Crystals

Different types of crystals may be identified

in SF and include
monosodium urate crystals (MSU)
calcium pyrophosphate crystals (CPPD)
miscellaneous types of crystals
Differentiation of MSU crystals associated with gout
vs. calcium pyrophosphate crystals representing
pseudogout is important
Differentiation of gout from pseudogout is
accomplished by first examining the crystals under
polarized light following by the use of a first order red
filter
MSU crystals are usually elongated and needle shaped
(monoclinic), while the crystals of pseudogout are
chunky (triclinic) or needle shaped like MSU
______________________

Monoclinic (needle shaped) Triclinic (chunky)

Gout and pseudogout Pseudogout
 Monoclinic crystal
Negative birefringent
monosodium urate crystal
 Differentiation of MSU crystals associated with
gout vs. calcium pyrophosphate crystals
representing pseudogout is important
Under routine polarized light, the crystals of both gout and
pseudogout polarize and are found either phagocytized by
neutrophils or free with the SF
When viewing the SF through a red filter and lining the crystals
up with the axis of the analyzer at the base of the microscope,
the crystals of MSU will appear yellow when parallel to the axis
of the analyzer, while the crystals of pseudogout will appear blue
when oriented parallel to the axis of the analyze.
The polarizing characteristics of MSU just described define
negative birefringence, while the findings just described for
calcium pyrophosphate define weakly positive birefringence.
Synovial fluid: From left: Normal,
Non-inflammatory, Inflammatory,
Septic, Hemorrhagic
 Group I: Non-inflammatory
Osteoarthritis
Definition: most common (MC) rheumatic
disease; characterized by progressive loss of
articular cartilage associated with reactive
changes at the margin of the joints and in
the subchondral bone
Age/sex: middle to old age; females (10X)
> males
 Group I: Non-inflammatory
Osteoarthritis
Pathogenesis:
although the exact etiology of osteoarthritis is
unknown, biomechanical, biochemical,
inflammatory, and immunologic factors have
been implicated
 Group I: Non-inflammatory
Osteoarthritis
Pathogenesis
increases with age and is almost universal in
people 65 years or older (age dependent)
genetic factors play a role in development of
osteoarthritis in the distal interphalangeal joints
of the hands (dominant in females)
most common cause (MCC) of joint disability
MC involves weight bearing joints like the hips
and knees
 Group I: Non-inflammatory
Osteoarthritis
Gross/microscopic:
initially, the cartilaginous surface of a joint is eroded and
clefts appear at right angles to the surface which
penetrate into subchondral bone, a process called
fibrillation
cartilage fibrillation in osteoarthritis may result in
fragments of cartilage breaking loose and the creation of
joint mice
eventual erosion of the cartilaginous layer in
osteoarthritis may result in reactive bone formation and
dense sclerotic bone resembling ivory (eburnation) as
bone rubs against bone
 Group I: Non-inflammatory
Osteoarthritis
Osteophytes (bony spurs) develop along the margins of the
joints and are responsible for
the lipping found in the vertebral bodies
Heberdens nodes found at the base of the distal
interphalangeal (DIP) of the hands
Bouchards nodes in the proximal interphalangeal (PIP)
joints of the hand
Subchondral bone develop cysts beneath the articular
surface, that are easily visible on x-ray of the joint
Reduction in the joint space on x-ray
OA: Narrowing of the Joint
Space
OA: Subchondral Bone Cysts
 OA: Swelling of the PIP
(Bouchard Nodes) and DIP
(Heberden Nodes) joints
Osteoarthritis: the arrow points
to narrowing of the joint space
with sclerotic bone
 Group I: Non-inflammatory
Osteoarthritis
Clinical
patients slowly develop joint pain with stiffness
and enlargement accompanied by limitation of
motion
secondary synovitis is common and is manifested
by pain on compression of the joint
joint disease is usually asymmetric
pain on passive motion of the joint and crepitus
(feeling of crackling in the joint) are common
Heberdens nodes develop in the DIP joints and
Bouchards nodes in the PIP joints of the hand
 Group I: Non-inflammatory
Osteoarthritis
Clinical (contd.)
osteoarthritis in the hip leads to the onset of pain and a limp
loss of hip motion on internal rotation or extension
osteoarthritis in the knee produces pain and muscle atrophy
from disuse
osteoarthritis of the spine results from involvement of the
intervertebral discs, vertebral bodies, or the posterior
apophyseal articulations
pain
stiffness
compression neuropathies
 Group I: Non-inflammatory
Osteoarthritis

Clinical (contd.)
pseudogout secondary to deposition of calcium
pyrophosphate can be associated with
osteoarthritis
 Neuropathic arthropathy
Definition: neuropathic arthropathy
(Charcots joint) refers to the development
of joint disease in neurologic disease
Pathogenesis appears to be a combination of
neurotrauma in a joint that cannot sense
pain as well as a neurovascular component
with alterations in blood flow to the joint
 Neuropathic arthropathy
Clinical:
both upper motor and peripheral lower motor
neuron disease can lead to this disease
diabetes i the MCC followed by syringomyelia
(25%) and tabes dorsalis (10%)
Charcots Joint
ID/CC A 47 year old white female visits her family
doctor complaining of painful swelling of the
right knee.
HPI She has a history of chronic pain along with
morning stiffness in the hand joints lasting for
at least two hours
PE Symmetrical deforming arthropathy; soft-
tissue swelling and tenderness in proximal
interphalangeal and metacarpophalangeal
point; wasting of small muscles of hand;
flexion of MCP joint; extension of PIP joint
and flexion of distal DIP joint; effusion on
right knee with overlying skin redness and
increased temperature; subcutaneous nodules
 Group II: Inflammatory
Rheumatoid arthritis (RA)
Definition: rheumatoid arthritis (RA) is a chronic,
systemic inflammatory collagen disease that eventually
results in progressive destruction of the joint,
deformity, and disability in the patient
Age/sex:
middle age females between 30-50 years
Pathogenesis:
MC autoimmune disease
microbial agent like EBV may be the initiator of
the inflammation in a DR4 patient
primarily immunologic
 Rheumatoid arthritis
Pathogenesis (contd.)
similar to delayed hypersensitivity reactions in
involving the secretions of T4 helper cells and
macrophages -->
elaboration of chemotactic factors to attract neutrophils--
>phagocytosis of immune complexes (rheumatoid factor
aggregates) by neutrophils (ragocytes) -->
their release of lysosomal enzymes -->
activation of the complement cascade plus the additional
destructive effects of collagenases and prostaglandins on
the joint
RA generally increases in incidence with age
 Rheumatoid arthritis
Pathogenesis (contd.)
HLA-DR4 relationship
rheumatoid factor (RF) is an IgM (most
common) or IgA antibody against the Fc
fragment of IgG
aggregates phagocytized by neutrophils (ragocytes)
 Rheumatoid arthritis
Gross/microscopic:
inflammation of the synovium (synovitis with
numerous plasma cells)
eventual proliferation of synovial tissue over the
surface of articular cartilage (pannus), which
destroys the articular cartilage
subsequent inflammation results in
erosions of bone
reactive fibrosis leading to fusion (ankylosis) of the
joint space and immobility
RA: Note swelling of the second
and third MCP joints
 RA: Note the classic ulnar
deviation and MCP involvement
in both hands
RA: Boutonniere deformity
Flexion of the PIP joint and
extension of the DIP joint
RA: Swan Neck Deformity
It is the opposite of the
Boutonniere deformity
Rheumatoid Nodules
 Rheumatoid arthritis
Clinical:
As a rule, the disease is insidious and presents
with symmetric involvement of the joints of the
hands (metacarpophalangeal and proximal
interphalangeal--not DIP)
wrists
foot
elbows
shoulders
atlanto-axial
 Rheumatoid arthritis
Clinical
morning stiffness lasting more than an hour is a
classic feature of the disease, although it can
also be seen in SLE and polymyalgia
rheumatica as well
accepted measure of the severity of the condition
joints in RA are generally warm and tender and
the fingers have a characteristic spindle shaped
appearance
 Rheumatoid arthritis
Extra-articular features of RA:
subcutaneous nodules (rheumatoid nodules)
appear in 20-25% of patients that are RF positive
(seropositive)
usually adjacent to a joint or bursa on the extensor
surface in areas of pressure
rheumatoid vasculitis may involve small to
medium sized vessels involving the digits or the
ankle
frequently associated with fever, neutrophilic
leukocytosis, a drop in serum complement levels
(immunologic vasculitis), and a high RF titer
limited to HLA DR4 seropositive patients
 Rheumatoid arthritis
Extra-articular features of RA:
fibrinous pericarditis (40-50%)
echocardiography is the most sensitive test for
detecting the effusions
 Rheumatoid arthritis
Extra-articular features of RA:
pulmonary manifestations
subpleural nodules
diffuse interstitial fibrosis with pneumonitis
(restrictive disease)
rheumatoid nodules in the lung parenchyma
chronic pleuritis
an association with certain pneumoconioses (coal
workers pneumoconiosis, silicosis) to produce the
Caplans syndrome
 Rheumatoid arthritis
Extra-articular features of RA:
pleural fluid in RA is frequently milky in
appearance (pseudochylous)(cholesterol
crystals, neutrophils, macrophages, low in
glucose,)
must be distinguished from a chylous thorax
triglyceride
lymphocytes
 Rheumatoid arthritis
Neurologic manifestations
peripheral neuropathy often leading to a foot or
wrist drop
 Rheumatoid arthritis
Ophthalmologic manifestations
uveitis
keratoconjunctivitis
Hematologic manifestations
microcytic or normocytic anemia with findings
consistent with anemia of chronic disease
Reactive (secondary) amyloidosis due to
chronic inflammation
 Rheumatoid arthritis
Laboratory
positive RF (70%)
standard RF tests measure the presence of IgM
antibody against IgG
RF titers correlate with
increased severity of the disease
presence of rheumatoid nodules
greater frequency of systemic complications
rheumatoid vasculitis
poorer prognosis
 Rheumatoid arthritis
Positive rheumatoid arthritis precipitin
(RAP) assay (85-85%)
RAP antibody is against a component of
the EBV virus
Serum complement (C3) is normal to
increased
decreased when vasculitis is present
(immune complex vasculitis)
Increased erythrocyte sedimentation
rate
not a good indicator of disease activity
 Differential features of RA from
osteoarthritis:
Osteoarthritis Rheumatoid arthritis

Joint involvement articular cartilage synovial tissue

Age older individuals all ages
Weight bearing joints yes smaller joints
Symmetry asymmetrical symmetrical
Hands DIP and PIP PIP and MCP
Type of disease degenerative HLA DR4
HLA relationship no HLA DR4
 Differential features of RA
from osteoarthritis:
Osteoarthritis Rheumatoid arthritis

Systemic features no yes

Laboratory unremarkable frequently abnormal
Osteophytes (spurs) yes no
Morning stiffness not prominent prominent
Joint fusion no yes
Group Group I Group II
 Gout
Definition: gouty arthritis is a heterogenous group
of disorders (multifactorial inheritance)
characterized by an increase in serum uric acid,
recurrent attacks of acute arthritis, formation of
deposits of monosodium urate (tophi), gouty
arthritis, and uric acid urolithiasis
Age/sex:
almost exclusively a disease of adult men
rare in premenopausal women and prepubertal children
MC inflammatory arthritis in men over 30
multifactorial inheritance
 Gout
Pathogenesis:
hyperuricemia is associated with gout but is not of
itself sufficient for the expression of gout
asymptomatic of hyperuricemia that is a
consequence of a disorder in uric acid
metabolism
primary hyperuricemia with gout refers to the
presence of hyperuricemia that is a consequence
of a disorder in uric acid metabolism
decreased excretion (MCC)
increased production
both
not associated with another acquired disorder
clinical picture is dominated by the features of
the gout syndrome
 Gout
Secondary hyperuricemia associated with gout can
be due to the same mechanism as primary gout but
the gout syndrome is not the major clinical feature
associated with
diabetes mellitus
polycythemia rubra vera
leukemia
multiple myeloma
diuretic therapy
hemoglobinopathies
the treatment of disseminated carcinomas
 Gout
Uric acid metabolism
uric acid is end-product of purine metabolism
Adult male uric acid range is 3.5-7.0 mg/dL
adult female range is 2.5-6.0 mg/dL
lower levels in females due to the action of
estrogen on promoting the excretion of uric
acid by the kidney
 Gout
Environmental factors affecting uric acid
levels include
sex
weight
diet
social class
hemoglobin levels
 Gout
Hyperuricemia can result from an
increase in production secondary to an
overactivity of PRPP
decrease in HGPRT (inhibits PRPP)
a decrease in excretion of uric acid by the
kidney
only 10-15% of cases of hyperuricemia relate to
overproduction, with the majority (90%)
representing an underexcretion in the kidney
 Gout
Complete deficiency of HGPRT is the sex-
linked recessive disease called the Lesch
Nyhan syndrome
self mutilation
hyperuricemia
Less than 20% of patients with
hyperuricemia will develop clinically
apparent crystal deposition
 Gout
Duration and magnitude of hyperuricemia
are directly correlated to the likelihood of
development of gouty arthritis or uric acid
urolithiasis
Hyperuricemia < 10 mg/dL, causes little if
any harmful effect on renal function; more
important factors in urate nephropathy are
coexistent hypertension
chronic lead exposure
ischemic heart disease
primary pre-existent renal disease
 Gout
Acute gouty arthritis is sudden, explosive
and often occurs at night
metatarsophalangeal joint (big toe) is MC
involved in the first attack (75% --> called
podagra) *****
attack subsides without treatment in 3 days to
10 days
triggered by stress, alcohol, drugs, surgery or an
acute medical illness
Acute Gouty Arthritis
 Gouty Tophi
Associated with Chronic Gout
Gout: Tophi under polarized
light
Gouty Tophus
 Gout
Pathogenesis of acute gouty arthritis
interaction of MSU with mononuclear
phagocytes -->
stimulates the production of interleukin I -->
initiates the inflammatory reaction -->
produces many of the systemic signs of the
disease, such as --> fever, increase in acute
phase reactants, neutrophilic leukocytosis
MSU crystals also lyse neutrophils, which
release lysosomal enzymes, thus exacerbating
inflammation
 Gout
Treatment of acute attack
purpose of therapy
reduce the inflammation in acute attack of gout
lower serum uric acid levels below the saturation
point (6.5 mg/dL)
reverse associated features that enhance gout, such
as hypertension, obesity and hypertriglyceridemia
indomethacin MC used non-steroidal
use for both the acute attack and for prophylaxis
 Gout
Treatment of acute attack
colchicine
diagnostic agent in differentiating gout from
other inflammatory arthritides, as an
anti-inflammatory agent
prophylaxis
significant gastrointestinal side-effects
corticosteroids can be used if either of the
above two drugs do not work or are
contraindicated
low dose aspirin is uricosuric
 Gout
Treatment of hyperuricemia
patients who are underexcretors of uric acid (urine uric acid
< 700 mg/day) should be treated with uricosuric agents
pre-existing renal insufficiency inhibits the effectiveness
of these drugs
alkalinization of the urine with bicarbonate or carbonic
anhydrase inhibitors is also recommended
probenecid (uricosuric)
sulfinpyrazone (uricosuric)
also has an antiplatelet effect
allopurinol is an xanthine oxidase inhibitor (decreases uric
acid production)
 Gout
Side effects of allopurinol
precipitation of acute gouty arthritis (MC)
enhance 6-mercaptopurine and azathioprine
drug hypersensitivity reaction in kidney
granulomatous hepatitis
skin rashes
marrow suppression
 Calcium pyrophosphate dihydrate
crystal deposition arthropathy
(CPPD)
Definition: CPPD, or pseudogout, is a type of degenerative
joint disease characterized by deposition of calcium
pyrophosphate in joints, MC the knee (> 50%)
Pathogenesis:
CPPD disease may be
hereditary
idiopathic
associated with metabolic disease (e.g. primary
hyperparathyroidism,. hemochromatosis)
associated with joint trauma (osteoarthritis, RA)
 Pseudogout (CPPD)
Clinical:
MC in knee
Crystals can deposit in cartilage (chondrocalcinosis),
synovial cavity, or synovium
precipitating events for acute arthritis include surgery or
an acute medical illness
majority show a progressive degeneration of the joints
involved
x-ray appearance of punctate and linear densities in
articular hyaline or fibrocartilaginous tissue is almost
diagnostic for CPPD
Laboratory: review the SF analysis section
Chondrocalcinosis: note the linear
density in the articular cartilage
representing pseudogout crystals
Pseudogout: Neutrophil has
phagocytized a crystal
ID/CC A 24 year old white male visits his
family doctor complaining of low back
pain and stiffness on active movement
of the spine for almost a year;
increasing in severity.
HPI The pain increases with movement and
radiates down the posterior thigh,
improving as the day progresses
PE Stooped posture; loss of lumbar
lordosis and fixed kyphosis; tenderness
over sacroiliac joints; reduced chest
expansion; prominent abdomen
 Ankylosing spondylitis (AS)
Definition: AS is a seronegative
spondyloarthropathy (RF negative) that is
related to other disorders such as Reiters
syndrome, psoriatic spondylitis, and
inflammatory bowel disease
it is not a variant of RA
 Ankylosing spondylitis (AS)
Age/sex:
young men between the ages of 15-30 years
who are HLA-B27 positive in 95% of cases
Pathogenesis:
association with HLA B27
approximately 20% of patients will eventually
develop AS or one of the other variants upon
exposure to certain environmental factors
10-20% risk for the disease in the offspring
 Ankylosing spondylitis (AS)
Clinical:
characteristic features include
insidious onset
age < 40 years
persistence for more than 3 months
morning stiffness that is relieved with exercise
characteristically affects the sacroiliac joints first
(sacroiliitis)
muscle spasm in the lower back and loss of the normal
lumbar lordosis
diminished anterior flexion of the spine, identified
with the Schoeber test
 Ankylosing spondylitis (AS)
Clinical:
vertebral column involved with
subsequent fusion of the vertebral column
and production of the bamboo spine
complications:
restriction of chest movement and subsequent
restrictive type lung disease
iridocyclitis (25%)
aortic valve incompetence with regurgitation
(3.5 to 10%)
reactive amyloidosis (10%)
AS: Bamboo Spine
 AS: Stooped appearance
(anterior flexion) of a patient
with ankylosing spondylitis
 Ankylosing spondylitis (AS)
Treatment:
indomethacin is the drug of choice
ID/CC A 23 year old man presents with
bilateral conjunctivitis, painful swelling
of the right knee, bilateral heel pain,
and painless ulcers on his penis.
HPI He was diagnosed and treated for
nongonococcal urethritis one week ago
PE Bilateral conjunctivitis with anterior
uveitis; circinate balanitis; kerato-
blennorrhagicum on palms and
soles; arthritis of right knee and ankle
 Reiters syndrome
Definition: Reiters syndrome is a
seronegative spondyloarthropathy
characterized by
urethritis
conjunctivitis
HLA B-27 positive arthritis
Cant Pee, Cant See, Cant Climb Trees
Age/sex: young male
 Reiters syndrome
Clinical:
frequently heralded in by
chlamydial urethritis
intestinal infection with
Shigella
Salmonella
Campylobacter
Yersinia
Reiters Syndrome:
Conjunctivitis
 Reiters syndrome
Clinical:
arthritis typically begins a few weeks after an
infectious episode
asymmetric
MC involves the knees, ankles, fingers and toes
fingers and toes have a characteristic diffuse sausage
shaped appearance
low back pain often associated with sacroiliitis
 Reiters syndrome
Clinical:
conjunctivitis (40%) is non-infectious
urethritis may be caused by Chlamydia
trachomatis
cutaneous lesions include
balanitis circinata (painless ulcers on the glans penis
and urethral meatus) in 25-50%
keratoderma blennorrhagia (a hyperkeratotic skin
lesions) in approximately 10%
 Reiters syndrome
Clinical:
laboratory:
positive HLA-B27 in 90%
treatment:
indomethacin is the treatment of choice for the
arthritis
 Psoriatic arthritis
Definition: psoriatic arthritis is a
seronegative spondyloarthropathy that
occurs in approximately 7% of patients with
psoriasis
 Psoriatic arthritis
Clinical:
the arthritis associated with psoriasis is
asymmetric and MC involves the hands or feet
swelling and deformity of the DIP joint with pitting
of the nails (sausage digits)
on x-ray, there is a pencil in cup appearance of the
DIP joint with severe erosive disease
Laboratory: positive HLA-B27
Psoriatic Arthritis
Psoriatic Arthritis: Pencil in a
Cup
 Enteropathic arthritis
Definition: Enteropathic arthritis refers to
arthritis associated with ulcerative colitis
and Crohns disease, or as a reactive
arthritis after infections with Shigella,
Campylobacter, Salmonella, and Yersinia
enteritis
 Enteropathic arthritis
Clinical:
peripheral arthritis and spondylitis occurs as a late
manifestation in approximately 15-20% of patients
with inflammatory bowel disease (UC more
common than Crohns)
it produces a symmetric arthritis involving the
large joints, especially the knee, ankles and wrists
negative RF test
no association with HLA-B27 antigen in the peripheral
arthritis (wrists, etc).
spondylitis with sacroiliitis occurs in 20% of
patients and is associated with HLA-B27 positivity
(< 50%)
 Group III: septic arthritis
Infectious arthritis: non-gonococcal and
gonococcal

Bacterial arthritis: non-gonococcal and

gonococcal
bacterial arthritis is the most destructive
form of infectious arthritis
subdivided into gonococcal and non-
gonococcal types
 Infectious arthritis: non-gonococcal and
gonococcal
Pathogenesis of infectious arthritis
secondary to
hematogenous spread
osteomyelitis (children in particular)
intraarticular injection
Staphylococcus aureus and gram negative bacilli
are extremely destructive bacteria within a joint
Infectious arthritis: non-gonococcal and
gonococcal
Neisseria gonorrhoeae and viruses are less
likely to cause irreversible damage
majority of non-gonococcal arthritis due to
Staphylococcus aureus
E. coli is the MC offender in the elderly
in children from 6 months to 2 years, H.
influenza is the MC offender
 Infectious arthritis:
non-gonococcal and gonococcal

Clinical (non-gonococcal):
fever
knee MC site
SF cultures positive in 50%
 Infectious arthritis:
non-gonococcal and gonococcal

Gonococcal septic arthritis is MC overall

cause of septic arthritis particularly in urban
populations
usually associated with disseminated GC in
asymptomatic young women
can be associated with deficiencies of C 5, 6,
7 or 8, which are required to phagocytize the
organism
N. gonorrhoeae recovered in SF culture in 50%
Disseminated gonococcemia
N. gonorrhea gram stain of SF
 Infectious arthritis:
non-gonococcal and gonococcal

Clinical: (STD - mnemonic)

septic arthritis involves 1-3 joints -->
knees, wrists or ankles
tenosynovitis typically involves more
than one joint --> wrists, fingers,
ankles and toes
dermatitis consisting of macules,
papules, vesicles or pustules is seen in
the majority of cases
 Lymes disease
Definition: Lymes disease is a multisystem
disease caused by a tick-borne (Ioxides
dammini) spirochete called Borrelia
burgdorferi (also carries Babesia--hemolytic
anemia)
 Lymes disease
Clinical:
early:
characteristic skin lesion called erythema
chronicum migrans
develops at the site of the tick bite
single most important finding in early disease
with a history of tick bite is diagnostic of Lymes
disease, since serologic studies are frequently not
helpful early in the disease
white tail deer and white footed mouse is reservoir
Correlated with 2-3 years after a large acorn crop
from oak trees
Lymes Disease
 Lymes disease
Clinical:
constitutional symptoms of
fever
malaise
myalgias
arthralgias
headache
 Lymes disease
Clinical:
late:
weeks to months later, some patients develop
neurologic (MC Bells palsy) symptoms
cardiac (AV blocks and myocarditis)
joint abnormalities (60%; knee MC site)- MC
manifestation of late disease
 Lymes disease
Laboratory:
diagnosis best made by serological
methods, with antibodies peaking 3-6
weeks after the onset of the disease
not worthwhile to try to demonstrate the
spirochete in tissue
Treatment:
tetracycline in early disease
ceftriaxone in neurologic, cardiac or
arthritic findings
IV penicillin very effective in CNS and joint
disease
 Connective Tissue Diseases
ANA testing
Antinuclear antibodies (ANA) develop
as a consequence of tissue injury or the
natural aging process
Serum ANA is a useful screen for
presence or absence of autoimmune
disease
 ANA testing

Major groups of ANA are

antibodies to DNA (both double stranded
and single stranded)
antibodies to histones
antibodies to nonhistone proteins
antibodies to nucleolar antigens
 ANA testing
Serum ANA test is a fluorescent antibody
test, which provides a pattern of nuclear
fluorescence and titer of the antibody
a rim, or peripheral pattern, suggests the
presence of
anti-DS DNA and the possibility of systemic lupus
erythematosus (SLE) with significant renal disease
all patients with a positive rim pattern should have a
separate antiDS-DNA study ordered
A homogenous, or diffuse ANA pattern
non-specific
Rim Pattern
Homogeneous pattern
 ANA testing
A speckled ANA pattern suggests the presence of
antibodies against nuclear RNA and acidic and basic
nuclear proteins
depending on the clinical presentation of the patient, a
speckled ANA pattern should prompt the ordering of the
following antibodies
anti-Sm (Smith) --> highly specific for SLE
anti-RNP (ribonucleoprotein) --> highly specific for
mixed connective tissue disease
anti-Scl-70 antibody --> progressive systemic sclerosis
anti-PM-1 and anti-JO-1 --> dermatomyositis and
polymyositis
Speckled Pattern
 ANA testing

A nucleolar pattern is virtually diagnostic

for progressive systemic sclerosis
Nucleolar pattern
 LE Prep

Definition: the LE cell is a neutrophil

that has phagocytized free DNA that
has been altered by anti-nucleoprotein
antibodies
an LE cell is not specific for SLE and
should never be ordered in the absence of
a positive ANA
most consider it an outmoded test
 Autoantibodies
Anti-acetylcholine receptor antibody
(AChR)
Present in generalized myasthenia gravis (90%)
and myasthenia gravis associated with
thymoma (60%)
Responsible for the defect in neuromuscular
transmission
Correlates with disease activity
 Autoantibodies
Anticentromere antibody
Associated with the CREST syndrome (60%) and
Progressive systemic sclerosis (10%)
Produces a speckled pattern
Anti-gliadin antibody
Associated with celiac disease (95%)
Alcohol extract of gluten in wheat
Anti-reticulum and endomysial antibodies
(endomysium of smooth muscle) are also elevated
in celiac disease
 Autoantibodies
Anti-glomerular basement membrane
antibody
Present in Goodpastures syndrome (>90%
sensitivity and specificity)
Antibody is against an epitope from type IV
collagen in the basement membrane of the
glomerulus and pulmonary capillaries
 Autoantibodies
Anti-insulin and anti-islet cell antibodies
Anti-insulin antibodies develop in pre-type I diabetes
mellitus before insulin is used in treatment.
They also develop in patients taking bovine or porcine
insulin but not human insulin
Anti-islet cell antibodies are noted in type I diabetes
mellitus (60-90%)
Anti-microsomal antibody
Associated with Hashimotos autoimmune thyroiditis
(97%) and autoimmune hepatitis (70%)
 Autoantibodies
Anti-mitochondrial antibody
Present in primary biliary cirrhosis (90-100%)
Anti-neutrophil cytoplasmic antibody (ANCA)
C (cytoplasmic) ANCA is present in Wegeners
granulomatosis (> 90% sensitivity); also a marker of
disease activity
P (perinuclear) ANCA is associated with polyarteritis
nodosa (> 80%) and other inflammatory conditions
(ulcerative colitis, crescentic glomerulonephritis).
The antibody is directed against myeloperoxidase
 Autoantibodies
Anti-parietal cell and intrinsic factor
antibodies
Parietal cell antibodies are present in 90% of patients
with pernicious anemia (PA); also noted in chronic
atrophic gastritis which limits its specificity.
Antibodies to intrinsic factor (IF) are type I (blocking
antibody that prevents B12 from binding to IF-most
specific for diagnosing PA) and type II (binding
antibody that binds to IF or the IF-B12 complex)
 Autoantibodies
Anti-smooth muscle antibody
Associated with autoimmune hepatitis (70%)
Anti-thyroglobulin antibody
Present in Hashimotos autoimmune thyroiditis
(85%) and Graves disease (30%)
Less sensitive than anti-microsomal antibody in
Hashimotos thyroiditis
 Autoantibodies
Anti-striated Muscle Antibodies
React with both skeletal and cardiac muscle
Seen in 50% of patients with Myasthenia gravis
and 95% of MG patients with a thymoma
Anti-histone antibody
Seen in 70% of SLE patients and 15% of RA
patients; 95% of drug-induced SLE
 Autoantibodies
Anticardiolipin Antibody
Hallmark of primary antiphospholipid
syndrome; also found in up to 50% of
SLE and other systemic rheumatic
disease
 Pathogenesis of autoimmune
diseases
Emergence of a sequestered antigen (e.g. lens protein,
sperm)
emergence of forbidden clones
loss of suppressor T8 cells
alteration of self-antigens by drugs, viruses or
infections
loss of serum suppressor antibodies
cross-reactivity between self and foreign antigens
an abnormal immune response genes on chromosome
6 (Ir genes)
 Classification of autoimmune
diseases
Examples of organ-specific autoimmune
diseases include
myasthenia gravis
Graves Disease
Addisons disease
pernicious anemia
Classification of autoimmune
diseases
Examples of autoimmune diseases that
are systemic in their presentation
include
SLE
progressive systemic sclerosis (PSS)
dermatomyosis
rheumatoid arthritis
Sjogrens syndrome
mixed connective tissue disease (MCTD)
 Systemic lupus erythematosus
(SLE)
Definition: SLE is a connective tissue
disorder resulting from an
immunoregulatory disturbance of
multifactorial etiology
Age/sex: MC in young women
SLE: Butterfly rash
 SLE: Skin Biopsy showing
chronic inflammatory infiltrate at
the dermal-epidermal junction
 Systemic lupus
erythematosus (SLE)
Arthritis is the MC presenting
symptom of SLE (95%)
involves both large and small joints
resembling RA in many respects, except
that the joint involvement in SLE is
usually less destructive
morning stiffness is common
avascular necrosis of the femoral head is
seen in those on long-term corticosteroids
 Systemic lupus erythematosus
(SLE)
Skin is involved in SLE (80%)
either as a localized disease (discoid lupus erythematosus)
or as part of the systemic disease
discoid lupus erythematosus, the skin lesion is the primary
abnormality and is the result of immune complex
deposition along the basement membrane that is restricted
to the area of the rash
skin lesion in SLE is also due to immune complex
deposition along skin as well as skin involved with the
disease
 SLE
a skin biopsy and direct immunofluorescence
testing (band test) is useful in diagnosing
either SLE or discoid lupus
butterfly rash of lupus (50%) of cases
livedo reticularis, a lace-like venular skin
change, is sometimes associated with the
presence of anti-cardiolipin antibodies
SLE: Band Test
Band pattern
Systemic lupus erythematosus (SLE)

Serositis is inflammation of the

pericardium (MC) and pleura (30-
50%)
pericarditis MC cardiovascular
manifestation of SLE
unexplained pleural effusion in a young
woman is suspect for SLE
Systemic lupus erythematosus (SLE)

Libman-Sacks endocarditis (< 10%);

warty, non-embolic vegetations
scattered over the valve surfaces and
endocardium; not clinically significant
Systemic lupus erythematosus (SLE)

Pulmonary involvement (40-50%)

pleuritis with effusion is MC
chronic interstitial lung disease with a
restrictive pattern
Systemic lupus erythematosus (SLE)

Generalized lymphadenopathy occurs

in 50% of cases
angioimmunoblastic lymphadenopathy
with
fever
generalized lymphadenopathy
hepatosplenomegaly
skin rash
polyclonal gammopathy
Coombs positive hemolytic anemia
Systemic lupus erythematosus (SLE)

Splenomegaly
renal disease (50-60%)
MC type is diffuse proliferative
glomerulonephritis characterized by
subendothelial deposition of immune
complexes
renal failure MCC of death
Systemic lupus erythematosus (SLE)

CNS (25-30%)
loss of orientation
mental deterioration
psychosis
Systemic lupus erythematosus (SLE)

Hematologic problems:
anemia (50%)
autoimmune warm hemolytic anemia
absolute leukopenia
autoimmune thrombocytopenia
combination of autoimmune
thrombocytopenia and anemia is called
Evans syndrome
Systemic lupus erythematosus (SLE)

Lupus anticoagulant (LA--10%) and

anti-cardiolipin antibody (50%--
ACLA)
associated with thrombosis and fetal
loss
Cross Reaction with VDRL
Systemic lupus erythematosus (SLE)

SLE frequently worsens in pregnancy

increased incidence of spontaneous abortions
associated with anticardiolipin and LA
antibodies
complete heart block in newborns is seen with
patients having anti SS-A (anti Ro) antibodies
Systemic lupus erythematosus (SLE)
Laboratory:
positive serum ANA in 95-99% of patients
positive double-stranded DNA in 50-75% of patients
high specificity for SLE and renal disease
titers correlate well with disease activity
positive anti-Sm in 30-35%; specificity is close to
100%
antiSS-A (anti Ro) is present in mothers who have
newborns with complete heart block
positive LE prep (50-80%)
low C3 complement when active
 Systemic lupus erythematosus
(SLE)
Drug-induced SLE
differs from SLE in having a
very low incidence of renal and CNS involvement
absent anti-double-stranded DNA and anti-Sm
normal complement levels
antihistone antibodies are elevated (95%)
anti-single stranded DNA (80%)
drugs implicated include procainamide (MC), phenytoin,
hydralazine, quinidine, methyldopa, isoniazid, and
chlorpromazine
syndrome resolves with discontinuance of the drug
ID/CC A 40 year old white female complains
of paleness and bluish discoloration of
the hands, mainly upon exposure to
cold, with redness upon rewarming,
together with increasing pain in the
knees, elbows, and hands over several
months and recent difficulty
swallowing solid food
HPI She also has mask-like facies with a
limited range of expression
PE Smooth, shiny, tight skin over face and
fingers; edema of hands and feet;
palpable subcutaneous calcinosis;
pigmentation and telangiectasis of face
Progressive systemic sclerosis
(PSS)
Definition: PSS (scleroderma) is a
generalized disorder of connective
tissue characterized by degenerative
and inflammatory changes that
subsequently lead to intense fibrosis
age/sex:
MC in females
onset in the 30-60 year old bracket
 Progressive systemic sclerosis
(PSS)
Pathogenesis:
involves a small-vessel vasculitis and the
excessive deposition of normal collagen in
tissue throughout the body
 Progressive systemic sclerosis
(PSS)
Clinical:
first symptoms include
Raynauds phenomenon
swelling and puffiness of the fingers or hands
polyarthritis/algias
a diffuse variant, as well as a variant designated
CREST syndrome (20-25%)
PSS: Tight facial features
PSS: Sclerodactyly (tapered
fingers), swelling, gangrene
Progressive systemic sclerosis
(PSS)
CREST syndrome is characterized by
Calcinosis
Raynauds phenomenon
esophageal motility problems
sclerodactyly
telangiectasia
positive anti-centromere antibody
Calcinosis
Raynauds Phenomenon
 Progressive systemic sclerosis
(PSS)
Clinical:
skin (100%)
bilateral symmetric swelling of the fingers and hands,
face (tight facial features resembling a mouse--
Mauskopf facies)
mall, punctate telangiectasias over the face, fingers,
and lips
Raynauds phenomenon (85%)
often antedates PSS
arthralgias or arthritis (85%)
not as severe as in RA
sclerodactyly
 Progressive systemic sclerosis
Clinical:
the gastrointestinal tract (80%)
distal esophagus MC (relaxed LES sphincter, dilated esophagus)
malabsorption secondary to fibrous tissue replacement of muscle
and lack of intestinal motility
wide-mouthed diverticular sacs develop in the colon
pericardial effusions (20-50%)
kidneys (60%)
vasculitis and immune-complex glomerulonephritis
malignant hypertension
renal failure (MCC of death)
pulmonary involvement (20%)
diffuse interstitial pneumonitis with fibrosis (restrictive lung
disease)
 Progressive systemic sclerosis
Laboratory:
positive ANA (70-90%)
positive anti-Scl-70 (70%)
positive anti-centromere in the CREST variant
(70-80%)
Treatment:
penicillamine may improve long-term survival
vasodilators may be useful
ID/CC A 52 year old white female complains to her
family doctor of difficulty climbing steps for
the past six months and difficulty washing her
hair for the past two weeks
HPI She states that she does not feel tired or short
of breath but that her legs and arms just will
not cooperate. She also complains of
intermittent fever
PE Periorbital edema with purplish discoloration;
butterfly rash on face and neck; Raynauds
phenomenon; scaling of skin with redness
around knuckles; proximal muscle weakness
with tenderness in all four extremities
Labs Elevated CK; Elevated ESR; ANAs present
against tRNA
ID/CC A 37 year old white female complains
of increasing weakness for several
months, especially on climbing stairs
and while combing her hair
HPI She also complains of difficulty
holding her neck upright. For the past
few weeks, she has also had difficulty
swallowing
PE Atrophy of neck, shoulder, and thigh
muscles; motor weakness in all
proximal muscle groups; no sensory
deficit; deep tendon reflexes reduced;
heliotrope and Gottrons papules seen
in addition to photosensitive rash in
exposed areas Labs Markedly elevated
CPK; ANAs are positive
 Dermatomyositis/Polymyositis
Definition: dermatomyositis/polymyositis
are characterized by primary muscle disease
with pain (polymyositis) with or without
involvement of skin, the latter designated
dermatomyositis
Age/sex: adult and childhood variants
 Dermatomyositis/Polymyositis
Clinical:
least common autoimmune connective tissue disease
severe atrophy of the shoulder and hip girdle muscles
dysphagia occurs in 60% of patients
puffy eyelids with a purple-red discoloration referred to as
heliotrope eyelids
silvery, scale-like patches over the dorsum of the MCP and
PIP joints (Gottrons sign)
subcutaneous calcification evident on x-rays
men with polymyositis/dermatomyositis at increased risk for
malignant neoplasms (15-20%), particularly of the lung
Gottrons Sign
 Dermatomyositis/Polymyositis
Laboratory:
muscle biopsies show a lymphocytic
infiltration; diagnosis
elevated serum CK and aldolase (~ 100%)
positive anti-PM-1 and anti-JO-1 titers in 10
and 30% of cases, respectively
ID/CC A 42 year old woman presents with dysphagia, butterfly
rash, arthralgias, myalgias, skin stiffness, swelling of the
fingers, proximal muscle weakness, and chronic pain in
the finger joints.
HPI She has had these symptoms intermitently over the years,
but they have worsened over the past year
PE VS: normotension. PE: erythematous rash over face in
butterfly distribution; sclerodactyly; telangiectasias in
periungual areas; nonerosive arthritis of wrist and ankle
joints; proximal muscle weakness and tenderness;
weakness of neck muscles; no sensory loss; normal
tendon reflexes; positive Raynauds
Labs Elevated ESR; diffuse hypergammaglobulinemia; positive
RF; high titer of ANA antibodies (speckled pattern); Anti-
RNP antigen; elevated CPK
 Mixed connective tissue disease
(MCTD)
Definition: MCTD has features of SLE, PSS, polymyositis; it
is not an overlap syndrome, which is a combination of 2
diseases (e.g. SLE and RA)
Clinical:
follows a more benign course than the other autoimmune
diseases
rarely involves the kidney
Laboratory:
anti-ribonucleoprotein (RNP) antibodies (>95%)
 Sjogrens syndrome (SS)
Definition: SS is an autoimmune disease
characterized by diminished lacrimal and
salivary gland secretions resulting in dry
eyes (keratoconjunctivitis) and dry mouth
(xerostomia)
 Sjogrens syndrome (SS)
Clinical:
majority are women with rheumatoid arthritis
xerostomia MC initial symptom (cannot eat dry crackers)
trouble with swallowing and chewing; increase in
dental caries
keratoconjunctivitis sicca (10-15%) MC ocular complaint
Schirmer filter paper test is a good screen
symmetric parotid or submandibular gland enlargement
(50%)
proximal renal tubular acidosis
increased incidence of malignant lymphoma
Xerostomia
 Sjogrens syndrome (SS)
Laboratory:
positive ANA (50-80%)
positive anti-SS-A/Ro and anti-SS-B/La (more
specific than anti Ro) in approximately 60%
positive RF (75-90%)
confirmatory test for Sjogrens syndrome is a
lip biopsy of a minor salivary gland
demonstrating lymphocytic destruction of the
glands
 Sjogrens syndrome (SS)

Treatment:
symptomatic
corticosteroid if very severe disease
 Congenital lesions of bone
Osteogenesis imperfecta
(too little bone)
Osteogenesis imperfecta (too little bone), or
brittle bone disease, is due to abnormal collagen
synthesis with resulting abnormalities in the
skeleton (fractures), eyes (blue sclera--too little
collagen), ears (hearing deficits), joints (laxity),
and teeth (deficiency of dentin in teeth--blue-
yellow color)
most common (MC) hereditary bone disease
most are autosomal dominant, some are recessive
pathologic fractures
Osteogenesis Imperfecta (Blue
sclera)
OSTEOGENESIS IMPERFECTA
BLUE SCLERA
Osteogenesis Imperfecta
 Congenital lesions of bone
Achondroplasia
Achondroplasia is an autosomal dominant
disease characterized by impaired formation
of cartilage and premature closure of the
epiphyseal plates of long bones
characteristic features of the circus dwarf
with a normal sized head and vertebral column
but shortened arms and legs
normal life expectancy
 Osteopetrosis
Osteoporosis, or marble bone disease, is due
to an overgrowth and sclerosis of cortical bone
(too much bone) due to a defect in
osteoclasts with replacement of the marrow
cavity by bone, thus requiring extramedullary
hematopoiesis
AR or AD inheritance
pathologic fractures
anemia
since osteoclasts derive from monocytes, marrow
transplant is sometimes performed
 Infections of bone
Infection of the bone marrow and bone is referred to as
osteomyelitis
The three most serious infections of bone include pyogenic
osteomyelitis, tuberculosis, and syphilis
Pyogenic osteomyelitis occurs most frequently in children and
young adults and is MC due to Staphylococcus aureus, which
reaches the bone via the hematogenous route
other routes of infection are trauma (open fractures) and
direct extension from subjacent tissue
characteristically involves the metaphyseal area of the long
bones of the extremities where vascularity is most prominent
in infants, there is subperiosteal spread and extension into
the joint space resulting in suppurative arthritis and
permanent damage to the joint
 Infections of bone
In acute osteomyelitis, the marrow cavity is
filled with acute inflammatory cells, which
enzymatically destroy bone and leave
devitalized portions of bone called sequestra
floating in a sea of pus
Staphylococcal Osteomyelitis
 Infections of bone
In chronic osteomyelitis, there is a mixture
of both acute and chronic inflammatory
cells with extensive reactive bone formation
in the periosteum called involucrum
 Infections of bone
In acute osteomyelitis, the patient presents
with high fever and pain in the affected
bone with an associated absolute
leukocytosis and positive blood cultures in
approximately 70% of cases
 Infections of bone
Patients with sickle cell anemia commonly
develop osteomyelitis secondary to
Salmonella species (? decreased splenic
function cannot filter out of the blood
stream)
 Bone fractures
Fractures of bone may occur in previously normal bone
from external trauma or from a preexisting disease in the
bone which produces a pathologic fracture (metastatic
disease, bone cysts, osteoporosis, etc.)
Fractures may be
complete or incomplete (green stick)
closed (simple) with intact overlying tissue
comminuted when the bone has been splintered
compound when the fracture site communicates with the
skin surface
 Bone fractures
There are three distinct stages of bone
healing characterized by
organization of a hematoma at the fracture site
conversion of the organized hematoma
(procallus) to a fibrocartilaginous callous
replacement of the fibrocartilaginous callous by
mature bone with eventual remodeling along
the lines of weight bearing to complete the
repair
 Fractures of bone
A greenstick fracture is commonly seen in
children and refers to a break in the cortex
on the convex side of the shaft but an intact
concave side
a femoral neck fracture is the most common
(MC) fracture of the femur and is MC in the
elderly
 Fractures of bone
the scaphoid (navicular) bone is the MC
fracture of carpal bones
with the fingers clenched into a fist, they should
all point to the scaphoid bone
very susceptible to avascular necrosis and non-
union
dislocation of the lunate bone is the second MC
injury to the carpal bones
 Fractures of bone
Supracondylar fractures of the humerus are
common in children
possible entrapment of the brachial artery and
median nerve
danger of developing Volkmann's ischemic
contracture of the forearm muscles due to loss
of the brachial artery blood supply; requires a
fasciotomy
 Fractures of bone
Pathologic fractures
the most common causes of pathologic
fractures are metastatic bone disease and
primary disease of bone
they are called pathologic, because there is a disease
in the bone as opposed to trauma resulting in a
fracture of normal bone
common primary sites that metastasize to bone
are-most common bone metasized to: vertebra
breast (most common)
lung (small cell carcinoma)
thyroid (follicular carcinoma)
 Fractures of bone
Multiple myeloma, the most common primary hematologic
malignancy of bone, is also associated with pathologic
fractures due to the presence of lytic lesions secondary to the
secretion of osteoclast activating factor by the malignant
plasma cells
Benign diseases causing pathologic fractures include
bone cysts
Pagets disease of bone
osteoporosis
 Avascular necrosis
Avascular necrosis is seen in patients with
SLE on corticosteroids (MCC)
sickle cell disease
trauma
Pain MC clinical finding
Bone has increased density on x-ray
MRI has highest sensitivity
 Avascular necrosis
MC in
femoral head (Legg Perthes disease)
scaphoid (navicular) bone (Keinbocks disease)
body of the talus bone in the ankle
Legg Perthes disease is more common in boys than girls
age range 3 to 12 years
slowly evolving painless limp is the MC presenting
sign
pain most frequently referred to the groin area
leg will be shorter on the affected side
Avascular Necrosis with new
bone formation
 Aseptic Necrosis
Legg-Perthe (femoral head; child under 10)
Femoral fracture in elderly (most common
cause)
Associated with corticosteroids; HbSS
Scaphoid bone in wrist
ID/CC A 70 year old male immigrant from
England presents with pain in the right
leg, producing an awkward gait,
together with bilateral hearing loss
HPI He also has noted a progressive
increase in hat size
PE Slight bowing of right tibia; normal
rectal exam; mixed conductive and
sensorineural hearing loss confirmed by
audiometry
Labs Markedly elevated AP; increased
urinary excretion of hydroxyproline
 Pagets disease of bone
Pagets disease of bone (osteitis deformans)
refers to an abnormal thickening and
architecture of bone that primarily occurs in
elderly males
etiology is unknown
may represent either a slow virus infection or something
related to the measles virus
involves one bone or many bones, which in
decreasing order of frequency include the pelvis,
skull, and femur
 Pagets disease of bone

Changes in Paget's disease relate to an

initial period of excessive osteoclastic
resorption of bone followed by excessive
bone formation with haphazard arrangement
of the new bone into what is called mosaic
bone
despite its thickness, the bone is extremely soft
 Pagets disease of bone
features:
excessively high serum alkaline phosphatase
levels
AV fistulas within bone producing high
output cardiac failure
pathologic fractures
enlargement of the head and increase in hat
size
increased risk for osteogenic sarcomas
 Fibrous dysplasia
A benign, nonneoplastic process of bone
(ribs and femur) where bone is replaced by
fibroconnective tissue (woven bone)
may involve a single bone (monostotic) or
many bones (polyostotic), the latter often
associated with Albrights syndrome
abnormal skin pigmentation
precocious sexual development usually in females
treatment: local excision
 Bone tumors

The age of the patient, location in bone,

radiographic appearance of the bone tumor, and
biopsy material are essential for making a
definitive diagnosis
osteogenic sarcomas tend to occur during childhood
during periods of active skeletal growth, while
chondrosarcomas and giant cell tumors more
commonly arise in the middle years of life
 Bone Tumors
chondroblastomas and giant cell tumors of bone
are characteristically located in the epiphyseal
ends of long bones
bone lesions that are osteoblastic (osteogenic
sarcoma, osteoid osteoma) commonly yield
radiodensities on x-ray
 Bone tumors
MC benign primary tumor of bone is an
osteochondroma
MC malignancy is metastatic carcinoma
(lung, prostate, breast in adults and
neuroblastoma in children
MC hematopoietic tumor is multiple
myeloma (some books say it is the most
common overall primary tumor of bone
 Bone tumors
MC primary nonhematopoietic tumors of
bone in descending order of frequency
(Mayo Clinic)
osteogenic sarcoma
chondrosarcoma
Ewings sarcoma (#2 in children)
order of increasing age: Ewing's --> osteogenic
sarcoma --> chondrosarcoma
 Cartilaginous bone tumors
Benign cartilaginous tumors

Include:
osteochondroma (MC benign bone
tumor)
chondromas
chondroblastomas
 Cartilaginous bone tumors
Osteochondroma, or exostosis
Lobulated outgrowth of bone capped by a
zone of benign proliferating cartilage that
usually occur in the long bones
they may be solitary or multiple
(osteochondromatosis)
risk for developing into a chondrosarcoma is
greatest when multiple lesions are present
Olliers disease refers to multiple enchondromas
that most frequently involve the bones of the
hands and feet
Osteochondroma
 Chondrosarcoma
MC primary malignant cartilaginous tumor
Older Patients
location in descending order
pelvic bones
upper end of a humerus or femur
low grade tumor having a 90% ten year survival and
high grade tumors less than a 50% ten year survival
with metastasis MC to the lung
lungs and bone are the primary metastatic sites
treatment is surgery
 Chondrosarcoma
Arises de novo or secondary to
osteochondromatosis or enchondromatosis
Male dominant; > 30 years of age
Pelvic bones > upper end femur, humerus
Grade determines biologic behavior
Low grade 90% ten year survival
High grade < 50% ten year survival
Metastasizes to lungs
Chondrosarcoma
 Bone forming tumors
Benign bone producing tumors include the
osteoma
osteoid osteoma
osteoblastoma
 Bone forming tumors
Osteoma
A solitary benign tumor usually confined to
the skull and facial bones which may be
associated with Gardners hereditary
polyposis syndrome
 Osteoid osteoma
Benign neoplasm presenting with a distinctive
radiographic pattern of a small radiolucent
focus (nidus) surrounded by densely sclerotic
bone
males>females
cortical lesions
characteristically associated with extreme pain in
the favorite sites of involvement, which include the
femur, tibia, and humerus
pain is characteristically nocturnal (excess production of
prostaglandin E2) and dramatically responds to aspirin
en bloc resection
 Bone forming tumors
Osteoblastoma

Benign tumors MC involving the vertebrae

giant osteoid osteoma with similar appearance
on x-ray
ID/CC A 12 year old male presents with a swelling
above the right knee and associated pain.
HPI There is no history of trauma at the site of
pain, and there has been no fever or
discharge from the swelling
PE Bony-hard, tender, roughly circular
swelling above right knee (distal femur);
overlying skin temperature normal;
mechanical restriction of movement at
right knee Labs Normal ESR; elevated
serum alkaline phosphatase
Imaging XR-Plain: osteoblastic bone lesion at distal
end of femur with sunburst or onion-
peel periosteal reaction
 Bone forming tumors
Osteogenic sarcoma
MC primary malignancy of bone proper
individuals in the 10-25 year old age bracket
predisposing factors
exposure to radiation
preexisting bone disease (Pagets disease of
bone)
association with retinoblastoma and loss of
suppressor genes
location
MC in the lower end of the femur (35%) and
upper end of the tibia (15%)
Osteogenic Sarcoma: sunburst
appearance
Sunburst Appearance
Codmans
Triangle
Codmans Triangle
Osteogenic Sarcoma
 Bone forming tumors
Osteogenic sarcoma
Destruction of metaphysis of bone and
invasion of the subjacent soft tissue with
elevation of the periosteum producing a
Codmans triangle on x-ray
also sunburst appearance from calcified
osteoid extending into soft tissue
early hematogenous metastases MC to the
lungs (remove metastasis, still a good
prognosis)
 Other bone tumors
Ewings sarcoma

Highly malignant primary bone tumor of

marrow origin
exhibit a primitive neural phenotype
11;22 translocation
male predominant tumors
bone tumor with the youngest age bracket (10-
15 years old: #2 MC tumor in children)
 Other bone tumors
Ewings sarcoma

Location
usually arise in the diaphysis of long tubular
bones like the femur and flat bones of the pelvis
extension into the surrounding soft tissue
producing concentric onion skin layering
composed of reactive new bone formation
visible on x-ray
 Other bone tumors
Ewings sarcoma

Clinical (mimics infection)

fever
localized heat
anemia
increased sedimentation rate
75% 5 year survival
 Metastases
MC malignancy of bone (50 times more
frequent than primary malignant tumors of
bone)
MC occur from malignancies of the breast (#1),
lungs, kidney, prostate, and intestine
bone frequently involved
vertebra
pelvis
ribs
skull
sternum
upper ends of the femur
 Metastases
Most metastases to bone are lytic and
produce radiolucencies on x-ray
Osteoblastic metastases producing
radiodensities on x-ray are MC secondary to
prostate and breast cancer
increase in serum alkaline phosphatase
MCC of hypercalcemia in the hospitalized
population is metastatic bone disease (breast
#1)
 Osteoporosis
Most common (MC) metabolic abnormality
of bone in the United States
In women, it is MC due to estrogen
deficiency after menopause
since most of the bone is lost in the first 3-6
years after menopause, early estrogen
replacement is the key to the prevention of
osteoporosis
 Osteoporosis
Pathogenesis:
imbalance between the resorption of bone
(osteoclastic activity) and the formation of bone
(osteoblastic activity)
the increased osteoclastic activity creates large
holes that the osteoblasts are unable to fill
this imbalance is not related to increased
secretion of osteoclast activating factor by
macrophages or increased secretion of
parathormone
 Osteoporosis
Partial list of other disorders that predispose
to osteoporosis
women who have estrogen deficiency
associated with exercise induced amenorrhea or
anorexia nervosa
primary hyperparathyroidism
Cushings syndrome
chronic metabolic acidosis
heparin therapy
lack of gravity in space
 Osteoporosis
Clinical:
stress fractures of the vertebral bodies (most
common) and femoral neck
a decrease in overall height
Dowagers hump of the cervical spine
pathologic fractures
Osteoporosis: Dowagers Hump
Osteoporosis: collapse of the
Intervertebral bone (most
common fracture)
 Osteoporosis
Diagnosis:
combination of studies that evaluate bone
density and the degree of bone turnover
non-invasive studies that measure bone density
dual photon absorptiometry (key test)
single photon absorptiometry
dual energy x-ray absorptiometry
quantitative computed tomography
 Osteoporosis
Diagnosis:
an increase in urinary concentration of the
following indicates increased bone turnover
hydroxyproline
osteocalcin
pyridinoline
densitometry is analogous to a static
photograph of bone, while the turnover studies
provide an evaluation of bone dynamics
serum calcium and phosphorous are usually
normal in most cases of osteoporosis
 Osteoporosis
Treatment:
if not contraindicated, estrogen is the gold
standard for the prevention of osteoporosis and
should be given to all postmenopausal women
additional benefit is a 50% reduction in the incidence
of ischemic heart disease
usual dose is 0.625 mg/day of premarin
contraindications for estrogen include
pregnancy
breast cancer
undiagnosed vaginal bleeding
active thrombophlebitis
thromboembolic disorders previously associated with
estrogens
 Osteoporosis

Treatment:
additional preventive measures
calcium supplementation
vitamin D
weight bearing exercise
 Osteoporosis
Treatment:
additional pharmacologic agents are under study for
their use in the prevention and/or treatment of
osteoporosis
sodium fluoride increases bone formation in the spine, thus
decreasing vertebral fractures, but does so at the expense of
reducing cortical bone mass
bisphosphonates are potent inhibitors of bone resorption and
have a place in the prevention and treatment of osteoporosis
calcitonin-salmon is primarily used in the treatment of
osteoporosis, but is also useful in the prevention as well if
estrogens are contraindicated
can use tamoxifen (weak estrogen) in women with breast
cancer who are ERA positive
 Osteoporosis
Treatment:
progesterone alone is not used in either the prevention
or treatment of osteoporosis
because the incidence of endometrial carcinoma increases
0.1% per year with unopposed estrogen, the addition of 2.5
mg of medroxyprogesterone is recommended
problem with menses
treatment of weight loss osteoporosis
advise to increase body fat so that they begin having periods
15% below ideal weight GnRH shuts off
20% below ideal weight FSH and LH shut off
give oral contraceptives if the above is not an option