Rheumatoid arthritis (RA) is a chronic inflammatory condition of the synovial membrane - the thin layer of connective tissue that lines the joints. If left untreated, chronic inflammation of the joints can lead to joint damage, deformity, and loss of function. The primary symptoms of RA include painful, swollen joints usually accompanied by morning stiffness lasting for 1 hour or longer. For reasons that are not well-understood, some patients with RA experience only a mild form of the disease with alternating periods of active disease and periods of remission while other patients develop a rapidly progressive form of the disease that results in extensive joint damage and physical disability.

Although rheumatoid arthritis (RA) can affect almost any area of the body, areas of common involvement include the wrists, ankles, knees, elbows, and shoulders. Most patients with rheumatoid arthritis have bilateral joint involvement, meaning that the disease affects corresponding joints on both sides of the body. The specific joints most often affected by RA include:

• Proximal interphalangeal (PIP) joints - the finger joints
• Metacarpophalangeal (MCP) joints - the "knuckle" joints
• Metatarsophalangeal (MTP) joints - the toe joints

Because damage to the joints occurs early in the disease process, early diagnosis and treatment with a class of drugs known as disease-modifying antirheumatic drugs (DMARDs) is crucial for halting further progression of the disease and preventing physical disability.

What Causes Rheumatoid Arthritis?

Despite extensive research over the past few decades, the exact cause of rheumatoid arthritis (RA) has not yet been determined. In general, the following theories have been proposed in an attempt to explain what "triggers" the chronic inflammatory process that leads to the development of rheumatoid arthritis:

• Genetic predisposition
• Autoimmune disease
• Infections

This theory proposes that some people may be genetically predisposed to developing rheumatoid arthritis (RA). Support for this theory comes from studies in twins as well as in families which have found that the chances for developing RA is higher in individuals with a family history of the disease. A specific genetic "marker" , which is often found in a specific gene, the HLA-DR gene and especially in its HLA-DR4 subtype , tends to occur more frequently in people with RA than in the general population. This finding lends additional support for a genetic basis of the disease.

Proponents of this theory argue that rheumatoid arthritis (RA)is an autoimmune disease in which the body's own immune system turns against itself by attacking the joints. Support for this theory is based on the fact that most patients with RA produce an autoantibody (an abnormal antibody that attacks the body's own tissues) called rheumatoid factor (RF) that can be detected with a blood test. Rheumatoid factor is an autoantibody belonging to the IgM class of antibodies that binds to normal antibodies to produce an antigen-antibody complex. Formation of these antigen-antibody complexes in the joints is thought to serve as the "trigger" for initiating the chronic inflammatory response leading to the development of rheumatoid arthritis. A majority of patients with RA also have an antibody against cyclic citrulinated proteins (anti-CCP antibody). This antibody is highly specific for RA and is rarely found in people without RA or people with other diseases. Anti-CCP antibody may be detected before the onset of RA.