Juvenile rheumatoid arthritis (JRA) is a rheumatic disease characterized by chronic inflammation (arthritis) of one or more joints in a child age 16 years or younger. Associated symptoms typically include swelling, abnormal warmth, tenderness or pain, and/or stiffness of affected joints that tends to be worse in the mornings. In severe cases, destructive changes may eventually result in limited mobility and possible deformity of affected joints.
Some children with JRA may also have generalized symptoms and findings, such as fever, lack of appetite (anorexia), enlargement of the liver and spleen (hepatosplenomegaly), and/or other abnormalities. In addition, some forms of JRA are associated with an increased risk for inflammation of certain regions of the eyes (iridocyclitis). The range and severity of associated symptoms and findings may vary, depending upon the specific form of the disease present. The exact cause of JRA is not known.
Juvenile rheumatoid arthritis (JRA) is characterized by inflammation of one or more joints (arthritis) that persists for six weeks or more in a child age 16 years or younger. The arthritis results in swelling, stiffness, limited range of motion, tenderness or pain, and/or abnormal warmth of affected joints. Associated symptoms and findings may vary, depending upon the form of the disease present.
There are three primary forms of JRA: systemic onset, which is also known as Still’s disease; polyarticular onset, and pauciarticular onset.
Systemic-onset disease is associated with joint abnormalities as well as “whole body” (i.e., systemic) symptoms. It may initially be characterized by a repeated high fever that may recur daily over weeks or longer. Feverish (febrile) periods may be accompanied by shaking chills and a flat, pale rash, primarily affecting the trunk and upper arms and legs. Many also have additional features, such as generalized enlargement of the lymph nodes (lymphadenopathy); enlargement of the liver and spleen (hepatosplenomegaly), increased levels of circulating white blood cells (leukocytosis), reduced levels of the oxygen-carrying component (hemoglobin) of red blood cells (anemia), inflammation of the membranes lining the chest cavity and lungs (pleuritis) and/or surrounding the heart (pericarditis), and/or additional features. Characteristic joint abnormalities, including joint swelling, pain, and stiffness, may be apparent at symptom onset or develop up to several months later. Although systemic features may resolve within several months, such features may recur. In addition, the arthritis may become chronic in some cases, persisting following improvement of systemic symptoms and findings. Still’s disease affects approximately 20 percent of individuals with JRA.
Polyarticular-onset disease affects multiple (i.e., at least five or more) joints, such as those of the fingers, wrists, elbows, knees, and/or ankles. Various other joints may also be affected, such as those of the neck, jaw, hips, and/or other areas of the body. The inflammation is often symmetrical, affecting the same joint on both sides of the body. Associated symptoms may include tenderness or pain, abnormal warmth, stiffness, and limited mobility of affected joints. In some cases, joint inflammation associated with polyarticular or other forms of the disease may lead to excessive or deficient growth of the affected bodily region, such as increased leg length due to knee involvement or abnormal smallness of the jaw (micrognathia) due to involvement of joints connecting the lower jaw to the lower skull (temporomandibular arthritis). Children with polyarticular disease may have additional symptoms and findings, such as low-grade fever; slight enlargement of the spleen, liver, and lymph nodes; mild anemia; lack of appetite (anorexia), irritability; and/or other abnormalities during active disease. This form of the disease is thought to affect approximately 40 percent of children with JRA.
Pauciarticular-onset disease affects fewer than five joints. It usually becomes apparent before five years of age; most commonly affects girls; and primarily involves the knee, ankle, and elbow joints. In some cases, active joint disease may be associated with low-grade fever; mild anemia, and slight enlargement of the liver, spleen, and lymph nodes. In addition, evidence indicates that affected children have a risk of developing chronic inflammation of the iris and surrounding muscles in the eyes (iridocyclitis). The condition often causes no apparent symptoms (asymptomatic) and is recognized only during examination of the eyes. Without treatment, visual impairment or blindness may result.
Pauciarticular-onset disease also affects a subgroup of older boys. In such cases, the onset of arthritis usually occurs after the age of eight. Affected joints may include those of the hips, knees, ankles, and toes. In addition, many subsequently develop chronic inflammatory disease of joints of the spine (spondyloarthropathies), such as ankylosing spondylitis. This subtype may also be associated with self-limited episodes of acute iridocyclitis with early symptoms of eye inflammation, such as redness and pain. Pauciarticular-onset disease types affect approximately 40 percent of children with JRA.
In about half to three-quarters of affected individuals, symptoms may gradually subside with little or no associated functional abnormalities. However, others may have active joint disease that continues into early adulthood. Evidence suggests that certain factors, such as involvement of multiple joints as well as rheumatoid factor, may be associated with an increased risk for functional abnormalities. (Rheumatoid factors are specific antibodies that are present in the blood of some individuals with rheumatoid arthritis.) Complications may include destructive joint changes, limited movement, and deformity of affected joints, such as permanent bending or extension of certain joints in fixed postures (contractures).
The exact cause of JRA is not known. However, it is thought to be due to an abnormal immune response in individuals with a genetic predisposition. Investigators indicate that it may result from an abnormal reaction to an unidentified virus or other environmental agent and/or to certain “self” proteins, representing an immune reaction directed against the body’s own tissues (autoimmune response). According to researchers, underlying genetic and immune mechanisms may be suggested by various findings, including an increased frequency of certain genetically determined “human leukocyte antigens” (HLAs) in some individuals with certain types of the disease. HLAs are proteins that play an important role in the body’s immune system, they influence the outcome of transplantation and appear to affect an individual’s predisposition to certain diseases. However, the implications of such findings are not fully understood.
JRA has an incidence of approximately 14 per 100,000 children per year among those aged 15 years or younger. Polyarticular- and pauciarticular-onset JRA occur more frequently in females than males. Systemic-onset disease appears to affect females and males relatively equally. JRA is considered one of the most common rheumatic diseases that affects children.
The diagnosis of JRA may be suspected based upon a thorough clinical evaluation, detection of characteristic physical findings, and a careful patient history. There is no single, specific diagnostic test to confirm JRA. However, certain studies may be conducted to help rule out other diseases or conditions and to detect or characterize particular abnormalities potentially associated with JRA. Such testing may include x-ray studies; blood counts, rheumatoid factor testing; HLA typing; erythrocyte (i.e., red blood cell) sedimentation rate (ESR), testing to detect certain "self-antibodies" (antinuclear antibodies [ANA]), and/or other studies. An elevated ESR may serve as a nonspecific indicator of inflammation. Detection of ANA in patients with JRA is a finding that may be associated with an increased risk of chronic iridocyclitis. In addition, slit-lamp examination should regularly be performed for affected children to ensure prompt detection and treatment of iridocyclitis, with the recommended frequency based on risk. During slit-lamp examination, internal structures of the eye are viewed with an illuminated microscope.
Recommended treatment for children with JRA may include the use of various drugs or drug combinations as well as physical therapy. The specific therapies used may depend on several factors, including type of JRA, disease severity, and response to treatment.
Drug therapy for JRA has gradually changed, with aspirin less frequently used in the United States due to its association with Reye syndrome in children. The initial medical treatment of JRA usually includes the administration of nonsteroidal anti-inflammatory drugs (NSAIDs), such as naproxen, tolmetin, or ibuprofen, to help relieve joint pain and inflammation.
In December 2006, the U.S. Food and Drug Administration (FDA) approved the drug celecoxib (Celebrex) for the treatment of JRA in patients two years of age and older. Celebrex is an NSAID.
If NSAID therapy does not sufficiently relieve symptoms, physicians may recommend treatment with a "disease-modifying antirheumatic drug" (DMARD) that may help to slow or prevent joint damage. Various DMARDs are available.
For example, such agents include the antimalarial drug hydroxychloroquine or sulfasalazine, a drug that has anti-inflammatory action and may be recommended for selected patients. Because therapy with such agents may cause significant adverse effects, such as eye damage with hydroxychloroquine therapy, their use must be carefully monitored.
In some cases, other DMARDs, such as gold salts or penicillamine, have been used to treat individuals who do not respond to NSAID treatment. However, with the increasing use of methotrexate, such agents are less commonly prescribed.
Therapy with the DMARD methotrexate, which is an immunosuppressive agent, has been shown to be effective in many children with severe JRA. It is often recommended as a treatment for patients who do not respond adequately to NSAID agents. Low-dose methotrexate may be administered orally or under the skin (subcutaneously) once weekly. Because immunosuppressive therapy may cause severe adverse effects (e.g., increased susceptibility to infections, liver disease), children who receive methotrexate therapy should be regularly monitored with kidney, liver function, and blood studies. Research is ongoing to study the long-term effects of the use of methotrexate in children with JRA.
Although corticosteroids are powerful anti-inflammatory drugs, their use may be avoided, if possible, since long-term therapy may cause growth retardation, reduced bone mass, Cushing syndrome, and other severe effects. (For further information, use "Cushing" as your search term in the Rare Disease Database.. However, oral corticosteroid therapy may be given in some instances, such as in extremely severe cases of treatment-resistant systemic disease. In addition, in some cases, corticosteroid injections may be advised to help relieve persistent inflammation in one or a few affected joints.
In individuals with iridocyclitis, treatment may include the administration of drugs that widen the pupils and corticosteroid eyedrops. In addition, treatment with oral corticosteroids may be recommended for individuals with iridocyclitis that is unresponsive to corticosteroid eyedrops. Patients should be under the care of eye specialists (ophthalmologists) during such therapy and regularly monitored with slit-lamp examinations.
Also approved for the treatment of JRA is etanercept (Enbrel). This drug is a biologic agent that blocks the actions of a naturally occurring protein involved in causing inflammation (tumor necrosis factor). The drug is used for the management of symptoms of moderately to severely active polyarticular JRA in children four years of age or older who have had an inadequate response to one or more DMARDs.
For patients with JRA, physical and occupational therapy and special exercises may play an important role in helping to improve mobility and muscle strength. The use of special splints may also be recommended to help prevent or correct contracture development and deformity. In some cases, surgical correction may be advised.
Other treatment for this disorder is symptomatic and supportive.
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Behrman RE, et al., eds. Nelson Textbook of Pediatrics. 16th ed. Philadelphia, Pa: W.B. Saunders Company; 2000:704-09.
Beers MH, et al., eds. The Merck Manual. 17th ed. Whitehouse Station, NJ: Merck Research Laboratories; 1999:2402-03.
Bennett JC, Plum F, eds. Cecil Textbook of Medicine. 20th ed. Philadelphia, Pa: W.B. Saunders Company; 1996:766.
Kelley WN, et al., eds. Textbook of Rheumatology. 4th ed. Philadelphia, Pa: W.B. Saunders Company; 1993:1189-1208.
Johnson CJ, et al. Etanercept in juvenile rheumatoid arthritis. Ann Pharmacother. 2001;35:464-71.
Kietz DA, et al. Clinical response to etanercept in polyarticular course juvenile rheumatoid arthritis. J Rheumatol. 2001;28:360-62.
Schmeling H, et al. A combination of etanercept and methotrexate for the treatment of refractory juvenile idiopathic arthritis: a pilot study. Ann Rheum Dis. 2001;60:410-12.
Lovell DJ, et al. Etanercept in children with polyarticular juvenile rheumatoid arthritis. New Engl J Med. 2000;342:763-69.
Lin YT, et al. Efficacy and safety of methotrexate therapy for juvenile rheumatoid arthritis. J Formos Med Assoc. 2000;99:623-29.
Cassidy JT. Medical management of children with juvenile rheumatoid arthritis. Drugs. 1999;58:831-50.
Gravallese EM, et al. Identification of cell types responsible for bone resorption in rheumatoid arthritis and juvenile rheumatoid arthritis. Am J Pathol. 1998;152:943-51.
Ruperto N, et al. Performance of the preliminary definition of improvement in juvenile chronic arthritis patients treated with methotrexate. Ann Rheum Dis. 1998;57:38-41.
Van Rossum MA, et al. Sulfasalazine in the treatment of juvenile chronic arthritis: a randomized, double-blind, placebo-controlled, multicenter study. Arthritis Rheum. 1998;41:808-16.
Ravelli A, et al. Oral versus intramuscular methotrexate in juvenile chronic arthritis. Clin Exp Rheumatol. 1998;16:181-83.
Coto C, et al. Use of recombinant interferon gamma in pediatric patients with advanced juvenile chronic arthritis. Biotherapy. 1998;11:15-20.
Miller ML. Clinical aspects of juvenile rheumatoid arthritis. Curr Opin Rheumatol. 1997;9:423-27.
Gottlieb BS, et al. Discontinuation of methotrexate treatment in juvenile rheumatoid arthritis. Pediatrics. 1997;100:994-97.
Imundo LF, et al. Sulfasalazine therapy for juvenile rheumatoid arthritis. J Rheumatol. 1996;23:360-66.
Kummerle-Deschner J, et al. Sulphasalazine desensitization in a pediatric patient with juvenile chronic arthritis. Acta Pediatr. 1995;84:952-54.
Gedalia A, et al. Sulphasalazine in the treatment of pauciarticular-onset juvenile chronic arthritis. Clin Rheumatol. 1993;12:511-14.
Rhodes VJ. Physical therapy management of patients with juvenile rheumatoid arthritis. Phys Ther. 1991;71:910-19.
Giannini EH, et al. Auranofin in the treatment of juvenile rheumatoid arthritis. Results of the USA-USSR double-blind, placebo-controlled trial. The USA pediatric rheumatology collaborative study group. The USSR cooperative children’s study group. Arthritis Rheum. 1990;33:466-76.
Pernice W, et al. Therapy for systemic juvenile rheumatoid arthritis with gamma-interferon: a pilot study of nine patients. Arthritis Rheum. 1989;32:643-46.
Wallace CA. Toxicity and serum levels of methotrexate in children with juvenile rheumatoid arthritis. Arthritis Rheum. 1989;32:677-81.
Rosenberg AM. Advanced drug therapy for juvenile rheumatoid arthritis. J Pediatr. 1989;114:171-78.
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Juvenile rheumatoid arthritis
eMedicine – Juvenile Rheumatoid Arthritis : Article by Michael L Miller MD
Juvenile rheumatoid arthritis – MayoClinic.com
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