Juvenile Idiopathic Arthritis (JIA)

Juvenile idiopathic arthritis is not a single disease; the term applies to a number of chronic, noninfectious 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 (1). 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 typically affects young girls. It is characterized by involvement of ≤ 4 joints during the first 6 months of disease. Oligoarticular JIA is further divided into 2 types: persistent (always ≤ 4 joints involved) and extended (≥ 5 joints involved after the first 6 months 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 analogous to adult rheumatoid arthritis. In both types, arthritis can be symmetric and frequently involves the small joints.

Enthesitis-related arthritis involves arthritis and enthesitis (inflammation at the insertion of tendons and ligaments). It is more common among older boys, and these patients may subsequently develop arthritis of their axial skeleton (sacroiliac and lumbar spine). Enthesitis-related arthritis tends to be in the lower extremities and asymmetric. The human leukocyte antigen–B27 (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 pitting or onycholysis, or a family history of psoriasis in a first-degree relative. Arthritis is frequently oligoarticular.

Nail Pits Caused by Psoriatic JIA

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Juvenile idiopathic arthritis (JIA) or psoriasis can cause pits in the nails such as these.

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Undifferentiated JIA is used to categorize patients who have JIA but do not meet criteria for any one category or meet criteria for more than one.

Systemic JIA (Still disease) is characterized by systemic inflammation and arthritis. The systemic features include fever, rash, hepatomegaly, splenomegaly, lymphadenopathy, and serositis.

The Pediatric Rheumatology International Trials Organization (PRINTO) has proposed newer classification criteria with fewer, more homogenous categories (2); however, these criteria have not been widely adopted and require further validation.

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

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.

Joint abnormalities in children typically include joint stiffness (especially upon awakening), swelling, effusion, pain, and tenderness, but some children have no pain. Joint manifestations may be symmetric or asymmetric, and involve large and/or small joints.

Enthesitis can cause tenderness of the iliac crest and spine, greater trochanter of the femur, patella, tibial tuberosity, Achilles insertion, or plantar fascia insertions.

Eye abnormalities may develop in several forms of JIA. The most common comorbidity is iridocyclitis (inflammation of the anterior chamber and anterior vitreous of the eye) that is typically asymptomatic but sometimes causes blurring of vision and miosis. Rarely, in enthesitis-related arthritis, there are also the more common uveitis manifestations of 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 exceedingly 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), serositis with pericarditis or pleuritis, and lung disease. 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. In 7 to 10% of patients, systemic JIA may be complicated by macrophage activation syndrome, a life-threatening cytokine storm syndrome.

• History and physical examination

• Rheumatoid factor (RF), antinuclear antibodies (ANA), anticyclic citrullinated peptide (anti-CCP) antibodies, 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 (> 2 weeks), especially if quotidian. Diagnosis of JIA is primarily clinical. It is made when a chronic noninfectious arthritis lasting > 6 weeks has no other known cause.

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; however, negative results for any of these tests do not rule out JIA. The test for ANA should be done by immunofluorescence because other methods may result in false-negative results.

HLA-B27 is present more commonly in enthesitis-related arthritis.

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.

In systemic JIA, laboratory abnormalities suggestive of systemic inflammation, such as elevated erythrocyte sedimentation rate (ESR), ferritin, and C-reactive protein, along with leukocytosis, anemia, and thrombocytosis are almost always present at diagnosis.

In systemic JIA, patients should have an eye examination once or twice a year.

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 months if ANA test results are positive and every 6 months if ANA test results are negative.

• Medications that slow disease progression (particularly methotrexate, tumor necrosis factor [TNF] inhibitors, interleukin [IL]-1 and IL-6 inhibitors)

• Sometimes intra-articular or systemic corticosteroids

• Sometimes nonsteroidal anti-inflammatory drugs (NSAIDs) for symptom relief

• Sometimes T-cell costimulation or Janus kinase inhibitors

Similar to treatment of adult rheumatoid arthritis, disease-modifying antirheumatic drugs (DMARDs), particularly methotrexate and the biologic agents (eg, etanercept, anakinra, canakinumab, tocilizumab, abatacept), have dramatically changed the therapeutic approach (Similar to treatment of adult rheumatoid arthritis, disease-modifying antirheumatic drugs (DMARDs), particularly methotrexate and the biologic agents (eg, etanercept, anakinra, canakinumab, tocilizumab, abatacept), have dramatically changed the therapeutic approach (1, 2, 3, 4).

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 complete blood count, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and albumin.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 complete blood count, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and albumin.

TNF inhibitors are used if methotrexate is not effective or if patients are at high risk of a poor outcome. Etanercept, adalimumab, and infliximab are TNF inhibitors that have been shown to be effective. is not effective or if patients are at high risk of a poor outcome. Etanercept, adalimumab, and infliximab are TNF inhibitors that have been shown to be effective.

The IL-1 inhibitors anakinra and canakinumab are particularly effective for systemic JIA. Tocilizumab, an IL-6 receptor antagonist, is also indicated for the treatment of systemic JIA and polyarticular JIA. The IL-1 inhibitors anakinra and canakinumab are particularly effective for systemic JIA. Tocilizumab, an IL-6 receptor antagonist, is also indicated for the treatment of systemic JIA and polyarticular JIA.

Abatacept, a T-cell costimulation inhibitor, and a Janus kinase inhibitor, such as tofacitinib or upadacitinib, are also options for the treatment of polyarticular JIA.Abatacept, a T-cell costimulation inhibitor, and a Janus kinase inhibitor, such as tofacitinib or upadacitinib, are also options for the treatment of polyarticular JIA.

Except for severe systemic or polyarticular disease, systemic corticosteroids can usually be avoided. When necessary, the lowest possible dose is used. Growth retardation, osteoporosis, and osteonecrosis are the major hazards of prolonged systemic corticosteroid use in children. Intra-articular corticosteroid injections can be given and help avoid the adverse effects of systemic corticosteroids. The dosage for children is adjusted based on weight. Some children may need to be sedated for intra-articular injection, especially if multiple joints require injection.

Symptoms of JIA may be reduced with NSAIDs, but these medications do not alter long-term joint disease or prevent complications. NSAIDs are most useful for enthesitis. Naproxen, ibuprofen, and indomethacin are among the most useful.Symptoms of JIA may be reduced with NSAIDs, but these medications do not alter long-term joint disease or prevent complications. NSAIDs are most useful for enthesitis. Naproxen, ibuprofen, and indomethacin are among the most useful.

Iridocyclitis is treated with ophthalmic corticosteroid drops and mydriatics and may require systemic methotrexate and anti-TNF therapy, and, occasionally, surgery.

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.

Remissions occur in approximately 50% of patients within 5 years of treatment (1).

Patients with RF-positive polyarticular JIA have a less favorable prognosis.