Juvenile idiopathic arthritis (JIA) refers to a group of disorders that are a major cause of chronic arthritis in children. It is the most common chronic rheumatic disease of childhood and can be a significant cause of both short-term and long-term disability. In the United States, approximately 294,000 children younger than 18 years have arthritis or other rheumatic conditions.

JIA is relatively common compared to other chronic diseases of childhood. There are as many children with juvenile-onset diabetes as there are those with juvenile-onset arthritis, and there are 10 times as many children with arthritis as there are children affected with muscular dystrophy.

Essentials of Diagnosis

• Six weeks or more of persistent joint swelling, and the exclusion of other causes of arthritis in childhood.
  
• There is no specific laboratory test that either confirms or excludes JIA.
  
• The type of JIA is determined by the age of the child at onset of symptoms; the number and type of joints involved; the presence of extra-articular symptoms, such as rash, fever, and iritis; and the course of the illness during the first 6 months after the diagnosis is confirmed.
  
• Significant complications, including macrophage activation syndrome (MAS), contractures, growth retardation, and visual loss, can be avoided by prompt diagnosis and treatment.

According to the International League Against Rheumatism, the types of JIA can be classified as oligoarticular, polyarticular (including seropositive and seronegative), systemic onset (SOJIA), psoriatic, enthesitis-related, and undifferentiated. The different subtypes of JIA are mainly determined by the pattern of joint involvement at the onset of the illness.

The subtypes of JIA are identified and classified based on the following factors: age at onset, number of joints involved initially, rheumatoid factor status, and associated extra-articular symptoms (Table 20–1). Identification of the correct subtype helps guide appropriate therapy and determine prognosis.

Oligoarticular JIA

Oligoarticular JIA occurs most commonly in very young children, ages 1–7 years.

Articular Symptoms

Symptoms of joint inflammation with morning stiffness can begin at any time after the child begins to walk. An asymmetric pattern of joint involvement is common and no more than four joints are affected. Morning stiffness is a prominent finding and, although the affected joint is often swollen and quite large, the child frequently has less pain than one would expect. Knees are the most commonly involved joint; there may also be diffuse swelling of a toe or finger, and ankles, wrists, and elbows are also commonly involved. The atlantoaxial (C1–C2) joint and the temporomandibular joint (TMJ) are relatively hidden sites where joint inflammation and loss of motion can occur.

Extra-Articular Symptom: Iritis

Children with oligoarticular JIA, especially very young girls with a positive antinuclear antibody (ANA) test, are at increased risk for iritis. This chronic, anterior, nongranulomatous uveitis or iridocyclitis is painless and typically occurs early in the course of the illness. One of five patients with oligoarticular JIA has asymptomatic iritis identified at a screening slit lamp examination. Seventy-five percent of these children with oligoarticular JIA and iritis have a positive ANA. The iritis of oligoarticular JIA responds well to treatment when the diagnosis is made early. One or both eyes can be involved at any time in the course of the disease, not only when joints are flaring. Initial treatment with glucocorticoid eye drops and mydriatics is usually sufficient. Sub-tenon injections of long-acting glucocorticoid preparations can also be used as needed to control inflammation in the anterior chamber of the affected eye. Systemic therapy with methotrexate or biologic agents (tumor necrosis factor [TNF] inhibitors) is sometimes necessary to control ocular inflammation, even in patients whose arthritis has responded well to more conservative therapy. Serious complications, such as blindness, glaucoma, cataracts, and band keratopathy, can result from untreated eye disease. Prevention and early treatment of both the iritis and arthritis are preferable to the disappointing results seen in cases that go unrecognized until a later stage. All children with oligoarticular JIA, regardless of ANA status, should have regular slit lamp examinations done until they reach 18 years of age, even in the absence of a red eye or ongoing joint symptoms (Table 20–2). Untreated iritis can cause serious long-term morbidity in these children, unlike the arthritis, which often resolves by the time they reach school age and typically does not lead to permanent joint damage.

Prognosis

In some children, oligoarticular JIA may begin in a few joints but progress to involve more than five joints early in the course of the illness. If this progression occurs within the first 6 months of disease, the arthritis is reclassified as polyarticular JIA. If an increasing number of joints (>4) become involved more than 6 months after diagnosis, the arthritis is referred to as extended oligoarticular JIA. Extended oligoarticular JIA is a more aggressive subtype, and arthritis in these children often persists into adulthood, with the possibility of joint destruction occurring over time. Patients with extended oligoarticular JIA have the same increased risk of iritis as the children with the persistent oligoarticular type and continue to require regular screening slit lamp examinations until they are 18 years old.

Polyarticular JIA

Polyarticular JIA presents in children of any age with persistent synovitis in five or more joints at onset. In this heterogeneous group of patients, the rheumatoid factor test is a useful prognosticator.

Seropositive Polyarticular JIA

Patients who have polyarticular JIA with positive rheumatoid factor are usually teenage girls with symmetric arthritis involving the small joints of hands and feet. This is the only one of the JIA subgroups that clinically resembles the adult form of classic rheumatoid factor–positive rheumatoid arthritis, with similar HLA-DR4 associations. These girls are more likely to have aggressive, erosive joint disease. Rheumatoid nodules occur in 5–10% of patients in this subgroup, and Felty syndrome, rheumatoid vasculitis, and rheumatoid lung disease are occasionally seen. Iritis is uncommon in this subgroup, occurring in <5% of these patients.

Seronegative Polyarticular Arthritis

Polyarticular JIA with negative rheumatoid factor typically affects younger children, more often girls than boys. The arthritis may or may not be symmetric but prefers large joints, knees, ankles, and wrists. There are no associated extra-articular features and iritis is rare. These children can have active arthritis for many years without erosive change seen on radiographs.

Prognosis

The course is variable, and transition to the positive rheumatoid factor polyarticular subgroup can occur. In patients with psoriatic arthritis, multiple joints can be involved at presentation, but the prognosis differs from both the polyarticular rheumatoid factor–negative and rheumatoid factor–positive JIA subgroup. Both the psoriatic subgroup and the polyarticular rheumatoid factor–positive subgroup of patients may have continued active disease into adulthood.

Systemic Onset JIA

This disease affects children and adults at any age, with boys and girls affected equally.

Articular & Extra-Articular Symptoms

The hallmarks of SOJIA are the daily spiking fever in a quotidian or “rabbit ears” pattern in association with a salmon-colored, macular, evanescent rash on trunk and extremities that is present only during fever. Painful myalgias, enlarged liver, spleen, lymph nodes and pleuro-pericarditis may be present at disease onset. True arthritis may not manifest until months after the onset of fever, which can make early diagnosis difficult.

Children appear acutely ill (with significant fever, fatigue, and pain). Extensive diagnostic studies, including a bone marrow examination, may be necessary to rule out infection and malignancy. Malignancy is often suspected initially at the onset of SOJIA because the child fails to thrive due to the significant fever, fatigue, and pain.

Marked leukocytosis, very high sedimentation rates, and elevated ferritin levels are the rule in this disease. Iritis is rare in this subgroup. Recurrent episodes of active SOJIA can occur into adulthood even after an extended disease-free interval.

Complications

Pericardial effusion, although common in SOJIA, usually does not become hemodynamically significant, yet children with SOJIA and pericarditis must be watched closely to ensure that cardiac function is not compromised.