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Juvenile Idiopathic Arthritis (JIA)

By Jay Mehta, MD, Assistant Professor of Pediatrics;Clinical Director, Pediatric Rheumatology, Perelman School of Medicine at The University of Pennsylvania;The Children's Hospital of Pediatrics ; Frank Pessler, MD, PhD, Helmholtz Centre for Infection Research;Hannover Medical School, Braunschweig, Germany;Hannover, Germany

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Juvenile idiopathic arthritis is a group of rheumatic diseases that begins by age 16. Arthritis, fever, rash, adenopathy, splenomegaly, and iridocyclitis are typical of some forms. Diagnosis is clinical. Treatment involves NSAIDs, intra-articular corticosteroids, and disease-modifying antirheumatic drugs.

Juvenile idiopathic arthritis (JIA) is uncommon. The cause is unknown, but there seems to be a genetic predisposition as well as autoimmune and autoinflammatory pathophysiology. JIA is distinct from adult rheumatoid arthritis, despite occasional similarities.

Classification

Juvenile idiopathic arthritis is not a single disease; the term applies to a number of chronic arthritides that occur in children and share certain features. The current classification system, from the International League of Associations for Rheumatology, defines categories of disease based on clinical and laboratory findings. Some of the categories are subdivided into different forms. Categories include the following:

  • Oligoarticular JIA (persistent or extended)

  • Polyarticular JIA (rheumatoid factor [RF] negative or positive)

  • Enthesitis-related arthritis

  • Psoriatic JIA

  • Undifferentiated JIA

  • Systemic JIA

Many of these categories likely include more than one disease but are useful to help group children with a similar prognosis and response to treatment. Also, children sometimes move to different categories during the course of their illness.

Oligoarticular JIA is the most common form and usually affects young girls. It is characterized by involvement of 4 joints during the first 6 mo of disease. Oligoarticular JIA is further divided into 2 types: persistent (always ≤ 4 joints involved) and extended (≥ 5 joints involved after the first 6 mo of disease).

Polyarticular JIA is the second most common form. It affects 5 joints at onset and is divided into 2 types: RF negative and RF positive. Typically, young girls are RF negative and have a better prognosis. The RF-positive type typically occurs in adolescent girls and is often similar to adult RA. In both types, arthritis can be symmetric and frequently involves the small joints.

Enthesitis-related arthritis involves arthritis and enthesitis (painful inflammation at the insertion of tendons and ligaments). It is more common among older boys who may subsequently develop classic features of one of the spondyloarthritides such as ankylosing spondylitis or reactive arthritis. The arthritis tends to be in the lower extremities and asymmetric. The HLA-B27 allele is more common in this form of JIA.

Psoriatic JIA has a bimodal age distribution. One peak occurs in young girls, and the other peak occurs in older males and females (who are equally affected). It is associated with psoriasis, dactylitis (swollen digits), nail pits, or a family history of psoriasis in a 1st-degree relative. Arthritis is frequently oligoarticular.

Undifferentiated JIA is diagnosed when patients do not meet criteria for any one category or meet criteria for more than one.

Systemic JIA (Still disease) involves fever and systemic manifestations.

Symptoms and Signs

Manifestations involve the joints and sometimes the eyes and/or skin; systemic juvenile idiopathic arthritis may affect multiple organs.

Children typically have joint stiffness, swelling, effusion, pain, and tenderness, but some children have no pain. Joint manifestations may be symmetric or asymmetric, and involve large or small joints. Enthesitis typically causes tenderness of the iliac crest and spine, greater trochanter of the femur, patella, tibial tuberosity, or Achilles and plantar fascia insertions.

Sometimes, JIA interferes with growth and development. Micrognathia (receded chin) due to early closure of mandibular epiphyses or limb length inequality (usually the affected limb is longer) may occur.

The most common ocular abnormality is iridocyclitis (inflammation of the anterior chamber and anterior vitreous) that is typically asymptomatic but sometimes causes blurring of vision and miosis. Rarely, in enthesitis-related arthritis, there is conjunctival injection, pain, and photophobia. Iridocyclitis can result in scarring (synechia), cataracts, glaucoma, or band keratopathy. Iridocyclitis is most common in oligoarticular JIA, developing in nearly 20% of patients, especially if patients are positive for antinuclear antibodies (ANA). It may occur in the other forms but is rare in polyarticular RF-positive JIA and systemic JIA.

Skin abnormalities are present mainly in psoriatic JIA, in which psoriatic skin lesions, dactylitis, and/or nail pits may be present, and in systemic JIA, in which a typical transient rash often appears with fever. Rash in systemic JIA may be diffuse and migratory, with urticarial or macular lesions with central clearing.

Systemic abnormalities in systemic JIA include high fever, rash, splenomegaly, generalized adenopathy (especially of the axillary nodes), and serositis with pericarditis or pleuritis. These symptoms may precede the development of arthritis. Fever occurs daily (quotidian) and is often highest in the afternoon or evening and may recur for weeks.

Diagnosis

  • Clinical criteria

  • Rheumatoid factor (RF), antinuclear antibodies (ANA), anticyclic citrullinated peptide antibody (anti-CCP), and HLA-B27 tests

Juvenile idiopathic arthritis should be suspected in children with symptoms of arthritis, signs of iridocyclitis, generalized adenopathy, splenomegaly, or unexplained rash or prolonged fever, especially if quotidian. Diagnosis of JIA is primarily clinical. Patients with JIA should be tested for RF, anti-CCP antibodies, ANA, and HLA-B27 because these tests may be helpful in distinguishing between forms. In systemic JIA, RF and ANA are usually absent. In oligoarticular JIA, ANA are present in up to 75% of patients and RF is usually absent. In polyarticular JIA, RF usually is negative, but in some patients, mostly adolescent girls, it can be positive. HLA-B27 is present more commonly in enthesitis-related arthritis.

To diagnose iridocyclitis, a slit-lamp examination should be done even in the absence of ocular symptoms. A recently diagnosed patient with oligoarticular or polyarticular JIA should have an eye examination every 3 month if ANA test results are positive and every 6 mo if ANA test results are negative.

Prognosis

Remissions occur in 50 to 70% of treated patients. Patients with RF-positive polyarticular JIA have a less favorable prognosis.

Treatment

  • Drugs that slow disease progression (particularly methotrexate, etanercept, and anakinra)

  • Intra-articular corticosteroid injections

  • NSAIDs

Similar to the therapy of patients with adult rheumatoid arthritis, disease-modifying antirheumatic drugs (DMARDs), particularly methotrexate and the biologic agents (eg, etanercept, anakinra), have dramatically changed the therapeutic approach (1).

Symptoms of juvenile idiopathic arthritis may be reduced with NSAIDs but they do not alter long-term joint disease or prevent complications. NSAIDs are most useful for enthesitis. Naproxen 5 to 10 mg/kg po bid, ibuprofen 5 to 10 mg/kg po qid, and indomethacin 0.5 to 1.0 mg/kg po tid are among the most useful.

Except for severe systemic disease, systemic corticosteroids can usually be avoided. When necessary, the lowest possible dose is used (eg, range for oral prednisone, 0.0125 to 0.5 mg/kg qid, or the same daily dose given once or twice daily). Growth retardation, osteoporosis, and osteonecrosis are the major hazards of prolonged corticosteroid use in children. Intra-articular corticosteroid injections can be given. The dosage for children is adjusted based on weight. A few children may need to be sedated for intra-articular injection, especially if multiple joints require injection.

Methotrexate is useful for oligoarticular, psoriatic, and polyarticular forms of JIA. Adverse effects are monitored as in adults. Bone marrow depression and hepatic toxicity are monitored with CBC, AST, ALT, and albumin. Occasionally, sulfasalazine is used, especially in cases of suspected spondyloarthropathy.

TNF-alpha blockade is used if methotrexate is not effective. Etanercept is used most commonly at doses of 0.4 mg/kg sc (up to a maximum of 25 mg) twice/wk or 0.8 mg/kg sc (up to 50 mg) once/wk. Adalimumab and infliximab are different TNF-alpha antagonists that have been shown to be effective. IL-1 blockade with anakinra or canakinumab is particularly effective for systemic JIA. Tocilizumab is an IL-6 receptor antagonist that is indicated for the treatment of systemic JIA (2).

Physical therapy, exercises, splints, and other supportive measures may help prevent flexion contractures. Adaptive devices can improve function and minimize unnecessary stresses on inflamed joints. Iridocyclitis is treated with ophthalmic corticosteroid drops and mydriatics and may require systemic methotrexate and anti-TNF therapy.

Treatment references

  • 1. 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) 63(4):465–482, 2011. doi: 10.1002/acr.20460.

  • 2. De Benedetti F, Brunner H, Ruperto N, et al: Tocilizumab in patients with systemic juvenile idiopathic arthritis: Efficacy data from the placebo-controlled 12-week part of the phase 3 TENDER trial. Arthritis Rheum 62 (supplement 10):1434, 2010. doi: 10.1002/art.29200.

Key Points

  • JIA encompasses a number of different arthritides in children that differ in clinical and laboratory manifestations.

  • Suspect JIA in children with symptoms of arthritis, signs of iridocyclitis, generalized adenopathy, splenomegaly, or unexplained rash or prolonged fever.

  • Diagnose JIA clinically; use laboratory testing (of RF, anti-CCP antibodies, ANA, and HLA-B27) mainly to distinguish between forms.

  • Slow disease progression with methotrexate and/or biologic drugs (eg, etanercept, anakinra) and treat symptoms with intra-articular corticosteroid injections and/or NSAIDs.

  • Treat iridocyclitis with ophthalmic corticosteroid drops and mydriatics, or systemic therapy if refractory.

Drugs Mentioned In This Article

  • Drug Name
    Select Trade
  • ENBREL
  • REMICADE
  • HUMIRA
  • ADVIL, MOTRIN IB
  • OTREXUP
  • INDOCIN
  • ALEVE, NAPROSYN
  • RAYOS
  • KINERET
  • ACTEMRA
  • AZULFIDINE

* This is the Professional Version. *