Juvenile Arthritis

Synonyms: Juvenile Rheumatoid Arthritis (JRA); Juvenile Idiopathic Arthritis (JIA); Juvenile Chronic Arthritis (JCA).

ICD-9 Codes: Juvenile arthritis, 714.3; systemic juvenile arthritis, 714.3; polyarticular juvenile arthritis, 714.31; pauciarticular juvenile arthritis, 714.32.
ICD-10 Codes:  M08

What is it?

Juvenile arthritis (JA) comprises a group of inflammatory arthropathies that affect children younger than the age of 16 years. Juvenile arthritis may be divided into four subsets that differ in their presentation (in the first 6 months) and outcomes: pauciarticular juvenile arthritis, juvenile spondylitis, polyarticular juvenile arthritis, and systemic-onset juvenile arthritis (Table 20).

What causes it?

The cause of juvenile arthritis is unknown. Disordered immunoregulation has been reported, and some have suggested a role for latent viral infection, especially rubella. Increased numbers of patients with juvenile arthritis are seen among those with IgA deficiency and hypogammaglobulinemia. Future research in this area must study subsets separately because they are unlikely to share a common cause.

Pathology: Synovial inflammatory changes are similar to those seen in RA.

Who gets it?

Juvenile arthritis may affect children at any age from birth to 16 years. Onset is usually before the age of 9 years. Incidence rates are roughly 12 to 20 cases per 100,000 population. Females are more commonly affected than males, with the exception of juvenile spondylitis (males predominate) and systemic juvenile arthritis (equally affected) (Table 20).

Table 20: Comparison of Juvenile Arthritis Subsets
Pauciarticular- Juvenile Polyarticular- Systemic
Onset JA Spondylitis Onset JA Onset JA
Frequency 50% 10% 30% 10%
Onset age (y) 1-10 9-16 3-16 3-16
Female:male 5:1 1:4 4:1 1:1
Joint pattern Mono- or pauciarticular Sacroiliitis or asymmetric oligoarthritis Polyarticular, symmetric Polyarticular
Extraarticular features Rare Psoriasis, enthesitis, inflammatory bowel disease Rheumatoid nodules, weight loss Fever, rash, lymphadenopathy, serositis, hepatosplenomegaly
Uveitis 10%-50% 10% Rare Rare
Laboratory findings RF (-), 85% ANA (+) 50% are HLA-B27 (+) 80% RF (-), 20% RF (+), 40% ANA (+) Leukocytosis, ESR > 50 mm/h, anemia, increased LFTs, negative ANA & RF
Prognosis Excellent for joints; guarded for eyes ? Risk of spondylitis and uveitis Severe erosive arthritis in 50% of RF (-) patients 50% develop chronic arthritis; 20% severe erosive arthritis

What are the symptoms?

Presentations and manifestations vary with each disease subset.

—Pauciarticular juvenile arthritis: This is the most common variety of juvenile arthritis, accounting for >50% of cases. Onset is usually before 6 years of age. Monarthritis or oligoarthritis (two to four joints) is seen in the first 6 months. The knee is most commonly and hip least commonly affected. Most achieve remission. However, there is a serious risk of uveitis in this subset. Blindness occurs in <10% of patients and can be prevented by early detection and treatment. Most patients are ANA positive.
—Juvenile spondylitis: This is also known as late-onset pauciarticular disease. Males are more commonly affected than females, and onset is usually between 9 and 16 years of age. Onset is typically characterized by pauciarthritis affecting the knee, ankle, or hip. Some patients have a family history of psoriasis or a SpA. Extraarticular features of an SpA rarely antedate and usually follow the onset of arthritis. HLA-B27 positivity is seen in nearly half, and sacroiliitis may be clinically or radiographically evident. Between 20% and 50% of these patients go on to develop a chronic SpA.
—Polyarticular juvenile arthritis: Nearly 30% of patients have involvement of five or more joints, often in a symmetric distribution similar to that seen in adult RA. RF positivity is seen in 20% to 30%, and ANA positivity is seen in 40% of patients with polyarticular disease. Constitutional features of low-grade fever, weight loss, and lymphadenopathy are occasionally seen. Rheumatoid nodules are only seen in RF-positive patients. This subset tends to have a chronic course and significant disability. More than 20% develop severe, erosive juvenile arthritis that is indistinguishable from seropositive adult RA.
—Systemic-onset juvenile arthritis: Also known as Still’s disease, this subset accounts for 10% of cases. Manifestations include daily spiking (quotidian) fevers of >102°F; an evanescent, salmon-pink rash; arthritis; generalizedlymphadenopathy; serositis; hepato- or splenomegaly; weight loss; myalgias; neutrophilic leukocytosis; anemia; increased ESR (often >50 mm/h); negative serologic tests for ANA and RF; and nonspecific elevations of hepatic enzymes. Systemic disease is seldom life threatening (i.e., pericardial tamponade or DIC), and prognosis is most often determined by the arthritis. Severe erosive, chronic, disabling arthritis develops in 20%. Juvenile arthritis is identical to AOSD, except for less prodromal sore throat in juveniles.Uncommon Findings: Patients with polyarticular disease are at risk for micrognathia and growth retardation. Patients with systemic juvenile arthritis may develop pleuritis, pericarditis, myocarditis, DIC, amyloidosis, or salicylate hepatotoxicity.Complications: Chronic nongranulomatous uveitis occurs in 10% to 50% of patients with pauciarticular disease. There is a questionable association of uveitis with ANA positivity. Most patients are asymptomatic, but some manifest pain and altered vision. It tends to be bilateral, chronic, and progressive and may lead to band keratopathy, posterior synechiae, cataracts, glaucoma, visual loss, or blindness. All patients with pauciarticular and polyarticular juvenile arthritis should undergo slit-lamp examinations every 3 to 6 months to identify early inflammatory lesions.Cervical arthritis, especially C2-3 apophyseal fusion, may be seen in patients with pauciarticular, polyarticular, or systemic disease.Diagnostic Tests: There is no diagnostic laboratory test for JA. Extreme elevations of WBCs and ESR are typical in the systemic subset. RF positivity is seen in a minority of patients with polyarticular disease. ANA positivity is common in both pauciarticular and RF-positive patients with polyarticular disease. HLA-B27 assay is seldom necessary to establish a diagnosis of juvenile spondylitis.

How is it diagnosed?

Imaging: Early radiographic changes may include soft tissue swelling, juxtaarticular osteopenia, or periostitis. Stunted or accelerated bone growth may be seen. With chronicity, loss of joint space and marginal erosions may develop. Fusion of cervical zygapophyseal joints (especially C2-3) may be seen. Atlantoaxial (C1-2) subluxation is less common than in RA.

Keys to Diagnosis: Juvenile arthritis should be suspected with development of a chronic (>6 weeks) inflammatory arthritis in a child. The diagnosis is further established by identifying the pattern of arthritis and associated extraarticular features.

Diagnostic Criteria: ACR criteria are shown in Table 21.

Differential Diagnosis: Other disorders may affect children in a similar fashion, including SLE, reactive arthritis, Lyme disease, DM, Kawasaki’s disease, rheumatic fever, infantile-onset multisystemic inflammatory disease, and the vasculitides. Acute-onset inflammatory mon- or oligoarthritis should raise the possibility of septic arthritis, toxic synovitis of the hip, and especially staphylococcal, streptococcal, or gonococcal arthritis. Arthritis may herald the onset of neoplasia (e.g., leukemia, neuroblastoma) in children.

How is it treated?

A comprehensive approach to treatment must be initiated from the time of diagnosis and must involve the patient and family. Ongoing patient/family education should be interspersed with assessments by the physical therapist, ophthalmologist, dentist, and orthopaedist, if necessary. Patients should be enrolled in a program of active exercise, passive stretch, and periods of rest when the disease is most active. The goal of drug therapy is to reduce pain and inflammation, maintain optimal function, and avoid drug toxicity. This is particularly important with regard to corticosteroids, which should be avoided in children because growth retardation may be an unfortunate consequence.

NSAIDs: Aspirin has historically been used to treat juvenile arthritis. Doses of 80 to 100 mg/kg per day are used to achieve serum levels between 18 and 25 mg/dL. Because of the risk of Reye’s syndrome, aspirin should not be used in children suspected of having influenza, varicella, or other active viral infections. Aspirin and NSAIDs do not alter the course of disease but are effective in ameliorating joint pain and stiffness. Children with juvenile arthritis may be at increased risk of salicylate hepatotoxicity. In recent years, a variety of NSAIDs have gained popularity, and few are FDA approved for use in juvenile arthritis. Commonly used NSAIDs are dosed according to body mass and include ibuprofen (30–50 mg/kg/day) q.i.d., tolmetin (15–30 mg/kg/day) q.i.d., naproxen (10–20 mg/kg/day) b.i.d., and indomethacin (1–3 mg/kg/day) t.i.d. These agents are dosed based on body mass. Less than 50% of patients respond to NSAIDs alone. Multiple NSAIDs should not be used at the same time because this increases the risk of serious GI toxicity.
—DMARDs: MTX (10–15 mg/m2/wk) or intramuscular gold (5 mg test dose, then 0.75–1.0 mg/kg/wk) is most commonly used in the treatment of chronic poly- or pauciarticular juvenile arthritis unresponsive to NSAID therapy and other conservative measures. Alternative DMARDs include hydroxychloroquine (5–7 mg/kg/day), D-penicillamine (5–10 mg/kg/day), auranofin (0.1 mg/kg/day), sulfasalazine (30–50 mg/kg/day), and cyclosporine. Patients with intractable systemic-onset arthritis (i.e., fever, rash) may benefit from long-term MTX therapy. Alternatively, patients may receive hydroxychloroquine, azathioprine, or cyclosporine to control their systemic manifestations. Etanercept has been approved for use in juvenile arthritis. Anakinra appears to be more effective than TNF inhibitors controlling the systemic manifestations of Still disease.
—Corticosteroids: Systemic steroids should be avoided unless absolutely indicated. Prednisone doses of 5 mg/day or more may result in growth retardation. Corticosteroid therapy should be reserved for intractable systemic disease, life-threatening pericarditis or pericardial tamponade, and visual compromise owing to iridocyclitis. Patients with refractory monarthritis or new joint contracture owing to synovitis may benefit from intraarticular corticosteroid injection(s).
—Eye disease: Inflammatory uveitis may respond to topical corticosteroid eye-drops and mydriatics. Systemic administration is seldom necessary. Secondary glaucoma may also require treatment.

Table 21: American College or Rheumatology Classification Criteria for the Diagnosis of Juvenile Rheumatoid Arthritis
1. Age at onset younger than 16 years
2. Arthritis in > 1 joints: defined as swelling or effusion or at least 2 of the following:
Tenderness or pain on motion
Increased heat
3. Duration of disease > 6 wk
4. Type of onset of disease during the first 6 mo classified as
a. Polyarthritis: >5 joints
b. Oligoarthritis: <4 joints
c. Systemic disease with arthritis and intermittent fever
5. Exclusion of other forms of juvenile arthritis

Adapted from: RheumaKnowledgy