Board Review:
Pediatric
Rheumatology
Kathy Haines, MD
Jennifer Weiss, MD
Chief of Pediatric Rheumatology
Joseph M. Sanzari Children’s Hospital
Hackensack University Medical Center
Associate Professor of Pediatrics
UMDNJ-New Jersey Medical School
Arthritis



More than 100 causes
of arthritis in children
Arthritis is common in
rheumatic diseases
But not all rheumatic
diseases are
associated with arthritis
Acute Causes of Arthritis





Traumatic
 Hemarthrosis
Infectious
 Bacterial (septic arthritis, osteomyelitis, Lyme)
 Viral (esp rubella, parvo)
Post-Infectious
 Reactive arthritis
 Toxic/transient synovitis
Allergy
 Serum sickness
Acute Inflammatory and Rheumatic Conditions
 HSP
 Kawasaki disease
 Rheumatic fever
Most Common Causes of Chronic
Arthritis in Children

Juvenile Idiopathic Arthritis




What we used to call “JRA”
PLUS
Juvenile Spondyloarthritis
Juvenile Psoriatic Arthritis
Other chronic rheumatic syndromes



SLE
Dermatomyositis
Vasculitis
Other causes of joint pain:
Mimics of arthritis

Mechanical abnormalities







Patellofemoral Syndrome
Hypermobility Syndromes
Malignancies
Endocrine abnormalities
Inherited bony dysplasias
Chronic pain syndromes
Psychogenic causes
Acute Rheumatic
Syndromes
Reactive arthritis
Transient/toxic synovitis
Henoch Schonlein Purpura
Kawasaki Disease
Acute Rheumatic Fever
Reactive Arthritis
(aka Reiter Syndrome)




Arthritis and other extra-articular features following infections
Classical triggers:
 Enteric (Salmonella, Shigella, Yersinia)
 Non-gonoccoal urethritis
Other infections commonly cause reactive arthritis
 Varicella
 Parvovirus
 Group A Streptococcus (rheumatic fever and post-strep reactive
arthritis)
 Many other nonspecific infections
Extra-articular features:
 Conjunctivitis or uveitis
 Urethritis
 Rash (keratoderma blenorrhagicum)
 Not common in children
Transient synovitis







Acute hip synovitis in toddlers-early school age
Often follows onset of URI
Usually unilateral leg (hip) pain
May have low grade fever
Labs usually normal
PE: Pain and limitation of motion of affected hip
Self-limited: resolves within a few days to weeks
Henoch Schonlein Purpura


Common acute vasculitis of childhood
Manifestations:






Purpura
 Usually limited to lower extremities and buttocks
Arthritis
Nephritis
Abdominal pain
Usually self-limited (resolves after a few weeks)
Often post-infectious (especially Strep)
HSP
HSP continued


Purpuric rash on the LE is almost pathognomonic
(in the absence of infection or coagulopathy)
Biopsy:



Leukocytoclastic vasculitis (seen in many other types of
vasculitis)
IgA deposits on IF (diagnostic for HSP)
Nephritis:




IgA nephropathy
Usually manifests as hematuria which resolves
Need to check urinalysis frequently (weekly) for a month
and then monthly
Some develop chronic renal disease
HSP Treatment

Symptomatic


NSAIDs (joints)
Steroids (reserved for significant GI involvement)
Kawasaki Disease



Most common vasculitis in young children
Usually 6 years or younger
Criteria (5 of 6 must be present for definite dx)
1.
2.
3.
4.
5.
6.
High grade fever for more than 5 days
Polymorphous rash (MP, scarlatiniform, morbilliform),
often starts in the groin and diaper area
Non exudative conjunctivitis
Cervical lymphadenopathy >1.5 cm (usually unilateral)
Mucositis (strawberry tongue, red lips and mouth, vertical
cracking of lips)
Extremity changes (red palms and soles, edema of hands
and feet)
KD conjunctivitis
Polymorphous rash of KD
Typical mucositis of KD
Unilateral lymphadenopathy
Acute Extremity Changes of
KD
Late extremity manifestations
of KD
Kawasaki Disease: Labs

Labs reflect highly inflammatory state






Elevated WBC, ESR, CRP
Thrombocytosis comes later (1 to 2 wks after
onset)
Elevated LFTs (transaminases) common
Sterile pyuria
Aseptic meningitis
No specific diagnostic test
Kawasaki disease treatment

Treatment




Complications:




IVIG (2gm/KG): best outcome if prior to 10 days of fever
Low dose aspirin
Other (for refractory cases):
 Pulse steroids
 Anti-TNF therapy
Coronary artery aneurysms
Myocarditis
Myocardial infarction
Atypical KD patients that do not fulfill criteria is not
uncommon

Fever, rash, conjunctivitis most common features
Acute Rheumatic Fever



Post-Streptococcal rheumatic syndrome
Fever (usually low grade) and migratory
polyarthritis 1-2 weeks following Strep
infection (which can be subclinical)
Carditis is common but not always present


Mitral insufficiency most common
Acute phase reactants (ESR and CRP)
always elevated
ARF Jones Criteria




2 Major criteria, or 1 Major and 2 minor criteria
Major
 Migratory polyarthritis
 Carditis (valvulitis, especially mitral)
 Erythema marginatum
 Subcutaneous nodules
 Chorea
Minor
 Fever
 Elevated ESR
 Arthralgias (doesn’t count if has polyarthritis as major)
Prolonged PR interval
Required: Evidence of recent Strep infection
Uncommon Manifestations of
ARF: Nodules and erythema
marginatum
Treatment of Acute Rheumatic
Fever

Aspirin or NSAIDs




The arthritis will “melt away”
Must be taken consistently until ESR normalizes
Steroids reserved for severe carditis
Penicillin prophylaxis (until adulthood?)


PO
Monthly IM bicillin
A 6 year old boy has a 24 hr history of fever,
malaise, and bruising. He appears ill and his
temperature is 103. He has widespread petechiae
and palpable purpura on the buttocks and lower
extremities. The hgb is 10.5, WBC 22.5, and
platelets are 25,000. The most likely diagnosis is:
30%
1.
2.
3.
4.
5.
Idiopathic
thrombocytopenic
purpura
HSP
Leukemia
Meningococcemia
Rocky Mountain spotted
fever
23%
23%
13%
10%
1
2
3
4
5
An 8 year old girl has a painful left knee. Two
days ago her right ankle was painful and swollen,
but today it seems fine. She has a fever to 101,
and her resting heart rate is 120. Her knee is
swollen and painful, but her ankle is completely
normal. She has a Grade 3/6 systolic murmur. The
most likely diagnosis is:
30%
30%
1.
2.
3.
4.
5.
Dermatomyositis
Systemic JIA
Acute rheumatic fever
Septic arthritis
Systemic lupus
erythematosus
23%
10%
7%
1
2
3
4
5
A 5 year old boy has been limping for 3
days. He had an URI earlier in the week and
there is no hx of trauma. His temp is 99.9,
and he is limping. There is pain with flexion
and internal rotation of his right hip. The
WBC is 4.5 and ESR is 20. The most likely
diagnosis is:
30%
27%
1.
2.
3.
4.
5.
Legg Perthes
disease
Slipped capitol
femoral epiphysis
Oligoarticular JIA
Septic arthritis
Transient synovitis
23%
13%
7%
1
2
3
4
5
Chronic Arthritis in
Children
Chronic Arthritis in Children
(JRA and JIA)


Pauciarticular JRA / Oligoarticular JIA
Polyarticular JRA / Polyarticular JIA





RF positive
RF negative
Systemic JRA / Systemic JIA
Spondyloarthropathies / Enthesitis related JIA
Psoriatic arthritis / Psoriatic JIA
JRA/JIA Definition



Must have had arthritis in at least one joint for
> 6 weeks
Must be less than 16 years old at onset of
symptoms
Must exclude all other conditions

No tests are diagnostic
Pauciarticular JRA
Oligoarticular JIA

Definition




Usually little girls (average
age: 2 yrs)
Insidious onset of a swollen
joint, most often the knee
Labs usually normal except:



Four or less joints
ESR may be mildly
elevated
ANA often positive
High risk of iritis/uveitis
Uveitis in JIA
Bone deformities, contractures
& atrophy
Polyarticular JRA
Polyarticular JIA

Definition:





5 or more joints involved
No systemic sx
RF serologic status is
important in classification
RF negative poly JIA
(young girls: mean age 4)
RF positive poly JIA
(older pre- to teen aged
girls >10 years)
RF Negative Polyarticular JIA






>5 joints, but usually has symmetrical arthritis in many
joints, including small joints
RF negative
ANA + in 50% or more
Elevated ESR, CRP, Ig’s
Usually younger girls than RF positive
Moderate risk for uveitis
RF Positive Polyarticular JIA






Positive rheumatoid factor
test
Identical to adult Rheumatoid
Arthritis
Pre-teen/teen onset most
frequent
Similar joint pattern to RF
negative polyarthritis
Elevated ESR, CRP
Hallmark: rheumatoid
nodules
Systemic JRA or JIA




Fevers
 High (>39)
 Quotidian pattern is common
Rash
 Non-fixed pink eruption
 Worsens with fever spike
 Koebner phenomenon
Arthritis (any number of joints can
be affected)
Other features:
 Generalized lymphadenopathy
 Hepato- or splenomegaly
 Serositis (Pleuritis or
pericarditis)
Quotidian Fever Pattern
Systemic JIA

Laboratory features







High WBC (poly predominant)
Anemia common
Thrombocytosis (often 5-800,000)
Very high ESR and CRP
Extremely high ferritin levels (500-10,000+)
Negative serologies
Other complications




Tamponade
Macrophage activation syndrome (can be fatal)
Pulmonary hypertension
Uveitis is not seen
Juvenile Spondylarthropathies
Enthesitis related JIA

Arthritis and enthesitis (usually calcaneal)



More common in pre-teens and teens
Boys > girls
Other features





HLA B-27 commonly positive
Acute anterior uveitis
Sacroiliitis
Inflammatory spine pain and limitation of flexion
Positive family history: anterior uveitis,
spondylarthropathies, especially ankylosing spondylitis,
Reiter syndrome and inflammatory bowel disease
Spondylarthropathy /
Enthesitis related JIA Features
Juvenile Psoriatic Arthritis
Psoriatic JIA


Arthritis and psoriasis
OR
Arthritis and a positive
family history of
psoriasis plus
 dactylitis
 nail pitting or
onycholysis
Psoriatic arthritis features
Psoriatic arthritis

Can mimic any of the following:




Oligoarticular JIA
Polyarticular JIA
Enthesitis related JIA and ankylosing spondylitis
Dactylitis (isolated swollen digits) is the most
specific type of arthritis associated with
arthritis
Dactylitis in psoriatic arthritis
JIA Treatment in a nutshell



Oligoarticular forms of JIA
 NSAIDs
 Intra-articular steroids
Polyarticular forms of JIA
 NSAIDs
 Methotrexate
 Prednisone is not usually needed
 Anti-TNF biologics
Systemic JIA
 NSAIDs
 Steroids for severe systemic symptoms (especially pericarditis)
 Methotrexate for arthritis
 Anti-IL1 and IL6 biologics
A 6 yr old boy has a 4 week hx of fevers to 40 deg
C once a day accompanied by a fleeting rash.
Physical examination reveals generalized
lymphadenopathy. Of the following, the most
common other manifestation of this patient’s
illness would be:
30%
1.
2.
3.
4.
5.
Marked
leukocytosis
Positive ANA
Positive RF
Joint pain
Uveitis
23%
20%
17%
10%
1
2
3
4
5
A 2 year old girl presents with a 2 month history of
intermittent limping. She cries when she first gets
up in the morning and won’t walk, but later on in
the day she is much better. She has had no fever.
On exam, she is happy and playful until you
examine her right knee, which is swollen and
warm and has decreased flexion. She is unable to
straighten it completely. Her labs are normal but
her ANA is positive. Which of the following is most
33%
likely to develop in this child:
1.
2.
3.
4.
5.
Psoriasis
Lupus
Uveitis
Rheumatoid
nodules
Muscle
weakness
27%
17%
13%
10%
1
2
3
4
5
Major Rheumatic
Conditions
SLE
Dermatomyositis
Scleroderma
Vasculitis
Childhood Systemic Lupus
Erythematosus



10% of pediatric rheumatology patients
It is a systemic disease that usually affects
more than one organ
Variable presentation


Acute fulminant onset with life-threatening
complications
Chronic insidious onset (can be difficult to
diagnose)
Lupus is a systemic disease






Rash (Malar rash classic, but many other skin manifestations)
Arthritis
Cytopenia
 Leukopenia and thrombocytopenia common
 Coombs’ positive hemolytic anemia
Nephritis (proteinuria alone or with hematuria)
 Can present with nephrotic syndrome or renal insufficiency
CNS manifestations
 Seizures
 Psychosis
 Other less common (transverse myelitis, coma, stroke)
Pulmonary and/or cardiac involvement (especially pleuropericarditis)
Laboratory testing for SLE



Basic labs are important:
 CBC (may see cytopenias)
 ESR usually elevated in active lupus
 Renal and hepatic function (chemscreen)
 Urinalysis: proteinuria and hematuria
Serologies:
 ANA (almost always positive, but not specific and can be falsely
positive)
 Anti-dsDNA (much more specific for lupus, and can be used to
follow disease activity)
Complement levels are low in active SLE
 C3 and C4
 Total complement
Other Antibody Tests in SLE

Anti-ENA



Anti-SSA (Ro) and SSB (La)



Anti-Sm or Smith (highly specific for SLE)
Anti-RNP (associated with mixed connective tissue
disease)
Associated with Sjogrens as well as lupus
Positive in mothers of babies who develop neonatal lupus
Anti-phospholipid antibodies


Anti-cardiolipin, anti-phosphatidyl serine, lupus
anticoagulant and beta-2 glycoprotein I
Associated with thromboembolic disease (pulmonary
emboli, deep vein thrombosis, frequent miscarriages,
arterial thrombosis)
Treatment of Lupus





Prednisone and pulse methylprednisolone
 For acute treatment of severe organ involvement
(kidneys, CNS, pericarditis)
Hydroxycholoquine (Plaquenil)
 Arthritis
 Rash
 General treatment of lupus
Methotrexate
 Arthritis
Cyclophosphamide, azathioprine or mycophenolate
 Significant renal and other organ system involvement
Anti-B cell therapies (Rituximab)
Neonatal Lupus

Babies born to mothers with
lupus or positive anti-SSA/SSB
antibodies:




Immune cytopenia
Rash
Congenital heart block
can cause hydrops and
fetal death
Congenital heart block highly
associated with:


Anti-SSA/Ro and/or AntiSSB/La
May be asymptomatic
but antibody positive
Juvenile Dermatomyositis


Inflammatory myositis (causing muscle
weakness, not usually pain) and specific
dermatitis
Triad



Diagnostic rash
Proximal muscle weakness
Elevated muscle enzymes
Skin Findings of
Dermatomyositis





Gottron’s papules
Heliotrope rash
Extensor rash
Nailfold telangiectasias and cuticular
hypertrophy
Photosensitive rash (can be mistaken for
lupus)


Malar rash
Shawl distribution of neck and shoulders
JDM Gottron’s Papules
Heliotrope rash
JDM Nailfold Telangiectasias
JDM extensor rash
JDM photosensitive malar rash
Muscle findings in
dermatomyositis


Symmetrical PROXIMAL>>>distal weakness of all
four extremities
Muscle enzymes ARE elevated



Trunk, neck flexors, pharyngeal and respiratory
muscles can be involved
EMG and muscle biopsy may not be necessary if
classical features present


CK, AST, ALT, LDH, Aldolase
Rash, proximal muscle weakness, elevated enzymes
MRI: edema of muscles consistent with myositis
JDM complications:
ulcerations
JDM complications: calcinosis
Gower maneuver in the younger
child
Dermatomyositis Treatment



Steroids
Methotrexate
Other





Cyclosporine
IVIG
Cellcept
Cyclophosphamide
Rituximab
Scleroderma

Systemic scleroderma



Progressive Systemic Sclerosis
CREST syndrome (Calcinosis, Raynaud’s,
Esophageal dysmotility, Sclerodactyly,
Telangiectasias)
Localized scleroderma


Morphea
Linear Scleroderma
Systemic Scleroderma


Severe Raynaud’s phenomenon
Diffuse tightening of the skin


Cardiopulmonary disease




Progresses from distal to proximal and truncal
Interstitial lung disease
Pulmonary hypertension
Cor pulmonale
Hypertensive renal crisis
Serologies in Scleroderma


ANA usually positive
Anti-SCL 70


Anti-Centromere


Systemic sclerosis
CREST syndrome
Anti-RNP

Mixed connective tissue disease often has
sclerodermatous features
Raynaud’s Phenomenon in
Scleroderma
Skin Features of Systemic
Sclerosis
Localized Scleroderma


Not related to systemic sclerosis
Two major types:


Morphea
Linear Scleroderma
Morphea
Linear Scleroderma
Treatment of Scleroderma

Systemic sclerosis

Symptomatic treatment





Raynaud’s (nifedipine, sildenafil)
Joints (steroids and methotrexate)
Pulmonary hypertension
Anti-fibrotic treatment may prove to be helpful
Localized scleroderma

Steroids and methotrexate may be effective for
linear scleroderma or severe morphea
A 9 year old girl has generalized weakness and a
rash. Findings include a malar rash and
erythematous papules over her PIP joints and
swollen red cuticles. Her proximal strength is 3/5.
Of the following, the most appropriate next step in
her evaluation is:
27%
1.
2.
3.
4.
5.
ANA titer
CK concentration
EMG
MRI of muscle
Complement
27%
27%
13%
7%
1
2
3
4
5
A male infant was delivered prematurely because
of progressive hydrops to a 34 yo woman. He was
found to have complete heart block. Of the
following, the most useful lab test in confirming
the diagnosis of neonatal lupus is:
27%
23%
1.
2.
3.
4.
5.
Antinuclear antibody
Anti-Ro (SSA) and
anti-La (SSB)
Human Lymphocyte
Antigens
Serum complement
level
Anti-Smith (Sm) levels
23%
17%
10%
1
2
3
4
5
A 13 year old female has fever, myalgias and joint
swelling for a month. She has arthritis, palatal
ulcers and small ulcerations on her fingertips. The
WBC is 3.5K and platelets are 120,000. Of the
following the most helpful test to confirm the
diagnosis is:
33%
27%
1.
2.
3.
4.
5.
17%
ASO titer
C3 level
C-reactive protein
Anti-dsDNA titer
ESR
13%
10%
1
2
3
4
5