Board Review: Pediatric

RheumatologyKathy Haines, MD

Jennifer Weiss, MDChief of Pediatric Rheumatology

Joseph M. Sanzari Children’s HospitalHackensack University Medical Center

Associate Professor of PediatricsUMDNJ-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 PurpuraKawasaki 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. High grade fever for more than 5 days2. Polymorphous rash (MP, scarlatiniform, morbilliform),

often starts in the groin and diaper area3. Non exudative conjunctivitis4. Cervical lymphadenopathy >1.5 cm (usually unilateral)5. Mucositis (strawberry tongue, red lips and mouth, vertical

cracking of lips)6. 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

IVIG (2gm/KG): best outcome if prior to 10 days of fever Low dose aspirin Other (for refractory cases):

Pulse steroids Anti-TNF therapy

Complications: 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:

1 2 3 4 5

13%

30%

23%

10%

23%1. Idiopathic

thrombocytopenic purpura

2. HSP3. Leukemia4. Meningococcemia5. Rocky Mountain spotted

fever

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:

1 2 3 4 5

30% 30%

7%

10%

23%1. Dermatomyositis2. Systemic JIA3. Acute rheumatic fever4. Septic arthritis5. Systemic lupus

erythematosus

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:

1 2 3 4 5

13%

23%

30%

27%

7%

1. Legg Perthes disease

2. Slipped capitol femoral epiphysis

3. Oligoarticular JIA4. Septic arthritis5. Transient synovitis

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 JRAOligoarticular JIA Definition

Four or less joints Usually little girls (average

age: 2 yrs) Insidious onset of a swollen

joint, most often the knee Labs usually normal except:

ESR may be mildly elevated

ANA often positive High risk of iritis/uveitis

Uveitis in JIA

Bone deformities, contractures& atrophy

Polyarticular JRAPolyarticular 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 SpondylarthropathiesEnthesitis 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 ArthritisPsoriatic 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:

1 2 3 4 5

20%

30%

17%

23%

10%

1. Marked leukocytosis

2. Positive ANA3. Positive RF4. Joint pain5. Uveitis

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 likely to develop in this child:

1 2 3 4 5

13%

27%

17%

10%

33%

1. Psoriasis2. Lupus3. Uveitis4. Rheumatoid

nodules5. Muscle

weakness

Major Rheumatic Conditions

SLEDermatomyositis

SclerodermaVasculitis

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 pleuro-pericarditis)

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-Sm or Smith (highly specific for SLE) Anti-RNP (associated with mixed connective tissue

disease) Anti-SSA (Ro) and SSB (La)

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 Anti-

SSB/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

CK, AST, ALT, LDH, Aldolase Trunk, neck flexors, pharyngeal and respiratory

muscles can be involved EMG and muscle biopsy may not be necessary if

classical features present 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

Progresses from distal to proximal and truncal Cardiopulmonary disease

Interstitial lung disease Pulmonary hypertension Cor pulmonale

Hypertensive renal crisis

Serologies in Scleroderma ANA usually positive Anti-SCL 70

Systemic sclerosis Anti-Centromere

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:

1 2 3 4 5

13%

27% 27%27%

7%

1. ANA titer2. CK concentration3. EMG4. MRI of muscle5. Complement

levels

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:

1 2 3 4 5

23%

10%

23%

17%

27%

1. Antinuclear antibody2. Anti-Ro (SSA) and

anti-La (SSB)3. Human Lymphocyte

Antigens4. Serum complement

level5. Anti-Smith (Sm) levels

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:

1 2 3 4 5

33%

27%

10%

13%

17%1. ASO titer2. C3 level3. C-reactive protein4. Anti-dsDNA titer5. ESR