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Rheumatoid Arthritis: So What's the Difference?

2008-05-05 13:39:00

Rheumatoid arthritis (RA) is a degenerative autoimmune disease in which the joints are attacked by an abnormal immune response and slowly destroyed. RA is much less common than osteoarthritis (OA), occurring in about 1 percent of the population and affecting women two to three times more frequently than men. The first symptoms typically appear between the ages of 25 and 50, although it can occur at any age, even childhood (juvenile RA). Unlike OA, RA is a systemic disease. It can affect organ systems throughout the body, not just the joints. Problems associated with RA include inflamed blood vessels, heart attack, neuropathy, lung complications, and others.

Although about 10 percent of people with RA have a first-degree relative with the disease, genetic factors do not fully explain the incidence of RA. Some researchers have suggested that RA is a response to an infectious agent in a genetically susceptible person. If this is the case, the disease may be caused by persistent infection in the synovial tissues, which protect joints, or by microbial by-products that remain in the synovial tissues after infection. This theory would explain the immune system activation that targets synovial tissue. Other theories propose that such an infectious agent would involve proteins that trigger an immune response or that the infectious microorganism might prime the immune system to attack synovial tissue through “molecular mimicry,” in which proteins in the synovial fluid are mistaken for the infectious agent.

The earliest signs of RA are tiny injuries to the synovial membrane and an increase in the number of synovial cells. At this point, long before symptoms are experienced, there is evidence of immune cell penetration into the synovial membrane. Over time, the immune response continues to gain momentum and inflict damage on the synovial membrane.

This entire process is characterized by inflammation. Mast cells, which secrete pro-inflammatory cytokines, migrate into the synovium, along with by-products of other immune cells, including lymphocytes, macrophages, and fibroblasts. The result is an increase in cytokines, which is responsible for the symptoms of RA. The exact mechanism of bone and cartilage destruction during RA is not completely understood. One theory suggests that the pro-inflammatory cytokines interleukin-1 and tumor necrosis factor-alpha (TNF-alpha) stimulate the production of enzymes that degrade cartilage and inhibit the production of new cartilage and also contribute to the local demineralization of bone by activating osteoclasts (cells that break down bone) (Kasper DL et al 2005).

RA symptoms are caused by chemical messengers called cytokines. It is thought that the release of interleukin-1, TNF-alpha, and interluekin-6 into the circulation system may account for systemic symptoms such as malaise and fatigue. In fact, these symptoms, along with weakness and vague musculoskeletal symptoms, are often the first indication of any disease. They may last for weeks or months, during which time a diagnosis may be difficult to make. It is not until specific, joint-related symptoms appear that RA is diagnosed.

The joint-related symptoms of RA are different from those of OA in that they are generally symmetrical. Specific symptoms may begin to appear in joints of the hands, wrists, knees, and feet. These symptoms include pain that is aggravated by movement. Stiffness is also common, with morning stiffness that lasts longer than one hour occurring frequently. Infrequently, the joints may also be warm to the touch. Motion may be limited by inflammation of the joints.

No specific tests are used to diagnose RA. However, more than 65 percent of people with RA will have rheumatoid factors, or autoantibodies that are produced during the disease, in their blood. The results of testing for rheumatoid factors are not always correct, because up to 20 percent of people over age 65 have rheumatoid factors but do not suffer from RA. Also, a number of other diseases, such as systemic lupus erythematosus, Sjogren’s syndrome, liver disease, hepatitis B, tuberculosis, and syphilis, are characterized by rheumatoid factors. Other tests that might help guide a physician, but will not confirm a diagnosis, include an examination of synovial joint fluid, biopsy of rheumatoid nodules, and increased erythrocyte sedimentation rate, which simply indicates that inflammation is present.

A definitive diagnosis of RA is usually made by identifying the characteristic symptoms of the disease. The disease is usually obvious within one to two years of its onset. To diagnose the disease, four of the following seven criteria are required:

Morning stiffness lasting one hour before improvement
Swelling and joint effusion in at least three different joints out of 14 specifically identified joints
Swelling of wrist or finger joints specifically
Symmetric swelling involving the same joint on both sides of the body
Rheumatoid nodules
Rheumatoid factors in the blood
Typical changes seen in x-rays, including erosions or decalcification in involved joints.