Juvenile Rheumatoid Arthritis
Juvenile rheumatoid arthritis (JRA) refers to a number of different conditions, all of which strike children, and all of which have immune-mediated joint inflammation as their major manifestation. JRA is also known as juvenile idiopathic arthritis or JIA. The European League Against Rheumatism, or EULAR, refers to the disorder as juvenile chronic arthritis, or JCA.
The skeletal system of the body is made up of different types of strong, fibrous tissue known as connective tissue. Bone, cartilage, ligaments, and tendons are all forms of connective tissue that have different compositions, and thus different characteristics.
The joints are structures that hold two or more bones together. Some joints (synovial joints) allow for movement between the bones being joined (articulating bones). The simplest model of a synovial joint involves two bones, separated by a slight gap called the joint cavity. The ends of each articular bone are covered by a layer of cartilage. Both the articular bones and the joint cavity are surrounded by a tough tissue called the articular capsule. The articular capsule has two components: the fibrous membrane on the outside, and the synovial membrane (or synovium) on the inside. The fibrous membrane may include tough bands of fibrous tissue called ligaments, which are responsible for providing support to the joints. The synovial membrane has special cells and many capillaries (tiny blood vessels). This membrane produces a supply of synovial fluid that fills the joint cavity, lubricates it, and helps the articular bones move smoothly about the joint.
In JRA, the synovial membrane becomes intensely inflamed. Usually thin and delicate, the synovium becomes thick and stiff, with numerous infoldings on its surface. The membrane becomes invaded by white blood cells, which produce a variety of destructive chemicals. The cartilage along the articular surfaces of the bones may be attacked and destroyed, and the bone, articular capsule, and ligaments may begin to be worn away (eroded). These processes severely interfere with movement in the joint.
JRA specifically refers to chronic arthritic conditions that affect a child under the age of 16 years, and that last for a minimum of three to six months. JRA is often characterized by a waxing and waning course, with flares separated by periods of time during which no symptoms are noted (remission). Some literature refers to JRA as juvenile rheumatoid arthritis, although most types of JRA differ significantly from the adult disease called rheumatoid arthritis in terms of symptoms, progression, and prognosis.
Causes & symptoms
A number of different causes have been sought to explain the onset of JRA. There seems to be some genetic link, based on the fact that the tendency to develop JRA sometimes runs in particular families, and based on the fact that certain genetic markers are more frequently found in patients with JRA and other related diseases. Recent research has shown that several autoimmune diseases, including JRA, share a common genetic link. In other words, patients with JRA might share common
Many researchers have looked for some infectious cause for JRA, but no clear connection to a particular organism has ever been made. JRA is considered by some to be an autoimmune disorder. Autoimmune disorders occur when the body's immune system mistakenly identifies the body's own tissue as foreign, and attacks those tissues, as if trying to rid the body of an invader (such as a bacteria, virus, or fungi). While an autoimmune mechanism is strongly suspected, certain markers of such a mechanism (such as rheumatoid factor, often present in adults with such disorders) are rarely present in children with JRA.
Joint symptoms of arthritis may include stiffness, pain, redness, warmth of the joint, and swelling. Bone in the area of an affected joint may grow too quickly or too slowly, resulting in limbs that are of different lengths. When the child tries to avoid moving a painful joint, the muscle may begin to shorten from disuse. This is called a contracture.
Symptoms of JRA depend on the particular subtype. According to criteria published by the American College of Rheumatology (ACR) in 1973 and modified in 1977, JRA is classified by the symptoms that appear within the first six months of the disorder:
- Pauciarticular JRA: This is the most common and the least severe type of JRA, affecting about 40–60% of all JRA patients. It affects fewer than four joints, usually the knee, ankle, wrist, and/or elbow. Other more general (systemic) symptoms are usually absent, and the child's growth usually remains normal. Very few children (less than 15%) with pauciarticular JRA end up with deformed joints. Some children with this form of JRA experience painless swelling of the joint. Others have a serious inflammation of structures within the eye, which if left undiagnosed and untreated could even lead to blindness. This condition is known as uveitis, and affects about 20% of children diagnosed with JRA. While many children have cycles of flares and remissions, in some children the disease completely and permanently resolves within a few years of diagnosis.
- Polyarticular JRA: About 40% of all cases of JRA are of this type. It is most common in children up to age three or after the age of 10, and affects girls more often than boys. Polyarticular JRA affects five or more joints simultaneously. This type of JRA usually affects the small joints of both hands and both feet, although other large joints may be affected as well. Some patients with arthritis in their knees will experience a different rate of growth in each leg. Ultimately, one leg will grow longer than the other. About half of all patients with polyarticular JRA have arthritis of the spine and/or hip. Others with polyarticular JRA will have other symptoms of a systemic illness, including anemia (low red blood cell count), decreased growth rate, low appetite, low-grade fever, and a slight rash. The disease is most severe in those children who are diagnosed in early adolescence. Some of these children will test positive for a marker present in other autoimmune disorders, called rheumatoid factor (RF). RF is found in adults who have rheumatoid arthritis. Children who are positive for RF tend to have a more severe course, with a disabling form of arthritis that destroys and deforms the joints. This type of arthritis is thought to be the adult form of rheumatoid arthritis occurring at a very early age.
- Systemic onset JRA: Sometimes called Still disease (after a physician who originally described it), this type of JRA occurs in about 10–20% of all patients with JRA. Boys and girls are equally affected, and diagnosis is usually made between the ages of five and 10. The initial symptoms are not usually related to the joints. Instead, these children have high fevers; a rash; decreased appetite and weight loss; severe joint and muscle pain; swollen lymph nodes, spleen, and liver; and serious anemia. Some children experience other complications, including inflammation of the sac containing the heart (pericarditis), inflammation of the tissue lining the chest cavity and lungs (pleuritis), and inflammation of the heart muscle (myocarditis). The eye inflammation often seen in pauciarticular JRA is uncommon in systemic onset JRA. Symptoms of actual arthritis begin later in the course of systemic onset JRA, and they often involve the wrists and ankles. Many of these children continue to have periodic flares of fever and systemic symptoms throughout childhood. Some children will go on to develop a polyarticular type of JRA.
- Spondyloarthropathy: This type of JRA most commonly affects boys older than eight years of age. The arthritis occurs in the knees and ankles, moving over time to include the hips and lower spine. Inflammation of the eye may occur occasionally but usually resolves without permanent damage.
- Psoriatic JRA: This type of arthritis usually shows up in fewer than four joints, but goes on to include multiple joints (appearing similar to polyarticular JRA). Hips, back, fingers, and toes are frequently affected. A skin condition called psoriasis accompanies this type of arthritis. Children with this type of JRA often have pits or ridges in their fingernails. The arthritis usually progresses to become a serious, disabling problem.
As of 2003, there is some disagreement among specialists about the classification of JRA. Some prefer the EULAR classification, also introduced in 1977, to the ACR system. In 1997, the World Health Organization (WHO) met in Durban and issued a new classification system for JRA known as the Durban criteria, in an attempt to standardize definitions of the various subtypes of JRA. None of the various classification systems, however, are considered fully satisfactory as of early 2004.
Diagnosis of JRA is often made on the basis of the child's collection of symptoms. Laboratory tests often show normal results. Some nonspecific indicators of inflammation may be elevated, including white blood cell count, erythrocyte sedimentation rate, and a marker called C-reactive protein. As with any chronic disease, anemia may be noted. Children with an extraordinarily early onset of the adult type of rheumatoid arthritis will have a positive test for rheumatoid factor.
One of the best natural therapies for JRA is resistance exercises, according to a 1999 study at the University of Buffalo in New York. In the study, children did lower body exercises three times a week for an hour per session. After eight weeks, the children had a 40–60% increase in muscle strength, speed, and endurance. The less fit the child, the more improvement that was shown. Also, pain was reduced by 50% and medication use was cut by 25%. In a related study, researchers found exercise decreased inflammatory agents while increasing anti-inflammatory compounds in the body, thereby improving immune function. Diet is also believed to play a role in treating juvenile rheumatoid arthritis. A strict vegetarian diet low in fats and free of glutens can also be helpful, as well as an allergy elimination diet. A number of autoimmune disorders, including JRA, seem to have a relationship to food allergies. Identification and elimination of reactive foods may result in a decrease in JRA symptoms.
Alternative treatments that have been suggested for arthritis include juice therapy, which can work to detoxify the body, helping to reduce JRA symptoms. Some recommended fruits and vegetables to include in the juice are carrots, celery, cabbage, potatoes, cherries, lemons, beets, cucumbers, radishes, and garlic. Tomatoes and other vegetables in the nightshade family (potatoes, eggplant, and red and green peppers) are discouraged. As an adjunct therapy, aromatherapy preparations use cypress, fennel, and lemon. Massage oils include rosemary, benzoin, chamomile, camphor, juniper, eucalyptus, and lavender. Other types of therapy that have been used include acupuncture, acupressure, and body work.
Also shown to be effective in some cases are the essential fatty acids: omega-3 fatty acids in fish oil, and the omega-6 fatty acid gamma liolenic acid (GLA) found in borage oil, currant seed oil, and evening primrose oil. Several alternative medicine doctors suggest there may be some benefit in taking cartilage supplements, although no definitive studies have been done on this treatment. Anti-inflammatory spices such as tumeric, ginger, and cayenne may be helpful. Natural remedies such as yucca, burdock root, horsetail, devil's claw, sarsaparilla, and white willow bark also can be helpful since they have anti-inflammatory and analgesic properties.
Nutritional supplements that may be beneficial include large amounts of antioxidants (vitamins C, A, E, zinc, selenium, and flavenoids), as well as B vitamins and a full complement of minerals (including boron, copper, manganese). One study showed 1,800 International Units (IU) of vitamin E a day could be helpful in relieving symptoms. Other nutrients that assist in detoxifying the body, including methionine, cysteine, and
Treating JRA involves efforts to decrease the amount of inflammation, in order to preserve movement. Medications that can be used for this include nonsteroidal anti-inflammatory agents (such as ibuprofen and naproxen). Oral (by mouth) steroid medications are effective, but have many serious side effects with long-term use. Injections of steroids into an affected joint can be helpful. Steroid eye drops are used to treat eye inflammation. Other drugs that have been used to treat JRA include methotrexate, sulfasalazine, penicillamine, and hydroxychloroquine. Physical therapy and exercises are often recommended in order to improve joint mobility and strengthen supporting muscles. Occasionally, splints are used to rest painful joints and to prevent or improve deformities.
The FDA approved a new drug, etanercept, marketed under the brand name Enbrel, in 1999. It is the most dramatic advancement in treating JRA in recent years. A study by Children's Hospital Medical Center in Cincinnati, Ohio, released in 1999, showed the drug was effective in 75% of children with severe JRA. The drug eases joint pain, reduces swelling, and improves mobility.
In 2003, a group of Japanese researchers noted that the blood serum of patients with JRA contains elevated levels of interleukin-6, a cytokine (nonantibody protein) that is critical to regulation of the immune system and blood cell formation. Because interleukin-6 is also associated with inflammation, the researchers think that compounds inhibiting the formation of interleukin-6 might provide new treatment options for JRA.
The prognosis for pauciarticular JRA is quite good, as is the prognosis for spondyloarthropathy. Polyarticular JRA carries a slightly worse prognosis. RF-positive polyarticular JRA carries a difficult prognosis, often with progressive, destructive arthritis and joint deformities. Systemic onset JRA has a variable prognosis, depending on the organ systems affected, and the progression to polyarticular JRA. About 1–5% of all JRA patients die of such complications as infection, inflammation of the heart, or kidney disease.
Little is known about the causes of JRA, therefore there are no recommendations available for preventing it.
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Ken R. Wells
Rebecca J. Frey, PhD