eMedicine Specialties > Pediatrics: General Medicine > Rheumatology

Juvenile Rheumatoid Arthritis

Author: Michael L Miller, MD, Associate Professor of Pediatrics, Feinberg School of Medicine, Northwestern University; Consulting Staff, Director of Clinical Service, Clinical Practice Director, Department of Pediatrics, Division of Immunology/Rheumatology, Children's Memorial Hospital
Contributor Information and Disclosures

Updated: Apr 15, 2008

Introduction

Background

Juvenile rheumatoid arthritis (JRA) is not a single disease. Rather, it is a group of diseases of unknown etiology, which are manifested by chronic joint inflammation.

Advances in treatment during the last 30 years have changed the prognosis for the more severe forms of this disease. Initial treatment limited to the use of salicylates and then other nonsteroidal anti-inflammatory drugs (NSAIDs) resulted in many patients becoming wheelchair bound. Other patients underwent synovectomies to remove excess tissue resulting from uncontrolled arthritis. The addition of second-line drugs, starting with gold salt injections and then replaced by the much more effective methotrexate (MTX), improved the outlook for these patients. These medications are administered in the context of a team approach in pediatric rheumatology centers, where physical and occupational therapy have permitted greatly improved physical function.

The approval of etanercept, a biologic antagonist to tumor necrosis factor (TNF), has ushered in a new era of treatment more closely tailored to the pathophysiology of the disease. Other biologic agents, such as anakinra, an interluekin-1 (IL-1) receptor antagonist, may play a role in selected patients who are unresponsive to second-line drugs. In the future, inhibition of IL-6 may prove to be effective in systemic patients with JRA who have elevated levels.

Pathophysiology

The etiology of JRA is unknown. Chronic inflammation of synovium is characterized by B lymphocyte infiltration and expansion. Macrophages and T-cell invasion are associated with the release of cytokines, which evoke synoviocyte proliferation. A 2001 study by Scola et al found synovium to contain messenger RNA for vascular endothelial growth factor, angiopoietin 1, and their respective receptors, suggesting that induction of angiogenesis by products of lymphocytic infiltration may be involved in persistence of disease. The resulting thickened pannus causes joint destruction. In many patients, predominance of cytokines associated with tissue destruction, including interleukin-6 and TNF, suggests the possibility of improved responsiveness to specific biologic agents targeting these factors.

Frequency

United States

Prevalence of JRA has been estimated to be 10-20 cases per 100,000 children. Prevalence data vary (11-83 cases per 100,000), depending upon the location of the study. Pauciarticular and polyarticular disease occur more frequently in girls, while both sexes are affected with equal frequency in systemic-onset disease.

International

JRA appears to occur more frequently in certain populations (eg, Native Americans) from such disparate areas as British Columbia and Norway. A study in Sweden found prevalence similar to that in Minnesota, approximately 85 cases per 100,000 population.

Mortality/Morbidity

• No recent studies have quantitated mortality in JRA. However, the mortality rate is less than 1% and is often associated with the evolution of disease to manifestations of other rheumatic diseases, such as systemic lupus erythematosus (SLE) or scleroderma. Such progression has been reported to be associated with high titer antinuclear antibodies (ANA) at presentation in some children.
• Patients with JRA may experience complications specific to their disease subset (see Clinical). The most typical type of morbidity in patients with JRA relates to adverse effects of medications, particularly NSAIDs. Abdominal pain related to gastritis or ulcer disease, hepatotoxicity, and occasionally, renal toxicity are sufficiently frequent to warrant routine laboratory screening.
• Significant psychologic morbidity (eg, situational depression, anxiety, problems functioning in school) can occur in all subtypes. Morbidity experienced in problems with quality of life is being actively investigated. Such problems may occur in children with all subtypes and may be the result of additional factors, such as socioeconomic status and family problems.

Race

Few studies documenting racial differences exist. However, in 1997, Schwartz and colleagues found that, compared to whites, blacks with JRA were older and less likely to test positive for ANA or to have uveitis; however, blacks were more likely to test positive for immunoglobulin M rheumatoid factor.

Sex

Pauciarticular and polyarticular JRA tend to affect girls more often than boys. Systemic-onset disease occurs with equal frequency in boys and girls.

Age

Pauciarticular JRA tends to affect children in early childhood. Systemic-onset disease can also occur in early childhood; however, it is sometimes observed in late childhood or early adolescence. Polyarticular JRA can occur throughout childhood and adolescence. Rheumatoid factor–positive disease, similar to rheumatoid arthritis in adults, is more often found in adolescents.

Clinical

History

Juvenile rheumatoid arthritis (JRA) is classified as systemic, pauciarticular, or polyarticular disease according to onset within the first 6 months.

• General history of JRA includes the following:
  • Disease onset is either insidious or abrupt, with morning stiffness and arthralgia during the day.
  • Individuals with JRA may have a school history of absences, and their abilities to participate in physical education classes may reflect severity of the disease. Typically, patients with JRA and their parents and/or caregivers are concerned about missing school; in contrast, when psychogenic factors predominate (eg, pain syndromes), patients and their parents and/or caregivers are more worried about returning to school than about missing school.
  • Limping may be observed in individuals with more severe JRA; however, the presence of limping also raises the possibility of trauma or another orthopedic problem.
  • Injury suggests the possibility of trauma to a joint (eg, meniscal tear).
  • A preceding illness raises the possibility of infectious trigger of JRA or postinfectious arthritis.
  • Illness in pets with a history of enteritis raises the possibility of reactive arthritis.
  • History of travel with exposure to ticks raises the possibility of arthritis caused by Lyme disease.
  • Gastrointestinal symptoms raise the possibility of inflammatory bowel disease.
  • Very severe joint pain raises the possibility of acute rheumatic fever (also suggested by migratory but not additive arthritis, with fevers), acute lymphocytic leukemia (with metaphyseal pain on examination, decrease in 2 or more cell lines), septic arthritis, or osteomyelitis.
  • Weight loss without diarrhea may be observed in individuals with active JRA and is sometimes associated with anorexia. This symptom is also observed in individuals with acute lymphocytic leukemia with other obvious findings (eg, decrease in at least 2 cell lines, severe bone pain).
  • Weight loss with diarrhea may be observed in persons with inflammatory bowel disease.
  • Photophobia may be observed in persons with usually asymptomatic uveitis.
  • Orthopnea suggests pericarditis in children with systemic JRA; the differential diagnosis includes SLE and viral pericarditis.
• Systemic-onset JRA is characterized by spiking fevers, typically occurring several times each day, with temperature returning to the reference range or below the reference range.
  • Systemic-onset JRA may be accompanied by an evanescent rash, which is typically linear, affecting the trunk and extremities.
  • Arthralgia is often present. Frank joint swelling is atypical; arthritis may not occur for months following onset, making diagnosis difficult.
  • Some children may have a generalized myalgia.
  • Localization to proximal muscles raises the possibility of a myositis.
• Pauciarticular disease is characterized by arthritis affecting 4 or fewer joints.
  • Typically, larger joints (eg, knees, ankles, wrists) are affected.
  • Monoarticular arthritis in a hip is highly unusual.
  • Consider Legg-Calvé-Perthes disease; toxic synovitis of the hip; septic arthritis; osteomyelitis; or, in an older child, slipped capital femoral epiphysis or chondrolysis of the hip.
  • When the knee is affected, limping may be noted, particularly in the mornings.
  • Chronic involvement can result in atrophy of extensor muscles in the thigh, tight hamstring ligaments, and knee flexion contractures.
• Polyarticular disease affects at least 5 joints.
  • Both large and small joints can be involved, often in symmetric bilateral distribution.
  • Severe limitations in motion are usually accompanied by weakness and decreased physical function.

Physical

A detailed physical examination is a critical tool in diagnosing JRA. Physical findings are important to provide criteria for diagnosis and to detect abnormalities suggestive of other possible diagnoses. The diagnosis of JRA is based on the physical finding of arthritis (or synovitis) in at least one joint that persists for at least 6 weeks, with other causes being excluded and with onset when the individual is younger than 16 years. Arthritis on examination is defined as either joint swelling (although trauma can also cause swelling and may need to be excluded) or the combination of limited motion with pain (on motion or to palpation). The hips and small joints in the spine, when affected by synovitis, do not demonstrate swelling but demonstrate the combination of loss of motion and pain.

• A definite diagnosis of systemic-onset JRA must await the eventual development of arthritis, which may not occur for months.
  • Evanescent salmon-pink rash, often linear, is found on the trunk and the extremities; this rash is worse with fever.
  • Hepatosplenomegaly is often present.
  • Lymphadenopathy is sometimes present.
  • Muscle tenderness to palpation may be observed.
  • Rarely, serositis, which raises the possibility of SLE, is found.
• In individuals with pauciarticular JRA, 4 or fewer joints are affected; often, only a single joint is affected (see Media file 1).
  • Typically, large weight-bearing joints, knees, and ankles are affected.
  • Involvement of a few small joints in the hands is atypical and suggests eventual development of polyarticular JRA or, occasionally, psoriasis years later, with retrospective diagnosis of psoriatic arthritis.
  • Muscle atrophy, often of extensor muscles (eg, vastus lateralis, quadriceps when knee affected) is found.
  • Flexion contractures in the knees and, less commonly, the wrists are found.
• In persons with polyarticular JRA, 5 or more joints are affected (see Media file 2).
  • Weight-bearing joints are affected, and symmetric involvement of small joints in the hands is found (see Media file 4).
  • Pain with decreased range of motion in the cervical spine is sometimes found.
• Other findings in persons with JRA are as follows:
  • Ocular: Photophobia, in uveitis (usually asymptomatic on onset), and synechiae (ie, irregular iris perimeter resulting from postinflammatory adhesions of iris to lens) may be found (see Media file 7).
  • Cardiovascular: Orthopnea and rub suggest pericarditis (rub may be absent with large pericardial effusion). S₃, basilar rales, and hepatomegaly suggestive of heart failure may rarely be observed, when myocarditis occurs in individuals with systemic JRA.

Causes

The specific causes of JRA remain undefined.

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