Arthritis, Juvenile Idiopathic (Rheumatoid)



Juvenile idiopathic arthritis (JIA) is defined as chronic synovial inflammation of unknown etiology in at least one joint, for at least 6 weeks. Age of onset must be <16 years old. It is classified as one of seven subtypes:

  • Oligoarticular arthritis affects <5 joints during the first 6 months of the disease. Tends to involve large joints, especially the knee. Peak age of onset is 1 to 6 years. Up to 80% are antinuclear antibody (ANA)-positive.
    • Persistent oligoarticular JIA remains in <5 joints after the 6th month of disease.
    • Extended oligoarticular JIA spreads to involve five or more joints (cumulatively) after the 6th month of disease; has worse prognosis than persistent oligoarthritis
  • Polyarticular JIA affects ≥5 joints. Can occur at any age; peak ages of onset are 1 to 4 years and 7 to 10 years; divided into two subtypes
    • Rheumatoid factor–positive (RF+) polyarticular JIA is like adult-onset rheumatoid arthritis (RA) that occurs in a child; often quite aggressive
    • Rheumatoid factor–negative (RF−) polyarticular JIA is usually less aggressive and easier to control.
  • Systemic-onset idiopathic juvenile arthritis
    • Characterized by high spiking, quotidian or diquotidian fevers and an evanescent pink/salmon-colored macular rash
    • Affected children may also have lymphadenopathy, hepatosplenomegaly, pericarditis, or pleuritis.
    • Arthritis may not appear until weeks to months after the onset of the systemic symptoms.
    • Can occur at any age
  • Enthesitis-related arthritis (ERA)
    • Entheses (e.g., osteotendinous junctions, osteoligamentous junctions) are sites where tendons or ligaments attach to bone.
    • ERA generally affects boys in late childhood or adolescence.
    • Many are human leukocyte antigen-B27–positive.
  • Psoriatic arthritis is associated with psoriasis. It often begins in a few joints and then becomes polyarticular. It often involves small joints of hands and feet, as well as knees. Dactylitis (inflammation of an entire digit with joint and tendon involvement) is seen in nearly 50% of patients.
  • Undifferentiated arthritis is arthritis that does not fall into any of the other categories or falls into more than one of the above categories.



Incidence ranges from 1 to 23/100,000 per year.


  • Prevalence ranges from 3.8 to 400/100,000; varies but is thought to be ∼1/1,000
  • Affects >100,000 children in the United States
  • Girls are affected twice as often as boys, but boys are affected more frequently with ERA.
  • ~50% of children with JIA have the oligoarticular type.
  • 30% have the polyarticular type.
  • 10% have systemic-onset JIA.



  • Rare in siblings, but many studies have demonstrated increased frequencies of various human leukocyte antigen markers in JIA
  • Each marker may be associated with a different subtype of JIA:
    • Human leukocyte antigen-DR4: RF+ polyarticular JIA
    • Human leukocyte antigen-DR1: oligoarticular disease without uveitis
    • Human leukocyte antigen-DR5: oligoarticular JIA with uveitis
    • Human leukocyte antigen-B27: ERA
    • Human leukocyte antigen-A2: early-onset oligoarticular JIA
  • Etiology is multifactorial and likely differs between onset types. Other susceptibility loci in immune response genes, both adaptive and innate, have been reported. Environmental (including infectious) and hormonal factors can also play a role in pathogenesis.
  • Activated T cells and macrophages produce synovitis.



  • Morning stiffness that improves after a warm shower/bath or with stretching and mild exercise is common in JIA. Many young children do not complain of pain but walk with a limp or refuse to walk down stairs in the morning.
  • Joints often become sore/painful again in the late afternoon or evening.
  • Patients with JIA generally do not complain of severe pain, but rather, they avoid using joints that are particularly affected.
    • If a child has severe pain in a joint, especially pain that seems out of proportion to the physical findings, diagnoses other than JIA should be entertained.
  • In systemic JIA, the fever curve is important to document.
    • Between fever spikes, the child is often completely afebrile.
    • The rash is evanescent, and patients often have a history of fatigue, malaise, and weight loss.


  • Arthritis must be present, not just arthralgias:
    • In addition to swelling, warmth, and tenderness, there may be restricted range of motion in the affected joints and soft tissue contractures.
  • Enthesitis and sacroiliac tenderness are often seen in ERA.
  • In systemic JIA, the rash, if present, is very suggestive of this disease.
  • Lymphadenopathy and hepatosplenomegaly may be seen in systemic JIA.
  • A careful cardiac and pulmonary examination must be done to assess for pericarditis and pleuritis.
Arthritis must be present for at least 6 weeks before a patient can be diagnosed with JIA. Many viral illnesses can produce joint pain and swelling that mimics JIA but resolves within 4 to 6 weeks.


  • Monoarticular JIA
    • Septic joint
    • Toxic synovitis
    • Trauma
    • Hemarthrosis
    • Villonodular synovitis
  • Monoarticular or oligoarticular JIA
    • Lyme disease
    • Acute rheumatic fever or poststreptococcal arthritis
    • Viral/postviral arthritis
    • Malignancies
    • Sarcoidosis
    • Inflammatory bowel disease
  • Polyarticular JIA
    • Viral or postviral illness (especially parvovirus)
    • Lyme disease
    • Lupus
  • Systemic-onset JIA
    • Infection
    • Oncologic process (leukemia, lymphoma)
    • Inflammatory bowel disease
    • Lupus



  • No laboratory finding is diagnostic for JIA.
  • Many patients with JIA, especially the polyarticular and systemic types, have elevated sedimentation rates and anemia.
  • ANA is a useful test in classifying patients with JIA and determining the risk of uveitis; positive in the following:
    • 80% of oligoarticular
    • 40–60% of polyarticular
    • 15–20% of normal population
  • RF will be positive in 15–20% of patients with polyarticular arthritis and usually indicates a more aggressive form of arthritis.
  • Radiography is often normal early in JIA.
  • Later, if arthritis persists, bone demineralization, loss of articular cartilage, erosions, and joint fusion may be seen.



  • Responses to treatments for JIA vary tremendously:
    • Some patients may respond to NSAIDs within 1 to 2 weeks. Others take 4 to 6 weeks to improve, and some may not respond at all.
    • Steroids usually start to relieve symptoms within a few days.
    • Methotrexate usually takes 4 to 8 weeks until a benefit is noted.
    • Biologic therapy can start decreasing symptoms in as little as a few days to 2 weeks or may take up to a few months to see the full benefit.
  • The waxing and waning nature of JIA adds to the variability of response to treatment.



  • Steroids (glucocorticoids)
    • Intra-articular steroids are often used when patients have only one or two active joints.
    • Systemic steroids
      • Systemic steroids are often needed to control flares or with the initial presentation of polyarticular or systemic JIA. Because of the many side effects, patients should be weaned off steroids as soon as possible.
      • Glucocorticoids can be given orally (daily or every other day) or as IV pulses (every 1 to 8 weeks).
  • NSAIDs
    • 1st-line therapy for mild JIA
    • If there is an inadequate response to the initial NSAID after 4 to 6 weeks, consider changing to another NSAID or adding a 2nd-line agent. Patients may respond differently to the various NSAIDs.
    • If arthritis remains active after 2 to 3 months, a 2nd-line treatment should be added.
  • Disease-modifying antirheumatic drugs (DMARDs)
    • If NSAIDs are ineffective in controlling the disease, or the patient has moderate to severe arthritis, a DMARD, such as methotrexate or leflunomide, is often added.
    • Methotrexate
      • Methotrexate is the most common 2nd-line agent for active arthritis. It can be given orally or subcutaneously, once weekly.
      • Laboratory values must be monitored closely, looking for bone marrow suppression or elevation of transaminase levels. Nausea/vomiting are common adverse effects.
    • Leflunomide is often used when methotrexate is ineffective or patients cannot tolerate the nausea associated with methotrexate. It is a daily tablet and can also cause liver toxicity.
    • Both methotrexate and leflunomide cause mild immune suppression.
  • Biologic agents
    • Biologic agents are often added when patients do not respond adequately to methotrexate, cannot tolerate its side effects, or have moderate to severe arthritis. All biologic agents suppress the immune system, and infections are the most common adverse effects.
      • Antitumor necrosis factor (anti-TNF) therapy is frequently used for moderate to severe polyarticular JIA.
        • Etanercept is a receptor for TNF, given SC once or twice a week.
        • Infliximab is a chimeric antibody to TNF, given IV every 4 to 8 weeks.
        • Adalimumab is a fully humanized antibody to TNF, given SC every other week.
      • Anti–IL-6 therapy (tocilizumab)
        • An IV medication given every 2 to 4 weeks
        • Approved for children with systemic-onset and polyarticular JIA
      • IL-1 inhibition is often used as a 1st-line agent, along with corticosteroids, in severe systemic JIA. It can also be used in patients with polyarticular JIA who do not respond to TNF inhibition.
        • Anakinra is a recombinant IL-1 receptor antagonist, given as a daily SC injection.
        • Canakinumab is a human monoclonal antibody against IL-1 β. It is given monthly as an SC injection.
      • Costimulation blocker: Abatacept blocks the interaction of CD28 on T cells with CD80 and CD86 receptors on antigen presenting cells.
        • IV is given at 2 and 4 weeks after first infusion and then every 4 weeks thereafter.
        • SC is given once weekly.
        • Approved as an SC or IV injection in children and adults
  • Rituximab
    • An antibody to CD20, which is present on certain B cells
    • Approved for use in adult RA but not JIA
  • Medications such as cyclophosphamide or thalidomide are sometimes necessary to control severe systemic-onset JIA when biologic treatments are ineffective.


  • Physical and occupational therapy are important in the management of JIA.
  • The goal is to maintain range of motion, muscle strength, and function.

Ongoing Care


  • Varies considerably
  • Children with oligoarticular JIA usually fare well and often go into remission within a few years of starting treatment. They may have flares, however, even up to 10 years after being symptom-free and off all medications.
  • Patients with polyarticular JIA who are RF+ often develop a severe arthritis that may persist into adulthood.
  • RF− polyarticular patients generally fare better and may outgrow their disease.
  • 50% of patients with systemic-onset JIA will develop severe chronic polyarticular arthritis.


  • Joint degeneration with loss of articular cartilage
  • Soft tissue contractures
  • Leg length discrepancy
  • Micrognathia
  • Cervical spine dislocation
  • Rheumatoid nodules
  • Growth retardation
  • Uveitis
    • Oligoarticular JIA, especially with a positive ANA test, is associated with chronic uveitis, which can lead to loss of vision if not detected early with routine slit-lamp eye examinations.
    • May be seen in polyarticular JIA but is less common
  • Pericarditis, pleuritis, and severe anemia may develop in patients with systemic-onset JIA.
  • Macrophage activation syndrome or hemophagocytic syndrome
    • Rare, but potentially lethal complication of systemic-onset JIA, resulting from an overproduction of inflammatory cytokines
    • May present as an acute febrile illness with pancytopenia and hepatosplenomegaly
    • Bone marrow aspiration can be diagnostic.
    • Treatment is often high-dose steroids and high-dose IL-1 inhibitors, or cyclosporine.

Additional Reading

  1. Andersson Gäre B. Juvenile arthritis—who gets it, where and when? A review of current data on incidence and prevalence. Clin Exp Rheumatol. 1999;17(3):367–374. [PMID:10410275]
  2. Beukelman T, Patkar NM, Saag KG, et al. 2011 American College of Rheumatology Recommendations for the Treatment of Juvenile Idiopathic Arthritis: initiation and safety monitoring of therapeutic agents for the treatment of arthritis and systemic features. Arthritis Care Res (Hoboken). 2011;63(4):465–482. [PMID:21452260]
  3. Patel H, Goldstein D. Pediatric uveitis. Pediatr Clin North Am. 2003;50(1):125–136. [PMID:12713108]
  4. Prakken B, Albani S, Martini A. Juvenile idiopathic arthritis. Lancet. 2011;377(9783):2138–2149. [PMID:21684384]
  5. Ravelli A, Martini A. Juvenile idiopathic arthritis. Lancet. 2007;369(9563):767–778. [PMID:17336654]
  6. Ringold S, Weiss PF, Beukelman T, et al. 2013 Update of the 2011 American College of Rheumatology recommendations for the treatment of juvenile idiopathic arthritis: recommendations for the medical therapy of children with systemic juvenile idiopathic arthritis and tuberculosis screening among children receiving biologic medications. Arthritis Rheum. 2013;65(10):2499–2512. [PMID:24092554]
  7. Weiss J, Ilowite N. Juvenile idiopathic arthritis. Pediatr Clin North Am. 2005;52(2):413–442. [PMID:15820374]



  • 714.30 Polyarticular juvenile rheumatoid arthritis, chronic or unspecified
  • 714.31 Polyarticular juvenile rheumatoid arthritis, acute


  • M08.80 Other juvenile arthritis, unspecified site
  • M08.849 Other juvenile arthritis, unspecified hand
  • M08.879 Other juvenile arthritis, unspecified ankle and foot
  • M08.869 Other juvenile arthritis, unspecified knee


  • 410502007 juvenile idiopathic arthritis (disorder)
  • 410801005 juvenile idiopathic arthritis, enthesitis related arthritis (disorder)


  • Q: Will the patient outgrow JIA?
  • A: Prognosis depends on the type of JIA. In some studies, up to 50% of patients with JIA still had active disease 10 years after diagnosis, but only 15% had loss of function.
  • Q: Will siblings of patients with JIA develop the disease?
  • A: Rarely, but it can occur.


Elizabeth Candell Chalom, MD

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