fever)
does not prevent the nephritis. lmmunoauppreaaion and low blood pressure but increased weight overall.
is not typically provided in limited cases of PSGN. Fluid has been shifted from the vascular space Into the
A high-protein diet would not Jessen the degree of interstitium, making him appear total body overloaded
protelnur1a. but intravascularly depleted. These patients benefit
from intravascular colloid, like albumin, but do not
VIGNETTE 2 Question 1 require blood transfUsions; typically the hemoglobin Is
1.AnswerB: elevated from intravascular contraction. Fluid should
This chUd has swelling because of the Joss of protein not be restricted. but preferably the patient should be
in his urine; he has nephrotic syndrome. This explains provided fluid that will remain primarily in the intravas-
the low-serum albumin of 1.8, associated with the loss cular space. Ulat, although IV steroids may be needed
Chapter 17 I Nephrclogy • 381
eventually for this patient's underlying dtsoraer If he of normoglycemia, diabetes mellitus is extremely un-
cannot tolerate oral medications, he has been doing likely, even mora so If there are no ketones In the urine.
well recently, so certainly steroid therapy is not what
is needed most urgently. VIGNETTE 3 Quastlan 3
3.AnswerA:
VIGNETTE 3 Question 1 In the setting of suspected RTA, determination of
1.Answer B: the type of RTA (mainly 1, 2, or 4) is esaential for
A VCUG would be indicated only to evaluate for the treatment and prcgnosis. Type 4 RTA is associated
presence of vesicoureteral reflux or other specific ana- with hyperkalemia and often occurs in the setting of
tomical abnormalities of the bladder. With no previous urinary obstruction; the low-serum potassium is not
history of febrile liTis and the fact that this is a girt explained by this potential diagnosis. Catheterizatio n
(making posterior urethral valves Impossible), a VCUG is unnecessary unless a sterile sample is required for
Is not Indicated In this case. The other studies, how- suspected UTI. Calculating the urine anion gap helps
ever, are all indicated in the evaluation for a possible discern between type 1 and type 2 RTA. Type 1 (dis-
renal-concentrating defect or metabolic abnormality tal) RTA is associated with a positive urine anion gap
as an etiology for the grcwth deficiency. ([Na + K] - CO, because there Is a failure to produce
ammonium (NH4+) distally and therefore less urinary
VIGNETTE 3 Question 2 chloride. In this scenario, there Is already some Indi-
2.Answer E: cation that this may be type 2 (proxJmaO RTA, because
The serum electrolytes reveal a hyperchloremic, nongap there ia trace glucose and protein on urinalysis. Other
metabolic acidosis. In the absence of diarrhea, this findings in type 2 RTA include low-serum phosphorus
is indicative of RTA, especially with a urine pH that is (from urine I088ee) and increased urine potassium
graater than 5.5. OJ (both nephrogenic and centraO excretion. A DOAVP test is useful for determining if
Is ruled out by the normal urine osmolarity and, to central 01 is present. A serum lithium level may assist
some degree, by the low-serum sodium. The renal in the setting of suspected acquired NDI. Elevated
ultrasound shows no evidence of dysplasia of either hemoglobin A1c may be seen with poorty controlled
kidney. There is trace glucosuria, but In the presence diabetes; however, the serum glucose was normal.
Urology
David 1-Wang Chu, EarlY. Cheng, and Katie S. Fine
Urology encompasses the surgical management of the kidney stones. In newborns, this is commonly due
kidneys, bladder, and genitalia. Urology overlaps with to intrinsic narrowing of the lumen at the UPJ.
nephrology for renal diseases with certain intrinsic The majority of neonatal UPJ obstructions can be
processes such as nephrolithiasis, but also addresses observed without surgery because spontaneous
extrinsic processes such as obstructive uropathy or resolution is possible. However, close serial mon-
reflux nephropathy that are secondary to bladder itoring is necessary with ultruounds and nuclear
pathologies. Medical management of entities such medicine diuretic renal scans to determine relative
as vesicoureteral reflux (VUR) and recurrent urinary renal function and radiotracer excretion. In older
tract infections (UTh) is common. Urologic diseases teenagers or adults, a UPJ obstruction can develop
can be either congenibll or acquired in nature. 'This because of a lower pole anomalous renal vessel
chapter discusses the most common urologic anom- crossing the UPJ. High-grade obstruction can lead
alies and diaorden. to a loss of kidney function, urinary stasis, the
development of kidney stones, and UTis. Should
surgery be needed, a pyeloplasty is performed to
HYDRONEPHROSIS allow better urine drainage from the renal pelvis
Hydronephrosis is dilation of the renal pelvi&. Con- to the ureter.
genital hydro~phrosu is found in approximately 1% In VUR. which is the second most common
ofall fetuses, often on prenabll ultrasound. Severity cause of hydronephrosis, the junction between the
depends on the degree of dilation and whether one bladder and ureter does not develop normally. In a
or both lddn.ey5 are involved, but most cases can normal collecting system, urine flows down to the
be observed initially. Very severe hydronephrosis bladder via a one-way valve mechanism. In VUR,
is often due to obstruction and can be associated this valve is faulty, allowing urine to reflux back up
with impaired renal function in the affected kidney. to the kidneys. VUR is present in one-third of all
"Physiologic hydronephrosis• is the most common febrile UTis in children. High-grade VUR can cause
cause of hydronephrosis. It is a benign entity that is hydronephrosis. Diagnosis requires a voiding cysto-
transient in nature. As the lddneys develop, the ultra- urethrogram (VCUG), whereby contrast is instilled
sound may capture a snapshot of urine momentarily through a urinary catheter into the bladder. .As the
trapped in the renal pelvis before it can be excreted bladder is slowly filled, some contrast may reflux
down the ureter to the bladder. Surveillance is all up the ureten. Treatment depends on the degree
that is required. of reflux and the number and severity of UTis. Be-
cause of the possibility of spontaneous resolution,
DIFFEREN11AL DIAGNOSES first-line treatment is usually a trial of low-dose
In ur~teropelvic junction (UP/) ob&truction, the continuous antibiotic prophylaxis, which reduces
most common pathologic etiology of hydrone- the risk of recurrent rebrile or symptomatic UTI by
phrosis, the area where the renal pelvis meets the 50%. Breakthrough UTI on prophylaxis may be an
ureter is narrowed or kinked. UPJ obstructions can indication for surgery, which consists of ureteral
be primary or &econdary, because of high-grade reimplantation or injection of a bulking agent into
VUR, iatrogenic causes, or scarring such as from the ureteral orifice.
-
382
Chapter 18 I Urology • 383
In posterior urethral valves (PUVs), a rare but (Wilms tumor, Aniridia, Genitourinary symptoms,
severe cause of hydronephrosis in males, leaflets of and mental Retardation); these cases carry a higher
tissue located near the urinary external sphincter risk of bilaterality. Evaluation includes cross-sectional
obstruct the outflow of urine from the bladder. PUV imaging via computed tomography (CT) or magnetic
can cause a spectrum of obstruction to the bladder resonance imaging (MRI). In the United States,
and lddneys, from nearly no initial pathology to severe treatment protocols for unilateral masses include
bilateral hydroureteronephrosis and dilated bladder surgery initially, then chemotherapy and radiotherapy
with rapid progression to renal failure. PUV may depending on stage and tumor genetic characteris-
also be associated with high-grade VUR. Diagnosis tics. Most children undergo a radical nephrectomy.
of PUV is often made on prenatal imaging, with a Overall survival for WT is 85% to 90%.
classic "keyhole" sign seen on bladder ultrasound Congenital mesoblastic nephroma (CMN), the
from the dilated posterior urethra. If the suspicion most common primary renal mass found in newborns
is high at birth, a urethral catheter must be placed less than 6 months old, is generally benign in nature.
to allow decompression of the urinary tract system. Like WT, it is most commonly noted by palpating
The gold-standard diagnosis is made via VCUG. an abdominal mass. CMN is often associated with
Treatment consists ofendoscopic valve ablation. Qc.. polyhydramnios. Treatment consisting of local re-
casionally, intermittent catheterization or temporary section, usually via radical nephrectomy, Is curative.
urinary diversion with a vesicostomy Is necessary. In
patients with PUV, long-term monitoring ofbladder
FLANK PAIN WITH NAUSEA AND
and renal function is indicated.
VOMITING
Multicystic dysplastic lddney (MCDK) describes
congenital renal parenchyma which is nonfunctional Remzl coUc manifests with acute flank pain associated
and littered with cysts, which can mimic dilated ca- with nausea and vomiting. Workup should always
lyces on renal ultrasound. The majority of MCDKs include renal ultrasound to rule out hydronephrosis
eventually involute spontaneously, although it may secondary to an obstructive ureteral stone or other
take many years. Historically, MCDK was thought acute process. In the setting offever and obstruction,
to be usociated with increased risk for Wdms tumor urinary diversion may be needed.
(WT) and hypertension; more contemporary data
have found no increased risk beyond the normal DIFFERENTlAL DIAGNOSES
population. Congenital MCDK is associated with The prevalence of urolithiasis is increasing in the
other congenital urinary tract anomalies, including United States, with lin 11 adults expected to have
a 15% to 2006 chance of contralateral VUR and an a stone episode. Incidence in the pediatric popula-
8% to 12% chance of contralateral UPJ obstruction. tion Is also rising, with the highest rate of increase
among adolescent females. The pathophysiology of
kidney stone formation is discussed elsewhere (see
KIDNEY MASS
Nephrology: Stones). Clinical presentation consists of
Primary renal masses in children are relatively rare. acute-onset flank pain that is sharp, possibly referring
Primary malignant renal tumors constitute 5% ofall down around the side to the bladdet and accompanied
malignancies in children, the most common after by nausea and vomiting (and occasionally fevers).
leukemia, brain tumors, and neuroblastoma. Care Among children, recurrence rates are highest within
must be taken to differentiate potential malignant the first several years. Diagnosis can usually be made
tumors from benign tumors, with surgical excision with renal bladder ultrasound. On rare occasions, CT
often constituting an integral component. may be needed. Treatment depends on the clinical
presentation. Ifa UTL fever, or other signs ofinfection
DIFFERENTIAL DIAGNOSES coincide with siiJ1S of obstruction, a ureteral stent
WT, the most common primary renal malignancy or percutaneous nephrostomy tube is indicated for
in children, is discussed in detail in Chapter 13. drainage, in addition to empiric anboiotics. In the
WT is most commonly found in 2- to 3-year-old absence ofacute infection. medical expulaive therapy
children. Diagnosis is often made by palpating an may be considered. Should conservative measures
abdominal mass. 1\unors may grow quite rapidly. faiL or the child develop signs of acute infection or
There is a predilection in select syndromes, including intolerance ofpain. surgery is indicated. For ureteral
Denys-Drash, Beckwith-Wiedemann, and WAGR stones, surgical optiom include ureteroscopy or shock
wave lithotripsy. L8l'ger stones (> 1 to 2 em in size) insensitivity syndromes), and otherwise "unclassified"
may require percutaneous nephrolithotomy (PCNL). DSD. Clinical presentation can be highly variable;
Although PCNL involves more pain and bleeding, prompt workup is indicated if suspicion is high.
stone-free rates are also higher for larger stones. Referral to a multidisciplinary center that includes
UPJ obstruction should always be in the differential a pediatric urologist, pediatric endocrinologist. and
for flank pain accompanied by nausea and vomiting. geneticist is highly recommended.
Intermittent colic due to UPJ obstruction is more Hypospadias constitutnl one ofthe most common
commonly found in older children; this may be due congenital defects of the penis, affecting nearly 1 in
to a crossing lower pole anomalous renal vessel 250 newborn males. It consists ofa ventrally located
that intermittently kinlcs the UPJ, causing upstream urethral meatus, ventral penile curvature, dysplasia
obstruction. of the corpus spongiosum, and a dorsal hooded
Pyelonephritis is an acute infection of the renal foreskin. Embryologically, hypospadias occurs be·
parenchyma. Classically associated with fevers, cause of early arrested development of the urethra.
flank pain, and nausea/vomiting, pyelonephritis Hypospadiss lies on a wide spectrum of phenotypes
reflects a bladder infection that has ascended via based generally on location of the meatus, with
the urinary tract along the ureters to the kidney, or, more proximal phenotypes- meaning the meatus is
less commonly, hematogenous seeding from ongoing closer to the perineum-associated with more severe
bacteremia. Diagnosis is made clinically, although disease. Hypospadias requires surgical correction,
radiographic signs can occasionally be seen on both which may be staged for more severe phenotypes. If
renal ultrasound and cross-sectional imaging. Urine accompanied by cryptorchidism, especially bilateral
culture is the gold standard; blood cultures may nonpalpable gonads, DSD should be suspected, and
also be indicated. Treatment consists ofantibiotics, an ambiguous genitalia workup should be performed.
tailored to susceptibilities if the infectious agent is Cryptorchtdlsm is one of the most common
recovered. Recurrent pyelonephritis can lead to genitourinary diagnoses made at birth. occurring
parenchymal scarring, which places the child at risk in 3\16 of full- term males and 30\16 of pretenn males.
for subsequent chronic kidney disease. Cryptorchidism can be categorized on the basis
of whether the testes are palpable or nonpalpable.
Cryptorchidism. if isolated, should be observed, as
AMBIGUOUS GENITALIA
the majority of undescended testicles will fall into
Ambiguous genitalia encompass a spectrum of their orthotopic scrotal position by 6 months ofage.
developmental disorders based on the appearance For nonpalpable testes or persistently undescended
of external sexual genitalia. The specific diagnosis testes, surgical orchiopexy is indicated by 2 years
requires a karyotype, lab tests, and imaging. at the of age for two primary reasons: to preserve fertility
minimum. When a newborn is found to have ambig- potential and to reduce the risk of testicular cancer.
uous genitalia, it is Imperative to rule out conditions If cryptorchidism. especially bUateral, is found con-
assoclated with potentiallylife·threatenlng salt·wasting currently with hypospadias, an ambiguous genitalia
disorders with a serum 17-hydroxyprogesterone workup is indicated.
test. The most common of these is congenital ad-
renal hyperplasia (CAH), discussed in Chapter 15
TESTICULAR PAIN
(Endocrinology). CAH is the most frequent cause
of ambiguous genitalia. and the most common type One of the most common presenting urologic
of CAH is 21·hyd~lase deficie1fCY. symptoms to a pediatric emergency department is
testicular pain. This symptom spans several possible
DIFFEREN11AL DIAGNOSES diagnoses, but the majority do not require surgical
Disorders of sexual development (DSD) include a intervention. A scrotal ultrasound can often be
wide and complex range of genetic, honnonaJ. and diagnostic.
developmental pathologies. DSD can be broadly
categorized into disorders of gonadal differentia- DIFFEREN11AL DIAGNOSES
tion (including Klinefelter and Thrner syndromes In testicular torsion. the testicle twists on its vascu~
and mixed gonadal dysgenesis), ovotesticular DSD, 1ar pedicle, causing ischemia and potential loss of
46XX DSD (including CAH), 46XY DSD (including the testicle. Torsion is one of the few true surgical
testosterone synthesis pathway defects and androgen emergencies in pediatric urology, affecting 1 in 4,000
males under 25 years of age with a predominance seminiferous tubules are extruded. Hematoma is
in 10- to 13-year-olds. It is commonly due to a bell common. Diagnosis is made with scrotal ultrasound.
clt~pper tkjormlty of the tunica vaginalis that allows Treatment is immediate scrotal exploration in the
the testicle to twist easily on its pedicle. Torsion is a acute setting, with washout and repair of the tunica
time--sensitive emergency, with lower salvage rates albuginea. Delayed presentation may respond to
the longer the testicle remains twisted Although observation alone.
diagnosis is clinically based (acute-onset pain accom- A hydrocele is accwnulation of simple fluid around
panied by a horizontal testicular lie. loss ofipsilateral the testicle. Usually painless in nature, hydroceles
cremasteric reflex, nausea, and vomiting), the con- can be classified into communicating and noncom-
dition is often confirmed with a scrotal ultrasound municating types. Communicating hydrocele& are
with Doppler. Surgical treatment entails reduction found more commonly in newborns, as the proces-
of the torsed blood supply and fixation ofboth testes sus vaginalls remains open after birth and permits
(if not necrotic) to prevent future torsion episodes. intennittent flow of peritoneal fluid through the
Epididymo-orchitis represents infuct:ion or in- open connection. The diagnosis of a hydrocele can
flammation of the epididymis or testis prope.t. In be made clinically, with a translucent blue color seen
younger males, chemical epididymo-orchitis may when shining a light through the hemiscrotum., or
occur due to the reflux of sterile urine through the radiographically with a scrotal ultrasound. Noncom-
ejaculatory ducts retrograde via the vas and into the municattnghydrocele& usually occur in older children,
epididymis. If the urine is harboring a UTI, then generally as a reactive condition secondary to trauma,
bacterial epididymo-orchitis can remit, requiring epididymo-orchlt:ia, or torsion ofthe appendix testis
treatment with antibiotics. In older males who are or epididymis. Management varies depending on the
sexually active, sexually transmitted infections (STis) type of hydrocele. Communicating hydroceles are
such as gonorrhea or chlamydia may be the culprit. observed until12 to 18 months of age, as the rate
A urinalysis and urine culture can help differentiate of spontaneous closure of the processus vaginalis
chemical from non STI bacterial epididymo orchitis.
4 4
is high. If the symptoms of fluctuating size persist
For tru~~picion ofSTI-related epididymo-orchitis. urine after 12 to 18 months of age, surgical correction
nucleic acid amplification tests can be diagnostic. A is indicated. For noncommunicating hydroceles,
scrotal ultrasound typically shows hyperemia in the the fluid around the testicle usually resolves over
affected organ. Treatment is with anti-Inflammatory time. Surgery is indicated only when the size ofthe
medications fur chemical epldidymo-orchitis as hydrocele becomes symptomatic. Hydroceles can
against appropriate antibiotics for bacterial causes. become loculated or infected, leading to pyoceles
In torsion oftM ~~ppendix t:utis, the appendix testis (purulent fluid around the testis). Pyoceles respond
is twisted and becomes ischemic, similar to testicular to antibiotics, but may also require drainage.
torsion. The appendix testis is a vestigial remnant of In a varicocele, the testiculu veins swell because of
the female Mullerian duct during embryogenesis. It incompetent valves. Varicoceles are common, found
has no significance or function except that it can be in 15% of all men and 40% of men presenting with
torsed, which causes acute unilateral testicular pain infertility, but often present initially in adolescence.
and swelling. Occasionally, there is a "blue-dot" sign Typically found on the left side because of the angle
seen through the scrotal skin. Scrotal ultrasound of the left testicular vein inserting into the left renal
is diagnostic. Management is conservative, with vein, a varicocele can present as a dull, throbbing sen-
anti-inflammatory medications and supportive care. sation in the left testicle. Most variooceles, however.
Similarly, in torsion of the appendix epididymis, are painless and found only on well-child or self-ex-
the appendix epididymis becomes twisted and aminations in standing position, with disappearance
ischemic. The appendix epididymis is part of the once supine. A typical description is palpation of a
male Wolffian duct. Similar to the appendix testis, "bag of worms• superior to the testicle. Varicocele&
it carries no significance or function except that it are significant because 15CJ6 of adolescent males
can be torsed. Presentation and management are who have one may develop subsequent infertillty.
identical to those for appendix testis torsion. However, methods to predict which adolescent male
In testicular rupture, the tunica albuginea sur- with a varicocele will have future fertility problems
rounding the seminiferous tubules tears, usually remain muddled. Scrotal ultra.sounds to compare
as the sequelae of blunt trauma to the testicle. testicular sizes may have some potential. with sur-
Symptoms are immediate pain and swelling as the gery indicated when there is a large (>2006) size
discrepancy. Other tests include a semen analysis ingestion ofcaffeinated drinb in the afternoon. Ad-
or serial semen analyBes once the adolescent has ditional therapy includes bedwetting aJarms, which
completed puberty, to test the quality and quantity require more patient and parental in"YOlvement but
of the sperm directly. If indicated. surgery consists achieve higher success rates, and nightly vasopressin
of ligation of the testicular veins whfle preserving (DDAVP), which works quickly but only whlle the
arterial and lymphatic Bow. child actively continues the medication.
Indy&junctional voiding, a child actively squeezes
pelvic Boor muscles during voiding, which can lead
VOIDING DYSRJNC110N to dysuria, UTis, detrusor overactivity, and elevated
One of the most common referrals to pediatric urology bladder pressures. Diagnosis can be made with
Is a child with enuresis, dysuria, or recurrent afebrile uroBow·electromyography (EMG), with an active
UTis. A detailed history is mandatory, especially EMG durq voiding when the pelvic floor should
pertaining to bladder and bowel habits. Frequency be relaxed. Treatment entails biofeedback training,
ofvoids, the quantity and timing offluid intake, the which teaches the child to relax the pelvic floor
presence and degree ofconstipation, and the presence during voiding.
of daytime or nighttime accidents are all helpful in In meatal&tenosis, a condition found almost exr
optimlzins management Most symptoms can be elusively in circumcised males, the slit-like urethra
improved with behavioral modifications, including meatus is narrowed to a pinpoint-like hole. As such, the
timed voids, preventing constipation, and increasing laminar Bow ofurine out of the meatus is disrupted,
water intake throughout the day. A small minority causing dysuria and occasional hematuria. Diagnosis
ofchildren with persistent daytime symptoms may is made on history and examination, with a patient
require additional imagi.ng, such as a renal and blad- often endorsing an upward deflection or spraying
der ultrasound (to rule out anatomic abnormalities) of the urinary stream. The etiology is thought to be
or urodynamic studies to assess bladder function. because of chronic irritation at the meatus against
underwear or clothing. Treatment may include an
DIFFERENTIAL DIAGNOSES office meatotomy or formal urethromeatoplasty in
In monosymptomatic nocturnal enuresi6 (MNE}, the operating room under anesthesia.
a child has no daytime voiding symptoms and has In tethered cord, an occultapina bifida may be the
Isolated bedwetting at night. The prevalence ofMNE underlying etiology behind persistent or new..-onset
decreases with age, but is still estimated at 5% for voiding dysfunction. Cutaneous stigmata Jncluding
10-year-olds. Rarely is MNE due to an anatomic sacral dimples, tufb of hall; or asymmetric gluteal
abnormality. Instead, .MNE is thought to be related creases may provide clues that prompt a spinal MRI
to maturational delay or reset of the neuronal sys- scan. Theatment involves surgical release of the
tem. General reconunendations include strict fluid tethered cord by neurosurgery, with subsequent
restriction 2 hours before bedtime and limiting surveillance to observe for any retetherlng.
KEY POINTS
• Congenital hydronephrosis ia a common prenatal • VUR ia found in one-third of childnln who have
diagnosis. Most cases F880ive spontaneously, febrie lJTis.
but close obseMdion is required. • wr Is the most common prtnwy renal maiP'ICY
• UPJ obstruction Is the most common pathologic of childhood, classically presenting in a 2- to
cause of hydronephrosis In children. 3-year-old child with a palpable abdonWlal mass.
• PUVs are a rare but severe cause of urinary • Kidney stones are Increasing in incidence In
obstruction that can result In chronic kidney chldren and should be lnttlally evaluated with
disease and prognMISion to end-stage renal a renal bladder ultrasound for symptoms of
disease. Prompt ur1nary drainage Is required. acute-onset flank pain, nausea, and vomiting.
• Newborns with ambiguous genitalia require a • Varicoceles are relatively common in adolescent
prompt workup Including ruling out salt-wasting males; the majority of patients with them will
pathologies that can be life-threatening. not have fertility problems.
• Severe hypospadias in combination with bilateral • MNE can be treated with general behav-
cryptorchidism should be treated as a DSD. ioral modification, bedwetting alanns, and
• Undescended testicles that persist after 6 DDAVP.
months of age should be surgically brought • Persistent voiding dysfunction or new-onset
down to the scrotum because of future concerns voiding dysfunction in an older child may
for impaired sperm production and testicular manifest as a sign of tethered cord, with cuta-
malignancy. neous stigmata of a sacral dimple, tuft of hair,
• Testicular torsion is a surgical emergency and or asymmetric gluteal crease.
requires prompt diagnosis and surgical correction.
CLINICAL VIGNETTES
VIGNETTE 1 c. Obtain an MRI scan.

A 33-week-old fetus undergoes a routine prenatal d. Perform a diagnostic laparoscopy.
fetal ultrasound. Dilation of the right kidney Is seen. e. Perform an exploratory laparotomy.
ShorHy after birth, a repeat uHrasound is performed
2. The appropriate study demonstrates a solid mass
showing persistent right hydronephrosis. VCUG is
In her left kidney. A subsequent, more special-
negative for VUR.
ized scan shows concern for a large mass that
1. What is the next step in evaluation or management? occupies most of her kidney. What is the most
a. Take the newborn to surgery for pyeloplasty. likely diagnosis?
b. Take the newborn to surgery for ureteral stent LWT
placement. b. CMN
c. Obtain a nuclear medicine diuretic renal scan ~ Rhabdoid tumor of the kidney
to assess for differential function and urinary d. Translocation renal cell carcinoma
excretion. e. Neuroblastoma
d. Discuss physiologic hydronephrosis with the
family and discharge tl'le newborn from clinic. VIGNETTE3
1. Place a percutaneous nephrostomy tube. A 14-year-old female presents to the Emergency
Department with acute-onset, sharp pain in her right
2. The appropriate study demonstrates high-grade
flank, accompanied with vomiting and nausea.
obstruction at the UPJ with 15% differential
function, consistent with a UPJ obstruction. The 1. What is the next step in evaluation or management?
Infant Is wtthout Infection. What Is the appropriate L Obtain a CT scan.
surgical management? b. Obtain a renal bladder uHrasound.
a. Place a ureteral stent. c. Obtain an MRI scan.
b. Place a percutaneous nephrostomy tube. d. Perform a diagnostic laparoscopy.
~ Removethek~ney. e. Perform an exploratory laparotomy.
d. Perform a pyeloplasty.
2. A 4 mm radiopaque stone is found in her right
e. Perform a diagnostic ureteroscopy. ureter. Which of the following Is NOT a viable
VIGNETTE2 option for tl'lis patient?
A 2-year-old otherwise heatthy-appeartng female child
a. Start medical expulsive therapy to pass the
stone.
presents after parents feel an abdominal mass.
b. Undergo shock wave lithotripsy.
1. What Is the next step In evaluation or management? c. Undergo ureteroscopy and laser lllhotrtpsy.
a. Obtain a CT scan. d. Undergo cystoscopy and ur&teral stent placement.
b. Obtain a renal bladder ultrasound. 1. Undergo PCNL.
388 • BWEPAINTS Pedlatr1cs
VIGNET1E4 VIGNET1E5
A newbom infant is found at birth to have proximal A 12-year-old male p.vsents with acute~nset right-sided
hypospadias in a short phallus with bilateral nonpal- testicular pain 1hat woke him up from sleep.
pable gonads.
1. What is the next step in evaluation or management?
1. Which of1he following is not a required next step L Obtain a CT scan.
in evaluation or management ? b. Obtain a renal bladder ultrasound.
L Obtain a karyotype. c. Obtain an MRI scan.
b. Obtain a hormonal assay including 17- d. Obtain a scrotal ultrasound.
hydroxyprogesterone. 1. Take him straight to 1he operating room for
c. Check an electrolyte panel. scrotal exploration.
d. Consider consulting endocrinology, urology,
2. Scrotal ultrasound showed a torsed appendix testis
and genetics.
but otherwise normal flow to both testicles. What
e. Discharge to home with follow-up in a month. is the next bast step in evaluation or management?
2. lhe karyotype retums XX and the 17-hydroxypro- L Take him straight to ttle operating room for
gesterone is elevated. What is the likely diagnosis? scrotal exploration.
L CAH b. Admit to inpatient and start antibiotics.
b. Klinefelter syndrome c. Check for STis.
c. Turner syndrome d. Supportive measures Including anti-Inflammatory
d. Mixed gonadal dysgen86is medications.
e. Normal female genotype and hormonal level e. Remove the testicle.
ANSWERS
VIGNETlE 1 o-tlon 1 VIGNETlE 3 o-tlon 1

1.Answer C: 1.AnswerB:
The next study should be a nuclear medicine renal Initial imaging for children who present w ith flank pain
scan to assess relative kidney function and excretion. should be a renal bladder ultrasound, given Its lack of
The patient has alr98dy undergone a VCUG that ruled irradiation and ability to diagnose secondary signs of
out VUR as an explanation for the hydronephrosis. obstruction such as hydronephrosis or hydroureter.
The differential diagnosis at this point includes
UPJ obstruction. VIGNETlE 3 Question 2
2.AnswerE:
VIGNETlE 1 QuNtlon 2 Given the small size of the stone In the patient's ureter,
2.Answer D: all options except for PCNL a.v viable. PCNL would
Given the low differential function, pyeloplasty would be a better option for large staghorn calculi within
be the appropriate surgical option of the ones listed. the kidney.
Nephrectomy could be considered ifthe relative func-
tion was Jess than 596. VIGNETlE 4 QuNtlon 1
1.AnswerE:
VIGNETlE 2 Question 1 For a newborn with ambiguous genitalia, it is critical
1.AnswerB: to rule out potentially life-threatening salt-wasting
Init ial imaging in children for an abdominal mass etlologl86, Including 21-hydroxylase deficiency (a type
should be a renal bladder ultrasound, given its lack of CAH). The newborn should be tested and referrals
of irradiation and ability to discern whether the kidney made to urology, endocrinology, and genetics before
truly has a solid concerning mass or a large benign discharge home.
cyst. Additional cross-sectional imaging such as CT
or MRI can be considered after the ultrasound. VIGNETlE 4 QuNtlon 2
2.AnswerA:
VIGNETlE 2 Question 2 An elevated 17-hydroxyprogesterone is indicative of
2.AnswerA: 21-hydroxylase deftclency, which Is the most common
Given the age of the child (2 years), the most common etiology of not only CAH but of ambiguous genitalia
solid renal mass is WT. overall. Some patients with this form of CAH will have
saH-wasting, which can be potentially life-threatening (i.e., pain wtth accompanying symptoms of nausea,
If not treated. vomiting, high-riding testicle, and lack of cremasteric
reflex), then select cases can be taken directly to the
VIGNET'IE 5 Qu..aan 1 operating room without a scrotal ultrasound.
1.Answer 0:
laolated acute acrotal pain can be testicular torsion but VIGNET'IE 5 Quwtlon 2
may also result from more benign nonopenrtive etiologi88, 2.AnswerD:
such as torsion of the appendix testis or epididymis. A Torsion of the appendix testis is managed conserva-
scrotal ultrasound can help differentiate among these. tively with nonsteroidal anti-inflammatory drugs and
If clinical suspicion of torsion is veK'f high, however supportive care.
Genetic Disorders
Paula Goldenberg and Bradley S. Marino
embryo. To disrupt organogenesis, a teratogenic

INTRODUCTION exposure typically occurs before 12 weeks' gestation.
Structural birth defects are categorized as minor Any teratogenic exposure after 12 weeks' gestation
or major. Minor birth defects such as skin tags, predominantly affects growth and central nervous
epicanthal folds, and rudimentary polydactyly are system development.
of little physiologic significance. Approximately Teratogens include intrauterine infections,
15% of newborn infants have at least one minor high-dosage radiation, maternal metabolic disorders,
anomaly; 0.5% of infants have three or more minor mechanical forces, and drugs. The moat common
anomalies. In contrast, major birth defects such as maternal metabolic disorder that has teratogenic po-
cleft palate, myelomeningocele, and congenital heart tential is diabetes mellitus; 10% ofinfant s ofdiabetic
disease have an adverse effect on the infant. Major mothers have a birth defect. Abnormal intrauterine
birth defects occur in 2% to 396 of all newborns. The forces such as uterine fibroids, breech positioning,
probability of having a major birth defect increases congenital uterine anomalies, or oligohydramnios
as the number of minor anomalies present increases may cause fetal constraint, resulting in club foot
(Table 19~ 1). Birth defects can be caused by enviro~ or hip dysplasia. Table 19-21ists the most common
mental or genetic factors. Genetic defects may be teratogenic drugs and their effects.
chromosomal, single gene, imprinting, cytogenetic,
or multifactorial disorders.
GENETIC FACTORS
Genetic disorders can be classified as disorders of
ENVIRONMENTAL FACTORS
single genes, chromosomes, imprinting, and molec-
Environmental factors are known to cause at least ular cytogenetics. Advances in molecular genetics
10% of all birth defects. Teratogens are environ- (.single-gene disorders) and molecular cytogenetics
mental agents that cause congenital developmental (submicroliCOpic deletions and duplications) have
anomalies by interfering with embryonic or fetal blurred the distinction among these categories.
organogenesis or growth. Exposure to a teratogen
before implantation (days 7 to 10 postconception)
can either have no effect or can result in loss of the
SINGLE-GENE DISORDERS
Normal human cells have 46 chromosomes (22
pairs of autosomes and 1 pair of sex chromosomes).
TillE 1~1. Incidence af Major Anomalies in the
Chromosomes contain genes, which occur in pairs
Presence af Minor Anomalies
I:--all Minar ......... at-::.......... ~) t
at a single locWl or site on specific chromosomes.
These paired genes, called alleles, determine the
genotype of an individual at that locUB. If the genes
!1 1 I at a specific lOCUB are identical, the individual is
homozygous; if they are different, the individual is
12 3 ! heterozygous. More than 4,000 different single-gene
:a
: . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .4 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..
20 I
. . . . . . .. . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . .: disorders have been described and are cla.s.sified by
390
Chapter 18 I Genetic Disorders • 391
TAILI1 ..2. Common Teratogenic Drugs

!llnll
IWarfarin (Coumadln)
!Ethanol
i Iaotm:inoin (Aoortane) Facial and ear anomalies, CHD
l Llthlum CHD (Ebatein anomaly, atrial septal defect)
i Penicillamine Cutis laxa syndrome
!Phenytoin (Dilantin) Hypoplastic nails, intrauterine growth retardation, cleft lip and palate
IRadloactiw iodine Coqenital golte%0 hypothyroldlam
! Diethylstilbestrol Vaginal adenocarcinoma during adolescence
!Streptomycin Deafnesa
1 Testosterone-like drugs Virlllzation of female
ITetracycline Dental enamel hypoplasia, altered bone growth
j Thalidomide Phocomella, CHD (TOF, septal defects)
!Trlmethadlone Typical faclea, CHD (TOF, TGA. Jill-IS)
!Valproate Spina bificla
~ AbiJnr,Aatlons: CHD, co~enltel heart disease; HLHS, hypoplastic left heart syndrome; TGA, transposition of the grut arteries;
~ TOF, tetralogy of Fellot. ,
:ooouoooouoooooo • •••••• •••••• ••••• oOoooooooooooooooo " " ' ' oooooooooooooooooooo,.oooooooooooo.,oooooooo oooooo oooooooooooou ooooouooooooooooou • •••••• •••••••••••••• ••••• • •••••• • • -• uoooooo oooooouOooOOo O.,.,, . . ,, . . , , . , , ,, , , , . , . ,, . , . , , , , , . , . ,, , , , , , , , , . . , ,, , , , , ,, . • • • • • • ••••••••••••••••• •
their mode of inheritance (autosomal dominant, genes of a gene pair (often coding for an enzyme).
autosomal recessive, or X-Unked). Because half of the normal enzyme activity is ade-
quate under moat circumstances, a person with only
AUTOSOMAL DOMINANT DISORDERS one mutant gene iJ not affected, whereas individuals
Autosomal dominant disorders are expressed after who are homozygous for a defective gene have the
alteration of only one gene in the pair (often cod- disorder. Both parents of a child with an autosomal
ing for a structural protein). Homozygous disease recessive disorder are usually heterozygous for that
states of autosomal dominant disorders are rare gene, and each child ofsuch a couple has a 2596 risk
and are usually severe or lethal. A mutant gene is of inheriting the disorder. Table 19-4lists the more
inherited from one parent with the same condition. common autosomal recessive disorders.
The risk for the affected parents' offspring is 50% Most inborn errors of metabolism, with the excep-
for each pregnancy. Sometimes an individual is the tion ofornithine transcarbamy.lase (OTC) deficiency,
first person in a family to display a trait because of are autosomal recessive disorders. Inborn errors of
spontaneous mutation. When a spontaneous muta- metabolism are discussed later in this chapter.
tion has occurred in a fetus, the risk of recurrence
in a subsequent pregnancy is slighdy higher than X-LINKED DISORDERS
the chance of the spontaneous mutation occurring X-linked disorders, which are usually recessive,
de novo, because of the rare possibility of gonadal occur when a male inherits a mutant gene on the X
mosaicism. Autosomal dominant genes often cause chromosome from his mother. The affected male,
conditions that manifest themselves with varying termed hemizygous for the gene, has only a single X
degrees of severity among affected individuals, a chromosome and. therefore, a single set ofX-linked.
phenomenon known as variable expressivity or genes. The mother of the affected individual is
'lltll'iabk penetrtmce. Table 19-31ists some important heterozygous for that gene, because she has both a
anto&omal dominant diseases. Other chapters discuss normal X chromosome and a mutant one. She may
some of these diseases in detail be asymptomatic or demonstrate mild symptoms of
the disorder because of lyonization, in which only
AUTOSOMAL RECESSIVE DISORDERS one X chromosome is transcriptionally active in each
Autosomal recessive disorders are only expressed celL Recurrence risk for X-linked disorders differs
after alteration of both the maternal and paternal depending on which parent has the abnormal gene.
I
TABLI11-3. Examples of Autosomal Dominant Diseases
!................nul . . . . . Fr:
AchondropU&a
1:25,000
iCJ aw--·-
4p
...
FGFR3
cu.......
Bm' new mutations; proxfmalllmb
lhorteninS
1Adult polycystic lddney 1:1,200 16p PKD1/PKD2 Renal cyau,intracranial aneurysm
Idiaease (PKD)
l Hereclliary qioedema 1:10.000 llq ClNH Defidency ofCl eat.erue inhibitor;
ep11od.Lc edema
!Hereditary spherocytoai.a 1:2,000 8p,14q ANKl See Olapter 12; some variants
autosomal recessive
1Marfm I}'Ilclrome 1:5,000 15q FBNl Aortic root dilatation, tall stature
INeurofibrom.atoalJ (NF) 1:3,000 2p,17q,22q NF1/NF2 50CJ6 new mutations; ~ au lait spots
1Protein c de6clency 1:15,000 2q Multiple genes Hyperc:oqul.able state
IThberow sclerosis (TSC) 1:6,000 9q, 16p TSC1,TSC2 "Ash·leaf" spots; seizures
!von Willebrand dJaeue 1:100 12p Multiple genes See Chapter 12
!..........................................................................................................................................................................................................................
:
AbbnMations: p, short arm of chromosome; q, long arm of c:tYomosome.
.........................................................................
An affected father will pass the defective X chromo- sol15 will have the disease. Table 19--Slists the most
some on to his daughters, who are carriers fur the common X-linked disorders.
disorder; his sons will not be affected. A mother with
an abnormal X chromosome is a carriet:. and there is CHROMOSOMAL DISORDERS
a 50% chance she will pass the abnormal chromosome
to her progeny. Daughters who receive the abnormal Ouvmosomaldisorders are responsible fur pregnancy
X chromosome will be carriers for the disease, and loss, amgenit:al malformation, and mental retardation.
TilLE
!AIIIDIImll.._ill ......
!Congenital adrenal
1..._ Examples of Autosomal Recessive Diseases
..._,
1:5,000-1:15,000; 6p
.....
CYP21A2, CYP17,
l hyperplasia 1:300 in Yupik CYPllAl, ACTHR
i Eskimos
l Cystic fibrosis 1:2,000 (Caucasians) 7q, 19q CFrR See Chapter 6
i Galactolemia disorder 1:40,000 9p GALT Carbohydrate
metabolism
! 1:2,500 (Ashkenazi 1q GBA Lysosomal storage
j Gaucher di.leue
Jews) disorder
llnfantilo ....,.,...,lddnoy 1:14,000 6p PKD4 Renal and hepatic
cym, bypertenaion
~ Phenylketonuria 1:10,000 12q PAR Aminoadd l
metabolian cllilorder 1
ISickle celldisease 1:500 llp HBB
g:71
(African·Americans)
iTay-Sacla di.seue 1:3.000 (Ashkenazi
Jew~)
l5q HEXA
I WllJon disease 1:30,000 13q ATP7B
i AbbnMalions: p, short arm of chromosome; q, long arm of c:tYomosome.

: ••u . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. .. . . . . . .. . . .. . . . . . . .. .. . . . . . . . . . . . . . . . .. .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .:
TilLE 1N. Examples of X-Unked Diseases

!x-u-.. a.... ,..._, eua ..,
l.lkuton agammaglobulinemia 1:100,000 Ablence ofimmunoglobuliN; recurrent lnfectio.N I
1Chronk: gran.ulomatoUI disease 1:1,000.000 Defective ldlling by phqocytea; recurrent infections
IColor blindneu
.
'',,,!
,
'
8% ofmales
=)
1Duchenne mu.cular dymophy 1:3,600 Proxlmal muscle weakness; Gower afgn ·
~ Glucose~6-phosphate dehydrosenue 1:10 (African~ Oxidant~ind.l.Dd hemolytic anemia dc6cienq I
IH=ophiliu A ond 8 See Cbaptm"ll I
!LeJc:h-Nyhan syndrome 1:100,000 Purine metabolism dlJorder; self-mutilation !,.
: Ornithine transc:arbamylase deficiency 1:14,000 Urea cycle disorder; hyperammonemia .

"""'" ''''"'''""""'''''•••••••-••••••••••••••"•ooooooooo"'"''''''''''''no•••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••-••••••••oooo"" ""'""''''''''''''''" '''' ' "''"" ''"" ''''•••••••••""'''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''''':
Although more than 50% of.first·trimester pregnancy live births. The r.lslc of Down syndrome increases
losses are due to chromosomal imbalances, only 0.6% with advancing maternal age. The risk ofhaving an
ofnewborn in&nts have chromosomal abnormalities. infant with Down syndrome is 1:365 for mothers
Most chromosomal defects arise de novo during ga- 35 years of age, and 1:25 for those 45 or older. Of
m.etngenesis, so that an .infimt can be conceived with children with Down syndrome, 95% have three
a chromosomal abnonnality without any prior family copies of chromosome 21, which results typically
history. Otromosomal abnormalities can also be passed from chromosomal nondisjunction during maternal
from parent to offspring. In rn.dt. cases, there is oftEn a meiosis. Four percent of Down syndrome patients
fumily history of multiple spontaneous abortions or a have a Robertsonian unbalanced translocation of
higher-than-chance frequency ofchildren with chromo- a third chromosome 21 attached to another auto-
somal problems. Disordersofchromosomenwnbermay some (46 total chromosomes). Many Robertsonian
involve autosomesorsex chromosomes. Birthdefects translocation cases are familial. meaning that one
caused byautosomal abnormalities are generally more of the parents has a balanced translocation involv-
.severe than those caused by sex chromosome abnor- ing the long (q} ann of chromosome 21 attached to
malities. Numeric defects of the autosomes include the long arm of another autosome. One percent of
trisomy of chromosomes 21, 18, and 13. Examples of children with Down syndrome have chromosomal
sex chromosome numerical abnormalities are Turner mosaicism, with some cella having two number 21
syndrome (45,X) and I<linefeher syndrome (47.xxY). chromosomes (46 total chromosomes) and some
Chromosomal copy nwnber abnormalities may be cells having trisomy 21 (47 total chromosomes). The
investigated by bryotype (aneuploidy, transl.ocations), mosaicism results from a mitotic division error that
fluorescent in situ hybridization (FISH; single-locus occurred during embryonic development.
DNA probes), or m.lcroarray, which contains hundreds Common dysmorphic facial features include
to a million submicroscopic DNA probes. Indications brachycephaly (flat occiput), flat facial profile,
for obtaining chromosomal studies include: con- upslanting palpebral fissures, small ears, flat nasal
firmation of a suspected chromosomal syndrome; bridge with epi.canthal folds, and a small mouth with
multiple organ system malformations; .significant a protruding tongue. Anomalies of the hand include
developmental delay or mental retardation without single palmar crease (simian creases), short, broad
an alternate explanation; short stature or extremely hands (brachydactyly) with an incurved fifth finger
delayed menarche in girls; infertility or a history of (clinodactyly) and hypoplastic middle phalanx, and
multiple spontaneous abortions; ambiguous genita- widened spacing between the first and second toes
lia; or advanced maternal age. Fetal chromosomal (•sandal gapj. Other features include short stature,
or molecular testing may be accomplished through generalized hypotonia, cardiac defects (endocardial
amniocentesis or chorionic villus sampling. cushion defectB and septal defecta are seen in 50% of
cues), gastrointestinal anomalies (duodenal atresia and
AUTOSOMAL TRISOMIES Hirschsprungdisease}, hypothyroidism, andmental
Trisomy 21 (Down Syndrome) retardation (IQ range 35 to 65). Leukemia is 20times
Down syndrome is the most common genetic syn· more common in child.ren with trisomy 21 than in
drome in humans, with an incidence of 1 per 700 the general population. Dwing the third and fourth
decades, an Alzheimer~like dementia can develop. The mosaicism results from a mitotic division error
With improved medical. educational. and vocational that occurs during embryonic development Clinical
management, life expectancyfur patients with Down manifeatations oftrisomy 13 are shown in Table 19-6.
syndrome now extends well into adulthood. Prognosis for patients with trisomy 13 is extremely
poor: SO% die before reaching 1 month of age. and
Trisomy 18 (Edwards Syndrome)
90% die by 1 year of age.
Trisomy 18 occurs in 1 per 3,000 live births. Eighty
percent ofcues are the result of meiotic nondisjunc- SEX CHROMOSOME ABNORMAUTlES
tion, which is associared with advanced maternal age. Sex chromosome anomalies involve abnormalities
The remaining20% may be partial (involving only a in the number or structure of the X or Y chrom~
portion of the chromosome) or mosaic, caused by somes or both.
mitotic nondisjunction in the zygote. Chromosome
translocation as the cause oftrisomy 18 is extremely Turner Syndrom•
rare, and its presence should prompt karyotyplng Turner syndrome occurs in 1 per 5,000 live births.
of the parents to exclude a balanced translocation. Approximately 98% offetuses with Turner syndrome
Clinical manifestations of trisomy 18 are shown in expire in utero; only 296 are born. Therefore, the
Table 19-6. The prognosis for patients with trisomy 18 recurrence risk for parents who have a child with
is extremely poor: 5096 die before reaching 2 months 'IUrner syndrome is no higher than that of the gen-
of age, and 90% to 951)6 die by 1 year of age. eral population.
Several genotypes can cause the Turner phe-
Trisomy 13 (Patau Syndrome) notype. In 6QCJ6 of cases, the karyotype is 45,X, in
Trisomy 13 occurs in 1 per 8,000 live births, but which the female lacb an X chromosome. Another
constitutes 1% of all spontaneous abortions. Ap- 15\16 of individuals are mosaics with a genotype of
proximately 75% ofsurviving cases are the result of 45.x/46,XX; 45.x/%.xxl47.XXX. or 45,X/46,xY.
meiotic nondisjunction, though the increased risk Mosaic individuals may have fewer physical stigmata.
with advanced maternal age is much less than that ofTurner syndrome. In the remaining 25~ ofcases,
for trisomy 21. Twenty percent of children with there are two X chromosomes but the short (p) arm
trisomy 13 have an unbalanced translocation of of one of the X chromosomes is missing.
an additional chromosome 13 attached to another
chromosome. Twenty percent of translocation cases CllnlcBJ MsnlfBstBtlons
are familial, meaning that one of the parents has a Dysmorphic features include lymphedema ofthe hands
balanced translocation involving one chromosome and feet, a shield-shaped chest, widely spaced hypo-
13 and another chromosome. The remaining 5% of plastic nipples, a webbed neck. low hairline, cubitus
children with trisomy 13 have mosaicism; some cells valgus (increased carrying angle), short stature, and
have 46 chromosomes with a normal karyotype, and multiple pigmented nevi. Additional abnormalities
some cells have 47 chromosomes with trisomy 13. include gonadal dysgenesis, renal anomalies, congenital
TilLE IN. Key Features of Trisomy 13 and Trisomy 18

........,13 ........,18
I He........... Microcephaly with sloping forehead
Cutis aplasia ofscalp
Prominent occiput
Narrow bifrontal diameter of forehead
!
Microphthalmia Low~aet, malformed eara
I
la-t....- Cleft lip and palate
Congenital heart disease (VSD, ASD, PDA)
Omphalocele
Mic:ropathla
Conpnital heart disease (VSD, ASD, PDA)
Short sternum
1- Cleru:hed banda with cmdapping fingers

Polydactyly
Polycystic lddney or other renal defecta
Clenched handa with overlapping fingers
Rocker bottom feet
Horseaboe lddney
Cryptorchlcliam. agenesis of corpus callosum Lack ofaulx:utaneoua fat
'Other
heart disease, autoimmwte thyroiditis, and learning Testosterone therapy during adolescence may
disabilities. Gonadal dysgenesis, present in 100% of improve secondary sexual characteristics and prevent
patients, is associated with primary amenorrhea gynecomastia.
and lack of pubertal development because of loss
ofovarian hormones. The gonads are appropriately IMPRINnNG DISORDERS
infantile at birth but regress during childhood and Imprinting refers to different phenotypes resulting
develop into •streak" ovaries by puberty. In mosaics from the same genotype, depending on whether the
with a Y chromosome in one of their cell lines, g~ abnormal chromosome ia inherited from the mother
nadoblastoma is common. Therefore, prophylactic or father. Uniparental disomy is the term used when
gonadectomy is necessary in these patients. Renal both chromosomes of a pair have been inherited
anomalies, usually duplicated collecting system or from only one parent. Prader-Wllll and Angelman
horseshoe kidney, occur in 40% ofthose with Turner syndromes are examples of imprinting, and some
syndrome. Congenital heart disease occurs in 20% cases are also examples of uniparental disomy.
of patients; common defects include coarctation of
Pradar-WIIII Syndrome
the aorta, aortic stenosis, and bicuspid aortic valve.
Prader-Willi syndrome occurs in 1 per 15,000
With only one functional X chromosome, females
newborns and is associated with a region of the
with Turner syndrome display the same frequency of
long arm of chromosome 15 (15qll-13). Approx-
sex-linked disorders as males. The diagnosis is made
imately 7096 of those affected have a chromosome
by karyotype and FISH. Because of their mosaicism,
deletion in the paternally derived chromosome 15
some girls suspected ofhaving Turner syndrome have
and a normal maternal chromosome 15. Another
a 46.XX karyotype in the peripheral blood.. and a
20% to 25% have normal-appearing chromosomes
skin biopsy may be necessary to make the diagnosis.
with two copies of maternal chromosome 15. This
Short stature hu been successfully treated using
is known as uniparental maternal disomy, and the
human growth hormone. Secondary sexual char-
syndrome results from the lack of a paternal copy
acteristics develop after estrogen and progesterone
administration. AB mentioned earlier, gonadectomy of chromosome 15. The remaining affected new-
borns have abnormalities ofimprinting because of
is indicated in patients with dysgenetic gonads and
translocations narrowing the region. The recurrent
the presence of a Y chromosome. With the rare
.risk for parents of an affected child is 1 in 100,
exception of a few mosaics, women with Turner
unless the chromosome 15 deletion results from
syndrome cannot become pregnant.
a parental translocation, which is extremely rare.
Kllnsfalbtr Syndrome The disorder is sporadic.
Klinefelter syndrome, caused by an extra X chrom~
some in males, affects 1 in 500 newborn males, 20% Clinical Manifslllations
Dysmorphisms include narrow bifrontal diameter,
of aspe.rmic adult men, and 1 in 250 men more than
almond-shaped eyes, a down-turned mouth, and small
6 ft tall. The karyotype is 47,XXY in 8096 of cases
hands and feet. Short stature and hypogonadotropic
and mosaic (XYIXXY) in 2096. Recurrence risk is
hypogonadism with small genitalia and incomplete
the same as the initial risk in the general population.
puberty are seen. These children suffer from severe
Clinical Manlfsstlltlons hypotonia, which is associated with feeding difficul-
The physical stigmata of Klinefelter syndrome are ties and fanure to thrive in infancy. By several years
not obvious Wltil puberty, at which time males are of age, these children develop an uncontrollable
incompletely masculinized. They have a female body appetite that leads to severe central obesity. These
habitus with decreased body hair, gynecomastia, children eat constantly unless food ill locked away.
and small phallus and testes. Infertility results from Obesity-related obstructi.ve sleep apnea and cardio-
hypospermiaor aspermia. Affected males are usually respiratory complications (Plckwicklan syndrome)
taller than average relative to their families and their may develop. There Js mUd mental retardation with
arm span can be greater than their height. There is characteristic impuJse control probJems.
an increased incidence of ]earning difficulties, but For the average patient, strict dietary control is
the average IQ is 98. Gonadotropin levels are usually attempted but difficult to enforce. Although those
elevated because of inadequate testosterone levels. affected can live normal life spans, complications of
Men with Kllnefelter syndrome have a 20-fold in- obesity such as obstructive sleep apnea and diabetes
creased Incidence of breast cancer. mellitus often Jead to earlier death.
Angalman Syndrome are at risk for Fragile X- associated tremor/ataxia

Approximately 6096 ofpatients withAngelman syndrome syndrome, a neurodegenerative disorder.
have a microdeletionon the maternal chromosome 15
(deletionof15qll- 13)andanormalpatemalchromo- CHROMOSOME 22011 DELETION SYNDROME
some 15. Five percent ofcases result from uniparental Microdeletion of22ql1.2 has been found in 9006 of
paternal disomy, where two normalropies of paternally children with DiGeorge syndrome, in 7006 ofchildren
derived chromosome 15 are inherited. Five percent with velocardiofacial syndrome, and in 15,.; of chlldren
result 6:mn imprinting center mutations, and s,.-. are with isolated conotruncal cardiac defects. Although
caused by a single-gene mutation (UBE3A). Ten per- the descriptive names of the above-mentioned dis-
cent to 2596 result from small subtelomeric deletions orders are still in use, the more general term22q11.2
or translocations, or are ofunknown etiology. deletion syndrome more appropriately encompasses
the spectrum of abnormalities found in these chil-
Clinical Manifeststions
dren. Its prevalence in the general population is 1
Dysmorphisms seen in Angelman syndrome include per 4,000 live births. The deletion can be inherited
muillary hypoplasia, large mouth, prognathism,
(896 to 2896 of cases), but more typically OCCUI'8 as a
and short stature. Patients are severely mentally
de novo event. However. ifa parent has the deletion.
retarded, with impaired or absent speech and
the risk to each child is 5096. The mlcrodeletion can
inappropriate paroxysms of laughter. Jerky arm
be detected using FISH probes or microarray.
movements, ataxic gait, and a characteristic tiptoe
walk result in marionette-like movements, leading Clinical Manlfeslatlons
to its designation as the •happy pupp~ syndrome. Classic cardiac features ofthis spectrum ofdisorders
Most patients have seizures. include conotruncal defects such as tetralogy ofFallot,
interrupted aortic arch, and vascular rings. Other
common findings are absent thymus, hypocalcemic
hypoparathyroidism, T-cell-mediated immune de-
FRAGILE X SYNDROME ficiency, and palate abnormalities. These children
Fragile X. an X-llnked form of mental retardation usually have feeding difficulties, learningdisabilities,
that occurs in 1 in 3,000 males, is an example of a and behavioral and speech disorders.
trinucleotide repeat disorder. The gene involved,
called FMR-1, is active in brain and sperm. In normal CHARGE SYNDROME
individuals, the DNA trinucleotide CGG is repeated CHARGE is an acronym for a syndromic associa-
about 6 to 54 times at the start of this gene. Those tion of features including Coloboma of the retina
affected with Fragile X have over 200 CGG repeats. or iris; Heart abnormalities; Atresia of the choanae;
The disorder received its name because a cytogenet- Retarded growth; Genital hypoplasia in males; and
ically detectable breakage occurs at a specific fragile Ear abnormalities that can include deafness and
site on the X chromosome. Currently, Southern inner ear anomalies. Fifty percent of individuals
blot analysis and polymerase chain reaction (PCR) with CHARGE syndrome can have a characteristic
are used to determine the number of CGG repeats. ~ckey stick" palmar crease. CHARGE syndrome
is caused by a point mutation in the gene CHD7.
Clinical Manlfaatatlons
Individuals with Fragile X syndrome may have
macrosomia at birth, macroorchidism because of OTHER MALFORMATIONS AND
testicular edema, dysmorphic facial features (large ASSOCIATIONS
jaw and large ears), perseverative speech, and mental
Some syndromes without a detectable chromosomal
retardation (9096 ofaffected males have an IQ between
abnormality have clinical features that suggest a
20 and 49). Some males with Fngtle X syndrome have
chromosomal disorder. Theae syndromes often
mental retardation as the sole manifestation. Up to
enter into the differential diagnosis of a suspected
6% of patients with autism have Fragile X syndrome.
genetic disorder.
There is no known treatment for Fragile X.
Female carriers of the Fragile X chromo&Ome may • VATER refers to the nonrandom association of
have a subnormal IQ or learning disabilities. Women Vertebral and Anal anomalies, 7lacheoesopha-
with premutation (54 to 200 repeats) are at risk for geal fistula with Esophageal atresia, and Radial
premature ovarian failure. Males with premutation or Renal abnormalities.
• Fetal alcohol •ynclrome results from exposure hyperbilirubinemia, disordered coagulation), renal
to significant levels of serum alcohol during the dysfunction (acidosis, glycosuria, aminoaciduria),
prenatal period. Typical findings include short emesis, anorexia, and poor growth. Cataracts may
palpebral fissure&, smooth philtrum, and thin up- develop by 2 months of age in untreated children.
per lip. Affected infants may also have hypotonia, Infants with galactosemia are at increased risk of
poor growth. developmental delay, congenital Eschuichla coU sepsis. Older children can have se-
heart disease, and renal anomalies. vere learning disabilities, whether or not they were
treated in infancy. Affected females have a high
incidence of premature ovarian failure. Detecting
METABOLIC DISORDERS reduced levels oferythrocyte galactose-1-phosphate
uridyitransferase is diagnostic. Laboratory findings
APPROACH TO METABOLIC DISORDERS include a direct hyperbilirubinemia, elevated serum
Although individual metabolic disorders are rare, aminotransferase, prolonged prothrombin and
collectively they are responsible for significant mor- partial thromboplastin times, hypoglycemia, and
bidity and mortality. Inborn urors ofmetabolism are aminoaciduria. Galactose in the urine is detected by
genetic diseases that occur when a defective protein a positive reaction for reducing substances and no
disrupts a metabolic pathway at a specific step. Pre- reaction with glucose oxidase on urine test strips.
cursors and toxic metabolites of excess precursors
accumulate, and products needed for normal me- TtBatmtmt
tabolism are deficient. Certain ethnic groups are at All formulas and foods containing galactose (including
increased risk for specific metabolic errors. lactose-containing formulas and breast milk) must
Clinical presentation and age at onset vary. Urea be eliminated from the infant's diet. Lactose-free
cycle defocU and organic acidemilu present early in soy-based formulas should be substituted.
life with acute metabolic decompensation. Fatty acid
oqddatlon and carbohydrate metabolum diJorders GLYCOGEN STORAGE DISEASES
usually present with lethargy, encephalopathy, and Glycogen is a highly branched polymer ofglucose that
hypoglycemia after low carbohydrate intake or tast- is stored in the liver and muscle. Glycogen storage
ing. Lysosomfll storage disorders are characterized diseases (GSDs) are a group ofconditions that result
by progressive hepatomegaly, splenomegaly. and, from deficiency of enzymes involved in glycogen
occasionally, neurologic deterioration. Findings synthesis or breakdown. Because many different
that should increase suspicion for an inborn error enzymes are involved in glycogen metabolism, the
of metabolism include emesis and acidosis after clinical manifestations ofGSDs are variable. Typical
initiation offeeding, unusual odor of urine or sweat, manifestations include growth failure, hepatomegaly,
hepatosplenomegaly, hyperammonemia, early infant and fasting hypoglycemia. The most common GSDs
death, failure to thrive, developmental regression, are type IJ von Gierke disease and type V, McArdle
mental retardation. and seizures. Several important disease. All are autosomal recessive disorders. Treat~
disorders are discussed here. ment is designed to prevent hypoglycemia while
avoiding storage ofeven more glycogen in the liver.
CARBOHYDRATE METABOUSM DISORDERS
Galactoaemia AMINO ACID METABOLISM DISORDERS
Galactosemia, the most common error ofcarbohydrate Phenylk8tanuria
metabolism, is caused by a deficiency of the enzyme Phenylketonuria (PKU), the most common of these
galactose-L-phosphate urldylyitransferase, resulting disorders, occun in 1 in 10,000 Uve births. PKU results
inimpaired conversion ofgalactose-I.-phosphate to from a deficiency of phenylalanine hydroxylase, the
glucose-L-phosphate (which can undergo glycolysis). enzyme that converb phenylalanine to tyrosine. With
GalactoJe-L-phosphate accumulates in the liver, kid- normal phenylalanine intake, patients develop high
neys, and brain. The disorder occurs in 1 of40,000 serum concentrations of toxic metabolites such as
Jive births, and inheritance is autosomal recessive. phenylacetic acid and phenyllactic acid.
Clinical Manifestations Clinical Manifestations
Clinical manifestations are noted within a few Unlike most amino acid disorders, symptoms of
days to weeks after birth. Initial symptoms include untreated PKU develop gradually with progressive
evidence of liver fallure (hepatomegaly, direct IQ loss during infancy. Neurologic manifestations
include moderate to severe mental retardation, protein. Milder forms of the condition are seen in
microcephaly, hypertonia. tremors, and behavioral heterozygoua remales and in some affected males.
problelllB. !yroaine is needed for the production of
Clinical Man/fssiBt/DnS
melanin, so the block in the oonversi.on of phenylal-
Wrthin 24 to 48 hours after the initiation of
anine to tyrosine results in a llght complexion. The
protein-containing feedings, the newborn beoomes
patient's urine smells mouse-llke from phenylacetic
progressively lethargic and may develop coma or
acid secretion.
seizures as the serum ammonia level rises. Female
1't'tJBtmtmt carriers may develop headaches and emesis after
Prevention of mental retardation in PKU is achieved protein meals and manifest mental retardation and
by early and lifelong dietary reatriction of phenylala- learning disabilities. Diagnosis iJ aided by measuring
nine. All states include PKU detection in mandatory the level of orotic acid, a by-product of carbamoyl
newborn screens. Women with PKU must decrease phosphate metabolism. in the urine.
phenylalanlne intake during pregnancy to avoid in-
Treatment
creasing their risk ofhaving a child with microcephaly,
Treatment centers on an extremely low-protein diet
mental retardation, and congenital heart disease.
and the exploitation ofalternative pathways for nitro-
HD~J~DeyStlnurla gen excretion using benzoic add and phenylacetate.
Homocystinuria is caused by a defect in the amino Early intervention may minimize deleterious effects,
acid metabolic pathway that converts methionine to but management is complex and extremely difficult
cysteine and serine. The incidence of the cystathi- for parents to maintain.
onine synthase deficiency is 1 in 100,000 live births.
LYSOSOMAL STORAGE DISORDERS
The neonatal screen used by most states detects
increased methionine levels in the blood. Deficiency of a lysosomal enzyme causes its sub-
strate to accumulate in lysosomes of tissues that
ctlniCBI ManlfflstBt/ons degrade it, creating a characteristic clinical picture.
There are no symptomJ in infancy. Oinical man- These •storage'" diseases are classified as mucopoly-
ifestations observed during childhood include a sacdtaridrues (e.g., Hurler. Hunter. and Sanfilippo
Marfan-like body habitus (long thin limbs and digits, syndromes), lipidoses (e.g., Niemann·Pi.ck. Krabbe,
scoliosis, sternal deformities, and osteoporosis), Gaucher, and Tay-Sachs diseases), or mucolipidoses
downward-dislocated eye lenses, mild to moderate (e.g., fucosidosis and mannosidosis), depending on
mental retardation (604Jii), and vascular thromboses the nature of the stored material
that result in childhood stroke, pulmonary embolism,
or myocardial infarction. Hurl• Syndrome
Deficiency ofa -L-iduronid.a.se leads to accumulation
7l'eiJ1ment of the dermatan and heparan sulfates in tissues and
Dietary management is extremely difficult because their excretion in urine. Typical features include
restriction of sulfhydryl groups leads to a very coarse facies, corneal clouding, exaggerated ky-
low-protein, foul-tasting diet. Approximately 50% phosis, hepatosplenomegaly, umbilical hernia, and
of patients respond to large dosages of pyridoxine. congenital heart disease. Developmental regression
begins in the first year of life. Most children with
Ornithine Transcarbamylase Deficiency
Hurler syndrome die in early adolescence; the disease
OTC deficiency, a urea cycle defect, is one of the
course and survival may be improved with stem cell
few inborn errors of metabolism with X-llnked
transplant or enzyme replacement therapy.
inheritance. Amino acid catabolism produces free
ammonia that is detoxified to urea throllih a series Pampe Diseasa
of reactions known as the urea cycle. In the urea A GSD, Pompe disease is caused by deficiency ofadd
cycle, ornithine joins with carbamoyl phosphate maltase that results in lysosomal accumulation of
through the action ofOTC to mrm citrulline within glycogen in moscle. It is characterized by profound
the mitochondria. When OTC levels are less than hypotonia and extreme hypertrophic cardiomyopathy.
20136 of normal, the nitrogen-containing moiety in Cognition is normal The infantile form is usually
ornithine cannot be quickly converted to urea for fatal, because of cardiorespiratory failure, by 1 year
excretion and instead forms ammonia, which results In of age. Early diagnosis and enzyme replacement
severe hyperammonemia when the patient consumes therapy can be lifesaving.
Gaucher Disease anemia, leukopenia, thrombocytopenia, and recurrent

Gaucher diseue is cauaed by deficiency of the en- episodes of bone pain. Radiologic changes include
zyme fl-glucosidase,leading to the accumulation of an Erlenmeyer flask shape of the distal femur. A low
glucocerebroside. The classic form does not Involve enzyme level in the white blood cells confirms the
the central nervous system. Patients charact:eristi- diagnosis. Recombinant enzyme therapy improves
callyhave hepatomegaly and splenomegaly. Storage most symptoms.
of glucocerebroside 1n the bone marrow leads to
KEY POINTS
ENVIRONMENTAL FACTORS CHROMOSOMAL DISORDERS
• Environmental factors account for 10% of • Approximately 50% of first-trimester spontaneous
birth defects. abortions have chromosomal abnormalities.
• Infectious agents, high-dose radiation, mater- • Birth defects caused by autosomal anomalies
nal metabolic disorders (e.g., diabetes, PKU), are generally more severe than those caused
mechanical forces, and drugs can all cause by sex chromosome anomalies.
birth defects. • Indications for chromosomal studies (karyotype,
• A teratogenic exposure before 12 weeks' FISH, microarray) Include continnation of a
gestation affects organogenesis and tissue suspected chromosomal syndrome, multiple
morphogenesis, whereas an exposurv thereafter organ system malformations, significant de-
usually retards fetal growth and a1rects central velopmental delay or cognitive mpalrment not
nervous system development otherwise explained, short stBtln or extremely
delayed menarche In girls, Infertility or a history
GENEnC FACTORS
of mu~ spontaneous abortions, ambiguous
• Single-gene detects are classified by their genitalia, or advanced maternal age.
mode of lnherttance as autosomal dominant,
autosomal racesaive, and X-linked disorders. METABOLIC DISORDERS
• Defective genes In autosomal dominant clsorders • Decompensation from Inborn errors of metaboism
typically encode structural proteins, whereas can be preceded by Introduction of cet1aln foods,
those In autosomal f8Ce88ive disorders encode changes in frequency of feeding or fasting states.
enzymes. • Age of presentation with decompensation can
• In variable penetrance, there may be variable be helpful In considering Inborn errors In the
expression of a detective gene with variable differential. Severa newborn illness may be as-
degree of severity In affected Individuals. sociated with galactosemia and OTC deficiency
(OTC Is X-llnked).
• Most inborn errors of metabolism are autoso-
mal recessive disorders, with the exception • Early identification of Hurler syndrome, Gaucher
of OTC deficiency and some mitochondrial disease, and Pompa disease would allow for
disorders. enzyme replacement therapy and/or stem cell
transplant (Hurter).
CLINICAL VIGNETTES
VIGNETTE1
You are called to the full-term nursery to evaluate The infant has brachycephaly, midface hypoplasia,
an Infant with dyamorphlc teatui'8S. The Infant Is the eplcanthal folds, upslantlng palpebral tlssurvs, small
product of a full-term pregnancy born via sponta- low-set rotated ears, a small mouth, and micrognathia
neous vaginal delivery to a 23-ye•-old G1PO mother. with protruding tongue.
1. What other finding might support a clinical diagno- c. Slightly higher than the general population risk,
sis when examining this Infant's hands and teat? to account for gonadal mosaicism
a. Hockey stick palmar crease d. Much higher than 1tle general population rtsk
b. Single palmar crease
c. Rocker bottom feet VIGNETIE2
d. Clenched hands with overtapping fingers During a 2-year well child examination, you note a
e. Polydactyly male with hyperactivity, motor and speech delay, and
autistic features. His pregnant mother mentions that
2. Which of the following tests would confirm the
she is concerned as her brother and her maternal uncle
diagnosis and elucidate the recurrence risk for
both have mental retardation, and these individuals
these parents?
behaved similarly as preschoolers. Physical examination
a. Chromosome 21 FISH for Down syndrome is remarkable for large ears, and the child is nonverbal
b. CHD7 sequencing for CHARGE syndrome
with hand-flapping behavior.
c. 22q11 FISH Btudiea for 22q11 deletion syndrome
d. Karyotype 1. Which of the following teeta is most likely to reveal
e. State newborn screening 1tlis child's diagnosis?
L Karyotype
3. Beyond the findings above, physical examination
b. DNA microarray
of this Infant Is completely unramat1<able. In ad-
c. FISH
dition to complete blood count with differential,
d. Southem blot for CGG repeats
renal ultrasound, and statewide newborn screen,
e. Serum amino acids and urine
which of the following should be obtained while
organic aclda
waiting for genetic teat reaulta, baaed on clinical
f. Methylation PCR for
suspicion?
Prader-WIIIVAngelman
a. Heed ultrasound to evaluate for brain anomalies
b. Swallow study to evaluate for tracheoesoph- 2. If this testing is positive, what is 1tle recurrence
ageal fiStula risk in the upcoming pregnancy?
c. Echocardiogram to evaluate for congenital a. 50% in male newborns
heart disease b. 50% in female newborns
d. Conjugated bilirubin for biliary anomalies c. 1DO% In male newboms
e. Spinal ultrasound to evaluate for dysraphlsm d. 50% In all newborns
e. 25% In all newborns
4. If there is an associated congenital heart anomaly,
which of the following is most likely to be present? VIGNETIE3
L Complete AV canal
You are caring tor infants in the neonatal intensive
b. Transposition of the great arteries (TGA)
care unit (NICU). You receive a STAT page to a delivery
c. Coarctation of the aorta room to resuscitate a full-term newborn male with
d. Ebsteln anomaly
cyanosis. His color does not improve with intubation.
e. Supravalvular aortic stenosis His chest radiograph is notable for absent 1tlymus.
5. Which of the following conditions is NOT a fre- Echocardiogram reveals truncus arteriosus. You sus-
quently noted comorbidity in individuals with pect a genetic diagnosis and following stabilization
Down syndrome? sand the appropriate testing.
a. Hirschsprung disease 1. What electrolyte is especially important to follow
b. Alzhelmer-llke dementia
in managing this Infant?
c. Leukemia L Potassium
d. Hlypothyroldllm
b. Magnesium
e. Hlyperphagia c. Glucose
I. The karyotype results for this infant suggest an d. Phosphorus
unbalanced 14q21q translocation with duplica- e. Calcium
tion of material on chromosome 21 . Study of
parental blood karyotype finds that this mother VIGNETIE4
is a balanced earner of this translocation. What You are caring for "feeders and growers" In the
would be the risk of this couple having another NICU. One Infant girt has very low muscle t one and
child with Down syndrome? requires nasogastrtc tube feeding, as she cannot
a. Approximately the same as the general pop- feed from a bottle. The feeding team has tried "ev-
ulation risk erything• with no success, and a gastrostomy tube
b. Dependent on matemal age is being considered. While prerounding, you notice
she has upslantlng almond-shaped eyes and small 2. What is the most likely inheritance of this syndrome
hands and feet. In this patient?
a. Matemal deletion of 15q1 1-13
1. Which of the following would be the most likely
b. Paternal deletion of 15q11-1S
diagnosis In this Infant?
a. Down syndrome (Trisomy 21) c. Mutation of imprinting center
d. Matemal uniparental disomy
b. Angelman syndrome
c. Prader-Willi syndrome e. Paternal unipal9ntal disomy
d. 22q 11.2 deletion syndrome
e. Pompe disease
ANSWERS
VIGNETTE 1 Quutlon 1 VIGNETTE 1 Quutlon 4

1.Answer B: 4.AnswerA:
Single palmar crease (simian crease), a horizontal Endocardial cushion defects are common in infants
crease extending across the palm, Is associated with with Down syndrome. Fifty percent of Infants with Down
Down syndrome. A superior palmar crease shaped syndrome may have a complete atrioventricular canal.
like a hockey stick Is present in 50% of individuals TGA is rarely found In syndromic conditions but may
with CHARGE syndrome. Rocker bottom feet are a be noted in cases of prenatal trimethadione exposure.
feature of trisomy 18 syndrome. Clenched hands with Coarctation of the aorta is commonly found in girts
overlapping fingers are features of both trisomy 13 and with Turner syndrome. Ebsteln anomaly Is associated
18 syndromes. Polydactyly is a feature of trisomy 13 with prenatal lithium exposure. Supravalvular aortic
syndrome. Of note, unaffected newborns may also stenosis is more common in patients with Williams
have single palmar creases. syndrome (7q1 1.23 deletion).
VIGNETTE 1 Quutlon 2 VIGNETTE 1 Quatlon 5

2.AnswerD: 5.AnswerE:
Karyotyping will confirm the diagnosis and provide Hyperphagia (excessive eating) is typically associated
information regarding the likelihood of these parents with Pracler-Willi syndrome. The other conditions listed
having another affected child. The patient In this are known possible comorbldltles of Down syndrome.
vignette has multiple features of Down syndrome.
A karyotype is indicated to assess for unbalanced VIGNETTE 1 Question 8
translocations, which are more common when the &.Answer D:
mother Is young and are associated with Increased Because one of the parents Is a carrier of a balanced
risk of recurrence. A chromosome 21 FISH would Robertsonian translocation, the risk of having another
detect trisomy 21 duplication but not unbalanced child with Down syndrome is greatly increased, about
translocations. Answers B and C test for conditions 10% overall. The risk for full trisomy 21 depends on
other than Down syndrome, as noted. State newborn maternal age (Answer B); however, this infant has an
screening varies from region to region but typically unbalanced translocation. In this scenario, the mother's
includes screening for hypothyroidism, metabolic balanced carrier status was confirmed on karyotype
disorders, congenital adrenal hypoplasia, and sickle from peripheral blood, so there Is no gonadal mosaicism.
cell disease.
VIGNETTE 1 Quatlon 3 1.AnswerD:
3. AnswerC: The most likely diagnosis is Fragile X syndrome. Frag-
The septal defects most commonly associated with ile X is the most common X-linked cause of mental
Down syndrome may not be discernible via auscultation retardation. It is also the most common genetic cause
In the newborn period. Congenital brain anomalies ars of autism. This patient's mother Is descr1blng X-linked
commonly found in infants with trisomy 13. A swaUow inheritance in her family; both she and her mother
study would be appropriate in an infant with VACTERL are carriers of this disease. Fragile X syndrome is
syndrome. Biliary anomalies are common in infants with detected with > 200 CGG repeats on Southam blot or
Alagllle syndrome. There Is no Increased association PCR testing. It would not be detected on karyotype,
of dysraphiam with Down syndrome. microarray, FISH, metabolic studies, or methylation
PCR tor Prader-WiiiVAngelman syndrome, any of calcium support. The magnesium level may also be
which may be employed In evaluating a child wtth affected (low), and phosphorus may be high because
developmental delay. Individuals with Angelman syn- af low parathyroid levels. Hypocalcemia would put this
drome can have autistic features; however, Angelman critically Ill Infant at risk for tonic seizures and possibly
is typically sporadic. heart failure. The appropriate genetic testing to send
for this infant is 22q11 FISH or microarray.
VIGNETTE 2 Q...Uon 2
2.AnswerA; VIGNETlE 4 Quedon 1
Newborn boys of a mother who is a carrier of Fragile 1.AnswerC:
X syndrome have a 50% risk of Fragile X syndrome, The correct answer is Prader- Willi syndrome, asso-
as they either inherit the affected X chromosome or ciated with extreme hypotonia and feeding problems
a normal X chromosome from their mother. Newborn in the newborn period and these physical character-
girts have a 50% risk of being carriers. Parents istic features. Individuals with Down syndrome may
with autosomal dominant disorders such as 22q11 have upslanting palpebral fissures and brachydactyly
deletion syndrome have a 50% risk of recurrence (short fingers), but their palms are normally sized. The
In all male and female pregnancies. In autosomal extremely low muscle tone and dysmorphlc features
dominant disorders, the progeny can either Inherit descr1bed In this patient are not consistent wtth An-
the normal allele or mutant allele from an affected gelman or 22q11.2 deletion syndrome. Pompa disease
parent. Autosomal recessive disorders, such as can be associated with extreme hypotonia, but this
galactosemia, have a 25% risk of recurrence in all is typically due to progressive glycogen deposition,
pregnanciee, where each parent carriee a mutant so is not present in the newborn period. Additionally,
allele with a normal allele, and the affected child individuals with Pompe disease do not typically have
inherits both mutant alleles. dysmorphic features.
VIGNETTE 3 Q..Uon 1 VIGNETTE 4 Queetion 2

1.Answer E: 2.Answer B:
This patient has a conotruncal heart defect (truncus Prader-Willi is an epigenetic disorder. It may be inher-
arteriosus) and did not have a visible thymus on ited via paternal deletion (70%), matemal uniparental
chest radiograph. These two conditions lead to high disomy (20% to 25%), or translocation involving the
suspicion for 22q 112 deletion syndrome. Individuals Imprinting center (5%). Maternal deletions (60%) and
with 22q11.2 deletion syndrome can have hypopara- patemal uniparental dlsomy (5%) In this same genetic
thyroidism leading to hypocalcemia, especially In the region result In Angelman syndrome, as do lmpr1ntlng
newborn period as they are weaning off maternal center mutations.
Emergency Medicine: The
Acutely Ill and Injured Child
Prtya G. JUI, Suzame M. Schmidt, Elizabeth R. Alpern,
and Bradley s. Mamo
primary assessment is to identify life-threatening

TliE CRITICAU.Y ILL CHILD conditions and begin CPR, ifnecessary (Table 20-3).
The critically ill child must be evaluated rapidly to
minimize morbidity and mortality. Whether present- CARDIOPULMONARY RESUSCITADON
ing to the physician's office, local clinic, community Cardiopulmonary arrest is defined as the absence of
hospital, or to the emergency department at a ter- central pulses in an unconscious patient who is not
tiary care center, the patient should be stabilized breathing. To assess the need for CPR, first check to
by administering basic and advanced pediatric life see if the patient is responsive to verbal or physical
support measures recommended by the American stimuli. A patient who is breathing regularly does
Heart Association. Concurrently with stabilization, not need CPR,, but may need other interventions. In
evaluation for the underlying etiology of the child's the unresponsive child, health care providers should
symptoms is begun. take no longer than 10 seconds to check for a pulse.
Updated guidelines from the American Heart Palpate the brachial pulse in infants and the femoral
Association recommend that assessment of the or carotid pulse in children. If there is no pulse and
critically ill child begin with circulation, followed the patient is not breathing (or merely gasping), the
by airway and breathing (C, A, B). In adult patients, patient is in cardiopulmonary arrest and you should
cardiopulmonary resuscitation (CPR) with com- call for help and/or 911 Medic, and initiate CPR,
pressions is recommended only for the lay rescuer starting with chest compressions. See Figure 20-1
and has been associated with a positive impact on for evaluation and treatment of the unresponsive
survival in out-of-hospital cardiac arrest. However, child or adolescent.
conventional CPR (compressions with rescue breaths) The goal of CPR is to provide high-quality chest
remains the superior method in children. compressions that generate blood flow to vital or-
gans. High-quality compressions require a rescuer
to push hard, at a rate of 100 to 120 compressions
Dl FFERENTIAL DIAGNOSIS
per minute. Effective compressions should depress
The majority of cases of pediatric cardiac arrest the chest to a depth of at least one-third of the an-
result from progressive respiratory failure. trauma, or terior-posterior diameter of the chest (1.5 in or 4
shock, rather than a primary cardiac cause. Table 20-1 em in infanb, and 2 in or 5 em in children). After
lists the differential diagnoses of cardiopulmonary the initial set of compressions, the airway is opened
arrest in children. using the head-tilt chin-lift maneuver (if no trauma
is suspectEd), and two rescue breaths are adminis-
CLINICAL MANIFESTATIONS AND tered, assuring that chest rise is visualized. In chil-
dren, a compression-to-ventilation ratio of 30:2 is
TREATMENT
appropriate for the lone rescuer, whereas a ratio of
PRIMARY SURVEY 15:2 is recommended if two rescuers are present. It
Care begins with the primary assessment. which is important to remember that fatigue during CPR
includes evaluation of Circulation, Airway, Breathing, can lead to ineffective chest compressions. Rotate
Disability, and Exposure (Table 2()...2). The aim of the the role of chest compressions every 2 minutes.
403
TABLE 20-1. The DlfferenUal Diagnosis of IHyperkalemJa

cardiopulmonary Arrest in Children ~ Hypocalcemia
i
RlspirBtrJty 1Hyponatremia
Upper alrwwy obstruc:tion (e.g., aoup. epjpott1til, lltfultllyslem
forei&n bocly,laryDppaam. congenital anomalies,
bacterlal tracheitis, neck trauma, thermal or chemical
ISudden unexplained infant death
burn., rmopharyngeal abscess, peritoollUar abecea) l Drug Intoxication (e.g., akohol. narcodcs, trlcydic
~ anlidepreaantl, barbltura• beozodiazepines,
Lower airway obJtruction (e.g., filreign body, reactive l calcium channel blocken, P-blocbra)
airway disease, bronchiolitis, congenital anomalies)
Ventihdion-perfulion m.i&mat:ch (e.g., pneumonia.
l! Trauma
pulmonary edema, pneumothorax. hemothorax, !Anaphylaxia
chronic lung dl.eue) IHypothermia
DiffuJJ.on abnormality acrou the alveoha (e.g., acute !Septic shock
respiratory cll.streu lf!Uirome) ! Rfnlfl
Mallive pulmoiW'}' embollam iAcute or chronic renal failure
i'''''''''''''''''''''''''''''''''''"""''"""'"'''''"""~'"""''"''''"""''"""'''''''''''''''''''''''''''''''''''uooooooooo:
Respiratory muscle failure (e.g., botulism, Guillain-
Barre syndrome)
Central hypoventiJation (e.g., primary apnea,
depresaion of the relpiratory c:ent2r of the brainatem) Care should be taken to minimize interruptions to
chest compressions ("hands-off• time) as coronary
C1udltlc
perfusion pressure declines rapidly during deJays.
Congenital heart dlleue (e.g,.lellona with ductal-
dependent -ratemJc blood Oow) CIRCUlAnON
Arrhythmia Circulation is assessed by evaluatins pulses (central
Myocarditis and. peripheral), capillary reBll. and blood pressure.
Perkarditia In children, heart rate is a sensitive, although less
.specific, measure of intravascular volume lltatus.
Card1a.c tamponade
Capillary refill is a sensitive measure of adequate
Congeltive heart failure circulation. Blood pressure is a less sensitive indica-
Myocardial trauma tor of volume status, as compensatory mechanisms
Centnll NtNvou& Symm may maintain adequate blood pressure in spite of
Meningitis hypovolemia. Hypotension is often a late finding in
children. Cardiorespiratory monitoring can be helpful
Encephalltis
in determining the electrical activity of the heart
Acute hydrocephalus and providing continuous feedback on the patient's
Head or spinal cord trauma cardiorespiratory status and any subsequent changes.
Seizure
AIRWAY
'1\unor
The goals ofairway management are to recognize and
Hypoxlc-llchemlc Injury or atroke relieve airway obstruction and to provide adequate
GalminiBmn.J ventilation. while preventing aspiration of gastric
Abdominal trauma contents. Common causes of airway obstruction
:Bcnm pedoration or obstruction include infection (e.g., aoup, epiglottitis, retropha-
ryngeal abscess), tonsillar hypertrophy, foreign object
Peritonitia
aspiration, congenital anomalies, and trauma or in-
Hypovolemic dehydration halational injury. Physical exam findings suggestive
llmbalic ofupper airwayobstruction include strido~ drooling.
Diabetic ketoadcloail and a hoarse or muffied voice. Oilldren in respiratory
Addison dUeue distress will often asswne a posture that optimizes the
mechanics of breathing, such as sitting up with the
Hyperthyroidiam
neck extended. They .should be allowed to remain in
Hypoglycemia their position of comfort, as much as possible.
Chapter 20 I Emergency Medicine: The Acutely Ill and Injured Child • 405
IPIIIIIIIJ..,., . . .
! CJreulation
.........
TilLE 20-2. Initial Assessment of the Pediatric Patient
Ablence of detectahle pulJea, poor perfusioo. hypotenllon. bradycardia

I Airway Co~ or ~eYa"e airway obltruction
lBreathing Apnea.llignificant wmk afbreathing, hypopnea, hypoxia

! Disability Unresponaiveness, reduced COllllclousneu
i Expo$ure Significant hypothemUa, bleeding. petechiae or purpura with sepsU, bruising from
I trauma, abdominal diatension from acute abdomen
i Modlfted from Nichols DG, Vester M, Lappe DG, et al. Golden Hour; 7he Handbook ofAdvanced Pedlattlc Ufe Support, 3rd od. !
i..~:..~.~~~--~.?.:..~~~-~.~--~-~-~.:~~.:.~.~. ..~~~-~-~-~.:...~~~.'::.~.~~--~!.~~-~:.....................................................................................................i
The airway 1s assessed and, if necessary, secured • Size of the cuffed endotracheal tube = 3.5 +(age
as follows: in years/4)
• Immobilize the cervical spine if there is a possi- If available, length-based resuscitation tapes can
bility of spinal cord injury. provide recommendations for endotracheal tube size,
• Open the airway via the jaw~thrust (if concern u well u sizes of additional equipment, especially
for cervical spine injury) or head-tilt. chin-lift for children less than 35 kg.
maneuver to relieve obstruction caused by the Blood oxygenation (via pulse oximetry or arterial
tongue or soft tissues of the neck. blood gas measurement) and blood C~ level (by
• Clear the airway (suction the nose and mouth blood gas or end-tidal C02 measurement) should
as needed). be assessed to help guide respiratory management.
• Remove any visualized foreign body ifthe patient To avoid hyperoxia, titrate oxygen administration to
cannot cough or vocali2e. maintain oxygen saturation around 94".
• Consider placiJl8 an oral or a nasopharyngeal Intubation ofthe infant or child is undertaken with
airway, if indicated. premedication, following the steps given herewith in
• Provide 100'1' oxygen via nasal cannula, simple face rapid sequence. Intubation should be performed by
mask, non-rebreather mask, or bag valve mask. providers who are proficient in the evaluation and
• Assist ventilation (e.g., bag mask ventilation) if management of the pediatric airway.
indicated.
BREATHING 1. Preoxygenate with 10006 oxygen (bag :mask
ventilation may be required).
Once an airway 1s established, adequacy ofventilation
2. Consider administering atropine in children less
is assessed. Examination ofchest wall movement will
than 1 year ofage to reduce bradycardic response
reveal the presence and effectiveness ofspontaneous
to intubation (administer 3 to 5 minutes prior
respirations. Ifrespiratory effort, chest wall excursion,
to intubation, if possible).
or oxygenation ia not adequate, additional respiratory
3. Consider administering lidocaine for patients
support is required. Noninvasive respiratory support
with suspected increased intracranial pressure.
with continuous positive airway pressure through
4. Administer a sedative, hypnotic, and/or op~
a specialized nasal cannula or mask may improve
oid drug (e.g., etomi.date, ketamine, versed,
ventilation. If breathing is still not adequate or if
fentanyl).
there is concern about the stability of the airway,
5. Administer a paralyzing dose ofa neuromuscular
endotracheal tube placement may be necessary.
blocking agent (e.g., rocuronium, vecuronium
Both cuffed and uncuffed endotracheal tubes are
[nondepolarizing agents], or succinylcholine
appropriate for intubating infants and children.
[depolarizing agent]).
Cuffed endotracheal tubes may reduce the risk of
6. Assess the patientfor apnea, jaw relaxation. and
upiration, and in circumstances where poor lung
loss of muscle tone.
compliance or high airway resistance are present, a
7. Intubate the trachea with direct visualization.
cuffed endotracheal tube may be preferable.
8. Confirm correct placement of the endotracheal
• Size of the uncuffed endotracheal tube = 4 + tube using at least two methods (auscultation,
(age in years/4) chest rise and fall. end-tidal co:! detector).
TilLE 20-3. CPR in Infants and Children

!..._. ~ 12111111 . .) Gild (1111 J 1D _.. ....,
----
IIIII_.and Mill
!Qeck for reaponaiveneu
1lfunn!lpOnaive. no breat:hJ.ns or only piping. begin CPR
j CIRCULATION
iHealth care piUYiden check fur pulse fur no more than 10 a
IBrachial or femoral Carotid Carotid
! lfpul.selaa, begin chest compreui.on1
~ Rate of approximately 100-120/min
!Allow complete cheat recoll between eompreaion.
!Landmark: Center of the chest. just below Landmark: Center of the chest. Landmark: Center of the
! nipple line between nipples chest, between nipples
i Technique: 1 re~a~er1 2 fingers OR 2 Technique: 2 hands: Heel of 1 hand Technique: 2 hands: heel of
! resc:aent 2 thumba, with banda endrcling with second on top OR 1 hand: heel one band, other hand on top
i cheat ofhand only Depth: at least 2 in (5 em)
! Depth: 1.5 in (4 em) or at leut 1/3 the Depth: 2 in (5 em) or at least 113 the
anterior-polterlor diameter of the chest anterior-posterior clfameter ofthe chest
AIRWAY
Position patient auplne
Head-tilt, chin-lift (or jaw throat for suspected trauma)
i lfairway obstructed with foreign body and patient is unable to breathe or talk
!Back blows and chest compressions Abdominal thrusts (Heimlich Abdominal thrusts
! maneuver) (HeimHc:h maneuver)
~BREATHING
!2 reacae breaths after comprelliona
i Mouth to mouth and 1101e Mouth to mouth Mouth to mouth
j Comprellllion:Ventilation Ratio
i 30-.2 (1 rescuer) 3()-.2
! 15:2 (2 rescuera)
llfpulse present and no eompreui.ons required
i 15-20 breaths per minute 10-12 breaths per minute
lOR OR
is-10 breaths per minute with an advanced airway in place. Breaths are 8-10 breaths per minute with
1 asynchronous with ch.elt oompre.ssiom. an advanced airway in place.
Breath. are asynchronous
!
with ch.elt oompressiom.
IDEFIBRILLATION (AED)
!Minimize interruption~ to oompreulona before and after shock
llleaume CPR with <lOinpreulona immediately after each shock
: Lesr tlum ly of.,. 1-8y old By old-Adult
~ Insufficient evidence to recommend fur Use pediatric pads for attenuated Use standard adult AED with
i or aplnat the 01e ofan AED. A manual dole ifavaflable. Use adult ~m if pad-able IJStelD
~ defibrillator is preRaed. ifavailable pediatric ~)'Stan is not available
~ Abbreviations: AED, automated axt.amllll clafibMalor; CPR. cardiopulmonary I'IIIIU9Cilation. i
·-~-··············--·······..·-·--·--···...- - - - · -..------······~··--·-··············-····················-··················-···..···················-··········-·~·····-···;
Applying cricoid pressure during rapid sequenal interferewith vmtilationorairwayv:isualiWion.Rarely.

intubation is not universally recommended as there is ifa pediatric patient cannot be intubated oradequately
insufficient evidence that it will prevent aspiration of ventilated with a bag and mask. an emergency needle
gastric contents during intubation in children, and it may aicothyrot.omy may be required to esblbllsh an airway.
Unreeponallle child/adolescent
!
Acllw 911 Medic and call for help
CIRCULATION
!
Check for central pulse
No central pulse Pulse
l
Not brealhlng or only gasping
1
Start CPR
One rescuer: Give cycles of 30

comprenlona and 2 b1'1111tha.
-r. ., .
Open AIFfNAY
Vee
Push hard and fast at a rate of
100 compressions per minute.
Allow the chest wall to recoil
completely. Mlnlmlm
Airway obstructed
l No ~airways
ManeiMirs lor
Interruptions In compressions. BREPJ"HING . - - - - -

Two rescuers: Give cydes of 15 Assess for chest
compreuloiUI and 2 br.ths.
Aaa888 peripheral pulses 4-------- Ventilate wlltl beg mask

and Blood pi'888UI'8 Gille Ot
~ Endotracheallntubatlon
Pulaea strong Pulse weak-----+ Ensure adequacy of

BP nonnal BP low ventilation
I IVaccess
-t Monitor closely
Obtain IVIIO Differential
-__ diagnosis
---.ECG
Bradycardia/
r-----~~~--VT~Mitlpulse asystole
Hemodynamically Hemodynamically
Hemodynamically Hemodynamically
unstalllei\IT refractory unstableiSVT
stable stable nllractory
to med8
l 1 1 1 Epinephrine
Atropin•
Arniodwone or Synchronized
Adenosine
Synohronizad Transcutaneous or
ptOOainamict• cardiowersion cardiO\Ietlion transwnous pacing
Defibrillate
FIGURE za-1. Management of the unresponsive child or adolescent. BP, blood pressure; CPR, cardiopulmonary
resuscitation; ECG, electrocardiogram; 10, lntraosseous; IV. Intravenous; SVT, supraventricular tachycardia; VT,
~~~~~~~..~.~!.~·...................................................................................-.....................................................................................................................................................
DISABILITY the context of normal childhood development. If

Disability refers to the assessment of neurologic possible, allowing the child to remain in the anns of
function. A rapid screening neurologic examina- a parent can improve the ability to get an accurate
tion should be performed. including pupillary examination. When encountering medically complex
response, level of consciousness, and localizing children with special needs, be sure to ask caregivers
neurologic findings. The Glasgow Coma Scale about the child's baseline level of functioning and
(GCS), initially developed for the evaluation specific concerns related to their medical history.
of head trauma, is a rapid, easily reproducible
method of quantifying neurologic function and EXPOSURE
impairment oflevel of consciousness (Table 20-4). When evaluating a critically ill patient, exposure
The score is the sum of three components: (1) refers to removing the patient's clothing to perform
eye opening, (2) motor response to pain, and (3) a thorough examination, looking for clues to indicate
verbal response. When calculating the GCS, it is the etiology of the illness (e.g., trauma, bleeding,
important to use the patient's best response for rashes). Children exposed to toxins may have rem-
each parameter. A GCS of 15 is a perfect score, nants of the substance on their clothing and/or skin
and indicates a patient who is awake, alert. and and should be decontaminated to reduce the risk of
cooperative. The minimwn score of 3 (1 point for continued chemical exposure to the patient and to
each component) is indicative of deep coma or medical providers. Care must be taken to monitor
death. In general, patients with a GCS of less than body temperature in infants and small children. Be-
8 are likely to require intubation. cause ofchildren's large surface-to-body mass ratio,
When assessing neurologic function in children. passive heat loss and drop in temperature can occur
it is important to consider the patient's behavior in quickly, especially in infants and patients with burns.
TilLE zo.•. Glasgow Coma Scale

...... . .• . , . . llld.ldull Mllllsllll-· . . . .
·-·--·1~
.....- .................--..--··- ·-·-·-·-·-..-·-.................................................- .........-...
rE;;~·-··············4······················~~
i
I Best motor
~ =
:r = c:=::mr Obeys commands, normal spontaneous
i
I
lnopo~ : =~.::~ore) ~~. l
~~- ~ §~~~&ctm -~ro~.-~ interact~
!
;~~c-
NT Factor Interfering with communication
severity of respiratory and circulatory abnormal-

ities. These tem often occur in conjunction with
the primary or secondary surveys. The timing of
specific testing is dictated by the clinical situation.
Ancillary studies that may assist with the assess-
ment ofcardiorespiratory abnormalities include the
following: arterial or venous blood gas, hemoglobin
concentration, oxygen saturation via pnlse oximetry,
"[
lnteroeeeoua needle
invasive arterial pressure monitoring, exhaled C02
monitoring, complete blood count, electrolytes,
chest radiographs, electrocardiogram (ECG), and
Resuecltatlon drugs
1 echocardiography.
SHOCK
Shock is a syndrome chara.cterized by the inability of
Crystalloid fluid administration aalndlcated the circulatory system to provide adequate delivery of
oxygen and nutrients to meet the metabolic demands
FIGURE 211-2. \lascular access management during of the body tissues and vital organs. Children will
~-~-~-i-~!?.!:!!.~~-~!Y...~.~!.~~~!~.~.:................................................................ initially compensate by increasing heart rate and
increasing systemic vascular resistance through pe-
VASCULAR ACCESS ripheral vasoconstriction. Once theae compensatory
Vascular access is critical for resuscitative fluid and mechanisms can no longer maintain adequate blood
drug administration during CPR. An algorithm for pressure, hypotension results, leading to cellular hy-
rapid vascular access Js outlined in Figure 20-2. poperfusion. metabolic acidosis, and cellular death.
When establir.hing vascular access, blood fur laboratory Three relationships are helpful in understanding the
studies (including complete blood count, blood gas, factors that determine blood pressure:
electrolyte and chemistry panel, bedside glucose, • Stroke wlume is determined by preload (ven-
and blood culture) is often obtained. If intravenous tricular end diastolic volume), afterload (systemic
access is difficult, establishing access takes priority vascular resistance), and myocardial contractility.
over obtaining laboratory studies, especlally ifit may • Cardiac output = stroke volume X heart rate
jeopardize the access. Ifingestion is a concern, serwn • Blood preuure = cardiac output X systemic
and urine toxicology, and serum acetaminophen, vascular resistance
.salicylate, and alcohol levels may be obtained.
Shock may be compensated, decompeilllated, or
SECONDARY ASSESSMENT irreversible. In compensated shock. homeostatic
After completion of the pr.imary assessment and mechanisms maintain essential organ perfusion by
appropriate interventions to stabilize the child, the increasing heart rate and systemic vucu1ar resistance
secondary assessment should be performed. This in an effort to preserve cardiac output and perfusion
assessment includes a focused history and a thorough pressure respectively. Blood pressure, urine output,
physical examination. The SAMPLE mnemonic may and cardiac function may all be normal. Ongoing de-
be utilized to identify important aspects ofthe child's creased tissue perfusion leads to ischemia, endothelial
history and presentingcomplaint (Signs and Symptoms, injury, and the accumulation of toxic materials. In
Allergies, Medications, Put medical history, Lut meal, decompeilllated shock, compensatory mechanisms
Events leading up to the injury and/or illness). The fail. leading to hypotension and organ dysfun.ctlon.
hiatory should focus on symptolll8 or events that might Signs of inadequate end-organ perfusion include
help explain impaired respiratory, cardiovascular, or delayed capillary refiJ1. mottling ofskin. weak central
neurologic function. A thoroup head-to-toe physical pulses, depressed mental status, tachypnea, decreased
examination should be done to look for additional urine output, and metabolic acidosis.
clues as to the etiology of child's illness. In infants and chlldren. hypotension is defined
by a systolic blood pressure that is less than the fifth
TERTIARY ASSESSMENT percentile for age:
The tertiary assessment refers to ancillary studies • <50 mm Hg in term neonates (0 to 28 days)
that are obtained to identify the presence and • <70 mm Hg in in&nts (1 month to 12 months)
• <70 mm Hg + (2 X age in years) in children 1 1. Hypovo~ lhockis the most common type
to 10years ofshock in children and is caused by decreased

• <90 mm Hg in children > 10 years of age intravascular volume, which results in decreased
venous return and myocardial preload. Because
Eventually, cellular function deteriorates and of the reduction in myocardial preload. there is
multiorgan system dysfunction results. When this a resultant decrease in stroke volume, cardiac
process has caused irreparable functional loss in output, and blood pressure. Pulses are often
essential organs, a terminal or irreversible shock state weak, and capillary refill is prolonged in patients
is reached. It is important to note that shock evolves with this form of shock.
along a continuum, and a patient in decompensated 2 Diltributivethoc:k results.fromabnonnal vasomo-
.shock can progress to cardiopulmonary arrest in tor tone with reduced systemic vascular resistance
minutes. Emphasis should be placed on recognizing and abnormal distribution of blood circulatory
impending .shock in its early stages and initiating volwne. Because of peripheral pooling of blood,
treatment to prevent deterioration. preload is reduced, causing a decrease in stroke
Shock can be categorized into hypovolemic, car- volume, cardiac output. and blood pressure. The
diogenic, distributive, and obstructive types. Specific reduction in both systemic vascular resistance
etiologies are outlined in Table 20-5. and cardiac output leads to severe hypotension.
• Septic shock, the most common cause ofdis-
tributive shock, results when a local or systemic
TABLE 21.!1. Etiology of Shock infuction cawes cardiovucular dyafunction. The
!#lyptMJitNnlc early, oompensated stage ofseptic shock (often
!Water and electrolyte loul!!l (diarrhea. emesis) referred to as "warm• shock) is characterized
[ Inadequate fluld intake
by reduced systemic vascular reslstana! and
normal to increased cardiac output. Patients
~ Osmotic diuresis (e.f., diabetic ketoAcidosis) may have bounding pulses, warm extremities
~ Hemorrhap (intemal or external)
I:=-.. ("thhr<l ........ "' aplllaey- I

with flash capillary refill (< 1 aemnd), and a
widened pulse pressure. In the late, decom-
pensated phase, there is hypovolemia from
third spacing and decreased cardiac output
~~ ! due to myocardial depression. Signs include
j Congenital heart cllseue ! de1ayed capillary re6ll, mottled extremities,
i:::""hart......
j Cardiomyopathlel (inherited or acquired abnormality I
I
and diminished pulses. Early identification of
sepsis and adminlstration ofbroad--spectrurn
antibiotics and intravenous .Ouids is aitical.
l ofventricular function) i • Anaphylacti.c mock is a form ofdistributive
shock caused by a hypersensitivity reaction to
~M~ ~ an allergen. It is a rapidly developing illness, and
IMyocardial traumatic: Injury ! may involve one or more organ systems (skin,
IPoisoning or drug toxicity (e.g., ~blocker, calcium I mucosal tissue, respiratory or gastrointestinal
! clwmel blocker lngeation, chemotherapy) i symptoms) in addition to hypotension. A cu-
i Distributiw I taneous reaction, such as urtlc:arla, is present
i Septic shock I in more than 90CJ6 of cases of anaphylaxis.
!Anaphylaxia ! • NeurcJiellic (lpiul) lhock occurs after injury
to the spinal cord or central nervous system
!Neurologic injury (head or spinal cord) ! (CNS) injury and is rare. Patients present
~~ l with bradycardia because of disruption ofthe
iCardiac tamponade ! sympathetic nervous system. in contrast to
ITension pneumothorax I the tachycardia seen in other forms of ~hock.
3. Cardiopaic: lhoc:k is the result of Mpump failure"
IMauive pulmonary embolllln l and is much less common in children. Inade-
!Congmital heart lealons with ductal-dependent I quate stroke volume, whether caused by poor
it,.,l)'ltemlc
..
blood flow !
,.,..,,.,,.,,,,..,.,,,.,.,,., ,.,.,., ,.,,,,,,.,,,._ ,,,,, , ,,.,,_ ,,,,,,,,,,,,,, ,,,,,,, ,,,,,,,noooon'"ooooooooooo.,oooooooooooooooooo contractility (e.g., cardiomyopathy, myocardial
ischemia) or due to arrhythmia, results in di- Provider MAnual. Table 20-6 describes the
minished cardiac output and hypotension. In indications and effects of the medications.
the patient with tachyarrhythmias (supraven- 4. Obltructive tho<:k is a condition of impaired
tricular tachycardia. ventricular tachycardia), cardiac output caused by physical obstruction
treatment is based on whether the patient is of blood flow into or out of the heart. Cardiac
hemodynamically stable or unstable. tamponade and tension pneumothorax cause
Suprtlllentricular Tachycardia (SVT): narrow obstruction ofblood flow into the heart, leading
QRS complex {:S0.09 second) to decreased preloact stroke volume. and cardiac
• Hemodynamically stable: Vagal maneuvers, output. Pulmonaryembol.i&m and congenital heart
adenosine disease lesions with ductal-dependent systemic
• Hemodynamically unstable or SVT refractory blood flow produce obstruction of blood flow
to medications: Synchronized cardioversion out of the heart, resulting in decreased stroke
at 0.5 to 1 }/kg; if initial cardioversion is volume and cardiac output.
Ulllluccessful increase to 2 J/kg. Sedate if
possible before cardioversion, but do not CLINICAL MANIFESTATIONS
delay cardioversion. HistDry and Physical Examination
Ventricular TacJfycardLa (VT) or Ventricular During stabilization, the clinician should attempt to
Fibrillation (VF): wide QRS complex (>0.09 identify the potential etiology ofshock on the basis
second) of the patient's history, exam, and initial studies.
• Hemodynamically stable VT: Consider adenos- The history obtained should focus on identifying
ine. Treathypomapesemia and hypokalemia. potential causes of shock. Historical clues that
Administer amiodarone or procainamide. suggest hypovolemic shock are a history of fluid
Multiple antiarrhythmic drugs should not be loss (from vomiting, diarrhea, polyuria, burns, or
used sJmultaneously because of the risk of poor oral intake) or blood loss (from trauma or
conduction abnormalities and hypotension. internal bleeding). Septic shock should be consid-
If medication therapy does not convert VT, ered in a patient who is immunocompromiaed, has
synchronized cardioversion at 0.5 to 1 Jlkg signs or symptoms of an infection. fever {temp ~
may be utilized; if initial cardioversion is 38SC), hypothermia, (temp < 36•C) or purpura.
unsuccessful. Increase to 2 J/kg. Distributive shock may be present if there is a
• VF, pulseless VT: Provide CPR until the toxic ingestion. exposure to an allergen. or head or
defibrilla.tor is ready to deliver unsynchro- spinal cord injury. A patient with congenital heart
nized cardioversion at 2 Jlkg followed by an disease, arrhythmia, or exposure to cardiotoxic
immediate reiUIDption ofCPR for 2 minutes. medications (such as chemotherapeutic agents)
If a shockable rhythm persists, shock again may have cardiogenic shock.
at 4 J/kg. Administer epinephrine 0.01 mg/ aose monitorJns of vital signs and perfusion is
kg every 3 to 5 minutes. critical in the diagnosis and management ofchildren
Patient:J with asystole or pulseless electri- with shock. In early septic shock, vasodilation, warm
cal activity should receive 2 minutes of CPR, extremities, tachycardia, a widened pulse pressure,
followed by a repeat rhythm and pulse check and adequate urine output may be seen. In contrast,
and epinephrine every 3 to 5 minutes. It is physical exam findings of hypovolemic, cardiogenic,
important to consider the reversible causes of and uncompensated septic shock include vasoconstric·
pulseless arrest in children (the "Hs and Ts•). tion, tachycardia, cold extremities, poor peripheral
They include hypovolemia, hypoxia, hydrogen pulses, dela~d capillary refill. altered consciousness,
ion (acidosiJ), hypoglycemia, hypo/hyperka- ileus, and oliguria. Monitoring vital sign trends over
lemia, hypothermia; tension pneumothorax. time is important to detect worsening trends in
tamponade (cardiac), toxins, and thrombosis hemodynamic parameters early.
(pulmonary or coronary).
A full discussion ofdrug physiology, indica- DIAGNOSTIC EYALUAnON
tions, dosage, route of administration, effects, All patients with shock should be placed on contin-
and side effects can be found in the American uous cardiac monitor and have frequent rea.uess-
Academy of Pediatrics and American Heart ment of blood pressure and perfusion. The degree
Association Pediatric Advanced Lifo Support of tachycardia .is the best determinant ofthe level of
TABLE 20.L Drugs Used in Pediabic cardiorespiratory Resuscitation

!Drill .ldDn
!-- AdeDOilne Jl:lmulms reeepton in the heart and C8llleS

temporary atrioventricula node conduction block and
interrupta reentry clrcuit:a that Involve the AV node.
Amiodarone blocb Na. K. and Ca channels and
~~
Atrial (refractory SVT) and
ventricular arrhytluniaA ~recepton in the myocardium. aa well u C£- and~
(refractory VF, refractory receptor& in the vascular periphery. Amiodaron.e slows
puJael.eu VT, hemodynamically AY conduction, prolonga the AV refractory period and
atableVT) QT interval, and alows ventricular conduction (widena
1-
!Calcium (calcium
: gluconate or
Bradycardia and AV block
Hypocalcemia, hyperkalemia,
hypermagnesemia, and cal.clum
the QRS complex).
Atropine Ia a parasympatholytic drug that Increases
heart rate, conduction through the AV node, and
cardiac output by blocking vagal Jl:lmulatlon.
Routine administration in cardiac arrest provides no
benefit. Calclum increases myocardial contractility,
: calcium chloride) channel blocker overdose Increases ventricular exdtablllty, and increases
conduction velocity through the myocardium.
IDextrote (Jlucose) Hypogi)UIIlia Increases blood glucose lewL
l...... hrine"
Asystole, bradycardia, pulselesa
arreat, VTNF, ahock
The a--adrenergic-mediated vasoconstriction of
epinephrine increases systemic vascular resistance,
aortic diastolic pressure. and coronary perfusion.
It also increases chronotropy and inotropy through
.fJt--adrenergic receptor stimulation. The increased
heart rate and stroke volume increase cardiac output.
I The increased cardiac output and systemic vascular
l~
realat:ance increase blood pre.taure.
Pulseleu VTNF, VT with pulse Lidoaaine decreues ventricular Mltomatidtyand
,_
suppresses wntricular arrbyt:luniaa. Not as ef&diw as
I amiodarone to prodiKle return ofspontaneous circu1ation
or survmu tD hospital admJMion after VF arrest
SVT, atrial flu~ YT (with Procainamicle prolongs the refractory period of
pulses) the atria and ventricles and decreases conduction
velocities in the atrium, bundle of His, and ventricle.
:Sadrum- Severe refractory metabolic

acldosia and/or hyperblemia,
sodium channel blocker overdose
Routine adminlatration il not recommended In cardiac
arrest. Sodium bicarbonate Increases blood pH.
!
!
! (e.g.. tricyclk: antideprelllant)
: •Drugs thai: can be given by the endotracheal tube Include lidocaine, atropine, naloxone, and eplnephrtne.
I
i Abbr&viations: AV, atriovent~cular; SVT, supraventricular tachycardia; VF, ventricular fibrillation; VT, wntricutar lac:tlycardia. !
ioooooooooo•oooooo•oooooo•ooooo•o""""""''''''' ''''''"''''''"""''''"""'''"'''''''''''''''''''''''''''''''''''''''''''''"''''''''"''"""''''''''''''''''''''''''''''''''''''""'"'''''"'"'"'"" " ' " " ' ' '' ' ' ' ' ' ' ' ' " " ' " " ' ' '' '''''''''''''''"''''''"'' ' ' '''"''''''''''''''"'' ' ' 'uoooooo•ooi
intravascular depletion or vasomotor abnormality. TREATMENT

Hypotension is a late finding and occurs only after The treatment of shock is aimed at maintaining
40% to 45% of the intravascular volume has been perfusion of critical vascular beds (coronary, cere-
depleted. Diagnostic wts are obtained on the basis bral, hepatic, renal) and preventing or correcting
ofthe suspected etiology of shock. In a patient with metabolic abnormalities arising from cellular hy-
suspected sepsis, labs including blood gas, complete poperfusion. All patients in shock should receive
blood count, lactate, coagulation studies, electrolytes, supplemental oxygen as a part oftheir initial therapy
kidney and liver function tests, and blood and urine to maximize oxygen delivery to tissues, regardless
cultures should be obtained. Radiologic studies to help ofoxygen saturation. Correcting metabolic acidosis
determine the source ofinfection may be indicated. results in better cellular function. better myocardial
performance, and reduced systemic and puhnonary and it should be presumed that multiple injuries are
vascular resistance. Additional treatment is based present until proven otherwise.
on the underlying etiology of shock.
Hypovolemic shock is treated with intravenous HISTORY AND PHYSICAL EXAMINAnON
fluid resuscitation with normal saline or lactated The priorities ofassessing children who are seriously
Rlnger's solution administered in 20 mLJkg boluses injured should follow the ABCDEs of a trauma
up to (and in some cases beyond) a total of 60 mLI evaluation. Howeve~; because of their size, develop-
kg, until hemodynamic status normalizes. If hypo- mental immaturity, larger head-to-body mass ratio,
tension is caused by hemorrhage, gaining control of and unique physiology, the causes and mechanisms
the hemorrhage and volume resuscitation with type of injury in children can vary widely. Most serious
0-negative or cros~matched blood is vital. pediatric injuries are caused by blunt trauma. often
Septic lhock has a high morbidity and mortality involving the brain. Apnea, hypoventilation, and
that can be reduced with early recognition and rapid hypoxia are five times more common than hypo-
initiation of treatment. Guidelines for treatment of volemia in seriously injured children.
sepsis include early Jnitiation of intravenous fluid Children have a smaller body mass, less fat and
resuscitation and administration of broad-spectrum. connective tissue, and a proportionately larger
antibiotics within 60 minutes. Intravenous fluids are head. These physiologic characteristics result in
given in rapid 20 mLJkg boluses, up to (or beyond) 60 greater force transmission to internal organs and
mLikg as needed. In fluid refractory shock, vasopressors a high frequency of intraabdominal and traumatic
should be initiated. ideallywithin60 minutes. Clinical brain injuries. Conversely, the child's skeleton is
monitoring for improvement in pulses, perfusion. incompletely calcified and more elastic than that
mental status, urine output. as well as heart rate and of an adult. Internal injuries may be present even
blood pressure should guide management. when fractures are not.
In dUtributive shock caused by anaphylaxis,
intram115CUlar epinephrine, intravenous fluid re- COMMON MECHANISMS AND PATTERNS OF
suscitation. steroids, and antihistamines are given. INJURY
Rarely. continuous infusion vasopressors are needed Although appropria~ car seat use drastically reduces
for intractable hypotension with anaphylaxis. the risk of injury and death, children involved in
In c:arcliopnic lh.ock resulting from a congenital motor vehicle accidents can still suffer serious
heart defect, inotropic support may be indicated injuries. Improperly restrained children may have
awaiting corrective surgery or catheter-based in- chest and abdominal injuries, as well as lower
terventional procedure (e.g., balloon angioplasty or spine fractures as a result of forward flexion of the
valvuloplasty, balloon atrial septostomy). Neonates spine against the lap belt, with compression of the
with congenital cardiac disease with ductal-dependent lumbar vertebrae. Unrestrained children are at an
systemic blood flow (e.g., critical coarctation of the increased risk for multiple Injuries, Including head
aorta) should be started on prostaglandin (PGE1) and neck injuries.
therapy to maintain ductal patency and systemic Children struck by a motor vehicle have different
blood flow. Pericardia! tamponade is treated by injury pattema than adults. Although adults may be
pericardiocentesis. Pneumothorax is treated by struck on the lower extremities, children are shorter,
needle or chest tube decompression, with removal and the vehicle's bumper may strike the head, chest.
of air from the pleural space. or abdomen, causing multiple injuries. Bike helmets
can greatly reduce the number ofserious head injuries
in children involved in bicycle accidents. Helmeted
PEDIATRIC TRAUMA children can still suffer upper extremity fractures,
Unintentional injuries are the most significantcause lacerations, and internal abdominal injuries should
of mol'bidity and mortality in children and adoles- their abdomen strike the handlebars.
cents. Timely evaluation and treatment of traumatic Children who fall from a height can suffer a
injuries may limit disability and preserve the quality multitude of injw'ies depending on the height of
of life. Motor vehicle-associated injuries are the the tan and the surface of impact. With a fall from
most common cause of death in children ofall ages, a low height, children often auffer upper extremity
whether the child is a passenger or is struck by a mov- injuries because they brace themselves against im-
ing vehicle. Blunt injury mechanisms predominate, pact by extending their arms. Children falling from
a moderate to high height can sustain head and trauma are typically epidural or subdural (Table 20·7;
neck injuries, as well as fractures of the upper and Fig. 20-3). Some severe brain injuries may remit in
lower extremities. subarachnoid injury and bleeding into the cerebro-
spinal fluid (CSF).
DIAGNDSnC EVALUATION
Injured children should ideally be evaluated and CL.INICAL MANIFESTATIONS
managed at a specialized facility with experienced HlsiDry
personnel, specialized equipment. and resources for Severe brain injury may occur in the absence ofexternal
pediatric patient s. Critically injured children should .signs of trauma. A severe mechanism of trauma is a
be transferred to a Level One Pediatric Trauma risk factor for intracranial injury. Trauma to the sides
Center as soon as they are stab111zed. or back of the head is associated with a higher rate of
skull fracture and intracranial bleeding because the
temporal, parietal, and occipital bones are weaker than
HEAD INJURIES the frontal bone ofthe skull. Recurrent vomiting, severe
headache, and mental st:atus changes are concerning
Head injuries are one of the most common reasons
for increased intracranial pressure. Confusion, loss of
pediatric patients present to the emergency depart- co118ciousness, amnesia, seizures, and visual impairment
ment. Head injuries in children often result from
may also be present with signlftcant inJury.
motor vehicle accidents, bicycle mishaps, falls, or
child abuse. Males are twice as likely as females to Physical Examination
sustain significant head trauma. Recovery from a head It is cruclal to get an accurate neurologic exam and
injury depends on the severity of the initial injury and to assess the child's mental status including a GCS.
factors contributing to secondary neuronal injury, In head trauma, a GCS of 13 to 15 is indicative of
such aa hypotension and hypoxia. Severe head injury mild traumatic brain injury, 9 to 12 moderate injury,
may be associated with death, functional limitations, and 8 or less severe injury. Signs and symptoms ofa
behaviotal changes, or memory problems. serious head injury include lethargy. decreased level
Head i.njlll'les include concussions, cerebral of consciousness, behavioral changes, persistent
contusions, diffuse axonal injury, and intracranial vomiting, abnormal pupil exam, and posturing.
hemorrhage. Cerebral contusions represent direct These symptoms may occur because of elevated
injury to the brain itself. Diffuse axonal injury results intracranial pressure, which can lead to herniation
from shearing forces on the white matter of the brain and death. if untreated. The combination of bra-
that occur with rapid deceleration of the head. It is dyt:ardia, hypertension, and irregular respirations,
frequently followed by cerebral edema, further dis- known as Cushing's triad is indicative of increased
ruption of blood flow, inflammation, and ischemia. intracranial pressure. Patients with Cushing's triad
Intracranial hemorrhages that occur secondary to are at risk for imminent herniation. Cranial nerve
TABLE 20.7. Differentiating Acute Subdural and Epidural Bleeds

IIMiral Ep._..
i
ILocation Between the dura and arachnoid layel'll Between the skull and the dura
: Symmetry Usually bilateral Usually unilateral
IEtiology Rupture of bridging cortical veins or
aubdural veina
Rupture of middle meningeal artery or ftin
I1YPical injury Direct trauma or lhaking Direct trauma in the temporal area
ICaoJdoomeu Intact but altered lmpalred-ludd·tmpaired

j Common associated Seizure&, retinal helllOl'l'bages lpailateral pupillary dilation. papilledema,
1findings contralateral hemiparais
i
1 Appearance on cr Crescentic Biconcave
! Prognosia High morbidity; low mortality High mortallty; low m.otbidity
! Complicationa Herniation Skull fracture; uncal herniation
! Abbrevtatlon: cr, computed tomography.
: . , , , , . , , , . , , " " " ' ' ' ' " " ' oooooooooooooo• •ooooooO ooooooO , . , , , ,. _, , , . , , • •• • • •• • o ooooou ooooooo oooooonoooonnoooonoooooooooooooooooooo' " • •••••• • • • • •• • • • • • • • • • • • • • • " " ' ' ' " " " ' " " ' " ' " " " ' ' " " " ' " " " " "' ' " "" " ' ' ' ' ' ' ' '" " '-
1
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a history ofloss ofconsciousness, persistent vomit-

ing, severe headache, or severe mechanism ofinjury
should prompt close observation or head imaging.
Noncontrast head computed tomography (CT) is
the preferred mode ofimaging. The primary goal of
imagingis to identify intracran1al bleeding (subdural
or epidural hematoma, or subaracluwid bleeding).
Children who do not meet the criteria listed earlier
and have a normal neurologic exam can be safely
observed without obtaining head .imaging. Cervical
FIGURE 211-3. Subdural (A) and epidural brain spine radiographs are .Indicated for any patient with
-~-~-~-~~.~.~-~.J~>.:.... .............. ...... . .. . ............................................................... significant head trauma or focal spln.al tenderness.
function, especially pupU size and reactivity, should TREATMENT

be assessed. Unequal pupils may be as sign of brain Specific treatment depends on the type and severity
herniation, as the brain tissue is pushed below the of the injury. Patients with suspected head or neck
tentorium, exerting pressure on the third cranial injury should have the cervical spine immobilized
nerve. Papilledema may be evident on visualization in the field. Children with a GCS of less than 8 fol-
of the fundus. Serial neurologic examinations track lowing head trauma are at risk for severe morbidity
evolving lesions and response to interventions. and death and require immediate intervention,
It is aJso important to look for signs ofa basilar skull including intubation. Early consultation with a
fracture on physical exam. incluclin8 hemotympanwn. pediatric neurosurgeon is necessary if considering
CSF rhinorrhea or otorrhea, signlflcant bruising invasive intracranial pressure monitoring or surgical
around the eyes (raccoon eyes), or postauricular intervention in patients with severe head trauma. It
bruising (Battle's sign). Palpation ofa depression or is important to remember that in contrast to older
step-off on the skull is concerning for a skull fracture. children and adults, infanta have open fontanelles and
Infantswith open fontanelles and cranial sutures may more potential spaoe in their skull cavity. Therefore,
tolerate rises in intracranial pressure better than older they may become hypovolemic and hypotensive from
chlldren. and may have more subtle symptoms. Look intracranial hemorrhage.
for bulging of the anterior fontanelle and widened In patients with traumatic brain injuries, it is
cranial sutures in addition to reduced mental status, imperative to prevent hypoxia and hypotension.
vomiting, or Cushing's triad. The combination of hypoxia and hypovolemia can
Almost all children who present with intracranial result in significantly reduced oxygen delivery to
hemorrhage requiring neurosurgical intervention the brain with devastating sequelae. Efforts should
will manifest aigniftca:nt symptoms or have abnormal be focused on assuring adequate CNS perfusion
exam findings within the first 4 to 6 hours after the and oxygenation. The goal is to optimize cerebral
initial injury. perfusion pressure, which is the difference between
mean arterial pressure and intracranial pressure.
DIAGNOSTIC EVALUATION Cerebral edema is the most significant complication
When evaluating a patient with a head injury, the in the acute period. Normal oxygenation, normogly-
question of head imaging typically arises. In patients cemia, hyperosmolarity, and elevation of the head of
less than 2 years of age, head imaging is indicated if the bed are recommended to minimize intracranial
they h~ a GCS ofless than 15, signs ofaltered mental hypertension and secondary brain injury. Mild hy-
status, or a palpable skull fracture. In these young perventilation, which reduces cerebral blood flow, is
patients, an occipital, parietal. or temporal region used to reduce intracranial pressure during the initial
scalp hematoma, losa ofoonscioum.esa for more than phase of therapy. Patients with evidence ofimpending
5 seconds, severe mechanism ofinjury, or not acting herniation should be hyperventilated and given an
themselves according to their parent would indicate osmotic agent such as mannitol and/or hypertnnic
close observation or head imaging. For children over (3%) saline to decrease int:racranial pressure acutely.
2 years ofage, imaging is recommended for patients Patients with evidence of significant cerebral edema
with a GCS ofless than 15, altered mental status, or may require intracranial pressure monitoring with a
signs ofa basilar skull fracture. In these older patients, subdural bolt or intraventricular catheter.
Patients with a known intracranial bleed and/or an the abdomen, viscera that extend below the costal
abnormal GCS should be admitted to the hospital for margins, and relatively weak abdominal muscles.
further observation, serial neurologic examinations, Patients with blunt abdominal injuries who are
and additional interventions as needed. conscious are often frightened both by the events
surrounding their injury and by their presence in
the emergency department. Obtaining an accurate
CERVICAL SPINE INJURIES examination of the abdomen can, therefore, be dif~
In injured children at r.i.ak for neck injury, careful ficult. The .IIW'face of the abdomen must be carefully
attention should be paid to maintaining immobilization inspected fur bruising, especiaUy for characteristic
of the cervical spine. Children should be placed in patterns caused by a car seat belt or bicycle han~
an approprlatel.y sized semirigid collar. The cervical dlebars. An assessment must be made for signs of
spine should be immobilized at all times, including significant injury, such as a rigid abdomen or invol~
during intubation. untary guarding. Children who have sustained blunt
In patients who have midline cervical spine ten- abdominal trauma and are hypotensive should be
derness to palpation or Umitation in range of motion rapidly assessed and resuscitated with intravenous
of the neck, cervical spine x~rays should be obtained crystalloid fluid boluses as well as packed red blood
to evaluate for fracture or subluxation. Ifx~rays are cells. Ifhypotension per&ists or there is concern for a
normal but pain and llrnltation in range of motion hollow viscus injury, emergency operative exploration
continue, patients may either undergo imaging ofthe may be indicated. The use of Focused Assessment
cervical spine (CT or magnetic resonance imaging Sonography in Trauma to identify intraabdominal or
[MRI]) or remain in the semirigid collar for 1 to 2 pericardial blood. although helpful in the management
weeks until repeat evaluation is done by a neuro- of the adult trauma patient, has unclear utility in the
surgeon for bony or llgamentous injury. Clilldren pediatric patient. In the hemodynamically stable
under 8 years of age are at risk for spinal cord injury child with significant abdominal pain, a contrast CT
without radiographic abnormality (SCIWORA). In of the abdomen and pelvis is indicated. CT scan can
SCIWORA, abnormalities may be seen on MRI that identify solid organ injuries, which require operative
are not visible on x-ray imaging. repair far less frequently than equivalent injuries in
adults. Less easily identified byCT scan. but equally
important to consider, are injuries to the pancreas
THORACIC INJURIES and small intestine (particularly the duodenum).
Penetrating trawna to the thorax is less common in Rupture of a hollow viscus requires immediate
children than in adults. Thoracic injury may result operative intervention. Conversely, a hematoma of
from blunt trauma to the chest. Careful auscultation the duodenum can present with delayed symptoms
of the lungs may reveal decreased or absent breath of abdominal pain and vomiting, and may not be
sounds, suggesting the presence ofa pneumothorax, recognized on initial imaging studies.
hemothorax, or pulmonary contusion. Muffled heart For children who have suspected blunt abdominal
sounds are characteristic of a pericardial effusion. trauma but no significant pain, laboratory screening
Tension pneumothorax puts pressure on intrathoracic studies are used in order to reduce the exposure to
structures, causing respiratory distress, deviation ionizing radiation of CT. The presence ofanemia on
of mediastinal structures to the opposite side, o~ complete blood count (hematocrit < 309(,), hematuria
structive shock, and rapid decompensation. During on urinalysis (> 5 red blood cells per high-power
the initial assessment of children with evidence of field), or elevated liver transaminase& (serum as~
thoracic injury, a chest x~ray should be obtained partate aminotransferase concentration >200 U/1
to evaluate for a pneumothorax. hemothorax. or a or serum alanine aminotransferase concentration
widened mediastinum (suggesting aortic dissection) > 125 U/L) increases the odds of an intraabdominal
before allowing the child to leave the resuscitation injury on subsequent CT scan. Children with any
area for additional studies, such as CT scan or MRI. of these abnormal lab values should be assessed
by contrast CT scan of the abdomen and pelvis.
Elevated lipase is not specific for intraabdominal
ABDOMINAL INJURIES injury in children. Of note, children with a femur
Children are vulnerable to blunt abdominal trauma fracture have increased odds of also having an
because of the small anterior- posterior diameter of intraabdominal injury.
l>i§! 3tii§ •I• ;f;!I!UJ ittl AA.'.I§ ;te 3:(3 Ifi indicated in patienu with concussion, but neuroim-
aging may be considered in those with high-risk head
CONCUSSION trauma signs and symptoms, as discussed previously.
Concus.sion is a type of traumatic brain injury caused Patients with persistent symptoms are monitored
by biomechanical forces. It may remlt from either with serial neuropsychiatric testing to document
a direct trauma to the head or significant trauma improvement/resolution of impairment.
elsewhere on the body with the force tran&mitmd
to the head. Structural changes are absent on head TREATMENT
i.mqing (CT or MRI). Patients with concussions may The cornerstones of treatment are physical and
improve within hours, or may have residual symp- cognitive rest. The exact amount and duration of
toms for months to years. The severity and duration rest has not yet been well defined in the literature.
of symptoms cannot be accurately predicted at the Some experts recommend complete rest until
time of initial evaluation. The developing brains of symptoms resolve entirely. Others recommend a
children and adolescents may be at an increased risk brief period of rest followed by gradual return to
for more severe or lingering impairment. cognitive and physical activities. It is important to
remember that activities requiring concentration
EPIDEMIOLOGY such as reading, doing homework, and looking at
Among sports, football has the highest rate of con- screens (computers, television, phones) may worsen
cussion, followed by lee hockey, soccer. and lacrosse. symptoms.
The use of helmets has been shown to reduce the risk "Return to pla~ and "return to learn" recommen-
ofconcussion in some sports, but does not eliminate dations are guided by symptoms as well as the severity
the risk entirely. ofthe Initial impairment. A stepwise increase in both
physical and cognitive exertion is recommended,
CLINICAL MANIFESTATIONS with a worsening ofsymptoms resulting in increased
History restriction. Most athletes recover to baseline within
Signs and symptoms ofconcussion may be physical 2 weeks of the injury. Athletes who return to play
(headache, nausea/vomiting, problems with balance too soon are at risk for Second Impact Syndrome,
or vision); cognitive (memory impairment, difficulty which may result in severe neurologic morbidity
con<lentrating, confusion, slowed reaction times, and caused by sustaining a second concussion while still
feeling •out of it" mentally); emotional (irritability, symptomatic from a first.
depression); and sleep/wakefulness disruptions
(somnolence or drowsiness). Amnesia for events DROWNING
immediately before and after the injury is common.
Loss of comciousness is less common, but when The World Health Organization defines drowning
prolonged (over 5 minutes), it may represent more "the process of experi.endng respiratory impairment
severe neurologic involvement from submersion/immersion in liquid~ Use of the
terms "near drowning'" and "dry drowning'" is no
Physical Exam longer recommended.
In a patient with suspected head trauma, the exam-
iner should look for evidence of external trawna., EPIDEMIOLOGY
including scalp lacerations, contusions, skull depres- Drowning is a frequent cause of morbidity and
sions indicating possible depressed skull fracture, mortality in the pediatric population. Approximately
hemotympanum. and CSF drainage from the ears/ 1,000 children under 18 years of age died because of
nose. Vision shouldbe evaluated and balance assessed. drowning in the United States in 2016.
A complete neurologic examination is essential.
RISK FACTORS
DIAGNOSTIC EVALUATION Those at the highest risk for drowning are toddlers
All children with suspected concussion should be and male adolescents. Risk factors for drowning
removed from sport play. There are several brief are male sex, less than 14 years of age, alcohol
neuropsychological tests that can be used on the use, low income, poor education, rural residency,
sideline or in the locker room to assess attention and a history of epilepsy, risky behavior, and a lack of
memory function. Acute CT or MRI is not routinely supervision.
Young children must be supervised at all times direct contact with ahotaurface (iron, stove). Flame
when in a bathtub or around pools or other bodies of burns are less frequent but result in a high mortality
water. Four-sided fencing with locked gates around rate because of associated smoke inhalation injury.
pools is recommended. Lifeguards, the use of personal Electrical bums may occur if a young child puts
flotation devices, CPR training. and swimming and conductive material into a wall socket or an infant
water-survival skills training in young children may sucks or bites on the connected end of an extension
lower drowning rates. cord. Chemical burns result from exposure to strong
acidic or alkaline material.
During drowning. water is aspirated into the airways, RISK FACTORS
which leads to coughing with or without laryngo- Boys and chlldren younger than 4 years of age, par-
spasm. Ifa patient is not rescued quickly, aspiration ticularly those with disabilities, are at the greatest
continues, leading to hypoxemia, loss ofconscious- risk for bum injury. In pediatric patients with bums,
ness and apnea, and finally cardiac dysrhythmias and physical child abuse must be considered. Scald burns
death. The drowning process occurs over a span of that end in demarcated lines without associated
seconds to a few minutes. splash marks suggest abuse. Contact burns caused
In rescued patients, the clinical picture is pri- by cigarettes are the most common burn injury in
marily determined by the amount ofwater that was abused ch1ldren. Patterned bum injuries consistent
aspirated. In patients with cardiac arrest caused by with abuse can be seen in Figure 20-4.
drowning, early resuscitation is crucial. A poor prog-
nosis is associated with drowning in warm water, a CLINICAL MANIFESTATIONS
prolonged time ofsubmersion, or a prolonged time Clinical severity of burns is based on the affected
to adequate resuscitation. Drowning in cold water body surface area and depth of injury. In chlldren,
leads to hypothermia and can be protective. the total body surface area affected can be calculated
using the .,rule of 9s• (Fig. 20-5). Burna are divided
TREATMENT into three categories: superficial, partial thickness,
All patients with a history of drowning should be and full thickness. Superficial burna involve only the
evaluated with a chest radiograph and a blood gas. epidermis. In these burns, the skin is red. dry, and
Supplemental oxygen should be provided to maintain tender, but there are no blisters. Superfi.dal burns
oxygen saturations within a normal range (>92%). heal in about a week with no residual scarring.
Even well-appearing patients are typically admitted to Partial-thickness burns are divided into superfidal
ensure that oxygen Jaturation remains stable. Those and deep partial-thickness bums. Superficial par-
with severe hypoxemia and mental status changes tial-thickness burna extend into the superficial der-
require aggressive respiratory and circulatory support mis. These burns are painful and form blisters. With
proper wound care, these wounds heal within 2 to 3
weeks. Deep partial-thickness burns involve most of
BURNS the dermis. These burns may or may not be painful.
In the United States, burns are an important cause They result in significant scarring and contractures.
of nonfatal injury in children under 4 years of age
and fatal injury in children under 14 years of age. A
significant portion of burns are the result of chlld Cigarette Immersion scald
physical abuse. Fortunately, the great majority of Lightbulb
bums are not life-threatening. Patienbii who survive
severe burna are often left with significant scarring
and disability.
•
EPIDEMIOLOGY
In children, the majority of bums are scald inju-
ries, resulting from contact with hot liquids. These
may occur in association with spillage of hot food
Iron Curling iron
or drinks or because of bathing injuries. Contact
burns are the next most common and result from -~~-~~-~~--~--~-~-.!~!~.~--~-~~-~-~-~-~-~~~~--~~~-~~~~:.
lnhlnt
Adult
FIGURE ZU·S. Rule of 9s.
Skin grafting is often required. Pull-thickness bums extensive (more than 10~ of the total body surface
extend into the subcutaneous tissue. These burns are area), or that involve the face, hands, feet, perineum.
not painful because of the loss of sensory nervous genitalia, or major joints benefit from receiving care
tissue, and feel leathery to the touch. Significant at a dedicated burn center.
scarring and contractures should be expected.
TREAtMENT CHILD ABUSE AND NEGLECT

Small, superficial burns often require only local wound Child abuse is the physical, sexual, or emotional
care. Burned areas should be placed immediately in maltreatment of a child. Child abuse is divided
lukewarm water or covered with. wet gauze or cloth. into physical chlld abuse and sexual chlld abuse. In
Minor burns respond to gentle cleansing, silver addition, failure to provide a child with appropriate
sulfadiazine (an antimicrobial agent), and frequent food, clothing, medical care, schooling, and a .safe
dressing changes until reepithelialization occurs. environment constitutes neglect.
Theatment of more significant burns includes
appropriate management of airway, breathing. and EPIDEMIOLOGY
drculation, effective electrolyte and fluid therapy to Oilldrenin the tlrstyear oflife are at thehighestrisk for
account for increued fluid loss, specialized nutritional child abuse or neglert. Seventy· five percent ofabuse.
support, prewntion of infection. pain management, related child fatalities occur in children under 3 years
excision and skin grafting to optimize cosmetic ofage. A significant portion ofemergency room injury
recovery, and early mobility and rehabilitation. visits involving children younger than 5 years of age
Children with bums that are severe, circumferential. result from abuse. The most frequent perpetrators are
themot:heJ;&ther. ormale partner ofa parent. Reports Physical Examlnl'llan

ofabuse that increase in number and severityofinjury A child who is neglected may have poor growth. With
over time are highly correlatedwith increased mortality. physical injury, the location or pattern ofinjury may
Reports ofchild sexual abuse are on the rise. The strongly suggest abuse (Fig. 20-6). Bruises, burns,
abuse may occur at any age. Relatives and family or lacerations in different stages of healing occur
acqualntances account for most cases; molestation in chronic or repeated abuse. Bruises associated
by strangers is uncommon. In the vast majority of with normal play are often located over the shins
reports, the victims are female and the abusers are and elbows. Brui5es on the torso, neck, or ean in
stepfathers, fathers, or other male family members. a child less than 4 yean old, or any bruising on a
Male sexual abuse is likely underrecognized. nonambulatory child are extremely suspicious for
Neglect of infants and children results in more inflicted injury. Practitioners should also bevipant
deaths than physicaland sexual abuse combined, and in evaluating for abusive head trauma (previously
children may present with concern for failure to~- known as shaken baby syndrome), which often
results from vigorous shaking of an infant. These
RISK FACTORS infants and children may present with vomiting,
Abuse and neglect occur at all socioeconomic levels fussiness, or abnormal movements. There should be
but are more prevalent among the poor. Children a low threshold to obtain head imaging. Intracranial
with special needs (developmental delay, cerebral (subdural) hemorrhage may be seen in child physical
palsy, prematurity, chronic illness) and those younger abuse as well as accidental head trauma. Retinal
than 3 years ofage are at particular risk. Having had hemorrhages are consistent with abuse. Falls from
Child Protective Services involvement in the past beds, changingtables, cribs, counters, or toilet seats
is predictive of future abuse. Caretakers who have do not cause the injuries seen in abusive head trauma.
themselves suffered abuse, have alcohol or substance
use disorders, or who are under extreme stress are DIAGNOSTIC EVALUATION
more likely to abuse or neglect children. A skeletal survey may reveal acute or healing frac-
tures from prior injuries that may not be evident
DIFFERENTlAL DIAGNOSIS on physical examination. Fractures that are highly
Cl.lnical providers should remember that the vast specific for abuse include bilateral fractures, bucket
majority ofcases ofsuspected abuse are subsequently handle fractures, metaphyseal chip fractures, and
subsmntiated by Olild Protective Services. Howevelo fractures of the posterior ribs, scapula, stemtun.
when consideringthe differential diagnosis, congenital spinous proce55e5, hands, or feet. Fractures that occur
dermal melanocytosi.s (previously referred to as Mon-
golian spot), which commonly occurs on the back or
buttodcs, should be differentiated from bruises. On rare
occasions, osteogenesis i.mperfect:a has been mistaken
fur abuse. Skin conditions such as bullOWI impetigo may Looped
mimic cigarette burns or other forms ofabuse. Otildren electrical cord Hairbrush
with extensive bruising should undergo coqulation
studies to rule out hematologic: abnormalities.
History
An injurythat is inamsineatwith the abd:edhiatoryor Coat hanger
cbild'a cleftlopmental ability, ahiltorythatchanps Board
owrtime, or a clelayln obtalnlas appropriate mecl-
ical care strongly suggests abuse. ABe-inappropriate
sexual behavior and knowledge are concerning for 3
~ ,--.
sexual abuse. VI.ctims ofphysical or sexual abuse may
act out by abusing others, attempting suici~ running
Belt Hand
away, orenpging in high-riskbehaviors. Children who Fist
Buckle
are abused are at an inaeased risk fur poor school
performance, low self-esteem. and depression.
in a nonambulatory infant or child are extremely EPIDEMIOLOGY

concerning lor child physical abuse. In children with The highest incidence of foreign body aspiration is
concerning findings on physical exam or skeletal noted in children less than 3 years of age. Food is
survey, head imaging evaluation for intracranial the most commonly aspirated foreign object, with
hemorrhage from abusive head trauma is typically frequent culprits being nuts, hot dogs, and hard candy.
warranted Small toys also pose an aspiration risk, especially to
When sexual abuse is suspected, rectal, oral, young children. Although the angle of the right main
vaginal, and urethral specimens should be examined stem bronchus in older children and adults favors
for Neisseria gono"hoeae, Chlamydia trachomatis, right-sided aspiration, children less than 10 years
and other sexually transmitted diseases. Other of age have more symmetric bronchial angles, and
studies include blood tests for syphllls and human aspiration may occur on either side.
immunodeficiency virus. It Is prudent to have the
exam lor suspected child sexual abuse completed DIFFERENTlAL DIAGNOSIS
by a practitioner who is trained to properly collect When an aspirated foreign object is in the upper
samples and maintain the Chain of Custody, in the airway, symptoms of stridor or drooling may mimic
event of legal action. It is also imperative that only upper airway infection (e.g., croup, retropharyngeal
a trained specialist interview the chlld who has dis- abscess). Patients with foreign body aspiration lower
closed abuse, as young children may be suggestible, in the tracheobronchial tree may present with cough.
making their true report difficult to obtain. unilateral wheezing, and focal decreased breath
sounds. Wheezing and respiratory distress may be
TREA'IMENTIPREVENTION mistaken lor asthma, and focal decreased breath
Health care workers are required by law to report sounds for pneumonia. Of note, with foreign body
any NJpiclon of child physical or sexual abuse or location distal to the carina, findings are localized
neglect to state protection agencies. Child Protective to one side of the chest only. Howeve~ the classic
Services should be notified immediately in cases of triad of cough. unilateral wheezing, and decreased
suspected abuse to ensure safe placement of the child breath sounds are not always present, and a high
and evaluation ofother children in the environment. level of suspicion should be maintained, especially
Family intervention programs that focus on social in a young child.
support, nursing staffvisits, and parenting sldlls are
being evaluated across the country in an attempt CLINICAL MANIFESTATIONS
to provide children with safer home environments. Patients may present acutely after an episode of
Pediatricians can aid in preventing child abuse by coughing and choking, or days to weeks after the
providing parents with realistic expectations for initial event, with no witnessed aspiration. Clinical
their child's development and behavior at each health presentation varies on the basis of the location of the
maintenance appointment. It is also important to foreign body in the respiratory tract (Table 20-8).
recognize when the famlly and/or caregiver experi- If obstruction to the involved bronchus is complete,
ences an acute crisis or social isolation. Referral for the chest radiograph may demonstrate atelectasis
supportive services may make a aignificant diffurence in the affected area of the lung, with deviation
in the home environment of the child. of the mediastinum toward that side with a large
area of involvement. A partial obstruction may
SELECTED MEDICAL EMERGENCIES occur, allowing air to enter the lung during in-
spiration, whereas obstruction during expiration
FOREIGN BODY ASPIRATION cau..es air trapping and hyperinflation (ball-valve
Children are at risk for foreign body aspiration because obstruction). In these cases, the inspiratory film
oftheir nablral curiosityand a toddler's tendency to put may appear normal, but the expiration radiograph
everything in 1he mouth. Aspiration is the accidental will show continued hyperinflation of the affected
inspiration of foreign material into the respiratory side, with possible mediastinal shift away from the
tract. Many aspirated objects or food particles are blockage (Fig. 20-7). In less obvious cases or in
i.mmediatcly expelled from the trachea by coughing. young children unable to comply with inspiratory/
Unfortunately, some foreign bodies can lodge in the expiratory radiographs, lateral decubitus chest
upper orlower respiratory tract, causing wrying de- films or fluoroscopy may detect subtle unilateral
grees of airway obstruction and respiratory distress. hyperinflation.
TABLI2G.B. Signs and Symptoms af Foreign Body Aspiration

!................,_. ...................,.....
I Total tracbeal obatruct:lon Acute uphyxia. severe retradlons with poor chea wall
movement. absent breatb.IOUDCII
l Extrathoradc airway, partial obstruction Inapiratory and expiratory stridor. retradions
!IDtrathoncic airway (trachea), partial Expiratm y wheezellltridor; frequently inlpirat.ory stridor- .. well
1 obstruction
!,, Main stem bronchw Unequal chest wall movement. hyperinflation on afi'ecred llde,
cough. unilateral expiratory wheeze
i Lobar/segmental bronchus
.
Decreased breath aoundJ over affected lobe, focal wheezing.

L......................................................................................................................~.~-~...................................................................................................................................................)
TREATMENT fill,].] S:lip! :):qtJ I:13·11: IN: I j ·P'J j: I
A child with suspected foreign body aspiration who
is actively coughing, crying, or speaking should be al- By definition, sudden unexplained infant death (SUID)
lowed to continue to try to expel the object on its own. is the unexpected death ofan infant less than 1 year
Ifthe airway is completely obstructed and the patient ofage for which the etiology remains unclear despite
is conscious, abdominal thrusts (Heimlk:h maneuver) a thorough history and posbnortem evaluation. It
should be init:iated in the toddler or older child. For is the leading cause of death in children between 1
infants, alternating back blowsand chest compressions month and 1 year ofage. The cause ofSUID remains
with the infant's body angled slightly head-down are
unproven, but is thought to be related to delayed
recommended. If the patient becomes unconscious, maturation ofbrainstem respiratory or cardiovascular
CPR is initialed with continued efforts 1xJ relieve the control and arousal mechanisms.
obstruction. Rigid bronchoscopyunderanesthesiaisused
to remove airway foreign bodies. PrognosiJ depends on RISK FACTORS
the type offtnign body, the locationofobstruction, and Although multiple factors have been associated with
the degree oflung damage. Overall morta1ityis low, and an increased risk ofSUID, none has proven prognos-
most patients recover qukklywith minimal sequelae. tic value (Table 20-9). Risk factors are related to the
1ULE ZO.I. SUID Risk Factors and Protective FaciDrs

i Rfskfac(m
IProne sleeping polition
!Soft bedding/sleeping in parents' bed
IPotentially obstructiw m.aterl.ab in the bed
ILow birth weight/intrauterine growth rertriction
! Prematurity
IMultiple gestation
i Young ma-ternal age
j Maternal smo1ci.ng
!l...atE/no prenabll care
1PITJtBcf/rf Fan
i Parenb and infiurtB sharins a room (without sharing
j abed)
IPaclfler use
FIGURE 20-7. Expiratory film in foreign body aspiration ! Breastfeeding
! AbbreY1atlon: SUID, sudden unaxplalned Infant death.
~-~--~~..!?..~~~~~--~~--~~-.!~.~!!..~.~-~~~~!!?..~.:............... ;,,,,,,.,,,,,,, ..,,,,.,.,,,,,,.,.,.,,.,.,.,,,.,.,,,,,,,.,,,,,,,,,,,,,,,.,, ,,,.,.,,, ,,,, ,,,,,,,,nooooooooooooooooooooooooooooooooooooooooono:
ingestions are often intentional, represent a suicide

TilLE 21.10. Differential Diagnosis of BRUEs
attempt or gesture, and may involve multiple sub-
!Sepail stances. Recreational drQg use in the adolescent
I Respiratory syncytial virus RSV-related apnea population may also lead to unintentional but fatal
IPertuuia overdoses. Intentional ingestions are more likely to
require medical intervention and result in death.
j MenlDgttis
i Metabolic clileue CLINICAL MANIFESTATIONS
!Gastroesophageal reflux The possibilityof toxic ingestion should be considered
!Aspiration in any patient presenting with acute-onset illness
i Seizures involving multiple organ systems, including altered
ICardiac arrhyt:lunlu mental status, acute behavior change, respiratory
compromise, seizUR, arrhythmia, and/or coma.
: Child physical abuse, especially abusive head trauma When caringfor a patientwith a known or suspected
j AbbreY!atlons: BRUE, br1ef rosolvad unexplained !Mints; RSV, ingestion, the history should include the substance and
!....................................................
respiratory syncytial virus.
............................................................................................ amount ingested, time elapsed since ingestion, early
mother, the infant, and the environment. Incidence symptoms, any change or progression in symptoms, and
peaks between 2 and 4 months of age. any attempts at treat:ment. In unlcnown ingestions, it Is
important to elicit potential exposures to prescription
DIFFEREN11AL DIAGNOSIS and over-the-counter medications, herbal supplements
Cases that initially appear to be SUID may result and vitamins, cleaning products. and pesticides. The
from infection, congenital heart disease, metabolic physical examination begins with the primary survey
di&orders, seizURs, accidenb.l trauma, or abuse. Brief ID evaluate the need for emergency cardiorespiratory
resolved unexplained events (BRUEs) are character- support, as mentioned previously. Other findings that
izedby a sudden. brie(. resolved episode in which an aid in diagnosis mayindk:atl! a tmddromeand include
infant has cyanosiB/pallo~ absent/decreased/irregular evaluation oftemperature and other vital signs, mental
breathing, hypo-/hypertonia, or an altered level of status, odor& on thebreath/skin/clothing. pupilsizeand
responsiveness. These events are understandably reactivity, and skin color and feel. The characteristic
frightening to the caregiver. The differential diagnosis clinical manifestations and treatments of common
for BRUEs is found in Table 20..10. poisonings in children are listed in Table 20-11.
PREVENTION DIAGNOSTIC EVALUAnON

Infants should be placed on their backs while sleep- In a patient presenting with an unknown ingestion.
ing. Contrary to popular b~ 24-hour home apnea initial evaluation should include a complete set of
monitoring does not reduce the risk of SUID. The vital signs and a thorough physical exam. Screening
use of monitors .should be reserved for infants with studies should include blood glucose, serum electro-
documented episodes ofapnea, bradycardia, or desat- lytes, a blood gas to determine pH, Pc~ bicarbonate
urati.on, and only ifprescribed by a medical provider. level, and base deficit/excess, and an ECG. In some
cases, additional labs such as serum osmolarity or
specific serum drug levels may be useful. In cases of
ACUTE POISONING intentional or multisubJtanee ingestion, it is prudent
to screen for a coi.ngestion ofethanol, acetaminophen,
EPIDEMIOLOGY or salicylates. Blood and urine toxicology screens
Poisoning is one of the more common pediatric may be helpful. but specific aubstances may not be
medical emergencies, resulting in over 100,000 detected on routine laboratory screens (e.g., many
emergency department viaits per year. Children illicit substances, iron, organophosphates). It is of-
younger than 5 years ofage account for over halfof ten helpful to consult with a Poison Control Center
all cases of poisonous ingestion. These ingestions while the patient is in the emergency department.
by young children are more likely ID be accidental
and involve only one substance, although abuse by TREATMENT
caretakers must be considered. Adolescents account At home, parents are encouraged ID call 911 for any
for a smaller proportion ofingestions. In adolescents, poisoning emergency, or to call Poison Control ifthe
i.........
1-.m.phm
.......-.........
TABLE 20.11. Signs, Symptoms, and Traabnent of Specific Pediatric Poisonings
May be initially Serum acetaminophen

level4 h after ingeation•;
OralN-aatylqsteine
(most effective withJn
uymptomatic.. Naasea/
vomiting, anorexia; may (late) serum hepatic 8-10 h of ingeltion)
Jll'OP'el& over days to transamm'""'', PT (1}, 140 mglkg PO X 1, then
Jaundice, abdominal pain. P'IT(t) 70mgllrgPOq4hX 17
liver failure doeea:
I Intravenous N~
acetyl.qsteine 300 mg/q
over21h
I! Antieho!Uuqlr ••••
(atropine, scopolamine,
•Mad as a hatter, red 85
a beet, blind 85 a bat, hot
No specific lab&/studies Ph)'BO&tigmine in
select caaes ofsevere
1'"-)
j first:~generation u a hare, dry 11.1 a bone";
drowsiness, delirium,
hallucinations, seizure; &kin
flushing: dilated pupils;
fever, cardiac dysrhythmias;
anticholinergic signs and
symptoms; supportive
care
dry mouth, speech and

swallowing clifficulties,
i urinary retention; nausea,
vomiting
ICarbon monoxide Headach~ dizziness, Blood carboxyhemoslobln 100" oxygen until
nausea, Jetharsy. irritability, levels (CO--Hsb); blood uymptomatlc and CO--
confusion, seimres, gas (metabolic ac:idom Hsb level <5"; coDJlder
Ii progression to coma, death;
cherry-red lldn
with normal PaoJ; pulse
ox 11 UD1'elJab1e (glvel
hyperbaric oxygen for
severe poisoning
fallely nomW. readinp)
Ii Ethanol~
(wine/beer/liquor; alto
Lethargy, CNS depression,
nauaea/vomiting, ataxia,
Serum ethanol level, blood Supportive care, gl.ueo~e
glucose(J-), bloodpH, (.J.), ifneed.ed
t found in hand sanldzers respiratory depression, osmolar gap (1)
~ and mouthwash) coma. hypotension,
hypothermia (in young
children)
i
1''"-)
E<h,leoe &lJ<ol Initially limilar to Serum ethylene glytlOI Fomeplzole (prmrred)
ethanoL after 4--12 h level; osmolal gap or edw1o.l to prevent
hyperventilation, seizures, (t); arterial blood gas metabolism,; sodium
coma. arrhythmias monitoring (metabollc bicarbonate to correct
acidoals}; serum metabollc acidosis;
electrolytes (i anion hemodialyals
gap); serum calcium (.I.);
! urlnalyals (caldwn oxalate
cryatala)
IiHydro-
(in fuels, household
........_ ""'"""""
Tachypnea. coughins.
Arterial blood gu
monitoring, chest x-ray
Supportive care,
oxygen u needeclJ
j cl.eanen, pollahes, and choking, respiratory (findings may be delayed spedtlc antidotes may
1, -uoMnb) ?cE? 12-24h) be avaJJahle fur some

hydrocamona-dlacuss
with Polson Conttol
lethargy, headache, coma,
l arrhythmia
Oooouooooooooooooooooooooooouooooo••••~•••oouoooooo"'''''''' ''''''-'''''"'''''''''''''''''''''''''''''''''''''''''''''"""'""""''"'''''''"'''"'"''"'''''''"""''~'''""''""'''''""''"--.o•••••o•••••uooooaoooooooooooo ooooooooooooo••••••••••••••••••••••••••••••••••••••••••••••o.oo:
TAIL! 20-11. Signs, Symptoms, and Treatment of Specific Pediatric Poisonings (continued)
!....... Clnlcll••........,..
!Ibuprofm/no~Wroldal Nawealvomiting,
!anti-Inflammatory drup anorexia, stomach pain;
pmointestinal bleeding
! =::..=::
IUD· ~~ Serum iron leva (4-6 h
post ingestion), lmll1l pH
(-!.), giUCOie (1), bilirubin
Deferoxamin.e chelati.oa;
whole bowel irrigation
If tablets vi&ible on
i §:§g;
liver failure. possible death
and liver function
tests (1), PT (i), WBC
(i); abdominal x-ray
(radiopaque materlal/
abdominal x-ray
': . -+ IICillTing from initial tablets)

' corrosive injury leads tD GI
ii Methanol
(wtndJhield wuher fluid.
=~th
vomiting, lnebria!ioa;
nausea, Serum methanol level;
arterial blood gues
Fomeplzole (prererred)
or ethanol to block
!paint remover); toxidty Up to 30 h later t minute (Ievere metabolic metabolilm; aodium
j related to formation of ventilation to oftiet addoUs); OIJDolal pp (f) bicarbonate Cor
!,_ formic acid lllfltabolic acidoais u lllfltabolk acidOiil;
fotic acid to hutm
!· ~~~
seizures, coma, act1te renal
formic acid elimination;
hemodialysia in lleYI!I'e
I
'
OplalnloploldJ :;._.......,...,..
decreaJJed respiratory
Toxicologic screen (urine
and/or &erWD)-utllity
Naloxone"; respiratory
mpport
1 rate. pinpoint pupill, varies on speclftc opiate
1 somnolence, coma taken
IOrganophoaphates SLUDGE (lllllvation, Plasma or red blood cell Atropine and/or
!, (pesticides) lacrimation, urination, cholineaterueactlvity pralldoxime; caregivers
defecation, gaatric (-!.)-not readllyavallable should take caution to
i Cl'llJDping, e01e11is); tests avoid being exp011ed by
=~====·
cli.rect contact with the
patient
ii excessive sweatint!;
!,
,_ muscle weakness and
fasciculatioN; confusion;
I Salicylatea ~;erpnea/tachypnea, Salicylate level, blood Supportive care," sodium !

l
==
1(upirin, over-the-counter nawea, vomiting, gas (respiratory alkalollil bicarbonate for acidosis
1analgesics, antidiarrheal hyperthermia, tinnitu&, + metabolic acidollil), and to promote renal j
.
:;_t'':
. .....ucat;on, . . . . .. .....,.. "'""""' (~) i
hemodialysla In severe 1,
cues
O.--oooooo-oooooo oooooo o-..oooooooooooooo•o,_o o-•oooooooooooo.o__,.oooooooooooooooooo-oooonoooo•ooooorooo--••onooooo9ooooo-••••••••••••••••-•-•••••••••••••"oooooo-ooooooooooooooooooooooooo•••••••••••••••"""•••o•o••••••••••n••••r••••••••••••••••••~•••••••••~•••••~•=
: .......
~ Sympathomimetic apnts
...................
TABLE 20-t t. Signs, Symptoms, and Treatment of Specific Pediatric Poisonings (continued)
Tachycardia. hypertension,
.....,.....
Toxicolosic screen (urine
~
Supportive ~ OOI1Iider
~ (clecoogatanta; a1Jo fever, tremor. large but and/or serum) -ut11lty beozodiazepines for
~ amphetamlnea, c:ocaine) reactlw pupils, sweating, varies on spedfk drug agitation
agitatloll. deUriuml taken. CK, tropollin
~- aeizures,
arrhytlunJaa, myoc:arctial
(c:ocaine), EKG
I llc:hemiallnfarction (with
cocame)
i Thoophyllino Tachycardia, hypotension,
tachypnea, vomiting,
Serum theophylline level
(every 2-4 h), blood
Supportive care;
hemodialyBJs in severe
tremor, agitation. seizures; glucose (t), potassium cases
ventricular arrhythmias (J.), pH (J.), caldum (t),
I phosphate (J,), EKG
ITricyclic antldepraeants Anticholinergic effects Sodium bicarbonate or
EKG (prolonsed PR
hypertonic saline for
u mentioned previously; intecval, widened QRS
tac:hyardla. hypertension complex, prolongation of EKG abnormalities; all
progressing to hypotension. the QT interval, AV block, patients with tricycl1c
confusion. drowllneu, ventrlcular arrhythmiu); antld.epreaant ingestions
dry mucoua membranes, these effects may be should be admitted and
cUJated but responsive delayed monltot'ed in an intensive
pupill, agitation, Jeizures, careunlt
Ii coma. dyuhythmiaa
j • An aocepted nomogram eldsts fCll' predicting the SlMirlty of the tmclclty on the basis of a blood aoatamlnophen meaeurament takan
~ at least 4 hours after ingestion.
j bphyaiclans should hiMI a high suspicion of colngesl!ons In adolesoents wllh ethanol Intoxication. The cllnloel manlfestallons of
j oolngestlon of a CNS stimulant may be attenuated, whereas Ingestion with a depressant may potentiate the etrects of alcohol.
~ "Naloxone admllistraUon may result In withdrawal symptoms (tachypnea, tachycardia. sweathg, agitation, seizures) In chronic users. !
i -Aspirin ingestion cau988 delayed gastric emptying, so gastrointestinal decontamination plays a significant rola. ~
iAl:ll:lnMations: AV. atrioYentricular; CK, cteatine kinase; CNS, central nervous system; EKG, electrocardiogram; Gl, gastrohteslinal; i
~ INA, international normaliz:ad ratio; PT, prothrombin time; PIT, partial prothrombin time; SWDGE, salivation, lacrimation, urination, ~
~ defecation, gastric aamping, emesis; WBC, white blood cell.
......................................................................-.......................................................................................................................................................................................................................;~
:
child is awake and alert. Emetics, such as ipecac, are no patients with decreased mental status who may not
longer recommended for known or suspected poisonings. be able to protect their airway. Activated charcoal is
In the emergency department, patients who ineffective in ingestions with alcohols, hydrocarbons,
present in an unstable condition are evaluated and iron, and lithium. Whole bowel irrigation is an option
treated acco.rdins to the CABDEs discussed earlier for ingestions involvins iron, lithium, sustained-release
in the chapter. With regard to ingestions, the "D" in or enteric-coated medications, or drug-filled packets
the mnemonic: may stand for: dextrose (as several or c:ondo.ll1S. Gastric lavage is not routinely used in
commonly ingested agents cause hypoglycemia); the management of poisoned patients, If used, it is
empiric drug treatment (referring to possible an- generally effective only ifit is performed in the first
tidotes, such as naloxone for opiate overdose), and hour after ingestion or if the compound ingested
appropriate decontamination. Treatment decisions slows gastric emptying (e.g., aspirin). Gastric la-
should be based on the estimated mtalmum dose nse is contraindicated in patients who are actively
the patient may have ingested. vomiting, who do not have a protected airway, and
ActivatEd charcoal may be recommended u a those with ingestion ofc:orrosive/ca115tic substances
method of gastric decontamination. depending on or hydrocarbom. Hemodialysis may be necessary
the substance ingested and the time since ingestion. for selected ingestions to prevent l.ife..threatening
It is administered by mouth or nasogastric tube and complications. Local Poison Control Centers can
minimizes absorption by binding the ingested substance help with recommendations for the management
and hastening its elimination. It is contraindicated in of children with toxic ingestions.
KEY POINTS
• The algorithms for pediatric basic and advanced complete blood count, t1ernatwia on urinalysis,
Clrdiac life support should be folowed regard- or elevated lver transaminaaee increases the
less of the cause ot cardiopulmonary arrest. odds of an intraabdomlnal injury being detected
A primary assessment (Circulation, Ajrway, on a subsequent CT scan.
Breathing, Dlaabllty, Exposure) should be • Concussion symptoms may last hours to
performed, with the Initiation of resuscitative months. Children w ith concussions should
measures at every step, as necessary. have a period of physical and cognitive rest,
• Approximately half of the causes of pediatric followed by gradual return to play and return
arrest ant due to respiratory arrest. to learn, guided by symptoms.
• If a patient Is not responding to resuscitation • After an Initial episode of coughing and/or
measures, the following mechanical or metabolic choking, the patient with foreign body aspira-
causes should be Investigated: hypothermia, tion may be asymptomatic for hours to days.
tension pneumothorax, hemothorax, cardiac Physical examination findings in a patient with
tamponade, profound hypovolemia, profound foreign body aspiration below the carina are
metabolic Imbalance, toxic ingestion, and localized to one side of tl'le chest.
closed head Injury. • Young children should be supervised any time
• Hypovolemic shock accounts for most cases they are near water, Including bathtubs.
of shock In children. • The majority of burna can be managed conser-
• For chldren In shock, hypotension is a late vatively. Bums that are severe, circurnfarential,
finding, and the degree ot tachycardia is the and extansive, or that Involve the face, hands,
most sensitive measure ot Intravascular volume teet, perineum, genttala, or m&IOt' joints should
status. be C3'8d tor at a bum center.
• In septic shock, early recognition and admi,_. • Red flags for abuse Include the following: an
tration of antibiotics and intravenous fluids are injury that is inconsistent with the history or
critical and should not be delayed. the child's developmental abilities, a history
• A patient In decompensated shock can progress that changes over time, and a delay in seeking
to cardiopulmonary arrest in minutes. approprtate medical care.
• Children with acute blood loss may not become • Abusive head trauma Includes intracranial
hypotensive until they have lost approximately bleeding, diffuse axonal Injury, and retinal
40% to 45% of their circulating blood volume. hemorrhages. Intracranial injuries in the
absence of substantiated significant head
• Children, with their smaller body mass, less
trauma are virtually pathognomonic of abuse in
fat, proportionally larger head and incompletely
Infants.
calcified skeleton, have different injury patterns
in the setting of trauma than adults. • Babies should be put to sleep on their backs
(supine) to reduce the risk of SUID.
• Not all children with head trauma need head
imaging. Head Imaging is indicated only for • The use of a home apnea monitor does not
higher risk Injuries or for those patients with reduce an infant's risk of SUID.
exam ftndlngslhlstory concerning for an intra- • Along with a careful l'llatory, information gath-
CIW'Iial bleed. ered from vital signa, physical examination,
• When obtai'llng labs da.ing the evaluation and early laboratory data may suggest the
of a hemodynamlcaly stable child with blunt substance ilgested by conforming to a~
abdominal trauma, the presence of anemia on clflc toxldrome.
CLINICAL VIGNETTES
VIGNETJE1 c. Splint and immobilize the injured extremity

While you are working at a community pediatric clinic, a d. Transfuse with 0-negative packed red blood cells
patient's mother calls for help from an adjacent examina- a. Administer supplemental oxygen
tion room. You are the first medical professional to enter
2. What is this patient's GCS score?
the room and see a 2-month-old infant lying motionless
on the table. He is not breathing spontaneously. He
L7
b. 9
has no pulses. You determine that this unresponsive
pulseless child Is In cardiopulmonary arrest.
c. 11
d. 13
1. What Is the correct ratio of cl'lest compressions e. 15
to rescue breaths for the lone rescuer in pediatric
CPR?
a The patient develops irregular breathing. He no
longer opens his eyes to stimuli, and his limbs are
L 3:1
extended. He does not vocalize. His pupils are
II. 10:1
c. 15:2 unequal, with the left being fixed and dilated. His
heart rate is 54 bpm, and his blood pressure is
d. 30:2
154/82 mm Hg. Which of the following is the most
•• 60:2
likely reason for this patient's clinical deter1oratlon?
2. Which of the following is the most appropriate L Hemorrhage from an intraabdominal injury
anatomic location and vessel for the assessment b. Seizures induced by his recent head trauma
of central pulses in this patient? c. Brain herniation
L The wrist/radial arteries d. Uncontrolled bleeding from a fractured lower
b. The upper ann/brachial arteries extremity
c. The neck/carotid arteries a. Tension pneumothorax
d. The feet/dorsalis pedis
t. The ankles/posterior tibial VIGNETIE3
3. Which of the following is the most common cause A 2-year-cld female is brought to the emergency
of pediatric cardiopulmonary arrest? department with the chief complaint of difficulty breathing.
L Cardiac arrhythmias She was in her high chair eating and suddenly started
b. Metabolic abnormalities coughing and sputtering. The parents called EMS, and
c. Overwhelming infections she was brought to the emergency department. She
d. Trauma has no significant past medical history. On physical
e. Respiratory problems examination, her vital signs ara normal except that
shels tachypneic and coughing. Pulse oxlmeby reads
VIGNE111:2 100% on room air. On auscultation, she has diffuse
You are evaluating a 1o-year-old male who was struck wheezes over the right hemithorax. The remainder of
while riding his bicycle by a car traveling 30 mph. He the physical examination is normal.
was not wearing a helmet. On physical examination, 1. Which of the following tests would most likely
he has strong central and peripheral pulses. His heart confirm the diagnosis?
rate is 11 0 beats per minute (bpm), and he Is breathing L Chest radiographs with decubitus views
spontaneously. His blood pressure is normaL There is b. Arterial blood gas
a large hematoma on his forehead. His eyes open in c. Peak flow measurements
response to painful stimuli, and his pupils are equal d. Cheat ultrasound
and reactive to light. He vocalizes by incomprehensibly e. Ttial of a bronchodilator (e.g., Albuterol)
moaning. When you pinch his right arm, he attempts to
push your arm away and appears to be moving all four 2. Chest radiographs demonstrate unilateral hyper-
extremities. His abdomen is soft and nontender. He has inflation of the R lung, suggesting airway foreign
an obvious deformity of the distal left lower extremity. body. Which of the following Is the best definitive
treatment for this patient?
1. All but which of the following are appropriate L Intubation in the emergency department and
immediate interventions in this patient? flexible bronchoscopy
L Immobilize the cervical spine in a semirigid collar 11. BronchodUator therapy
b. Obtain intravenous access c. Rigid bronchoscopy in the operating room
d. Heimlich maneuver c. Fundoscopic examination

e. This condition will self-resolve and does not d. Complete blood count
require acute Intervention e. Chest radiograph
S.ln this patient with an airway foreign body for a
VIGNETTES
brief period of time, Which of the following is the
most likely prognosis regarding lung function? A 3-month-old female is brought to your office. Earlier
& Bronchiectasis and emphysema of the af- that morning, the mother called 911 because of a
fected lobe cyanotic spell. Soon after a feeding, the mother heard
b. Quick recovery, minimal sequelae gasping and returned to the baby's room. The infant
c. Recurrent pneumonlas was awake and struggling but appearad unable to
d. Chronic asthma bnNlthe. The mother noted circumoral cyanosis. On
e. Exercise Intolerance further questioning, she reports that the baby seemed
stiff but did not have any shaking movements. She
VIGNETTE4 was frightened that ttle baby might die; however, by
A 8-month-old male is brought to the emergency depart- the time EMS arrived, the child appeared well. EMS
ment with increasing sleepiness. His mother states that declined to transport the infant to the hospital. At your
after returning home from work, she noticed that the baby office, the baby has a normal physical examination.
was initially irritable and has since become somnolent. 1. Which of the following findings in the above-mentioned
The mother's boyfriend, who was caring for the infant, vignette does not support the diagnosis of BRUE?
had stated to the mother that tne baby was crying a lot L Color change
and wouldn't take a bottle. The mother brought the child b. Patient Is now back to baseline
in because he has stopped feeding altogether. He was a c. Change in muscle tone
premature baby at 30 weeks' gestation and has known d. Gasping respirations
gastroesophageal reflux. On physical examination, the •· Event occurs after feeding
vital signs are normal, but he Is dtmcult to arouse. His
neck and trunk have bluish disoolorations that look like 2. Which of the following diagnoses is not typically
bruises. The mother, when questioned, has no expla- Included In the differential diagnosis for BRUE?
nation for the discolorations-they appear new to her. L Infantile colic
You begin to suspect child abuse. b. Gastroesophageal reflux
c. Congenital heart disease
1. Following Initial stabilization, your best response d. Child physical abuse
to your suspicion at this time consists of which
•· Seizures
of the following?
a. Refer the patient to the pediatrician for a mora S. The mother states that her nephew died of SUID
in-depth workup. a few years ago, and she Is woi'Tied the same
b. Perform a skeletal survey and, if negative, may happen wtth her Infant. She 19quests a home
discharge home. apnea monitor. Which of the following represents
c. Document concern in the medical record and the most appropriate response?
fax immediately to the child's pediatrician. L The use of a home apnea monitor at night
d. Interview the boyfriend and mother separately reduces the risk of SUID.
and determine the likelihood of abuse. b. The use of a 24-hour home apnea monitor does
e. Immediately report your suspicion to state not reduce the incidence of SUID.
protective agencies. If available, consult the c. Placing the infant prone in the crib is more
Child Protection Team. effective than home apnea monitoring.
d. A 24-hour home apnea monitoring only re-
2. Which of the following is not a risk factor for
duces the risk of SUID in children without prior
pediatric abuse or neglect? medical problems.
L Low socioeconomic status
e. A 24-hour home apnea monitoring should be
b. Child with a history of prematurity used only In conJunction with medical supervision
c. Extreme caregiver stress and prescription medications such as catrelne.
d. Male caregiver gender
e. Child with a history of chronic illness VIGNETTE&
3. Which of the following is the most appropriate A 4-year-old male is brougtrt to the emergency department
diagnostic study following initial stabilization of with the chief complaint of altered mental status. The
this patient? parents note that their child has become increasingly
L Head CT sleepy over the last hour and Is now unresponsive. The
b. Skeletal survey EMS team reports that he responds to deep sternal
rub and that his saturations are 100% on room air. c. Acetaminophen
There Is no history of seizure disorder. On physical d. Decongestants
examination, heart rate is 65 bpm, respiratory rate 7 .. Aspirin
breaths per minute, and blood pressure is 70130 mm
2. Which of the following tests would most likely
Hg. The child has sonorous breathing, stirs to deep
confinn the diagnosis?
painful stimulus, and has pinpoint pupils. The rest of
L Complete blood count
his physical examination Is normal. A rapid bedside
b. Arterial blood gas
glucose is 140 mgldL You suspect drug ovetdose. While
c. Serum osmolarity
waiting for the establishment of an intravenous line,
d. Prothrombin time
further history is obtained from the child's grandmother.
1. Urine drug screen
On questioning, she states that several medlcaHons
are accessible at home. These include oxycodone, 3. While in the resuscitation room, the child becomes
ibuprofen, acetaminophen, decongestants, and aspirin. apneic and is unresponsive to painful stimuli. In
They are located in a pillbox, and she doesn't recall addition to providing appropriate respiratory sup-
locking it away this morning. port, which of the following Is the best immediate
treabnent for this patient?
1. Ingestion of which of the following medications L Flumazenil
is most likely to cause this patient's constellation b. Digibind
of symptoms? c. Naloxone
L Oxycodone d. Physostigmine
b. Ibuprofen e. Fomepizole
ANSWERS
VIGNETTE 1 Quatlon 1 commonly result from initial respiratory compromise

1. Answer D: progressing to respiratory fallul'1t/arrest, which com-
The goal of CPR Is to provide high-quality chest com- promises coronary perfusion and oxygenation and
pressions that generate blood flow to vital organs at results In full cardiopulmonary arrest. The other four
a rate of 100 to 120 compressions per minute. The answer choices are all potential causes of pediatric
American Heart Association recommends alternating cardiopulmonary arrest, but are less common than
chest compressions wtth rescue breaths in children in respiratory etiologies.
cardiorespiratory arrest. For the lone rescuer, a comi)I9S-
sion-to-ventilation rate of 80:2 is recommended. Because
even a brief interruption of compressions can result in a 1.AnswerD:
loss of coronary perfusion pr96Sure, an increased ratio This patient has multiple injuries. Bicyclists struck by
of compressions to breaths Is recommended when a moving vehicle are at risk for injuries to the brain
providing CPR as a lone reacuer. The ratio of 15:2 is and cervical spine. The cervical spine should be
appropriate if at least two providers are present. None Immobilized with a semirigid collar to protect against
of the other options are racommended in pediatric CPR. further injury in the absence of reliable examination
and radiographic findings. It is appropriate to obtain
VIGNETTE 1 Question 2 intravenous access as soon as possible in order to
2.Answer B: access helpful laboratory studies and to administer
The most appropriate places to palpate for central medications and fluids. Splinting and immobilizing
pulses in a small infant are the brachial arteries or the injured 6mbs with suspected fractures can reduce
femoral arteries. Evan experienced health care pro- pain and mitigate further hemorrhage from long bone
viders often have difficulty reliably feeling the carotid fractures. Mhough this patient is breathing on his own,
pulses in an infant of this age and size. The radial he does have examination findings suggesting a closed
artery, dorsalis pedis, and posterior tibial arteries are head injury, including his depressed mental status
examples of anatomic locations for the assessment and a hematoma on his forehead. The injured brain is
of peripheral, rather than central, pulses. sensilive to hypoxia and hypovolemia. Supplemental
oxygen Is recommended for this patient. A transfusion
VIGNETtE 1 Question 3 of red blood cells is not immediately nece88ary in this
3.AnswerE: patient, as he is not tachycardic or hypotensive and has
In adults, cardiac etiologies are the most common no obvious active internal or external hemorrhaging.
causes of arrest. In contrast, pediatric arrests most Although it is possible to exsanguinate from a femur
fracture, skeletal injuries 1D the distal appendicular in the aforementioned case. Bilateral decubitus lung
skeleton rarely lead to hemorrhagic shock unless an radiographs are more sensitive than expiratory films
overlying m&~or artery has been InJured. The admin- and easier to obtain In young children. The arterial
istration of isotonic crystalloid is appropriate as the blood gas will help determine the respiratory status
initial fluid therapy. of the patient but will not elucidate Its etiology. Peak
flow measurements do not differentiate air trapping
VIGNETTE 2 Question 2 from a reactive airways component versus an airwsy
2.Answer B: foreign body. Although chest ultrasonography may
This patient has a GCS of 9. The GCS consists of sometimes detect lung atelectasis, its sensitivity is quite
scores for eyes, motor, and verbal response. He limited. Chest ultrasonography is unable to differentiate
opens h is eyes to painful stimuli, which earns him 2 hyperinflated lung from normal lung tissue. In some
points for eyes. He attempts to push the examiner's patients with an aspirated foreign body, bronchodilator
nand away (moves to localized pain), giving him 5 therapy may resuH in some improvement In wneezing
points for best motor response. He is moaning in- and aeration if there is a reactive airway component.
comprehensible sounds, which gives him a score of Improvement with bronchodilator therapy, or lack
2 on the verbal assessment. He, therefore, scores a thereof, Is not diagnostic of foreign body aspiration.
GCS of 2 (eyes) + 5 (motor) + 2 (verbaO = 9. A GCS
of 9 Indicates that this patient has at least a moderate VIGNETTE 3 Question 2
traumatic brain InJury. 2.AnswerC:
In cases of suspected airway foreign body, removal
VIGNETTE 2 Quasllan 3 should be attempted by rigid bronchoscopy in the
3.AnswerC: operating room. Although flexible bronchoscopy may
This patient has suffered from cerebral herniation aid in diagnosis, the utility in treatment o.e., foreign
(uncal), a severe complication of traumatic brain body removal) is quite limited. Therefore, rigid bron-
injury. He has Cushing's triad, which includes brady- choscopy is the treatment of choice. The operating
cardia, nypertension, and irregular breathing. These room is a more controlled environment for children
are tnougnt to occur because of pressure exerted who require semiurgent airway control. Bronchodilator
on the brainstem by herniating cerebral tissue. tnerapy may ameliorate any airway reactive compo-
This patient requires emergent management with nent, if present, but is not a definitive therapy. The
hypertonic saline, mannitol, hyperventilation, and Heimlich maneuver may be performed in the field in a
potential neurosurgical intervention. Uncontrolled patient who has complete obstruction of the trachea
hemorrhage from various injuries would likely lead but Is not appropriate In the aforementioned patient.
to hypotension, rather than hypertension as seen An aspirated foreign body will not resolve w ithout
In this patient. Although seizures can manifest w ith intervention; therefore, prompt diagnosis and timely
abnormal vital signs and posturing, the unequal removal are imperative.
pupils are more suggestive of herniation. A ten-
sion pneumothorax presenta with decompensated VIGNETTE 3 QuM'IIon 3
obstructive shock, characterized by absent breath 3.Answer B:
sounds in the affected hyperinflated hemithorax, a The prognosis of patients with airway foreign bodies
deviated trachea, hypoxia, and hypotension. The depends on the amount of lung damage sustained. This
treatment of tension pneumothorax consists of is usually a function of the duration the foreign body has
immediate needle decompression. been in the airway. The longer an object remains in the
airway, the longer the chronic inflammatory response
VIGNEnE 3 Qu181ion 1 has a chance to damage the airway. In this case, the
1.AnswerA: acute pruentation and prompt removal would most tikely
In cases of suspected foreign body aspiration, a chest result in a rapid recovery and minimal complications.
radiograph w ith lateral decubitus views would be Bronchiectasis Is often encountered In patients w ith
most helpful In establishing the diagnosis of airway cystic ftbrosls complicated by hemoptysis. However,
foreign body. Although most airway foreign bodies It may also present In cases of long-standing airway
are not radio-opaque, Indirect nndlngs such as ln8S foreign body. Emphysema Is very rare In children In
of atelectasis/hyperinflation on chest radiograph may the absence of conditions predisposing to air-leak
increase diagnostic certainty. The decubitus views syndromes. On occasion, a child with an airway for-
will demonstrate dependent areas of lung that remain eign body may be diagnosed with pneumonia more
hyperinflated, signifying areas of ball valve--type than once before the foreign body is suspected and
obstruction. Alternatively, expiratory views may be removed. When an airway foreign body is removed
taken to localize areas of hyperinflation. Although a before major lung pathology develops, reactive lung
normal lateral decubitus chest radiograpn does not disease and exercise intolerance are not associated
fully rule out airway foreign body, it is the best answer complications.
VIGNB'TE 4 Quesllan1 VIGNETTE 5 Quesllan 1

1.Answer E: 1.Answer E:
Health care workers who suspect that a pediatric BRUEs are characterized by a sudden, brief, and now
patient has been the subject of abuse and/or neglect resolved episode of one or more of the following: cya-
are required by law to notify state protective agencies nosis or pallor, absenVdecreasedlirregular breathing,
of their concerns. The suspicion does not have to be hyper-/hypotonia, or altered responsiveness. Although
substantiated before the report is prepared. This report these events may occur in relation to feedings, this is
should be made immediately. At many institutions, a not part of the definition.
Child Protection Team may be consulted to assist with
further investigation and to help file the formal report. VIGNETtE 5 Question 2
Suspicious injuries, stories1tlat are inconsistent w ith 2. Answer A:.
a child's development abilities (e.g., a broken arm or Infantile colic is characterized by excessive, inconsol-
leg in a child who is not yet mobile) or histories that able crying In an Infant without underlying pathology or
change over time are concerning for child abuse. Identifiable need. It occurs most commonly between
Discharging the child home for subsequent follow-up the ages of 3 weeks and 3 months. Cyanosis or pallor,
with the pediatrician is Inappropriate. The skeletal absent/decreased/irregular breathing, hyper-/hypotonia,
survey may be normal even in cases of severe child or altered responsiveness are not present. Although
abuse, and the decision to refer should not rely on the symptoms of colic may be distressing, they are
findings of this test. Finally, repeated interviews and generally exhausting rather 1tlan acutely frightening
interrogations of the caregivers should be carried to the observer. The presence of any of the findings
out by properly trained providers, typically the Child characteristic of a BRUE should make one question
Protection Team or other trained specialists. This is the diagnosis of colic. Gagging associated w ith gas-
not w ithin the purview of the treating clinician. troesophageal reflux may occur in relation to feedings
and can produce symptoms of BRUE. Congenital
VIGNmE 4 Qlllltion 2 heart disease may cause cyanosis and difficulty in
2.Answer D: feeding (such as increased work of breathing}, which
Abuse is perpetuated at all socioeconomic levels may result in gagging or choking along with apnea.
but Is more prevalent at lower socioeconomic levels. Infants who have sustained Intracranial hemorrhage
Children with special needs (developmental delay, from child physical abuse may manifest with abnonnal
cerebral palsy, prematurtty, and chronic Illness} are movements, seizures, or apnea. Seizure disorder, with
at incAJased risk. Caretakers who have themselves changes in muscle tone and cyanosis, is an important
suffered abuee, who are alcohol or substance abus- part of the differential diagnosis in patients with BRUE.
ers, or who are under extreme stress are more likely
to abuse or neglect. There is no known increased risk VIGNETTE 5 Question 3
of child abuse based on caregiver gender. 3.AnswerB:
Twenty-four-hour home apnea monitoring has not
VIGNmE 4 Q...Uon 3 been shown to reduce the Incidence of SUID in
3. Answer A:. healthy children. Use should be reserved for infants
In a child with suspected abuse and depressed with documented episodes of apnea, bradycardia, or
mental status, consideration should be given to desaturation. Prone sleeping position has been asso-
Intracranial hemorrhage. CT of the head Is the best ciated with an Increased Incidence of SUID; Infants
Initial test In this scenario. VIctims of child physical should be placed on their backs to sleep. There Is
abuse may have subdural hemorrhages, retinal also no evidence to suggest that 24-hour home apnea
hemorrhages, and characteristic fractures such monitoring In concert with medication such as caffeine
as posterior rib fractures or metaphyseal corner reduces 1tle incidence of SUID.
fractures (bucket handle fract ures). The prompt
identification of intracranial injury is necessary for VIGNETTE 8 Question 1
devising the appropriate treatment plan of this infant. 1. Answer A:.
The skeletal survey and ophthalmologic exam are Oxycodone is an opiate agonist that binds to opiate
helpful in the diagnosis and management of children receptors in the CNS, causing the inhibition of ascending
with suspected abuse, but evaluation for intracranial pain pathways and producing generalized CNS de-
hematoma by head CT should take precedence. pression. An overdose of opiates produces the clinical
Complete blood count and chest radiograph are constellation portrayed: generalized CNS depression,
not part of the standard diagnostic evaluation for hemodynamic compromise, and miosis. Acetaminophen
child physical abuse, but may be indicated on the overdose results from an acute Ingestion of more 1tlan
basis of clinical circumstance. 150 mglkg. The patient Is typically asymptomatic over
the first 24 to 48 hours. Gastrointestinal symptoms the arterial blood gas may show hypoventllatlon, but
such as abdominal pain and vomiting manifest later. this Is not speclftc and can occur In other disorders
Thereafter, serum hepatic enzyme levels begin to with depressed mental status. Measurement of serum
rise. Finally, In severe Ingestions, liver failure ensues osmolarity assists In the diagnosis of ethylene glycol
with prolongation of the prothrombin time, elevation toxicity. In this type of Ingestion, an osmolar gap can
of ammonia, and the development of cerebral edema be calculated, suggesting the diagnosis. Opiate toxicity
and hepatic encephalopathy. Overdose with ibupro- doea not influence the osmolar gap. The prothrombin
fen, a nonsteroidal anti-inftammatory drug (NSAID). time is prolonged in liver failure as a consequence of
results in gastrointestinal irritation. Over the short acetaminophen toxicity. This is a late finding and not
term, reduced mental status is not a feature of NSAID present in opiate toxicity.
overdose. Decongestants such as pseudoephedrine
have side effects quite opposite from those of opiate VIGNETtE 8 Question 3
overdose; excessive ingestion produces agitalion, 3.AnswerC:
hypertension, tachycardia, seizuf'9S, and mydriasis. Naloxone is the antidote for acute opiate toxicity. It
Aspirin toxicity causes hyperpnea/tachypnea, fever, competes with and displaces opiates from opiate
nausea and vommng, agitation, and seizures. Older receptor sites. The onset of action Is rapid, revers-
children may report tinnitus. Depressed mental status Ing respiratory and mental status depression within
Is a late ftndlng of salicylate toxicity. seconds of Intravenous administration. Naloxone
may also be given subcutaneously or Instilled Into an
VIGNETIE 6 Quedon 2 endotracheal tube. The effects are short lived, and
2.Answer E: patients frequently require multiple boluses or the
Standard toxicology reeults for urine drug screens institution of a continuous drip. In patients who are
include the detection of opiates, benzodiazepines, and chronic opiate users, the administration of naloxone
the active chemical in marijuana. These screens are may result in symptoms of drug withdrawal and
easy to obtain, and the results are rapidly available. should be given w ith caution. Flumazenil is used for
It should be noted 1tlat urine drug screens may not benzodiazepine overdose and works quickly after
detect many of the newer synthetic drugs. A negative intravenous administration. It has no use in cases
1'8Sult may simply indicate the inability of the test to of opiate intoxication. Digibind is the antidote for
detect a drug, rather than the lack of presence of the acute digoxin poisoning. Physostigmine Is used to
drug. A complete b lood count Is not helpful In con- reverse the effects of organophosphate poisoning. Its
ftrmlng the diagnosis of opiate t oxlcHy. It may have mechanism of action Involves stopping the hydrolysis
utility In determining alternate diagnoses In patients of acetylcholine at the neuromuscular junction, thus
with altered ment al status. The arterial b lood gas preserving synaptic transmission at the neuromus-
may be helpful in evaluating a patient with suspected cular junction. Fomepizole is used in ethylene glycol
aspirin toxicity. The classic blood gas finding in sa- poisoning. It serves as a competitive substrate that
licylate toxicity is a mixed respiratory alkalosis with interferes with the metabolism of ethylene glycol,
a concomitant metabolic acidosis. In opiate toxicity, thereby limiting the production ofthe toxic metabolite.
Questions
1. A 2-year-old female child presents with ventrtc- 5. A mother brtngs her 6-year-old son to your of-
ular tachycartlia, severe ventlicular dysfunction, nee In New Mexico for his regular health main-
hypotension, and metabolic acidosis. The patient tenance visit. A quick review of the patient's
is cartlioverted into ventricular fibrillation which chart reveals that he and his family are strict
degenerates into asystole. What is the most vegans ~.e., they eat no animal products of any
appropriate indication for using intravenous (IV) kind). Their house is very small, so all the chil-
epinephrine in this patient? dren spend a good deal of time outside. The
a. Ventricular ectopy mother states that her son eats plenty of dark
b. Asystole green vegetables and iron-fortified grains. She
c. Severe refractory metabolic acidosis and/or does not believe in providing supplemental vi-
hyperkalemia tamins and minerals. This child Is most at risk
d. Torsades de pointes for nutrttlonal deficiency Involving which of the
a. Supraventrtcular tachycardia following?
L V"rtamin 8 , 2
2. A 16-year-old female patient presents with short
stature and no secondary sex\.lal characteris- b. VItamin Be
tica. What diagnosis must be considered? c. Niacin
a. Turner syndrome d. Riboflavin
b. Isolated growth honnone deficiency e. V"rtamin D
c. Cushing disease &. A 6-year-old boy presents with a newly appre-
d. Familial short stature ciated heart munnur. He is asymptomatic, with
e. Addison disease nonnal growth and development and normal ex-
3. Galactoaemia, a disorder of carbohydrate me- ercise tolerance. On examination, S, and~ are
tabolism, is inher'ited in an autosomal recessive nonnal; a liM low-frequency midsystolic mur-
fashion. What Is the risk of galactosemia In a child mur Is heard at the left lower sternal border. His
whose parents 1n both carrters for the disorder? pulses are nonnal. The most likely diagnosis is
a. 100% a. bicuspid aortic valve
b. 75% b. Still's munnur
c. 50% c. ventricular septal defect
d. 25% d. atrfal septal defect
.. 0% a. coarctation of the aorta
4. Which of the following statements Is true regard- 7. You are called to the delivery room for a routine
ing children with sickle cell disease? birth. The Infant cries when the cord Is cut. You
a. Vaccinations are not required because they examine the child under the wanner and notice
receive penicillin prophylaxis. that when he stops crying, his chest heaves and
b. Gallstones typically develop before the age he turns blue. You are unable to pass the na-
of3. sogastric tube through the nares for suctioning.
c. Episodes of dactylitis should be treated with Which condition Is most likely causing this In-
antibiotics. fant's respiratory distress?
d. Hydroxyurea maintenance therapy reduces 1. Choana! atresia or stenosis
the number and severity of vaso-occlusive b. Vocal cord paralysis
crtses. c. Subglottic stenosis
e. Acute chest syndrome requires only sup- d. Recurrent laryngeal nerve damage
portive care. e. Laryngeal web
434
Questions • 435
8. A 3-year-old girt is diagnosed w ith new-onset 12.. A woman with a seizure disorder under medi-
insulin-dependent diabetes mellitus. Which of cal management wants to conceive a child. Her
ltia following laboratory findings Is consistent risk of having a child w ith a neural tube defect
with diabetic ketoacidosis? is greatest if her gestational medical 1'8gimen in-
a. Hypoglycemia c ludes which of the following?
b. Hypercarbla L Phenobarbital
c. Ketonea In urine b. Phenytoin
d. Increased venous blood pH c. Ethosuximide
e. Decreased blood urea nitrogen (BUN) d. Carbamazepine
9. Durtng a male newborn examination, the testes
e. Primidone
are not palpable In the scrotal sacs. One testis 13. A 2-month-old infant presents to your emer-
Is palpable high In the right Inguinal canal and gency department with a heart rate af 220 beats
cannot be gently manipulated into the anatom- per minute (bpm), palpable pulses, and ade-
Ically correct position. The left testis is not pal- quate perfusion. After giving the Infant oxygen,
pable but is discovered in the abdomen after you note abnormal P waves and a narrow QRS
consultation with a pediatric urologist and an (:S0.08 seconds) on the cardiac monitor. Which
abdominal ultrasound. In counseling the par- of the following Ia the beat course of action?
ents, which one of these statements regarding L Administer IV/10 epinephrine
cryptorchidism is true? b. Administer IV adenosine by rapid bolus
a. Mora than 99% of males have bilateral de- c. Administer IV calcium chloride
scended testes at age 1. d. Administer IV atropine by rapid bolus
b. Impaired sperm production Is not a concern e. Administer IV sodium bicarbonate
If nailtier testis descends.
1.. A 3-month-old infant presents with a history
c. Malignant degeneration is not a rtsk fac-
of abnormal movements that his parents think
tor for testes that do not descend as long
m ight be seizures. You observe an episode of
as ltiey are placed within the scrotal sac
recurrent rhythmic flexor-extensor spasms that
through surgery by 1 year af age.
repeat about 30 times before subsiding. The
d. This infant is no more likely than his peers to
electroencephalogram (EEG) shows hypsar-
manifest an inguinal hemia.
rhythmia, and a Wood lamp exam is positive
e. Microphallus Ia a commonly aaeociated
for several flat, hypopigmented macules scat-
condition.
tered over the skin surface. This child's infantile
10. A 5-yaar-old boy presents with a waddling limp spasms are mos1likely a result of which of the
and has had a stiff rtght hlp for the last 2 months. following underlying disorders?
He has minimal complaints of pain. Which af the L Von Reckllnghausen disease
following is the moet likely diagnosis? b. Tuberous sclerosis
L legg-calv&-Perthea disease c. Von Hlppei-Lindau disease
b. Slipped capital femoral epiphysis d. Sturge-Weber disease
c. Toddler's fracture .. Bilateral acoustic neurofibromatosis
d. Septic arthritis
15. A 21 -month-old girt arrtves at your clinic in May
e. Juvenile idiopathic arthritis with a vaccination 1'800rd that indicates that
11. A 17-year-old young girt on oral contraceptive she has received three DTaP doses, three HIB
therapy for regulation of her menstrual periods doses, three Inactivated polio vaccine (IPV)
presents with a 1-week history of left leg pain doses, three pneumococcal conjugate vaccine
and swelling. Evaluation with a Doppler ultra- doses, two hepatitis A vaccine doses, and three
sound reveals absence o1 flow in the left femoral hepatitis B vaccine doses. Which of the follow-
and popliteal veins. The clot extends proximally ing should be administered at this visit?
to the left external iliac vein. The most important a. DTaP, Hib, IP\1, varicella
potential complication that one should be cau- b. DTaP. Hib, pneumococcal conjugate ~
tious about in this girf is cine, measles, mumps, and rubella (MMR),
a. venous insufficiency and varicella
b. limb overgrowth c. DTaP. hepatitis A, IPv. pneumococcal conju-
c. pulmonary embolism gate vaccine
d. edema d. DTaP. hepatitis B, MMR, and varicella
.. gangrene e. DTaP. hepatitis A, IPv. MMR, and varicella
438 • Questions
11. lhe mother of a 3D-month-old boy is concerned L Initiate chelation therapy in a lead-free envi-
that the child's speech Is •garbled.• The child ronment within 48 hours.
uses "ma-ma" and "da-da" appropriately. He II. Redraw the blood lead level in 1 week and
usee about 30 other words, but most of them test all siblings; treat if 0!!:50 jlgldL
are mispronounced (for instance. •boo" instead c. Optimize calcium and iron intake and repeat
of "blue"). The boy's aunt, uncle, and cousins the b lood lead level in 1 month; treat if
came to visit for a weekend and were unable to ~50 J.&Qfdl.
understand more than half of what he said. Ex- d. Refer the family to a lead-removal company;
amination of the ears 1'8Veals nonnal canals with repeat the blood lead level 1 month after
translucent, mobile tympanic membranes and decontamination of the home, and treat If
visible landmarks. Which of the following eval- ~50 Jtg/dl.
uations for speech delay should be performed t. Refer the case to child protective services
first? for parental neglect.
& Receptive language testing
20. A young couple is In your office for their prena-
b. Phonetic testing tal visit, and you are discussing infant feeding.
c. Dysfluency evaluation The father states that he prefers that the mother
d. Tympanogram testing breastfeed the baby. The mother Is hesitant to
e. Audiologic (hearing) assessment commit to breastfeedlng because she plans on
17. A 13-year-old girl presents with recurrent ab- returning to full-time employment 6 weeks af-
dominal pain over the last 3 months. She has ter the child is bom. Neither her mother nor her
missed a total of 8 days of school. There is no sisters chose to breastfeed. She is concemed
associated fever, weight loss, and gastroin- that human breast milk may not provide all the
testinal bleeding, and the pain does not oocur nutrients that the child needs, and she believes
in relation to meals or awaken her from sleep. formula is a more complete nutritional source
There is diffuse abdominal tenderness but no for infants. She is willing to consider exclusive
other abnormal findings on examination. Which breastfeeding on the basis of the recommen-
approach is likely to help in the diagnosis and dation of the American Academy of Pediat-
management of her condition? rics. If her baby is exclusively breastfed, when
& Abdominal computed tomography (Cl) scan should the child begin receiving oral vitamin D
with contrast supplementation?
II. Upper and lower endoscopy and biopsies a. Never
c. Explaining the likely etiology of her symp- b. WHhln the first several days
toms using a biopsychosocial model and c. Age 2 months
symptomatic therapy d. Age 4 months
d. A diet history and a diet elimination trtal e
•• Age months
e. Referral to a psychiatrist 21. A 12-year-old female patient presents with fever,
night sweats, weight loss, fatigue, anorexia, and
18. A newborn male child has a flat facial profile, painless, rubbery, cervical lymphadenopathy.
upslanted palpebral fissures, epicanthal folds, What is the most common presentation of Hod-
a small mouth with a protruding tongue, small gkin disease?
genitalia, and simian creases on his hands. a. Fever, night sweats, and/or a weight loss of
Which of the following chromosomal disorders more than 10% In the preceding 6 months
Is most likely In this child? (i.e., B symptoms)
& Trisomy21 b. Mediastinal lymphadenopathy
b. Trisomy 18 c. Painless, rubbery, cervical lymphadenopathy
c. Trisomy 13 d. Pruritus
d. Klinefelter syndrome e. Extreme fatigue and anorexia
e. Turner syndrome
22. Which of the foUowlng medication groupings
19. At a 2-year well-ehild visit, you collect informa- Is most appropriate for a patient 12 years old
tion that your patient liVes in a very old rental w ith persistent asthma who has failed to achieve
home with peeling paint. Both the capiDary well-controlled asthma while receiving Step 2
(screening) and venous blood lead measure- treatment?
ments are 50 JLQ/dl. The patient has a history a. None
of constipation but is otherwise asymptomatic. b. A daily low-dose inhaled corticosteroid
Which of the following courses of action is most c. A daily medium-dose inhaled corticosteroid
appropriate? and a long-acting inhaled 112-agonist
Questions • 437
d. A dally low-dose Inhaled corticosteroid and d. Begin empiric amoxicillin and schedule the
a long-acting ~-agonist child for a renal ultrasound and voiding cys-
e. A dally medium-dose Inhaled corticosteroid tourethrogram within the next 6 weeks.
and nedocromll e. Admit the child to the hospital for IV am-
23. Crops of papular, vesicular, pustular lesions picillin and gentarnycln and schedule a dl-
starting on the trunk and spreading to the ex- mercaptosuccinic acid scan.
tremities, in addition to small, Irregular red spots 'D. A 3-month-old Infant presents with cyanosis
with central gray or bluish-white specks that ap- and an echocardiogram reveals that the child
pear on the buccal mucosa, Is the classic de- has tetralogy of Fallot. What four associated le-
scr1ptlon of which of the following Infections? sions describe tetralogy of Fallot?
a. Measles L Ventricular septal defect, overriding aorta.
b. Erythema lntectlosum {fifth disease) pulmonary stenosis, right ventricular
c. Roseola infantum hypertrophy
d. Zoster (shingles) b. Ventricular septal defect, atrial septal de-
e. Rubella fect, pulmonary stenosis, right ventricular
f. Hand-foot-mouth disease hypertrophy
g. Chickenpox c. Ventricular septal defect, atrial septal defect,
2A. A 20-month-old boy who was 1reated with aortic stenosis, right ventricular hypertrophy
high-dose amoxicillin (90 mg/kglday) for acute d. Ventricular septal defect, coarctation of
otitis media 3 weeks ago now presents with the aorta, aortic stenosis, right ventricular
acute-onset ear pain, a bulging, erythematous hypertrophy
right tympanic membrane, and 1'9duced mobility t. Ventricular septal defect, mitral valve pro-
on pneumatic otoscopy examination. Which of lapse, pulmonary stenosis, left ventricular
the following is the most appropriate antibiotic hypertrophy
choice for this child? 28. A 3-year-old boy with a known diagnosis of fac-
L Azithromycin tor XI deficiency presents to the emergency de-
b. Amoxicillin-clavulanate partment with uncontrolled bleeding from a lip
c. Erythromycin laceration following a fall. The most appropriate
d. Trimethoprim-sulfamethoxazole product that can be used for fac1or replacement
e. Dlcloxaclllln in this child before suturing is
25. Which of the foUowing is considel'9d a risk factor L cryoprecipitate
for neonatal respiratory distress syndrome? b. granulocyte Infusions
L Neonatal sepsis c. fresh frozen plasma
b. Poorly controlled maternal diabetes d. platelet transfusion
c. Maternal preeclampsia e. DDAVP
d. Neural tube defects
29. At the health maintenance visit for a 12-year-old
e. Trisomy 21 male, you note that he has entered his pubertal
28. A mildly febrile 6-year-old patient presents to height growth spurt. The patient's mother asks
your office with dysuria and urinary frequency about what changes her son should be expect-
and urgency. She has a history of one prior uri- Ing In his body over the next several years. As
nary tract infection about 8 months ago. You part of your 1'9View, you mention that the most
obtain a dipstick urinalysis and send a urine typical sequence of pubertal events in males is
culture. The dipstick is positive for nittites and which of the folowing?
leukocyte esterase. Which of the following Is a. Peak height velocHy, pubarche, penile en-
the most appropriate course of action at this largement, testicular enlargement
t ime? b. Peak height velocity, testicular enlargement,
a. Awalt culture results and tailor therapy on penile enlargement, pubarche
the basis of bacterial sensitivities. c. Testicular enlargement, pubarche, penile en-
b. Begin empiric antibiotics; monitor with uri- largement, peak height velocity
nalysis every month x 3. d. Testicular enlargement, peak height velocity,
c. Begin empiric amoxicillin and schedule the penile enlargement, pubarche
child for a renal ultrasound within the next 6 1. Pubarche, testicular enlargement, peak
weeks. height velocity, penile enlargement
438 • Questions
30. A 4-year-old chUd wHh known asthma pres- c. Anti-double-stranded DNA (dsDNA) antibody
ents to the emergency department w ith a chief d. Anti-5mith (Sm) antibody
complaint of wheezing for the past 8 hours. On e. Anti-Ro (SS-A) antibody
examination, he is alert and cooperative, mildly
33. A 3-month-old female infant presents to your
tachypneic, has diffuse loud expiratory wheeze,
emergency department unresponsive and with
and has a pulse oximetry reading of 89% while
fever, tachypnea, bradycardia, and hypoten-
breathing room air. He has already taken three
sion. What order should you follow in your initial
albuterol aerosols at home in the past hour. He
assessment?
is unchanged after receiving another albuterol
L Airway, breathing, clrculatton, disability,
inhalation treatment in the emergency depart-
exposure
ment. Appropriate next management would
include b. Breathing, airway, circulation, disability,
exposure
a. supplemental oxygen
b. albuterol inhalation c. Circulation, airway, breathing, exposure,
disability
c. lpratropium bromide inhalation
d. oral corticosteroids d. Exposure, breathing, airway, circulation,
e. all of the above disability
e. Exposure, airway, breathing, circulation,
31. A pi'8Viously healthy 3-year-old boy pi'8Sents disability
with a history of fever and diarrhea for the past 34. A 4-year-old male child presents with abrupt-
2 days. The fever has not responded to Ibupro- onset petechiae and ecchymoses. Other than
fen, and his urine output has decreased today. the sldn findings, the child appears well and
On examination, he is alert, has a temperatul'9 of Is hemodynamically stable. No splenomegaly
101•F, has a heart rate of 115 bpm, has a blood Is noted. A CBC reveals a normal WBC count,
Pl'888ure of 105160 mm Hg, and has mild diffuse a nonnal hematocrit, and a platelet count of
abdominal tenderness. The serum electrolytes 12,000/mm8 • Large platelets are seen on the
are normal, but his BUN is 60 mgldl and his peripheral smear. No premature white cell forms
serum creatinine is 1.8 mgldl. The complete are seen on peripheral smear. The parent reports
blood count (CBC) is normal. Urinalysis shows that the child had a viral illness 2 weeks before
1+ protein, small blood, and occasional hyaline presentation. Which of the following Is the most
casts. The kidney ultrasound is normal. Which likely diagnosis?
of the following statements regarding his acute a. lsoimmune thrombocytopenia
renal failure is most accurate? b. Leukemia
a. It is due to hemolyti~uremic syndrome. c. Sepsis
b. It Is due to pyelonephritis. d. Immune thrombocytopenic purpura
c. It Is due to Interstitial nephritis. e. Hypersplenism
d. It Is due to the use of Ibuprofen In a dehy- 35. A child presents with a reduced number of
drated state. CDS.. T cells, an increased number of B lympho-
e. It Is due to urinary tract obstruction. cytes that are mildly abnormal in function, has
32. A 14-year-old girl presents with several weeks of a conotruncal heart lesion, hypoplastic thymus,
profound fatigue, Intermittent low-grade fevers, and hypocalcemia. Which of the following chro-
a facial rash, and Joint pain. The rash recently mosomal disorders is most likely in this child?
worsened markedly after sun exposure. On a. Zellweger syndrome
physical examination, she has a malar rash ex- b. Mlcrodeletlon of 22q112
tending over the bridge of the noaa (but sparing c. Trisomy 13
the nasolabial folds), painless oral ulcers, and d. Gaucher disease
painful limitation of movement in her wrists and e. Wilson disease
finger joints. On laboratory testing, her white 38. A 4-month-old, former 30-week premature in-
blood cell {WBC) count is 3,500/mm' , Hgb is 9.5 fant is seen in late October for well-child care.
gldL, and platelet count is 120,000/mm'. A uri- His mother is concemed about the transfusions
nalysis shows 15 to 19 red blood cells per high that the Infant required during her course in the
power fteld and an elevated protein of 100 mgl neonatal Intensive care unit and wishes to re-
dl. Which of the following tests will most likely strict her exposure to blood products. Refer-
be positive? ral for administration of which of the following
1. Antinuclear antibody (ANA) would be most appropriate to limit her rtsk of
b. Rheumatoid factor aevere bronchiolitis?
Questions • 439
L Rlbavlrtn the following is the most likely etiology of his be-

b. Nasal Influenza vaccine havior problems?
c. InJected lnftuenza vaccine a. Tay-Sachs disease
d. Riboflavin b. Gaucher disease
• · Intramuscular palivizumab c. Nlemann-Pick disease
d. Adrenoleukodyat.n:>phy
37. llle mother of a 2-month~ld infant brings her
daughter to your office durtng the summer for
e. Rett syndrome
her regular heatth maintenance vlsH. The child 411. An 8-year-old girl thought to have attention-defi-
Is cal8d for by her maternal grandmother 3 cit disorder Onattentlv&-type) undergoes EEG
days a week while the mother is at work. The testing and Is found to have a 3-Hz spike-and-
infant is exclusively fed a cow milk-based com- wave pattern. Results of the EEG, coupled w ith
mercial fonnula when she is with the mother; videotaping of episodes of the patient's •Inatten-
the grandmother believes that the child should tion, • lead to a diagnosis of childhood absence
also receive juice diluted with water because of epilepay. Which of the following is moat app~
the wann weather. Which of the following rep- priate for initial treatment of the child's disorder?
resents the most appropriate dietary counseling L Methylphenidate
regarding this infant's diet? b. Carbamazepine
L Formula-fed infants at this age require free c. Adrenocorticotropic hormone
water supplementation during warm months d. Ethosuximide
to maintain optimal hydration. e. Phenobarbital
b. Formula-fed Infants at this age
raquiM glucose supplementation during
41. A child presents with lymphedema of the hands
and feet, a shield-shaped chest, widely spaced
the wann months to maintain optimal
hypoplastic nipples, short stature, and multiple
calortc Intake.
pigmented nevi. In addition, she had a coarcta-
c. Formula-fed Infants do not require any addi-
tion of the aorta that was repaired and has renal
tional vitamin, mineral, caloric, or fluid sup-
d isease. Her parents continue to be worried that
p lementation beyond their fonnula for the
1here is something in addition to her heart condi-
first 6 montha of life.
tion that is causing failure to thrive. Which of the
d. Dilution of this infant's formula with water
foDowing chromosomal disortlers is most likely
or juice on the days that she is with 1he
in this child?
maternal grandmother is unnecessary but
L Trisomy 21
harmless.
b. Trtsomy 18
e. This infant should be switched to a soy pro- c. Trtsomy 13
tein-based fonnula.
d. Klinefelter syndrome
38. No red reflex is seen on funduscopic examina- e. Turner syndrome
tion of a newborn. Which of the following is the
42. A 14-year-old patient familiar to the emergency
most likely diagnosis?
room staff because of multiple visits in the last
L Retinoblastoma
3 months Is brought In by her mother for Inges-
b. Leukocorla
tion of an unknown number of acetaminophen
c. Congenital cataract
tablets. The mother states that she keeps all
d. Congenital glaucoma
the medicines In the house locked up because
e. Toxocariasls
''this is just the sort of thing my daughter would
38. A 5-year~ld boy is brought to your office com- do to me." She aaw the girt stuffing something
plaining of progressive fatigue, weakness, and into her bedside drawer while she was passing
nausea over the past few months. He was a the girt's room and discovered a bottle marked
model student, but he is now having trouble in "acetaminophen 500 mg. 250 tablets." Only four
school and displaying frequent outbursts, the tablets remained in the bottle. The mother did
last of w hich resuHed in his being sent home for not believe that her daughter took the tablets
hitting another child. Initial lab results show mild until she began vomiting about an hour later.
hypoglycemia, hyponatremia, and hyperkale- The girl refuses to speak in her mother's pres-
mia. The child Is diagnosed with adMnal Insuf- ence but eventually admits that she took •many
ficiency and treated approprtately; however, his tablets" about 4:00 PM (3 hours ago). Which of
behavior continues to worsen, and he begins to the following Is recommended as an antidote for
have difficulty walking and speaking. Which of this patient's ingestion?
440 • Questions
L Atropine sulfate of two separate agents In the past. You believe

b. Hemodialysis that the patient may benefit from switching to
c. Whole bowel irrigation a nonstlmulant medication. Which of the follow-
d. Oral N-acetyl cysteine Ing medications approved for the treatment of
e. ActiVated charcoal attention-deficit/hyperactivity disorder Is classi-
fied as a nonstlmulant?
43. Which of tl'le following scenarios is consistent
L Oral atomoxetine
with abuse rather than accidental injury?
b. Oral lisdexamfetamine
L A 30-month-old child wtth a bucket handle
fracture
c. Oral methylphenidate
d. Oral dextroamphetamine
b. A 12-month-old infant w ith a lib fracture
c. A 6-monttl-old infant with retinal hemor-
e. Oral mixed amphetamine salts
rhages in the absence of signs of external 48. A 9-month~ld girl presents with a 3-day history
head trauma of fever to 103°F (39.4°C). This morning, the girt
d. Abdominal bruises In a 9-mon1h-old Infant developed a rash. On physical examination, the
e. All of the above girl is afebrile and has an erythematous, macu-
lopapular rash over her trunk, arms, and legs.
44. A 2-year-old presents wilt1 painless rectal bleed-
Which of the following Is the most likely cause of
ing. The hemoglobin Is 9 gfdl. Capillary refill re-
this patient's illness?
mains normal. The next best step to positively
L Human parvovirus 819
Identify the cause of bleeding Is
L colonoscopy
b. Measles
b. transfusion with packed red blood cells c. Human herpesvirus 6
d. Chickenpox
c. Meckel diverticulum scan
e. Group A ji-hemolytic streptococci
d. gastric lavage
e. stool culture 48. A 2-year-old child is brought to the emergency
department following a brief (< 2 minut es) gen-
45. A 3-week-old male infant presents to the emer-
eralized seizure. Initial vitals include a tempera-
gency department with a 24-hour history of
ture of 102.9°F. Following the history, physical
vomlltng and poor feeding. He Is found to be hy-
examination, and laboratory studies, you deter-
potensive and hypoglycemic. His serum electro-
mine that the patient has had a febrile seizure.
lyte values are as follows: Na 121 mmoVL, K 6.9
The parents are appropriately concerned and
mmoVL, C02 20 mmoVL. chloride 105 mmoVL.
have a number of questions. You would be cor-
BUN 17 mg/dL, creatinine 0.7 mgldl, and glucose
rect In telling them which of the following?
36 mgldL He receives 20 mllkg normal saline
L Children who experience a single febrile
fluid bolus and 2 mllkg dextrose 25. What other
seizure have no greater risk or subsequently
life-saving intervention should this infant receive?
developing epilepsy than children who have
a. IV aztthromycln
not experienced a febrile seizure.
b. IV bicarbonate
b. The morbidity and mortality 888ociated with
c. IV hydrocortisone
d. IV albumin febrile seizures is extremely high.
e. IVcalcium c. At least half of patients who experience an
initial febrile seizure will experience seizures
48. A 7-year-old girl presents with a 3-week history wtth subsequent episodes of fever.
of dozens of asymptoma11c red, scaly 5 to 10 d. Patients who have experienced a single fe-
mm plaques appearing on the trunk. When the brile seizure should be placed on preventa-
scales are pulled otr, they bleed. Her nails are tive anticonvulsant medication.
pitted. The most appropriate laboratory test Is e. Febrile seizures are usually assocla1ed wHh
a. A bacterial culture of the red plaques Intracranial Infections.
b. A fungal culture of the red plaques
c. A throat culture 50. A 3-year-old boy presents with an elbow hemar-
throsis after falling on his elbow. There is no
d. A Tzanck smear
history of spontaneous bleeding. There is no
e. ACBC
history of epistaxis, gingival bleeding. or cuta-
47. An 8-year~ld patient of yours with attentlon- neous bruising. The child's maternal grandfa1her
deflcttlhyperactlvlty disorder Is experiencing had frequent spontaneous bleeding and hemar-
unacceptable adverse effects because of his throses after trauma on multiple occasions.
stimulant medication. You have prescribed Im- Laboratory results revealed a prolonged partial
mediate- and extended-release preparations thromboplastin time, normal prothrombin time,
Questions • 441
and a platelet count of 150,000/mm'. The fac- position. A uid is obtained via thoracentesis for
tor VIII coagulant activity (VJII:c) is low and the Gram stain and culture. Which of the following
factor IX level Is normal. What Is the most likely is the most likely pathogen responsible for this
diagnosis? boy's pneumonia?
•· Idiopathic thrombocytopenic purpura •· Staphylococcus aureus
b. von Willebrand disease b. Nontypeable HaernophHus influenzas
c. Vrtamin K deficiency c. Ch/amydophila pneumoniae
d. Hemophilia A d. Klebslslla pn6Umonlae
e. Uver disease e. Mycoplasma pneumoniae
51. A 10-week-old boy Is brought to the emergency 54. During a routine annual physical examination,
department by his mother with a history of fail- a 9-year-old previously healthy girl has a blood
ure to thrive and poor feeding. He occasion- pressure of 140175 mm Hg in all four extremities.
ally vomita small amounts of formula. His birth The physical examination Is otherwise com-
weight, length, and head circumference were pletely normal, except for obesity. The family
at the 50th percentile; however, his weight has history is positive for hypertension in the father
dropped to the 1Oth percentile and his length and paternal uncle. The blood pressure remains
to between 25th and 40th percentiles. His vi- In the 140/70 mm Hg range on two repeat ex-
tal signs are normal, and the physical exam is aminations performed 1 week apart, using a cuff
otherwise unrevealing. Venous blood gas and that is appropriate for her obesity. The urinalysis,
electrolyte study results include pH 7.32, so- serum electrolytes, and serum c1'88tlnlne levels
dium 134 mEq/L, potassium 4.5 mEq/L, chlo- are normal. Which of the following is the moat
ride 106 mEqll, and bicarbonate 10 mEq/L appropriate next step in the management of this
Which of the following diagnoses Is the most patient?
likely? L Reassure the patient that her blood pressure
L Inborn error of metabolism is normal for her size.
b. Renal tubular acidosis b. Advise observation, with repeat blood pres-
c. Pyloric stenosis sure checks every month.
d. Chronic diarrhea c. Advise an immediate evaluation by a ne-
e. Cystic fibrosis phrologist and cardiologist.
52. A 2-year-old girl presents with a swollen left d. Advise a regimen of weight reduction and
knee, limping, and moming stiffness in the left regular exercise.
knee of 3 months' duration. On physical exam- e. Advice a regimen of diuretic therapy.
Ination, there Is a left knee Joint effusion, syno- 56. A parent brings her 12-week-old child to your
vial thickening, and limitation of movement. In office because he has a scaly facial rash. The
addition, the left leg is longer than the right and boy was exclusively breastfed for 8 weeks but
there is atrophy of the quadriceps. The remain- was switched to commercial cow milk-based
der of the review of systems and physical ex- formula about a month ago when his mother
amination is normal. On laboratory testing, CBC went back to work. She has been putting lotion
Is normal. An ANA test is positive at a titer of on the rash, but It has not helped. The child's
1:320. This child is at most risk for which of the birth weight was at the 50th percentile but has
following sequelae/complications? now dropped toward the 25th percentile line.
a. Glomerulonephritis The physical examination reveals an eczema-
b. Hemolytic anemia tous rash over both cheek$. The stool is guaiac-
c. Chronic, nongranulomatous anterior weitis positive but not grossly bloody. On the basis of
(lr1docyclltls) history and physical examination, you suspect
d. Acute anterior uveitis Or1docyclltls) that the patient may be allergic to cow milk pro-
e. Rheumatic heart disease tein. Which of the following is the best next step
53. A 9-year-old boy diagnosed with pneumonia 2 in the management of this patient?
days ago presents to the emergency depart- L Recommend that the mother sea her obste-
ment via ambulance in respiratory distress. His trician about medication to help her begin
past medical history is noncontributory, and he lactating again.
is at low risk for contracting tuberculosis. He b. Switch the patient from cow milk4)ased for-
Is hypoxic and requires oxygen. A STAT porta- mula to whole cow's milk.
ble chest radiograph 1'8Veals a large r1ght-slded c. Switch the patient from cow milk4)ased for-
pleural effusion, which shifts In the decubitus mula to soy formula.
442 • Questions
d. Switch the patient from cow milk-based for- 59. An unresponsive adolescent patient is brought
mula to a protein hydrolysate fonnula. to the emergency department with suspected
e. Begin parenteral alimentation to permit total Ingestion of an unknown substance. Emergency
bowel rest. medical services received a call from the hotel
room where the youth was found, but no one
58. A 16-year-old male is brought to your office by
else was there when they arrived. The patient
his mother, who insists that you perform a urine
is on 100% inspired oxygen and has required
drug screen on her son. You begin by interview-
several bouts of positive pressure ventilation in
ing the mother and the young man together,
the ambulance. On exam, 1he patient has a heart
but explain to the parent that you will also be
rate of 55, blood pressure 85/50, pinpoint pu-
conducting part of the interview and the physi-
pils, and track lines on his left arm. Along with
cal examination without her present in the room.
ongoing cardiovascular and respiratory support,
She states that she will only agree to let you
which of the following should be administered
speak with him alone It you agree to discuss
with her any high-risk behaviors that he admits
to this patient?
to engaging ln. Concerning patient confidential- a. Pralidoxime chloride
b. Physostigmine
ity in regard to adolescents, you are required by
law to inform the parent of this minor of which of
c. Naloxone
d. Atropine sulfate
the following?
L Use of marijuana
e. Desterrloxamlne
b. Suicidal ideation 80. A 15-month-old boy Is brought to the emer-
c. Petty theft gency department with a fever and difficulty
d. Consensual sexual relations with another breathing. Right-sided wheezing Is noted on the
minor of the opposite gender physical examination. The patient does not im-
e. Consensual sexual relations with another prove with aerosolized nebulizer treatment. An
minor of the same gander Inspiratory chest radiograph Is nonnal; however,
the expiratory film demonstrates r1ght-slded
57. You see a 4-year-old child for declining school
hyper1nflatlon, with mediastinal shift to the left.
performance and behavior problems. His
This patient's respiratory symptoms are most
mother notes that he is a poor sleeper. He
likely caused by which of the following?
snores loudly and often gasps in his sleep.
L Pneumonia
Sometimes she sleeps with him because she is
b. Foreign body aspiration
afraid he will stop breathing. You note a slight
c. Pneumothorax
fall off the growth curve and very large tonsils. A
d. Empyema
neck film demonstrates large adenoids as well.
The child's Insurance company will not pay to
e. Viral upper respiratory infection
have the tonsils and adenoids removed unless 61. You are seeing an 18-month-old boy who is
you can prove they are causing him significant new to your practice. His father Is concerned
health problems. Which test is the most likely to about his child's development in relation to his
give you that infonnatlon? two older brothers. The boy avoids eye contact
L Bronchoscopy and does not respond to efforts to engage him
b. Overnight pulse oximetry monitoring in reciprocal play such as peek-a-boo and patty
c. Polysomnography cake games. He does not generate spontaneous
d. Fluoroscopy language but can repeat certain words if spoken
e. Overnight EEG monitoring to him over and over. He spends a lot of time
by himself rocking back and forth and becomes
sa. An Infant who was discharged from the hospital very agitated If this actlvtty Is Interrupted. Which
on day-of-life presents to your otnce 3 days later
of the following condlttons Is most consistent
for follow-up. The mother did not receive prena-
with this child's reported behaviors?
tal care. You notice bilateral purulent discharge
L Down syndrome
from the eyes. There is marked eyelid edema
b. Hearing impairment
and conjunctival swelling (chemosis). What is
1he most likely pathologic agent?
c. Autism
d. Attention-deficit/hyperactivity disorder
a. Chlamydia trachomatis
e. Asperger syndrome
b. Neisseria gonorrhoeae
c. Group B Streptococcus 82. An 8-year-old boy is referred to the emergency
d. Toxoplasma gondH department by his pedlab1clan for a chief com-
e. Treponema pall/dum plaint of weakness. The weakness has been
Questions • 443
slowly progressive over the last several weeks. A d. Inflammatory bowel disease
review of symptoms rwveals a history of consti- e. Necrotizing enterocolitis
pation, polyuria, and polydipsia. The child is on
no medications, and past medical history is non- ffl. A 4-year-old boy was seen by his pediatrician
for fever and abdominal pain. The pain began
contributory. In the primary physician's office,
the patient had a serum potassium measure- after a sledding accident the day before his visit
ment of 2.8 mEqiL A blood pressure measure- in which he fell on his right side. His mother
ment in the emergency department is normal for noticed that his abdomen appeared distended
today, particularly on the tight side. In the pedi-
age, height, and gender. Urine electrolyte stud-
atrician's office, he Is noted to be hypertensive
Ies reveal an elevated urine potassium value.
and has gross hematuria. What Is the most likely
Which of the following conditions is the most
d iagnosis?
likely cause of this patient's hypokalemia?
a. Excessive sweating a. Pyelonephritis
b. Renal tubular acidosis b. liver contusion
c. Anorexia nervosa c. Renal contusion
d. Cushing syndrome d. Wilms tumor
e. Renovascular disease e. Neuroblastoma
83. A 2-week-old female infant preaenUI with gen- 88. You are called to evaluate a newborn with an
eralized hypotonia, duodenal atresia, and hypo- apparent foot deformity. On close examination,
thyroidism. What other structural defect is she you note adduction of the forefoot, inversion of
most likely to have? the foot, and plantar flexion at the ankle that is
a. Malrotation relatively fiXed. Which of the following is true of
b. Endocardial cushion defects this patient's condition?
c. Cleft palate L This clinical picture is most consistent with
d. Renal disease metatarsus adductus.
e. Sensorineural hearing loss b. This deformity will respond to stretching
exercises.
84. Which of the following condttion(s) is (are) often
c. This deformity will correct spontaneously
associated with polyhydramnios?
when the child Is able to bear weight.
L Duodenal atresia
d. This deformity will require surgical repair.
b. Tracheoesophageal fistula
c. Congenital hydrocephalus w ith e. This deformity may be associated with other
congenital malformations.
myelomeningocele
d. Renal agenesis
88. A 12-year-old boy with Crohn disease for
e. a, b,and c 2 years is seen with an acute exacerbation. He
85. A 3-year-old boy presents w ith violent episodes is complaining of abdominal pain and diarrhea
of intermittent colicky pain, emesis, and blood and has right lower quadrant fullness. The most
per rectum. A tubular mass is palpated in the effective approach in this acute setting is which
right lower quadrant. The abdominal radiograph of the following?
reveals a dearth of air in the right lower quadrant L Perform a colonoscopy for cancer
and air-fluid levels consistent with ileus. Which surveillance.
of the following procedures will best assist In di- b. Obtain a stool culture to exclude acute In-
agnosis and treatment? fectious colitis and Imaging studies to evalu-
L Esophag~roduodenosoopy ate for abscess or fistula.
b. Rectal b iopsy c. Initiate therapy with mercaptopurine or
c. Air contrast or double-contrast enema azathioprine.
d. Stool culture d. Perform a capsule endoscopy.
1. Colonoscopy e. Start biologic therapy with anti-TNF alpha
antibody.
88. An 18-month-old female child presents with
blood-streaked stool. The stool Is grossly posl- 70. A 3-year-old girl periodically experiences swell-
ttve on occult blood testing. Which of the follow- Ing around her lips and breaks out In hives when
Ing diagnoses Is most likely? she eats the snacks provided at daycare. Which
a. Anal fissure of the following is the most appropriate for de-
b. Peptic ulcer disease termining whether the child's symptoms are
c. Mallory-Weiss tear caused by food allergies?
444 • Questions
L Skin prick testing to foods d. Acute leukemia

b. Food--specific immunoglobulin E levels e. Sickle cell disease
c.Skin prick testing to foods followed by
74. An adolescent comes to you w ith a chief com-
doubl~blind placebo-(X)ntrolled food
plaint of painless vaginal discharge. You note
challenges
projection of the breast areola as a secondary
d. Open-label food challenges
mound above the contour of the breast and pu-
e. Endoscopy bic hair of adult texture and color with no spread
71. An 11-year-old girl is referred to your office fol- to the medial surface of the thighs. This patient's
lowing an abnormal screen for scoliosis. You examlna1ton Is most consistent wHh which Tan-
diagnose idiopathic scoliosis on exam using ner stage of development?
Adam's forward bending test. Subsequent ra- L Stagel
diographs reveal a lateral curvature of 35°. The b. Stagell
patient is premenarchal. You refer the patient to c. Stage Ill
an orthopedic surgeon and counsel the parent d. Stage IV
that the specialist will probably recommend e. StageV
L extemal bracing
75. Which of the following statements about acute
b. follow-up radiographs every 6 months
myeloid leukemia (AML) Is true?
c. stretching exercises L The preferred treatment tor all types of AML
d. surgical fixation is bone marrow transplant.
e. no intervention b. Chemotherapy used for AML is more in-
72. A child in the emergency department has point tense than that used for acute lymphocytic
tenderness over the proximal tibia and an appro- leukemia.
priate history of trauma. The radiograph shows c. Hyperleukocytosis is not a problem
a fracture through the growth p late that extends withAML
into the epiphysis and joint space. This type of d. Patients w ith Down syndrome and AML
fracture would be character1zed as which of the have a worse prognosis.
foUowing? e. Secondary AML has a good response to
L Satter41arris type I therapy.
b. Salter4iarrls type II 78. A 13-year-old male patient preaenbJ with inter-
c. Salter-Harris type Ill mittent abdominal pain, diarrhea, weight loss,
d. Satter41arris type IV and growth failure and is noted on colonoscopy
e. Salter-Harris type V to have inflammatory skip lesions throughout
73. A 4-year-old Caucasian boy presents for evalu- the colon with rectal sparing. Which of the fol-
ation of persistent jaundice. The family reports lowing statements is true?
that the boy had neonatal Jaundice on the ftrst L Ulcerative colitis is typically characterized by
day of life and was treated with phototherapy. rectal sparing.
He has always had mild icterus, but has had b. Ulcerative colitis is typically characterized by
Increased Icterus at times, especially following skip lesions.
other mild illnesses, such as ear infections and c. Crohn disease Is typically character1zed by
colds. There is a family history of his father and transmural disease.
patemal grandmother having undergone sple- d. Ulcerative coiHis Is more likely than Crohn
nectomy. On examination, the boy has mild disease to be associated with growth failure.
scleral icterus, and his spleen is palpable about e. Ulcerative colitis is typically associated with
3 em below the left cos1al margin. The laboratory perianal disease.
evaluation reveals a to1BI bilirubin of 1.9 mgldl 77. You are moonlighting In the pediatric emergency
(unconjugated fraction is 1.5 mgldl), normal liver department when a 10-year-old male arrives by
1ransaminases, hemoglobin of 112 gldl. a nor- ambulance wnh lethargy, confusion, dizziness,
mal mean corpuscular volume, and an elevated and a severe headache. His parents and mater-
reticulocyte count of 8%. An osmotic fragility nal grandmother are in the aduH em91gency de-
test is performed and demonstrates positive re- partment w ith less severe but similar symptoms.
sults. What is the most likely diagnosis? The emergency medical technicians report
L Iron-deficiency anemia that they were called by the police who found
b. Hereditary spherocytosis the family sleeping in their car with the engine
c. Acute blood loss running at their Christmas tree stand. Carbon
Questions • 445
monoxide poisoning is suspected. Which of the •. 2years

following should be the first step in the evalua- b. 3years
tion and management of this patient? c. 4years
L Obtain an electrocardiogram d. 5years
b. Draw an arterial blood gas e. 6years
c. Draw a blood carboxyhemoglobin level
81. A child weighing 27 kg with a history of vomiting
d. Administer 100% oxygen
for 36 hours is judged to be 10% dehydrated
•· Stabilize the patient for transfer to a hyper-
on the basis of vital signs and physical exam-
baric oxygen chamber
Ination. The serum sodium measurement Is 134
78. An unvaccinated 5-year-old girt presents to the mEq/L An Initial 540-ml bolus of normal saline
emergency department with a 12-hour history results In stabilization of the heart rate and Im-
of fever and 1'88piratory distl'988. On physical proved capillary refill. Which of the following Is
examination, the girl appe&r.~ toxic, is drooling, the most appropriate parenteral fluid choice for
and leaning forward with her chin extended. She the next 8 hours?
has a temperature of 104°F (40°C) and a respira- a. 0 5 0.2 normal saline with 20 mEq/L KCI
tory rate of 32 breaths per minute. Which of the (added after urination) at 120 mLJhr
following is the most likely diagnosis? b. D5 0.2 normal saline with 20 mEq/L KCI
L Epiglottitis (added after urination) at 180 mLJhr
b. Croup c. D6 0.45 normal saline with 20 mEq/L KCI
c. Bacterial pneumonia (added after urination) at 220 mLJhr
d. Diphtheria d. D6 0.45 normal saline with 20 mEq/L KCI
e. Anaphylaxis (added after urination) at 90 mllhr
e. D5 0.45 normal saline wtth 20 mEq/L KCI
1'9.ln response to your question concerning guns (added after urination) at 180 mllhr
in the home during a routine adolescent health
maintenance visit, the mother of the patient 82. An 8-year~ld boy presents with growth failure
tells you that her husband, the boy's stepfa- and vague abdominal pain. The abdomen is dis-
ther, keeps a loaded handgun In the bed tabla tended. There is no perianal disease, abdominal
drawer for protection. You would be ccrract In mass, or tenderness. The next set of diagnostic
telling this family that an adolescent who lives In tests should Include the following:
a home with a gun L CBC, C-reacttve protein, tissue transglutam-
a. is less likely than peers who do not live with lnueassay
guns to die from homicide. b. CT of the abdomen
b. is less likely than peers who do not live with c. urinalysis, sweat chloride, laparotomy
guns to commit suicide. d. colonoscopy, upper endoscopy
c. is mature enough to use good safety pre- e. stool culture for ova and pa111Sites
cautions, so storing the handgun separately 83. A 3-year-old boy presents to the pedlatr1clan
from the ammunition is unnecessary. with fever, pallor, anorexia, Joint pain, petechiae,
d. has a 10-fold greater risk of dying from sui- and hepatosplenomegaly. Which of the follow-
cide than peers who do not live in homes ing is the most likely diagnosis?
with guns. a. Acute lymphoblastic leukemia
e. Is less likely than peers who do not live with b. Acute myelogenous leukemia
guns to be shot during a domestic dispute. c. Juvenile chronic myelogenous leukemia
d. Aplastic anemia
IIJ. You are seeing a new patient for a health main-
1. Osteosarcoma
tenance visit. The child is able to tell you his
age and gender and speaks in five-to-eight- 84. A 16-year-old girl who Is 2 years postmenarche
word sentences. His grandmother tells you that presents wtth mild ly uneven shoulders and a
he is able to pedal a tricycle. He can perform small degree of one--aided r1b prominence. Ra-
a broad Jump when the behavior Is modeled d iographs reveal a 25° scoliosis. Which of the
and Is able t o copy a circle. However, he can- following represents the best treatment?
not yet balance on one foot or copy a cross. a. Posterior spinal fusion
You record that the patient's developmental b. Intensive physical therapy
achievement is consistent with his age. Which c. Scoliosis bracing
of the following most closely correlates with d. Spinal manipulation
this child's age in years? 1. Observation w ith repeat x-ray in 1 year
446 • Questions
85. A 5-year-old boy who returned from a camp- 88. A 12-year-old male adolescent presents with a
Ing tr1p to his grandparents' farm In VIrginia 1-month history of fever, weight loss, fatigue,
develops a fever of 103°F, a headache, vom- and pain and localized swelling of the midprox-
iting, and an erythematous, macular rash on imal femur. Which of the following is the most
his wrists and ankles. On physical examination, likely diagnosis?
he is moderately tachycardic with otherwise a. Ewing sarcoma
stable vital signs and no focal signs of infec- b. Osteosarcoma
tion. A CBC reveals a normal WBC count and c. Chronic osteomyelitis
differential and normal hemoglobin. However, d. Benign bone tumor
the boy's platelet count is 65,000/mm3 • Serum e. Eosinophilic granuloma
electrolytes are normal. Blood cultures and im-
munofluorescent studies are sent. Which of the a. You are examining a 3-year-old girl at her well-
following is the most appropriate next course child visit. While she is staring at her stuffed cow
of action? in your hands, you quickly cover her right eye
•· Discharge home on amoxicillin with close with an Index card. When the Index card Is re-
follow-up and reliable caregivers moved seconds later, you notice that the right
b. Discharge home on amoxlclllln-clavulanlc eye •drifts" back toward the center. This reac-
acid with close follow-up and reliable tion in response to the cover test indicates what
caregivers abnormal condition?
c. Hospitalization for observation pending fur- a. Strabismus
ther test reeul18 b. Amblyopia
d. Hospitalization for IV doxycycline and c. Leukocorla
cefotaxlme d. Retinoblastoma
1. Hospitalization for IV doxycycline e. Nasolacrimal duct obstruction
a&. A 5-year-old boy presents with painful swelling 90. A 14-year-old gir1 is brought to your office by her
of the hand and feet since the day before. Since mother because she Is complaining of •seeing
ear1ier today, he has palpable purpura on the double.• The history is significant for headaches
lower extremities, and also developed intermit- that waken the patient from sleep In the morning
tent, colicky midabdominal pain. Prior to these but are relieved by vomiting. On physical exam-
events, he had a cold for 1 week. He did not have ination, you note that she is unable to abduct
fevers and overall is well appearing. On physical either eye. Lower-extremity reflexes are slightly
examination, he has normal vital signs. He has exaggerated. Which of the following physical
palpable purpura on the lower extremities and signs is moat likely to be present in this patient?
buttocks. He has scrotal swelling. His hand and a. Hypotension
feet are puffy, and he has pain with movement b. Papilledema
of the ankle joints. His abdominal examination is c. Tachycardia
unremarkable. A CBC shows normal results with d. Patency of the anterior fontanelle
a platelet count of 360,000/mm3 • Which of the e. Erythema migrans
following laboratory tests Is most often abnor- 91. A previously healthy 4-year-old girl presents
mal in this disease process? with a history of diarrhea and vomiting for the
a. ANA
past 3 days and decreased urine output for
b. Antineutrophil cytoplasmic antibody the past 12 hours. On examination, she has a
c. Complement CS and C4 levels heart rate of 120 bpm, blood pressure of 105165
d. Urinalysis mm Hg, and no edema. The blood tests reveal
1. Serum creatinine
a serum sodium of 128 mEqll.. potassium 5.6
87. A 12-month-old male Infant presents with a he- mEq/L. bicarbonate 12 mEq/L, BUN 55 mgldl,
moglobin of 7.5 and a hematocrit of 22%. The and creatinine 1.6 mgldL. The urine tests reveal
mean corpuscular volume is 65 and the ad- a fractional excretion of sodium of 0.1. The kid-
justed reticulocyte count is 1.0%. What is the ney ultrasound is normal. Which of the follow-
most likely cause of anemia in this child? ing constitutes the most appropriate immediate
a. Iron-deficiency anemia management of this child's acute 1'8nal failut'8?
b. Anemia of chronic disease a. IV normal saline bolus to correct the renal
c. Transient erythrocytopenia of childhood hypoperfusion
d. Thalassemia syndrome b. IV bicarbonate to correct the metabolic
1. Parvovirus 819 aplastic crisis acidosis
Questions • 447
c. IV furosemide to correct the fluid overload a. restrained in a rear-facing infant car seat in
d. IV antibiotics to correct the infectious the back seat of the car until he has 1'98Ched
gastroenteritis 2 years of age
e. Initiation of dialysis to correct the acute renal b. restrained in a forward-facing infant car seat
failure In the back seat of ttle car since he Is now
Oi!: 1 year of age
92. A very tired mother brtngs her 6-week-old In-
fant to your office because •he screams for c. restrained in a rear-facing infant car seat in
hours and hours a day and nothing makes him the front seat of the car until he has reached
atop." His parent describes the crying spells as 20 lb in weight
occurring daily and lasting several hours, usu- d. restrained in a forward-facing infant car seat
ally through the late afternoon and early eve- In the front seat of the car since he Is now
ning. Nothing seems to console 1he child during ;t!:1 year of age
1hese episodes. While he is crying, the infant e. restrained in a forward-facing booster seat
often pulls his knees to his abdomen as if he is in the back seat of ttle car since he is now
In pain. Other than the crying spells, 1he child ;t!:1 year of age
Is asymptomatic. He feeds well and moves his 98. A 4-week-old male infant born at term presents
bowels regularty. The child's weight, length, and with emesis, dehydration, and poor weight gain.
head circumference are normal, and his physical The pediatrician evaluating the child palpEdes an
examination is normal. This patient's history and olive-sized mass in the child's epigastrium. She
physical examination are most consistent w ith believes the Infant may have pyloric stenosis.
which of the following condmons? Which of the following clinical pl'88entations is
L Feeding lntolelllllce most consistent with pyloric stenosis?
b. Cow milk protein allergy L Projectile nonbilious emesis
c. Intussusception b. Bilious emesis
d. Hirachaprung disease c. Bloody diarrhea
e. Colic d. Violent episodes of intermittent colicky pain
93. A newborn Infant has a slight hlp click on hlp and emesis
examination. Which of the following risk factors e. Right lower quadrant abdominal pain
would moat strongly support further evaluation? '¥1. A 5-year-old boy presents to the emergency
L Female patient
department w ith complaints of dizziness and
b. First bom confusion. Three days before presentation,
c. Torticollis he developed a low-grade fever and vomited
d. Metatarsus adductua twice. Since then, the fever and vomiting have
e. Breech presentation or a family history of resolved, but the patient has passed 8 to 10
developmental dysplasia of the hip loose, foul-smelling stools per day. The boy's
94. A 14-year-old patient In your practice with an- mother has been afraid to give him anything but
orexia nervosa has fallen to 80% of her Ideal water or diluted juice because of his history of
body weight for height and gender. She has not vomiting. Deep tendon reflexes are diminished
menstruated in 9 months. She has postural hy- ttlroughout. This patient's ataxia and confusion
potension and a low heart rate. Which of the fol- are most likely caused by which of the following
lowing murmurs is most likely to be present on electrolyte imbalances?
1his patient's cardiac examination? L Hypomagnesemia
L A midsystolic click followed by a murmur b. Hyperkalemia
II. A fixed split ~ c. Metabolic alkalosis
c. A vibratory holosystolic murmur in both d. Hypochloremia
axilla e. Hyponatremia
d. A third heart sound
91. A 13-year-old male presents to ttle office with
e. A nonspecific ejection murmur at the base
short stature. Growth data demonstrate that he
of the heart
has been growing between the third and fifth
85. You are offering preventive counseling to 1he percentile at a steady rate since age 4. His fa-
parent of a 12-month-old child at a health main- ther started shaving at age 17 and completed
tenance visit. The child weighs 18 1b. You would his growth at age 19. What examination and
be correct in informing the parent that this child wor1cup would support the diagnosis of consti-
should be tutional delay of growth and puberty?
448 • Questions
a. Acne and axillary hair, Tanner Ill pubic hair, b. Refer the family to the local governmental
testicular volume 12 ml, bona age 14, lead-management agency.
thyroid-stimulating hormone (TSH) 1.5 (0.5 c. Obtain a venous lead laval for confirmation.
to 4.8), Insulin-like growth factor 1 (IGF-0 d. Start the patient on oral succlmer on an out-
340 (152 to 540) patient basis.
b. No axtllary hair, Tanner I pubic hair, testicular t. Obtain naurodevelopmental testing for the
volume 4 ml, bone age 11 years, TSH 12 patient.
{0.5 to 4.8), IGF-1200 (152 to 540)
1111. A 1o-year-old girl presents with linear straaks of
c. Scant axillary hair, Tanner II pubic hair, tes-
thickened and Indurated skin on the right ann
ticular volume 5 mL. bone age 11 years,
and trunk. The linear streak on the right ann
TSH 2.1 (0.5 to 4.8), IGF-1420 (152 to 540)
has a longttudlnal orientation and extends from
d. No axillary hair, Tanner I pubic hair, testicular
the upper arm to the dorsal aspect of the hand,
volume 4 ml, bone age 11 years, TSH 3.1
whereas the linear streak on the trunk is trans-
(0.5 to 4.8), IGF-162 (152 to 540)
versely oriented. The leeions are surrounded by
98. A 24-month-old male in your office for his reg- a halo of erythema with a violaceous appear-
ular health maintenance visit has the following ance. The central portion Is hyperpigmented
results on screening tests: hemoglobin 9.6 gl and thickened. Which of the following complica-
dL; capillary blood lead level 16 ~g/dl. He lives tions is this child most likely to develop?
in Section 8 housing in poor repair built before a. Esophageal dysfunction
1960. Which of the following is the most appro- b. Pulmonary fibrosis
priate next course of action? c. Contracture of the right elbow
a. Counsel the family regarding lead removal d. Raynaud phenomenon
and racheck the level in 6 months. e. Digital necrosis
Answers
1. b (Chapter 20) 4 to 6 years of age. Gallstones typically develop during

Epinephrine Is used for asystole, bradycardia, and/or adolescence as a result of chronic hemolysis. Dactyli-
pulseless ventricular tachycardia (VT) or ventricular tis, or hand-foot syndrome, is an early manifestation
fibrillation (VF). Epinephrine increases systemic vas- of vaso-occlusive disease. It is caused by avascular
cular resistance, chronotropy, and inotropy, thereby necrosis of the metacarpal and metatarsal bones
increasing cardiac output and systolic and diastolic and requires analgesics, not antibiotics. Acute chest
blood pressure. By increasing systolic blood pressure, syndrome requires both supportive care (supplemental
cerebral blood flow is increased; by increasing dia- oxygen, red blood cell1ransfusions) and antibiotics.
stolic blood pressure, coronary perfusion is increased.
Epinephrine may change fine VF to coarse VF and 5, a (ChBpter 4)
promote successful defibrillation. Children with vegan diets are at risk for vitamin 8 12
deficiency, iron deficiency, and, if exposed to inade-
2. a (CIIapter 11) quate sunlight, vitamin D deficiency as well. A child
Female patients with Turner syndrome present with who lives In New Mexico and spends a lot of time
short stature and delayed puberty caused by primary outdoors can be assumed to have adequate vitamin D
ovarian failure. Other stigmata, including webbed neck, levels. Calcium is unlikely to be a concern if the child
a low hairline, and increased carrying angle, may not be is indeed eating many dark green, leafy vegetables.
present. Patients with Cushing syndrome present with Finally, the boy is fed iron-fortified grains regularly,
other physical characteristics, including moon facies, so unless a screening hematocrit is low, iron stores
buffalo hump, and abdominal striae. In isolated growth are likely sufficient. Vitamins 8 12 and S.. niacin, and
hormone deficiency and familial short stature, patients riboflavin are aU B vitamins. Of these, vitamin 8 12 is
do not have delayed puberty. Patients with Addison found only in foods of animal origin, so vegans in
disease present with fatigue, weakness, nausea, and particular are at risk for deficiency of this substance.
vomiting. In the acute setting, they may present with
cardiovascular shock. &. b (CIIal*r 11)
Functional or Mlnnocent" murmurs are heard In up to
3. d (Chapter 11) 80% of children at some point and represent normal
The child has a 25% chance of acquiring the autosomal blood flow through a structurally normal heart. They
recessive disorder. Because each parent is a carrier are accentuated by increased cardiac output o.e.,
for the disorder; each parent has one normal allele and during exercise, with fever, or with anemia). A Still's
one mutant allele. The probability of the child receiving murmur is the most common innocent murmur. It has a
an affected allele is 0.5 from each parent. Therefore, low-pitched, vibratory quality and is heard best in the
the child has a 25% risk {0.5 x 0.5). supine position. A bicuspid aortic valve is associated
with an 5 2 click. If stenoeis or regurgitation is present,
4. d (Chapter 12) an associated murmur will be heard. The murmur of
Hydroxyurea maintenance therapy has been shown a ventricular septal defect (VSD) is higher frequency
to reduce the number and severity of vase-occlusive and occurs throughout systole. Small VSDs may have
crises In Individuals with sickle cell disease. Children pronounced murmurs with an associated thrill, and not
with sickle cell disease, like all children, require all uncommonly undergo spontaneous closure during the
routine childhood vaccinations. Despite penicillin first 2 years of life. An atrial septal defect is charac-
prophylaxis, children with sickle cell disease are still terized by ftxed and wide splitting of~ because of
at high risk of sepsis caused by Streptococcus pneu- delayed closure of the pulmonary valve. A soft systolic
moniae. These children require both the pneumococcal ejection murmur may be present because of increased
conjugate vaccine (7-valent) during infancy and the flow across the pulmonary valve. The hallmark findings
pneumococcal polysaccharide vaccine (23-valent) at in coarctation of the aorta are discrepant pulses and
449
4SO • Answers
blood pr9Ssures In the upper and lower extremities. 10. a (CIIapler11)

A systolic eJection munnur may be present at the Legg-calvt\-Perthes (LCP) disease. Ahhough LCP can
left upper sternal border. Continuous munnurs may have associated hlp or knee pain, It Is commonly known
also be present across the chest or back, If coUateral as "the painless limp.~ The peak age of onset Is 3 to
arteries are present. 8 years. Slipped capital femoral epiphysis (SCFE) Is
incorrect because the peak age range of this disorder is
7. a(CIIapler2) peripubertal, approximately ages 8 to 14 year8. SCFE
Upperairway obstruction in the neonate can result from typically has pain associated. A "toddler's fracture" is
all the conditions listed. However, the child does not a nondisplaced fracture of the tibia in children aged
turn blue when crying (mouth breathing). Inability to 2 to 4 years, which is often not appreciated on plain
pass the nasogastric (NG) tube in this clinical setting films at presentation. Most heal within 4 weeks, and
is virtually diagnostic of choanal atresia or significant any associated limp would disappear within 2 months.
stenosis. There is no communication between the nose Septic arthritis is usually acute In presentation and has
and pharynx, and thus no air flow. Bilateral choanal associated pain, fever, Inability to walk, and elevations
atresia is an emergency. This patient will likely require of C-reactive protein and erythrocyte sedimentation
endotracheal Intubation and surgery to correct the rate. Juvenile Idiopathic arthritis (JIA) rarely pr9Sents
defect. Vocal cord paralysis may resuh from recurrent In the hlp; the most common location Is the knees.
laryngeal nerve damage during delivery. If this were Morning stiffness Is a common complaint with JIA.
the case, the Infant should have a soft, hoarse cry,
and stridor might be noted. Subglottic stenosis and 11. c (CMpter 12)
laryngeal web would also result in stridor. In all three Pulmonary embolism (PE) is a potentially fatal com-
of these conditions, passage of the NG tube would plication of deep vein thrombosis (DVD. The classic
not be impeded. signs and symptoms of PE include sudden chest pain,
dyspnea, anxiety, and cyanosis. Hemoptysis is uncom-
a. c (CIIapter 15) mon. A helical computed tomography (CT [spiral C1]
The child with diabetic ketoacidosis (DKA) usually or a ventilation/perfusion (1/Q} is the recommended
exhibits some combination of polyuria, polydipsia, diagnostic study. Although small emboli can be man-
fatigue, headache, nausea, emesis, and abdominal aged by anticoagulation therapy and close monitoring,
pain. When DKA occurs, ketones are fanned in the massive PE may require thrombolytic therapy with
blood and cleared In the urine. Hyperglycemia, and recombinant tissue plasminogen activator (r-tPA) or
not hypoglycemia, Is typical. Primary metabolic ac- thrombectomy. Venous Insufficiency Is also a common
Idosis with secondary respiratory alkalosis Is noted complication noted after DVT but Is not a significant
(decreased venous blood pH and hypocarbia). De- issue in the acute setting. Limb overgrowth, edema,
hydration results in an elevated blood urea nitrogen and gangrene from a venous ulcer are all potential
level. When DKA is present, the patient's total body complications of ovr.
potassium is depleted from significant potassium loss
in the osmotic diuresis. However, serum potassium 12. d (CIIapter 2)
measurements at presentation may appear high, Women who are taking carbamazepine or valproic
low, or nonmal. acid are at an increased risk of producing a child with
a neural tube defect if they are treated with this drug
I. a (Chapter 2) during their pregnancies. The mechanism for this
Although more than 99% of males have bilateral is unclear. The other anticonvulsants listed do not
descended testes by 12 months of age, testes that increase the risk for neural tube defects specifically,
do not descend on their own by 3 to 6 months of although they may be associated with a higher risk for
age are unlikely to do so. Testes that remain outside other birth detects. Other drugs that do Increase the
the scrotum develop ultrastructural changes and risk of neural tube defecta Include aminopterin, pyri-
impaired sperm production, result ing in possible methamine, trimethoprim, sulfasalazine, methotrexate,
infertility. There is also an increased risk of malig- phenothiazines, and cyclophosphamide.
nancy, even after the testis is surgically relocated
(and even in the contralateral testis). Ninety percent 13. b (CIIapl8r 20)
of patients with cryptorchidism also have inguinal Wrth probable supraventricular tachycardia (SVD, the
hernias. Cryptorchidism may occur as an isolated best course of action listed is to administer intravenous
defect or be a part of a genetic syndrome; however, (IV) adenosine by rapid bolus to temporarily block the
there is no known increase in the risk of microphallus atrioventricular flr.V) node and interrupt the likely re-
in these patients. entrant circuit causing the SVT. In a hemodynamically
Answers • 451
unstable patient, synchronized cardioversion 0.5 to 1.0 as speak fluently, Is part of a comprehensive speech
Jlkg Is recommended with an Increase to 2 Jlkg If Initial assessment following the heartng test.
cardloverslon Is unsuccessful. lhe use of epinephrine
Is Indicated In cases of asystole, bradycardia, pulseless 17. c (CIIapter 1ol)
VT, or VF. The use of atropine is indicated in cases of Functional abdominal pain is best treated with a
bradycardia and AV block. calcium may be used for biopsych080Cial model. Medical tt'98tment might in-
hypocalcemia, hyperkalemia, hypermagneeemia, and clude acid reduction therapy for pain associated with
calcium channel blocker overdose. Sodium bicarbonate dyspepsia, antispasmodic agents, smooth muscle
may be used if the infant is acidotic secondary to de- relaxants, or low doses of tricyclic psychotropic agents
creased perfusion and oxygen delivery to the tissues. for pain or nonstimulating laxatives or antidiarrheals
for pain associated with aHered bowel pattern. A CT
14. b (CIIapter I) and endoscopy are unlikely to identify abnormalities
Infantile spasms typically present between 2 and 7 on the basis of the history and physical examination.
months of age and may be idiopathic or associated A diet history and elimination diet is unlikely to provide
with other neurologic or developmental diseases. additional insight because the pain is not related to
Hypsarmythmla, charactertzed by widespread random, meals. Psychlatrtc referral Is pt'9mature and sends the
hlgh-vohage slow waves and spikes that spread to all message that there Is only an emotional component
cortical areas, Is the charactertstlc electroencepha- to these symptoms.
logram (EEG) ftndlng In Infantile seizures. All children
with infantile seizures should receive a Wood lamp 18. • (CIII.plw 11)
exam to detennine whether ash-leaf spots, the lesions The clinical description is that of a patient with trisomy
described here, are preeent. Ash-leaf spots are the 21 or Down syndrome. Common dysmorphic facial
earliest manifestation oftuberous sclerosis, a neurocu- features include flat facial profile, upslanted palpebral
taneous disease that may present with infantile spasms. fissures, a flat nasal bridge with epicanthal folds, a
Von Recklinghausen disease and bilateral acoustic small mouth with a protruding tongue, micrognathia,
neurofibromatosis are fonns of neurofibromatosis. and short ears with downfolding eartobes. Other dys-
Cafj-au-lait spots, which are hyperpigmented, are morphic features at'9 excess skin on the back of the
seen in these diseases. Von Hippei-Lindau disease neck, microcephaly, a flat occiput (brachycephaly),
prasents primarily In adults. Infants with Sturge-Waber short stature, a short sternum, small genitalia, and a
may have seizures, but the port wine stain Is present gap between the first and second toes ("sandal gap
at birth and Is the primary skin lesion. toe•). Anomalies of the hand Include single palmar
creases (simian creases) and short, broad hands
15. b (CII•pter 1) (brachydactyly) with fingers marked by an incurved
She needs a fourth dose of DTaP, a fourth dose of HiB, fifth finger and a hypoplastic middle phalanx (clincr
and a fourth dose of pneumococcal conjugate vac- dactyly), Features of trisomy 18 include hypertonia,
cine. She needs the measles, mumps, and rubella and microcephaly, corneal opacities, micrognathia, and
varicella vaccines unless there is a reliable history that rocker bottom feet. Features of trisomy 13 include
she has had chickenpox. She has already completed microcephaly, occipital scalp defects, iris coloboma,
the required vaccination courses for hepatitis A and microphthalmia, cleft lip and palate, and clenched
hepatitis B. Three doses of inactivated polio vaccine hands. Boys with Klinefelter syndrome do not have
at'9 appropriate for her age. physical features identifiable at birth that could lead
to suspicion of the disorder. Girls with Turner syn-
18. e (ChQtera 1 ud I) drome have a webbed neck, low posterior hairtine,
Speech delay Is the most common developmental wide-spaced nipples, cubitus valgus (wide carrying
concern raised by parents. As many as 15% of children angle}, and edema of the hands and feet.
have soma sort of speech/language delay a:t one time
or another during the preschool years. Any child with 18. • (CIIaplw 1)
suspected language delay should ~eive a full audiologic Asymptomatic patients with blood lead levels greater
assessment, followed by rvferral to a speech pathol- than 45 IJg/dL require chelation within 48 hours. The
ogist for further workup and treatment {if indicated}. family should be removed from the home while decon-
The most common cause of mild-tcrmoderate hearing tamination is taking place. Siblings of any patient with
loss in young children is otitis media with effusion, but elevated lead levels should be tested, and nutritional
this child has clear, mobile tympanic membranes, so a therapy is certainly not contraindicated; however,
tympanogram is unnecessary. Evaluation of the boy's patients with levels exceeding 45 ~gfdl require che-
ability to understand and produce language, as well lation treatment.
462 • Answers
20. b (CMpter 4) Koplik spots, and an erythematous maculopapular

Breastfed Infants should receive oral vitamin D sup- rash. Kopllk spots are small, Irregular red spots with
plementation beginning In the flrs'l several days after central gray or b luish-white specks that appear on
birth to pravent rtckets, a condition In which devel- the buccal mucosa. Rubella Is caused by rubella virus
oping bone fails to mineralize because of inadequate and is characterized by mild fever and erythematous
1 ,25-dihydroxycholecalciferol. Rickets is rare in maculopapular rash, with generalized lymphadenop-
bi'98Slfed infanta but does occur. Dark-akinned infanta athy, especially of the posterior auricular, cervical,
and those exposed to limited sunlight in northern and suboccipital nodes. Roseola infantum is caused
latitudes are particularly at risk. Rickets in breastfed by herpesvirus 6 and is characterized by high fever
infants becomes clinically and chemically evident in followed by a maculopapular rash that starts on the
late infancy; rickets due solely to vitamin D deficiency trunk and spreads to the periphery. The fever typically
begins to respond to supplementation within weeks. resolves as the rash appears. Erythema infectiosum
The American Academy of Pediatrics recommends is caused by parvovlrus 819 and is characterized by
exclusive breastfeeding during the first 6 months of life a marked erythema of the cheeks ("slapped cheek"
and continuation of breastfeeding during the second appearance) and an erythematous, pruritic, maculo-
6 months for optimal Infant nutrttlon. Studies have papular rash starting on the arms and spreading to the
shown that breaatfed Infants have a lower Incidence trunk and legs. Hand-foot-mouth disease Is caused
ot Infections, Including otitis media, pneumonia, sep- by coxsackie A virus and Is charactertzed by ulcers
sis, and meningitis. Braastfed Infants are less likely to on the tongue and oral mucoea and a maculopapular
experience feeding difficulties associated with allergy vesicular rash on the hands and feet. Chickenpox
(eczema) or intolerance (colic). is caused by the varicella-zoster virus and is char-
acterized by fever and a pruritic papular, vesicular,
21. c (Chapter13) pustular rash starting on the trunk and spreading to
Although all of the choices are possible presentations the extremities. The infected child Is Infectious until
of Hodgkin disease, choice c is the most common the last lesion is crusted over. Zoster, or shingles, is
presentation, occurring in approximately 80% of pa- caused by reactivation of the varicella-zoster virus
tients. Approximately two-thirds of patients will have from the dorsal root ganglion and is characterized
mediastinal lymphadenopathy, and 20% to 30% wiD by fever and painful pruritic crops of vesicles along a
expertence choice b symptoms. Prurttus, fatigue, and derrnatomal distribution In an Individual wHh previous
anorexia are also common pntSentlng symptoms. The varicella-zoster Infection.
prurttus Is often extremely dtnlcult to control before
diagnosis but resolves very rapidly once chemotherapy 24. b (CIIapter 7)
begins. Patients will often have more than one of the High-dose amoxicillin Is the recommended first-line
presenting signs or symptoms listed here. antibiotic treatment for acute otitis media. Children
who have been treated with antibiotics within the past
22. d (Cblpter I) month are eligible for second-line therapy with amox-
The preferred therapy regimen for a patient more than icillin-clavulanate, an oral second- or third-generation
12 years with persistent asthma (symptoms [before cephalosporin, or IM ceftriaxone. The most common
treatment] > 2 days per week or waking with symptoms bacteria that cause acute otitis media are Strepto-
>2 nights per month, or use of an inhaled ~-agonist coccus pneumonlae, Haemaphilus influenzae, and
>2 times per week) that Is not well controlled on Step Moraxella cstarrlJalis. Azithromycln, erythromycin, and
2 Oow-dose inhaled steroids) is daily low-dose inhaled trimethoptim-sulfamethoxazole are minimally effective
corticosteroid and a long-acting inhaled !J2-agonist. against P-lactamase-producing strains of H. influenzae
Answer a Is most appropriate tor patients with lntermH- or M. catarrha/ls. Dlcloxaclllln Is not active against
tent asthma, who can control their sporadic symptoms gram-negative organisms such as H. Influenzas and
with an Inhaled P2-agonlst as needed. Artswer b Is the M. catarrhal/s.
preferred therapy for a patient with mild persistent
asthma. Answer c is an acceptable Step 4 treatment. 25. b (CII•pter Z)
Nedocromil is an older drug and presumed mast cell Infants with neonatal sepsis or pneumonia typically
membrane stabilizer that may be an alternative to have normal surfactant production and do not benefit
low-dose inhaled corticosteroids in patients with mild from surfactant replacement therapy. Preeclampsia is
persistent asthma. associated with an acceleration of lung maturation and
surfactant production. Full-term infants with neural
23.. • (Chaplllr 7) tube defects have normal lung maturation. Newborns
Measles Is caused by a paramyxovirus and characterized with trisomy 21 are at risk for pulmonary hypertension
by malaise, high fever, cough, coryza, conjunctivitis, because of delayed development of the pulmonary
Answers • 453
vasculature, but typically have appropriate surfactant succession by pubic hair growth, penile enlargement, and
production. Infants of diabetic mothers, especially those maximal height growth velocity (approaching 9 crnly).
with poor control, have delayed maturation of surfac-
tant production and are at Increased risk for neonatal 30. e (CIIapter &)
1'8Spiratory disti'8SS syndrome at any gestational age. A patient with an acute asthmatic episode who has
already taken multiple dosages of albuterol at home
28.. d (CIIapter 11) should still receive a trial of another dose in the
A child with a suspected urinary tract infection (UTO emergency department. Failure to respond to initial
and positive leukocyte esterase on dipstick urinalysis treatment and the prusence of hypoxemia signal a
should be treated for presumptive UTI until culture moderate to severe acute asthma episode that will
results become available. Children older than 5 years require more aggressive treatment. The addition of the
of age with a recurrent UTI wanant further wor1rup to anticholinergic agent ipratropium results in significant
rule out anatomic abnormalities (renal ultrasound) and improvement in a large percentage of patients. The lack
vesicourateral reflux. A nontoxic-appearing child of this of response to initial treatment is also an indication to
age does not need to be admitted to the hospital for begin treatment with systemic corticosteroids to help
treatment. On the contrary, emplrtc treatment should naver relieve airway Inflammation. Supplemental oxygen will
be withheld In a tabrtle child with a suspected U1l and a help relieve the hypoxemia caused by va mismatch
dipstick urtnalysls that Is positive for leukocyte esterase. and can also produce mild bronchodllatlon.
27. a (Chapl•11) 31. d (CIIapter 17)

The central feature of tetralogy of Fallot (fOF) is a This patient displays the characteristic findings of acute
malaligned VSD. The malalignment in the septum is renal failuru because of the use of ibuprofen in a subject
characterized by an anteriorly displaced infundibulum with decreased renal perfusion. He would be expected
(the septal muscle in the outlet area). This leads to to have decreased renal perfusion on the basis of
subpulmonary narrowing and an aorta that appears to symptoms and signs of mild to moderate dehydration
override the inferior portion of the septum. The amount of (tachycardia, decreased urine output). In the presence
pulmonary stenosis (right ventricular outflow obstruction) of decreased renal perfusion, the intrarenal vasodilatory
varies in patients with TOF. Right ventricular outfbw prostaglandins comprise a powerful mechanism for
obstruction leads to tight ventricular hypertrophy in maintenance of glomerular filtration rate. Interference
these patients. Atrial septal defact, aortic stenosis, with this compensatory mechanism, by the use of non-
coarctation of the aorta, mitral valve prolapse, and lett steroidal anti-Inflammatory drugs as In this case, Is a
ventrtcular hypertrophy are not associated with TOF. common mechanism that can pn:~Cipltate lntrtnslc acute
Left ventricular hypertrophy may be found in patients renal failure. This patient does not have hemolytic uremic
with coarctation of the aorta or aortic stenosis. syndrome because his complete blood count is normal
(no hemolysis, thrombocytopenia, or schistocytes). He
2&. c (Chapter 12) does not have any evidence for pyelonephritis (no cos-
Fresh frozen plasma (FFP) is indicated for ruplacement tovertebral angle tenderness, no white blood cells in the
of missing coagulation factors when the specific factor urine, no bacteria in the urine). He does not display any
concentrate is unavailable. FFP is prepared by either clinical features characteristic of interstitial nephritis (no
separating the liquid portion of whole blood or by skin rashes, no white blood cells In the urine) or urinary
collecting the liquid portion of the blood by apheresis tract obstruction (nonnal kidney ultrasound).
technology and freezing it within 8 hours of collection.
FFP contains all of the nonnal coagulation factors and 32. • (Ciaapler 8)
naturally occurring Inhibitors of coagulation. Cryopre- This child most likely haa classical systemic lupus
cipitate Is a rich source of fibrinogen and clotting factors erythematosus (SLE), given that she fulfills 6 out of 11
VIII and XIII. Granulocyte Infusions are usually used crtterta for the classlflcadon for the condition: malar rash,
In the neonate or Infant with prolonged neutropenia photosensitivity, oral ulcers, arthritis, cytopenias, and
and life-threatening sepsis. Platelet transfusions are active urine sediment. A positive antinuclear antibody
effective in cues of thrombocytopenia or functional (ANA) is preeent in eesentlally all patien18 with SLE;
platelet defects. DDAVP is used in von Willebrand therefore, the correct answer is a. Anti-double-stranded
disease or mild hemophilia A patients. DNA antibodies are present in up to 7096 of patients
with active SL.E, anti-Smith antibodies in up to 5096,
29. c (Cbaptar 3) anti-Ro antibodies in up to 60%, and meumatoid
The typical sequence of pubertal events in the male factor is rare in SLE. Anti-double-stranded DNA and
begins with testicular enlargement from the prepubertal anti-Smith antibodies are highly specific for SLE;
size of about 2.5 mm in length. This is followed in rapid therefore, its presence is highly suggestive of SLE.
464 • Answers
33. a (Chapter 2D) than 24 months who are fonner premature infants or
The pr1mary assessment Is the Initial evaluation of the have chronic pulmonary disease (bronchopulmonary
crttlcally Ill or Injured child when life-threatening prob- dysplasia) requiring oxygen therapy within the last 6
lems are Identified and prtorltlzed. The proper ortler months. Neither the nasal nor the InJectable Influenza
of the primary survey or Initial assessment Is airway, vaccine is approved for infant~ younger than 6 months
breathing, circulation, disability, and exposul'9. After of age.
the primary survey is complete, 1'98uscitation should
occur if the condition is lif&-threatening. Once the 37. c (CMpter 4)
life-thl'98tening issues al'9 addressed, the secondary Formula-fed infants do not require supplementation
survey should be perfonned. with vitamins. minerals, additional caloric sources, or
free water during the first 8 months of life, regardless
34. d (Chapter 12) of local climate. Dilution of tne formula is potentially
The most likely diagnosis Is Immune thrombocytopenic harmful to an infant under 8 months of age because of
purpura. lsoimmune thrombocytopenia is noted in the inability of the immature kidney to fully dilute urine.
newborns, not in children. lsoimmune immunoglobulin If this infant is feeding well, growing appropriately, and
G antibodies are produced against the fetal platelet tolerates the formula, there Is no reason to switch to
when the fetal platelet crosses the placenta and has a soy protein-based fonnula at this time.
anllgens that are not found on the maternal platelet.
The maternal antibodies cross the placenta and attack 38. c (Chapter 2)
the fetal platelets. Leukemia, sepsis, and hypersplen- The absence of a red reflex on funduscopic examination
ism may all cause thrombocytopenia in the child's age (also called "leukocoria,R for "white pupi1'1 calls for im-
group, but are unlikely in this caae. The white blood mediate consultation with a pediatric ophthalmologist.
cell count is nonnal, and no immature white cells are The most common cause is a congenital cataract, which
seen on the peripheral smear. Sepsis is unlikely given may occur spontaneously, secondary to a genetic
that the child appears well and is hemodynamically predisposition, or as a result of metabolic disease
stable. Hypersplenism is unlikely when the spleen is or intrauterine infection. Retinoblastoma, congenital
normal on palpation. glaucoma, and toxocariasis may also cause leukocoria
but are much less common than congenital cataracts.
3!. b (CMpter 11)
Mlcrodeletlon of 22q1 1 .2 has been found In 90% of 38. d (CIIapblr I)
children with DIGeorge syndrome, In 70% of children The child In the vignette Is Initially diagnosed with
with velocartllofaclal syndrome, and In 15% of children adrenal lnsufftclency, which can be associated with
with isolated conotruncal cartliac defects. Although adrenoleukodystrophy. Treatment of the insufficiency
the above-mentioned names al'9 still in use, the more does not help with the personality changes and declining
general term 22q11.2 deletion syndrome more appro- cognitive faculties. His difficulty with walking is likely
priately encompasses the spectrum of abnormalities due to increasing spasticity. The first three disorders
found in these children. Its prevalence in the general listed are all gray matter degenerative diseases that
population is 1 per 4,000 live births. The deletion can present earlier in life with hypotonia, mental retardation,
be inherited (8% to 28% of cases), but more typically and seizures. Rett syndrome Is a disease of general
occurs as a de novo event. However, if a parent has cerebral atrophy that presents almost exclusively in
the deletion, the risk to each child is 50%. The mi- girts earty in the second year of life.
crodeletion can be detected using fluorescent in situ
hybridization (FISH) probes. Classic cardiac features of 40. d (CIIapter I)
this spectrum of disorders Include conotruncal defects Absence seizures begin between ages 4 and 9 years
such as TOF, Interrupted aor11c arch, and vascular rings. and consist of brtef episodes of startng associated
Other common ftndlngs are absent thymus, hypocal- with alterad consciousness. The typical duration Is
cemic hypoparathyroidism, T-cell-medlated Immune 5 to 10 seconds. Often, the staring is accompanied
deficiency, and palate abnonnalities. These child1'9n by subtle clonic activity in the face or arms or sim-
usually have feeding difficulties, cognitive disabilities, ple automatisms (such as eye blinking, chewing, or
and behavioral and speech disorders. perseverative motor activity). Absence seizures start
and stop abruptly and have no postictal phase. Al-
38. e(CIIa,..7) though brief, absence seizures can occur in clusters
Palivizumab is a respiratory syncytial virus (RSV) many times a day and interfere with learning and
monoclonal antibody approved for monthly injection socialization. In a typical absence seizure, the EEG
during the winter months in infants at high risk for shows abrupt onset and offset of 3/second general-
severe RSV disease. These Include children younger ized symmetric spike and slow-wave complexes. In a
Answers • 455
child with untraated absence epilepsy, 3 to 5 minutes •2. d (CII•pter 20)

of hyperventilation will often precipitate a typical ab- Oral N-acetyl cysteine Is t he antidote for acetamin-
sence seizure. Ethosuximide has higher efftcacy and ophen Ingestion. It Is moat e1'f8ctlve If administered
a lower side-effect profile and Is the praferred drug within 8 to 10 hours of Ingestion. Multiple doses are
for treating absence epilepsy (vs. valprolc acid). For required. If the patient refuses, a NG tube may be
children with partial-oneet epilepsy, oxcarbazepine placed. The administration of N-acetyl cysteine should
should be considered for initial monotherapy on the not be delayed until after the 4-hour acetaminophen
basis of current eflicacy evidence. Considering all level is drawn if the patient preeents before this time.
factors, including cost, carbamazepine, valproic acid, Activated charcoal may be beneficial if used within
topiramate, and phenytoin are other reasonable choices 4 hours of ingestion and is often followed by whole
to treat partial-onset seizures. Methylphenidate is a bowel irrigation, but neither of these is considered an
stimulant medication that is often beneficial in the antidote specific to acetaminophen poisoning. Neither
treatment of attention-deficitl- hyperactivity disorder. hemodialysis nor atropine sulfate, which is used in
cases of organophosphate poisoning, affects blood
41. • (CMptw 11) levels of acetaminophen.
Approximately 98% of fetuses with Turner syndrome
expire In utero; only 2% are born. Therafore, there- •a. • (CII•pt.r 20)
currence risk for parents who have a child with Turner Fractures that are highly specific for abuse Include
syndrome Is no higher than that of the general popula- bilateral fractures, bucket handle fractures, metaph-
tion. Dysmorphic featul'98 include lymphedema of the yseal chip fractures, and fractures of the (especially
hands and feet, a shield-shaped chest, widely spaced posterior) ribs, scapula, sternum, or spinous processes.
hypoplastic nipples, a webbed neck, low hairline, cu- Fractures that occur before ambulation are usually in-
bitus valgus Oncreased carrying angle), short stature, flicted. Bruises on the chest, head, neck, or abdomen
and multiple pigmented nevi. Additional abnormalities and bruises on a nonambulatory child are extremely
include gonadal dysgenesis, gonadoblastoma, renal suspicious for abuse. Vigorous shaking may lead to
anomalies, congenital heart disease, autoimmune shaken baby syndrome (SBS), which results from
thyroiditis, and learning disabilities. Gonadal dysgen- acceleration/deceleration forces to the head. Virtually
esis, present in 100% of patients, is associatad with pathognomonic injuries include intracranial (subduraQ
primary amenorrhea and lack of pubertal development hemorrhage, diffuse axonal Injury, and widespread
because of loss of ovarian hormones. The gonads are retinal hemorrhages, which may result In permanent
appropriately Infantile at birth but regress during child- vision loss. SBS has the highest mortality rate of any
hood and develop Into •streak• ovaries by puberty. In reported fonn of child abuse. Falls from beds, changing
mosaics with a Y chromosome in one of their cell lines, tables, cribs, counters, or toilet seats do not cause
gonadoblastoma is common. Therefore, prophylactic the injuries seen in SBS. Injuries in different stages of
gonadectomy is necessary in these patients. Renal healing occur in chronic or repeated abuse.
anomalies, usually duplicated collecting system or
horseshoe kidney, occur in 40% of those with Turner 44. c (CII•pter 14)
syndrome. Congenital heart disease occurs in 20% Painless rectal bleeding sufficient to lower hemoglobin
of patients; common defects include coarctation of in a 2-year-old is a common presentation of Meckel
the aorta, aortic stenosis, and bicuspid aortic valve. diverticulum. A colonoscopy would not reveal this
As a consequence of having only one functional X because the bleeding point is sufficiently proximal to
chromosome, females with Turner syndrome display the ileocecal valve. Transfusion is not needed at this
the same frequency of sex-linked disorders as males time. However, hemoglobin levels should be monitored
do. The diagnosis Is made by karyotype and FISH. frequently. Gastric lavage would likely not Identify a
Because of their mosaicism, aome girls suspected of source of bleeding because the most likely cause Is
having Turner syndrome have a 46,XX karyotype In the distal to the ligament ofTreltz. Bacterial colitis is usu-
peripheral blood, and a skin biopsy may be necessary ally associated with bloody diarrhea, not with painless
to make the diagnosis. rectal bleeding.
Short stature has been successfully treated using
human growth hormone. Secondary sexual charac- G. c (CII•ptar 15)
teristics develop after estrogen and progesterone This infant presents with classic clinical and biochem-
administration. As mentioned earlier, gonadectomy is ical evidence ofadrenal crisis from congenital adrenal
indicated in patients with dysgenetic gonads and the hyperplasia (21 -hydroxylase deficiency). This classic
presence of a Y chromosome. Wrth the rare exception presentation consists of hypotension, hypoglycemia,
of a few mosaics, women with Turner syndrome cannot hyponatremia, hyperkalemia in a 2- to 6-week infant,
become pregnant. typically male (females are usually identified in the
466 • Answers
newborn period with ambiguous genitalia). All emergency an increased risk of suicidal ideation. Individuals with
personnel should think of adrenal Insufficiency when a ADHD should continue to take their medications over
child presents In this fashion. lhese Infants need fluid, the weekends and durtng holidays for good control
salt, dextrose, and stress dosing of hydrocortisone for of symptoms In academic and nonacademic setUngs.
survival. Arlswer a (azithromycin) is not a wide-spectrum Pharmacologic intervention should be administered
antibiotic or one that is considered a drug of choice along with behavioral management and support for
for sepsis in the infant. The infantil HC03 level is not the patient and family in order to achieve the best
low enough to warrant the consideration of IV bicar- possible outcome.
bonate. Albumin could help improve intravascular
volume but would not add any additional therapeutic 41. c (Cialpter 7)
benefit beyond the fluid resuscitation that was already Roseola is a febrile illness caused by human herpesvi-
provided. Hypocalcemia is not generally present in rus 6. Children have elevated temperatures for 3 to 5
patients with adrenal insufficiency. If the patient has days, followed by a rash that develops after an abrupt
cardiovascular issues related to hyperkalemia, calcium defervescence. The rash consists of erythematous,
is a useful adjunct to stabilize the myocardium as the maculopapular lesions that begin on the trunk and
extracellular potassium level Is lowered. subsequently spread to the neck, face, and extremities.
The character1stlc rash of erythema lnfectlosum
4&. c (Chapter 1 0) (fifth disease; human parvovlrus B19) Is facial erythema
The patient described In the question has psoriasis. giving a "slapped cheek'' appearance, followed by
The scaly red plaques concentrated on her trunk spread to the extremities in a reticular pattern. Measles
demonstrate the Auspitz sign that is pinpoint bleeding is a confluent, erythematous, maculopapular rash that
when the scale is removed. Nail pitting is a common starts on the head and progressea caudally. Children
finding in patients with psoriasis. Psoriasis is a chronic with measles have high fever and associated cough,
disease but is often exacerbated by infection in many coryza, and conjunctivitis. The rash of chickenpox
patients, particularly group A p-hemolytic Streptococcus begins as pruritic, erythematous macules that evolve
(GAS) in genetically susceptible patients. In addition, to vesicles and later crust. AJJ initial lesions resolve,
GAS may be the precipitating factor in a subtype of new crops form, so that lesions in different stages are
psoriasis known as "guttate psoriasis." Recognizing observed simultaneously. The rash of acartet fever,
and treating streptococcal pharyngitis In guttate psori- caused by group A ~-hemolytic streptococci, Is an
asis may Improve the patient's outcome. Patients with erythematous, "sandpaper-like'" rash that first appears
psoriasis are also directed to try and avoid exacerbating on the neck or trunk, spreads to the extremities, and
factors such as streptococcal Infections. may desquamate 10 to 14 days later. Fever and phar-
Because this patient has psoriasis, a bacterial (a) yngitis accompany the rash.
or fungal (b) culture of the plaques would not be nec-
essary and could be misleading if a skin contaminant 49. c (CMpter 9)
was found. Tzanck smears (d) are used to look for Febrile seizures are typically brief, generalized seizures
multinucleated giant cells consistent with herpes viruses with fever that occur in up to 5% of otherwise healthy
such as HSV-1 and -2 or varicella, neither of which children aged 6 months to 5 years. Febrile seizures,
is associated with psoriasis. A complete blood count even when recurrent, are not considered epilepsy. How-
(e) would not be necessary in patients with psoriasis ever, children with febrile seizures have an increased
and, if checked, should be normal. risk of developing epilepsy. Between 2% and 7% of
all children with febrile seizures develop epilepsy if
47. a (Chapter I) followed to age 25 years. Overall, the morbidity and
lhe goal of pharmacologic therapy for attention deftcH mortality associated with febrile seizures Is extremely
hyperactivity disorder (ADHD) Is sustained symptom low. Only about a third of patients with an Initial fe-
reduction throughout the day with a tolerable minimum brile seizure will experience recurrent febrile seizures.
of adverse effects. Atomoxetine is a highly specifiC Anticonvulsant medication is not indicated in the vast
norepinephrine reuptake inhibitor, its nonstimulant majority of patients with initial or even recunent febrile
status sets it apart from the stimulants commonly seizures. By definition, the diagnosis of febrile seizure
used to treat ADHD (methylphenidate, dextroam- excludes children with intracranial infection or a prior
phetamine, and mixed amphetamine salts). Unlike the history of nonfebrile seizure.
psychostimulants, atomoxetine has a generally low
incidence of side effects and low abuse potential. In 50. d (CIIapter 12)
the United States, atomoxetine carries a Mblack box" The most likely diagnosis is hemophilia A. Hemophilia
warning mandated by the Food and Drug Adminis- A is an X-linked disorder that Is caused by a deficiency
tration alerting physicians and patients because of of factor VIII. Hemophilia B is also an X-linked disorder
Answers • 457
and is caused by factor IX deficiency. Hemophilias A hemolytic anemia). Acute anterior uveitis with conjunc-
and B ara characterized by spontaneous or traumatic tival Injection, severe pain, and photophobia occurs
hemorrhages, which can be subcutaneous, IM, or most commonly In patients with HLA-B27-associated
within joints (hemarthroses). Llt.threatenlng Internal disease but not In the context of ollgoartlcular JIA.
hemonhages may follow trauma or surgery. The partial Rheumatic heart disease Is a consequence of acute
thromboplastin time is prolonged, the prothrombin rheumatic fever, but not of JIA.
time (Pl) is normal, and in hemophilia A, the factor VIII
coagulant activity (VIII:c) is decreased. Other than their 53. a(ala..._.1)
factor replacement regimens, there is no distinguishable Cases of suspected bacterial pneumonia that are com-
difference between hemophllias A and B. Idiopathic plicated by large (compromising) pleural effusions (or
thrombocytopenic purpura is unlikely in this patient, pleural abscesses) are most likely caused by S. aureus.
because the platelet count is normal at 150,000. With Streptococcus pneumoniae is the most common
no history of epistaxis, gingival bleeding, or cutaneous cause of bacterial pneumonia after infancy and can
bruising, von Willebrand disease is unlikely. Hemarthroses result in an effusion; however, the effusions seen with
ara not typical for von Willebrand disease. VItamin K S. pneumonia& (and the other pathogens listed) ara
deficiency occurs In the neonate who Is exclusively usually small.
breastfed and has not received prophylactic vhamln Bilateral diffuse lnterstltlallnflhrates era common
K Injection after birth or In the child with slgnlftcant In pneumonia because of M. pneumonlae. Focal
tat malabsorption. In vitamin K deficiency and In liver abnormalities such as lobar consolidation and small
disease, there Is a prolonged PT and normal factor effusions may oocur. The effusions seen in pneumonia
VIII coagulant activHy. The most appropriate therapy because of nontypeable H. lnfluenzae are usually small.
for complications of hemophilia A is to infuse factor Diffuse interstitial infiltratee may be present in pneu-
VIII concentrate. monia because of C. pneumoniae. Pleuritis and small
pleural effusions may occur. Klebsiella pneumoniae is
51. • (CIIapl• 5) an uncommon cause of lobar pneumonia in children.
This patient has a metabolic acidosis (pH ~7.4) with an It may cause pneumonia in adults with underlying
increased anion gap ([134 + 4.5] - (106 + 10) = 22.5, problems such as alcoholism, diabetes mellitus, and
outside the normal range of 12 ± 4). Metabolic ac- chronic obstructive pulmonary disease.
Idosis with an Increased anion gap usually resuhs
from lnci88Sed acid production (such as In diabetic M. d (CIIapter 17)
ketoacidosis), deci88Sed acid excretion (renal failure), This patient most likely has prtmary essential hy-
or Inborn errors of metabolism. Chronic dlanhea usu- pertension. Given her obesity and family history, the
ally causes either normal anion gap acidosis or, less hypertension is most likely to benefrt from weight loss
commonly, metabolic alkalosis. Pyloric stenosis also and exercise.
results in metabolic alkalosis (HCIIoss via vomiting). This patient has sustained hypertension. Reassur-
Children with cystic fibrosis may exhibit alkalosis. ance or further observation is inappropriate, because
Renal tubular acidosis results in a metabolic acidosis the high blood pressure has already been verified
with a normal anion gap. with the appropriate technique. The kidney function
is normal, so an underlying renal etiology is unlikely.
52. c (Chapter I) The cardiac examination is normal and four extremity
This child has a chronic arthritis as evidenced by the blood pressures ara equally elevated, so an urgent car-
presence of joint swelling, limitation of movement, diology evaluation is not needed. If the blood pressura
limping, and morning stiffness of mora than 6 weeks' is not controlled by exercise and weight loss, then this
duration. Of note, pain Is commonly absent In chronic patient may benent from diuretic therapy.
arthrhls (In contrast to acute arthrttts or mechanical
derangements). The most common cause of chronic ss. d (CII•pter t)
arthritis In childhood Is JIA. The Involvement of less Feeding intolerance may lead to food averliiion and
than five joints indicates oligoarticular JIA. About 70% failure to thrtve; the most significant cause is cow milk
of children with oligoarticular JIA have a positive ANA protein intolerance or allergy. Allergy may be accom-
test. A common complication is chronic, nongranulo- panied by eczema or wheezing. A severe local allergic
matous anterior uveitis in up to 30% of individuals (c). reaction within the bowel results in colitis. indicated
This form of uveitis is asymptomatic but can lead to by anemia and/or obvious blood in the stools. Other
severe sequelae including blindness. For this reason, possible nonspecific symptoms include vomiting,
frequent surveillance slit-lamp examinations are indicated. irritability, and abdominal distention. If there is no
These children are not at risk for the development of evidence of any undertying disease In formula-fed
SLE and its complications (e.g., glomerulonephritis or infants with characteristic symptoms, substitution
468 • Answers
of a protein hydrolysat e formula is recommended. 58. II (CII•pters 2 ud 7)

Soy formula Is not an approprtate Initial substitution Gonococcal ophthalmia neonatorum has an onset
because as many as 25% of c hildren w ith cow milk of symptoms at 2 to 4 days of age. Characteristic
protein allergy are also Intolerant of soy protein. Whole features Include bilateral Involvement, purulent
cow milk should not be given to infants younger than d ischarge, marked eyelid edema, and chemosis.
1 year of age and would contain the same offending Diagnosis is suggested by Gram s tain and con-
protein. Parenteral alimentation is not indicated for firmed on conjunctival culture plated on chocolate
protein intolerance but may be necessary following or Thayer-Martin agar. The infant must be treat ed
surgery for another gastrointestinal (GO condition with parent eral antibiotics to prevent blindness and
Ontussusception, volvulus). other complications. The great majority of gonococ-
cal eye infections are prevented by the instillation of
511. II (Chapter 3) silver nitrate or erythromycin in the neonatal nursery.
A portion of the adolescent health maintenance visit is Chlamydia! infections of the eye usually present at 4
dedicated to interviewing the parent and child toge1her to 10 days of life with unilateral or bilateral mucopu-
to evaluate family dynamics, explore past medical and rulent discharge and conjunctival injection. Group B
family history, and gather nonsensitive health-related Streptococcus does not typically cause ophthalmia
Information. Additional time should be set aside to neonatorum, although It can cause sepsis and other
Interview and evaluate the adolescent alone, which complications In the neonatal period. Congenital
permits open discussion of more sensitive Issues. toxoplasmosis can cause chortoretlnltls that persists
laws regarding confidentiality and consent vary from long term. Congenital syphilis does not have any
state to state, but in all caeea, behaviora that represent characteristic findings on eye examination.
a serious threat to the adolescent's health must be
disclosed. These include being subjected to physical 59. c (CbBpter 20)
or sexual abuse and plans to harm oneself or others. On the basis of presentation and physical examination,
That said, the physician can ask the patient's permission this patient most likely has overdosed (accidentally or
to disclose information to the parents when he or she intentionally) on a narcotic. Opiates cause bradycardia,
deems it in the best interest of the child . For instance, hypotension, respiratory depression, somnolence, and
patients may be willing to d iscuss issues related to pinpoint pupils. Naloxone is the antidote for opiate
their sexual behavior, drinking, or drug use with their poisoning. Atropine and pralldoxlme chloride ara Indi-
parents In the presence of a supportive physician cated for organophosphate poisoning. Physostigmine
that they would never bring up at home. Depending Is used to counteract the effects of anticholinergic
on the stat e, adolescents below the age of 18 can agents. Deferoxamlne (desterrtoxamlne) chelation Is
provide confidentia l consent for their own health beneficial in patients with iron Ingestions. Because
care regarding (1) contraception, prenatal care, and this patient is likely a chronic user of narcotics, the
sexually transmitted diseases and (2) issues related to naloxone should be infused s lowly and at a relatively
mental health and/or substance abuse evaluation and low dose to reduce the likelihood of seizures.
treatment. In addition, various states grant •mature"
or •emancipated~ minors (those who have children, eo. b (CII1pters 1 and 20)
are married, are enlisted in the service, or are living Aspiration is the accidental inspiration of foreign
apart from their parents) the right to consent to or material into the respiratory tract. Foreign body as-
decline health care. piration is most common in children 6 to 30 months
old. Food, coins, and small toys constitute the most
57. c (Chapter I) commonly aspirated objects. Aspiration into the
Polysomnography Is not always necessary to lower airways Is much more common than tracheal
diagnose obst ructive sleep apnea, but It Is the obstruction. Although the angle of the right malns1em
gold standard. This test Is usually performed In bronchus In adults favors rtght-slded aspiration,
the hospital overnight and includes monitoring of no such propensity exists in young children, given
the 1'9Spiratory effort, a irflow, oxygenation, sleep the symmetric bronc hial angles in this age group.
state, and heart rat e. Bronchoscopy would show Patients who do not acutely obstruct their airways
enlarged adenoids but does not measure airflow. may present up t o a week after the initial event with
Overnight EEG monito ring may be done in children no witnessed episode of choking. Wheezing and
who have central sleep apnea or are suspected of respirat ory distress may be mistaken for asthma;
having certain types of seizures (nocturnal seizures). pneumonia is a consideration when breath sounds are
Pulse oximetry monitoring is performed as part of decreased. Of note, findings on auscultation in cases
polysomnography. Fluoroscopy has no role in the of foreign body aspiration are localized to one side
diagnosis of obstructive sleep apnea. of the chest only. In cases of complete obstruction,
Answers • 459
the chest radiograph demonstrates significant one- M. e (CIIapter 2)

sided atelectasis, and the heart Is drawn toward the Congenital malformations causing fetal bowel ob-
affected lung throughout the entire respiratory cycle. struction frequently lead to polyhydramnios. Most
However, a partial obstruction allows air to enter tracheoesophageal fistulas are accompanied by
during inspiration, where it becomes trapped (ball- esophageal atresia. Congenital or genetic defects
valve obstl\Jct.ion). In these cases, the inspiratory film that impair fetal swallowing also promote polyhy-
may appear normal, but the expiration radiograph will dramnios. Therefore, hydrocephalus with myelome-
show a hyperinflated obstructed lung with mecfaastinal ningocele is also correct. Fetal urine production is
shift away from the blockage. Lateral decubitus films a maior contributor to amniotic fluid volume. Renal
should be obtained if a foreign body is suspected agenesis causes profound oligohydramnios or the
and expiratory studies are normal because the child absence of amniotic fluid.
is too young to expirate.
15. c (CIIapter 14)
11. c (CIIQtw I) The history, physical examination, and abdominal ra-
This patient exhibits behaviors that are consistent with diograph are classic tor a diagnosis of Intussusception,
the diagnosis of an autism spectrum disorder. He has the ~telescoping• of a proximal segment of bowel into
Impaired social Interaction, does not communicate a more distal segment. In cases of Intussusception, air
with others, and engages In repetitive, stereotyplc or double-contrast enema demonstrates a coiled spring
behavior (rocking). Patients with Down syndrome have appearance to the bowel In the r1ght lower quadrant. The
developmental delay but socialize with others and at-
contrast or air enema results in hydrostatic reduction
tempt to communicate at this age; their development
of the Intussusception In 75% of cases.
is not described 88 deviant, 88 this patient's could be.
A child with an isolated hearing impairment would II. a (aaapter 14)
communicate nonverbally but clearly and, depending
lhe most common cause of rectal bleeding in toddlers
on the severity, may be unable to repeat works spoken
is an anal fissure. If there were significant upper G l
to him, as this child does. Although rocking and other
tract b leeding from peptic ulcer d isease or a Mallory-
self-stimulatory behaviors are found in developmentally
Weiss tear, the child would likely have melena instead
normal chDdren as well as those with autism and other
disorders, Its presence In this setting lends support for
of blood-streaked stooL Inflammatory bowel disease
the diagnosis of autism spectrum disorder. and necrotizing enterocolms could both cause lower
Gl tract bleeding (hematochezia or blood-stl'98ked
12. b tl*•pter 17) stool) but are unlikely In an 18-month-old.
Normal serum potassium levels range from 3.5 to 5.5
mEq/l.. This patient has symptomatic hypokalemia. 17. d (CIIapter 13)
The two studies that are most helpful in categorizing This Is a classic p18S8ntatlon of Wilms tumor. Patients
hypokalemia ara patient blood pressure and urine with Wilms tumor may come to medical attention after
potassium value. Both blood pressure and urine po- abdominal trauma. The trauma causes hemormage Into
tassium levels are elevated in patients with Cushing the tumor, resulting in pain, abdominal distention, and
syndrome and renovascular disease. Normotensive hematuria. The patient may also have an associated
patients with decreased potassium levels may be anemia, depending on the degree of hemorrhage.
anorexic or losing potassium from the skin or Gl tract Hypertension is frequently found in patients with Wilms
{e.g., laxative abuse). Renal tubular acidosis is the tumor and resolves with treatment.
only condition listed for which one would expect 'the
patient to have a normal blood pressure and elevated 18. e (allapter 18)
urine potassium measurement. This clinical picture Is most consistent w ith Idiopathic
talipes equinovarus. Dorsiflexion at the ankle is not
13. b p.pter 15) possible In patients with this disorder. Metatarsus
Functional and structural abnormalities in children with adductus, or in-t oeing of the forefoot, is a less se-
trisomy 21 include generalized hypotonia (obstructive vere condition t hat often responds to regular passive
sleep apnea), cardiac defects (endocardial cushion stretching. Talipes equinovarus will result in a severe
defects and septal defects are seen in 50% of cases), limp and foot ulcerations if con9ction is not achieved
Gl anomalies (duodenal atresia and Hirschsprung by the time the child begins to ambulate. Many but not
disease), atlantoaxial instability, developmental delay, all cases do require surgical repair; serial bracing or
moderate mental retardation, and hypothyroidism. casting has enjoyed a revival of sorts in recent years.
There is a higher frequency of leukemia in children One in seven patients w ith talipes equinovarus will
with trisomy 21 than in the general population. have an associated congenital malformation.
480 • Answers
II. b (CMpter 1•) plate. Type Ill fractures such as the one described in
Evaluation tor other conditions (e.g., bacterial colitis, C. the vignette may require open reduction and fixation
dlfflclle Infection) Is Important before starting therapy but have a relatively good prognosis.
directed against Inflammatory bowel disease (IBD).
Similarly, complications of IBD may require antibiotics 73. b (CII..-r 12)
or surgery rather than anti-inflammatory drugs (e.g., On the basis of the information provided, this patient
prednisone). Cancer risk is somewhat increaaed in most likely haa hereditary spherocytosis (HS) which
long-standing Crohn disease. Therapy with mercap- gives a positive result on the osmotic fragility test.
topurine and azathioprine will not provide symptom Patients with HS have a history of neonatal jaundice,
relief tor weeks. Therapy with anti-TNF a-antibody may occurring usually in the first 24 hours of life. HS is
be helpful, but other options may be preferable and caused by a defect in the red blood cell membrane
excluding an abscess is the first order of business. A proteins (spectrin, ankyrin, or band 3 protein). Inheri-
capsule endoscopy is helpful for occutt small intestinal tance is usually autosomal dominant, but 25% of cases
disease but less likely to be the teS1 of choice in an are caused by new mutation or autosomal recessive
acute setting. forms. None of the other listed diagnoses would give
positive results on the osmotic fragility test.
70. c (Chapter 8)
Food allergy Is an Immunoglobulin E OgE)-medlated 7._ d (CII1pt8r 3)
clinical response triggered by antigen-specific lgE The examination described Is most consistent with
bound to mast cells and basophile, resulting in cellular Tanner stage IV development. Stage Ill is character-
degranulation and the resultant immediate clinical ized by enlargement and elevation of the breast and
response. Although skin prick tests measure the areola without separation of1heir contoura, and pubic
wheal-and-flare response of food-specific lgE bound hair spread sparsely over the pubis which is less dark
to skin mast cells, this response is frequently falsely and curly than adult pubic hair. In stage V, the areola
positive. As such, a positive test has to be followed regresses to the general contour of the breast, and
by the development of clinical symptoms in response pubic hair is adutt in texture and amount and has
to oral challenges to the implicated food (but not the spread to the medial thighs.
placebo) via a double-blind placebo-controDed food
challenge, a pmcedure that must be performed In a 7S. b (CIIapt.r 13)
hospltaVofftce setting equipped to respond to acute The chemotherapy used In acute myeloid leukemia
life-threatening anaphylaxis. Food-specmc lgE levels {AML) Is more Intense than that used In acute lym-
can often be falsely positive and should not be used phocytic leukemia (ALL), and the myelosuppression
alone to diagnosis food allergy. Open-label food chal- is severe. Patients require hospitalization for aggres-
lenges are often helpful but are not used for definitive sive supportive care until they begin to show signs of
diagnosis. Finally, an endoscopy is useful to examine count recovery. Hyperleukocytosis is more likely to be
Gl anatomy and possible pathology but does not symptomatic in AML (and thus more likely to require
diagnose food allergy. treatment) than in ALL because AML blasts are larger
and stickier than All. blasts. Patients with Down syn-
71. a (Cha~~W11) drome and AML have an excellent overall survival rate,
Scoliosis in a premenarchal female is likely to prog- whereas secondary AML Is extremely difficult to treat
ress and should be treated aggressively. Curvature of and outcomes are poor. Not all patients with AM L will
25° to 45• requires bracing to halt progression of the go on to bone marrow transplantation. Low-tisk AML
curve. If extemal bracing is not successful and the is treated with chemotherapy alone.
curve progresses to greater than 40° to so•, surgery
Is required. Stretching exercises are not effective In 76. c (CIIIpter 1.)
the treatment of scoliosis. Crohn disease typically Is associated with transmural
Inflammatory disease resulting In fistulae or stricture
72. c (CIIapler 11) formation. Lesions may be found from the mouth to
A fracture through the growth plate that extends into the anus but most commonly appear in the ileum and!
the epiphysis and into the joint space is consistent with or colon involvement with skip lesions, rectal sparing,
a Salter- Harris type Ill fracture. lfthe fracture extended segmental narrowing of the ileum (string sign), granuloma,
into the metaphysis only, it would constitute a type perianal disease, and growth failure. Ulcerative colitis
II fracture. Fractures through both the metaphysis is typically characterized by rectal involvement, rectal
and epiphysis into the joint space are type IV. Type I bleeding, and dtr'fuse superficial mucosal ulceration.
fractures occur along the growth plate only, whereas Ulcerative colitis is associated with an increased risk
type V fractures result from compression of the growth of colon cancer.
Answers • 481
77. d (Citapter 2G) 10. II (CIIapter 1)

Carbon monoxide poisoning presents with lethargy, A 36-month-old child with typical development should
lrr1tablllty, confusion, dizziness, headache, and nausea. be able to pedal a tricycle, broad Jump, copy a circle,
Signs Include lrragular breathing, cyanosis, and mental use five- to eight-word sentences, and know his or
status changes. Unconscious patients are severely her own age and gender. Two-year-old children can
affected and have a high risk for death. Oxygen is jump with 2 ft off the floor and copy straight lines
considered an Bl'ltidote for carbon monoxide poison· but CBI'lnot broad-jump or copy circles. In contrast,
ing; immediate administration of oxygen is indicated 4-year-old children can generally balance on one
for affected patients. Although all the other options foot, copy a cross, dress themselves, and wash Bl'ld
listed should also be perfonned in this patient, the dry hBI'lds. At age 5, a child can skip with alternating
most immediate need is oxygen. feet, draw a person with six or more body parts, and
name four colors. Six-year-olds can ride bikes and
write their own names.
71. • (Cll•pt• 7)
Epiglottitis consists of inflammation and edema of the
epiglottis and aryepiglottic folds. Most cases occur 11. c (Cita..-r I)
during the winter months in childran 3 to 5 years of This child, Judged to be 10% dehydrated, Is 3,000 mL
age. Fever, sore throat, hoarseness, and progressive behind on fluids (3 kg). A total of 540 mL Is subtracted
stridor develop over 1 to 2 days. On examination, from the deficit, leaving 2,460 mL to be given over the
the child appears toxic, drools, and leans forward to next 24 hours. Half of this Is provided over the nrst
maximize airway patency. Epiglottitis is considered a 8 hours (1 ,230 mL at 153 mi.Jhr) along with maintenance
life-thraatening emergency because of the propensity fluids (67 mLJhr). The most appropriate fluid choice for
of the swollen tsssues to cause sudden and Irreversible a child this age is 0 5 0.2 normal saline (with 20 mEqiL
airway occlusion. KCI to be added after the patient has urinated). If the
Children with croup typically experience the child had hypematremic dehydration, the deficit would
sudden onset of a hoarse voice, barky cough, and need to be replaced over a longer period.
inspiratory stridor, which may progress to respiratory
distress. Patients may have a prodrome consisting 82. • (Chapter 14)
of low-grade fever and rhinorrhea 12 to 24 hours Both cellae disease and Crohn disease are possible.
before the onset of stridor. Children with bacterial Anemia may be present with both. The tissue trans-
pneumonia may present with nonspecific constitu- glutaminase assay (lgA) should be elevated In cellae
tional complaints, including fever, irritability, vomiting, disease. Inflammatory markers such as elevated
abdominal pain, and lethargy. Abrupt onset of fever, c-reactlve protein and platelet count are often elevated
chills, dyspnea, and chest pain is typical. Drooling in Crohn disease. Physical examination does not justify
and other symptoms related to the upper airway are a CT as the initial study. A UTI, hydronephrosis, or
rarely present. The onset of diphtheria may be abrupt, cystic fibrosis may be the etiology of the complaint,
with a low-grade fever, sore throat, mild pharyngeal but a laparotomy is not yet indicated. Colonoscopy
Injection, and development of a membrane on the and upper endoscopy are not yet indicated, but either
tonsils. The membrane may extend to Involve the or both may be in the next round of testing. Without a
nasopharynx and laryngotracheal areas. Because history of diarrhea, the symptoms and signs are unlikely
of the use of the diphtheria-tetanus-acellular per- because of bacterial or parasitic infection.
tussis vaccine, diphtheria is a rare disease in most
areas of the world. Anaphylaxis is a life-threatening 13. • (Chapter 13)
lgE-mediated allergic reaction that may occur with The leukemias account for the greatest percentage of
foods, medicines, and other triggers. Children often childhood malignancies. Acute leukemias constitute
present with respiratory distress, wheezing, pruritus, 97% of all childhood leukemias and are divided Into
and hives. ALL and AML. ALL accounts for 75% of all childhood
acute leukemias. A history of fever, pallor, ano~a.
bone pain, lymphadenopathy, petechiae, and hepa-
78. d (CIIapter 3) tosplenomegaly ia consistent with ALL Leukemic cell
Although guns are often bought with the intention of dissemination results in bone marrow failure, reticu-
making a home safer, they actually increase the risk loendothelial system infiltration, and penetration of
of gun death in family members living in the home. sanctuary sites (central nervous system and testicles).
Adolescents who live in a home with a gun are 3 times Marrow infiltration results in crowding out of normal
more likely to die of homicide and 10 times more likely marrow blood cell precursors, which then results in
to commit suicide with a gun than their peers who live anemia (pallor) and thrombocytopenia (petechiae).
in homes without guns. Infiltration of the reticuloendothelial system results in
482 • Answers
lymphadenopathy and hepatosplenomegaly. Bone pain greater than 2.0. The mean corpuscular volume is used
Is caused by expansion of the manow cavity, destruc- to descr1be the anemia as microcytic, macrocytic, or
tion of cortical bone by leukemic cells, or metastatic normocytic. All of the anemias noted In the question
tumor. Although fever and petechiae ara consistent result from decreased red cell production and have
with aplastic anemia, bone pain, lymphadenopathy, an inadequate raticulocytosis (ARC < 2.0). Decreased
and hepatosplenomegaly are not. red cell production is cauaed by either deficiency of
hematopoietic precuraors or bone manow failure. The
84. • (CIIapler 11) microcytic anemia described in the question is most
Observation is the best answer because this girl is likely caused by iron deficiency, which is not only
skeletally mature and her curve is unlikely to progress the most common microcytic anemia, but also the
significantly in the future. If no progression is seen in most common cause of anemia during childhood. It
1 year on radiograph, then minimal further follow-up is most often seen between 6 and 24 months of age.
would be indicated, and she should have an essentially Thalassemia syndromes 81'8 also microcytic anemias
normal spine in the future. Posterior spinal fusion is but are less common than iron-deficiency anemia.
indicated only for scoliosis over 40° to 50° in skeletally Anemia of chronic disease may be microcytic or nor-
mature patients. Intensive physical therapy has not mocytic. Transient erythrocytopenla of childhood Is a
been shown to alter the natural history of scoliosis. normocytic anemia that Is an acquired red cell aplasia.
Bracing Is Indicated only for curves over 25° to 30° In Parvovlrus 819 aplastic crisis Is a normocytic anemia
patients who are still growing. Spinal manipulation has that results from parvovlrus B 19 marrow suppression
not been shown to effect scoliosis curve progression. of erythropoietic precursors.
85. d (Cblpter 7) 88. a (CIIapt• 13)

The boy's history and clinical picture are most consistent The clinical description is most consistent with Ewing
with Rocky Mountain spotted fever or ehrlichiosis. He sarcoma. Unlike osteosarcoma, Ewing sarcoma tends
is significantly ill (and vomiting) and should be admitted to involve systemic symptoms, such as fever, weight
to the hospital. Both Rocky Mountain spotted fever and loss, and fatigue. Ewing sarcoma usually involves
ehrlichiosis are rapidly progressive; treatment should the diaphyseal portion of the long bones. The most
be initiated immediately when these diseases are sus- common sites for Ewing sarcoma are the mid proximal
peded. Delay In treatment can be fatal. Because this femur and the bones of the pelvis. The most common
boy has no history of a t ick btte and Is sulftclently Ill, sHes of osteosarcoma are the distal femur, proximal
empiric antibiotic treatment should Include coverage tibia, and proximal humerus. Benign bone tumors
for Rocky Mountain spotted fever and ehrtlchlosls and eosinophilic granuloma are generally not painful.
(doxycycline) and meningococcemia (cefotaxime or Chronic osteomyelitis may present with fever, pain, and
ceftriaxone). localized swelling, but weight loss is unlikely.
88. d (Cblpter 8) 89. a (CIIapt. . 1, 2, and 13)

Henoch-Schonlein purpura (HSP) is the most com- A positive cover test Is consistent with strabismus
mon vasculitis in childhood, and the classic tetrad or misalignment of the eyes. This child is at risk for
of findings consists of skin (purpura), joint (acute amblyopia (reduced vision In the affected eye) and
arthritis), Gl (abdominal pain, Gl bleeding), and kidney loss of depth perception. She should be referred to a
disease. Approximately 20% of patients will have renal pediatric ophthalmologist for evaluation and treatment,
involvement early in the disease course, most often which may include surgical realignment. Leukocoria
microscopic hematuria. Severe renal involvement with describes a white pupil o.e., absence of the red reflex).
azotemia Is rare (< 5% of cases). Autoantibodies are Retinoblastoma Is a potential cause of leukocor1a.
negative. Even though HSP Is an lgA-medlated Immune Nasolacrimal duct obstruction occurs In Infancy and
complex disease, C3 and C41evels are usually nonnal. presents with tearing.
87. a (Chaplll' 12) 10. b (CIIaptar I)

The adjusted reticulocyte count (ARC) = ([measured In older patients with acute courses, the signs of hy-
hematocritl/[normal hematocrit for ageD x reticulocyte drocephalus with increased intracranial prassure are
count. An ARC less than 2.0 suggests ineffective eryth- relatively clear and include morning headache that
ropoiesis. whereas an ARC greater than 2.0 signif'teS improves after upright positioning or vomiting; irrita-
effective erythropoiesis. Anemia caused by a lack of bility and/or lethargy; and papilledema and diplopia
production of red blood cells will, therefore, have an (CN VI palsy). Spasticity, clonus, and hyperreflexia
ARC less than 2.0, whereas anemias resuHing from most prominent in the legs are additional neurologic
hemolysis or chronic blood loss will have an ARC signs of hydrocephalus. The Cushing triad, consisting
Answers • 483
of hypertension, bradycardia, and slow irregular 114. • (aaapter 3)

respirations, Is a late and ominous sign of Increased As many as 40% of patients with anorexia nervosa
Intracranial pressure Implying Imminent rtsk of brain develop mitral valve prolapse, evidenced by a mldsya-
herniation. Hypotension and tachycardia would not tollc c lick and/or murmur. Other cardiac abnormalities
be expected. The anterior fontanene typically closes (arrhythmias) can occuras a complication of anorexia,
before age 2. Erythema migrans is a rash associated but n less common. Anoruxic patients will often present
with Lyme diaease; although Lyme diseue can be with bradycardia; however, bradycardia alone does not
associated with abducens nerve palsy, the presence result in a click or murmur. A prolonged QTc interval
of additional signs and symptoms of increased intra- may develop in patients who purge by vomiting (which
cranial pressu~ on examination makes this etiology is more common in bulimia) because of hypokalemia.
mo~ likely.
15. • (aaaptw 1)
11. a (CIIapt. . 5 and 17) The routine use of seat belts and child car seats has
This patient displays the characteristic findings of been shown to be highly effective in reducing the
prarenal acute renal failure because of decreased renal incidence of severe injury and death in the pediatric
perfusion from dehydration. She has tachycardia, de- population. All states require car seat Atstralnt of
creased urine output, and a low fractional excretion of passengers under 40 lb. Children who are 72 years of
sodium. Recognition and prompt treatment of prerenal age or older may ride facing forward, whereas lighter/
failure Is essential to prevent progression to Intrinsic younger Infants must face the rear. When a child pas-
renal failure. The treatment of choice is restoration of senger has reached the height/weight limit for his or her
renal perfusion by correcting the intravascular volume car seat (usually up to 40 lb), a booster seat should be
deficit with an IV bolus of normal saline. This will usually employed. The child should be restrained in a booster
result in restoration of kidney function and urine output seat until the standard lap belt fits correctly (across
as well as correction of the acidosis and hyperkalemia. the chest and thighs) and the child is tall enough for
The metabolic acidosis does not requi~ urgent the legs to bend at the knees with the feet hanging
specific correction with bicarbonate. The patient down. This usually does not occur until the child is 8
does not d isplay signs of significant fluid overtoad to 12 years old or approximately 57 inches in height.
and therefore does not requiAt furosemide (which Because air bags aAt designed primarily for adults,
may cause more harm than good In this situation). chlldAtn should always ride belted In 1he back seat.
The gastroenterttla Ia moat likely viral In etiology and
does not require Immediate antibiotic therapy. Dialysis 11. a (aaaptw 1")
would be Indicated only If the patient had persistent Projectile nonblllous vomiting Is the cardinal feature
fluid overload, hyperkalemia, or acidosis that is unr&- seen in virtually all patients with pyloric stenosis.
sponsive to other medical therapies. Physical findings vary with the severity of the obstruc-
tion. The classic finding of an olive-sized, muscular,
92. • (Chapter 4) mobile, nontender mass In the epigastric area occurs
Colic is a syndrome of recurrent irritability that occurs in most cases. Dehydration and poor weight gain are
most commonly in Infants 3 weeks to 3 months of common when the diagnosis is delayed. Hypokalemic,
age. The episodes occur daily and persist for several hypochloremic metabolic alkalosis with dehydration
hours, usually in the late afternoon or evening. During is seen secondary to persistent emesis in the most
the attacks, the child draws the knees to the abdomen severe cases.
and cries inconsolably. The crying resolves as suddenly
and spontaneously as it begins. Colic is often mistaken 17. e (CII•pter S)
for cow milk protein allergy, although the latter typically Children who lose electrolytes In their stool and are
occurs In slightly older Infants and may Involve bloody supplemented with free water vary dilute Juices are
stools, an eczematous rash, poor growth, abdominal prone to the development of hyponatremia. Symptoms
distention, and vomiting. Intussusception is rwe in a child of hyponatremia include anorexia, nausea, confusion,
this young and is not temporally cyclical. Hirschsprung and lethargy. The ataxia may be caused by weakness
disease is unlikely because the child ia stooling normally. or by lethargy. Hypomagnesemia ia uncommon unless
the patient has been Ateeiving medication or parenteral
93. • (CMpter 18) nutrition. Hyperkalemia presents with symptoms of
Breech presentation and family historyof developmental paresthesias and weakness but is less likely, given
dysplasia of the hip (DDH) are significant risk fac- the history of present illness. Patients with protracted
tors; the presence of either on history warrants a hip vomiting and those who are being treated with loop or
ultrasound. The remaining options a~ all minor risk thiazide diuretics may develop metabolic alkalosis, but
factors for DDH. acidosis would be expected in 1his patient. This patient
484 • Answers
may Indeed have hypochloremia, but It Is unlikely to testing all children at the ages of 12 and 24 months.
be the prtmary cause of his symptoms. Research Is under way to determine how to better dallne
and target high-risk groups and decraase the number of
1L c (CIIIpler 11) tests performed on the general populadon. Many omces
Scant axillary hair/Tanner II pubic hair, testicular volume screen for elevated blood lead levels by performing a
5 ml, and a bone age of 11 with normal screening labs capillary micro-lead measurement. Arly capillary blood
deacribe a boy with prepubertal phyaical exam findings, level 10 pgldl must be confirmed by a venous blood
a delayed bone age, and likely euthyroid with normal lead test because of a relatively high false-positive rate.
growth hormone screening parameters. Answer a is a All elevated screening (capillary) blood tests should be
more pubertal advanced boy with an advanced bone confirmed with a venous sample before treatment is
age. Answer b describes a boy with pubertal delay initiated unless the child is acutely symptomatic.
but with biochemical evidence of hypothyroidism.
Answer d describes a boy with pubertal delay but 1ao. c (Chapter 1 D)
with biochemical concerns that may suggest growth Tllis child has linear scleroderma, a condition charac-
hormone deficiency. terized by linear streaks of indurated and thickened skin
and underlying soft tissues. Major sequelae Include
18. c (CIIIpler 1) growth restriction and limitation oftheatrected areas.
Lead poisoning Is an Ideal condition for which to screen, In this case, there Is a high risk tor the development of
given Its lack of earty symptoms, Its harmful effect on a right elbow contracture because the linear sclero-
cognitive development at preclinical levels, and its derma extends over the elbow joint. The child is at very
amenability to treatment. Children aged 9 months to 6 low risk for the development of systemic sclerosis,
yeara should be assessed for an increaaed risk of lead a condition in which internal organ disease, such as
exposure with a questionnaire. Current recommendations esophageal dysfunction, cardiopulmonary disease,
vary depending on practice location, with most areas severe Raynaud phenomenon, and peripheral arterial
under universal saeening coverage, which involves disease, is commonly seen.
Appendix
Additional Images
FIGURE A-Z. Herpes zoster. Tender-grouped

papulovesicles on an Ell)'themstous bese invoMng the
upper right back in a darmatomal distribution. ~mage
~~..~-~~~-~·...~~~~!...~!?...L. . .-·-·-··-··-··-
RGURE A-1. Papular acrodermatitis of childhood.

A toddler with erythematous, edematous papules
concentrated on the extremities and strikingly sparing
the trunk that are typical of this condftlon. It appears
to be a reaction to a viral Infection. (Image courtesy of
~~-~..'!!.:.~.~~~ ..~.~:~ . ...................... . .............................................................
FI&URE A-3. Pityriasis rosea. A salmon-pink annular

patch with a collarene of scale developed on the back
of the patient's left arm followed several days later
by an eruption of smaller salmon-colored lesions in
a •christmas-tree~ distribution on the trunk. ~mage
c~~~ ~~~.~·...~~~~!...~~:.l . .._. _,_·-·---·-
485
486 • Appendix
FIGURE A-4. Bullous Impetigo. Intact fluid-filled thin

bullae with scale peripherally and a hemorrhagic crust
centrally 1hat can be mistaken for cigarette burns
especially following bullae rupture. To.xln-produclng
S. aureus Is causative. Omage courtesy of Anne
Y.'!:...~~!...~.P.:L............................................................. . ...................................
FIGURE A-6. Diffuse areas of erythema with superficial

flaccid vesicles and ruptured bullae associated wi1h
significant pein and fevers are seen in Staphyloooccal
Scalded Skin Syndrome because of a toxin-
producing strain of S. au!SUS. Qmage courtesy of
~~!..~:..~~!:%..~~.J.............. . . . . . . . . . . . . . . . . ....-·-·······..· · ·..·····--
FIGURE A-5. Nonbullous impetigo has a honey-

colored crust on an erythematous ulcerated base.
Streptococcus or Staphylococcus species can usually
be cultured from the lesion. omage courtesy of Anne
Y.'!:...~~~---~.P.:L............... . . ............................ .................................................
FIGURE A-1. Typical inflammatory hemorrhagic bullae of

the oral mucosa noted in Stevens-Johnson Syndrome.
~~~~'?.~~~ ~!..~~9 \Y..:..~.~-~!-~~.:t_................. _ ...........
Appendix • 487
RGURE A-8. A hemangioma wilh superficial and deep

components invoMng the glabella. Qmage courtesy of
~~!.~:..~!--~-~:L......................................................................................
RGURE A-10. Transposition of the great arteries with

an Intact ventricular septum, a large patent ductus
arteriosus, and an atrial septal defect. Note the
following: (a) the aorta arises from the morphologic
right ventricle; fiJ) the pulmonary artery arises from the
morphologic left ventricle; (c) mixing occurs across
the atr1al septal defect; (a) shunting from the aorta
to the pulmonary artery vta the ductus arteriosus.
Q!!.~-~~~-~~--~..~~~-~-~~..~-~~).... ................................................................
RGURE A-1. Truncus arteriosus. Typical anatomic findings

include (a) a si'lgle truncal vessel arising from the heart
gMng off the coronary arteries, pulmonary arteries, and
aortic arch; fiJ) abnormal truncal valve; (c) left aortic arch
shown (right aortic arch occurs in 30% of cases); (a)
~~!~-~~E..~-~..~-~J!!.~-~~-~..-~Y...~~~-~-~~-~:L. . . .
488 • Appendix
...... .......
........ _______ ,.,_..,
RliURE A-11. Supradiaphragmatic total anomalous FIGURE A-12. Tricuspid atresia with normally related
pulmonary venous connection. Note the following: great arteries and a patent ductus arteriosus. Typical
(a) pulmonary veins join into a connuence; (b) the anatomic findings include {a} atresia of the tricuspid
connuence joins a vertical vein that ascends to connect valve; (b) hypoplasia of the right ventricle; (c) vmtricular
with the (c) innominate vein and then drains via the septal defect; (d) patent foramen ovale (PFO). Note: All
superior vena cava into the right atrium; (d) venous systemic venous return must pass through the PFO to
return must cross the patent foramen ovaJe to ftll the left reach the left atrium and the left ventricle. Ollustratlon by
~~~~.'!l.:..I~~~~~~~.~...~.~~~.~~..~.~:.L................................................ .1:~~.~~~~..~.~~:9.........................................................................................................
Appendix • 489
RGURE A-14. Ebstein anomaly. Typical anatomic findings

RGURE A-13. Tetralogy of Fallot. Typical anatomic include (a} inferior displacement of the tricuspid valve
findings include (a} an anteriorly displaced infundibular into the right ventricle {the normal placement of the
septum, resulting in subpulmonary stenosis; (b) large tricuspid valve is noted in dashed lines); (b) small right
anterior malalignment ventricular septal defect; (c) ventricle; (c) marked enlargement of the right atrium
overriding of the aorta over the muscular septum; (a) because of the •atr1altzed" portion of the r1ght ventr1cle
hypoplasia of the pulmonary valve and main pulmonary as well as tricuspid regurgitation; (a) right-to-left
artery; (e) right ventricular hypertrophy, secondary to ~~-~-~-~-~-~--~-~..~-~!...~~~..~~-~:..~.~~~-~-~~!~~. .~. ~~~!.~!~..§~1.
right ventricular outflow tract obstruction. ~llustration by
-~~~~~~..§.~.:L.......................................................................................................
470 • Appendix
FIGURE A-15. Hypoplastic left heart syndrome. Typical RGURE A-1&. Coarctation of the aorta. Possible
anatomic findings include (a) atresia or hypoplasia of the anatomic findings Include (a} narrowing distal to the left
mitral valve and hypoplasia of the left venbicle; (b) aortic subclavian artery; (b} patent ductus arteriosus supplying
atresia or stenosis and a diminutive ascending aorta systemic flow to the descending aorta. Ollustration by
and transverse aortic arch; (c) patent ductus arteriosus
supplying systemic blood flow; (d) patent foramen ~!~.~~--~~:2.................................................................. .......................................
ovale, with a Jeft-to-11ght shunt. Qllustra11on by Patrtcla
~-~:1 .............................................................................................................................
RGURE A-17. Chancre of primary syphilis. (From

Goodheart HP. Goodheart's Photoguide of Common
Skin Disorders, 2nd ed. Philadelphia, PA: Lippincott
Williams & Wilkins, 2003.) ooooooooo..
-~·--~-•••--••-••••·•-•••.,000000000,.0000,,0. . 000 0 o·•o••••~••••••-•• ••••-••••n-••n•-•••••••-••••-
Appendix • 471
FI&URE A·11. Typical lesions of seoondary syphilis FIGURE A-21. Typical roseola exanthem. (From
(palms, soles). (From Goodheart HP. Goodheart's Goodheart HP. Goodheart's Photoguide of Common
Photoguide of Common Skin Disorders, 2nd ad. Skin Disorders, 2nd eel. Philadelphia, PA: Uppincott
!:~!.~.~P.~!.~. . .~~:..~P.P.!~~. ~!!!!~~-~. ~--~!!~.~-~. . .~.9.9.~.1..... Williams & Wilkins, 2003. Image courtesy of Bernard
~-~~~...~~:L..........................................................................................................
FI&URE A·1!l Genital herpes {multiple erythematous FIGURE A·22. •slapped cheeks• of erythema infecliosum
ulcerations). {From Goodheart HP. Goodheart's (frflh disease). (From Goodheart HP. Goodheart's
Photoguide of Common Skin Disorders, 2nd ad. Photoguide ofCommon Skin Disordets, 2nd ad.
!:~!~~P.~!.~~. ~~:. ~P.P.!~~--~!!!!~.~-~--~. ~!!~.~-~....~9.~~).____ !:~!~.~!?.~!.~.. .~~:. ~P..~~~!?.!!.~!!!~!.!!~.!. ~!~~~..-~.9.2~.1......
FIGURE A-23. Typical varicella lesions. (From Sweet RL,

Gibbs AS. Atlas ofInfectioUs Diseases of the Female
FI&URE A-lD. A child with measles. (Photo courtesy of Genital Tract. Philadelphia, PA: Upplncott Williams &
~~~-~..~~..~~~-~~.9.?D.!.~!...~~~...!:r.~.~!!~~:L_...._._ _ ~~~~~..:?..g~:.~...............-....- ......---·-·--·-·- ..-....- -
472 • Appendix
FIGURE A-25. Lyme disease {erythema migrans). (From

Goodheart HP. Goodheart's Photoguide of Common
Skin Disordefs, 2nd ed. Philadelphia, PA: Uppincott
~~~~~~-~~--~-~~!.~~-~!..?Q9.~.:L............................................. ....... ....................
FIGURE A-24. Petechial lesions of Rocky Mountain

spotted fever. (Image from Rubin E, Farber JL.
Psthology, 3rd ed. Philadelphia, PA: Uppincott Williams
~-~kins, 1~9.}_ _·--·-············--··············...·--...··-········ ··-- F16URE A-2&. Leukokoria caused by advanced
intraocular retinoblastoma of the right eye. (From
Tasman W, Jaeger E. The Wdls Eye Hospital Attas
of Clinical Ophthalmology, 2nd ed. Philadelphia, PA:
.~.P..!?.~.~-~-~!!.I_i_~-~..!.~.~~~-~-~!. ~.9.-~~.:L..............._. . .... . ... . . .. . . . ..
Index
A clinical p.re.seotat:ion 289t c::oogmitalabnonnalities, 104

AAP (American Academy of PedW:rlca), dlagnoltic evaluation. 290 c::oogmital tracheallt.enotdJ, 104
11 cll1ferential cllagnosls, 290 tracheomalada. 105
AAPD (American Academy of Pediatric epidemiology, 289 AKI (acu~ kidney injury), 374-376,
Dentistry), 14 history, 290 374t
Abdomen. 24o pbylk:al examination. 290 Alagllle syndrome (AGS), 321
Abdominal pain, 305-B07 risk fac:tnrs, 289 Alanlne amlnotranlferue (ALT), 320
Abnormal head shapes, 190-191 treatment. .290-292 Alcoho~59t
Abnormalities in amniotic fluid volume, Acute otitis media. (AOM), 113-115 ALF (acute livu failure), 320-321
26 Acute phase. 157 ALL. See Acute lymphoblutic leukemia
ABO IDrompatlbWty, 37 Acute poisoning, 423-426, 424-425t (ALL)
Absence selzures, 175 Acute poststreptoc:ocr:al AllelJ{c drug reactions, 204
Acetaminophen, 424t glomerulonephritis (APGN), 116. Allergy, 147-150, 312t
Admndropluia. 356 368 allergic reaction~, 280
.Add-ban phydology, 78 Acute promyelocytl.c leukemla, 292 allergic: rhinitis, 148-149
Al:ne vulpril, 201-202 Acute rheumatic &vu CARP), n6 lllsfoeclern-. 149
Acquired bleeding cliJord.era. '1:17-279 revised Jones criteria for, 116t uthma,149
diaeminated inlravuc:ular Acute transfusion. reac:tl.on.t, 280 atopic clumatit1s, 147-148
ooagu1atioA, 271 m
Acutely chlld, 403-433 clinical manlfemJions, 148
DVT and PE, 278-279 Acyanotic congenital heart disease, differenttal dlapom,l48-149
Acquired struc:tura1 hevt dinase, 221-226 epidemiology. 148
227-228 atrial septal de!ecU, 221 food~ 149-150
.Aaoc:yanolla, 23, 21.2 coarctation of the tort».. 225 history, 148
Acute abclomlnlll pain, aos common atrioftntrlcular canal .,.tbopnesis, 148
Acute appendic:itU. 306 defect. 223-224 phyrical examination, 148
Acute cerebellar atuia, 187 pawn duc:tul arterioaut, 224-225 riak facton,148
Acute cerebellltil, 187 pulmonic stenom, 226 ur1ic:ula, 149
Acute chat syndrome. 261-262 vmtrlcular septal defem, 221-223 Allolmmune hemolytic anemi., 263
Acute diarrhea, 312t Addison disease, 337 Alloimmunization. 280
Acute gutroenterilill (AGE), 313 Adenollne, 412t Alport l)'lldrome. 369
Acute hem.o1ytic: tl'anlfua!on reactioJu;, adenosine 1riphosphate, 7l ALT (alanlne amlnotranlferue), 320
280 ADHD (attent!on-de6clt/hyperactivity Ambiguous genJtaHa. 24, 384
Acute kidney injury (AKI), 374-376. disorder), 168 Americm Academy of Pediatric
374t Adoleacence, 51, 52t Dentistry (AAPD), 14
Acute liver failure (ALF), 320-321 Adolescent medicine, 51-64. Su Aawicm Academy ofPecllalrlc:a (AAP),
Acute lymphoblastic leukemia (All.), allo Eating dison:len; Sexual 11
287 development/reproductive health; Aminot:ransferuea, 320
B-cell ALL, 288 Subftance use and abuse Amiodarone, 412t
chloroma, 290 Adolescent office vl.sl.t. 51-52 AML. S. Acute myeloid 1eukemla
claulfic:ation, 288-289 Adolescent population, violence in, (AMI.)
clinical rnanifmations. 290 59-60 Amniotic fluid YO!wne, abnormalities
clinic:al presentation, 289t Adrenal dysfunction, 336-339 in,26
dJagnoltlc evaluation, 290 Adrenoleukoctystrophy,171, 337 Amlphyl.actic lhoc:k, 410
dif£erml:lal dlapom, 290 AGA (appropriateness for gestational ANCA (antioudear cytoplasmic
epidemiolosy, 289 age), 20 antibody), 368
histo~290 AGE (101te gutroenterit:U), 313 AJwnJa. 247-251. SH IIUo Autoimmune
phydcal exam1nation, 290 Ages and Stages (ASQ), 13 hemolytic anemia; Mlcrocytk:
risk fac:ton, 289 AGS (Alaafl1e syndrome), 321 mem1u
T -c:ell All., 288 AIHA. S. Alltoimmune heroolytic birth history. 247
trealment. 290-292 uwnia (An{A) dJagnoltlc evaluation, 2.49
Acute ~ld leulcem1a (AML), 267, Airway, 404-405 dietary hiltory, 247
287,292 Airway ob&truc:tlon in c:hildren. enluatioD, physical findinp, U9t
chloroma. 290 104-105. See tdso Lower airway m:rinJic dmc:b, ~
classification, 288-289 obstructive dlaeue guiding the uwnia differential,
clinical manlfemJions, 290 bronchomalada, 105 247-251
473
474 • Index
Anemia (cmdinrurtl) usessing mntrol and adjlllting Blalock-Tauuig shunt. 217

hemolytic anemia, 256-25'7 therapy, 94r-95t Blood pre&lure, 409
hktory.247 ages 0 to u. 94r-95t Blood produ.cts, 279
increued deltructioD, 248/ ages greater than or equal to 12, pRBC tland1uioNI, 279
of Inflammation, 255 96t Blood urea n1tropn (BUN), 73
intrlnlic de&cta, l4Bf clinical manlfeatatiom, ':Tl Bloom syndrome•, 293
macroqt:ic, ~ di.poatic evaluation, 97-98 Boneap.334
meplobiNtic, 248/ dit!erential diagnoab, ':Tl Bone marrow f'ailwe (BMF) syndromes,
miuoc:ytic:, U8f epidemiology, 97 248
noomeploblutic, 248/ long tenn in management in children. Bone twnon. 298-300
nonnocyt1c. ~ 99-100t Boot..wped. heart, 218
nonnocyt1c IJlelnlu, 256 ages 0 to 11, 99t Bortktell4 putvull, 120
slderoblutk: anerru.., 255 ages greater than or equal to 12, Brach~haly, 393
typea,24.3f lOOt Bradya.rrhytluniu, 235--237
Anplmen .yruirome, 396 risk factors, ':Tl ~astutilkj~ce.37
Angioe<lem.. 149 severity and initiating therapy in ~..tfeeding, 65-66
Ankyloglolllia, 23 children, 90-93t ~at:hlDg. 405--40'7
Anorex:la nervoa, 55, 57t ages 0 to 11, 90-91t Brief l'eiOlved unexplained event
Amid.patory guidance, 10-11 ages greater than or equal to 12, (BRUE), 106, 107t
Antlcoagulation. '1:19 92---93t Brlvaracetam, 180t
Antl.dromlc reen1rant tachycanUa. treatment, 98-101 Bronchiolltia, 119-120
(ART),233 Ataxia, 186-187 Broncho~,105
Antinuclear antibody (ANA) 1m. 152 Ataxia-telangiectasia, 187 BRUE (brief resoM:d unexplained
Antinuclear cytoplumlc antibody Atonic seizures,175 ewnt),l06, 107t
(ANCA),368 Atopic dermatitis,l47-148 Bulim1a nervo.sa., 55, 57t
Antiseizure medic:atiold, llide effEcts Atrial fibrillation, 233 Bulloua lmpetJso, 1§19
ot 180t Alrla!Outter, 233 BUN (blood urea nitrogen), 73
AOM. See Acute otldJ medJa (AOM) Alrlal septal defects, 221 B~~102
Aortic stenosis, 225-226 Atropinea. 412t Burkitt lymphoma. 292
Appr scora, 26-ao Attention-ddcltlhyperac:tivity disorder Burn.,l1, 418-419
prenatal and delivery recorda, 27t (ADHD),168
tranlmiJiion. presentdoo, .AWam 1pedrum dborders (ASD), 13, c
identific:atioo. and treatment. 167-168 CAH (mngenital adrenal hyperpluia),
28-301 Autoilnmune hemolytic anemia (AIHA), 73, 337- 339, 384
cytomegakMrua. 28t 263---264 Calcium. d.lsorclen ot; 340-341
herpea simplex vltua, 28t Autolomal dominant dlaeues, 391, 392t Calcium hom.eoatula, 78
human immunodeftdency Yirul, Autolomalncessm dlaorden, 391, 392t Clllfllldll lllblCIIIU, 201
l9t Autolomal trlaomles, 393-394 Caput medu.ae, 317
rubella. 29t AVP (arJinine vuopresain), 331 Caput au.ccedanew:o, 2l
syphila. 30t Azithromycin. 122 C'Arb.rna.zepine, 32t, 176, 180t
tmoplasmom, sot CArbohydrate metaboliam disorden,
varicella mater virwl, 29t I 3':Tl
APGN (acute poatmeptncoc:cal B<ell ALL, 288 CardW:: output, 409
gl.omtrulonephrlt!a), 116, 368 Bacteremia, 113 Cardlogenic: lhock, 410, 413
Aplutk: crWa, 262-268 Bacterid endocarditis (BE), 227 Cardiology, 210-246. s~ clio Acqulmi
Apnea, 106-107 Bacterid lnfectlona, skin manlfestltiona structural heart disease; Acyanotic
Appendec:tomy, 3C11 of,199-201 COliJCflltal heart dbeue;
Appendicitia,307 bullous impetigo, 1§19 Arrhythmiu; Cyanotic amgenita1
Appropriateneu £'or pstaiional age folliculitis, 200 heart diaeue; Functional heut
(AGA),20 nonbulloualmpetigo, 200 dUeue
AQP2 (aquaporin 2 channels), 331 staphyl.oooc:cal scalded akin cyanotic neonate, 212- 214
Aquaporin 2 clwmela (AQP2), 331 syndrome, 200 heart mlli'IDIIra, 21~211
ARf (acute rheumatlc: fewr), 116 Bacterid vqinosls, 131 Cardiopulmonary reausdtatlon (CPR),
rnised Jone1 crllierla .for, 116t Bal.lanl scorin& 20 403-404
Argininevuoprcllin (AVP), 331 Band c:clls. 268 clUldren. 406t
Arrhytluniu. 230-237 Below and OriiDlani provocative tests, drup uaed, 412t
bradyardtyt:luniu, 235- 237 348,349/ in infmtJ, 406t
~.231-237 Barrett eaophagua, 311 management 4/.Tlf
ARr (antidromic reentrant tachycanlla), Bual-bolua method, 330 Catarrhal phue, 120
233 Basophilia, 269 CBC (complete blood COUDt), 290
ASD (autism apectrwn diaordera), lll, BuopbilJ, 268 Ceftrfamne, 355
167-168 &tde'• Jign, 415 Celiac dlaeue, 305
AJeptic meningitis, 122 BE (bacterW endocerditia), 227 Cell-mediated immunity diaorc:len, 144t
Aaput.te aminotr&nlferue (AST), 320 Bell dapper deformity. 385 Central diUJetea inaipidu., 331
Aaperaer syndrome. 168 Benign premature thelarche. 339 Central nervous system (CNS) tumors.
Aspiration ayndrome1, 106 BenJgn tenaon~type headachea, 182 295- 296
ASQ (Ages and Stages), 13 Benzodlazepines, 180t Cephalohematoma, 2l
AST (aspartate~). 320 Bidlrectional Glenn shunt. 217 Cephalosporin, 355
Aaduna, 89-101,149 8Wary ltrella, 42, 320 Cerebral paky (CP), 169--171
Index • 475
Cerebral venou& linus thrombo.sis, 185 Communic:ating hydmc:ephalul, 189 clinical manifestations, 101-102
Cervicalapine InJuries, 416 Communication skills In pedjatric diagnoltic ewluation, 102-103
CFrlt (C)'Itlc flbtom ttansmembraDe primary care. 10 epld.emlology,l01
~r) ptoteiD.101 Complement Immunity dilorcltn, 147 ~thogeneai8, 101
CGD (c:htonk: granulomatous dileue), Complete blood count (CBC), 290 pulmonarypnventive Jtratesfes, 103
146 Conaallion, 417 treatment. 103-104
or (c:onpnitaJ hypothyroldiJm), 335 Congenital abnormalities, 104 Cystic: fibrwia trammembr.ne reauJ,uor
Ol.qe syndrome. 396 Congenital adren.l hyperpluia (CAH), (CFTit) prvt:ein, 101
Otickenpax (variczlla), 133t 73,337-339, 384 Cytomeplovjrus (CMV), 28t
auld abuse and neglect, 419-421 Congenital dlaphragmatic hernia, 41
auld Dewlopnwrtlnwntory, 13 CongeDJtal. disorders of plateleU, 274 D
Ctlldhocd and Juvenile ablence Congenital. hydronephrolls, 382-BSS D·TGA (0-trlnlposltlon of the great
epilepsy, 178t Coqmltal. hypothyroidism (CH), 335 arterles), :us
OtiJdhood, health IUpervifion in, 2-9 Congenital. mepbryocytic hypoplu~ D-transpodtion of the pat arteries
Otildhood nephrotic Jfl\drome. 366- 271 (o-TGA), 215
367,366t Congenital me10blastic: nephroma Dandy-Walker malfannation, 189
Cht.mydt. trru:ho_,tir, 82 (CMN),383 DAT (dlrect antiglobulin test}, 250
Chloroma. 290 Congenital nevi. 204 DBA (Dlamond-Blaclcfan anemia), 256,
Qoanal atresia, 23, 88 Congenital tracheal stenom, lot 266
Choking,ll Congen.ltal./perinatal. infections, 26 DCM (dila~ catdl.omyopathy), 229
Chordae,24 Conjupted hyperbilirubinemia, 37, 42 DDAVP (desmopressin acetate), 27S
Chromosomal disorders, 392-396 Connective tissue disorders, 156-157 DDH (developmental hip dyspluia),
Angelman Jfl\clrome, 396 Concm:ntricular VSD, 221 348
autosomal trilomles, 393-394 Constipation, 314-315, 31St Dehydntion, 73-75, 74t
imprinting disorders, 395-396 Continuous po.titive airway pressure Delayed hemolytic transCusion
Prader~Wllll syndrome, 395-396 (CPAP).33 react:iom, 280
sex chromoJome abnormalltlel, Conwl.escent phue, 120, 157 Delayed lntendflalfton, 291
394-395 Coronary artery disease, 229 Dental cartes (tooth decay), 11
triJomy 13 (Patau syndrome), 394; CP (cerebral palsy), 169--171 Dental development and care, 14
39-k CPAP (continuous positive airway Denver Dlftl.opmental ScreeningTeat,
truomy 18 (Edwards syndrome}, 394. pre•ure), 33 13
394.t CPR. See Cardiopulmonary Dermatolosy, 197-209. S• abo
triJomy 21 (Down lylldrome), reJUicitmon (CPR) ln&ntile hemanpmau; PlUllmed
393--394 ~191 vital eDDthema; Supedldal fungal
'1\Jmer syndrome, 394-395 Crifu:al pulmonic stenom, 226 lnfec:tiou; Vlmllnfectlom
Chromosome 22.qll deletion syndzome, Cr1tU:allymchild, 403 hyperp!gmented ledons, 204-205
396 Croup, 118-119 hypenenaltMty ID.d .nerp:
Omm1c: atui«, 186 Cryopreclpitate, 279 ractionl, 203-204
Ou-onic diarrhea, Bl2t Crypt al»cesses, 318 Derm.ato~,1SS-156
Ou-onic: granulam.atnus cliaeue (CGD), Cryptmchidism, 25, 384 Demtopreallin aatat2 (DDAVP), 275
146 Cushing diseue, 333, 339 Developmental delays, 13
Chronic kidney d1leue (CKD), 'n6-377 CVID (common varlahL! Developmental hip dyaplula (DDH),
Chronic otp4 clyl(wlrtlon II.Dd damage, lmmunocleflclency), 145 348
263 Cyanosis, 121 Developmental. rnlleat:ollel, 13
CirculadoD. 404 Cyanotic consenftal heart d1seue, Dextrose (Jl.uc:o~e), 412t
Clrailatory abnormalitiel, 409 214-216 Dlabete1 inal.pldu. (DI), 331-332,
Citrate toxic:ity. 280 Cyanotic neonate. 212-214 371-372
CKD (chronic: lddney disease), 376-m duc:tal~independent mixing lellians, Diabetes mellitus (DM), 828-331. St!ll!l
Clarithromycin, 122 214-216 ttho Type 1 dlabetes mellitus
Clavicle fracture, 25 D-tranapos.ltlon of the great (TlDM); Type 2 dlabetes mellitus
Cleft llp, to arteries, 215 (T2DM)
Clobazam, 180t total anomalous pulmoDary Dlamond-Blackfan memia (DBA), 256,
GJ~trldtum dljJklkJ, ll4 venoUII connection, 215-216 266
Clottfns,269 truncus arteriosus, 214-216 Diaper rub, 201
Clubfoot. 350 evaluation, 212-214 Diarrhea, 312-314, 312t
CMN (mng:enital mesoblastic: lesimu with duc:t.l-dependent DIC (disseminated intnvucular
nephroma), 383 pulmonary blood flow, 216-219 c:oagulation), 'Z17
CMV (cytomeplovlruJ), 2& E~ anomaly, 218-219 Dlfrerential cyanom, 213
CNS (central nervouslfltem) tumon, Tetralogy ofFallot, 217-218 Dl1fuse l.ntriDIIc poD11ne gliomas
295-296 trk:uspld atrella. 216-218 (DIPGa), 295
Coarctal1.on of the aon.. 225 lesion~ with ductal-dependent DIGeorp f7I1drome, 214
Cocaine/ampiletamlDa, 3lt, SSt IJilemk blood flow, 219- 220 DUated c:ardJomyopUby (DCM), 229
Combined immunodefidency hypoplutic leCI: heart ayndrotne. DIPG• (ciiffwe intrinaic pontine
.yndromes. 146 219 sliomu),295
Common atriovmtricular canal defect, interrupted aortic: an:h. 220-221 Diplegia. 170t
224.-225 Cyproheptlldine 184 Direct mtiglobulln teA (DAT), 250
Common varlable l.m.m.llnodeBd.ency CyJtk: clbeues, 363-364 Dlaablll1y, 408
(CVID), 146 CyJtk: fibroid&, 101-104 Dlaorden ofsexual deftiopment (DSD),
Commun1c:atin( hydrocelu, 385 acute pulmonary exacerbations, lOS 384
476 • Index
Di.ueminatEd intravuc:ular coagulation disability, 408

(DIC), 277 drowning, 417-418
Dlstrlbutlw chock. 410. 413 expoiiUle, 408
DMD (Dudl.enne-type muacular fure1gn body aspiration, 421
dystrophy), 186 llljured child, 403-4-33
Double bubble sip, 41 pedlat:d.c trauma. 413-414 F
Drawt 1)'!\drome. 172-173 primary JUrvq. 403 Face,22-23
Drowning,10-11,417-418 tec:ondary assessment. 409 Factor replacement. 275
Drug use, 57 se1ectMmedical emergencies, 421 Falla, 10
DSD (diaorders ofsema1 development), se1ectM traumatic emergencies, 417 Famlllal (geoetlc) short ltldure, 332
384 chock. 409--411. SH tiUtJ iN:liiiJtJM.l Famlllal M.edJterranean feom' (FMF),
Dubowla or Ballard. acoriDg. 20 tmtl? 158
Duchenne-type .IDI1ICUl.u dystrophy sudden unexplained infant death, Fanco.n1 anemll, 266-267
(DMD),186 422-423 Fatty add oxidation, 397
Ductal-dependent pul.monary blood tertiary aaessment, 409 Febrile react:lom, 280
flow, 216-219 thoracic injuries, 416 Fe~e~~~172-173
Ductal-independent mixiDg lesions, treabnent. 403-413 Fecal calprotectln. 3(1}
214-216 treabnent. 412-413 Felbamate, 180t
Duodenal atresia, 41 VBICI1!ar access, 409 Fetal alcoholl)'lldrome, 397
Dysfluency, 13, lfiS Emesa, 308--310 Fever ofunknown orlgiD (FUO),
Dysfwu:1ional voiding. 386 Encephalopathy, 181-182 112-118
D}"Pepda, 305 In c:hil.dnm, 182t FGID (func:tional pstroint:estina
Dystonia,170 Encopresis, 314 clisorder), 305
Endocardi&. 227-228 Pires, 11
E Endocrinology, 328-347. See tdso Flank palo. 383-384
Early childhood c~ (ECC), 14 Adrenal dylfu.ru:tion; Congenital Fluid. 72-80. See tlbo Maintenance
Early neonatal aepc!a, 36 adrenal hyperplula (CAH); fluids
Early-onset aepdl, 36 Congenital hypothyroidism FMF (Familial Medit2rranem fever),
Ears, 23 (CH); Dlabetes mellituJ 158
Euinl dborders, 55-57 (DM); Hyperth}Toidlsm; Focal tepnental Jlomerulolclerosis
anorexia nervo... 55 Hypoadrenoc:orti.cilm; (FSGS), 366
bulimia nerw... SS Hypothyroidism; Short stature; Focaladzures,177t
clinical manifellmtions, 56 Thyroid d¢unction Folat2 defid.ency, 26S-266
hiatory.56 hyperoortisaiWn, 339 Folllcu1ltla, 200
phydcal exanWWioD, 6 pUnful thyroid gland. 336 Food allergies, 149-150
dlagnoltic evaluation, 56 thyroid nodule, 336 Foot defonnltiea, 349-350
clif£ereDtial diaanosia, 56 Ent«'obllll ~.125 Fozelp body uplntlon, 421
epld.emiolo1f, 55-56 Enthesl.tis-related arthrltla, 153t Formoterol, 98
laboratory testa. 57t Enqme-llnked immunosorbent assay FrKtures in c:hildren. 352-354
pathogenesU, ss (ELISA), 135 ~X syndrome, 396
risk &dora, 56 EcWnophilia, 269 Fresh-t'rmen plasma. 279
treatment, 56-57 E<Wnophils, 268 Frledteich ataxia, 187
Ebst:eln anomaly, 218- 219 EpidldyJl1CM)l'ChitU, 385 FSGS (focal segmental
ECC (early chlldhood c~). 14 E~UitlJ,118,119J' glomerulosderom), 366
ECMO (extrarorporeal mmnbrme Epilepsy, 171-181 Functional c:onJtlpatl.on, 305
~tion),33 classification, 174-180 Functional pstrointatinal dltorder
Eczema,148 compln febrile Mures, 172 (FGID),305
Electrolyte, 72-80. See 11llo epilepsy in first-degree ret.tives. 172 Functional GH cWiclency, 333
Maintenaruz fluids preexi.rting neurodevelopmental Functional heart disease, 228-230
ELISA (enzyme-linked Jmmuno~arbent abnormality,172 COJ.'On&ry artery dlleue. 229
assay),135 Epinephrlnea. 412t dilmd cardiomyopathy, 229
Eltrombopag, 273 Erb palsy, 25 hyper1rophlc: obatructtve
EM (erythema mWtifonne), 203 Erythema inRctiosum (flflh disease; cardiomyopathy, 229
Ernerpocy medicine, 403--433. Ses lll8o parvm1rus 819), 133t myocarditis, 228
Acute poiJoninl; Head injuries Erythema mWtifonne (EM), 203 Functional heart murlllUl'll, 210t
.bdominal injurieJ, 416 Erythema toxicum, 22 PUO (kverolunknownorigin),112-113
acutely ill child. 403-433 Erytluvcyte ~edimentaticm rate (ESR),
airway, fM..-405 25(), 294 I
b~405-407 Erythromydn. 122 G6PD ~-phosphate
bums,4184l!il Elophap!ai atreda, 40 dehyd.ropoue), 250, 259
cardlopulmonary rullldtiUon, ESR {erythrocyte sedimentation rate), Gabapentln. 180t
403--4IK 25(), 294 Galac:toRmia, 397
child abuse end neglect, 419-421 Ethosuximide, 180t Gutroentaitis, 1..24-125
cin:ulaticm, 404 Eustachian tube dyslunction. 113 Gutroentaology, 305-327. See «Uo
clinical manifellmtions, ~3 Ewing Al'a)ma, 298-299 Abdominal pain; .Appendicitis;
clinical manifumtions, 411 Excl\ange traMfuslon. 40 eon.tipatlon; Diarrhea;
c:ritkaliy Jll c:hlld. 403, 40tt Expiratory obstructlcm. 87 Emel!a; Hlrlchlprung diJeue;
dlagnoltic evaluation, 411-412 Expo~ure, 408 lntuau.scepdon; Malrotation;
clif£ereDtial diaanosia, 403 Expressive diaoxden, 13 Pyloric Jtmow; Volvulus
Index • 477
Gutroesophgeal reflux (GER), vlruJes retpon.sible Cor, 126t

310-312
Gutroi.Dtelt!JW (GI) bleecllng.
"
H2RAs (histamine type-2 receptor
BDDgoo!m), 311
HepalospleDomeply, 152
Hereditary nephrttil, 369
316-318 H~llus hfjl~Wf%4, 102, 145 Hereditary Jpherocytow, 257-259
Gut:roac:hllil, 41-42 Halludnogaa, 58t HerolD. SSt
Gaucher ditaae. m Halo nevi, 205 Herpu Simplex VJrUS (HSV), 28t
GBS (Guillain-Blllft l'fll(home), 185 Hand. foot. and mouth disease (HFMD), Herpu zostJ:r (thingle.s}, 198
GCS (Giugow Coma Scale), 408. 408t 197 HPMD (hand. £oot, and mouth disease),
GDPP (gonadot:Mpfn-<lependent Hand!oot-and-mouth cllseue. 115 197
prec:odolll puberty), 339 Happy puppet ayndrome, 396 Hip dylpWia, 25
General pedJat:rtca, 1- 19 Haahlmoto thyroJdl&. 335 Hlrachsprung disease, 315--316
antidpatory guidaDce,10-ll hATG (bone-derived mtl-thymoc:yte HiltamiDe type·2 receptor antagonists
COIIUIIWiication lldlb, 10 slobulin), 268 (HlllAI), 311
dental clewloprnent mel c.re, 14 Hb H disease, 253 Histre1in, 340
developmental milestone•, 13 He.d. 22 HIV (Human Immunodefkienc:y VirUS),
health supervision, 2-9. See tll&o Head injuries, 414-416 29t
hfdivldlllfl Dlt/'y acute subdural versus epidural HIV and AIDS, 132-133
i.aDguage delay, 13 bleed&, 414t HLH (hemophagoc:ytlc:
parent(s) and chll.cl, 1 cllnical maalfestatJ.oDJ, 414-415 lymphohlltiocytolll), 321
partnerlng with fam.llles, 1-10 d1agnos1ic evaluation, 415 HLHS (hypoplastic left heart
sc:reeniq, 11-12 history, 414 syndrome), 219
vaccinationJ, 12 physical examination, 414-415 HMD (hyaline membrane disease), 33
Generalized seizw:ea, 175, 177t trmment. 415-416 Hodgkin lymphoma, 293-295
Genetic disorden, 390-402. S.. Headaches.182-184 clinial manifeJtations. 293
tll&o Chromosomal c!Uorders; benign tension-type headaches, 182 c:liqnostic evaluation, 294
Metabolic dlJorderl; Molecular cllnical maalfestatJ.oDJ, 183 diff'etemial dlagnom, 293-294
cytogenic dkordetl; Stnsle-gene cllagnoatic evaluation, 183 epidemiology, 293
disorders cllfl'erentlal diagnolis, 183-184 hlstory, 293
erMrorunental factors, 390 history,183 pa.1hopneall. 293
.talalcohol syndrome, 397 physical examination, 183 phyaical eumination, 293
genetic &don, 390 trmment. 184 states. 294t
nwjor birth defect:l, 390 Health maintrnanre visib, 43 treatment, 294-295
minor birth dSec:ts, 390 Health su.pervision, 2-9 Homicide, 10
VATEll.396 goalllett:IDg during, 10 Homocyttfnuda, 398
Genital herpea almplex vtrua 1Dfect1on, Heart m1ll'mUl'St 21B-211 HomoiJBOlU ct·thaluwm!a maJor, 253
129--130 functional, 210t Homer lfDdrome, "J9l
Genitalia examination, 24-25 . . lllt Hone-clerlved anti-~ pbulln
.male,24 Hemanglomu, 205-206 (hATG),l68
male.24-2.5 Hem.temelb, 316 Howell- Jolly bocliea, 261
GER (gutroesophreel reOux), Hematochezia, 316 HSP (Henoc:h-5c:hilnlein purpura), 154,
310-312 Hematulogy, 247-286. s.. 111m Anemia; 305,369
GeltalioDaiBFo 20 HerecUtary spherocytolil; Sickle HSV (Herpea Simplex Vlrlll), 28t
appropriateneu for, 20 c:ell disease (SCD) Human lmmwlodefldenc:y Vlrua (HIV),
GH deficlenc:y, 333 lead poisoning. 255-256 29t
Gl (pstrointeldnal bleeding, Hemi-Fontan, 217 Humoral inununlty dlJorderJ, 144t,
316-318 Hemiplegia, 170t 145-146
Gianotti-Croati syndrome, 197 Hemolytic anemia. 'Sl, 256-257 Hurler syndrome, 398
Gitudia ltmrblill. 125 Hemolytic thromboqtopenia, 272 HUS (hemolytic: uremic syndrome),
GIPP (gonadotropin-independent Hemolytic uremic syndrome (HUS), 369-370
prec:odolll puberty), 339 369-370 Hyaline membrane cliJeue (HMD), 33
Glanzmann thrombasthenJa, 274 Hemophagocytlc lymphohistiocytolil Hybrid technique, 220
Glasgow Coma Scale (GCS), 408, 408t (HLH),321 Hyclroc:ela, 25, 385
Global developmental delay, 167 Hemophilia A, 274-276 Hydroc:ephallll, 189-190
Glomerulonephritis, 367- 369 HemophiliaB, 274 HydronephrodJ, 382-383
Gluc:olle-6-photphate <iehydrogenue Hemoptyli&, 104 11-Hydralcy.ta.e delkiency, 337
(G6PD), 250, 259 Hemom.lis disorder, 269--270 21-Hydrolcy.ta.e deikiency, 337, 384
Glycogen stor.ge diseues (GS.O.), 397 Henoc:h-SchDnlein purpura (HSP), 154, Hyper--IgM .ryndrome, 146
Gonadotropin-dependent precodous 305,369 HyperbJllrubinemla, 37, 320
puberty (GDPP), 339 Hepatitis, 126-128 Hypercalcemia, 341
Gonadotropln-independent precodoul cllnicaJ. mgni!PdaUODS, 126-128 Hyperchloremia, 76
puberty (GIPP), 339 dlasnostic ewiuatlon, 127 Hypercort:!soiiJ 339
Granulocyte infuJfonl, 279-280 cllfferentlal diaposb, 127 Hyperhemolydc eplsodet. 258
Granuloc:ytes, 268 epidemiolOIY, 126 Hyperlcal.emia. 75-76,290
Grna diseue, 335 history, 126-127 Hyperleukoc:yCDiis, 291
Gray matter diso~n, 171 pathogenelb, 126 Hyperoatremia. 75
Grey plmlet syndrome, 274 physical examlnatl.on, 127 Hyperoxia lett, 214
Ground-glua patW'n. 33 preveodml, 127-128 Hyperphosphatemia, 77- 78, 290
GSDs (glyoogen storage c111eaaes), 397 prognoail, 128 Hyperpi&mented.lu1om, 204-205
Gulllaln-Barri syndrome (GBS), 185 risk factors, 126 Hyperpnea, 78
478 • Index
Hypersensitivity md allergic reactio.os, InfEctious diseue, 112-142. St~e lflso JIA. S« Juvenile l.d1opathic arthrilil
203-204 Acute otilil media (AOM); (}lA)
alWglc drug reactions, 204. Bronchiolltis; Croup; Fever Junctional rhythm. 236
erythema multlfbrme, 203 of unknown origin (FUO); Juvenile ldJopathl.c: arthritls (JIA),
Stevena-Johnson syndrome, 203-204 GutroeDterltll; Genilal herpes 150- 154
toJdc epidermal necrolyala. 203-204 dmplex vlrua: infection: Hepatitis; clinial manifntationa, 153t
HyperspleniJm.ln Meningiti3; HIV and AIDS; Lyme olip.rticular JIA, 152
Hypertension. 372-37f dbeue; Pelvic inflamm.tory polyuticular JIA, 152
Hyperthyroidism, 335-336 dbeue (PID); Pertussis; Pinwonn ..,mmk: JIA. 152
Hypertrophic obstructive iDfeclion; Pneumonla; Rocky Juvenile myoc:1onk eplle~ 178t
catd1omyopathy, 229 mountain spotted feftr (RMSF);
Hyperuricemia, 290 Syphilll; Urethritis; Vulwvaginal I.
Hypervtacos1ty, 290 IDfectiona I<apos!form heJIWIIIoend.otheliomu
Hypoadrenoc:ortlclsm, 337 baauemia, 113 (Kulbu:h-Merritt syndrome),
Hypocalamia, 214, 341 herpangina, 115 'ln
Hypo<:hloremia. 76-77 inkctious mononucleosb, 116-117 Kawuald di.sease, 1S7t, 2Z7
Hyposlycemia. 33~331 sepsis.l13 Kernicterus, as
Hypokalemia. 76, 77f sinusilil, 115 Kidney mua, 383
Hyponatremia, 75 lltreptococcal pharyngltls, 115-116 Klaalngdiseue, 117
Hypophosphatemia, 77 vlrallnfectlona of childhood. 133 I<llnefelter I)'Ddrome, 3515
HypoplasUc left heart syndrome ln!Ectlow mononucleosla, 116-117 Klumpke paral}'lla, 25
(HlHS),219 Infoalous rhlrd"" 148 Koebner phenomenon, 202
Hypospadias, 24, 384 Infiltrative diseues, 331 KUJ&mml breathing in DKA. 78
Hypothennia, 280 InfWnmatory bowel disease (IBD), Kyphoccoliom, 356
Hypothyroidiam, 333, 335 318-320 Kyphosis, SS6
Hypotonia, 171.191 Inguinal hernia. 25
Hypovolemic llhock. 410, 413 lnherited. bleeding disorde!; 7:74-277 L
clesmopressln acetate, 275 LARA (iong·act!Dg IJ·agonim), !il8
I HanophlliaA, 274-276 Laoosamlcle, 180t
lBD ("mfWnmatory bcnnl dis-), Hemophilia B, 274 Lactate dehydrogenase (LDH), 250, 290
318-320 mild hemophilia. 274 LAD {leukoC)W adhWon cleficiency),
Ibupro&n. 184 modemte hemopbilia. 274 146
Idiopathic aplutic anemia. 2G7-268 RYete hemophilia. 7:74 Lamotrigine. 1801
J.dlopathk: hypertrophic lllbaortic von Willf:bnmd diaeue, Zl6-277 Language delay. 13,165-167
aenom,229 InJured chl1cl, 403---433 La{lQl'OtOmy, am
Icliopathlc sc:ollDa1a, 356 InJured while ricllng blcydea, 10 Large for pltitloDil age (LGA), 21
Icliopathlc short stature, 3M Inlet VSD. 221 larynaomalacla, 88
Idiopathic thrombocytopenic purpura, Inapiratory obstruction. 87 Latle-onset neonatal septla, 36-37
272 Intd1ectua1 dbability, 167 lAbe--on&et sepab, 36
Idiaventricular rhythm. 236 lntEmive phototherapy, 40 IDH (lactate clehydrorenue), 250, 290
IgA nephropathy, 369 Interim maintenanoo, 291 Le.d poisoning. 25S-256
Dlldtdrugl,59t Interrupted aortic arch, ~221 Leg-C~Perthea dlaeue. 350-351
1M (1ntramuacular) ceftrlaxoDe, 114 lnteltlnal i.Dfectlona, 312t LeMox-Gutaut I)'Ddrome, 178t
Inunune hemolytic anemia, 257 Intraawacular (1M) ceflrlaxone, 114 Leukemia, 287-292, 2881
Inunune thrombocytopenia, 272-274 Intrauterine growth retardation (IUGR), Leukocyte adhelion deflclency (LAD),
Inununodeftdency, 31.2t 20,llt 146
Inununology,143-147. Su~tl&o Intrinsic hemolysis. 257 Leukocyte function. disorders ot; 269
Combined immunodeiiciency Intrinsic kidney injury, 374t Leuk~ab,268-269
syndromes; Humoral inunwU.ty Intussusception 307-308 Leukopenia. 268-269
dilordera; T-cell immunity Iron-de1iciency anemia, 251-252 Leukotrime receptor antagonist
disordera Iron overload. 280 (LTRA),89
complement lmmwl11y disorder~, 147 llchemlc:/hemorrhaglc strokes, 184-185 Leuprolicle, 340
lmprint!Jll dlaozderl, 395-396 lsolmmune hemolytic anemia, 263 Levetira.c:etar 1801
A.ngelman syndrome, 396 IUGR (intrauterine growth retardation), LGA (la.rp for gestational age), 21
Prader-Wiill syndrome, 395-396 20,2lt Lidoc:ai.Dca, 41:2t
Inborn ernJI"' of metabolism. 397 Limp, 350-35.2
Induction therapy, 291 J UP (lymphoid intentitial pneumcmia),
Infancy, health 1Upervilion ID, 2-9 Jaundl.~. 37-40 132
In&nt feeding intnlermoe, 66 ABO incompatibWty, 37 Llpidocea, 398
In&nt feeding laues, 65-69 breast~jauxKUce,37 LlihJwn, 32t
breutfeed1Jl3o 65-66 cllD1cal manllest:atf.on, 38 IJwr diHue, 320-a:z:z
infant feedint intoieraNle, 66 conjugated hypedillirutrinemta. 37 Loc:albed lderoderma (morphea}, 156
mUnmition. 66-67 diqnoatic evaluation, 38 Long..ain( ~ru.ts (LABA), 98
obesity, Dl-69 factors uaoc:iatecl. 37t Lower airway obltructive dbea.se, 89-
In&nt mortality, 43 nonphysiologic jaundice, 37 105. St~e tdso Cystic: fibrom
Infantile hemanpmu, 205-206 phyllologic Jaundice, 37 airway obltructlon In children,
Infantile seborrhea, 22 SUJpected nODphyslologic, 39/ 104-105
Infmtlle lpum&, 179t treatment, 38-40 asthma, 89-101
lni!ctiona, 280, 281 un~upted hyperbWrublnemla, 37 primary c:Wary dyddnes1a, 104
Index • 479
Lower extremitiet, 25- 26 Measles, mumps, and rubella (MMR) chromosome 22qll deletion
LTRA (leukotrW1e receptor anblgonlrt), VllCCine,l67 syndrome, 396
89 Meatal stmosls, 386 Fragile X syndrome, 396
Lumbar lordoals, 356 Meckel dhmiculum, 318-319 MolWscwn cootapmun, 198
l.wlp/chut, 24 Mec:onlllm uplratkm J)'lldrome (MAS), MonaoUan ~pots (conpnit.al damal
Lyme dlseue,1M-13S 33 melanoc:ytolis), 21
Lymphadenopathy, 152. 2H Meconiwn-ftained amniotic fluid, ~32 Monoc:yt:es. 268
Lymphocyta. 268 Meploblastic~ anemiN, 264-266 Monoc:ytolis, 269
q.mphoc:ytou, 269 £olate deficiem:y, 265-266 Monosymptomatic noctumal. emuesiJ
qomphoid intentitial pDeWII.OJ\1a (UP), vitamin B12 defldmcy, 264-265 (MNE),386
132 Melena,316 Moro reflex. 26
Lyoniza1:ion, 391 Meningitla, 122-124 Motor aelzures,l74
Lylosomalstorap dJiorden, 397- 399 causa, by age, 123t Motor vehicle lojuriea, 10
Gaucher dileue, 399 di.oic:al manifeltati.cnu, 123-1.24 Mouth/throat, 23
Hurler syndrome. 398 diagnostic evaluation. Ul-124 MRSA (methicillin-resistant S. ~).
lipiclolle!l, 398 differential diagnosis, 123 354-
mucollpidoses, 398 epidemiology,l22-123 Mw:ollpidoses, 398
mucopolylaccharidoie8, 398 hlatory, 123 Mw:opolywaa:haridotel, 398
Pompe ci!Jeue, 398 pathogenesis, 122 Multlcystlc dYJPlartlC kidney (MCDK),
phyJical examination, 123 363,383
•
Macrocephaly, 190
Macrocytic anemias, 264-268. SH fdso
rUk .facton, 123
Meningoceles, 189
Meningococ:cal c:onju.gate vaccine
Mumpe,l33t
Muscular VSD, 221
Myuthenia gravis (MG), 185
Meploblutic mac:rocytic anemias (MCV),52 Mymp.lwna pneumonia, 263
with dec:reued reel c:ell production. MeRJtteric lymphadenitill, 305 Myelodysplutic syndrome (MDS), 267
264-268 Metabolic addosls. 78-79 Myelomeningocele 189
nonmegal.oblutic .macrocytic Metabolic alkalosJs, 79 Myocard.ttls, 228
anemlal, 266-268 Metabolic dlsordezs, 397-399 Myringltll, 114
Macrosloll1a.. 88 amino add metaboli&m disonlen.
~ activatioD ryodrome, 397-398 I
153 homoc:ystinuria, 398 NA.Al's (nudek add. amplifu:ation
Magnesium homeottuia, 78 ornithine tnnsarbunylue terta),l30
MAHA (~hemol.ytic de6cieru:y, 398 NA.FLD (oanalcohol.ic .fatty l.iYel'
anemia), 272 approach to, 397 dlaeue), 321- 322
Maintmance 11ukk, 72- 80 carbohydrate, 397 Naproxen,1M
add-base p}tydology, 78 gaW:toaemla. 397 Narrow-compla: tac:hyardlu, 233
calcium and mqneslwn homeostasis, gl~n storap dlaeue1, 397 atrial fibrillation, 233
78 I)'IOSOmal~tazap c!Uonien, 398-399 atrial flutteJ; 233
dehydration, 73-75 Metabolic dbturbanc:es, 280 ORT, 233
hyperch.lorer:nia, 76 citrate toxicity, 280 ainua tacltycarclla. 233
hyperkalemia, 75- 76 hypothermia, 280 NASH (nonaloohollc ateatohepatitill),
hypernatremia, 75 potaaal.um tnxidty, 280 320
hyperphosphatemla, 77- 78 Metabolic syndrome. 68 NAT (nonaa:ldental trauma), 270
hypochlorunJa. 76-77 Metatarsus adductua, 25, 349 Neck,23
hypokalemia, 76 MetiUdllin-resfstant S. 1J11Te111 (MRSA), N~~WWrrlwMI (gonorrhea), 32,
hyponatremia, 75 354 130
hypophosphatemia, 77 MG (myasthenia gravis), 185 Neonatal acne, 22
metabolic: acldoais, 78- 79 Miaoangiopathk hemolytic: anemia Neonatal medicine, 20-50
metabolic: alblos:ls, 79 (MAHA),272 c:onpnital/perinatal infections, 26
rapJratory acldolil, 79-80 Microcephaly, 190 health maintenance visits, 43
respiratory allcal.oaiJ. 79-80 Microc:ytic anemias, 251-256 Infant mortallty, 43
Maintenance therapy, 291 c:c-t.halacaemta, 252-255 lnftlal care, 32
Major birth defec:ta, 390 j5-thalecaemla, 252-255 late-onaet neODatalatpS!a. 36-37
Malallgnment VSD, 221 lron-defid.encyanemla, 251- 252 meconium uplratlon syndrome, 33
Malignant hyperthyroidiJm. 336 Microsporum. 201 neonatal pneumonia, 35
Malnutrition, 66-67, 68t Migraine, 305 neonatal sepab, 36-37
Malrotation, 310 Migraine headadtes, 183 physic:a] examination, 20-26. Sat t~&o
Mariluana. 3lt, 58t Mild hemophilia. 274 lrullvldrllll etlt7'y
MAS (meconium upfmd.oo I)'Ddrome), Milia. 22 prescription medication~ UIOdamd
33 Minimal chaDge dlreue (MCD), 366 with birth defects, 3:U
Mutoh:lliis, 114 Minwbirth defects, 390 raplratory dilt:reiii)'Ddrome, 33-35
Matem.l aubltance use, 311 Mitochondrlal db!eues, 171 in newborn, 32-35, 34-35t
McArdle cliaeue, 397 MMR (meules, mumps, and rubella) beCor:e the ddivuy, prenatal
MCDK (mult:ic:ymc: dysplutic lddney), vaa:ine,167 cxmditiOIU, 26
363,383 MNE (nwnosymptomatic nocturnal in the cle1ivery room, 26-32. See
MCV (menfn&ocloccal oonjup~ enurew), 386 • Appr IClO.I'el; Matanal
vaccine), 52 Moden~ hemophllla, 274 IUbltuce Ule
MDS (myeloclyspl.uUc syndrome), 267 Molecular cytogenk: clison!era, 396 tral\llent tachypnn ofthe newborn,
Mea.sles, 133t Clarge syndrome, 396 35
480 • Index
Neonatal~3S NOJU'habdomyo.tarcomas 301 p

Neonatal ReiiUSdtation Program (NRP) Normal wsopreiS!n regulation, 331 Palnful thyroid gland, 336
guJdelin.u, 32 Normocytic anemlu, 256 Palate,40
Neonatal &elzures, 179t Nose, 28 Paroxysmal phue. 1.20
Neonatal sepsk, 36- 37 NRP (Neonatal Ruuscltation Program) Patent ductus arwioJUI (PDA),
Neonaufyouns Infant, upper airway suideJ.ines, 32 224--225
obstruction in, 88 Nucleic add amplific:ation tntJ Patient-c:cn11:red medical home, 1-10
Nephrogenic di.betea inJipidua, 331 (NAA'lll), 130 PCD (prinwyc:iliary clylkineJia), 104
Nephrology, 363-378. Sft•l.o Diabete1 Nutrition, 65-71. See •ilo Infant feeding PDA (patent dua:tua IU'tel.ioeuJ),
insipidus (DI); Urinary tnc:t Limes 224--225
infl!ctlou (UTI&) Peakexpitatoryflow (PEF),101
acute .kidney !.lljury, 374--376 a Pectus c:arlnatwn, 106
c:hronlc .kidney cllaase, 876- 377 Obelity, 67-69 Pectus emrvatwn, 105
cystic diseuu, 363-364 in childruJ., 69t Pediatric: primary c:are, c:ommuniation
glomerukmephrit, 367-369 Oblip.te noiJe breathers, 23 slcillJ in, 10
hemolytic uremic syndrome, Obstructive shoclc, 411 PedJabic pulmonology, 87
369-370 Obstructive sleep apnea syndrome diagnostic techniqu.ell, 87
h~n.372-374 (OSAS),89 upper airwa.y obstructive dlseue,
nephrotic ayndrome, 366-367 Occult spina bifida. 386 87-89
renal dyaplula, 363-364 Oligoarthritis, 153t Ped1atr1c: tnuuna, 413-414
renal tubular acldosil, 37o-371 OJisoartic;ular JIA. 152 PEF (peak expiratory flow), 101
Nephrotic syndrome, 366-367, 366t OJ.isohydram.nios. 26 ~lvic: inflammatory disease (PID),
Neural tube clefecta, 188-189 OME (otitis media with effusion), 114 130-131,305
Neuroblastoma. 296-297 Omphalocele. 41--42 Perunpanel.180t
Neurodegenerative disorders, 171 Oncology, 287-304. See tdso Bone Perimembranoua VSD. 221
Neurodevelopment, 165- 167 twnon; Ceal:ral nervous Perlnat:allnfectlona, 26
developmental delay, 165 l)'ltem (CNS) tumors; Hodgkin Periodic fever, aphthou.stwnatitil,
developmental milestones, 166t lymphoma; Non-Hoclgldn pharyngitis, adenitis syndrome
global developmental delay, 167 lyrnphomu (NHI.s) (PFAPA), 158
nonna1 development, 165 Ewing llafCOIDa, 298-299 Pmodk fever syndromes (PFS), 150,
speech and language delay, 165- 167 Homer syndrome, 297 158
Neurodevelopmental diubilities, neuroblutoma, 296-297 Penilteot uthma. 97
167-171 0~299-300 Pertusais, 120
attellti.on-de1ldtJhypetacty retlnoblutoma, 300 PervuJve developmelltal dUoJ'der, 168
dlsordelo 168 WJhn. tumor, 297-2.98 PFA (platelet flmdion analyzer), 274
autilm spectrum disord.en,167- 168 Opiolds, 3lt PFAPA (perioclk: fever, aphthouJ
cerebralpllay, 169-171 Opaodonus, 176 atomatitk, pharyDgltb, admitls
mallec:tual dbabllity, 167 opsoc:lonns myocloous atuia syndrome), 158
N~b~nudo~, 187-188 syndrome, 176 PFS (perioclk: ~ syndromes), 150,
N~ (~) lhoc:k, 410 Oral rehydration therapy (ORT), 73 158
Neurology, 165-196. See IIIUo Ataxia; Orpnic ac:idemiu. m pH management. 72-80. Su llho
Epilepty; lachemiclhemorrhaglc Ornithine tranacarbam.yiue (OTC) MainteDance flulda
strokes; Phakomatoses; Seizures deficlency, 391, 398 Phagocytic: dJsorden, lW
weakneu,18S-186 Oropharyngeal swab cultures, 87 Phagoc:yt:lc lmmuDlty dllonlers, 146-147
Neutropenia, 269 ORT (orthodromic: reentnm Phakomatoees, 187- 188
Neutrophilla, 269 tachyardia), 233 new:oflbromatmb, 187-188
Neutrophil.&, 268 ORT (oral rehydrstion therapy), 73 Phenobarbital, 180t
NHLs (non-Hodgkin lymphomu), Orthodromic reentrant tachycardia Phenylketonuria (PI<U), 397
292-293 (ORT),233 Phenytoin, 32t, 180t
Non-Hodgldn lymphomas (NHL1), Or1hopedic1, 348-362. See IIlio Foot Phonetic dlaorderl, 165
292- 293 cleformltlel; Fracturelln childteD; Phyllcal examination oflnfimt, 20-26
Nonacddental trauma (NAT), 270 Ump; Osgood-5chlatter dJseue; abdomeD, 24
Nonalcoholic fatty llver clkeue O.teomyellt1J back, 25-26
(NAFLD), 321-322 achondroplasia, 356 ardiac/pulset, 23- 24
Nonalcoholic ~a1xiliepetitis (NASH), 320 developmental dialoc:ation of the hip, ears. 23
Nonbullous impetigo, 200 348-349 eyes,23
Nonc:ommunicating hydroczles, 385 r.dial head subluxation, 3S4 fac:2. 22-23
Nonc:ommunlcatlng hydrocephalWI, 189 leptic arthritis, 355 genitalia, 24--25
NonepJleptic myoclonWI, 176 OSA.S (obstructive &1eep apnea. growth parameters, 20-21
Nonfunctional CODittp!ltion, 315t syndrome), 89 head,22
Nonlmmune hemolytic anemia. 257 Osfood-Sc:hlatter dlaeue, 355-856 lower ememitlel, 25-26
Non.lnfec:doul, 312t Olteopnesl.s Imperfecta, 356-357, 357t lunplc:heat, 24
Nonmeploblutk mac:roc:ytic; ane.miN, Osteomyelitis. 354-355 mouth/throat, 23
266-268 Osteosarcoma, 299-300 neclc, 23
Diamond-Biack&n anemia, 266 OTC (ornithine tnmcarbamylue) neuralosic. 26
Fanconl anemia, 266-'lGl defJdency, 391, 398 nose, 23
Jdlopattde aplalttc anemia, 'lGl- 268 OtWI e:xterna, 114 lldn, 21- 22
Nonmotor seizures, 174 OtWI meclla with effuaion (OME), 114 upper ememl• 25
Nonph}'lloiopc jaun.dlce, 87 Oxcarbueplne, 176, 180t vitlla and pneral appearmce, 21
Index • 481
Phy!iologic: j~. 37 Psoriasis, 202-203 Rotavirus,l2S

PID (pelvic intlammat.ory diJeue), Psoriatic arthritis, 153, 153t, 203 RTA (renal tubular addolill), 370-371
~131,305 Psychogenic nonepileptic relzures Rubella, 29t, 133t
Plnworm.IDfec:tion, 1.25-126 (PNES), 176 RuftDamlde, 180t
Pttultary gland. 328 PTU (propylthlouradl), 336 Rule of 91, 418, 419/
Pityrluilrosea. 199 Pubertal delay, 340
PJP ~ jirrwfci pner.unonia), Puberty. 51 I
132 disorders, 339-340 Salbutuno~ 98
PKU(p~). 3tn Puerto lUcan ethniclty, 97 Selmon patd1 (nevus almplex), 21
Plastic cleformation, 353 Pulmonary hypertmsion, 33 Salter-Harrla clu&l8cation, 353, 353/
Platelet function ualy%et (PFA), 274 Pulmonk: stenosls, 226 Sandal pp, 393
Plateleta, 269 Pulmonology, 87-111. See IIlio Lower SCD. SM S1clde cell diaeue (SCD)
tranafualona, 'rl9 airway obstruc:ttve dlaeue SCFE (slipped capital. femoral
trappm,. 27.2 apoea,l06-107 epiphy.is), 350
Platelets disorders. 270-.279. See .UO aspiration syndromes, 106 Sch.iJ.Iinc test. 265
Acquired bleedioc disorders; brief resomd unexplained event, SCID (severe combined
Inherited bleeding dilorder; 106, 107t immunode.flclency), 143
Shortened platelet survival pedlatrk: pulmono1ogy. ffl SCIWORA (spinal cord injury without
decreued platelet production, restrictive iwlg diaeues, 105-106 racUographl.c abnormality), 416
270-271 PUVs (posterior urethral valves), 383 Screening, 11-12
PNES (psychogenic noneplleptl.c ~,884 SE (ltatulepilepticus), 11KH81
seizures), 176 Pyloric: stenosis, 310 emerJency management 0~ 180-181
F~Numocyms jiroNci, 143 Secondary IWe1$1Dent, 409
FtN~ jiroNci pneumonia (PJP), Q Secnrt:ion of RD1id..iuretic hormone
132 22q11.2 deletion .syndrome, 396 (SIADH), 332
Pneumonia, 120-1.22 Quadrlplegta, 170t Sel.tures, 171-181
Olldel, by age. 121t absence seizures, 175
c:lhW:al manifestations, 121- 122 R antl&elzure medlc:at1ona, side efi'ectl
diqnostl.c evaluation, 122 Rad1al had subluxation, 854 o£ 180t
differeotial diqnoai.a, 122 Radial sunburst, 299 atonic Mizures, 175
epidemiology,120-121 Radioallelgoaorbenttest (RAST), 149 c:lwacteriJtia,177-179t
histDry, 121 Ruhkind procedure, 215 clusifialicm, 17._180
~ogenem, 120 RAST (radiollllergosmbeot te.tt),l49 febriluei.zures, 172-173
phyllcal examlnatioQ, 121 Raynawl phenomenon. 156 genet'lllzecllehures,175
rJsk &.ctora, 121 RDS (respiratory cUstreu syndrome), lnternatioGal League Against
treatment, 122 33-35 Epilepcy 2017 Seizure
.PoisonlnJ, 11 In newbom. 82-35, M-35t Cluslflc:ltlon, 174t
PolyuthritiJ, 153t Reed-&tembel'l celb, .294 motxlr~174
Polyarticular JIA. 152 R.ekeding syndrome, n noom.otor aeizure•. 174
Polyhydramni011, 26 Rena1 colic, 383 mtus epi.lepticus, 180-181
PolysoiDI1CJiRPhy. 89 Rena1 dysplasia. 363-364 Sepsis,113
Pompe~398 Renal tubular addolill (RTA), 370-371 Septic arthritil, 355
Popular acroderm.atltlJ of chJldhoocl, Relpiratory abnormalWes, 409 Septic &hock, 410, 413
197 Respiratory add.osil, 79-80 Severe combined lnununodetldency
Port-wine stain, 183 Respiratory alkalosis, 79-80 (SCID), 143
Pcnitional plagiocephaly, 191 Respiratory dlstrus syndrome (RDS), Severe hemophilia, 274
Posterior urethral. nlves (PWa), 383 33-35 Sex clu:omo110me abnormalities,
Potassium toxicity, 280 in newbom. 32-35, 34-35t 394-395
Potter syndrome, 26 Restrictive iwlg diseases, 105-106 I<linefelter ayndrome. 395
PPI.I (proton pwnp Jnhibltors), 311 Retained fetal iwlg liquid syndrome, 35 Turner ayndrorne, 394-395
pRBC'I'raDJfu&lona,279 Reticulonodular pattern, 33 Sexual development/reprodw:tlve
Precocious puberty, 339-340 Retinoblasmma, 300 health, 52-SS
Premature adrenarcltt, 339 Retinolc ac1d, 32t pubertal events in female, 58-54t
Prerenal kidney l.njury, 374t Retract:Ue tutes, 25 secondary .a: chancterlstlc:s, 53t
Presumed virl1 ~. 199 R.ett syndrome, 171 SGA (amall fur p:atational qe), 20
pityriasis ro-, 199 Reversible airway obat:ruc:t:ion. 89 Sh!Pla dpcntm.., 1.24
unilataal thoracic eonduma. 199 Revised Jones criteria fur ARF, 116t Shock, 409-411
Primary adrenal inlufBdency, 337 Reye ayndrome, 198 Short lta1ure, 332-335
Primary cWary dyskinesia (PCD), 10. Rh incompatlbWly, 38 Shortened plateletsurvtnl. 271-274
Primary h«petic gingivom>matlda, 115 Rhabdomyosarcomu, 300 COAgtn!tal dlsoMe:a ofplatelets,
Primarypaew:lotumor ctrebrt Rheumatic heart diJeue, 227 'rl4
syrufrome, 183 Rhewnatology, 150-158 hemolytic thrombocytupen.ia, 272
Primary syatem.ic vuc:u.l.itiJ, 157 RinFd sideroblNts. 255 immune thrombocytopenia, 272-274
Proc:ainamide, 412t RMSF (Rocky Mountain spotted fever), platelet tnppina, 272
ProphylaxiJ, 184 133-134 SIADH (secrdion of RD1id..iuretic
FropwnUutcteriiiiPC t~a~U, 202 Rocky Mountain spotta:l. fe-ver (RMSF). hormone), 332
Propylthlouracll (PTU), 336 133-134 SIADH (ayndtome of Inappropriate
Proton pump lnhlbltors (PPI.s), 311 Romlpbtlm. .273 secretion of antidlureUe hormone),
Fuudom.oiUU llm'Ufi/IOitl, 10.2 Roleola {human herpesvirus 6), 133t 75
482 • Index
Sickle cell dileue (SCD), 2.50, 259-263 I.CUte intoxication, clinical TEC (tranalent erythroblutopenia or
acute chest syndrome. 261-262 manlfestal:loJu:, 5& childhood), 256
apiMtic crlm, 262-263 chronic use, clinical mani!eltatlon.&, TEF (tracheoesophageal flltula), 40--41
chroD1c organ dyafunct1oo and 58t TEN (toxic epidermal necrolyJa),
damage,263 dlDlcal manlfeatationJ, 59 203- 204
common dlseua, 260t diqnoatic evaluation. 59 Tel11topnf, 390
Howell-Jolly bodies, 261 epidemiology, 59 drup,391t
laboratory findiop, 261t management. 59 Thrtiary utesanent, 409
splenic sequestration, 262 physical dependence. 57 Ti!lticular pain, 384-386
Jtrob,263 paycl\ological. dependeace, 57 Telticular toralon, 384
Siduobla&tie anemJa. 255 ride fadon, 59 Tet apella, 218
SIDS (suddm lDfiUit death .yndrome), ride factors fur substance use, 59t Tethered cord. 386
11, 106,311 Sudden IDfant death syndrome (SIDS), TetnloJY ofFallot (TOP), 217-218
Slleot carriers, 254 11,106,311 Tetnplqi.l, 170t
Sin&le-pne diaorders, 39G-392 Sudden unexplained inhnt death Thalusemi•s, 253
autoaomal recesaive dborden, 391 (SUID), 422--423 a-thalusemia, 252-255
X-linked disordera. 391- 392 Suicide, 10 ~thalusemia. 252-255
Sinus tachycardia, 233 SUlD (sudden unexplained lDfiUit Hb H c!Ueue, 253
Sl.nulitis, 148 death), 422--423 homozygous a-thalasaemia major,
SJ~ syndrome, 166 Super6dal f\mgallnfectiona, 201-203. 253
SJS (Steve1111-Johnson syndrome), &Je tdso Acne vulpris; Psoriasis lntermedla, 253
203-204 Superior vena cava syndrome, 291 !Qjor,253
Skin,21-22 Suppumive thyroiditis (bac:terial minor,253
Skin manifeatatiOilJ infection), 386 Thorac:lc injuries, 416
ofbacterial. infedio!UI, 199-201 Supraventricular tachycardia (SVT), 411 Thrombocytopenia-absent raclius (TAR)
ofviral infectionJ, 197-199 Surfactant, 33 syndrome. 271
SLE (l}'ltemic lupus erythemato1ua), Survival motor neuron (SMN) proteiD. Thromboc:ytopeDlu by age of
154-155 186 preaentaUon, 271/
SUpped capital femoral eplphyla s~ nonphysiologtc Jaundic:e 1n c:h1ldhood, 27lf
(SCFE),350 neonate, 39j infant, 271/
SMA (spinal mUJcle atrophy), 186 SVT (•upruentric:ulart:achycaldia), 411 neonate. 271/
Small for ~tational ap (SGA), 20 Syndrome ol inappropriate secretion of Thrombom, 185
SMN (llllrVival motor ommn) p.roteio. antidiuretic hormone (SIADH), 75 Thyroid dyd'unction. 335-336
186 Syplll&. 30t, 128-129 Thyroid nodule. 336
Sodium bicarbonate, 412t Systemlc art:iuitbi, 153t TIBC (tDtaliroo-blDdlng c:apadty), 250
Soft-tlslue la1'eOII'IU (STS), 300-301 Systemlc JIA. 152 nbfal. tuberoaty. as6
Speech. 165-167 Systemic lupu5 erythematotus (SLE), Th:k pualyall, 185
Speech dlaorden, 165 154-155 Tinea (pityrlula) wrslcolor, 201
Spina bifl.da. 189 Systemic sclerosis, 156 Tinea capitis (JC:alp), 201
Spinal cord injury without radiopaphk Tinea corporis (body), 201
.Jmormality (SCIWORA), 416 T Tinea c:ruN (genitocrural), 201
Spinal muscle atrophy (SMA), 186 T-cell ALL. 288 Tinea pedla (athlete's foot), 201
Spirometry, 101 T-<:elllmmuntty dlsorders, 143---145 Tobacco, 59t
Spitz nevt. 205 T1DM (type 1 diabetes mell1tw1), TOF (Tetralogy offallot), .217-218
Splenectomy, 258 328-380 Toplnmate, 180t
Splenic sequeJt:ration, 262 T2DM (type 2 diabetes mellitus), 330 Torsion of the appendilt tuda, 385
Spolltt.MoiiiJ""JmWthoru, 104 TA-GVHD (transfusion-associated Torti.<:ollia, 23, 191
Staphylocoa:al. scalded akin syndrome graft-vei'!lus-hmt di&eue), 281 Total anoma!OWI pulmonaryvencJWI
(SSSS),200 Tachyurhythmiu, 231-237 connection (TAPVC), 215
Statui epllepticul (SE), 180-181 narrow~complex. 233. See also 1btal iron-binding capacity (TIBC), 250
emergency management~ 18o-181 llldtvldual elltry Tourette syndrome, 176
s~~.321-322 wide-complex. 231. See also Toxic epidermal necrolyail (TEN),
Sumosl&, 88 llldtvldual Wry 203- 204
&~Johnson tyn.drome (SJS), TACO (t:ransfusion-usodated ToxoplaPilOtiJ, 30t
203-204 circu1.tory overload), 279 Tracheoeaophap.l fistula (TEF), 40--41
Stork bite. 21 Talipes equinO\'IlrUS (clubfoot), 25 Tracheomalacla, 105
Streptococcal pharyngit:iJ,llS- 116 Ttdipa erpilwMomts, 350 Transfulion-UIOc:iated acute lung
S~p.uflltlollill,145 TID1W' Sexual Maturity Rating Scale, inJury (TILW), 280
Stroke, 184-185, 263 53t Transfudon-aaoclated circulatory
Stroke ¥O!nme. 409 female brem development, 54{ overload (TACO), 279
STS (aoft-tialue lll'CIOmas), 800-301 female pubk: hair devdopment, 55/ Tranlfuaion1110dated paft-wraus-
Saup- Weber ayncirolM. 188 male pnitai.Uld pubic: hair Mit dlaeue (TA-GVHD), 281
Subecute phue. 157 deYclopment, 54/ llaNfuaional hemoc:hromatoei, 280
Subecute thyroiditis (viral infect:ion), TAPVC (total anomalOWI pulmonary Tranafuaiona, 279
386 YellOW! connection), 215 c:ryaprecipitate, 279
Subpleal hemorrhages, 22 TAll (thrombocytopenia-absent raciJul) delayed or loni·tenn compllcttiou
Subluxation olradial head. 354 l}'lldrome, 271 oG 280-281
Substance use and abuse, 57-59 TB (tubercul.oal&), 11 alloirnmunlzation, 280
Index • 483
d&yed hemolyt:ie traufus1on in necmaiE/young infant, 88 VItamin Bu de.ftdency. 261-265

reaction&, 280 in older child. 88-89 Vitamin K defldeDcy. 277-278
lnfectiotu, 281 Upper exttemit:ie1, 25 Voldlng dylfunc:tJoll. 386
Iron overload. 280 Urea cycle cle&en, 3'¥7 Volvuhu, 310
ll'anlfulion-usodattd sraft- UreWOpelvk: Junction (UPJ) Vomitfns, 308-310. Ses tllso .EmeG.
wn~hostdiseue, 281 oblttuction, 382 - G"'*- diRue, 397
&esh-frozen plum.a. 279 UretluitiJ, 131-132 wnlle~ diJeue, 187
granulocyte in!uaions, 279- 2a0 Urinary tract inkc:tioiQ (UTb), 36'-- von Wlllebnnd. dilleue, 276-277
platelet tranJCusionl, 279 366, 31!iSf von Wlllebrand factoa- (vWF), 274
rlab, 280-281. s~ .uo Acu~ Urolit:biaas, 383 vsns. ~ Ventricular septal de&:cu
trusfuslon reactlora; Metabolic Urologic obstruction, 30I!i (VSD1)
cl1aturbancec Urology, 382-389. ~ allo VT (wntru:ular~). 231,411
whole bloocl tranafualons, 280 Hydronephrosis Vu1rwab1e child l}'lllirome, 11
Transient erythroblastQpenia of IUilbipoWI gm.italia. 384 Vul.wvqinal inUction&, 131
childhood (TEC), 256 flanlc: pain with nausea and vomiting, vWF (von Willebr.nd factx:lr), 274
Transient Uc:hypnea of the newborn 383-384 VZV (vvicella-zo5ter virus), 29t, 197
(ITN),35 kidney .lllUI, 383
Tt"aDDVee.''e myellt!J, 185 testicular pain, 384.-386 w
TRAPS (tumor nec:ro.Ja fa.ctnr vokllDg dyafunctlon, 386 Waiter'• tip, 25
recepto.r-uaociated periodic Urtlauia, 149 Wartl,198
syndrome), 158 UTh (urloarytract lnfectionJ), 364- Water regulation dlaorders, 331-332
1J-epone1Mptdlid~~m, 128 366, 31!i!if normal vuoprel8in rqulati.on, 331
'1richonwul testing, 53 WBC.. Ses White blood c:elb (WBCs)
TrichophytDn. 201 v ~~.185-186
Tricuspid atresia. 216-218 VacdnalionJ, 12 WerduJi-Hoftinann dlseue, 186
Trimethoprim-IU!Camethoxazole, 133 VACTERL syndrome. 40 White blood cella (WBCI) dlaorders.
Trl&omy 13 (Patau qnclrome), 394, 394.t Vaglnal. cancl!diasis, 131 268- .269
Tr!Jomy 18 (.Edwards I)'Ddrome), 394, Valproic acid, 32t, 180t leukocy1x)lll, 269
394t Vancomyclo. 124. 355 leukopenia, 268-269
TNomy 21 (Down syndnmte), 393-394 v.nable penetrance. 391 Whi~ matter dborders
Tnmcua arteriDftJ, 21....215 VariceiJa-zoa~ viru. (VZV), 29t. 197 (leukodyatrophie•),171
TTN (transient tachypoea o( the Varicoceles, 385 Whole blood trmafusiom, 2aO
newborn), 35 Vucular aa:e.u, 409 WJde.complex tacbyardla. 231
Thben:ubla (TB). 11 Vucull.tia, 312t ~tricular flbrllatlon, 231
Thberous aclerom, 188 Ventricular flbrl1latloo. (VF), 231. fll ~trlcular tadlyardla, 231
'IUmor lyala syndrome, 290 Ventricular septal defect~ (VSDs), Wlllebnod cllleue, 298
'IUmor necroels .w:tor recepto.r- 231-223 'Wilms tumor (WT), 2'¥7-298, 383
usodated periodic syndrome c:onoventricul.aJ; 221 Wilson dbeue, 320
(TRAPS),158 inlet. 221 WtSlcott-Aidrich syndrome. 146, 271,
'fun.ble (pulsed) dye laser therapy, 199 malalignment. 221 293
1iuner syndrome, 333, 394-395 lllWICUlar. 221 WT (Wilms tumor), 297-298, 383
Type 1 cUabe~ meWtua (TlDM), Ventricular tachycardia (VT), 231. f11
328-330 Verrucae, 198 I
Type 2 ~mellitus (T2DM), 330 VF (ventric:ular fibrillation), 231, 411 :X.llnlced apmmaglobullnemJa (XLA.),
Vlralinfect1oJUI, 197-199 145
u of childhood, 133, 133t X-.11nbd diJorden, 391-392
U1cerat:ive colitiJ, 318 aldnmanHestationa of.197-199 XeropJrthalmia. 156
Umbilical hem.iu. 24 Herpes zo.~~ (shingles), 198 Xerostomia, 156
Unconjupted hyperbilirubinemia, mollu.tcum oontagio5um, 198 XLA (X-linked apmmagiobulinemia),
37-38 Reye syndrome, 198 145
Ullllateral. thoracic exanthema, 1519 unilateral thoradc exanthema, 199
UPJ (ureteropelvic Junction) ~rucae, 198 z
obstruction, 382 warts,198 Zafirlukast, 100
Uppereirway obat:ru<:tM dbeue, 87-89 Vitals and general appe~ 21 Zonlsamide, 18(lf

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( BLUE IQ;JI~II# ~

Bradley S. Marino, MD, MPP, MSCE

Pediatric Inpatient Specialist

Copyright© 2020 Wolters Kluwer.

Library of Congress Cataloging-in-Publication Data

CollbtbiiiDrs • ••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••• 'VII

"I General Pediatrics 1

5 Fluid, Electrolyte, and pH Management 72

7 Infectious Diaeasa 112

a Immunology, Allergy, and Rheumatology 143

"12 Hematology 247

"13 Oncology 7li1

115 Endocrinology 328

"18 Orthopedics 348

"17 Nephrology 383

"18 Urology 382

"'a Genetic Disonlers 390

2 Emergency Medicine: Tbe Acutely IU and InJured ChUd 403

Rudy Allen, MD Jeffrey B. Brown, MD

Megan L. Curran, MD Northwestern University Feinberg School of

Katie S. Fine, MD Aroop Kar, MD

Tomitra Latimer, MD Praati Patel Matkins, MD, F.AAP, FSAHM

Joshua Daniel Prozialeck, MD, MSA Suzanne M. Schmidt, MD

Maheen Quadri, MD, MS Vineeta Swaroop, MD

Jane A. Rivas, MD Maria V. Talamo-Guevara, MD

R. Gregory Webster, MD, MPH Barry K. Wershil, MD

ABG arterial blood gas fVC forced vital capacity

RVH right ventricular hypertrophy liD upper respiratory infection

INTRODUCTION OBSERVING THE PARENT(S) AND CHILD

TABLE 1-2. Recommandations for Lead Scraaning as Primary Pravention

i state pub!Jc health authorities for guld.ance).

Autism spectrum disorder (ASD) is a de-

Delayed dentition, defined as no teeth by 16

VIGNETTE1 2. The parent asks you if fluoride drops should be

VIGNB'TE4 c. All families should have working smoke alarms

VIGNETTE 1 Qul81ion 1 VIGNETTE 1 Question 3

VIGNETTE 2 Question 2 common cause of conductive hearing loss in children

VIGNETIE 6 Quesllan 2 VIGNETIE 7 Question 3

TAil.E 2-1. Factors Conbibuting to lntrautBrine hypoglycemia (because of hyperinsulinism), are

EYES in 50~ to 60~ ofinfants with choanal atresia. This

TOLl 2·2. Review of the Prenatal and Delivery Reamls

TABLE 2-3. Transmission, Presentation, Identification, and Treatment of Perinatal Infections

~~ Matemalsuppressive antmral therapy beginning at 36 wit' gestation.~ infants by

TAILII-3. Transmission, Presentation, Identification, and Treatment of Per1natallnfectlons (continued)

~..,.,.,.. None, if &:tua IW'ViveB pregnancy and perinatallnterveatlona.

Sawai1rQp'l'fl!RtiOIJ: None routine.

Lo~~.K-W7n ~All of the above listed under "Presentation•; death.

TilLE 24. Transmission, Presentation, Identification, and Treatment of PerinatallnfBctions (continUBd)

Alcobol (Oillel: • Gtowth retardation•

I • Umb reduction defects

TABLE M. Prescription Medications Associated with TABLE Z-8. Apgar Scoring

when pre~ent in preterm pregnancies. ~ a group, neonatal conjunctivitis, in particular infections

.............. ......... ............

Spontaneous Often minimal when

Clinical )aundloe Follow bilirubin

Direct bllrubln ~ mgld... or

Direct bilirubin <2 mWdL Consider biliary atresia,

Evaluate Normal reticulocyte

!!~~.~!:~.~.~~'!!..!!?.r..~..~~~~~--~~ed nonphyslo~~ ~~~.~~ t~~..MC?n~e··-·-·--·----

!!~~.~!:~.~.~~'!!..!!?.r..~..~~~--ed nonphyslo ~. t..MC?n~e··-·-·--·----

L~~~-······--. . . . .. . . --.. . . . . . . ...-.. . .~. . .... ........_ . _. . . .~.~--·-·-·. -'-~~~-. .-