Pediatrics Review: Create Your Own E-Library

Searchable e-Archives from Vol. 1, Issue 1 www.pedsinreview.org Vol. 35 No. 3 pp.
97-143 March 2014
PediatricsinReview
®
Create
your own
e-Library.
MY FILE CABINET
A BENEFIT OF YOUR AAP JOURNAL SUBSCRIPTION
Create your own customized e-library of clinically relevant articles – all in one
place for quick access. With My File Cabinet tool, you can manage all the critical My File Cabinet
information you need more efficiently. • Save articles and searches for
quick retrieval
Create a virtual library of the information that matters most to you. When you
• Create, remove, and delete folders
want to save an article, simply click “Add to My File Cabinet” in the right-hand as your collection grows for improved
organization
navigation bar. You can even create folders within your file cabinet for organized
• Delete articles when needed to
and quick access. ensure storing of only the most
relevant information
pediatrics.org aapnews.org aapgrandrounds.org pedsinreview.org hospitalpediatrics.org neoreviews.org Online Now...

Gynecologic Pediatric MRI The Slow, Steady
Examination of of the Brain: Development of
@AAPJournals
Supported, in part, through an educational grant from the Prepubertal A Primer Pediatric Ethics
aap.org/journals Abbott Nutrition, a division of Abbott Laboratories, Inc.
Girl – Patra, Lancaster, Committees, 1975–2013
– Jacobs, Alderman Hogg, Carpenter – Myers, Lantos
Editor-in-Chief: Joseph A. Zenel, Sioux Falls, SD
Associate Editor: Hugh D. Allen, Houston, TX.
Editor, In Brief: Henry M. Adam, Bronx, NY
Consulting Editor, In Brief: Janet Serwint, Baltimore, MD
Editor, Index of Suspicion: Deepak M. Kamat, Detroit, MI
Editor, CME: Paula Algranati, Longmeadow, MA
Editor Emeritus: Lawrence F. Nazarian, Rochester, NY
contents
Founding Editor: Robert J. Haggerty, Canandaigua, NY
Managing Editor: Luann Zanzola
Editorial Associate: Sara Strand
Pediatrics in Review® Vol.35 No.3 March 2014
Medical Copyediting: Laura King
Editorial Board
Denise Bratcher, Kansas City, MO Michael Macknin, Cleveland, OH
Brian Carter, Nashville, TN Susan Massengill, Charlotte, NC
Deborah M. Consolini, Wilmington, DE Jennifer Miller, Gainesville, FL
Stephen E. Dolgin, New Hyde Park, NY
B. Anne Eberhard, New Hyde Park, NY
Philip Fischer, Rochester, MN
Carrie A. Phillipi, Portland, OR
Peter Pizzutillo, Philadelphia, PA
Mobeen Rathore, Jacksonville, FL
Articles
Lynn Garfunkel, Rochester, NY E. Steve Roach, Columbus, OH
Rani Gereige, Miami, FL
Joseph Gigante, Nashville, TN
Nupur Gupta, Boston, MA
Jacob Hen, Bridgeport, CT
Sarah E. Shea, Halifax, Nova Scotia
Andrew Sirotnak, Denver, CO
Alfred Tenore, Udine, Italy
Miriam Weinstein, Toronto, ON
97 Gynecologic Examination of the Prepubertal Girl
Amanda M. Jacobs, Elizabeth M. Alderman
Jeffrey D. Hord, Akron, OH
Publisher: American Academy of Pediatrics

Michael J. Held, Director, Division of Scholarly Journals and Professional Periodicals
Pediatrics in Review®
106 Pediatric MRI of the Brain: A Primer
Kamakshya P. Patra, Jeffrey D. Lancaster, Jeffery Hogg, MOC | CME | Board Review
(ISSN 0191-9601) is owned and controlled by the American Academy of
Pediatrics. It is published monthly by the American Academy of Pediatrics, Jeffrey S. Carpenter
141 Northwest Point Blvd., Elk Grove Village, IL 60007-1098.
Statements and opinions expressed in Pediatrics in Review® are those of the
authors and not necessarily those of the American Academy of Pediatrics or
its Committees. Recommendations included in this publication do not indicate
an exclusive course of treatment or serve as a standard of medical care.
Subscription price for 2014 for print and online/online only: AAP/CPS
113 The Clinician’s Guide to Autism: Correction New! Stay current in pediatric pulmonology with
Member $194/$148; AAP National Affiliate Member $153/$104; Nonmember
$243/$188; Allied Health or In-training $180/$122.
Complementary, Holistic, and Integrative Medicine: the online self-assessment program that delivers
Institutions call for pricing (866-843-2271). For overseas delivery, add $120.
Current single issue price is $10 domestic, $12 international. Replacement
issues must be claimed within 6 months from the date of issue and are limited
to three per calendar year. Periodicals postage paid at ARLINGTON
HEIGHTS, ILLINOIS and at additional mailing offices.
114 Utilization Surveys of the Pediatric Literature
Soleil Surette, Sunita Vohra clinically relevant, peer-reviewed questions, in-depth
© AMERICAN ACADEMY OF PEDIATRICS, 2014. All rights reserved.
Printed in USA. No part may be duplicated or reproduced without permission
of the American Academy of Pediatrics.
POSTMASTER: Send address changes to PEDIATRICS IN REVIEW®,
American Academy of Pediatrics Customer Service Center, 141 Northwest
Index of Suspicion discussions of preferred answers, and references for
Point Blvd., Elk Grove Village, IL 60007-1098. Case 1: Fever, Diarrhea, Jaundice, and Confusion in an
Pediatrics in Review
Print Issue Editorial Board Disclosures 18-Year-Old Male further study – all mapped to the ABP pediatric
The American Academy of Pediatrics (AAP) Policy on Disclosure of Financial
Case 2: Severe Anemia in a 6-Month-Old Girl
129
Relationships and Resolution of Conflicts of Interest for AAP CME Activities is
designed to ensure quality, objective, balanced, and scientifically rigorous AAP CME
activities by identifying and resolving all potential conflicts of interest before the
confirmation of service of those in a position to influence and/or control CME content.
Case 3: Red Urine in a 4-Month-Old Boy pulmonology content specifications.
All individuals in a position to influence and/or control the content of AAP CME Case 1: Elaine Ku, Michelle Thomas, Cynthia H. Ho
activities are required to disclose to the AAP and subsequently to learners that the
individual either has no relevant financial relationships or any financial relationships with Case 2: Nicholas S. Whipple, Omar Abdul-Rahman,
the manufacturer(s) of any commercial product(s) and/or provider(s) of commercial
services discussed in CME activities. Commercial interest is defined as any entity Gail C. Megason, Betty L. Herrington
producing, marketing, reselling or distributing health-care goods or services consumed Case 3: J. Bryan Carmody, Jennifer R. Charlton
by, or used on, patients.
Each of the editorial board members, reviewers, question writers, PREP Coordinating
Committee members and staff has disclosed, if applicable, that the CME content he/
2014 PREP PULMONOLOGY
she edits/writes/reviews may include discussion/reference to generic pharmaceuticals, WHAT SUBSCRIBERS ARE SAYING
off-label pharmaceutical use, investigational therapies, brand names, and manufacturers.
None of the editors, board members, reviewers, question writers, PREP Coordinating
Committee members, or staff has any relevant financial relationships to disclose, unless
In Brief ABOUT PREP SUBSPECIALTIES…
PRICING
noted below. The AAP has taken steps to resolve any potential conflicts of interest.
Section Member . . . . . . . . .$177
Disclosures
• Athos Bousvaros, MD, MPH, FAAP, disclosed that he has research support
from Prometheus Laboratories, Inc.; and that he is a paid consultant for Cubist
Pharmaceuticals, Dyax Corp., and Millennium.
136 Von Willebrand Disease
Stacy Cooper, Clifford Takemoto
AAP Member . . . . . . . . . . . .$199
• Lynn Garfunkel, MD, FAAP, disclosed that her family member is an employee “The online activity is the best way for me to Non-member . . . . . . . . . . . . .$219
137
of Philips Healthcare.
• Blaise Nemeth, MD, MS, FAAP, has disclosed he has an unrestricted learn because all the questions are presented
educational grant for fellowship from Biomet. Corrections
• Paul Graham Fisher, MD, has disclosed that he owns stock/bonds in
as scenarios. I am able to learn much better
Johnson & Johnson and that he serves on the editorial board of the Journal of Pediatrics.
• Richard Sills, MD, FAAP, disclosed that he receives a research grant from Novartis. What comes with an annual
• Miriam Weinstein, MD, disclosed that she is a consultant for Pediapharm Visual Diagnosis: 15-Year-Old Girl With from this type of format rather than reading
and SunCorp. She also has received honoraria from Dermik and Leo Pharma.
The journal extends special thanks to the following question writers who
contributed to this issue:
• Paul Graham Fisher, MD
138 Fever, Extremity Pain, and Unusual Rash
David Toturgul, Megan Yunghans, Jessica Kosut
a review of a topic, which I will later forget.”
subscription to PREP
Pulmonology?
• O.J. Sahler, MD
• H. Stephen Williams, MD
PA
RT U U
• Clinically relevant cases with
U
PREP Pulmonology is approved for 20 points by
Online-only Article multimedia aids and references
UU
2
U MO
the American Board of Pediatrics (ABP) for MOC
UUUU
UU
Abstract appears on page 143.
UU UUU
U
U
Part 2: Lifelong Learning and Self-Assessment.* • Instant feedback and the
ability to bookmark questions
The Slow, Steady Development of Pediatric Ethics for further study
Pediatrics in Review® is supported, in part, through an

e15 Committees, 1975-2013
Doug Myers, John Lantos
For more information on ordering, including • Easy-to-read, case-based
questions with clear, succinct
educational grant from Abbott Nutrition, a division of
Abbott Laboratories, Inc.
a FREE Trial, visit http://preppulm.aap.org explanations
Pediatrics in Review offers 36 CME articles per year. A maximum of one AMA PRA Category 1 CreditTM is earned after
achieving a 60% score on each designated quiz.
Cover: The artwork on the cover of this CME statements:
month’s issue is by one of the winners The American Academy of Pediatrics (AAP) is accredited by the Accreditation Council for Continuing Medical Education
(ACCME) to provide continuing medical education for physicians.
of our 2013 Cover Art Contest, 9-year-old The AAP designates this journal-based CME activity for a maximum of 1.00 AMA PRA Category 1 CreditTM. Physicians should claim
PREP Pulmonology is co-sponsored in collaboration
Stephanie P. of Monroe, NY. Stephanie’s only the credit commensurate with the extent of their participation in the activity.
with the American College of Chest Physicians.
pediatrician is Amina Elkassir, MD. This activity is acceptable for a maximum of 1.00 AAP credit. These credits can be applied toward the AAP CME/CPD* Award
available to Fellows and Candidate Members of the AAP.
The American Academy of Physician Assistants accepts certificates of participation for educational activities certified for AMA PRA
Category 1 CreditsTM from organizations accredited by ACCME. Physician assistants may receive a maximum of 1.00 hour of Category
1 credit for completing this program. PREP Pulmonology is co-sponsored in collaboration
This program is accredited for 1.00 NAPNAP CE contact hour; pharmacology (Rx) and psychopharmacology contact hours to be with the American Thoracic Society.
determined per the National Association of Pediatric Nurse Practitioners (NAPNAP) Continuing Education Guidelines.
It has been established that each CME activity will take the learner approximately 1 hour to complete.
Answer key appears on page 142. *Continuing Professional Development
How to complete this activity:
Pediatrics in Review can be accessed and reviewed in print or online at http://pedsinreview.aappublications.org. Learners can The American Academy of Pediatrics (AAP) is accredited by the Accreditation Council for
claim credit monthly online upon completion of each CME article. The deadline for completing this activity is December 31, *All approved activities must be completed by the MOC Credit Approval End Date.
Continuing Medical Education to provide continuing medical education for physicians.
2016. Credit will be recorded in the year in which it is submitted. It is estimated that it will take approximately 1 hour to com- All deadlines and MOC point values should be confirmed with the ABP.
plete each CME article. This activity is not considered to have been completed until the learner documents participation in that This activity has been approved for AMA PRA Category 1 Credit ™.
activity to the provider via online submission of answers. Course evaluations are online.
Article gynecology
Gynecologic Examination of the Prepubertal

Girl
Amanda M. Jacobs, MD,*
Educational Gap
Elizabeth M. Alderman,
MD* The prepubertal genitalia in girls varies in appearance and function compared with the
pubertal genitalia of adolescent girls and as such is subject to a unique spectrum of dis-
orders that require appropriate screening, identification skills, and management.
Written in
collaboration with the
Objectives After completing this article, readers should be able to:
North American Society
for Pediatric and 1. Describe techniques necessary for examining the external genitalia of prepubertal
Adolescent Gynecology girls.
(NASPAG). 2. Identify the normal variations and natural history of the female prepubertal external
genitalia.
3. Identify, evaluate, and manage common vulvar symptoms in prepubertal girls: labial
Author Disclosure adhesions, vaginal irritation, bleeding, itching, discharge, and ulcers.
Drs Jacobs and
Alderman have
Introduction
Genital examination should be a routine part of a comprehensive physical examination for any
disclosed no financial
girl at any age. The vulva of a prepubertal girl has a unique appearance compared with that of
relationships relevant a postmenarchal girl. It is important to become familiar with the normal variations of the
to this article. This genital anatomy of a prepubertal girl, including the vulva’s features and characteristics, so that
commentary does not abnormalities are recognized (Fig 1). Abnormalities, such as the imperforate hymen, signs of
contain a discussion sexual abuse, or rare malignant tumors, require prompt evaluation and treatment. Labial ad-
hesions are frequently noted; vulvar symptoms, such as irritation and erythema, are common,
of an unapproved/
and most causes are benign. Causes of vaginal discharge in prepubertal girls vary from those
investigative use of
of pubertal females.
a commercial
product/device. Physical Examination
The performance of a thorough genital examination can be challenging and anxiety pro-
voking for young patients, their caregivers, and health care clinicians. Patients may be ap-
prehensive about the examination because many children have been counseled not to allow
that area to be touched. Estrogen thickens and imparts elasticity to the vagina and vulva’s
mucosa and stimulates vaginal secretions, changing the vaginal climate. The prepubertal
vulva and vagina lack some of these characteristics, making it susceptible to irritation, in-
flammation, and bacterial growth not seen in the estrogenized perineum. The mucosa of
the prepubertal vulva is relatively thin, atrophic, redder in color, and more sensitive to
touch compared with an estrogenized vulva. For this reason, prepubertal girls are at risk
for irritation, infection, and sensitivity to touch.
To reduce anxiety and ensure the patient’s assistance during an external genital exam-
ination, the clinician should explain what will occur and elicit the patient’s assistance during
the examination. The clinician should reinforce that no one
other than a clinician or a trusted caregiver should examine
these areas. Permission to conduct the examination should
Abbreviations be explicitly sought from the caregiver, in the child’s pres-
AAP: American Academy of Pediatrics ence, and used as a model for open communication and co-
HPV: human papillomavirus operation with the young girl. The reason for the genital
NAAT: nucleic acid amplification test examination should be explained to the patient and caregiver
using correct medical names for the anatomy. This explanation
*Albert Einstein College of Medicine, Children’s Hospital at Montefiore, Bronx, NY.
Pediatrics in Review Vol.35 No.3 March 2014 97

gynecology prepubertal exam
There are many normal variations of the prepubertal

female genitalia. A total of 77% of girls with suspected
sexual abuse have a normal-appearing hymen or nonspe-
cific findings. (2) The appearance of the hymen in non-
abused girls varies widely. (3) Hymen variations include
redundant hymen, posterior rim or crescentic hymen,
and circumferential or annular hymen. Congenital anom-
alies of the hymen include imperforate, microperforate,
cribriform, and septate hymens (Fig 3). A girl with any
of these hymenal anomalies should be referred to a pedi-
atric gynecologist for evaluation and possible surgical
intervention.
The hymen in a girl from infancy to age 2 years may be
Figure 1. Anatomical terms for structures of the prepubertal thick, pale, and redundant under the influence of mater-
female introitus. Reprinted from Figure 1 in Fortin K, Jenny C. nal estrogen. However, the prepubertal hymen is usually
Sexual abuse. Pediatr Rev. 2012;33(1):19-32. thin and pink-red because of a lack of estrogen (Fig 4). As
puberty nears, estrogen again increases the thickness and
ideally occurs before the girl is undressed, giving her a sense elasticity of the hymen and vulva, and a physiologic thin
of control. The patient should be shown the light source white vaginal discharge, leukorrhea, may be appreciated
and swabs, if their use is planned. Giving the patient a sense (Fig 5).
of control often helps reduce anxiety and even the percep- Examination of the inner vagina and cervix is often un-
tion of discomfort. Mentioning that she may say stop the necessary in prepubertal girls unless there is a suspected
examination at any point may also encourage participation foreign body, persistent vaginal bleeding, or microbial
and reduce fear. In most cases, the caregiver can be present specimens that need to be obtained. The inner vagina
in the room during the examination, and the clinician can and cervix may be best visualized in the knee-chest posi-
enlist the support of the caregiver for reassurance. tion, with an otoscope light or cystoscope if necessary. A
The genital examination for the prepubertal girl can be speculum examination is not appropriate for prepubertal
performed with the child supine in a frog-leg position or girls. Evaluation of the pelvic organs to assess for a sus-
prone in the knee-chest position. While supine, her feet pected mass may be employed if necessary through a
should be placed together and knees apart either on the recto-abdominal exam, however this is not a part of a rou-
examining table or on the caregiver’s lap (Fig 2). The labia tine examination. Imaging with pelvic ultrasonography
majora can be visually inspected in this position. Separation can be useful. In cases where examination of the inner va-
of the labia minora allows for visualization of the vaginal gina is necessary, such as in the case of trauma or bleeding
introitus, hymen, urethra, and clitoris. This can be done of unclear origin, an examination performed in the oper-
by separating the posterior aspect of the labia minora at ating room by a gynecologist with the patient under an-
the 5 and 7 o’clock positions, laterally and posteriorly. Al- esthesia may be necessary.
ternatively, the labia minora can be retracted by grasping In addition to the developing changes in the vulva,
the posterior aspect of the majora and pulling away from predominantly due to estrogen effects described above,
the patient and toward the clinician with labial traction. pubic hair develops on the mons pubis predominantly
The prone knee-chest examination position allows for im- due to androgens. The Tanner staging system is used
proved visualization of the inner vagina and perhaps even to describe the progression of puberty. This system is also
the cervix. The American Academy of Pediatrics (AAP) has used to describe breast development and correlates with
provided guidelines for the use of chaperones during the the timing of menarche and linear growth velocity. Tan-
examination. (1) For the prepubertal girl, the AAP recom- ner stage 1 correlates with the prepubertal stage where
mends caregiver presence. Where the caregiver is posi- there is downy fine vellus hair on the mons pubis. Tanner
tioned should be the choice of the girl. Privacy can be stage 2 describes an increasing coarseness and dark color
ensured by performing the examination with a large sheet to this hair. Tanner stage 3 describes the hair increasing
over the girls’ legs with the caregiver behind the girl so that and becoming curly. Tanner stage 4 is similar to the adult
the genitals are not in sight. However, if sexual abuse is hair pattern; however, it does not extend beyond the in-
suspected in a prepubertal girl or an adolescent girl needs a guinal folds. Tanner stage 5 describes the adult hair pat-
genital examination, a medical chaperone should be present. tern, which extends beyond the inguinal folds onto the
98 Pediatrics in Review Vol.35 No.3 March 2014

Figure 2. Prepubertal girl genital examination positions. Adapted with permission from Herman-Giddens ME, Frothingham TE.
Prepubertal female genitalia: examination for evidence of sexual abuse. Pediatrics. 1987;80(2):203-208.
inner thighs. To evaluate abnormalities of puberty, knowl- reports that she noticed that the area was unusually red
edge and documentation of Tanner stages are necessary. and that there has been wetness of her underwear. She is
Marshall and Tanner provide a description of these stages afebrile without diarrhea, constipation, abdominal pain,
with pictures. (4) and foul-smelling urine. She has had no recent illnesses.
There is no caregiver or clinician suspicion of abuse. On ex-
Genital Problems in Prepubertal Girls amination, her vulva appears erythematous, surrounding
Case 1: Irritation and Redness the vaginal orifice without any discharge appreciated.
A 6-year-old girl is brought in by her mother with symptoms Nonspecific or irritant vulvovaginitis is the most com-
of vaginal irritation and redness. The mother states that the mon reason for vulvar irritation with or without vaginal
girl has experienced burning in her vagina. The mother discharge in prepubertal girls. (5) Vulvovaginitis is

and avoidance of occlusive clothing

may be helpful. Caregivers can be in-
structed to double rinse underwear
and avoid using fabric softeners.
If the measures above do not re-
solve the symptoms in 1 to 2 weeks
or if marked erythema that involves
the perianal area is present, a bacte-
rial vulvovaginitis may be the diag-
nosis. Bacterial vulvovaginitis often
Figure 3. Variations of hymenal anatomy. A. Normal central hymenal orifice; B. normal causes vaginal discharge in addition
fimbriated hymen; C. hymen with midline septum; D. thick posterior hymen; and E. to erythema and irritation. This in-
cribriform hymen. Reprinted with permission from Fisher MM, Alderman, EM, Kreipe, RE,
fection occurs through autoinocula-
Rosenfeld, WD, eds. American Academy of Pediatrics Textbook of Adolescent Healthcare.
Elk Grove Village, IL: American Academy of Pediatrics; 2011:552.
tion of respiratory and enteric flora.
Group A b-hemolytic streptococcus
frequently caused by irritants, such as bubble baths, is the most common pathogen that causes vulvovaginitis.
shampoo, soap, or clothes that are bleached or laundered Other bacteria involved include Staphylococcus aureus,
with strong detergents. In addition, tightly fit pants and Haemophilus influenza, Streptococcus pneumonia, Neisse-
occlusive clothing, such as swimsuits, leotards, Spandex, ria meningitis, Branhamella catarrhalis, Shigella, and
or nylon underwear, act as irritants. Developmentally Yersinia. (6) A culture should be performed and oral
normal thin mucosa, small labia minora, relatively alkaline antibiotics administered based on culture result. Group
pH, obesity, poor hygiene, and foreign bodies also in- A streptococcus is treated with a 10-day course of oral
crease the risk of vulvovaginitis. amoxicillin or penicillin.
Irritant vulvovaginitis can be treated and prevented
with the improvement of thorough hygiene, sitz baths, Case 2: Fused Labia Minora
and the avoidance of bubble bath, soap, or shampoo in An otherwise healthy 6-month-old girl presents for a health
the bathtub. An affected girl can sit in clean water in maintenance examination. On examination, it is noted
the bathtub, then shower with soap to clean nongenital that her labia majora are normal but her introitus cannot
areas just before getting out of the bathtub. Caregivers
should be instructed to fully and gently pat dry the genital
region after bathing. In addition, wearing cotton un-
derwear, nightgowns instead of pajama pants, sleeping
without underwear, quickly removing wet swimsuits,
Figure 4. The unextrogenized hymen of a schoolaged child. Figure 5. The thick estrogenized adolescent hymen. Reprinted
Reprinted from Figure 2 in Fortin K, Jenny C. Sexual abuse. from Figure 3 in Fortin K, Jenny C. Sexual abuse. Pediatr Rev.
Pediatr Rev. 2012;33(1):19-32. 2012;33(1):19-32.

be visualized due to fused labia minora. Her parent reports occur with the menstrual cycle. Purulent, foul-smelling, or
no unusual urinary or vaginal symptoms. blood-tinged discharge is not leukorrhea and, if present,
The precise cause of labial adhesions is unknown; how- should warrant further investigation. Patients or caregivers
ever, recurrent vulvovaginitis can contribute to its forma- concerned about leukorrhea should receive reassurance only.
tion (Fig 6). Labial adhesions may be asymptomatic and Most cases of nonphysiologic vaginal discharge result
identified on physical examination only or may present from nonspecific vulvovaginitis. (7) In a study of 110 girls
with recurrent urinary tract infections due to poor drainage ranging in age from 15 weeks to 12 years, 82% of girls
of urine from the vulvar vestibule, difficulty with urination, with vaginal discharge were diagnosed as having nonspe-
a pulling sensation, or recurrent vaginal infections. Labial cific vulvovaginitis. Other causes include suspected sexual
adhesions usually resolve with estrogen exposure during abuse (5%), foreign body (3%), and labial adhesions (3%).
puberty. However, if the adhesions are significant, causing Vaginal foreign bodies can cause discharge, intermit-
symptoms or interference with voiding, a topical estrogen tent bleeding, and a foul odor. The knee-chest position
cream may be applied directly to the adhesion twice daily may allow visualization of the inner vagina. Toilet paper
until it resolves. After resolution of the adhesions, careful is the most common vaginal foreign body. A swab moist-
attention to hygiene and the application of petroleum jelly ened with saline may be used to remove the foreign body
or diaper rash ointment to the vulva for several months without disturbing the hymen; gentle irrigation with
should protect from reoccurrence. warm water may lead to expulsion of the material. Unfor-
tunately, many young girls with vaginal foreign bodies
Case 3: Vaginal Discharge may need to go to the operating room for an examination
A 10-year-old girl presents with wetness in her underwear under anesthesia.
that appears white. There is no vaginal bleeding. Otherwise, Frequent rubbing of the vulva, seen in chronic mastur-
she has been well without any urinary tract infection symp- bation and sexual abuse, can cause nonspecific vulvovag-
toms, vomiting, or diarrhea. On examination, there is a initis. Caregivers of girls with vaginal symptoms may have
small amount of thin white discharge collected in the pos- a spoken or unspoken concern about sexual abuse. Sex-
terior fourchette. ually transmitted infections by Chlamydia trachomatis
During puberty, estrogen stimulates the vaginal mu- and Neisseria gonorrhea can present with vaginal dis-
cosa to secrete a physiologic vaginal discharge called leukor- charge. Chlamydia can be transmitted via an ascending
rhea. This usually begins 6 to 12 months before menarche. infection from the mother in girls up to age 3 years.
Leukorrhea is a thin, white, non–foul-smelling liquid. (8) However in the prepubertal girl, chlamydia or gonor-
Once menarche occurs, the leukorrhea may vary in rhea often result from sexual abuse. Chlamydia can pres-
amount and viscosity according to hormonal changes that ent with a clear or white vaginal discharge or can be
asymptomatic. Gonorrhea usually presents with profuse
discharge that may be green. Trichomonas vaginalis is
a rare cause of vaginal discharge, resulting from sexual
abuse. Diagnosis of gonorrhea and chlamydia can be
made through nucleic acid amplification tests (NAATs).
These tests are highly sensitive and specific; however, be-
cause of the serious nature of sexual abuse and need for
definitive evidence, an additional NAAT using another
method (DNA or RNA) or a positive culture result is
needed for confirmatory diagnosis. Culture or NAAT
can be used to assess for T vaginalis. A full discussion
about sexual abuse may be found in the 2012 Pediatrics
in Review article entitled “Sexual Abuse” and is beyond
the scope of this article.
Human papillomavirus (HPV) may cause genital le-
Figure 6. A commonly found presentation of labial adhesion in
sions in the prepubertal girl. HPV causes the formation
a 3-year-old. Reprinted from Figure 290-1 in McInerny TK, of condylomata acuminata or genital warts (Fig 7). Gen-
Adam HM, Campbell DE, Kamat DM, Kelleher KJ, eds. American ital HPV infection is not necessarily due to sexual abuse.
Academy of Pediatrics Textbook of Pediatric Care. Elk Grove HPV can be transmitted from the mother to an infant
Village, IL: American Academy of Pediatrics; 2008:2229. at the time of delivery, even in the absence of maternal

Figure 8. Perineum of a child who has lichen sclerosus,

Figure 7. Anogenital warts are visible in the vestibule and on showing pallor of the labia and erythema, hemorrhage, and
the hymen of a 9-year-old girl who was an incest survivor. excoriation. Reprinted from the Figure in Index of Suspicion.
Reprinted from Figure 2 in Sinclair KA, Woods CR, Sinal SH. Pediatr Rev. 2003;24(3):99-105.
Venereal warts in children. Pediatr Rev. 2011;32(3):115-121.
resolution, the steroid cream should be tapered and
lesions. (9) Condylomata acuminata infection may be the area watched closely for reoccurrence. Recurrent
a result of maternal transmission in girls younger than courses may be necessary. Tacrolimus has also been
2 years. In addition, genital condylomata acuminata may found to be effective. (11) Untreated lichen sclerosis
be due to autoinoculation from hand to genital contact. may cause sexual dysfunction because of scarring with
However, sexual abuse should be considered and asked loss of normal vulvar or vaginal architecture.
about in all prepubertal girls with genital warts. Girls with Vaginal bleeding in prepubertal girls can also result
condylomata acuminata can also present with vaginal from foreign bodies, urethral prolapse, bacterial vulvo-
bleeding due to the friable nature of these lesions. The di- vaginitis, or trauma. Trauma can result from straddle in-
agnosis of condylomata acuminata is usually made clini- juries or sexual abuse. A careful history and examination
cally. A girl with suspected sexual abuse should be are required if sexual abuse is considered. In general, in-
referred to an experienced clinician for evaluation and col- juries to the anterior genital area, such as the clitoris,
lection of evidence. mons pubis, and anterior labia, often result from uninten-
tional injuries. Trauma that occurs to the posterior gen-
Case 4: Vaginal Bleeding ital tissues, such as the posterior fourchette or hymen, can
A 7-year-old girl presents after her mother notices some result from sexual abuse. A study documenting the gen-
blood staining her underwear. The girl is not experiencing ital examinations in 392 girls with and without sexual
any irritation, dysuria, or constipation. She is otherwise well. abuse found that girls with sexual abuse did not differ
On examination, the vulva appears pale with thin, white from girls who were not sexually abused with regard to
skin in a figure-eight shape around the vulva and anus. labial adhesions, increased vascularity, friability, a perineal
There are 2 areas of dried blood on punctuate excoriations depression, or a hymenal bump, tag, longitudinal intrava-
in the perineum. ginal ridge, external ridge, band, or superficial notch. (3)
Lichen sclerosis may present with bleeding, itching, However, sexual abuse was associated with hymenal tran-
vulvar discomfort, or vaginal discharge. The cause of this section, perforation, or deep notch. If the injury does not
condition is unclear. Diagnosis is made clinically based on fit the history of the mechanism of injury, sexual abuse
a white, atrophic, onion skin–like appearance in an hour- must be considered. If sexual abuse is suspected, a referral
glass shape around the vulva and perianal tissues (Fig 8). to an experienced clinician is recommended for docu-
The atrophic skin involved is friable, resulting in bleeding mentation and evidence collection.
with minor trauma. High-potency steroid ointment, such Urethral prolapse is another cause of vaginal bleeding.
as clobetasol, 0.05%, or halobetasol, 0.05%, ointment ap- In addition, urethral prolapse can cause dysuria, vaginal
plied twice daily until resolution, which may take weeks discomfort, or a mass that appears at the vulva (Fig 9).
to months, is the treatment of choice. (10) On The mass can appear as red or purple mucosa in a ring

Coagulopathies, arteriovenous malformations, and

primary hypothyroidism could present with vaginal
bleeding. Ovarian estrogen production, not mediated
centrally, as seen in some estrogen-secreting ovarian
cysts and McCune-Albright syndrome may also present
with vaginal bleeding without other signs of puberty
(thelarche and adrenarche). McCune-Albright syndrome
is a rare disorder that includes precocious puberty, cafe-
au-lait skin pigmentation, and fibrous dysplasia of bone.
Discussion of precocious puberty is beyond the scope of
this article. For further information, refer to the article
by Muir. (15)
Case 5: Vaginal Itching

A 4-year-old girl presents with vaginal itching. Her mother
states that she is rubbing her crotch during the day and is
having difficulty falling asleep at night due to itching. She
has not noticed any vaginal bleeding or discharge. There
are no recent illnesses. Genital examination findings are
unremarkable.
Pinworms can cause vaginal itching. Although pin-
worms do not infect the vagina, they can travel from
the anus to the vaginal introitus. Itching may be more
prominent at night when pinworms exit the anus to lay
eggs on the perianal skin. The predominant symptom
with pinworm infection is itching. Worms may be de-
tected in the perineal area at night by the caregiver. They
are white, pin-shaped, and approximately 1 cm long. Al-
though the diagnosis can be made with anal pinworm
preparation, treatment can be empiric and should include
Figure 9. Urethral prolapse: a donut of red, purple, or dark the entire family. Treatment is a one-time administration
tissue surrounds the urethra and obscures the hymenal orifice.
of mebendazole by mouth. Lichen sclerosis is also asso-
Reprinted from Figure 5 in Sugar NF, Graham EA. Common
ciated with bleeding and/or irritation in addition to itch-
gynecologic problems in prepubertal girls. Pediatr Rev. 2006;
27(6):213-223. ing. Candida infections can cause pruritus and although
less common after infancy may be seen in association with
recent antibiotics, immune suppression, diaper use, dia-
shape located at the introitus. The cause of urethral pro- betes, and obesity. Treatment is with topical vaginal an-
lapse is unknown; however, it is more common in African tifungal cream used daily or twice daily for 3 to 5 days.
American than white girls. (12)(13) If the distal portion
of the urethra has prolapsed, the tissue may become fri- Case 6: Vulvar Ulcers
able and/or infected. Treatment consists of a topical es- An 11-year-old girl presents with pain in her genital area
trogen cream applied twice daily, along with sitz baths. for several days. Her caregiver reports that she has been
Less commonly, vaginal bleeding can result from vag- tired for the past week and has had a headache. On exam-
inal polyps or tumors (eg, rhabdomyosarcoma or sarcoma ination, there is a single ulcer, approximately 1 cm in di-
botryoides). If a girl presents with persistent bleeding that ameter, located on the left medial labia minora.
does not resolve with hygiene measures and has negative Aphthous ulcers are the most common cause of ulcers
culture results with no clear cause, examination with the in the vulva. (16) These ulcers often occur in girls aged
girl under anesthesia is recommended. (14) It is not un- 10 to 15 years and may accompany systemic symptoms,
common for newborn girls to have vaginal bleeding sev- such as fatigue, fever, headache, or malaise. These ulcers
eral days to several weeks after delivery, as a result of are also known as Lipschutz ulcers. They are often more
maternal estrogen withdrawal. than 1 cm in diameter and located on the medial labia

minora. These ulcers can appear as a single lesion or mul- References

tiple lesions and are extremely painful. The cause is not 1. Committee on Practice and Ambulatory Medicine. Use of
well established; however, associations with viruses, such chaperones during the physical examination of the pediatric patient.
as Epstein-Barr virus, cytomegalovirus, and influenza, Pediatrics. 2011;127(5):991–993
2. Adams JA, Harper K, Knudson S, Revilla J. Examination
have been reported. The differential diagnosis of vulvar findings in legally confirmed child sexual abuse: it’s normal to be
ulcers includes herpes simplex virus infection, varicella, normal. Pediatrics. 1994;94(3):310–317
syphilis, Crohn disease, and Behçet disease. Evaluation 3. Berenson AB, Chacko MR, Wiemann CM, Mishaw CO,
of a vulvar ulcer should include herpes simplex virus cul- Friedrich WN, Grady JJ. A case-control study of anatomic changes
ture, rapid plasma reagin for syphilis evaluation, and an resulting from sexual abuse. Am J Obstet Gynecol. 2000;182(4):
820–834
Epstein-Barr virus titer. A history of oral ulcers, arthritis, 4. Marshall WA, Tanner JM. Variations in pattern of pubertal
uveitis, and/or previous vulvar ulcers may suggest Behçet changes in girls. Arch Dis Child. 1969;44(235):291–303
disease. A history of abdominal pain, systemic symptoms, 5. Garden AS. Vulvovaginitis and other common childhood
and weight loss may suggest Crohn disease. Treatment of gynaecological conditions. Arch Dis Child Educ Pract Ed. 2011;
aphthous vulvar ulcers is supportive and includes topical 96(2):73–78
6. Stricker T, Navratil F, Sennhauser FH. Vulvovaginitis in pre-
anesthetics and pain management. If the pain is severe pubertal girls. Arch Dis Child. 2003;88(4):324–326
and the girl is unable to urinate, inpatient admission for 7. McGreal S, Wood P. Recurrent vaginal discharge in children.
pain control and catheter placement may be warranted. J Pediatr Adolesc Gynecol. 2013;26(4):205–208
Treatment of vulvar ulcers due to Behçet disease includes 8. Bell TA, Stamm WE, Wang SP, Kuo CC, Holmes KK, Grayston
topical corticosteroids, such as triamcinolone cream or JT. Chronic Chlamydia trachomatis infections in infants. JAMA.
1992;267(3):400–402
10 mg/d of oral steroids for 2 to 3 weeks. If the ulcer 9. Sinclair KA, Woods CR, Kirse DJ, Sinal SH. Anogenital and
is caused by a sexually transmitted infection, evaluation respiratory tract human papillomavirus infections among children:
and/or referral to child protection specialist is warranted. age, gender, and potential transmission through sexual abuse.
Pediatrics. 2005;116(4):815–825
10. Chi CC, Kirtschig G, Baldo M, Brackenbury F, Lewis F,
Summary Wojnarowska F. Topical interventions for genital lichen sclerosus.
In summary, on the basis of strong evidence, (5) nonspe- Cochrane Database Syst Rev. 2011;(12):CD008240
cific or irritant vulvovaginitis is the most common cause 11. Hengge UR, Krause W, Hofmann H, et al. Multicentre, phase
of genital concerns in prepubertal girls. An empiric trial of II trial on the safety and efficacy of topical tacrolimus ointment
for the treatment of lichen sclerosus. Br J Dermatol. 2006;155(5):
hygiene and environmental measures should be used if
1021–1028
nonspecific vaginitis is suspected. If the symptoms con- 12. Valerie E, Gilchrist BF, Frischer J, Scriven R, Klotz DH,
tinue despite hygiene and environmental measures, bacte- Ramenofsky ML. Diagnosis and treatment of urethral prolapse in
rial cultures should be performed. On the basis of strong children. Urology. 1999;54(6):1082–1084
evidence, (7) if discharge with a foul odor is present, con- 13. Hillyer S, Mooppan U, Kim H, Gulmi F. Diagnosis and
treatment of urethral prolapse in children: experience with 34 cases.
sider a foreign body and a knee-chest examination to visu-
Urology. 2009;73(5):1008–1011
alize the inner vagina for the cause. If sexual abuse is 14. Striegel AM, Myers JB, Sorensen MD, Furness PD, Koyle MA.
suspected, careful evaluation and/or referral to a child pro- Vaginal discharge and bleeding in girls younger than 6 years. J Urol.
tection specialist is warranted with testing for sexually 2006;176(6 Pt 1):2632–2635
transmitted infections. If there are physical signs that indi- 15. Muir A. Precocious puberty. Pediatr Rev. 2006;27(10):
373–381.
cate another diagnosis, such as the appearance of lichen
16. Huppert JS, Gerber MA, Deitch HR, Mortensen JE, Staat
sclerosis, trauma, urethral prolapse, or labia adhesions, MA, Adams Hillard PJ. Vulvar ulcers in young females: a manifes-
evaluation and management of these specific problems tation of aphthosis. J Pediatr Adolesc Gynecol. 2006;19(3):195–
should be used as described above. 204
Parent Resources from the AAP at HealthyChildren.org

• English: http://www.healthychildren.org/English/ages-stages/gradeschool/puberty/Pages/Pelvic-Exams.aspx
• Spanish: http://www.healthychildren.org/spanish/ages-stages/gradeschool/puberty/paginas/pelvic-exams.aspx

PIR Quiz Requirements

To successfully complete 2014 Pediatrics in Review articles for AMA PRA Category 1 CreditTM, learners must demonstrate a minimum performance
level of 60% or higher on this assessment, which measures achievement of the educational purpose and/or objectives of this activity. If you score
less than 60% on the assessment, you will be given additional opportunities to answer questions until an overall 60% or greater score is achieved.
NOTE: Learners can take Pediatrics in Review quizzes and claim credit online only at: http://pedsinreview.org.
1. You are reviewing with a resident the effects of different hormonal environments on the vulva and vagina from
birth through menopause. You would expect the resident to correctly state that the appearance of the mucosa
of the vulva and vagina of a normal 7-year-old girl is more like that of:
A. A newborn than that of an adolescent.
B. A newborn than that of a postmenopausal woman.
C. A postmenopausal woman than that of a newborn.
D. An adolescent than that of a newborn.
E. An adolescent than that of a postmenopausal woman.
2. A 7-year-old girl has foul-smelling, slightly bloody vaginal discharge. You suspect a vaginal foreign body. With
proper draping, you prepare to examine the genitalia. The position that affords the best view of her inner vagina is:
A. Frog-leg prone.
B. Frog-leg supine.
C. Knee-chest.
D. Left lateral decubitus.
E. Right lateral decubitus.
3. A previously well 7-year-old girl has been experiencing dysuria for the past week. On examination, her vulva is
red. The hymen is unremarkable, but there is a small amount of yellowish discharge at the introitus. The
perianal area is normal. The MOST likely explanation is
A. Urinary tract infection.
B. Behçet disease.
C. Candidal infection.
D. Nonspecific vulvovaginitis.
E. Sexual abuse.
4. A previously well 7-year-old girl has been experiencing dysuria for the past week. On examination, her vulva
and perianal area are intensely erythematous. The hymen is unremarkable. There is a small amount of yellowish
discharge at the introitus. The MOST appropriate first step is a:
A. Referral to a dermatologist.
B. Referral to protective services.
C. Speculum examination.
D. Streptococcal culture of the throat and vulva.
E. Urine culture.
5. A previously well 7-year-old girl has been experiencing dysuria for the past week. On examination, her vulva
and perianal area are intensely erythematous, and she has a deep posterior hymeneal notch. No vaginal
discharge is present. The MOST important step is a:
A. Referral to a dermatologist.
B. Referral to a pediatric gynecologist.
C. Referral to protective services.
D. Streptococcal culture of the throat and vulva.
E. Urine culture.

Article neurology
Pediatric MRI of the Brain: A Primer

Kamakshya P. Patra, MD,*
Educational Gap
Jeffrey D. Lancaster, MD,*
Jeffery Hogg, MD,† Jeffrey Because of recent advances in magnetic resonance imaging (MRI) techniques, pediatri-
S. Carpenter, MD † cians should be aware of the different modalities and their unique advantages and ap-
propriateness in different clinical situations.
Author Disclosure
Objectives After completing this article, readers should be able to:
Drs Patra, Lancaster,
Hogg, and Carpenter 1. Understand the pros and cons of MRI and computed tomography of the brain.
have disclosed no 2. Know the basic principles of MRI and its different image modalities.
financial relationships 3. Be aware of the appropriateness of different modalities in specific clinical situations.
relevant to this article.
This commentary does Introduction
not contain
Magnetic resonance imaging (MRI) is based on the absorption and emission of radiofre-
quency energy by hydrogen protons whose spin is influenced by changing magnetic fields
a discussion of an
(0.3 to 1.5 T). Unlike computed tomography (CT), there is no radiation exposure.
unapproved/ T1-weighted images cause fat (eg, myelin in white matter) to appear bright and water (eg,
investigative use of cerebrospinal fluid [CSF] or edema) to appear dark on this sequence. The gray-white inter-
a commercial product/ faces of the brain are well depicted on these sequences, especially if with the images are thinly
device. sliced. T2-weighted images cause water (eg, CSF and edema) to appear bright and fat to ap-
pear dark. The MRI-based intravenous contrast agents (eg, gadolinium) are frequently used in
T1-weighted images (Fig 1A and B) to make serum appear bright. The blood-brain barrier
typically serves to limit the passage of many molecules out of the blood vessels. If disease pro-
cesses break down this barrier (such as infection, tumors, or inflammation), intravenous con-
trast agents can cross into the brain, causing areas of contrast entry to appear very bright.
MRI vs CT
MRI and CT are complementary diagnostic tools with mutually distinct advantages and dis-
advantages. CT can be performed quickly and is preferred in cases of trauma and emergency
circumstances. CT is more sensitive for detecting calcification and better delineates cortical
bone. CT angiography has a better resolution compared with magnetic resonance angiog-
raphy; however, the latter has the advantage of not absolutely requiring the use of contrast
agents. MRI cannot be performed in claustrophobic patients
and those with ferromagnetic medical devices, such as pace-
Abbreviations makers. Further, MRI takes longer to perform and might re-
quire sedation, precluding its use in emergency situations.
ADHD: attention-deficit/hyperactivity disorder However, for evaluating posterior fossa disease, white matter
CSF: cerebrospinal fluid disease, temporal lobe epilepsy, and vascular diseases, MRI is
CT: computed tomography preferable to CT. In this article, we present some common
DWI: diffusion-weighted magnetic resonance imaging pediatric case vignettes that illustrate the role of brain MRI
FLAIR: fluid-attenuated inversion recovery to acquaint the reader with the common modalities of MRI.
fMRI: functional magnetic resonance imaging
MRI: magnetic resonance imaging
MRV: magnetic resonance venography Case 1
NAA: N-acetylaspartate A 7-year-old girl with a history of migraine headaches pre-
SDH: subdural hematoma sented with a head tilt to the left and worsening headaches.
Optic disc edema was found on ophthalmoscopy. A brain
*Department of Pediatrics, Section of Hospital Pediatrics, West Virginia University Children’s Hospital, Morgantown, WV.
†
Department of Neuroradiology, West Virginia University Health Sciences Center, Morgantown, WV.

neurology MRI of the brain
and erythematous, she had difficulty opening her right

eye, and she had double vision with all gazes. Clinical
findings included proptosis, ptosis, restriction of ocular
motility, ocular pain, and chemosis. Laboratory tests re-
vealed neutrophilic leukocytosis and elevated C-reactive
protein. Head MRI was performed. Coronal postcontrast
T1-weighted imaging revealed inflammation in the right
orbit with diffuse stranding in orbital fat, enhancing myo-
sitis of the inferior and medial rectus muscles (Fig 3).
Figure 1. T1-weighted image at the level of midbrain. A. The Orbital cellulitis is an infection of the soft tissue pos-
cerebrospinal fluid (CSF) appears dark. B. The CSF appears bright. terior to the orbital septum, whereas preseptal cellulitis
Note the gray and white matter differentiation in the 2 images. affects anterior to the orbital septum. The former is dis-
The anatomical structures identified here are the caudate tinguished from the latter by the presence of proptosis,
nucleus (i), lenticular nuclei (ii), thalamus (iii), frontal horn of chemosis, ophthalmoplegia, or decreased visual acuity.
lateral ventricle (iv), and atria of the lateral ventricle (v). MRI is superior to CT when there is suspicion of intra-
cranial extension, optic nerve involvement, and cavernous
MRI was performed, which revealed a large heteroge-
sinus thrombosis because MRI is better for discerning soft
neous intermediate signal mass that filled and obstructed
tissue disease. Gadolinium is a paramagnetic contrast agent
the fourth ventricle on the axial T2-weighted images at
that prolongs the spin of water protons, resulting in post-
the level of the fourth ventricle (Fig 2). She underwent
contrast enhancement of areas of inflammation on T1-
surgical resection, and the histologic diagnosis was
weighted imaging. The most sensitive technique for
medulloblastoma.
demonstrating orbital infection is postgadolinium, fat-
Apart from sparing the effects of radiation, MRI is supe-
suppressed T1-weighted imaging.
rior to CT in delineating tumor extent, spread, mass effect,
vascularity, necrosis, and edema. T2-weighted sequences
are sensitive for the detection of tumor and edema. Case 3
A 16-year-old girl presented to the emergency depart-
ment with a chief symptom of “vision loss in right eye.”
Case 2 She denied eye pain, diplopia, photophobia, or headache.
A 6-year-old girl presented with swelling of her right eye.
She had a history of sinusitis. Her right eye was swollen
Figure 3. Coronal postcontrast T1-weighted image shows in-

flammation in the right orbit with diffuse stranding in orbital
Figure 2. Axial T2-weighted image at the level of the fourth fat, enhancing myositis of the inferior and medial rectus
ventricle shows a large heterogeneous intermediate signal muscles (solid yellow arrow indicates the right inferior rectus;
mass (blue arrow) that fills and obstructs the fourth ventricle. solid blue yellow indicates the right medial rectus muscle).

Her medical history was unremarkable. Visual acuity was magnetization of CSF to return to the null point preced-
normal in the left eye (20/20); however, it was decreased ing the conventional spin echo imaging. It also has a tre-
in the right eye (20/200). Her right pupil constricted in mendous role in early detection of cortical gray matter
response to consensual but not to direct light (ie, deaffer- infarcts. The cortical gray matter is vulnerable to ischemia
ented pupil). Bilateral fundi appeared normal. MRI of the because of its high metabolic activity. However, cortical
brain revealed a normal-appearing left optic nerve. The gray matter immediately adjacent to CSF within the sulci
left optic nerve was round with distinct borders and was makes infarction hard to delineate when this area under-
appropriately surrounded by CSF as demonstrated by goes conventional imaging sequences that emphasize
T2-weighted fluid-attenuated inversion recovery (FLAIR) fluid signal. FLAIR suppresses the CSF signal and makes
imaging. The right optic nerve, however, had poorly de- the cortical or periventricular area more conspicuous.
fined borders, suggesting an inflammatory process. The in-
flamed right optic nerve also enhanced with gadolinium
administration (Fig 4).
Case 4
A 3-month-old boy was admitted to the pediatric inten-
Given the patient’s visual disturbance and the evi-
sive care unit for bilateral subdural hematomas (SDHs)
dence of optic nerve inflammation on MRI, optic neuritis
and concern for intentional trauma. Per his parents, he
was suggested as a diagnosis. Other MRIs obtained re-
had emesis for 24 hours and had been unable to keep for-
vealed demyelination in the pons and cerebellum. The
mula down. He also had 2 episodes of arm stiffening and
presence of CSF oligoclonal bands supported multiple
breath holding followed by agitation and crying. Neuro-
sclerosis as the diagnosis.
logic examination revealed an enlarged head circumfer-
FLAIR is an extremely useful technique in brain imag-
ence, dilated scalp veins, and a bulging anterior fontanel.
ing. Like conventional T2-weighted imaging, edema ap-
He had brisk tendon reflexes. Brain MRI FLAIR images
pears bright, but this technique nulls (or makes dark)
revealed localizing tissue loss in the right parietal region
CSF signal. FLAIR is a sensitive technique for displaying
from an older injury and 2 SDHs of different densities,
demyelination within the brain, thus clearly revealing le-
with the more acute-appearing SDH on the left and
sions in proximity to CSF, such as periventricular plaques
the more subacute SDH on the right (Fig 5).
in multiple sclerosis. The technique is accomplished via
The presence of SDHs of varying ages and of skull frac-
a relatively long inversion time to allow the longitudinal
tures, which are depressed or multiple or diastatic or involve
multiple or nonparietal bones, is a key neuroimaging find-
ing that is consistent with the diagnosis of intentional
trauma. CT is the modality of choice to detect acute hem-
orrhages and skull fractures. MRI is superior to CT in de-
tecting extra-axial hemorrhages, diffuse axonal injury, and
early recognition and prognostication of parenchymal in-
jury. SDHs over the falx, posterior fossa, and tentorium are
more characteristic of intentional trauma. (1) T2-weighted
gradient echo MRI enhances the sensitivity for recogniz-
ing acute bleeds and old shear bleeds. Diffusion-weighted
imaging (DWI) is also helpful for revealing early and pro-
gressive edema. Of note, bleeding diathesis, birth injury,
inborn errors of metabolism (such as glutaric academia type
1 and Menkes disease), lymphohistiocytosis, infection,
and unintentional trauma can have similar appearance with
DWI. DWI and its uses are further described in case 6.
Case 5
Figure 4. The left optic nerve (solid yellow arrow) is round A 4-year-old previously healthy girl was admitted for left-
with distinct borders and is appropriately surrounded by sided weakness and increased somnolence. A week before
cerebrospinal fluid as demonstrated by T2-weighted imaging. presentation, she had severe gastroenteritis. Her oral in-
The right optic nerve (solid blue arrow), however, has poorly take was drastically reduced, and she had presented to a
defined borders, suggesting an inflammatory process. local emergency department 2 days earlier with persistent

Figure 6. A. Magnetic resonance venography (MRV) reveals

large filling defect that occludes and occupies the superior
sagittal sinus (broken blue arrow) and medial portion of both
transverse sinuses (broken yellow arrows). B. On the right,
coronal MRV with contrast reveals restoration of normal
contrast enhanced filling of sagittal (solid blue arrow) and
both transverse sinuses (solid yellow arrows).
sigmoid, and straight sinuses. MRI and MRV are impor-

tant for demonstrating venous occlusion and its conse-
quences, infarction, and edema. Of note, a thrombus in
its subacute phase can be recognizable as a high signal
on a T1-weighted scan, thereby making MRV unnec-
essary to perform for a suspected clot.
Figure 5. Fluid-attenuated inversion recovery image localizing
tissue loss in right parietal region from an older injury and 2
different densities of subdural hematoma (more acute Case 6
appearing on the left and subacute on the right). A term infant developed right-sided clonic seizures on
her second day of life. The pregnancy was well supervised,
vomiting. On the day of her presentation, she was unable

to walk. Her vital signs were stable. On examination, she
was drowsy. She had left-sided upper motor neuron facial
weakness. Her muscle strength in the left upper and
lower extremities was 0/5 and 1/5, respectively, and
she had a positive Babinski sign. The rest of her examina-
tion findings were unremarkable. Her head CT was un-
remarkable. MRI and magnetic resonance venography
(MRV) of the brain demonstrated a large filling defect,
occluding and occupying the superior sagittal sinus and
medial portion of both transverse sinuses (Fig 6). A con-
ventional head MRI revealed venous infarctions in the
left parietal and frontal areas without any hemorrhage.
Her coagulation profile was normal. She was treated with
intravenous heparin and fluids. Her weakness improved
gradually, and subsequent MRV revealed restoration of
normal contrast enhanced filling of sagittal and both
transverse sinuses (Fig 6).
MRV is the optimal noninvasive technique of delineating
cerebral venous anatomy. Time-of-flight, phase-contrast Figure 7. Coronal T2-weighted image shows loss of gray white
angiography, and contrast-enhanced MRV are the differentiation and swelling in the posterior cerebral artery
means commonly used to evaluate the cerebral venous territory on the left side with ventricular effacement secondary
structures, commonly the superior sagittal, transverse, to swelling.

Coronal T2 revealed left-sided loss of gray white differen-

tiation and swelling in the region of the posterior cerebral
artery with obscuring of the ventricular surface (ventric-
ular effacement) (Fig 7).
The hyperintense signal in the posterior cerebral artery
region on DWI and the hypointense signal in the same
distribution on apparent diffusion coefficient imaging
confirmed the presence of restricted diffusion character-
istics of an evolving acute infarction (Fig 8).
By disrupting the cellular metabolism and Naþ/Kþ
adenosine triphosphatase pump, ischemia results in loss
of transmembrane ionic gradients, thereby restricting dif-
Figure 8. A. Hyperintense signal in posterior cerebral artery fusion of water through cellular membranes. DWI was
territory on diffusion-weighted imaging. B. Apparent diffu- performed by adding 2 strong diffusion-sensitizing mag-
sion coefficient image has marked hypointense signal in the netic field gradient pulses. DWI depicts recently infarcted
same distribution, confirming restricted diffusion character-
brain as a very bright signal. The actual diffusion in the tis-
istics of acute evolving infarct.
sue is decreased as seen on apparent diffusion coefficient
maps. This period of restricted diffusion can last 5 to 10
and her delivery was uneventful. Her physical examina- days (but sometimes less) in the pediatric population.
tion findings were normal on the first day of life. Maternal DWI can detect ischemic stroke within minutes, in contrast
drug screen result was negative. Metabolic profile, blood to conventional MRI, which may take hours for diagno-
cell count, transfontanel ultrasonography, and CSF study sis. DWI is invaluable in detecting lesions not usually
results were normal. A head MRI was performed. identifiable with conventional MRI and can distinguish
new and old strokes and acute and
chronic ones. Because abscesses, pa-
renchymal contusions, and cysts can
also demonstrate restricted diffusion,
DWI also helps detect brain ab-
scesses and cystic tumors.
Other MRI Modalities

Magnetic resonance spectroscopy
monitors biochemical changes in
brain tumors, head trauma, stroke,
epilepsy, metabolic disorders, and
infections. The metabolites predomi-
nantly measured are N-acetylaspartate
(NAA), creatine, choline, and myo-
inositol. NAA, an amino acid found
exclusively in neurons, is regarded
as a nonspecific marker of neuronal
viability. NAA levels are decreased
in conditions such as infarction and
neuronal inflammation. Lactate is
absent in normal brain tissue, and
Figure 9. A 16-year-old with a 1-week history of “bumping into things.” Contrast-
its presence is indicative of anaero-
enhanced magnetic resonance imaging (MRI) shows an enhancing lesion in the occipital bic glycolysis at the cellular level. El-
lobe. MRI spectroscopy reveals decreased N-acetylaspartate peak, maintained choline- evated lactate levels are associated
creatine ratio, and the presence of a large lactate peak. These findings are indicative of an with ischemia or neurometabolic dis-
ischemic stroke. orders (with predominant anaerobic

glycolysis). An elevated choline-creatine ratio is sugges-

tive of malignancy. Choline is involved in the synthesis Summary
of phospholipid cell membranes; in aggressive neoplasms,
choline is elevated because of rapid cell turnover. Crea- • On the basis of strong recommendation, magnetic
tine, a precursor of adenosine triphosphate, gives a mea- resonance imaging (MRI) and computed tomography
sure of brain energy stores. In high-grade brain tumors, (CT) are complementary diagnostic tools with
mutually distinct advantages and pitfalls. MRI is
due to increased metabolic activity, creatine is depleted. preferred to CT in posterior fossa disease, white matter
Figure 9 shows magnetic resonance spectroscopy image disease, temporal lobe epilepsy, and vascular diseases.
from a 16-year-old girl with ischemic stroke in the occip- • On the basis of strong recommendation, diffusion-
ital area. There is a large lactate peak, decreased NAA weighted imaging is superior to noncontrast CT for
peak, and maintained choline-creatine ratio. These find- diagnosis of acute ischemic stroke in patients who
present within 12 hours of symptoms. (5)
ings are characteristic of an ischemic stroke. • On the basis of strong recommendation, fluid-
Functional MRI (fMRI) reveals brain activity by chang- attenuated inversion recovery MRI is a sensitive
ing magnetization between oxygen-rich and oxygen-poor technique for displaying demyelination within the
blood. fMRI is useful for presurgical mapping, epilepsy, brain, especially in lesions near the cerebrospinal fluid,
stroke, trauma, tumors, language lateralization, and neuro- such as periventricular plaques in multiple sclerosis. In
clinically isolated syndrome, 3 or more white matter
behavioral disorders, such as attention-deficit/hyperactivity lesions on T2-weighted MRI is highly predictive of
disorder (ADHD) and autism. The diagnosis and man- future development of clinically definite multiple
agement of ADHD can be a challenge because diagnosis sclerosis. (6)
relies on parents’ and teachers’ reporting of behavioral • There is insufficient evidence to support or refute
symptoms that might be biased and subjective. fMRI neuroimaging in a child presenting with status
epilepticus. (7)
has shown that in patients with ADHD there is reduced
activation of striatum and frontal lobes during tasks that
warrant attention. Thus, in the future, fMRI could be
useful to diagnose, prognosticate, and treat patients with References
ADHD. 1. Hall EJ. Lessons we have learned from our children: cancer risks
Children with ventriculoperitoneal shunts for hydro- from diagnostic radiology. Pediatr Radiol. 2002;32(10):700–706
cephalus require subsequent follow-up CT to evaluate 2. Rajaram S, Batty R, Rittey CD, Griffiths PD, Connolly DJ.
Neuroimaging in non-accidental head injury in children: an
shunt integrity, assess ventricle anatomy, and rule out important element of assessment. Postgrad Med J. 2011;87
complications. However, multiple lifetime exposure to (1027):355–361
ionizing radiation is associated with potential risk for car- 3. Iskandar BJ, Sansone JM, Medow J, Rowley HA. The use of
cinogenesis. (2) Single-shot fast-spin echo (quick-brain) quick-brain magnetic resonance imaging in the evaluation of shunt-
MRI can be used in children with shunt-treated hydro- treated hydrocephalus. J Neurosurg. 2004;101(2 Suppl):147–151
4. American College of Radiology. ACR Appropriateness
cephalus for workup and follow-up in lieu of CT to cir- CriteriaÒ. www.acr.org/ac. Accessed November 20, 2013.
cumvent radiation exposure. Because of its ability to 5. Schellinger PD, Bryan RN, Caplan LR, et al; Therapeutics and
generate required data with a single excitation impulse, Technology Assessment Subcommittee of the American Academy
single-shot fast-spin echo is fast and does not require se- of Neurology. Evidence-based guideline: the role of diffusion and
dation. Multiplanar images are obtained in less than a sec- perfusion MRI for the diagnosis of acute ischemic stroke: report of
the Therapeutics and Technology Assessment Subcommittee of the
ond, reducing the motion artifacts. (3) American Academy of Neurology. Neurology. 2010;75(2):177–185
6. Frohman EM, Goodin DS, Calabresi PA, et al; Therapeutics and
MRI vs a Good History and Physical Technology Assessment Subcommittee of the American Academy
of Neurology. The utility of MRI in suspected MS: report of the
Examination Therapeutics and Technology Assessment Subcommittee of the
Although MRI can be significantly informative, a good American Academy of Neurology. Neurology. 2003;61(5):602–611
history and clinical examination are sufficient for diagnos- 7. Riviello JJ Jr, Ashwal S, Hirtz D, et al; American Academy of
ing and managing many clinical situations, such as primary Neurology Subcommittee; Practice Committee of the Child
headache (chronic or recurrent headache, including migraine Neurology Society. Practice parameter: diagnostic assessment of
the child with status epilepticus (an evidence-based review): report
without permanent neurologic signs or signs of increased of the Quality Standards Subcommittee of the American Academy
intracranial pressure), simple syncope, simple febrile seizures, of Neurology and the Practice Committee of the Child Neurology
and benign positional vertigo. (4) Society. Neurology. 2006;67(9):1542–1550


1. An infant in the newborn nursery has just experienced 3 focal seizures of her right arm, yet she appears well
and is afebrile. You suspect a neonatal stroke. Among the following, the MOST appropriate brain imaging to
establish this diagnosis is:
A. Computed tomography.
B. Magnetic resonance angiography.
C. Magnetic resonance imaging with diffusion-weighted imaging.
D. Magnetic resonance spectroscopy.
E. Single-shot fast-spin echo magnetic resonance imaging.
2. You are counseling the parents of a toddler with shunted hydrocephalus. His family is concerned about the
long-term effects of radiation exposure used to image the brain for evidence of shunt malfunction. Among the
following, you are MOST likely to say:
A. Computed tomography has a limited radiation exposure, far less than therapeutic radiation, and the couple
should not be concerned.
B. Head ultrasonography should always be used as a screening tool before considering computed tomography.
C. Magnetic resonance imaging with diffusion-weighted imaging will be useful to distinguish acute from
subacute shunt failure.
D. Magnetic resonance imaging with fluid-attenuated inversion recovery (FLAIR) differentiates
cerebrospinal fluid as dark from other water, which appears bright, and FLAIR is an optimal way to
diagnose shunt failure.
E. Single-shot fast-spin echo magnetic resonance imaging is a promising technique to obtain imaging
in just seconds without sedation and is optimal to evaluate shunt integrity and assess ventricular
anatomy.
3. A 6-year-old presents with progressive occipital headaches, nausea, and vomiting for 2 weeks. Head
computed tomography in the emergency department reveals a possible lesion in the posterior fossa. You
now request brain magnetic resonance imaging with gadolinium contrast because this contrast will help
highlight:
A. Arachnoid cyst.
B. Cerebral dysgenesis.
C. Chiari malformation.
D. Hydrocephalus.
E. Tumor.
4. A 15-year-old boy presents to the emergency department with severe headache after striking his
head without a helmet while skateboarding. You decide to perform imaging of his head. Among
the following, the MOST appropriate modality to detect a skull fracture or acute parenchymal
hemorrhage is:
A. Computed tomography.
B. Magnetic resonance imaging with diffusion-weighted imaging.
C. Magnetic resonance spectroscopy.
D. Single-shot fast-spin echo magnetic resonance imaging.
E. Ultrasonography.

5. A 16-year-old girl was found to have a right parietal mass with computed tomography. She is scheduled to
undergo magnetic resonance imaging, and the radiologist suggests adding spectroscopy to determine the
nature of the mass. Among the following, the finding MOST suggestive for tumor on spectroscopy is:
A. Decreased lactate.
B. Decreased phospholipid.
C. Elevated choline-creatine ratio.
D. Elevated creatine.
E. Elevated N-acetyl aspartate.

• English: http://www.healthychildren.org/English/health-issues/conditions/treatments/Pages/Imaging-Tests.aspx
• Spanish: http://www.healthychildren.org/spanish/health-issues/conditions/treatments/paginas/imaging-tests.aspx
Correction
In the February 2014 Pediatrics in Review article “The Clinician’s Guide to Autism” (PediatrRev. 2014;35(2):62–78,
doi:10.1542/pir.35-2–62), there is an error in CME Quiz Question 1. The child’s age should be 4 years old, and the correct
answer should be “B. Childhood Autism Screening Test.” The online version of the quiz was resupplied to correct this error.
The journal regrets the error.

Article complementary medicine
Complementary, Holistic, and Integrative

Medicine: Utilization Surveys of the Pediatric Literature
Soleil Surette, MLIS,* Editor’s Note:
Sunita Vohra, MD, MSc*†
Whether you believe in the effectiveness of complementary and alternative medicine (CAM) or not, some of your
patients and their parents do. As you read this article, please note the number of patients who use CAM. Joseph A.
Zenel, MD Editor-in-Chief
Author Disclosure
Ms Surette has Educational Gap
disclosed no financial
Health care professionals do not ask consistently about complementary, holistic, and in-
relationships relevant
tegrative medicine use by their patients, yet it is important to do so because patients and
to this article. Dr.
families often pursue this course of therapy for specific medical conditions and do not
Vohra has disclosed
volunteer this information.
that she has grants as
principal investigator Introduction
or co-investigator from No thorough assessment has been made of the literature on the use of pediatric comple-
Health Canada, SERIN- mentary and alternative medicine (CAM) since 1999, when Ernst published a systematic
ETD Acupuncture
review on this topic. (1) As part of its horizon scanning, the Complementary and Alterna-
tive Research and Education (CARE) program (www.care.ualberta.ca) tracks the use of
Research Fund, Alberta
CAM in the pediatric literature and, as of March 2011, has identified 160 English-language
Innovates Health studies dating back to 1982. Utilization literature can be a valuable source of information
Solutions, Canadian for determining what CAM practices and products warrant further pediatric research. This
Institutes of Health article explores the 5 most studied pediatric specialty populations: oncology, asthma, au-
Research, Women & tism spectrum disorder (ASD), gastrointestinal diseases (eg, inflammatory bowel disease
Children’s Health
and irritable bowel syndrome), and pediatric emergency care. The Table lists these studies,
with references.
Research Institute,
National Health and
Medical Research Oncology
Council (Australia), EU
Thirty-one studies on the use of CAM by pediatric oncology patients were identified be-
tween 1977 and 2011 from the United States, Canada, Europe, the Middle East, Malaysia,
Commission, Lotte &
Mexico, Singapore, the United Kingdom, Taiwan, and Australia. Sample sizes ranged from
John Hecht Memorial 15 to 1063 children; 19 studies had fewer than 100 participants. Rates of use ranged from
Foundation, and a low of 6% reported in 1983 to a high of 84.5% reported in 2009. Only 5 studies reported
Alberta Health rates below 20%. Spirituality/prayer, positive mental imagery, and natural health products
Services. This were the most popular CAM interventions.
commentary does
Of natural health products, multivitamins, megavitamins, and herbals were reported
most often. Patients, parents, and families described perceived efficacy from 0% to 83%
contain a discussion of
in the 16 articles that reported these data. Some of this variation appears to be re-
an unapproved/ lated to the expectation of what the CAM therapy will accomplish, as families reported
investigative use of multiple goals, including reinforcing the immune system, supplementing conventional
a commercial product/ medicine, counteracting adverse effects of conventional medicine, alleviating symptoms,
device. improving general well-being (psychological, emotional, and spiritual), and satisfaction
that everything had been tried. Of concern, but perhaps
not surprising, 11 studies also reported curing the cancer
as one of the family’s goals.
Abbreviations Fourteen articles reported on adverse events, which var-
ASD: autism spectrum disorder ied from 0% to 28%, but few details were provided. Only 8
CAM: complementary and alternative medicine articles reported on disclosure of CAM use to health care
practitioners, which varied from 0% to 89.9%. Eight studies
*CARE Program, University of Alberta, Edmonton, Alberta, Canada.

†
Edmonton General Hospital, University of Alberta, Edmonton, Alberta, Canada.

Table. Articles on the 5 Most Studied Pediatric Specialty Populations
Discussed
Most Popular CAM Use With
Citation Study Population Type of Study Main Results Interventions Physician Adverse Events
Laengler A, Spix C, Sample Size: 1063 Survey 37% of CAM Homeopathy 71% discussed 4% reported AEs
Seifert G, et al. Sample population: users had family (37%), dietary with GP,
Complementary children registered members who supplements pediatrician,
and alternative by German previously used (21%), and/or pediatric
treatment Childhood Cancer CAM; 35% of anthroposophic oncologist
methods in Registry in 2001 participants used medicine
children with Location: Germany; CAM, patients used (including
cancer: German hospitals between 1 and 15 mistletoe
a population- that treat pediatric types of CAM; 69% therapy, 22%)
based cancer of treatments were
retrospective whole medical
survey on the systems and 53%
prevalence of were biologically
use in Germany. based practices;
Eur J Cancer. most used CAM for
2008;44 more than 1 year
(15):2233–
2240.
Clerici CA, Sample size: 97 Self- 12.4% used Homeopathy, Not reported Asked but none
Veneroni L, Sample population: administered at least one plant therapy reported any AE
Giacon B, Children who survey type of CAM
Mariani L, were hospitalized,
Fossati-Bellani F. attending the
Complementary outpatient clinics
and alternative and either receiving
medical therapies treatment or being
used by children followed up by the
with cancer pediatric oncology
treated at an unit
Italian pediatric Location: Italy,
oncology unit. Hospital
Pediatr Blood
Cancer.
2009;53
(4):599–604.
Genc RE, Sample size:112; Self-administered 77% used one Nettle, 63%; 26% Not reported
Senol S, Sample population: questionnaire or more prayer, 55%; discussed
Turgay AS, pediatric cancer types of CAM salvia with
Kantar M. patients; officinalis, 29%; oncologist
Continued

complementary medicine utilization surveys
Table. (Continued)
Discussed
Complementary Location: Turkey, vitamins or

and alternative University Oncology supplements, 28%
medicine used by Hospital
pediatric patients
with cancer in
Western Turkey.
Onc Nurs Forum.

2009;36(3):
e159–e164.
Hamidah A, Sample size: 97 Questionnaire 84.5% use at Water therapy, 15% of users Not reported
Rustam ZA, Sample population: least one form 78% (drinking sought advice
Tamil AM, Children of CAM; 62% spring water from from medical
et al. Prevalence with cancer used more than the well of ZAM practitioners
and parental diagnosed between one type ZAM in Mecca and on CAM use
perceptions of 1995 and 2006 Diamond Spring
complementary Location: Malaysia, Water; Spirulina,
and alternative pediatric oncology 33%; vitamin C,
medicine use by center at University 27%; multivitamins,
children with Hospital in Kuala 23%; traditional
cancer in a multi- Lumpur healers, 22%; sea
ethnic southeast cucumber, 15%;
Asian population. TCM, 15%
Pediatr Blood
Cancer. 2009;52
(1):70–74.
Lengler A, Sample size: 1063 Questionnaire 35% had used 18% used 89.8% of Most parents did
Spix C, Sample population: anthroposophic anthroposophic - anthroposophic not answer this
Edelhuser F, children younger medicine homeopathic medicine users question
et al. than 15 years medication; 16% had spoken with
Anthroposophic diagnosed as received mistletoe a physician about
medicine in having cancer therapy the use of CAM
paediatric in 2001
oncology in Location: Germany
Germany: results
of a population-
based
retrospective
parental survey.
Pediatr Blood
Continued
Table. (Continued)
Discussed
Cancer. 2010;55
(6):1111–1117.
Tomlinson D, Sample size: 77 Questionnaire 55% had 22.1% considered, Not reported Not reported
Hesser T, Ethier Sample population: considered using 7.8% received
MC, Sung L. children with CAM, 29% had Whole Medical
Complementary cancer in actually used it Systems (including
and alternative palliative care homeopathy,
medicine use in Location: Canada, naturopathy, and
pediatric cancer Hospital for Sick TCM); 19.5%
reported during Children, Toronto considered, 5.2%
palliative phase of received)
disease. Support biologically based
Care Cancer. therapies
2011;19
(11):1857–
1863.
Al-Qudimat MR, Sample size: 69 Interview, 65.2% had used at 70.5% used 22.2% discussed Not reported
Rozmus CL, Sample population: questionnaire least one type of biological and the CAM
Farhan N. Family children with CAM during nutritional CAM strategies with
strategies for cancer under treatment of their (herbs/vitamins/ their attending
managing treatment and children; however, diet); 22.2% health care
childhood follow-up in 40% stopped using used body professionals
cancer: using a pediatric CAM for multiple and soul CAM
complementary oncology reasons strategies
and alternative department (music/imagery/
medicine in Location: Jordan acupuncture)
Jordan. J Adv
Nurs. 2011;67
(3):591–597.
Naja F, Sample size: 125 Telephone Overall, 15.2% of Dietary Of CAM users. No CAM AEs
Alameddine M, Sample population: survey respondents supplements 6 discussed reported
Abboud M, all pediatric reported using (most popular use, 13
Bustami D, Al oncology one or more was “black seed”), did not
Halaby R. patients from CAM therapies prayer/spiritual
Complementary 2005 to 2009 for their child healing, and
and alternative in 2 oncology unconventional
medicine use facilities cultural practices
among pediatric Location: Lebanon (ingesting bone
patients with ashes)
leukemia: the

Continued
Table. (Continued)
Discussed
case of Lebanon.
Integr Cancer
Ther. 2011;10
(1):38–46.
Paisley MA, Sample Size: 44 Questionnaire When frontline Prayer/spiritual 56% of Not reported
Kang TI, Insogna Sample population: therapy failed, healing (83%) respondents
IG, Rheingold SR. patients 52% increased and oral/dietary said their

Complementary 0-25 years their use of CAM, supplements oncologist
and alternative of age with 35% did not (31%) was aware of
therapy use in a diagnosis of change their all use, 39%
pediatric cancer being treated use of CAM, said their
oncology in the Division of and 13% oncologist was
patients with Oncology at The decreased their aware of
failure of Children’s Hospital use of CAM none or only
frontline of Philadelphia with some of their
chemotherapy. failure of frontline CAM use
Pediatr Blood therapy within last
Cancer. 2011; 60 days
56(7):1088– Location: United
1091. States, Children’s
Hospital
Philadelphia
Singendonk M, Sample size: 288 Prospective 42.4% reported Homeopathy Only one-third Not reported
Kaspers GJ, Sample population: multicenter CAM use; more (18.8%) of the
Naafs-Wilstra children attending study than 80% of the and dietary parents had
M, et al. High pediatric outpatient respondents supplements discussed
prevalence of clinics in academic identified a (11.5%) CAM use
complementary hospitals need for with their
and alternative Location: Netherlands information pediatric
medicine use in about CAM from oncologist
the Dutch their pediatrician
pediatric and 85.7% were
oncology positive toward
population: research on CAM;
a multicenter half of the parents
survey. Eur J were interested in
Pediatr. participating in
2013;172 future CAM trials
(1):31–37.
Asthma
Continued
Table. (Continued)
Discussed
Babayigit A, Sample size: 250 Questionnaire 46.4% had Herbal medicine, Not reported Not reported
Olmez D, Sample population: used CAM 29.7%;
Karaman O, children with in the past; quail eggs,
Uzuner N. asthma 23.6% used it 16.1%; Turkish
Complementary Location: Turkey in the last 6 honey, 14.4%;
and alternative months, and 11% used
medicine use in 39.6% of vitamins and
Turkish children them used minerals; 35.6%
with bronchial CAM in the used multiple
asthma. J Altern last 12 months CAM therapies
Complement
Med. 2008;14
(7):797–799.
Torres-Llenza V, Sample size: 2027 Questionnaire 13% used CAM; Vitamins (24%), Not reported Not reported
Bhogal S, Davis Sample population: used more homeopathy
M, Ducharme F. physician- in patients who (18%),
Use of diagnosed asthma were of acupuncture
complementary Location: Canada, preschool age, (11%)
and alternative Asthma Center, of Asian
medicine in Montreal ethnicity, or
children with Children’s who had
asthma. Can Hospital episodic
Respir J. 2010; asthma or poor
17(4):183–187. asthma
control
Cotton S, Sample size: 151 Questionnaire 71% used CAM 64% used 59% disclosed Not reported
Luberto CM, Sample population: in the past relaxation, their use
Yi MS, adolescents with month; 30% 61% prayer, of yoga; 57%
Tsevat J. asthma from the used prayer 33% reported
Complementary Teen Health Center; specifically for meditation, dietary
and alternative Location: United asthma symptom 31% guided changes
medicine States, Cincinnati management imagery
behaviors and Children’s Hospital
beliefs in Medical Center
urban (CCHMC)
adolescents
with asthma. J
Continued

Table. (Continued)
Discussed
Asthma. 2011;
48(5):531–538.
Luberto CM, Sample size:129 Self-report High and low Not reported Not reported Not reported
Yi MS, Tsevat J, Sample population: measures CAM users differed
Leonard AC, urban adolescents significantly
Cotton S. with asthma in terms of several
Complementary Location: United psychosocial health

and alternative States, Ohio outcomes, both
medicine use and cross-sectionally

psychosocial and longitudinally;
outcomes among in cross-sectional
urban adolescents multivariable
with asthma. J analyses,
Asthma. 2012;49 greater frequency
(4):409–415. of praying was
associated with
better
psychosocial
HRQoL
Philp JC, Maselli J, Sample size: 187 Cohort study CAM use is not Not reported Not reported Not reported
Pachter LM, Sample population: necessarily
Cabana MD. caregivers of “competitive” with
Complementary patients with conventional
and alternative asthma asthma therapies;
medicine use and Location: United families may
adherence with States incorporate
pediatric asthma different health
treatment. belief systems
Pediatrics. simultaneously in
2012;129(5): their asthma
e1148–1154. management
Shen J, Oraka E. Sample size: 5435 Survey 26.7% of children Breathing Not reported Not reported
Complementary Sample population: with current techniques
and alternative children with asthma reported (58.5%);
medicine (CAM) asthma from BRFSS CAM use in the vitamins
use among states report previous (27.3%) and
children with Location: United 12 months herbal products
current asthma. States (12.8%)
Prev Med.
Continued
Table. (Continued)
Discussed
2012;54(1):
27–31.
Autistic Spectrum Disorder
Christon LM, Sample size: 248 Online survey More than 70% had Lifetime use: Not reported 2.6% of parents
Mackintosh VH, Sample population: tried at least one special diet reported CAM
Myers BJ. Use of diagnosed as having CAM treatment and (29.4%), special made it worse
complementary autism at 21 years approximately half vitamins (27.0%),
and alternative or younger recruited were currently using animal therapy
medicine (CAM) through a number of one or more CAMs (23.8%), auditory;
treatments by autism centers/ current use:
parents of organizations vitamins (19.8%),
children with (national, state, special diet
autism spectrum and county) (14.1%)
disorders. Res Location: United
Autism Spectr States
Disord. 2010;4
(2):249–259.
Article I. Wong Sample size: 98 Interview- 40.8% used CAM Acupuncture, 22.4% 92.5% reported no
VCN. Use of Sample population: administered 47.5%; informed AEs; those AEs
complementary ASD children questionnaire TCM, 30% their reported
and alternative Location: China, physicians included: allergy,
medicine (CAM) Hospital diarrhea,
in autism assessment vomiting, general
spectrum center for ill health,
disorder (ASD): children with worsening of
comparison of neurodevelopmental disease symptoms
Chinese and disabilities
western culture
(Part A). J
Autism Dev
Disord. 2009;39
(3):454–463.
Frye RE, Sample size: 1023 Online survey Ketogenic diet Ketogenic diet Not reported Rate of AEs was
Sreenivasula S, Sample population: was perceived to higher with
Adams JB. Finnish children improve both traditional
Traditional and with ASD seizures and other antiepileptic
non-traditional Location: Finland clinical factors drugs than in
treatments for nonantiepileptic
autism spectrum drugs
disorder with

Continued
Table. (Continued)
Discussed
seizures: an on-
line survey. BMC
Pediatr.
2011;11:37.
Hall SE, Sample size: 452 Web-based Four general Gluten-free/ Not reported Not reported
Riccio CA. Sample population: survey factors emerge casein-free diet,
Complementary parents/caregivers as influencing the probiotics,

and alternative of children with decision-making v3 fatty acids,
treatment use for an ASD processes of and melatonin
autism spectrum Location: Internet, parents/caregivers

disorders. but mostly from this study:
Complement United States severity, child
Ther Clin Pract. willingness to
2012;18(3): engage in the
159–163. treatment, marital
status, and
educational level
Perrin JM, Sample size: 3173 Cross-sectional 28% reported CAM Special diets Not reported Not reported
Coury DL, Sample population: analysis use; 17% special
Hyman SL, et al. Autism Speaks diets and 20% other
Complementary Autism Treatment CAM; higher rates
and alternative Network patient of CAM use were
medicine use in registry associated with GI
a large pediatric Location: Canada symptoms
autism sample. and United
Pediatrics. States
2012;130
(suppl.2):S77–
S82.
Gastrointestinal Diseases
Gerasimidis K, Sample size: 86 Questionnaire 61% reported prior Dairy-free 27% discussed 1 respondent
McGrogan P, Sample population: CAM use to manage diet, 28%; with physician mentioned AEs
Hassan K, pediatric IBD IBD, 37% using at gluten-free diet, and 1 mentioned
Edwards CA. patients who time of recruitment; 15%; aloe, 19%; deterioration of
Dietary attended most had no opinion probiotics, 44%; disease condition
modifications, follow-up about CAM safety fish/v-3 oils, 27%
nutritional clinical
supplements appointments
and alternative Location: United
medicine in
Continued
Table. (Continued)
Discussed
paediatric Kingdom, Yorkhill

patients with Royal Hospital of
inflammatory Sick Children,
bowel disease. Scotland
Aliment
Pharmacol Ther.
2008;27(2):
155-165.
Vlieger AM, Sample size: 749 Questionnaire 37.6% had Herbal remedies, 51% discussed Not reported
Blink M, Sample population: used CAM in 46%; food CAM use with
Tromp E, outpatient patients past 12 months; supplements, their
Benninga MA. with functional and 63.7% of them 36%; manual pediatrician or
Use of organic GI disease had visited a CAM therapies, 23.7%; pediatric
complementary Location: Netherland, provider; the other homeopathy, gastroenterologist
and alternative GI outpatient clinics 36.3% used OTC 21.9%; energy
medicine by in academic remedies or received medicine, 17.3%;
pediatric patients hospitals and treatment from TCM. 10.8%
with functional teaching parents; 93% of
and organic hospitals parents consider it
gastrointestinal important for
diseases: results pediatricians to
from initiate research
a multicenter
survey. Pediatrics.
2008; 122(2):
e446–451.
Wong AP, Sample size: 362 Survey 49.6% use IBD: spiritual Not reported Some patients
Clark AL, Sample population: CAM in IBD intervention, reported that
Garnett EA, children with group; 23% in nutritional some therapies
et al. Use of IBD or chronic chronic supplements, worsened their
complementary constipation constipation herbal remedies condition
medicine in Location: United Constipation:
pediatric States, pediatric herbal remedies,
patients with IBD centers in alternative
inflammatory San Francisco, practices,
bowel disease: Houston, Atlanta nutritional
results from supplements
a multicenter
survey. J Pediatr
Continued

Table. (Continued)
Discussed
Gastroenterol
Nutr. 2008;48
(1):55–60.
Cotton S, Sample size: 67 Questionnaire No correlation 62% used Not reported Not reported
Humenay Sample population: with quality prayer, 40%
Roberts Y, 12- to 19-year of life and CAM relaxation, 21%
et al. Mind-body old patients with use, except lower imagery used

complementary IBD (including HRQoL scores with in last month
alternative Crohn disease) those that practice
medicine use and Location: United yoga; females, those

quality of life in States, Cincinnati with severe
adolescents with Children’s Hospital symptoms, younger
inflammatory Medical Center and adolescents, and
bowel disease. University Hospital, those with worse
Inflamm Bowel Cincinnati HRQoL more likely
Dis. 2010;16 to try CAM
(3):501–506.
Wadhera V, Sample size: 98 Cross-sectional 79% were using Nutritional More than Not reported
Lemberg DA, Sample population: study or had used CAM; supplements two-thirds
Leach ST, children 75.4% expressed (n[ 37, 56% discussed
Day AS. attending that they would use of CAM users) CAM use (47
Complementary gastroenterology CAM again; 80% and probiotics of 62 families)
and alternative clinics believed that (n[ 33, 50%)
medicine in Location: Sydney, physicians should
children Australia support the
attending use of CAM
gastroenterology
clinics: usage
patterns and
reasons for
use. J Paediatr
Child Health.
2011;47
(12):904–910.
Pediatric Emergency Care
Zuzak TJ, Zuzak- Sample size: 1143 Onsite self- 58% reported Not reported 50% did not Not reported
Siergast I, Sample population: complete patient had used discuss
Simoes-Wust Children attending questionnaire some form of CAM; CAM use
AP, Rist K, ED; 25% at present
Staubli G.
Continued
Table. (Continued)
Discussed
Use of Location: Switzerland, illness, 49% for

complementary University former illness
and alternative Children’s
medicine by Hospital, Zurich
patients
presenting to
a paediatric
emergency
department.
Eur J Pediatr.
2009;168:
431–37.
Goldman RD, Sample size: 1804 Questionnaire 32.3% of Multivitamins 38% did not Not reported
Vohra S, Sample population: families used discuss
Rogovik AL every third vitamins in CAM use
Vitamin use pediatric family in preceding 3
among children the ED from 12 pm months; of these
attending to 12 am, March to children, 61% used
a Canadian November 2004 them daily, 23%
pediatric Location: Canada weekly, 9.3% once
emergency a month, and 7.2%
department. in last 3 months
Fundam Clin
Pharmacol.
2011;25(1):
131–137.
Zuzak TJ, Zuzak- Sample size: 1143 Questionnaire Respondents Homeopathy Not reported 93% of the
Siegrist I, Rist L, Sample population: perceived the (77%), herbal respondents
Staubli G, Simo Children effectiveness of medicine (64%), indicated
AP. Medicinal attending ED CAM therapies in anthroposophic no AEs
systems of Location: Switzerland, general to be medicine (24%),
complementary University inferior to that of TCM (13%)
and alternative Children’s CM, although 49%
medicine: a cross- Hospital, Zurich of all respondents
sectional survey stated that CAM
at a pediatric therapies were more
emergency effective than CM in
department. certain cases/
J Altern against certain
Complement diseases and 13%

Continued
included some discussion of costs of CAM, with families

reporting spending US $0 to more than US $10,000.
Two studies reported cost as a deterrent to CAM use
Adverse Events
AE¼adverse effect; ASD¼autism spectrum disorder; BRFSS¼Behavior Risk Factor Surveillance System; CAM¼complementary and alternative medicine; CM¼complementary medicine; for some families.
ED¼emergency department; GI¼gastrointestinal; GP¼general practitioner; HRQoL¼health-related quality of life; IBD¼irritable bowel disease; TCM¼traditional Chinese medicine.
Asthma
Twelve studies on pediatric asthma and CAM use have
been identified from 1998 to 2010 from the United
States, the United Kingdom, Australia, Turkey, Canada,
Israel, and New Zealand. Sample sizes ranged from 48 to
CAM Use With
2027 children. Statistics on use of CAM ranged from 13%

to 89%, with 7 studies reporting rates higher than 50%
Discussed
Physician
and only 2 reporting rates below 20%. Concurrent use

was reported commonly, but 2 studies described CAM
as the primary treatment option by 27% and 44% of their
respondents.
The most popular CAM therapies used in asthma were
natural health products (eg, vitamins, minerals, herbals,
Most Popular
Interventions
oils, teas, and honey). Also common were prayer, home-

opathy, and massage therapy. Five of the studies provided
no description of how CAM was defined for the partici-
pants. Seven studies reported on perceived efficacy, which
were as effective as
varied from 12.4% to 70%. Three studies discussed rea-

that CAM therapies
sons for using CAM, which included avoiding or reduc-

ing the amount of conventional medicine used, believing
Main Results
that CAM was natural and not harmful, and for treating
asthma symptoms. Only 3 studies reported on whether
the participants had informed their physicians of their
CM
CAM use, which varied from 18% to 54%. Only 1 study

reported on adverse events. One study reported a mean
of US $66 (median, US $44) per month spent on various
CAM modalities.
Type of Study
Autistic Spectrum Disorder

Eight studies on the use of CAM by children with ASD
were identified from 2003 to 2009. The studies were con-
ducted in the United States, Canada, and China, and there
was 1 international study. Sample sizes varied from 50 to
552 children, and rates of use ranged from 31.7% to 95%.
Study Population
Special diets, such as the gluten-free, casein-free, or Fein-

gold diets, and vitamin and mineral supplements were the
most common forms of CAM used. Four studies reported
on perceptions of efficacy, which were positive more than
50% of the time. Two studies reported on reasons for use,
which included following advice from family or medical
(Continued)
Med. 2010;16
(4):473–479.
practitioners, intending to treat general or specific symp-

toms to improve quality of life, or maintaining general
health. One study reported users having high expectations,
Citation
with 1 in 20 expecting the child to become healthy.

Table.
The 3 studies that discussed perceived efficacy all

reported positive rates above 50%. Three studies reported

on adverse events: 1 study described that “very few families (eg, vitamins, minerals, and oils) were the most com-
reported that any therapy was actually harmful,” and 2 monly reported CAM therapies. Two studies reported
reported rates of adverse effects between 2.6% and 7.5%. on perceived efficacy: a positive perception occurred in
Only 1 study reported on how many families or patients 90% and 91% of respondents.
discussed their CAM use with their health care professio- Four studies asked about adverse events: 2 reported
nals (22%). Only 2 studies reported on costs: 1 study found none, whereas the other 2 provided few details. Six of
that, on average, 44.7% of the families found the costs as- the studies reported on whether patients discussed CAM
sociated with some CAM therapies difficult to meet. use with their physicians and whether this practice meant
that the emergency physicians or their family physicians
Gastrointestinal Diseases were aware was not always clear. One study found that
Seven studies were published from 2002 to 2010 on the families reported CAM use only if they were asked.
use of CAM by pediatric patients with gastrointestinal Reporting rates varied from 45% to 72%. No studies
diseases, primarily inflammatory bowel disease and irri- reported on how often physicians inquired about CAM
table bowel syndrome, from the United States, United use. Two studies reported on economic issues through
Kingdom, Europe, and Australia. Sample sizes ranged the discussion of insurance coverage for CAM.
from 46 to 749 patients. The reported rates of use ranged
from 36% to 72%. Six studies reported on CAM most
commonly used by their study populations: herbal med-
icines, dietary supplements (vitamins, fish oils, and probi- Summary
otics), and special diets (eg, dairy-free and gluten-free
diets) were the most popular. Six studies included in- We have reaffirmed the heterogeneity in pediatric CAM
formation on the perception of efficacy. Most studies re- use research identified by Ernst in 1999. (2) Although
ported rates of at least moderate satisfaction in perception CAM use is common, the types of CAM used and pat-
of efficacy by more than half of the respondents. Reasons terns of use vary among specialty populations, as do the
for using CAM included to feel better, to complement patients’ perceptions of effectiveness. Health care prac-
standard care, to address dissatisfaction with prescribed titioners do not ask consistently about CAM use, but it
medications vis-à-vis adverse effects and efficacy, to fol- is important to do so because patients and families of-
low advice from a trusted individual, and the belief that ten do not volunteer that information, and many want
CAM is always natural and safe. Only 3 studies reported physicians to ask. The American Academy of Pediatrics
on the occurrence of adverse events related to CAM ther- Section on Integrative Medicine offers a comprehensive
apy, and none provided rates. Four studies reported list of resources for health care professionals, including
whether families spoke with their physicians about their a parent education brochure and a How to Talk to Your
CAM use; disclosure rates ranged from 24% to 51%. Doctor poster. Health care practitioners also should in-
Two studies reported on costs associated with CAM ther- quire about reasons for use, perceptions of efficacy, ad-
apy, but they discussed only whether families found CAM verse events, and cost. Contextualization of CAM use
expensive and not how much was spent. will allow better patient counseling.
Pediatric Emergency Care

Seven studies on the use of CAM by pediatric emergency
patients have been identified from 2001 to 2010 in the
United States, Canada, and Switzerland (the 2 from References
Switzerland used the same data set). Sample sizes ranged 1. Ernst E. Prevalence of complementary/alternative medicine for
children: a systematic review. Eur J Pediatr. 1999;158(1):7–11
from 142 to 1804 patients. Published rates of use ranged 2. Surette S, Vanderjagt L, Vohra S. Surveys of complementary and
from 7% to 58%. Homeopathy, naturopathy, and use alternative medicine usage: a scoping study of the pediatric literature.
of natural health products and dietary supplements Comp Ther Med. 2013;21(suppl 1):S48-S53.


1. Which of the following forms of complementary and alternative medicine (CAM) is used most commonly by
patients with childhood cancer?
A. Herbals.
B. Megavitamins.
C. Multivitamins.
D. Massage therapy.
E. Spirituality/prayer.
2. Which of the following statements about the incidence of adverse events associated with CAM therapies is
correct?
A. Use of CAM in patients with cancer is most likely to be associated with an adverse event.
B. Homeopathy is associated with the highest incidence of adverse events.
C. The incidence of adverse events is higher in patients receiving conventional medicine.
D. The overall mean incidence of adverse events appears to be approximately 1%.
E. The incidence cannot be determined because many studies do not report adverse events.
3. Pediatric patients who use CAM are:

A. Likely to refuse conventional treatment.
B. Likely to use 2 or more CAM modalities concurrently.
C. Likely to use vitamin-based modalities exclusively.
D. More likely to disclose use if a practitioner asks.
E. Unlikely to try a special diet.
4. An important myth to dispel among users of CAM is:

A. CAM should be used in conjunction with conventional therapy.
B. CAM remedies are natural and always safe.
C. CAM treatments can worsen an underlying condition.
D. Treatments may reduce adverse effects of conventional medicine.
E. Two modalities can be used concurrently.
5. Among the following, the effect that CAM therapy is LEAST likely to have during cancer treatment is:
A. Alleviating symptoms.
B. Counteracting adverse effects of chemotherapy.
C. Curing the disease.
D. Improving general well-being.
E. Reinforcing the immune system.

• English: http://www.healthychildren.org/English/health-issues/conditions/treatments/Pages/Complementary-and-
Alternative-Medicine.aspx
• Spanish: http://www.healthychildren.org/spanish/health-issues/conditions/treatments/paginas/complementary-and-
alternative-medicine.aspx
• English: http://www.healthychildren.org/English/health-issues/conditions/treatments/Pages/Natural-Therapies.aspx
• Spanish: http://www.healthychildren.org/spanish/health-issues/conditions/treatments/paginas/natural-therapies.aspx

index of suspicion
Case 1: Fever, Diarrhea, Jaundice, and Confusion in an

18-Year-Old Male
Case 3: Red Urine in a 4-Month-Old Boy
Case 1 Presentation 7.3 mg/dL (124.9 mmol/L); albu-
An 18-year-old male with a 3-year min, 2.7 g/dL (27 g/L); prothrombin
history of alcohol abuse is referred time, 19.2 seconds; and international
from a rehabilitation center for fever, normalized ratio, 1.4. Ethanol and
The reader is encouraged to write nausea, and nonbloody diarrhea for acetaminophen were not detected
possible diagnoses for each case before 3 days. Six weeks ago, he enrolled in the serum.
turning to the discussion.
in an alcohol rehabilitation program A chest radiograph reveals a right
and stopped drinking alcohol. Three pleural effusion (Figure 1). A finding
weeks later, he noticed yellowing of on physical examination leads to the
The reader is encouraged to write his eyes and skin, difficulty sleeping, diagnosis.
possible diagnoses for each case and dyspnea.
before turning to the discussion. We On examination, his temperature
is 100.6°F (38.1°C), blood pressure
invite readers to contribute case Case 2 Presentation
is 99/62 mm Hg, pulse is 124 beats
presentations and discussions. Please A 6-month-old girl becomes ill with
per minute, and respiratory rate is 24
inquire first by contacting Dr. Deepak fever, vomiting, and diarrhea after
breaths per minute. He is slow to an-
Kamat at [email protected].
drinking tap water during a boil wa-
swer questions. There is no asterixis.
ter alert in the Southeast region of
He appears thin and jaundiced with
the United States, which had recently
enlarged parotid glands. Decreased
been devastated by Hurricane Katrina.
Author Disclosure breath sounds are noted on the right. She presents to an overwhelmed local
Drs Ku, Thomas, Ho, Whipple, Abdul- A tender, enlarged liver and mild ab- emergency department in shock with
Rahman, Megason, Herrington, dominal distension are noted. Trace severe anemia. She is stabilized and
bilateral lower-extremity edema is pres- evacuated to our institution.
Carmody, and Charlton have disclosed
ent. No stigmata of chronic liver dis- On arrival, her rectal temperature
no financial relationships relevant to
ease are found. is 100.4°F (38.0°C), heart rate is 179
this article. This commentary does not Laboratory findings reveal the fol- beats per minute, respiratory rate is
contain a discussion of an lowing: white blood cell count, 47 breaths per minute, and blood
unapproved/investigative use of 25,600/mL (25.6 109/L) (87% pressure is 66/18 mm Hg. Growth
a commercial product/device. neutrophils); hemoglobin, 8.2 g/dL parameters reveal that her weight is
(82 g/L); mean corpuscular volume, below the fifth percentile, her length
106 fL; platelets, 40 103/mL is at the 25th percentile, and her head
(40 109/L); sodium, 135 mEq/L circumference is at the 10th percen-
(135 mmol/L); potassium, 3.5 tile. She is lethargic and hypotonic
mEq/L (3.5 mmol/L); chloride, 106 with diffuse pallor. Capillary refill time
mEq/L (106 mmol/L); bicarbonate, is prolonged at 4 seconds. The rest of
15 mEq/L (15 mmol/L); blood urea the examination findings are normal.
nitrogen, 24 mg/dL (8.6 mmol/L); Initial laboratory results are as fol-
creatinine, 1.01 mg/dL (89 mmol/L); lows: white blood cell count, 1.4
glucose, 118 mg/dL (6.6 mmol/L); al- 103/mL (1.4 109/L) (neutrophils-
kaline phosphatase, 182 U/L; aspartate segmented, 42%; neutrophils-bands,
aminotransferase (AST), 194 U/L; 16%; lymphocytes, 20%; monocytes,
alanine aminotransferase (ALT), 71 20%; and basophils, 2%); hemoglo-
U/L; total bilirubin, 11.8 mg/dL bin, 1.9 g/dL (19.0 g/L); platelet
(201.8 mmol/L); direct bilirubin, count, 106 103/mL (106 109/L);

index of suspicion
external genitalia. There is a small

amount of orange-red, chalky residue
in the diaper.
Results of laboratory evaluation
indicate normal serum electrolyte,
blood urea nitrogen, and creatinine
levels. A dipstick urinalysis reveals a
specific gravity of 1.007, pH 5.0,
and no protein, blood, glucose, leu-
kocyte esterase, or nitrite; the micro-
scopic examination reveals a few
amorphous urate crystals but no
casts and 1 to 3 red blood cells per
high-power field. The urine calcium-
creatinine ratio is calculated to be
0.68 (normal for age, <0.86). Addi-
tional laboratory evaluation confirms
the diagnosis.
Case 1 Discussion
A hepatic bruit was heard on auscul-
tation. The history and physical exam-
ination findings led to the clinical
Figure 1. Chest radiograph reveals a large right-sided pleural effusion. diagnosis of acute alcoholic hepatitis.
Abdominal ultrasonography re-
vealed a fatty liver and trace ascites.
corrected reticulocyte count, 0.2%; occurred on 2 occasions in the past Thoracentesis revealed a transudative
serum sodium, 143 mEq/L (143 week. He was well until 5 days earlier, pleural effusion, consistent with he-
mmol/L); potassium, 3.7 mEq/L when he developed a temperature of patic hydrothorax. The results of se-
(3.7 mmol/L); chloride, 111 mEq/L 100.9°F (38.3°C), congestion, rhi- rologic evaluation for viral hepatitis
(111 mmol/L); bicarbonate, 6 norrhea, and cough. His interest in (A, B, and C), autoimmune hepati-
mEq/L (6 mmol/L); blood urea ni- breastfeeding has decreased, although tis, hereditary hemochromatosis, a1-
trogen, less than 3 mg/dL (<1.1 he continues to feed every 3 to 4 antitrypsin deficiency, and Wilson
mmol/L); creatinine, 0.3 mg/dL hours. History is negative for vomit- disease were negative.
(27 mmol/L); glucose, 136 mg/dL ing, diarrhea, irritability, excessive
(7.6 mmol/L); and lactic acid, 64.9 crying, or edema. The Condition
mg/dL (7.2 mmol/L). Viral studies He was born at 38 weeks’ gesta- Acute alcoholic hepatitis is a clinical
and cultures for bacteria are performed, tion, weighing 3,520 g. He has never diagnosis that is easily missed in the
the results of which are negative. Addi- been hospitalized or undergone sur- absence of a high index of suspicion.
tional investigations, including bone gery. The family history is negative Patients often present with acute on-
marrow examination, help to confirm for hematuria, end-stage renal dis- set of jaundice, abdominal pain, and
the diagnosis. ease, and nephrolithiasis. fever after a brief period of absti-
On physical examination, he is nence. On examination, tender hepa-
happy and well-appearing, with nor- tomegaly and ascites are common.
Case 3 Presentation mal vital signs for age and normal hy- The presence of a hepatic bruit, which
A previously healthy 4-month-old dration status. The abdomen is soft occurs due to turbulent arterial blood
boy is brought to the clinic by his par- and nontender. There is no bruising flow through the liver, can help con-
ents, who are concerned about bright or cutaneous trauma noted. He is firm the diagnosis, although its pres-
red urine in his diaper that has now circumcised, with normal-appearing ence is not required for diagnosis.

index of suspicion
Typical laboratory findings in- utility of liver biopsy must be Education on abstinence is crucial
clude leukocytosis with neutrophil weighed against the risk of bleeding because continued alcohol abuse is
predominance and immature band because these patients often present detrimental to recovery.
forms seen on peripheral blood smear. with coagulopathy. Patients with severe alcoholic hep-
Conjugated hyperbilirubinemia and atitis who do not respond to treat-
elevated AST and ALT levels are hall- Differential Diagnosis ment but achieve a 6-month period
mark features. The AST:ALT ratio is Alternative diagnoses to consider in- of sobriety should be referred for liver
greater than 2:1, and transaminase clude viral- and drug-induced liver transplantation evaluation. Transplan-
levels are usually elevated but less injury, Wilson disease, a1-antitrypsin tation is challenging in patients with
than 500 U/L. Evidence of impaired deficiency, and autoimmune liver dis- alcoholic hepatitis because many pa-
hepatic synthetic function, including ease. In addition, ascending cholangitis tients continue to consume alcohol.
hypoalbuminemia and prolonged pro- and pyogenic hepatic abscesses should Unfortunately, patients with severe
thrombin time, may be present. Mac- also be considered. In up to 20% of alcoholic hepatitis often do not sur-
rocytosis in the absence of B12 or individuals, an underlying liver disor- vive long enough to become eligible
folate deficiencies is suggestive of der is present concomitantly with al- for transplantation.
long-term alcohol abuse. coholic hepatitis. Our patient’s Maddrey DF score
Although alcoholic hepatitis usu- was 40. He was treated with prednis-
ally occurs in the setting of chronic Management and Prognosis olone for 1 month with a slow taper,
alcohol abuse, it can occur after a The mainstay of treatment for severe and his laboratory values normalized
short duration of alcohol abuse as alcoholic hepatitis is corticosteroids. after 3 months.
well. The development of alcoholic Mild cases of alcoholic hepatitis may
hepatitis is not entirely dose depen- not require any treatment; however, Lessons for the Clinician
dent; comorbidities and genetic sus- corticosteroids decrease mortality in
• Alcoholic hepatitis is a clinical di-
ceptibility may also contribute. Our severe disease. The decision to treat
agnosis that requires a high index
patient reported only a 3-year history with corticosteroids is based on the
of suspicion.
of intermittent binge drinking; how- Maddrey discriminant function (DF)
• Acute onset of jaundice, fever, ten-
ever, underreporting was suspected, score, which is calculated as 4.6
der hepatomegaly, and a hepatic
which is common in patients with al- (prothrombin time – control pro-
bruit should prompt consideration
coholic hepatitis. thrombin time) þ serum bilirubin.
of alcoholic hepatitis.
Abdominal ultrasonography is A DF greater than 32 predicts 35%
• Typical laboratory results include
recommended to exclude biliary ob- to 45% mortality at 1 month and is
leukocytosis with neutrophil pre-
struction as a cause of direct hy- an indication for steroid therapy.
dominance, immature band forms,
perbilirubinemia. Treatment with The recommended treatment reg-
direct hyperbilirubinemia, and ele-
broad-spectrum antibiotics, such as imen is prednisolone for 4 weeks fol-
vated AST and ALT levels of less
piperacillin-tazobactam or carbapenems, lowed by a taper. After 1 week of
than 500 U/L.
is often empirically initiated after therapy, the Lille score, which is
• Prompt diagnosis and treatment
performing blood and urine cultures based on age, prothrombin time, bil-
with prednisolone can improve
because the clinical presentation can irubin, albumin, and serum creatinine,
mortality in patients with severe al-
closely mimic ascending cholangi- should be calculated to determine
coholic hepatitis and a Maddrey
tis. In addition, an acetaminophen whether continued corticosteroid ther-
discriminant function score greater
level should be determined early to apy is beneficial.
than 32.
avoid missing drug-induced liver In patients in whom corticoste-
• Infection and toxic ingestion should
injury. roids are contraindicated, pentoxifyl-
be ruled out early and before initi-
The histologic progression of line may be an alternative option.
ation of corticosteroid therapy.
alcohol-induced liver damage begins Pentoxifylline may improve morbid-
with steatosis and inflammation and ity in patients with hepatorenal syn- (Elaine Ku, MD, University of
progresses to cirrhosis. Liver biopsy drome; however, its effect on overall California, San Francisco, CA;
is not necessary for definitive diagno- mortality is unclear. Because most Michelle Thomas, MD, and Cynthia
sis; however, biopsy is useful to ex- patients with alcoholic hepatitis have H. Ho, MD, Los Angeles County and
clude other causes of liver disease evidence of malnutrition, close atten- University of Southern California Med-
and can aid in prognostication. The tion to calorie intake is paramount. ical Center, Los Angeles, CA)

index of suspicion
with a nonneuromuscular expres- and a Southern blot analysis of blood

Case 2 Discussion sion. There is no ethnic or racial and bone marrow confirms a mtDNA
Bone marrow examination revealed predilection. deletion. Death in infancy is common
vacuolated hematopoietic precursors A diagnosis of Pearson syndrome and is usually due to severe infection,
(Figure 2). Stool pancreatic elastase may be suspected when a child pres- metabolic crisis, liver failure, or heart
levels were less than 10 mg/g of fe- ents, usually in the first year of life, block.
ces, implying severe pancreatic in- with any combination of the follow- The etiology of Pearson syndrome
sufficiency. Thus, our patient was ing: refractory sideroblastic anemia is complex and not well understood.
diagnosed as having Pearson syn- (usually macrocytic), pancytopenia, In addition to mtDNA, certain trans-
drome (Pearson marrow-pancreas syn- infection, chronic diarrhea with fatty fer RNAs and ribosomal RNAs may
drome). Southern blot analysis of stools, lactic acidemia, and metabolic be deficient, impairing the translation
blood and bone marrow confirmed acidosis. Bone marrow failure and exo- of messenger RNA into proteins. De-
a mitochondrial DNA (mtDNA) de- crine pancreas involvement are prom- fective iron metabolism, manifesting
letion of approximately 4 kb, span- inent. The extent of multiple organ as sideroblastosis and hemosiderosis,
ning the ND4 gene to the CYTB involvement is variable and includes may be a key feature and can cause
gene. She was presumed to have a vi- hepatic, renal, cardiac, and endo- cellular injury to target tissues.
ral infection with metabolic crisis and crine failure. A diagnosis is made
acidosis—a characteristic presentation when a child’s bone marrow exami- Differential Diagnosis
of Pearson syndrome. She received a nation reveals the characteristic vac- Although disorders due to mtDNA
blood transfusion and supportive care. uolated hematopoietic precursors mutations are inherited maternally,
Levocarnitine, coenzyme Q10, fat sol-
uble vitamin supplementation, and
pancreatic enzyme replacement were
prescribed. She clinically improved
with therapy but continued to re-
quire additional blood transfusions.
At age 9 months, she was hospital-
ized again with infection and meta-
bolic crisis. Her care was subsequently
transferred to a medical facility closer
to her home, and, unfortunately, she
died of overwhelming sepsis at age 15
months.
The Condition
Pearson syndrome is 1 of 3 overlap-
ping phenotypes due to a deletion
in mtDNA, the other 2 being
Kearns-Sayre syndrome and progres-
sive external ophthalmoplegia. As
with many disorders of energy me-
tabolism, Pearson syndrome presents
with multiorgan system failure due to
the deficiency of components of the
electron transport chain that results
in defective oxidative phosphorylation.
Defined as refractory sideroblastic
anemia with cytoplasmic vacuoliza-
tion of hematopoietic precursors and
deletion of mtDNA, it is the first Figure 2. Hematoxylin-eosin staining of bone marrow cells reveals cytoplasmic
mitochondrial disorder reported vacuolization of hematopoietic precursors.

index of suspicion
most cases of Pearson syndrome supplementation of fat soluble vita- and hearing loss. Other survivors
are sporadic due to the low likeli- mins help to alleviate the symptoms may be neurologically healthy.
hood that affected individuals will re- of pancreatic exocrine insufficiency.
produce. Absence of family history No dietary restrictions are required. Lessons for the Clinician
can often help distinguish it from The use of medications toxic to mito-
• Pearson syndrome is probably
similar causes of anemia and syn- chondria, including chloramphenicol,
underdiagnosed and must be
dromes of bone marrow failure, such aminoglycosides, linezolid, valproic
considered in infants and children
as X-linked sideroblastic anemia and acid, and nucleoside reverse transcrip-
with cytopenias associated with
Diamond-Blackfan anemia. Heredi- tase inhibitors, should be avoided.
failure to thrive, refractory anemia,
tary sideroblastic anemia lacks the The anemia is refractory, and patients
sepsis, acidosis, pancreatic insuffi-
characteristic vacuolization of hema- may be transfusion dependent. Prompt
ciency, and renal or liver disease
topoietic precursors, is not associated evaluation of fever, including paren-
and in infants with a history of hy-
with pancreatic insufficiency, and re- teral antibiotics and blood culture,
drops fetalis.
sponds to pyridoxine. In Diamond- and management of intermittent
• In the past, children with Pearson
Blackfan anemia, impaired ribosome metabolic crises with hydration and
syndrome were not expected to
biogenesis is the cause of erythroid correction of electrolyte abnormali-
survive past infancy or early child-
failure, and elevation in erythrocyte ties are critical. Because Pearson
hood. With proper diagnosis,
adenosine deaminase enzyme activity syndrome affects numerous organ
careful monitoring, and support-
supports the diagnosis. Nearly 50% of systems, collaboration from a multi-
ive care, children can live longer.
affected individuals have a variety of disciplinary team is the best therapeu-
physical abnormalities, including cra- tic approach. (Nicholas S. Whipple, MD, St. Jude
niofacial anomalies, hand and upper Children’s Research Hospital, Mem-
limb defects such as triphalangeal phis, TN; Omar Abdul-Rahman,
thumbs, and cardiac and urogenital Prognosis MD, Gail C. Megason, MD, Betty L.
malformations. Shwachman-Diamond Pearson syndrome is often fatal in in- Herrington, MD, University of Missis-
syndrome also consists of pancreatic fancy or early childhood (median sur- sippi Medical Center, Jackson, MS)
exocrine insufficiency, neutropenia, vival time, 4 years). The usual causes
and anemia; however, epiphyseal and of death are bacterial sepsis due to
metaphyseal dysostosis also occur, neutropenia, unremitting metabolic
and the anemia is much less prevalent crisis, and hepatic failure. The features
Case 3 Discussion
The infant’s serum uric acid level was
and severe when compared with Pearson of Pearson syndrome may change
found to be low at 2.1 mg/dL (125
syndrome. Exposure to chloramphen- over time. Some children may experi-
mmol/L) (reference range, 2.4-6.4
icol and dietary deficiencies of copper, ence a spontaneous recovery from
mg/dL [143-381 mmol/L]). How-
phenylalanine, and riboflavin may the hematologic and pancreatic dys-
ever, his urinary excretion of uric acid
also lead to vacuolization of hemato- function. Such case reports document
was elevated, particularly in the con-
poietic precursors and should be a phenotypic shift in these individuals
text of a low serum uric acid, with
ruled out by determining drug serum as a result of heteroplasmy, the coex-
a urine uric acid–urine creatinine
concentrations before diagnosing Pear- istence of both wild-type and mu-
ratio of 2.06 (reference range, 0.03-
son syndrome. tated mtDNA within the same cell.
1.03). These findings were support-
The mtDNA genotype can shift dur-
ive of a diagnosis of idiopathic renal
Management ing cell replication, and clinical fluc-
hypouricemia, a renal tubular disor-
There is no specific treatment avail- tuations may be due to the selective
der in which there is an isolated de-
able for individuals with Pearson syn- expansion of normal or abnormal
fect in the tubular reabsorption of
drome. Accurate diagnosis, supportive clones. However, these individuals
uric acid, leading to hypouricemia
care, and the awareness of possible often undergo a transformation from
and hyperuricosuria.
complications are essential in reduc- Pearson syndrome to Kearns-Sayre
ing morbidity and mortality. Levo- syndrome. Kearns-Sayre syndrome
carnitine and coenzyme Q10 are is characterized by progressive ptosis, The Finding
given to enhance the function of re- ophthalmoplegia, skeletal muscle The discoloration of the diaper was
sidual respiratory enzyme activity. weakness, impaired cognitive function, due to the presence of urate crystals,
Pancreatic enzyme replacement and cardiac conduction abnormalities, a frequent finding in many otherwise

index of suspicion
healthy infants. It is particularly com- IRH from Fanconi or Hartnup syn- experimental evidence implicates dam-
mon among breastfed newborns in dromes in which uric acid wasting age from reactive oxygen species. In
the first few days of life, when uric is a component of the syndromes. the context of vigorous exercise, vol-
acid excretion is high and urine vol- Evidence of proteinuria, glycosuria, ume depletion and renal vasocon-
umes tend to be low. However, in metabolic acidosis, or potassium or striction occur, which leads to
older infants and children with red phosphorus wasting suggests more subsequent reperfusion injury in
urine or in patients with a personal generalized proximal tubule dysfunc- the absence of intracellular urate-
or family history of nephrolithiasis, tion and should prompt further free radical scavengers. In addition,
overexcretion of uric acid should be evaluation. uric acid precipitation within the tu-
considered. Uric acid is a waste product—the bules further contributes to AKI.
Distinguishing uric acid crystalluria end product of dietary and endoge- Under this theory, renal reabsorp-
from hematuria is of great clinical im- nous purine metabolism—and hypo- tion of uric acid evolved as a protec-
portance. A urinalysis that indicates uricemia alone does not appear to tive mechanism to prevent oxidative
the absence of blood by dipstick and cause any clinically significant prob- injury to the proximal tubule in times
red blood cells on microscopic exam- lems. However, the hyperuricosuria of stress.
ination excludes hematuria, as it did in seen in IRH can lead to 2 noteworthy
this case. Alternatively, if the diaper is complications: uric acid nephrolithia- Management
allowed to dry, urate crystals typically sis and exercise-induced acute kidney Because IRH is caused by a molecular
turn into a salmon-colored residue injury (AKI). In most patients, it is defect, no specific therapy is yet avail-
that disintegrates into powder when these complications that lead to the able for the underlying disease pro-
scratched. This simple bedside test diagnosis, often much later in life. cess, and treatment focuses on
can allow distinction between hema- Uric acid stones occur in approxi- preventing the associated complica-
turia and urate crystalluria at home or mately 12.5% to 25% of patients with tions. Stones can be prevented in
in settings where urinalysis is not im- IRH. Importantly, uric acid stones most patients by increasing fluid in-
mediately available. are often radiolucent on plain radio- take and maintaining urinary alkalin-
graphs, necessitating a higher index ization. Allopurinol (a competitive
The Condition of suspicion and the use of computed inhibitor of xanthine oxidase, the en-
Idiopathic renal hypouricemia (IRH) tomography or ultrasonography for zyme that catalyzes the production of
is a rare autosomal recessive disorder diagnosis. uric acid) may also be helpful in pa-
caused by altered renal tubular urate Exercise-induced AKI occurs in tients with recurrent stones and per-
transport. The defect appears to be approximately 6.5% of patients with sistent hyperuricosuria. No treatment
a mutation in the human urate trans- IRH. In a reported case series, there has been proven to be effective for
porter 1 (hURAT1), an organic anion was a 200-fold increase in exercise- the prevention of exercise-associated
transporter in the proximal tubule en- induced AKI compared with the gen- AKI in controlled trials, although al-
coded by the gene SLC22A12, which eral population. The diagnosis of lopurinol appears to be helpful in
maps to chromosome 11q13. A vari- IRH should, therefore, be considered some patients.
ety of mutations have been described, in any patient in whom this complica- Our patient was treated with
each of which leads to absent or sig- tion develops without evidence of sodium and potassium citrate for
nificantly decreased hURAT1 acti- rhabdomyolysis (a much more com- urinary alkalinization and kidney
vity. URAT1 is expressed in the mon cause of exercise-induced AKI). stone prophylaxis, and counseling
luminal membrane of proximal tu- Paradoxically, the diagnosis of IRH was provided to his parents regard-
bular cells and is responsible for may be difficult to establish in the ing the inheritance pattern of IRH.
most proximal urate reabsorption. context of AKI because serum uric At age 2 years, he remains clinically
IRH has been identified in patients acid levels may be artificially elevated asymptomatic and well-appearing.
from a variety of ethnic backgrounds, into the reference range by the low
although it seems to be more com- glomerular filtration rate. Establish-
Lessons for the Clinician
mon in patients of Japanese ancestry. ing the diagnosis definitively may re-
Heterozygote carriers are clinically quire repeating the serum uric acid • Urate crystals are a common and
silent. levels on resolution of the AKI. normal finding in newborns in
It is important to distinguish the The pathogenesis of AKI remains whom feeding has not been well
isolated proximal tubule defect in unclear, although theoretical and established, but this finding in

index of suspicion
older infants should raise suspicion stones and exercise-induced acute Nephrology, University of Virginia
for hyperuricosuria. kidney injury. Children’s Hospital, Charlottesville, VA)
• Idiopathic renal hypouricemia is • Treatment with allopurinol may be
To view Suggested Reading lists
caused by defects in renal tubular helpful in severely affected patients.
for these cases, visit http://pedsinreview.
urate transport and can lead to 2 (J. Bryan Carmody, MD, and Jennifer aappublications.org and click on the
important complications: uric acid R. Charlton, MD, Division of Pediatric “Index of Suspicion” Link.

in brief
In Brief
Von Willebrand Disease
Stacy Cooper, MD identified in this protein, encompassing anti-inflammatory drugs the most
Clifford Takemoto, MD the spectrum of single missense muta- common pediatric culprits but aspi-
Charlotte Bloomberg Children’s Center, tions to large deletions. Because of var- rin-containing products also worthy
Johns Hopkins Hospital iation in the diagnostic criteria for vWD, of consideration). Other important in-
Baltimore, MD debate exists regarding the prevalence; formation to obtain is the patient’s
however, some studies estimate it to be history of bleeding with hemostatic
as high as 1% to 2% of the population challenges (such as operations and
Author Disclosure when including children and adults. minor trauma). However, young chil-
Dr Cooper has disclosed no financial There are 3 major categories of vWD, dren with vWD may have an unremark-
relationships relevant to this article. classified as partial deficiency of vWF able bleeding history because of their
Dr Takemoto has disclosed a research (type 1), functional defects (type 2), young age and not yet having experi-
and complete deficiency of vWF (type enced any bleeding challenges or past
grant from Novo Nordisk for
3). Type 2 can be further subcategorized surgical history. Thus, a comprehensive
hemophilia factor trials at Johns based on the 4 subtypes of specific family history is also an essential part
Hopkins University. This commentary qualitative defects of the multimers of the workup for suspected bleeding
does not contain discussion of (types 2A, 2B, 2M, and 2N). The differ- disorders.
unapproved/investigative use of ent types of vWD vary in severity. Type 1 The evaluation and diagnosis of a
a commercial product/device. is the most common, an autosomal dom- child with vWD are complicated by the
inant disorder that comprises approxi- mild bleeding symptoms encountered
mately 75% of vWD patients, and is in the healthy population. Several bleed-
usually confined to mild bleeding. Type ing scoring systems have been developed
Von Willebrand Disease (VWD):
Evidence-Based Diagnosis and 2 may demonstrate either dominant or to determine the likelihood of vWD in
Management Guidelines, The recessive inheritance, and type 3 is au- adults; however, many of these have
National Heart, Lung, and Blood tosomal recessive, with types 2 and 3 not been validated in children. Further-
Institute (NHLBI) Expert Panel often involved in more serious bleeding more, although these bleeding scores
Report (USA). Nichols W, Hultin MB, presentations. may be useful to identify individuals
James AH, et al. Haemophilia. 2008; Most often vWD presents with muco- who have a low likelihood of vWD, asymp-
14(2):171–232 cutaneous bleeding. Common symptoms tomatic children with a positive family his-
Bleeding Scores: Are They Really Useful? include epistaxis, easy bruising, and tory may still deserve a workup because of
O’Brien SH. Am Soc Hematol Educ menorrhagia. Bleeding episodes are usu- the lack of hemostatic challenges.
Program. 2012;2012(1):152–156
ally mild and self-resolving but in some The initial workup for all children with
Von Willebrand Disease. Montgomery G,
cases may be significant and require in- a suspected bleeding disorder should in-
Cox JG. In: Orkin SH, Nathan DG,
Ginsburg D, Look AT, Fisher DE, Lux SE, tervention. Type 3 vWD and other more clude a complete blood cell count with
Lantigua CJ. Nathan and Oski’s severe forms may present with less com- a blood smear to evaluate for anemia or
Hematology of Infancy and Childhood. mon serious bleeds, such as hemarthrosis thrombocytopenia and prothrombin time
7th ed. Philadelphia, PA: Saunders; or gastrointestinal bleeding. and activated partial thromboplastin time
2009:1487–1524 When evaluating a child with con- to screen for coagulation factor deficien-
cern for abnormal bleeding, it is impor- cies. The activated partial thromboplastin
Von Willebrand disease (vWD) is an in- tant to detail the age at onset, location time may be prolonged in some patients
herited bleeding diathesis. It is caused of bleeding, and whether the bleeding with vWD but is most often normal. Thus,
by quantitative or qualitative defects occurs spontaneously or is trauma in- a directed vWD workup may still be ap-
in von Willebrand factor (vWF), which duced. Additional assessments include propriate based on clinical assessment
functions to bind platelets to damaged the duration of bleeding, whether inter- even if the initial screen result is normal.
endothelium and to stabilize factor VIII vention was needed, and any concurrent Specific vWD testing begins with 3
(FVIII). A range of mutations have been medications taken (with nonsteroidal laboratory tests: vWF antigen (vWF:

in brief
Ag), vWF activity (vWF ritocetin cofac- warrant treatment or intervention if options available for active bleeding
tor [vWF:RCo] activity), and FVIII level. significant. and surgical prophylaxis.
The most common type of vWD, type Treatment of vWD is reserved for ac-
1, is characterized by a quantitative re- tive bleeding symptoms or prophylaxis Comments: Drs Cooper and Takemoto
duction of both vWF:Ag and vWF:RCo. for surgical procedures. Desmopressin, summarize the challenges of diagnosing
The rarer vWD type 2 mutations usually a synthetic vasopressin analog, is com- vWD. A patient can present at any age
exhibit discordance between vWF:Ag monly used to promote release of vWF and may have negative laboratory results,
and vWF:RCo, with reduced activity from endothelial storage, also resulting yet a primary care clinician may still want
for antigen. vWD type 3 has no detect- in an improved FVIII half-life. Patients to pursue the diagnosis and repeat testing
able vWF antigen, and activity of FVIII with type 1 often respond well to desmo- if the bleeding history is significant. Use of
levels may be markedly decreased be- pressin; however, this treatment results bleeding scores may be helpful for primary
cause of the role of vWF in stabilizing in a variable response in type 2 and inad- care clinicians because the high negative
FVIII. equate response in type 3. Desmopressin predictive value may identify those for
Additional evaluation may also in- is generally well tolerated, but an impor- whom further testing or referral is not
clude platelet function testing, the re- tant adverse effect to be aware of is warranted. Several factors may influence
sults of which may be abnormal in hyponatremia. Hyponatremia is usually the levels of vWFs, such as the presence
vWD. Bleeding time can be abnormal avoided with water restriction, but in rare of lower plasma levels in those with O
in some patients with vWD; however, cases, seizures have been reported, par- blood type, whereas levels may be elevated
this test has been largely abandoned ticularly in young children. When desmo- in those with increased estrogen, such as
because of poor specificity and variabil- pressin is insufficient or contraindicated, during pregnancy or while taking an estro-
ity in execution and interpretation. Fur- plasma-derived vWF and FVIII purified gen-containing oral contraceptive. vWF is
ther testing for the vWF multimers is concentrates can be given. When con- also an acute-phase reactant, so it can be
helpful to distinguish the various sub- centrate is not available, cryoprecipitate elevated in those with an acute inflamma-
classes of type 2 vWD. may be used; however, this is usually re- tory process. Because different laboratories
Repeat testing may be needed if served for life-threatening bleeds, given may use different assays, it is important to
clinical suspicion is high but results infectious risks with this product. Ad- interpret results in consultation with a he-
were normal because numerous factors junctive measures include antifibri- matologist. Consultation is also helpful for
can affect vWF levels, such as estro- nolytic agents, such as aminocaproic patients with a concerning bleeding his-
gens, active bleeding, and stress. It is acid and tranexamic acid, which help tory and for assistance in patients with di-
also important to recognize that many clot stabilization. agnosed conditions who are experiencing
individuals may have borderline low As a common bleeding disorder, significant bleeding.
levels of vWF but not meet criteria vWD should be considered in patients
for vWD. However, these patients with a concerning personal or family Janet Serwint, MD
may have bleeding symptoms that bleeding history, with several treatment Consulting Editor, In Brief
Corrections
• In the February 2014 Pediatrics in Review article “Muscle Disease” (Tsao, C-Y. Pediatr Rev. 2014;35(2):49–61.
doi: 10.1542/pir.35-2–49), answer option “D” for quiz question 4 should read “Dermatomyositis.” This correction has
been made in the online quiz and the online version of the journal. The journal regrets the error.
• In the February 2014 article “Congenital Torticollis and Positional Plagiocephaly” (Kuo AA, Tritasavit S, and Graham Jr JM.
Pediatr Rev. 2014 ;35(2):79–87. doi:10.1542/pir.35-2–79), one of the images in Figure 3 is mislabeled. The second row of
printed headings should read, from left to right, “Prom Lrot¼ 86 . Prom Rrot¼78.” The Journal regrets the error.

visual diagnosis
15-Year-Old Girl With Fever,

Extremity Pain, and Unusual Rash
David Toturgul, MD,* Megan Yunghans, MD,† Jessica Kosut,
MD†
Presentation
A 15-year-old girl presents to the clinic with fever, rash,
and extremity pain associated with difficulty walking. The
patient had been in her usual state of health until 6 days
before admission, when she developed diffuse abdominal
pain, nonbilious and nonbloody emesis, and subjective
fever. The patient initially had been seen in the emer-
gency department (ED) 2 days before presentation and
underwent abdominal computed tomography (CT),
blood work, and urine studies. The abdominal CT re-
vealed a normal-appearing appendix and no evidence
of gastrointestinal obstruction. The blood work was no-
table for the following: white blood cell (WBC) count,
18,700/mL (18.7 109/L) with 39% band cells; hemo-
globin, 15 g/dL (150 g/L); hematocrit, 43.1; platelet
count, 94.0 103/mL (94.0 109/L); erythrocyte sed-
imentation rate, 30 mm/h; and C-reactive protein, 111
Figure 1. Nonblanching, tender, erythematous nodules are
located along the thenar eminences of the hands. mg/L (1057 nmol/L). The urinalysis revealed 0 to 5
WBCs, 2 to 5 red blood cells, a protein level of greater
than 300 mg/dL (3.0 g/L), and moderate bacteria
Author Disclosure (10-30 casts) but normal pH and negative leukocyte es-
Drs Toturgul, Yunghans, and Kosut have disclosed no terase and nitrite test results. A rapid streptococcal test
financial relationships relevant to this article. This result was negative. The patient was given a single dose of
ceftriaxone and sent home with a prescription for a 10-day
commentary does not contain a discussion of an unapproved/
course of cephalexin for presumed urinary tract infection.
investigative use of a commercial product/device. The next day she followed up with her pediatrician
and by that time had developed chills, extremity pain that
began in her lower extremities with progression to her
upper extremities, and a new rash on her palms and soles.
She had not filled the cephalexin prescription and was
given a new prescription for amoxicillin by her pediatri-
cian. Later, a blood culture obtained during the ED visit
was positive for gram-positive cocci in clusters, and the
patient was asked to return to the ED. By the time the
patient arrived at the ED for admission, her lower-
extremity pain had worsened and she was having diffi-
culty ambulating.
She has no known sick contacts, and her medical his-
tory is unremarkable. She had traveled to the Philippines
*Atlantic Health Sports Medicine, Morristown Medical Center, Morristown, NJ.

†
Division of Hospital Medicine, John A Burns School of Medicine, Honolulu, HI.

visual diagnosis
1 month before her illness. Her immunizations are up to of the left occipital lobe. A full-body bone scan revealed no
date, and she is not taking any medications. She is not abnormalities.
sexually active, denies drug or alcohol use, and resides
at home with her parents and sister. Discussion
On physical examination, the patient appears tired and Infective endocarditis (IE) currently accounts for 1 in ev-
weak. Her temperature is 101.9oF (38.8 oC), blood pres- ery 1,300 to 2,000 pediatric admissions each year, al-
sure is 98/56 mm Hg, respiratory rate is 20 breaths per though the incidence is increasing. Recently, the
minute, and heart rate is 101 beats per minute. She has overall percentage of patients with rheumatic heart dis-
bilateral nonpurulent conjunctivitis. Her oropharynx is ease has decreased, whereas the number of patients with
clear and her neck supple without significant lymphade- preexisting structural heart disease has increased. Reasons
nopathy. Cardiac examination reveals a III/VI harsh, sys- for this shift include better survival in patients with con-
tolic murmur over the entire precordium. The lungs are genital heart disease, advances in cardiac surgery, and reg-
clear to auscultation. The abdomen is mildly distended, ular use of indwelling central venous catheters in
nontender, and without hepatosplenomegaly. There is hospitalized children. Distribution of IE is bimodal,
no costovertebral angle tenderness. Nonblanching, tender, peaking in infancy and then again in late adolescence.
erythematous nodules were present on her hands and soles
of her feet, most notably along the thenar eminences (Fig 1).
She has generalized muscular pain in all 4 extremities that Skin Manifestations in IE
is worse with palpation and movement; however, there is Osler nodes are nodular, painful, erythematous lesions with
no specific localization, except for a maximal point of ten- pale centers found most commonly on the pads of the fin-
derness to the muscular aspect of her right shoulder. She gers or toes, the thenar and hypothenar eminences, and the
has full range of motion of her joints. Her neurologic ex- arms (Fig 1). These lesions occur in both acute and sub-
amination findings are within normal limits, including acute endocarditis and typically resolve within hours to days.
cognition and strength. Janeway lesions, in contrast, are macular, painless,
Blood work on admission is notable for a WBC count of hemorrhagic lesions that occur on the palms and soles
9,400/mL (9.4 109/L) and an elevated creatine kinase (Fig 2). These lesions occur more commonly in the acute
level of 661 U/L. Urinalysis reveals a low leukocyte esterase form or stage of illness, in association with S aureus infec-
level and 30 mg/dL of protein. A lumbar puncture is nota- tion, and may take several weeks to resolve. This case is
ble for 40 WBCs. Coagulation study findings are unremark- unique because of the observance of Janeway lesions,
able. Liver enzyme levels are elevated, with an aspartate which occur in less than 5% of children with endocarditis.
aminotransferase level of 153 U/L and an alanine amino- Osler nodes occur more commonly and in the preanti-
transferase level of 182 U/L. Two days after admission, biotic era were present in 10% to 90% of patients with
she develops nonblanching, erythematous, painless macules bacterial endocarditis. However, more recently, Osler
to the plantar region of her toes and her finger pads (Fig 2). nodes were observed in less than 10% of cases.
A study performed the next morning reveals the diagnosis.
Diagnosis: Infective Endocarditis With

Janeway Lesions and Osler Nodes, Myositis,
and Hepatitis
Echocardiography was performed and revealed vegeta-
tion on the mitral valve that measured 0.24 0.71 cm
(Fig 3), as well as mild mitral insufficiency. Original
and subsequent blood culture results were positive for
methicillin-sensitive Staphylococcus aureus (MSSA). A
clean-catch urine culture performed during the ED en-
counter 2 days before admission also yielded MSSA.
Brain magnetic resonance imaging (MRI) was notable
for small septic emboli in the gray-white matter, junc-
tional regions of the frontal-parietal lobes, and the left oc- Figure 2. Nonblanching, nontender, erythematous macules
cipital lobe. Mild edema was noted in the right corona are present on the plantar region of her toes. Similar lesions
radiata, the right cerebellar hemisphere, and the meninges are also present on her finger pads.

visual diagnosis
Classic findings typically associated with IE, such as Roth

spots, Janeway lesions, Osler nodes, and splinter hemor-
rhages, are uncommon in children, with less than 5% of pe-
diatric patients with IE presenting with any of these
findings. Most children with IE have a new or changing
murmur, which is likely due to the presence of the vegeta-
tion in conjunction with a high-cardiac-output state second-
ary to systemic illness. These findings may also be
accompanied by petechiae, hepatosplenomegaly, and con-
gestive heart failure.
The Duke Criteria, established in 1994 to achieve con-
sistency in the diagnosis of IE, incorporate clinical signs,
echocardiographic findings, and microbiologic cultures.
Figure 3. The echocardiogram revealed vegetation (arrow) on The clinical criteria are split into major and minor criteria,
the mitral valve, measuring 0.24 3 0.71 cm, and mild mitral and a diagnosis of IE may be established with 2 major, 1
insufficiency. major and 3 minor, or 5 minor criteria. The patient can
then be classified as having definite IE, possible IE, or re-
Both Janeway lesions and Osler nodes develop as a re-
jected IE. The major criteria include 2 positive results on
sult of small emboli from the cardiac vegetation, and the
blood cultures of typical microorganisms (>2 for less typ-
lesions may be septic or bland. Osler node culture results
ical organisms) and an echocardiogram supportive of IE.
have been consistently negative, whereas Janeway lesion
The minor criteria include the following: (1) predisposing
culture results tend to be positive. The Osler nodes, his-
heart condition, (2) fever, (3) vascular phenomena (eg,
tologically, are microabscesses adjacent to arterioles, con-
major arterial emboli, septic pulmonary infarcts, Janeway
sistent with a localized vasculitis. Janeway lesions are
lesions, and conjunctival hemorrhage), (4) immunologic
microabscesses with neutrophilic infiltration from small
phenomena (eg, glomerulonephritis, Osler nodes, Roth
vessels, such as capillaries.
spots, arthritis, and rheumatoid factor), and (5) a single
positive blood culture result.
Pathophysiology Blood culture results are positive in most patients with
Traditionally, viridans group streptococci was the most IE. Bacteremia in IE is generally continuous and pro-
common cause of IE. However, in some series, S aureus longed, so blood sampling need not be timed with fever.
has taken over as the major etiologic organism, followed To optimize the recovery of an organism, however, mul-
by viridans group streptococci, other streptococci, and tiple blood cultures should be performed. At least 3
coagulase-negative staphylococci. blood cultures from separate sites should be performed
IE remains relatively rare, despite the fact that bacter- during the first 24 hours in the non–ill-appearing child.
emia occurs more commonly. Indeed, IE occurs when If there is no growth from these cultures after 1 day, then
bacteremia is present in the face of damage to vascular additional cultures should be performed before the initi-
or cardiac endothelium. Gram-positive cocci are a com- ation of antibiotic therapy. Subsequently, additional cul-
mon cause of IE due to their predilection for subendo- tures should be performed every 24 to 48 hours until
cardial connective tissue that is exposed in disrupted negative results are produced per American Heart Asso-
endocardium. In contrast, gram-negative bacteria (the ciation (AHA) guidelines. For a few cases (5%), blood
AACEK organisms: Aggregatibacter sp, Actinobacillus culture results may be persistently negative. There are
actinomycetemcomitans, Cardiobacterium hominis, Eikenella several reasons for such false-negative blood cultures: dif-
sp, and Kingella kingae) are less common causes of IE. ficulty in culturing the organism (eg, AACEK, anaerobes,
Fungal organisms remain an infrequent cause of IE. or fungi), inadequate volume of blood collected (optimal
volumes for blood cultures are 1-3 mL in infants and
Clinical and Laboratory Findings young children and 5-7 mL in older children), perform-
Common symptoms of IE include headache, myalgia, ar- ing fewer than 3 blood cultures, antibiotic administration
thralgia, malaise, anorexia, and weight loss, with fever oc- before performing blood cultures, or sequestration of the
curring in 75% of patients with IE. Although streptococcal etiologic agent within the vegetation. If a patient’s blood
endocarditis usually presents with low-grade fever, S aureus culture results remain negative and IE is suspected, the
endocarditis typically causes high, spiking temperatures. laboratory should be notified that IE is being considered

visual diagnosis
and the cultures incubated for at least 2 weeks in an effort cardiologists, cardiovascular surgeons, microbiologists,
to isolate fastidious organisms. and pharmacists decreases the overall mortality.
Differential Diagnosis Prognosis

The differential diagnoses of Osler nodes include rashes Children with IE have greater risk of complications in the
associated with Rocky Mountain spotted fever, secondary presence of prosthetic valves, cyanotic heart disease, S
syphilis, rickettsial disease, meningococcemia, and poly- aureus or fungal IE, left-sided IE, history of prior IE, symp-
arteritis nodosa. Osler nodes are tender, whereas the toms for more than 3 months, and/or poor response to
rashes included in the differential are all painless, with antibiotic treatment. Vegetations are considered the cause
the exception of polyarteritis nodosa. of most complications in IE. If present on valve leaflets,
valve regurgitation can result, leading to heart failure. Ac-
cording to a recent study, valvular insufficiency may occur
Management
in 18% of patients with pediatric IE, whereas heart failure
Empiric treatment should be started after blood cultures
may be diagnosed in 7% of these children. Fragments of
are performed. The AHA has guidelines for recommen-
the vegetation(s) can embolize to various organs (particu-
ded therapy once the causative organism is identified.
larly with vegetations >10 mm), including the brain,
These guidelines are considered the gold standard for
lungs, kidney, and extremities. The bacterial nidus may
treatment. While awaiting organism identification, how-
even evolve locally and lead to an abscess. Heart block, ar-
ever, empiric therapy should be based on the suspected or
rhythmia, mycotic aneurysms, seizures, renal abscess, and
most common organisms, which, as stated above, are
osteomyelitis are other possible sequelae.
Staphylococcus and then Streptococcus in pediatric pa-
tients. Per the AHA guidelines, the recommended first-line
agents for treatment of staphylococcal IE without pros- Patient Course
thetic valve material include oxacillin-nafcillin with an Transthoracic echocardiography revealed mitral valve in-
aminoglycoside (if not penicillin allergic), cefazolin with sufficiency. She had no previous echocardiograms for
an aminoglycoside (if penicillin allergic), or vancomycin. comparison, so it was unknown whether this mitral valve
These agents are bactericidal rather than bacteriostatic insufficiency was present before developing IE and there-
agents. In addition, the patient’s medical history, any re- fore a predisposing risk factor for developing IE or
cent antibiotic use, presentation and severity of illness, whether it was the result of the IE. However, both infec-
and local antimicrobial susceptibility patterns must be tious disease and cardiology consultations agreed that the
considered when choosing empiric antibiotic therapy. mitral valve insufficiency probably predated the IE. Be-
In patients who are not acutely ill, antibiotics can be held cause the patient grew up in the Philippines, it was hy-
for up to 48 hours to allow for more blood cultures to be pothesized that the patient developed mitral valve
obtained in an effort to maximize yield of an organism. insufficiency in the past due to rheumatic heart disease
Once the organism and its susceptibilities are isolated, an- because rheumatic heart disease in Asia is reported to af-
tibiotic therapy is chosen based on both the AHA guide- fect 1.2 to 2.2 per 1,000 children ages 5 to 14 years.
lines and input from infectious disease consultants based The patient had a long, complicated treatment course
on the other considerations. Intravenous antibiotic treat- for her septic emboli to the liver and brain, despite having
ment for IE is then continued for a minimum of 2 weeks a cardiac vegetation of less than 10 mm. Despite adequate
but more typically for 4 to 6 weeks. For staphylococcal IE antibiotic therapy, the patient’s blood culture results re-
of native valves, a 6-week course of intravenous antibiotics mained positive for 7 days, which is longer than the 3 to 5
is generally preferred. A longer antibiotic course may be days reported in the literature for S aureus endocarditis.
indicated for patients with infection of prosthetic valves She received a total of 55 days of parenteral antibiotics.
and infections with methicillin-resistant S aureus. On admission, she was empirically prescribed vancomy-
Surgical intervention is indicated in the case of persis- cin, ceftriaxone, and gentamicin. This drug regimen
tent bacteremia 2 weeks after appropriate therapy, the was chosen to provide broad-spectrum coverage before
presence of fungal vegetations, the formation of abscess, the causative organism was isolated and was recommen-
recurrent systemic embolic events, worsening heart fail- ded by our infectious disease consultants. Knowing that
ure, heart block, or failure of medical management. In S aureus is one of the most common causes of IE in the
many patients with IE, a multidisciplinary approach with developed world, we chose the combination of vancomy-
the involvement of infectious disease specialists, cin and gentamycin per the AHA guidelines to treat both

visual diagnosis
MSSA and methicillin-resistant S aureus. The ceftriaxone Summary

was added to cover for possible gram-negative bacteria IE occurs in pediatric patients and should be considered in
(such as AACEK organisms). Approximately 1 week after the differential diagnosis of bacteremic patients who pres-
initiation of therapy, the patient developed a rash and ent with a new or changing murmur. The presentation of
acute renal insufficiency (ultimately diagnosed as acute these patients may be nonspecific; use of the Duke Criteria
interstitial nephritis). These symptoms were attributed may assist in confirming the diagnosis. Although skin find-
to the vancomycin and ceftriaxone. By now, the causative ings, such as Janeway lesions and Osler nodes, are seen
organism had been identified as MSSA, so her antibiotic with greater frequency in the adult population, they can
regimen was narrowed to oxacillin and clindamycin. also be found in children. Staphylococcus and Streptococcus
However, an additional MRI taken shortly after alter- continue to be isolated as the primary organisms involved
ation of antibiotic therapy revealed a new lesion consis- in IE, suggesting that initial antibiotic treatment regimens
tent with a septic embolus in the occipital lobe of her should routinely target these organisms.
brain. In an effort to increase cerebrospinal fluid penetra-
tion, the clindamycin was changed to linezolid. While Suggested Reading
taking linezolid and oxacillin, the patient developed neu- Alshammary A, Hervas-Malo M, Robinson JL. Pediatric infective
tropenia and anemia. At this time, she was prescribed endocarditis: has Staphylococcus aureus overtaken viridans group
daptomycin. However, a subsequent MRI conducted 5 streptococci as the predominant etiological agent? Can J Infect
Dis Med Microbiol. 2008;19(1):63–68
weeks into her total course (and >2 weeks into her course
Baddour LM, Wilson WR, Bayer AS, et al. Infective endocarditis:
of daptomycin) revealed a new enhancing lesion in the diagnosis, antimicrobial therapy, and management of complica-
left frontal lobe consistent with a new septic embolus. tions: a statement for health care professionals from the
Treatment with daptomycin was stopped, and treatment Committee on Rheumatic Fever, Endocarditis, and Kawasaki
with chloramphenicol was started. She then completed Disease, Council on Cardiovascular Disease in the Young, and
the Councils on Clinical Cardiology, Stroke, and Cardiovascular
her course of antibiotic therapy with chloramphenicol
Surgery and Anesthesia, American Heart Association. Circula-
without any further complications. She remained in the tion. 2005;11:e394–e434
hospital for the duration of her therapy because of the Cardullo AC, Silvers DN, Grossman ME. Janeway lesions and
multiple complications she experienced with her antibi- Osler’s nodes: a review of histopathologic findings. J Am Acad
otic regimen. During her treatment, the cardiac vegeta- Dermatol. 1990;22(6 pt 1):1088–1090
Ferrieri P, Gewitz MH, Gerber MA, et al. Unique features of
tion gradually decreased in size and ultimately resolved
infective endocarditis in childhood. Pediatrics. 2002;109(5):
before discharge. At the time of discharge, she continued 931–943
to have a soft 2/6 systolic murmur, and echocardiogra- Marrie TJ. Osler’s nodes and Janeway lesions. Am J Med. 2008;121
phy revealed persistence of the mitral insufficiency. (2):105–106
Answer Key for March 2014 Issue:

Gynecologic Exam of the Prepubertal Girl: 1. C; 2. C; 3. D; 4. D; 5. C.
Pediatric MRI of the Brain: 1. C; 2. E; 3. E; 4. A; 5. C.
Complementary Medicine, Utilization Surveys: 1. E; 2. E; 3. D; 4. B; 5. C.

M a r c h 2 0 1 4
Abstracts of articles in Pediatrics in Review online-only pages appear on this page. The complete articles are available only
online so that Pediatrics in Review can provide you with even more original pediatric content. These online-only articles
are indexed in Index Medicus, MEDLINE, and PubMed, among other services.
Pediatrics in Review online is the journal of record. It contains the full content of each print issue (including all figures and
tables) from January 1979 to the present. The full online text is searchable by keyword and author, and the cited references
include hyperlinks to MEDLINE and to the full text of many other online journals. Although continuing medical education
(CME) quizzes for all issues also can be accessed online, the journal will not be adding CME quizzes to the 2014 online-only
articles; however, most of the online-only articles cover content specifications used by the American Board of Pediatrics to
prepare the cognitive examination in their Program for Maintenance of Certification. Subscribers can access this content by
visiting http://pedsinreview.aappublications.org.
T a b l e o f c o n t e n t s a n d c u r r e n t a b s t r a c t
e15 The Slow, Steady Development of Pediatric Ethics Committees, 1975–2013 D. Myers, J. Lantos
e15. ABSTRACT. The Slow, Steady Development of They are endorsed by the American Academy of Pediatrics,
Pediatric Ethics Committees, 1975–2013. Doug Myers, by the Joint Commission, and in many legal decisions. Al-
John Lantos. During the last 30 years, most children’s hos- though well accepted by many physicians and nurses, ethics
pitals in the United States have created pediatric ethics com- committees are only consulted approximately once a month
mittees or other formal methods to address the ethical issues or less in most children’s hospitals.
that arise in the clinical practice of tertiary care pediatrics. In this article, we review the history of pediatric ethics
Ethics committees or consultants are called on to advise committees, discuss their roles, and examine some critiques
physicians, nurses, other health care professionals, and of ethics committees. We then discuss attempts to define
parents in cases that raise controversial ethical issues. They the process of ethics consultation and measure the quality
take many forms and use many different processes to iden- of such consultations. We conclude with a tentative agenda
tify and resolve ethical dilemmas. for future research on the efficacy of pediatric ethics commit-
Such committees have themselves been somewhat con- tees. Pediatrics in Review. 2014;35:e15–e19. URL: pedsinre-
troversial. On the surface, they seem to be well accepted. view.aappublications.org/cgi/content/full/35/3/e15.

Article ethics
The Slow, Steady Development of Pediatric

Ethics Committees, 1975-2013
Doug Myers, MD,*
John Lantos, MD† During the last 30 years, most children’s hospitals in the United States have created pe-
diatric ethics committees or other formal methods to address the ethical issues that arise in
the clinical practice of tertiary care pediatrics. Ethics committees or consultants are called
Author Disclosure on to advise physicians, nurses, other health care professionals, and parents in cases that
raise controversial ethical issues. They take many forms and use many different processes
Drs Myers and Lantos
to identify and resolve ethical dilemmas.
have disclosed no Such committees have themselves been somewhat controversial. On the surface, they
financial relationships seem to be well accepted. They are endorsed by the American Academy of Pediatrics,
relevant to this article. (1) by the Joint Commission, (2) and in many legal decisions. (3) Although well accepted
This commentary does by many physicians and nurses, ethics committees are only consulted approximately once
not contain a discussion a month or less in most children’s hospitals. (4)
In this article, we review the history of pediatric ethics committees, discuss their roles,
of an unapproved/
and examine some critiques of ethics committees. We then discuss attempts to define the
investigative use of process of ethics consultation and measure the quality of such consultations. We conclude
a commercial product/ with a tentative agenda for future research on the efficacy of pediatric ethics committees.
device.
Pediatric Ethics Committees: A (Very) Brief History

The idea of hospital ethics committees was first proposed by a pediatrician. In 1975, Dr
Karen Teel, a Texas pediatrician, published a short article in the Baylor Law Review. (5)
She chose to publish in a law journal rather than a medical journal, suggesting that the
climate at the time within medicine was not receptive to the idea of committees to review
the ethics of clinical decisions. Clinical-ethical issues were seen more as dilemmas for the
legal profession than for physicians.
Teel suggested that the role for ethics committee consultation was to help physicians
deal with clinical-ethical dilemmas that arose in the practice of pediatrics. She expressed
dismay at the “lines (drawn by the law) beyond which the rights of parents and other in-
dividuals do not extend. These lines must be more clearly defined . and there must be
a system of advocacy . which ensures that a child’s rights are observed.” Teel acknowl-
edged that medical education did not provide much training about the ethical and legal
dilemmas frequently encountered by physicians. Thus, she suggested, the potential benefits
of ethics committee consultation were likely to outweigh the potential harms of committee
involvement in dilemmas such as the removal of life-sustaining treatments and concerns
primarily related to euthanasia.
Teel’s article was cited by the New Jersey Supreme Court in its 1977 decision approving
the removal of Karen Ann Quinlan’s ventilator. (6) The court recommended that all hos-
pitals create ethics committees to help with such dilemmas. However, the role of such com-
mittees was not clear. In Teel’s article, she conceptualized them as “prognosis committees”
whose role would be to bring together groups of experts to help attending physicians clarify
whether, in a particular case, there was any hope of recovery. In an analysis of the ways that
ethics committees evolved, Moreno suggested that the term
ethics committee may have led to confusion. (7) Prognosis
committees for individual cases were engaged in a different
Abbreviations activity than were committees that addressed issues such as
ICRC: infant care review committee resource allocation or hospital policies.
IEC: institutional ethics committee Despite Teel’s article being the first formal call for ethics com-
mittees, some hospitals had already created such committees.
*Department of Pediatrics, Division of Hematology/Oncology/Bone Marrow Transplant, Children’s Mercy Hospitals and Clinics,
Kansas City, MO.
†
Children’s Mercy Bioethics Center and Department of Pediatrics, University of Missouri-Kansas, Kansas City, MO.
Pediatrics in Review Vol.35 No.3 March 2014 e15

ethics pediatric ethics committees
The Human Rights Committee at the children’s hospitals form infant care review committees
Children’s Hospital of Pittsburgh (ICRCs). (9) To aid institutions in forming such commit-
A year before Dr Teel’s publication, the Children’s Hos- tees and, likely, to provide some consistency in their for-
pital of Pittsburgh renamed its research review commit- mation and function, in 1984, the American Academy of
tee. They called it the Human Rights Committee and Pediatrics published guidelines for ICRCs. (10) The
imagined for it a role in reviewing both research protocols guidelines suggest that ICRCs should only make recom-
and ethical dilemmas that arose in clinical care outside the mendations on courses of action when agreement be-
research context. In 1984, Michaels and Oliver (8) re- tween the treating team and a family cannot be reached
ported the experience of the committee in a review of and that the status quo should be maintained while legal
the first 12 years of existence. This is one of the first pub- proceedings are being instituted. It is not just hospitals or
lished reports of a clinical ethics committee in a children’s courts that dictate the formation of ethics committees. The
hospital. 1992 Accreditation Manual for Hospitals Supplement from
A few aspects of the work of the Pittsburgh Human the Joint Commission on the Accreditation of Healthcare
Rights Committee are noteworthy. First, they expanded Organizations (JCAHO) cites a role for committees as a
the research review committee to include nonmedical mechanism for consideration of ethical issues arising from
members, including a number of members with no insti- patient care. (11) Although such committees were created,
tutional allegiance. They did this to bring more perspec- there were few studies of how they functioned. There
tives to bear on dilemmas that were primarily about seemed to be little uniformity in the ways they would de-
human values and ethics, not science or medicine. Sec- cide particular cases. (12)
ond, from the beginning, consultation with the Chil- Many critics, particularly lawyers and physicians, were
dren’s Hospital of Pittsburgh Human Rights Committee concerned about the nonuniform, unregulated approach
was optional and the committee’s role was advisory. to the development of pediatric ethics committees. These
The committee’s recommendations were not binding. critics feared that such committees might have more power
The role of the committee was to gather facts, facilitate than was appropriate without the safeguards of either med-
conversation, and help the clinicians better understand ical professionalism or legal due process to prevent abuse
all of the medical facts, options, and ethical implications of that power. Many questions arose. Did ICRCs simply
of decisions. The committee had a standard approach to diffuse responsibility for controversial decisions? Was the
this task. They started by interviewing the physician and committee, in fact, responsible for the decision? Were their
clarifying the medical facts. Sometimes, they sought fur- recommendations truly just advisory or were they, in ef-
ther information and specialist consultation. Although fect, binding? Did different committees decide similar
the consultations in particular cases were always advisory cases differently and, if so, was that a problem? Was there
and optional, the committee also became involved in any standard approach to the process of consultation? The
shaping clinical care through the “establishment of hos- questions seemed valid because ethics committees had no
pital policy and education.” Policy guidelines concerning credentialing, no due process procedures, and no common
brain death, cardiopulmonary resuscitation, innovative method for actually performing consultations. Some com-
therapy, and human rights consultation have been the fo- mittees use multiple consultants. Some involve the whole
cus of the committee. committee in each consultation.
Although some, such as Dr Teel, were identifying an The 1984 American Academy of Pediatrics guidelines
urgent need and requesting the formation of committees for ethics committees suggest the inclusion of all inter-
to assist in the resolution of difficult ethical dilemmas, ested parties. However, they don’t define interested par-
others were beginning to experiment with how such ties, so these guidelines may be interpreted differently in
committees realistically function. different hospitals. This might allow some people to have
undue influence while other people are excluded from
the decision-making process. The Texas Advanced Direc-
The Legacy of Baby Doe tive Act, which specifies specific roles for ethics commit-
Many hospitals formed ethics committees in the wake of tees, has been criticized for allowing only certain voices to
the Quinlan decision. The process was accelerated by the be heard. Truog wrote, “The ethics committee is acting,
Baby Doe case in the early 1980s. That case involved an under Texas law, as a surrogate judge and jury, with the
infant with Down syndrome whose parents refused sur- statutory power to authorize clinicians to take actions
gery to correct esophageal atresia. The case eventually against the wishes of a patient and family, with protection
led to federal regulations that recommended that all against civil and criminal liability. But whereas the judicial
e16 Pediatrics in Review Vol.35 No.3 March 2014

system assures Americans of having a ‘jury of peers,’ hos- concerning failure to disclose conflicts of interest or com-
pital ethics committees are not held to this standard. Al- munications that focus on matters that concern risk man-
though it is true that most committees include one or two agement for the sake of the institution.
members of the community (often grateful patients of the Spielman’s critiques are thoughtful and powerful.
hospital), most members are physicians, nurses, and other There clearly is a potential for abuse in the largely unreg-
clinicians from the hospital staff. Without in any way call- ulated practice of ethics consultation. Efforts to standard-
ing into question their motivations or intentions, we ize approaches to consultation and study the outcomes of
must recognize that they are unavoidably ‘insiders,’ com- consultation in the field of pediatrics and effects on the
pletely acculturated to the clinical world and its attendant treating team, patients, and parents have been inade-
values. This is hardly a ‘jury of peers’ for a low-income quate, but they have not been entirely absent.
woman of color and her infant son.”
The lack of standards and the variability in formation Three Examples of Professional Regulation and
and function of institutional ethics committees (IECs) Study of Ethics Committees
have led to significant concerns about the integrity of Development and Sharing of Consultation
ethics consultation. Guidelines
In 1991, Baylis published Guidelines for Bioethics Con-
Critiques of Ethics Committees sultations at the Hospital for Sick Children [Toronto,
By the early 21st century, ethics committees had been Ontario]. (14) The stated purpose of consultations was
around long enough to have developed standard ap- to “assist patients, parents, legal guardians, and members
proaches to consultation; however, these approaches at- of the health care team in their management of situations
tracted critics. In 2001, Spielman (13) published an that have ethical implications.” Requests for consultation
indictment of ethics consultation by IECs. Spielman ar- could be made by a patient, family member, legal guardian,
gues that, starting with the Quinlan case, “lawmakers, or a member of the health care team. The initial consultant
hoping to improve health care decision-making, began discusses the case with the chair of the bioethics committee
to delegate powers to health care ethics consultants. Law- to triage the case. Referral to another body or committee,
makers have contributed to the growth of a practice that a discussion between the consultant and person requesting
has no professional standards but that now includes the consultation, a larger discussion with interested parties
decision-making, providing legal immunity, providing le- and one or more members of the committee, or any com-
gal opinions, attesting, and administering patient rights in bination of these options might come of a consultation re-
life-and-death matters.” Spielman cites several cases quest. The guidelines also list a requirement for certain
where misuse of institutional bioethics committee consul- information for the consultation to take place, thus provid-
tation has resulted in violation of rights of patients and ing some standardization to the process.
where personal values of ethics consultants have influ-
enced advice and recommendations. Lack of professional Identification of Core Competencies
standards would prevent consultants from adequately The American Society of Bioethics and Humanities has
performing in their role as educators, leading to limited written extensive Core Competencies for Bioethics Con-
education of interested parties in the case. She also points sultation. In 2010, the Clinical Ethics Consultation Ad-
out the varied role of such committees from state to state. visory Committee provided a report to the American
She criticizes ethics committees and consultants for the Society of Bioethics and Humanities. (15) In the report,
“. lack of professional ethics or regulation in the field the Clinical Ethics Consultation Advisory Committee
[and] the potential misuses of power and privilege.” suggested certification of individuals conducting clinical
She suggests, “Ethics consultants’ privileges and powers ethics consultation. They recommended that to be certi-
to affect others’ legal rights have grown considerably, fied an ethics consultant should function at the level of
without concomitant checks and balances to safeguard the advanced practitioner and should be able to demon-
the public.” She proposes a statute to deal with the “two strate working knowledge of the core competencies. In
most critical problems . ethics consultants’ failure to treat the wake of this report, there seems to some movement
their own conflicts of interest seriously and their failure to toward certification of consultants. (16)(17)
give adequate attention to the scope of their practice, espe-
cially to legal communications, and by extension, to the Peer-Reviewed Surveys of Practice
legal rights of the consultation participants.” The proposed Levine-Ariff surveyed children’s hospitals. In Institu-
statute suggests a monetary penalty for violations, primarily tional Ethics Committees (IEC): A Survey of Children’s

Hospitals, she found that 80% of these hospitals had an the ethical implications of their decisions. These goals
ethics committee. (18) This number was slightly higher are admirable. It is unclear, however, whether ethics
if the hospital had a neonatal intensive care unit and/ committees are successful at improving patient care.
or a pediatric intensive care unit. Most were medical staff We do not know whether or to what degree they are
committees (55%), but more than one-third reported to hampered by lack of well-trained ethics consultants, con-
the hospital administration. All committees had multiple flicts of interest, inadequate procedural safeguards during
functions, with 55 of 58 hospitals with ethics committees ethics consultation, or other factors that might lessen the
reporting consultation as a duty. A total of 39.6% devel- effectiveness of ethics consultation. As leading children’s
oped policy and 77% performed education. Ninety-five hospitals develop more formal bioethics programs, one
percent of hospitals reported that IEC decisions and rec- urgent task of such programs should be to study the pro-
ommendations were nonbinding, but 5% reported that cess of ethics consultation and develop metrics for assess-
decisions were binding. The study concluded that there ing the quality and effectiveness of ethics committees and
was a “clear movement toward effective multidisciplinary consultants.
committees to help guide practitioners.” The authors of
this study acknowledge the need to better understand References
“the effectiveness of the committees, the impact of edu- 1. American Academy of Pediatrics, Committee on Bioethics.
cation, the types of policies established and whether Institutional ethics committees. Pediatrics. 2001;107(1):205–
environments that have IECs promote more open discus- 209
2. Joint Commission on Accreditation of Healthcare Organiza-
sion and shared decision-making.” These findings are tions. Comprehensive Accreditation Manual for Hospitals: Update 1.
similar to conclusions of other surveys such as the ones Oakbrook Terrace, IL: Joint Commission on Accreditation of
by Fox et al in 2007 (19) and Kesselheim et al in Healthcare Organization; 1999:RI-R11
2010. (4) These noted that all large (>400-bed) hospitals 3. In re L. W., 482 NW2d 60 (Wis 1992) or In re A. C., 573 A2d
have ethics committees or consultative services, but only 1235 n2 (DC 1990)
4. Kesselheim JC, Johnson J, Joffe S. Ethics consultation in children’s
5% of consultants had formal training in ethics consulta- hospitals: results from a survey of pediatric clinical ethicists. Pediatrics.
tion. Less than 50% of consultants had been consulting 2010;125(4):742–746
more than 5 years, and they found little clarity in the 5. Teel K. The physician’s dilemma: a doctor’s view—what the law
standards for consultative practice. Understanding the should be. Bayl Law Rev. 1975;27(1):6–9
reasons why physicians and other staff contact ethics con- 6. In re Quinlan 70 N.J. 10, 355 A.2d 647 (NJ 1976)
7. Moreno JD. Deciding Together: Bioethics and Moral Consensus.
sultants is also under investigation, and the results of such New York, NY: Oxford University Press; 1995
study may contribute to the focus and objectives of edu- 8. Michaels RH, Oliver TK Jr. Human rights consultation: a 12-
cational efforts for potential consultants. For example, year experience of a pediatric bioethics committee. Pediatrics. 1986;
DuVal et al (20) suggest that most consultations are trig- 78(4):566–572
gered by “conflicts and other emotionally charged con- 9. Fleming GV, Hudd SS, LeBailly SA, Greenstein RM. Infant care
review committees: the response to federal guidelines. Am J Dis
cerns (rather than) other cognitively based concerns.” Child. 1990;144(7):778–781
Research in such areas can guide training of consultants 10. American Academy of Pediatrics. American Academy of
in the future. Pediatrics Infant Bioethics Task Force and Consultants: guide-
Still, although many members of ethics committees at lines for infant bioethics committees. Pediatrics. 1984;74(2):
pediatric or adult institutions have not had training in 306–310
11. Joint Commission. Accreditation Manual for Hospitals Supple-
ethics consultation, efforts to certify ethics consultants ment from the Joint Commission on the Accreditation of Healthcare
have been controversial and have lagged behind the de- Organizations (JCAHO). Oakbrook Terrace, IL: Joint Commis-
velopment of the committees and policies relevant to sion; 1992
their function. Although many institutions may support 12. Kopelman LM, Irons TG, Kopelman AE. Neonatologists judge
an ethics committee, these authors were unable to find the “Baby Doe” regulations. N Engl J Med. 1988;318(11):
677–683
evidence that consultative services were monetarily reim- 13. Spielman B. Has faith in health care ethics consultants gone too
bursed in any way. Such practices would be very contro- far? risks of an unregulated practice and a model act to contain
versial. Burda (21) points out that most bioethicists them. Marquette Law Rev. 2001;85(1):161–221
would likely agree that consultative services should be 14. Baylis FE. Guidelines for bioethics consultations at the Hospital
for Sick Children [Toronto, Ontario]. HEC Forum. 1991;3(5):
available to all, not just those with insurance coverage
293–297
that happens to cover such consultations. 15. Clinical Ethics Consultation Advisory Committee (CECA)
Children’s hospital ethics committees endeavor to im- Report to ASBH. Chicago, IL: American Society for Bioethics and
prove patient care by improving clinicians’ awareness of Humanities; 2010
e18 Pediatrics in Review Vol.35 No.3 March 2014

16. Acres CA, Prager K, Hardart GE, Fins JJ. Credentialing the 19. Fox E, Myers S, Pearlman RA. Ethics consultation in United
clinical ethics consultant: an academic medical center affirms pro- States hospitals: a national survey. Am J Bioeth. 2007;7(2):13–
fessionalism and practice. J Clin Ethics. 2012;23(2):156–164 25
17. Schiedermayer D, La Puma J. Credentialing and certification in 20. DuVal G, Sartorius L, Clarridge B, Gensler G, Danis M. What
ethics consultation: lessons from palliative care. J Clin Ethics. 2012; triggers requests for ethics consultations? J Med Ethics. 2001;27
23(2):172–174 (suppl 1):i24–i29
18. Levine-Ariff J. Institutional ethics committees: a survey of chil- 21. Burda M. Certifying clinical ethics consultants: who pays? J Clin
dren’s hospitals. Issues Compr Pediatr Nurs. 1989;12(6):447–461 Ethics. 2011;22(2):194–199

Editor-in-Chief: Joseph A. Zenel, Sioux Falls, SD
Associate Editor: Hugh D. Allen, Houston, TX.
Editor, In Brief: Henry M. Adam, Bronx, NY
Consulting Editor, In Brief: Janet Serwint, Baltimore, MD
Editor, Index of Suspicion: Deepak M. Kamat, Detroit, MI
Editor, CME: Paula Algranati, Longmeadow, MA
Editor Emeritus: Lawrence F. Nazarian, Rochester, NY
contents
Founding Editor: Robert J. Haggerty, Canandaigua, NY
Managing Editor: Luann Zanzola
Editorial Associate: Sara Strand
Pediatrics in Review® Vol.35 No.3 March 2014
Medical Copyediting: Laura King
Editorial Board
Denise Bratcher, Kansas City, MO Michael Macknin, Cleveland, OH
Brian Carter, Nashville, TN Susan Massengill, Charlotte, NC
Deborah M. Consolini, Wilmington, DE Jennifer Miller, Gainesville, FL
Stephen E. Dolgin, New Hyde Park, NY
B. Anne Eberhard, New Hyde Park, NY
Philip Fischer, Rochester, MN
Carrie A. Phillipi, Portland, OR
Peter Pizzutillo, Philadelphia, PA
Mobeen Rathore, Jacksonville, FL
Articles
Lynn Garfunkel, Rochester, NY E. Steve Roach, Columbus, OH
Rani Gereige, Miami, FL
Joseph Gigante, Nashville, TN
Nupur Gupta, Boston, MA
Jacob Hen, Bridgeport, CT
Sarah E. Shea, Halifax, Nova Scotia
Andrew Sirotnak, Denver, CO
Alfred Tenore, Udine, Italy
Miriam Weinstein, Toronto, ON
97 Gynecologic Examination of the Prepubertal Girl
Amanda M. Jacobs, Elizabeth M. Alderman
Jeffrey D. Hord, Akron, OH
Publisher: American Academy of Pediatrics

Michael J. Held, Director, Division of Scholarly Journals and Professional Periodicals
Pediatrics in Review®
106 Pediatric MRI of the Brain: A Primer
Kamakshya P. Patra, Jeffrey D. Lancaster, Jeffery Hogg, MOC | CME | Board Review
(ISSN 0191-9601) is owned and controlled by the American Academy of
Pediatrics. It is published monthly by the American Academy of Pediatrics, Jeffrey S. Carpenter
141 Northwest Point Blvd., Elk Grove Village, IL 60007-1098.
Statements and opinions expressed in Pediatrics in Review® are those of the
authors and not necessarily those of the American Academy of Pediatrics or
its Committees. Recommendations included in this publication do not indicate
an exclusive course of treatment or serve as a standard of medical care.
Subscription price for 2014 for print and online/online only: AAP/CPS
113 The Clinician’s Guide to Autism: Correction New! Stay current in pediatric pulmonology with
Member $194/$148; AAP National Affiliate Member $153/$104; Nonmember
$243/$188; Allied Health or In-training $180/$122.
Complementary, Holistic, and Integrative Medicine: the online self-assessment program that delivers
Institutions call for pricing (866-843-2271). For overseas delivery, add $120.
Current single issue price is $10 domestic, $12 international. Replacement
issues must be claimed within 6 months from the date of issue and are limited
to three per calendar year. Periodicals postage paid at ARLINGTON
HEIGHTS, ILLINOIS and at additional mailing offices.
114 Utilization Surveys of the Pediatric Literature
Soleil Surette, Sunita Vohra clinically relevant, peer-reviewed questions, in-depth
© AMERICAN ACADEMY OF PEDIATRICS, 2014. All rights reserved.
Printed in USA. No part may be duplicated or reproduced without permission
of the American Academy of Pediatrics.
POSTMASTER: Send address changes to PEDIATRICS IN REVIEW®,
American Academy of Pediatrics Customer Service Center, 141 Northwest
Index of Suspicion discussions of preferred answers, and references for
Point Blvd., Elk Grove Village, IL 60007-1098. Case 1: Fever, Diarrhea, Jaundice, and Confusion in an
Pediatrics in Review
Print Issue Editorial Board Disclosures 18-Year-Old Male further study – all mapped to the ABP pediatric
The American Academy of Pediatrics (AAP) Policy on Disclosure of Financial
129
Relationships and Resolution of Conflicts of Interest for AAP CME Activities is
designed to ensure quality, objective, balanced, and scientifically rigorous AAP CME
activities by identifying and resolving all potential conflicts of interest before the
confirmation of service of those in a position to influence and/or control CME content.
Case 3: Red Urine in a 4-Month-Old Boy pulmonology content specifications.
All individuals in a position to influence and/or control the content of AAP CME Case 1: Elaine Ku, Michelle Thomas, Cynthia H. Ho
activities are required to disclose to the AAP and subsequently to learners that the
individual either has no relevant financial relationships or any financial relationships with Case 2: Nicholas S. Whipple, Omar Abdul-Rahman,
the manufacturer(s) of any commercial product(s) and/or provider(s) of commercial
services discussed in CME activities. Commercial interest is defined as any entity Gail C. Megason, Betty L. Herrington
producing, marketing, reselling or distributing health-care goods or services consumed Case 3: J. Bryan Carmody, Jennifer R. Charlton
by, or used on, patients.
Each of the editorial board members, reviewers, question writers, PREP Coordinating
Committee members and staff has disclosed, if applicable, that the CME content he/
2014 PREP PULMONOLOGY
she edits/writes/reviews may include discussion/reference to generic pharmaceuticals, WHAT SUBSCRIBERS ARE SAYING
off-label pharmaceutical use, investigational therapies, brand names, and manufacturers.
None of the editors, board members, reviewers, question writers, PREP Coordinating
Committee members, or staff has any relevant financial relationships to disclose, unless
In Brief ABOUT PREP SUBSPECIALTIES…
PRICING
noted below. The AAP has taken steps to resolve any potential conflicts of interest.
Section Member . . . . . . . . .$177
Disclosures
• Athos Bousvaros, MD, MPH, FAAP, disclosed that he has research support
from Prometheus Laboratories, Inc.; and that he is a paid consultant for Cubist
Pharmaceuticals, Dyax Corp., and Millennium.
136 Von Willebrand Disease
Stacy Cooper, Clifford Takemoto
AAP Member . . . . . . . . . . . .$199
• Lynn Garfunkel, MD, FAAP, disclosed that her family member is an employee “The online activity is the best way for me to Non-member . . . . . . . . . . . . .$219
137
of Philips Healthcare.
• Blaise Nemeth, MD, MS, FAAP, has disclosed he has an unrestricted learn because all the questions are presented
educational grant for fellowship from Biomet. Corrections
• Paul Graham Fisher, MD, has disclosed that he owns stock/bonds in
as scenarios. I am able to learn much better
Johnson & Johnson and that he serves on the editorial board of the Journal of Pediatrics.
• Richard Sills, MD, FAAP, disclosed that he receives a research grant from Novartis. What comes with an annual
• Miriam Weinstein, MD, disclosed that she is a consultant for Pediapharm Visual Diagnosis: 15-Year-Old Girl With from this type of format rather than reading
and SunCorp. She also has received honoraria from Dermik and Leo Pharma.
The journal extends special thanks to the following question writers who
contributed to this issue:
• Paul Graham Fisher, MD
138 Fever, Extremity Pain, and Unusual Rash
David Toturgul, Megan Yunghans, Jessica Kosut
a review of a topic, which I will later forget.”
subscription to PREP
Pulmonology?
• O.J. Sahler, MD
• H. Stephen Williams, MD
PA
RT U U
• Clinically relevant cases with
U
PREP Pulmonology is approved for 20 points by
Online-only Article multimedia aids and references
UU
2
U MO
the American Board of Pediatrics (ABP) for MOC
UUUU
UU
Abstract appears on page 143.
UU UUU
U
U
Part 2: Lifelong Learning and Self-Assessment.* • Instant feedback and the
ability to bookmark questions
The Slow, Steady Development of Pediatric Ethics for further study
Pediatrics in Review® is supported, in part, through an

e15 Committees, 1975-2013
Doug Myers, John Lantos
For more information on ordering, including • Easy-to-read, case-based
questions with clear, succinct
educational grant from Abbott Nutrition, a division of
Abbott Laboratories, Inc.
a FREE Trial, visit http://preppulm.aap.org explanations
Pediatrics in Review offers 36 CME articles per year. A maximum of one AMA PRA Category 1 CreditTM is earned after
achieving a 60% score on each designated quiz.
Cover: The artwork on the cover of this CME statements:
month’s issue is by one of the winners The American Academy of Pediatrics (AAP) is accredited by the Accreditation Council for Continuing Medical Education
(ACCME) to provide continuing medical education for physicians.
of our 2013 Cover Art Contest, 9-year-old The AAP designates this journal-based CME activity for a maximum of 1.00 AMA PRA Category 1 CreditTM. Physicians should claim
PREP Pulmonology is co-sponsored in collaboration
Stephanie P. of Monroe, NY. Stephanie’s only the credit commensurate with the extent of their participation in the activity.
with the American College of Chest Physicians.
pediatrician is Amina Elkassir, MD. This activity is acceptable for a maximum of 1.00 AAP credit. These credits can be applied toward the AAP CME/CPD* Award
available to Fellows and Candidate Members of the AAP.
The American Academy of Physician Assistants accepts certificates of participation for educational activities certified for AMA PRA
Category 1 CreditsTM from organizations accredited by ACCME. Physician assistants may receive a maximum of 1.00 hour of Category
1 credit for completing this program. PREP Pulmonology is co-sponsored in collaboration
This program is accredited for 1.00 NAPNAP CE contact hour; pharmacology (Rx) and psychopharmacology contact hours to be with the American Thoracic Society.
determined per the National Association of Pediatric Nurse Practitioners (NAPNAP) Continuing Education Guidelines.
It has been established that each CME activity will take the learner approximately 1 hour to complete.
Answer key appears on page 142. *Continuing Professional Development
How to complete this activity:
Pediatrics in Review can be accessed and reviewed in print or online at http://pedsinreview.aappublications.org. Learners can The American Academy of Pediatrics (AAP) is accredited by the Accreditation Council for
claim credit monthly online upon completion of each CME article. The deadline for completing this activity is December 31, *All approved activities must be completed by the MOC Credit Approval End Date.
Continuing Medical Education to provide continuing medical education for physicians.
2016. Credit will be recorded in the year in which it is submitted. It is estimated that it will take approximately 1 hour to com- All deadlines and MOC point values should be confirmed with the ABP.
plete each CME article. This activity is not considered to have been completed until the learner documents participation in that This activity has been approved for AMA PRA Category 1 Credit ™.
activity to the provider via online submission of answers. Course evaluations are online.
Searchable e-Archives from Vol. 1, Issue 1 www.pedsinreview.org Vol. 35 No. 3 pp. 97-143 March 2014
PediatricsinReview
®
Create
your own
e-Library.
MY FILE CABINET
A BENEFIT OF YOUR AAP JOURNAL SUBSCRIPTION
Create your own customized e-library of clinically relevant articles – all in one
place for quick access. With My File Cabinet tool, you can manage all the critical My File Cabinet
information you need more efficiently. • Save articles and searches for
quick retrieval
Create a virtual library of the information that matters most to you. When you
• Create, remove, and delete folders
want to save an article, simply click “Add to My File Cabinet” in the right-hand as your collection grows for improved
organization
navigation bar. You can even create folders within your file cabinet for organized
• Delete articles when needed to
and quick access. ensure storing of only the most
relevant information
pediatrics.org aapnews.org aapgrandrounds.org pedsinreview.org hospitalpediatrics.org neoreviews.org Online Now...

Gynecologic Pediatric MRI The Slow, Steady
Examination of of the Brain: Development of
@AAPJournals
Supported, in part, through an educational grant from the Prepubertal A Primer Pediatric Ethics
aap.org/journals Abbott Nutrition, a division of Abbott Laboratories, Inc.
Girl – Patra, Lancaster, Committees, 1975–2013
– Jacobs, Alderman Hogg, Carpenter – Myers, Lantos

Pediatrics Review: Create Your Own E-Library

Uploaded by

Copyright:

Available Formats

Pediatrics Review: Create Your Own E-Library

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Pediatrics Review: Create Your Own E-Library

Uploaded by

Copyright:

Available Formats

Searchable e-Archives from Vol. 1, Issue 1 www.pedsinreview.org Vol. 35 No. 3 pp.

97-143 March 2014

pediatrics.org aapnews.org aapgrandrounds.org pedsinreview.org hospitalpediatrics.org neoreviews.org Online Now...

Publisher: American Academy of Pediatrics

Pediatrics in Review® is supported, in part, through an

Gynecologic Examination of the Prepubertal

*Albert Einstein College of Medicine, Children’s Hospital at Montefiore, Bronx, NY.

Pediatrics in Review Vol.35 No.3 March 2014 97

There are many normal variations of the prepubertal

98 Pediatrics in Review Vol.35 No.3 March 2014

Pediatrics in Review Vol.35 No.3 March 2014 99

and avoidance of occlusive clothing

100 Pediatrics in Review Vol.35 No.3 March 2014

Pediatrics in Review Vol.35 No.3 March 2014 101

Figure 8. Perineum of a child who has lichen sclerosus,

102 Pediatrics in Review Vol.35 No.3 March 2014

Coagulopathies, arteriovenous malformations, and

Case 5: Vaginal Itching

Pediatrics in Review Vol.35 No.3 March 2014 103

minora. These ulcers can appear as a single lesion or mul- References

Parent Resources from the AAP at HealthyChildren.org

104 Pediatrics in Review Vol.35 No.3 March 2014

PIR Quiz Requirements

Pediatrics in Review Vol.35 No.3 March 2014 105

Pediatric MRI of the Brain: A Primer

106 Pediatrics in Review Vol.35 No.3 March 2014

and erythematous, she had difﬁculty opening her right

Figure 3. Coronal postcontrast T1-weighted image shows in-

Pediatrics in Review Vol.35 No.3 March 2014 107

108 Pediatrics in Review Vol.35 No.3 March 2014

Figure 6. A. Magnetic resonance venography (MRV) reveals

sigmoid, and straight sinuses. MRI and MRV are impor-

vomiting. On the day of her presentation, she was unable

Pediatrics in Review Vol.35 No.3 March 2014 109

Coronal T2 revealed left-sided loss of gray white differen-

Other MRI Modalities

110 Pediatrics in Review Vol.35 No.3 March 2014

glycolysis). An elevated choline-creatine ratio is sugges-

Pediatrics in Review Vol.35 No.3 March 2014 111

PIR Quiz Requirements

112 Pediatrics in Review Vol.35 No.3 March 2014

Parent Resources from the AAP at HealthyChildren.org

Pediatrics in Review Vol.35 No.3 March 2014 113

Complementary, Holistic, and Integrative

*CARE Program, University of Alberta, Edmonton, Alberta, Canada.

114 Pediatrics in Review Vol.35 No.3 March 2014

Pediatrics in Review Vol.35 No.3 March 2014 115

Complementary Location: Turkey, vitamins or

116 Pediatrics in Review Vol.35 No.3 March 2014

Pediatrics in Review Vol.35 No.3 March 2014 117

118 Pediatrics in Review Vol.35 No.3 March 2014

Pediatrics in Review Vol.35 No.3 March 2014 119

120 Pediatrics in Review Vol.35 No.3 March 2014

medicine use and cross-sectionally

Pediatrics in Review Vol.35 No.3 March 2014 121

122 Pediatrics in Review Vol.35 No.3 March 2014

autism spectrum Location: Internet, parents/caregivers

paediatric Kingdom, Yorkhill

Pediatrics in Review Vol.35 No.3 March 2014 123