Juvenile Idiopathic Arthritis (JIA)

Basic Information

1. ▪JIA is a chronic autoimmune condition affecting the joints and eyes
2. ▪By definition, age of onset is <16 years, and symptoms of arthritis must be present for at least 6 weeks
3. ▪Untreated arthritis leads to joint contractures and permanent joint damage
4. ▪Untreated uveitis (eye inflammation) leads to blindness
5. ▪There are six subtypes with varying prognosis and clinical manifestations:
   • ▪Oligoarticular JIA
   • ▪Polyarticular JIA with negative rheumatoid factor (RF)
   • ▪Polyarticular JIA with positive RF
   • ▪Psoriatic JIA
   • ▪Enthesitis-related JIA
   • ▪Systemic-onset JIA

Clinical Presentation

1. ▪In all subtypes, stiffness and joint swelling are more prominent than joint pain
   1. ▪Decreased range of motion progresses over time
   2. ▪Leg length discrepancies or even growth retardation can result from chronic lower-extremity arthritis
   3. ▪Micrognathia and jaw asymmetry can result from temporomandibular joint arthritis

Oligoarticular JIA
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Most commonly occurs in toddler-age (3 years old) Caucasian females

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Four or more joints are involved initially

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Large joints, knee > ankle > wrist (but almost never hip or shoulder)

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Insidious onset

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Frequently antinuclear antibody (ANA) positive → highest risk of uveitis

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Uveitis is usually asymptomatic; therefore all patients require regular ophthalmologic screening

Polyarticular JIA
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Bimodal peak at age 1 to 3 years, and then adolescence, with female predominance

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More than five joints are involved

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Symmetrically involves small joints of hands and feet, in addition to large joints

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RF positivity confers a worse prognosis:

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Similar to adult rheumatoid arthritis; subcutaneous rheumatoid nodules may be present

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Asymptomatic uveitis is less common than in oligoarticular JIA

Psoriatic JIA
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Arthritis and psoriasis or other features that overlap with psoriasis:

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Dactylitis (“sausage digits”), nail pits or onycholysis, family history of psoriasis

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Asymmetrically involves small joints (especially distal interphalangeal [DIP]) and large joints

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Asymptomatic uveitis (especially if ANA positive)

Enthesitis-related JIA/juvenile ankylosing spondylitis

• ▪Frequently HLA-B27 positive, and more common in adolescent boys
• ▪Family history of other HLA-B27-positive spondyloarthropathies (ankylosing spondylitis, sacroiliitis with inflammatory bowel disease, reactive arthritis)
• ▪Peripheral arthritis, enthesitis, or axial involvement:
  1. ▪Inflammatory back pain is associated with sacroiliitis
     • ▪Back stiffness that is worse in the morning or with prolonged sitting and that improves with activity
       1. □Difficulty with forward flexion and flattening of the natural lumbar lordosis
       2. □Tenderness over the sacroiliac joints
  2. ▪Enthesitis is tenderness at insertion sites of tendons/ligaments into bone
  3. ▪Enthesitis-related JIA can progress to ankylosing spondylitis in adult years (fusion of lumbar vertebrae results in the classic “bamboo spine” radiographic finding)
• ▪Uveitis presents as an acute, painful red eye rather than asymptomatic uveitis
• ▪Significant overlap with inflammatory bowel disease–associated arthropathies, so close monitoring for gastrointestinal symptoms is necessary

Systemic-onset JIA

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Previously known as Still disease, it is a completely separate disease from other JIA subtypes

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Characterized by severe autoinflammation with peak onset at 1 to 5 years old:

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High-spiking fevers for at least 2 weeks, classically in a quotidian (daily) pattern

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Evanescent salmon-colored macules appear in conjunction with fever

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May appear in linear streaks or look urticarial with surrounding pallor

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Lymphadenopathy and hepatosplenomegaly

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Serositis (pleural/pericardial effusions, ascites)

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Polyarticular arthritis (especially hip and cervical spine)

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Not associated with a risk of uveitis

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Frequently complicated by macrophage activation syndrome (MAS), also known as secondary hemophagocytic lymphohistiocytosis, which is a severe, life-threatening state of dysregulated systemic inflammation and organ failure

Diagnosis and Evaluation
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Laboratory testing can help characterize the type of JIA but is not used to make a diagnosis of JIA:

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ANA determines risk of uveitis

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A positive ANA at low titers (1:160) can be detected in up to 20% of healthy children, and therefore it is not useful for diagnosis

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RF and HLA-B27 help determine JIA subtype

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Lyme should be excluded as a cause of chronic arthritis

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A mild leukocytosis, thrombocytosis, normocytic anemia, and mildly elevated ESR/CRP may be associated with active oligoarticular or polyarticular JIA

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In contrast, systemic-onset JIA is characterized by prominent leukocytosis, thrombocytosis, anemia, and elevated acute-phase reactants, especially ferritin

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± Transaminitis, hypoalbuminemia, prolonged coagulation time

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Cytopenias and dropping ESR (from fibrinogen consumption) in the setting of rising ferritin levels are indicators of MAS

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Synovial fluid analysis confirms that the effusion is inflammatory (WBC 5,000–20,000; up to 100,000 in systemic-onset JIA)

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Ultrasound can be used to demonstrate joint effusions if clinical examination is equivocal

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Demonstration of uveitis on slit-lamp examination can substantiate the diagnosis

Treatment
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All children suspected of having JIA should be referred to a rheumatologist

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Those diagnosed with JIA require ophthalmologic screening at regular intervals

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Mono- or oligoarticular arthritis is usually amenable to intraarticular corticosteroid injections

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Immunosuppressants such as low-dose methotrexate are usually needed for polyarticular arthritis

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NSAIDs can be helpful for pain and very mild arthritis

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Systemic-onset JIA is treated with systemic corticosteroids in combination with other antiinflammatory medications