1. 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

2. Arthritis More than 100 causes of arthritis in children
Arthritis is common in rheumatic diseases
But not all rheumatic diseases are associated with arthritis

3. 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

4. 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

5. 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

6. Acute Rheumatic Syndromes
Reactive arthritis
Transient/toxic synovitis
Henoch Schonlein Purpura
Kawasaki Disease
Acute Rheumatic Fever

7. 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

8. 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

9. 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)

10. HSP

12. 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

13. HSP Treatment Symptomatic NSAIDs (joints)
Steroids (reserved for significant GI involvement)

14. Kawasaki Disease Most common vasculitis in young children
Usually 6 years or younger
Criteria (5 of 6 must be present for definite dx)
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)

15. KD conjunctivitis

16. Polymorphous rash of KD

17. Typical mucositis of KD

18. Unilateral lymphadenopathy

19. Acute Extremity Changes of KD

20. Late extremity manifestations of KD

21. 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

22. Kawasaki disease 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

23. 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

24. ARF Jones Criteria 2 Major criteria, or 1 Major and 2 minor criteria
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

25. Uncommon Manifestations of ARF: Nodules and erythema marginatum

26. 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

27. A 6 year old boy has a 24 hr history of fever, malaise, and bruising
A 6 year old boy has a 24 hr history of fever, malaise, and bruising. He appears ill and his temperature is 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:
Idiopathic thrombocytopenic purpura
HSP
Leukemia
Meningococcemia
Rocky Mountain spotted fever

28. An 8 year old girl has a painful left knee
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:
Dermatomyositis
Systemic JIA
Acute rheumatic fever
Septic arthritis
Systemic lupus erythematosus

29. A 5 year old boy has been limping for 3 days
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:
Legg Perthes disease
Slipped capitol femoral epiphysis
Oligoarticular JIA
Septic arthritis
Transient synovitis

30. Chronic Arthritis in Children

31. 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

32. 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

33. Pauciarticular JRA Oligoarticular 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

34. Uveitis in JIA

35. Bone deformities, contractures & atrophy

36. 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)

37. 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

39. 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

40. 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)

42. Quotidian Fever Pattern

43. Systemic JIA Laboratory features Other complications
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

44. 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

45. Spondylarthropathy / Enthesitis related JIA Features

46. Juvenile Psoriatic Arthritis Psoriatic JIA
Arthritis and psoriasis OR
Arthritis and a positive family history of psoriasis plus
dactylitis
nail pitting or onycholysis

47. Psoriatic arthritis features

48. 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

49. Dactylitis in psoriatic arthritis

50. JIA Treatment in a nutshell
Oligoarticular forms of JIA
NSAIDs
Intra-articular steroids
Polyarticular forms of JIA
Methotrexate
Prednisone is not usually needed
Anti-TNF biologics
Systemic JIA
Steroids for severe systemic symptoms (especially pericarditis)
Methotrexate for arthritis
Anti-IL1 and IL6 biologics

51. 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:
Marked leukocytosis
Positive ANA
Positive RF
Joint pain
Uveitis

52. 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:
Psoriasis
Lupus
Uveitis
Rheumatoid nodules
Muscle weakness

53. Major Rheumatic Conditions
SLE
Dermatomyositis
Scleroderma
Vasculitis

54. 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)

55. 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)

59. 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

60. 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)

61. 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
Cyclophosphamide, azathioprine or mycophenolate
Significant renal and other organ system involvement
Anti-B cell therapies (Rituximab)

62. Neonatal Lupus Immune cytopenia Rash
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

63. Juvenile Dermatomyositis
Inflammatory myositis (causing muscle weakness, not usually pain) and specific dermatitis
Triad
Diagnostic rash
Proximal muscle weakness
Elevated muscle enzymes

64. 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

65. JDM Gottron’s Papules

66. Heliotrope rash

67. JDM Nailfold Telangiectasias

68. JDM extensor rash

69. JDM photosensitive malar rash

70. 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

71. JDM complications: ulcerations

72. JDM complications: calcinosis

73. Gower maneuver in the younger child

74. Dermatomyositis Treatment
Steroids
Methotrexate
Other
Cyclosporine
IVIG
Cellcept
Cyclophosphamide
Rituximab

75. Scleroderma Systemic scleroderma Localized scleroderma
Progressive Systemic Sclerosis
CREST syndrome (Calcinosis, Raynaud’s, Esophageal dysmotility, Sclerodactyly, Telangiectasias)
Localized scleroderma
Morphea
Linear Scleroderma

76. 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

77. 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

78. Raynaud’s Phenomenon in Scleroderma

79. Skin Features of Systemic Sclerosis

80. Localized Scleroderma
Not related to systemic sclerosis
Two major types:
Morphea
Linear Scleroderma

81. Morphea

82. Linear Scleroderma Linear scleroderma: leg
Linear scleroderma of 6 years duration, involving the right lower extremity, is seen in this 10-year-old girl. #

83. 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

84. ANA titer CK concentration EMG MRI of muscle Complement levels
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:
ANA titer
CK concentration
EMG
MRI of muscle
Complement levels

85. 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:
Antinuclear antibody
Anti-Ro (SSA) and anti-La (SSB)
Human Lymphocyte Antigens
Serum complement level
Anti-Smith (Sm) levels

86. 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:
ASO titer
C3 level
C-reactive protein
Anti-dsDNA titer
ESR