Arthritis, Juvenile Idiopathic (Rheumatoid)

Basics

Description

Chronic synovial inflammation of unknown etiology in at least 1 joint, for at least 6 weeks. Age of onset must be <16 years old.

Juvenile idiopathic arthritis (JIA) is classified as one of 7 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 1–6 years; 80% are antinuclear antibody (ANA)-positive:
    • Persistent oligoarticular JIA remains in <5 joints.
    • Extended oligoarticular JIA spreads to involve 5 or more joints. Has worse prognosis than persistent oligoarthritis.
  • Polyarticular juvenile idiopathic arthritis affects ≥5 joints. Can occur at any age: Peak ages of onset are 1–4 years and 7–10 years.
    • Rheumatoid factor–positive (RF+) polyarticular juvenile idiopathic arthritis is like adult-onset idiopathic arthritis that occurs in a child. Often quite aggressive
    • Rheumatoid factor–negative (RF−) polyarticular juvenile idiopathic arthritis 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 is seen in nearly 50% of patients.

Epidemiology

Incidence

  • Incidence ranges from 1 to 22/100,000/year.
  • Affects ∼70,000–100,000 children in the United States

Prevalence

  • Prevalence ranges from 8 to 150/100,000; varies, but is thought to be ∼1/1,000
  • 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.

Risk Factors

Genetics

  • 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

Diagnosis

History

  • 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.

Physical Exam

  • 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 look for pericarditis and pleuritis.
ALERT
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 4–6 weeks.

Diagnostic Tests and Interpretation

Lab

  • No laboratory finding is diagnostic for JIA.
  • Many patients with JIA, especially the polyarticular and systemic types, have elevated sedimentation rates and anemia.
  • Antinuclear antibody 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
  • Rheumatoid factor will be positive in 15–20% of patients with polyarticular arthritis and usually indicates a more aggressive form of arthritis.

Imaging

  • Radiography is often normal early in JIA.
  • Later, if arthritis persists, bone demineralization, loss of articular cartilage, erosions, and joint fusion may be seen.

Differential Diagnosis

  • 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

Treatment

Medication (Drugs)

First Line

  • Steroids (glucocorticoids):
    • Intra-articular steroids: Triamcinolone hexacetonide injections are often used when patients have only 1 or 2 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 1–8 weeks).
  • NSAIDs
    • 1st-line therapy for mild JIA
    • If there is no response to the initial NSAID after 4–6 weeks of an adequate dose, a different one should be tried. Patients will often respond differently to the various NSAIDs.
    • If patients experience GI upset or excessive bruising, COX-2 inhibitors may be used. If arthritis remains active after 2–3 months, a 2nd-line treatment should be added.

Second Line

  • If NSAIDs are ineffective in controlling the disease, or the patient has moderate to severe arthritis, a 2nd-line agent should be used, such as methotrexate or sulfasalazine.
  • Methotrexate
    • If the arthritis does not respond to NSAIDs, methotrexate is the most common 2nd-line agent for active arthritis in multiple joints.
    • Laboratory values must be monitored closely in these patients, looking for bone marrow suppression or elevation of transaminase levels.
  • Sulfasalazine
    • Most often used in ERA

Third Line

  • Biologic agents are often added when patients do not respond adequately to methotrexate or cannot tolerate its side effects, or when the arthritis is severe.
  • Antitumor necrosis factor therapy is frequently used:
    • Etanercept is a receptor for tumor necrosis factor; given SC once or twice a week
    • Infliximab is a chimeric antibody to tumor necrosis factor; given IV every 4–8 weeks
    • Adalimumab is a fully humanized antibody to tumor necrosis factor; given SC every other week
  • IL-1 inhibition may work better than TNF inhibition in systemic JIA.
    • Anakinra is a recombinant IL-1 receptor antagonist. Given as a daily SC injection
    • Canakinumab is given SC once monthly.
    • Rilonacept is an SC injection given weekly.
  • Anti–IL-6 therapy (tocilizumab)
    • An IV medication given every other week.
    • It has been approved for children with systemic-onset and polyarticular JIA.
  • Abatacept
    • Costimulation blocker. It blocks the interaction of CD28 on T cells with CD80 and CD86 receptors on antigen-presenting cells.
    • It is given IV every 4 weeks.
    • It is currently being tested as an SC injection in children (SC form is approved in adults).
  • Rituximab
    • An antibody to CD20, which is present on all 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.

Additional Treatment

General Measures

  • Responses to treatments for juvenile idiopathic arthritis vary tremendously:
    • Some patients may respond to NSAIDs within 1–2 weeks.
    • Others take 4–6 weeks to improve, and some may not respond at all.
    • Steroids usually start to relieve symptoms within a few days.
    • Methotrexate usually takes 4–8 weeks until a benefit is seen.
    • Antitumor necrosis factor therapy can start decreasing symptoms in as little as 1–2 weeks, or it may take up to 3 months.
    • Other 2nd-line agents can take up to 16 weeks until the maximum benefit is seen.
  • The waxing and waning nature of JIA itself adds to the variability of response to treatment.

Additional Therapies

  • 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

Prognosis

  • Varies considerably
  • Children with oligoarticular JIA usually do 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 many outgrow their disease.
  • 50% of patients with systemic-onset JIA will develop severe chronic polyarticular arthritis.

Complications

  • 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. Ilowite NT. Update on biologics in juvenile idiopathic arthritis. Curr Opin Rheumatol. 2008;20(5):613–618.  [PMID:18698187]
  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 idiopathing arthritis. Lancet. 2011;377(9783):2138–2149.  [PMID:21684384]
  5. 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]
  6. Schneider R, Passo MH. Juvenile idiopathic arthritis. Rheum Dis Clin North Am. 2002;28(3):503–530.  [PMID:12380368]
  7. Weiss J, Ilowite N. Juvenile idiopathic arthritis. Pediatr Clin North Am. 2005;52(2):413–442.  [PMID:15820374]

Codes

ICD-9

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

ICD-10

  • 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

SNOMED

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

FAQ

  • 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.

Authors

Elizabeth Candell Chalom


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