Description

  • Polyarticular JIA is defined as chronic (>6 weeks) inflammatory arthritis in children <16 years old involving ≥5 joints during the first 6 months of illness
  • 2 subtypes:
    • Rheumatoid factor (RF)-positive subtype
      • Resembles adult rheumatoid arthritis
      • Symmetrically affecting small joints
      • Higher risk of rheumatoid nodules
      • Overall poor functional outcome
    • RF-negative subtype
      • Typically asymmetric
      • Higher risk of uveitis
      • Fewer rheumatoid nodules

Epidemiology

  • JIA is one of the most common chronic diseases in children
    • Reported prevalence of 3.8 to 400 cases per 100,000 children
    • Reported incidence of 1.6 to 23 new cases per 100,000 children per year
  • Approximate prevalence of International League of Associations for Rheumatology (ILAR) subtypes among children with JIA
    • Oligoarticular 50%-60%
    • Polyarticular 30%-35%
    • Systemic-onset 10%-20%
    • Psoriatic 2%-15%
    • Enthesitis-related 1%-7%
  • Reported frequency of polyarticular subtypes among all JIA
    • 2%-7% for rheumatoid factor (RF)-positive polyarthritis
    • 11%-28% for RF-negative polyarthritis
  • Possible risk factors include
    • Human leukocyte antigen (HLA) associations; increased likelihood for
      • RF-positive polyarthritis with DRB1*04, DQA1*03, DQB1*03
      • RF-negative polyarthritis with A2, DRB1*08, DQA1*04, DPB1*03
    • Increased antibiotic exposure in infancy

Etiology and Pathogenesis

  • Complex disease with multiple environmental and genetic risk factors 
  • Cause of JIA appears to be breakdown in immunologic self-tolerance
  • Increasing evidence for role of the microbiome (involved in immune system development/function)
    • Changes in microbiome composition similar to those seen in other autoimmune diseases (type I diabetes, inflammatory bowel disease)
    • Early exposure to antibiotics may increase risk via mechanism that alters intestinal microbiota
  • Pathogenesis of synovitis and joint damage
    • Inflammatory synovitis in JIA similar to synovitis in adult rheumatoid arthritis
    • Inflammation prompts pannus formation, with cartilage and bone erosions mediated by degradative enzymes, such as metalloproteinases
  • Complex role of genetics
    • Role of genetic factors supported by
      • Increased prevalence of autoimmunity among first-degree relatives of patients with JIA
      • Reported monozygotic twin concordance rates (ranges from 25% – 40%)
    • Human leukocyte antigen (HLA) region (encodes major histocompatability complex) is most important genetic contributor
    • Many non-HLA regions reported to be associated with oligoarticular and rheumatoid factor (RF)-negative polyarticular JIA subtypes
    • CD80-KTELC1 and JMJD1C -genetic associations not found in other autoimmune diseases; includes genes involved in
      • T-cell development/activation
      • regulating gene expression via demethylation of DNA histones

History

  • Ask about history of
    • Joint pain and/or decreased range of motion, may present as
      • Swollen joint(s)
      • Refusing to walk or use joint/limb
      • Excessive guarding
      • Limping
    • Systemic symptoms
      • Irritability
      • Fatigue
      • Anorexia
      • Low-grade fever
    • Anemia
    • Growth disturbance/retardation
    • Bony overgrowth or accelerated growth of affected joint
    • Leg length discrepancy
  • Considerations for subtypes
    • RF-positive polyarthritis
      • Predominantly affects adolescent girls
      • Similar to adult RF-positive rheumatoid arthritis with nodules reported in one-third
    • RF-negative polyarthritis has ≥ 3 distinct subsets
      • Similar to oligoarticular JIA (≥ 5 involved joints in first 6 months)
        • Early onset with female predominance
        • Asymmetric arthritis
        • Higher prevalence of uveitis
        • Frequent antinuclear antibody (ANA) positivity
      • Similar to adult-onset RF-negative rheumatoid arthritis
        • School age onset
        • Symmetric synovitis  
        • High erythrocyte sedimentation rate (ESR)
        • ANA negativity
      • Presenting as dry synovitis characterized by
        • Stiffness with negligible joint swelling
        • Flexion contractures
        • Normal/slightly elevated ESR

Physical

  • Skin exam; assess for
    • Pallor
    • Subcutaneous nontender “rheumatoid nodules” with variable size/consistency; commonly found on extensor surfaces
    • No skin rash (if evanescent erythematous rash presents, systemic-onset JIA likely)
  • HEENT exam; assess for
    • Uveitis
      • More common in polyarthritis RF-negative JIA
      • Often asymptomatic; may present with redness, pain, photophobia, and/or blurred vision
    • Temporomandibular joint (TMJ) involvement
      • Micrognathia and retrognathia  
      • Pain on palpation or mandibular movement
      • Maximal mouth opening and mouth opening deviation
  • Extremities – assess joints for
    • Symmetric vs. asymmetric pattern of involvement
    • Tenderness
    • Limited range of motion
    • Deformity
    • Swelling

Diagnosis

  • Identify JIA using definition from International League of Associations for Rheumatism (ILAR)
    • Signs of arthritis (joint swelling, or ≥ 2 of limitation of motion, tenderness, or pain with motion) in ≥ 1 joint
    • Onset < 16 years old and persists > 6 weeks
    • Other causes ruled out
  • Diagnose polyarticular JIA
    • Polyarthritis rheumatoid factor (RF)-positive if both
      • ≥5 affected joints in first 6 months of disease
      • ≥2 positive immunoglobulin M (IgM) RF > 3 months apart during first 6 months of disease
    • Polyarthritis RF-negative if both
      • ≥5 affected joints in first 6 months of disease
      • negative test for RF
  • Further testing for classification by disease subtype includes
    • Anti-citrullinated protein antibodies (ACPA)(positive ACPA common in RF-positive polyarticular JIA)
    • Human leukocyte antigen (HLA)-B27 (supports diagnosis of enthesitis-related arthritis)
    • Antinuclear antibody (ANA) (more common in oligoarticular JIA)
  • Other testing may include
    • Complete blood count
    • Erythrocyte sedimentation rate
    • Imaging of affected joints if diagnosis unclear
  • Differential diagnosis
    • Other juvenile idiopathic arthropathies (oligoarticular, systemic onset, psoriatic, enthesitis related)
    • Rheumatic and inflammatory diseases (systemic lupus erythematosus, Sjogren syndrome, sarcoidosis,scleroderma)
    • Infections (poststreptococcal reactive arthritis, Lyme disease, septic arthritis)
    • Scurvy
    • Sickle cell disease and other hemoglobinopathies
    • Hypermobility joint syndrome
    • Amplified musculoskeletal pain syndrome
    • Trauma
    • Faber disease

Management

  • Treatment goals include controlling inflammation and pain, preserving function, preventing long-term sequelae, and enabling normal growth and development
  • Initial therapy
    • Nonbiologic DMARD such as methotrexate often recommended as initial therapy unless presence of certain risk factors (involvement of high-risk joints, high disease activity, positive ACPA, positive RF, or joint damage)
    • Options for initial therapy include
      • Nonbiologic disease modifying antirheumatic drugs (DMARD) (methotrexate, leflunomide, sulfasalazine, tofacitininb)
      • Biologic DMARDs (etanercept, adalimumab, infliximab, golimumab, abatacept, tocilizumab, rituximab)
  • Bridging therapy
    • Oral glucocorticoids (< 3 month course) during initiation or escalation of therapy in patients with moderate or high disease activity
    • Not recommended in patients with low disease activity
    • Not recommended to give chronic low-dose glucocorticoids irrespective of risk factors or disease activity
  • Adjunct therapy may include
    • Nonsteroidal anti-inflammatory drugs (NSAIDs)
    • Intraarticular corticosteroid injections
  • Subsequent therapy depending on level of disease activity
    • In patients with low disease activity despite DMARD or biologic, consider escalation of therapy with either
      • Intraarticular glucocorticoid injection
      • Increasing dose of DMARD or biologic
      • Changing biologic therapy
    • In patients with moderate or high disease activity who have received
      • DMARD monotherapy, consider adding biologic to original DMARD (preferred over changing to triple DMARD therapy)
      • Tumor necrosis factor inhibitors (TNFi), consider changing to abatacept or tocilizumab
      • A second biologic, consider TNFi, abatacept, or tocilizumab (preferred over rituximab)
  • Supportive therapy with physical and/or occupational therapy especially in patients with joint contractures and/or muscle wasting
  • Frequent follow up required to monitor for
    • Possible toxicities from treatment
    • Disease activity
  • Periodic ophthalmologic exams are recommended

Complications

  • Joint damage
  • Flexion contractures
  • Anterior uveitis (iridocyclitis)
  • Growth disturbances

Kendra Church MS, PA-C, is a physician assistant at Dana-Farber Cancer Institute/Brigham & Women’s Hospital, and is also a senior clinical editor for DynaMed, an evidence-based, point-of-care database. 

Sources

Ringold S, Angeles-Han ST, Beukelman T, et al. 2019 American College of Rheumatology/Arthritis Foundation Guideline for the treatment of juvenile idiopathic arthritis: therapeutic approaches for non-systemic polyarthritis, sacroiliitis, and enthesitis. Arthritis Care Res (Hoboken). 2019;71(6):717-734.

Barut K, Adrovic A, Şahin S, Kasapçopur Ö. Juvenile idiopathic arthritis. Balkan Med J. 2017;34(2):90-101.

Continue Reading

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Topics:

Arthritis Pediatrics