Rheumatoid arthritis (RA) affects 2.1 million Americans, three times more women than men. Onset is usually in middle-age, but often occurs in the 20s and 30s. RA is an inflammatory disease that causes pain, swelling, stiffness, and loss of function in the joints. It has several special features that make it different from other kinds of arthritis. For example, RA generally occurs in a symmetrical pattern which means that if one knee or hand is involved, the other one is also. The disease often affects the wrist joints and the finger joints closest to the hand but can also affect other parts of the body besides the joints. It can be accompanied by fatigue, occasional fever, and a general sense of not feeling well (malaise). Inflammatory arthritis, which includes rheumatoid arthritis, are the most serious of the joint diseases. The disease is characterized by pain, swelling and morning stiffness lasting more than an hour. In addition, the symptoms are predominant in the morning and there is a tendency to fatigue through the day.

RA varies a lot from person to person. For some it lasts only a few months to a year or two and goes away without causing any noticeable damage. Others have mild or moderate disease, with periods of worsening symptoms, called flares, and periods in which they feel better, called remissions. Still others have severe disease that is active most of the time, lasts for many years, and leads to serious joint damage and disability.

Although RA can have serious effects on a person's life and well-being, current treatment strategies - including pain relief and other medications, a balance between rest and exercise, and patient education and support programs - allow most people with the disease to lead active and productive lives. In recent years, research has led to a new understanding of RA and has increased the likelihood that, in time, researchers can find ways to greatly reduce the impact of this disease.

The Development and Progression of RA
Researchers suspect that some type of microorganism may be the trigger in some people who have an inherited tendency for the disease. Dr. Hoekstra, MD has found that virtually all the patients he has studied have had significant amounts of a bacteria called Propioni bacterium acnes. "This is the genus and species of the organism we believe is responsible for propagating and perpetuating this disease," says Dr. Hoekstra. "It is a very common bacteria in an altered state of being - it is cell wall deficient."

The bacterium was first identified and described in 1981 by G.A. Denys at Wayne State University in Detroit, Michigan. "This bacteria is passed transplacentally, from mother to fetus, and this may be responsible for RA showing up in generations in a single family," says Dr. Hoekstra. Why this bacteria is prevalent in seemingly all cases of RA is not clear; but overuse of antibiotics may be a factor encouraging its growth. "The use of antibiotics is one of the most potent ways of inducing cell wall deficiency; bacteria seem to do this as a survival mechanism." In other words, when a bacterium is transformed into a cell wall deficient form, it assumes different characteristics from the whole or native type of microorganism it used to be.

Dr. Hoekstra explains, "The organism remains intact except for losing its cell wall and its antigenic characteristics, enabling it to function as a cellular chameleon." When it loses its antigenic signature, the bacteria are able to mask themselves against destruction by the immune system's antibodies which can no longer recognize them as antigens (foreign proteins).

Dr. Hoekstra's mentor, Lida Holmes Mattman, Ph.D., also of Wayne State confirmed the causal role of P. acnes in a laboratory experiment. Dr. Mattman extracted the bacteria from the synovial fluid (which lubricates joints) of human arthritis patients, and injected it into chicken embryos. The chicks then exhibited symptoms of RA. When she treated the chicks with antibiotics known to disable P. acnes, the disease disappeared.

Another recently discovered aspect of RA is that sufferers who were previously thought to have overactive immune systems, instead may have exhausted immune systems. ''What this study has shown for the first time is that patients with RA have prematurely aged immune systems'' said lead author Dr. Cornelia Weyand, a rheumatologist at the Mayo Clinic.

''Until now we have thought that these patients had overactive immune systems, which is why we have aggressively treated the symptoms of rheumatoid arthritis with medications that suppress the immune system." Weyand and colleagues studied the immune systems of 51 patients with rheumatoid arthritis and compared them to 47 people of similar age who did not have the condition. They found that the T-cells - the immune cells that are programmed to recognize and attack invaders such as bacteria and viruses - were worn out. ''They do not make new T-cells.'' [Proceedings of the National Academy of Sciences, 2000]

A normal joint (the place where two bones meet) is surrounded by a joint capsule that protects and supports it. Cartilage covers and cushions the ends of the two bones. The joint capsule is lined with a type of tissue called synovium, which produces synovial fluid. This clear fluid lubricates and nourishes the cartilage and bones inside the joint capsule.

In cases of RA, the immune system for reasons unknown attacks a person's own cells inside the joint capsule. White blood cells that are part of the normal immune system travel to the synovium and cause a reaction. This reaction, or inflammation, called synovitis, results in the warmth, redness, swelling, and pain that are typical symptoms of RA. During the inflammation process, the cells of the synovium grow and divide abnormally, making the normally thin synovium thick and resulting in a joint that is swollen and puffy to the touch.

As RA progresses, these abnormal synovial cells begin to invade and destroy the cartilage and bone within the joint. The surrounding muscles, ligaments, and tendons that support and stabilize the joint become weak and unable to work normally. All of these effects lead to the pain and deformities often seen in RA. Doctors studying RA now believe that damage to bones begins during the first year or two that a person has the disease and this is one reason early diagnosis and treatment are so important.

Other parts of the body
Some people also experience the effects of RA in places other than the joints. About one-quarter develop rheumatoid nodules, bumps under the skin that often form close to the joints. Many people with RA develop anemia, or a decrease in the normal number of red blood cells. Other effects, which occur less often, include neck pain and dry eyes and mouth. Very rarely, people may have inflammation of the blood vessels, the lining of the lungs, or the sac enclosing the heart.

What are the signs and symptoms of RA?

• Pain and stiffness lasting for more than 30 minutes in the morning or after a long rest.
• Tender, warm, swollen joints. Joint inflammation often affecting the wrist and finger joints closest to the hand; other affected joints can include those of the neck, shoulders, elbows, hips, knees, ankles, and feet. Rheumatoid nodules are sometimes present.
• Symmetrical pattern. For example, if one knee is affected, the other one is also.
• Fatigue, occasional fever, a general sense of not feeling well (malaise).
• Symptoms possibly lasting for many years.
• Symptoms affecting other parts of the body besides the joints.

How is RA diagnosed?
RA can be difficult to diagnose in its early stages for several reasons. First, there is no single test for the disease. In addition, symptoms differ from person to person and can be more severe in some people than in others. Furthermore, symptoms can be similar to those of other types of arthritis and joint conditions, and it may take some time for other conditions to be ruled out as possible diagnoses. Finally, the full range of symptoms develops over time, and only a few symptoms may be present in the early stages.

Doctors use a variety of tools to diagnose the disease and to rule out other conditions: medical history, physical examination, laboratory tests. One common test is for rheumatoid factor, an antibody that is eventually present in the blood of most RA patients. Not all people with RA test positive for rheumatoid factor, especially early in the disease; indeed some who do test positive never develop the disease.

Other common tests include some that indicate the degree or severity of inflammation in the body (the erythrocyte sedimentation rate, or C-reactive protein), a white blood cell count, and a blood test for anemia. X-rays can be used to determine the degree of joint destruction but are not useful in the early stages of RA before bone damage is evident. They can be used later to monitor the progression of the disease.

Tea and decaffeinated coffee intake were individually associated with an increased risk of developing rheumatoid arthritis in a prospective study of 64,000 black women followed for up to 4 years. Caffeinated coffee intake was not associated with the risk of developing RA. [65th Annual Scientific Meeting of the American College of Rheumatology and the 36th Annual Scientific Meeting of the Association of Rheumatology Health Professionals, November 11-15, 2001, San Francisco, CA; presentation 1938]