Juvenile idiopathic arthritis (JIA) is characterized by chronic arthritis in one or more joints for at least 6 weeks. There are four main subtypes of JIA: (1) oligoarticular, (2) polyarticular, (3) systemic, and (4) enthesitis-associated. The exact cause of JIA is not known, but there is substantial evidence that it is an autoimmune process with genetic susceptibility factors.

Clinical Findings

A. Symptoms and Signs

The most common type of JIA is the oligoarticular form, which constitutes approximately 30%–40% of patients and is characterized by arthritis of four or fewer joints. This type of JIA often affects medium to large joints. Because the arthritis is often asymmetrical, children may develop a leg-length discrepancy in which the involved leg grows longer due to increased blood flow and growth factors. The synovitis is usually mild and may be painless. Systemic features are uncommon except for inflammation in the eye. Up to 20% of children with this type of JIA develop insidious, asymptomatic uveitis, which may cause blindness if untreated. The activity of the eye disease does not correlate with that of the arthritis. Therefore, routine ophthalmologic screening with slit-lamp examination must be performed at 3-month intervals if the antinuclear antibody (ANA) test is positive, and at 6-month intervals if the ANA test is negative, for at least 4 years after the onset of arthritis, as this is the period of highest risk.

Polyarticular disease is defined as arthritis involving five or more joints. This type of JIA affects 25% of patients. Both large and small joints are involved, typically in a symmetrical pattern. Systemic features are not prominent, although low-grade fever, fatigue, rheumatoid nodules, and anemia may be present. This group is further divided into rheumatoid factor (RF)-positive and RF-negative disease. The former resembles adult rheumatoid arthritis with more chronic, destructive arthritis.

The systemic form, previously known as Still disease, comprises 5%–10% of patients with JIA. The arthritis can involve any number of joints and affects both large and small joints, but may be absent at disease onset. One of the classic features is a high fever, often as high as 39°C–40°C, typically occurring one to two times per day. In between fever spikes, the temperature usually returns to normal or subnormal. Ninety percent of patients have a characteristic evanescent, salmon-pink macular rash that is most prominent on pressure areas and when fever is present. Other systemic features that may be present, but are not specific for JIA, include hepatosplenomegaly, lymphadenopathy, leukocytosis, and serositis.

Enthesitis-associated arthritis is most common in males, older than 10 years of age, and is typically associated with lower extremity, large joint arthritis. The hallmark of this form is inflammation of tendinous insertions (enthesopathy), such as the tibial tubercle or the heel. Low back pain and sacroiliitis are also commonly seen in this form of arthritis which comprises approximately 10%–20% of patients with JIA.

There are two additional subtypes of JIA. Children with psoriatic arthritis may have typical psoriasis, but may also present prior to the onset of the classic thick scaly plaques and have more subtle changes such as nail pitting (see Chapter 15). Patients with psoriatic arthritis may also present with dactylitis or “sausage digit,” which is painful swelling of an entire finger or toe. Undifferentiated JIA, comprising 10% of patients, includes children with chronic arthritis that do not meet criteria for any of the other subgroups or meet more than one criterion and therefore could be classified into multiple subgroups.

B. Laboratory Findings

There is no diagnostic test for JIA. A normal erythrocyte sedimentation rate (ESR) does not exclude the diagnosis of JIA. However, patients with systemic JIA typically have significantly elevated markers of inflammation, including ESR, C-reactive protein (CRP), white blood cell count, and platelets. RF is positive in about 5% of patients, usually when the onset of polyarticular disease occurs after age 8 years. A newer test, anti-cyclic citrullinated peptide (anti-CCP) antibody, has a very high specificity for rheumatoid arthritis and may be detectable prior to the RF. ANAs are associated with an increased risk of iridocyclitis in patients with oligoarticular disease. A positive ANA test is also fairly common in patients with the late-onset RF-positive form of the disease. Carriage of HLAB27 antigen is associated with an increased risk of developing enthesitis-associated arthritis.

Table 29–1 lists the general characteristics of joint fluid in various conditions. The main indication for joint aspiration and synovial fluid analysis is to rule out infection. A positive Gram stain or culture is the only definitive test for infection. A leukocyte count over 2000/μL suggests inflammation; this may be due to infection, rheumatologic diseases, leukemia, or reactive arthritis. A very low glucose concentration (< 40 mg/dL) or very high polymorphonuclear leukocyte count (> 60,000/μL) is highly suggestive of bacterial arthritis.

C. Imaging Studies

In the early stages of the disease, only soft tissue swelling and possibly periarticular osteoporosis may be seen. Magnetic resonance imaging (MRI) of involved joints may show early joint damage and, if obtained with gadolinium, can confirm the presence of synovitis. Later in the course of the disease, particularly in patients with RF-positive disease, plain films may demonstrate joint space narrowing due to cartilage thinning and erosive changes of the bone related to chronic inflammation.

Differential Diagnosis

Table 29–2 lists the most common causes of limb pain in childhood. JIA is a diagnosis of exclusion; therefore, it is important to rule out other causes of the clinical signs and symptoms prior to settling on this diagnosis. The differential diagnosis is often quite broad, including orthopedic conditions, infectious diseases, and malignancies. A few key features can help distinguish these different entities, including the timing of the pain and associated signs and symptoms. In inflammatory conditions, patients frequently have increased symptoms in the morning with associated stiffness. In contrast, patients with an orthopedic abnormality typically have increased symptoms later in the day and with activity. Growing pains, a common cause of leg pain in childhood, are characterized by poorly localized pain at night, which frequently wakes the child from sleep; no objective signs of inflammation; and no daytime symptoms. Patients with growing pains often ask to be massaged, which is not typical of those with arthritis.

It is particularly important to establish the diagnosis in the case of monoarticular arthritis. Bacterial arthritis is usually acute and monoarticular except for arthritis associated with gonorrhea, which may be associated with a migratory pattern and hemorrhagic pustules, usually on the distal extremities. Fever, leukocytosis, and increased ESR with an acute process in a single joint demand synovial fluid examination and culture to identify the pathogen. Pain in the hip or lower extremity is a frequent symptom of childhood cancer, especially leukemia, neuroblastoma, and rhabdomyosarcoma. Infiltration of bone by tumor and a joint effusion may be seen. Radiographs of the affected site and examination of the blood smear for unusual cells and thrombocytopenia are necessary. An elevated lactate dehydrogenase value should also raise concern about an underlying neoplastic process. In doubtful cases, bone marrow examination is indicated.

Reactive arthritis is joint pain and swelling triggered by an infection. The infection is nonarticular and can be either viral or bacterial. A preceding illness is identified in approximately half of cases. Patients often have acute onset of arthritis, and there may be a migratory pattern. The duration of symptoms is a very important distinction between reactive arthritides and JIA. Symptoms associated with reactive arthritis typically resolve within 4–6 weeks. In contrast, to meet criteria for chronic arthritis, symptoms must be present for at least 6 weeks.

The arthritis of rheumatic fever is migratory, transient, and often more painful than that of JIA. Rheumatic fever is very rare in children younger than 5 years of age (see Chapter 20). In suspected cases, evidence of rheumatic carditis should be sought based on examination and electrocardiographic findings. Evidence of recent streptococcal infection is essential to the diagnosis. The fever pattern in rheumatic fever is low grade and persistent compared with the spiking fever that characterizes the systemic form of JIA. Lyme arthritis resembles oligoarticular JIA, but the former usually occurs as discrete, recurrent episodes of arthritis lasting 2–6 weeks and children should have a history of being in an endemic area. The typical bull’s-eye rash is called erythema chronicum migrans. Approximately 70%–80% of patients have a history of a compatible rash, although it is usually resolved by the time the arthritis appears. For children suspected of having Lyme disease, testing for antibodies against Borrelia burgdorferi should be performed, with confirmatory testing by Western blot (see Chapter 42).

Treatment

The objectives of therapy are to restore function, relieve pain, maintain joint motion, and prevent damage to cartilage and bone.

A. Nonsteroidal Anti-Inflammatory Medications

First-line therapy is nonsteroidal anti-inflammatory drugs (NSAIDs). A wide range of agents is available but only a few are approved for use in children, including naproxen (10 mg/kg per dose twice daily), ibuprofen (10 mg/kg per dose three to four times daily), and meloxicam (0.125 mg/kg once daily). NSAIDs are generally well tolerated in children, as long as they are taken with food. The average time to symptomatic improvement is 1 month, but in some patients a response is not seen for 8–12 weeks.

B. Disease-Modifying and Biologic Agents

For patients with JIA who fail to respond to NSAIDs, weekly methotrexate is the second-line medication of choice. Symptomatic response usually begins within 3–4 weeks. The low dosages used (5–10 mg/m²/wk or 1 mg/kg/wk as a single dose) are generally well tolerated. Potential side effects include nausea, vomiting, hair thinning, stomatitis, leucopenia, immunosuppression, and hepatotoxicity. A complete blood count and liver function tests should be obtained every 2–3 months. Several additional disease-modifying agents are available for use in patients with persistently active disease or those intolerant to methotrexate. Leflunomide is an antipyrimidine medication that is administered orally. Side effects may include diarrhea and alopecia. Biological modifying medications that inhibit tumor necrosis factor, a cytokine known to play an important role in the pathogenesis of JIA, include etanercept, infliximab, and adalimumab. These drugs are generally quite effective in controlling disease and preventing cartilage and bone damage, and have been associated with healing based on radiologic changes. However, their potential long-term effects are unknown, they are very expensive, and require parenteral administration. Newer biologic agents, including anakinra, rituximab, abatacept, and tocilizumab, have demonstrated some efficacy in patients who have not responded to other treatments.

C. Corticosteroids

Local steroid joint injections may be helpful in patients who have arthritis in one or a few joints. Triamcinolone hexacetonide is a long-acting steroid that can be used for injections and is often associated with at least several months of disease control. Oral or parenteral steroids are reserved for children with severe involvement, primarily patients with systemic disease.

D. Uveitis

Iridocyclitis should be closely monitored by an ophthalmologist (see Chapter 16). Typically treatment is initiated with corticosteroid eye drops and dilating agents to prevent scarring between the iris and the lens. In patients who fail topical treatments, methotrexate, cyclosporine, and/or a tumor-necrosis factor inhibitor such as infliximab or adalimumab may be used.

E. Rehabilitation

Physical and occupational therapies are important to focus on range of motion, stretching, and strengthening. These exercises, as well as other modalities such as heat, water therapy, and ultrasound, can help control pain, maintain and restore function, and prevent deformity and disability. Young children with oligoarticular disease affecting asymmetrical lower extremity joints can develop a leg-length discrepancy, which may require treatment with a shoe lift on the unaffected side.

Prognosis

The course and prognosis for JIA is variable, depending on the subtype of disease. Children with persistent oligoarticular JIA have the highest rate of clinical remission, while patients with RF-positive disease are the least likely to achieve this status and are at highest risk for chronic, erosive arthritis that may continue into adulthood. The systemic features associated with systemic arthritis tend to remit within months to years. The prognosis in systemic disease is worse in patients with persistent systemic disease after 6 months, thrombocytosis, and more extensive arthritis.

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