Arthritis, Juvenile Rheumatoid
Arthritis, Juvenile Rheumatoid
National Organization for Rare Disorders, Inc.
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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.
Symptoms of the following disorders may be similar to those of JRA. Comparisons may be useful for a differential diagnosis:
Ankylosing spondylitis is a chronic progressive disease characterized by inflammation (arthritis), stiffness, and pain of various joints of the spine and potential loss of spinal mobility. It may involve joints between the spine and the pelvis (sacroiliac joints), joints in the spinal column of the lower and upper back and neck to varying degrees, as well as joints of the limbs, particularly of the legs. In addition, some affected individuals may develop additional symptoms, such as low-grade fever, weight loss, recurrent episodes of acute iridocyclitis, and/or other abnormalities. The exact cause of ankylosing spondylitis is not known. However, genetic and immune factors are thought to play some role. (For more information on this disorder, choose "ankylosing spondylitis" as your search term in the Rare Disease Database.)
Rheumatic fever is an inflammatory syndrome that can occur following streptococcal infections, usually of the throat (strep throat). Associated symptoms and findings may include high fever; heart inflammation (carditis), which may lead to heart valve damage in severe cases; and inflammation (arthritis), swelling, and pain of one or more joints. As arthritis begins to improve in one joint, symptoms may tend to develop in another (migratory polyarthritis), although multiple joints may sometimes be affected at the same time. Rheumatic fever may also be associated with a rash, small nodules under the skin, and involuntary, jerky movements with characteristic facial grimaces (Sydenham's chorea). (For more information on this disorder, choose "Rheumatic fever" as your search term in the Rare Disease Database.)
Systemic lupus erythematosus (SLE) is a chronic, inflammatory disease of connective tissue that may affect multiple organ systems and tissues, such as the skin, joints, membranes lining the walls of certain body cavities, kidneys, and/or nervous system. The disease is thought to result from an abnormal response in which the body's immune system acts against its own cells and tissues, leading to inflammation and malfunction of various organ systems. The range and severity of associated symptoms and findings may vary from case to case. However, many affected individuals may initially develop generalized symptoms, such as excessive fatigue, fever, a general feeling of ill health (malaise), loss of appetite (anorexia), weight loss, and joint swelling, inflammation, and pain. The disorder may also be associated with skin abnormalities, such as a scaling, reddish rash in a "butterfly" pattern across the cheeks and the nasal bridge; increased sensitivity to light (photosensitivity); reddish swelling around the nails; tender, reddish-purplish skin swellings; and/or other findings. Additional abnormalities may include enlargement of the liver, spleen, and lymph nodes, inflammation of the filtering units of the kidneys, neurologic symptoms, such as headaches, seizures, and/or personality changes, and/or inflammatory changes of the membranes lining the chest cavity and lungs, lining the abdominal wall and organs, and/or surrounding the heart. Disease progression may also affect other tissues, leading to additional symptoms and findings. (For more information, choose "lupus" as your search term in the Rare Disease Database.)
Lyme disease is a tick-transmitted inflammatory disease that may be characterized by an early skin rash and subsequent joint, neurologic, and heart abnormalities. Early symptoms and findings may include fatigue, chills, fever, headache, swollen lymph nodes, and an enlarged spleen. Symptoms of arthritis, such as swelling and pain of certain joints, particularly the knees, may occur within weeks or months following infection. Experts indicate that Lyme disease should be considered in children with suspected JRA who live in or have visited tick-infected areas. (For more information on this disorder, choose "Lyme" as your search term in the Rare Disease Database.)
A number of additional infectious diseases, rheumatic disorders, and other conditions may also be characterized by certain joint symptoms and other features similar to those associated with the different forms of JRA. Such disorders are typically associated with additional, characteristic features that may help to differentiate them from JRA. (For further information on such disorders, choose the exact disease name in question as your search term in the Rare Disease Database.)
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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