Charles A. Bertrand, M.D., FACP, DIM-CD (Ret.)
Associate Clinical Professor of Medicine at New York Medical College
and at the Medical University of South Carolina


GUEST EDITOR: John Brittis, MD

Arthritis is a general term used to describe many different types of inflammatory diseases, although pain, stiffness, and usually inflammation in one or more joints are common to all forms. Unfortunately, many people still view arthritis as a crippling disease that causes severe disability.

The two most common forms of arthritis are osteoarthritis and rheumatoid arthritis. This article describes rheumatoid arthritis (RA) and its treatment. Many new and developments have occurred recently.

RA is the second most common form of arthritis and its exact cause still remains unknown. Certain genetic factors are known to increase susceptibility, although the disease itself is not inherited. It is likely that several different factors are involved in initiating the process in genetically susceptible people.

It is considered an autoimmune disease whereby the immune system of a person becomes defective and mistakenly perceives the bodies own tissue, especially in the joints, as foreign. As a result, white blood cells and other self-defenders (cytokines) are released into the joint space and begin to attack the body's own joint tissue. The synovium surrounding the joint becomes inflamed, resulting in joint pain, swelling and stiffness.

The disease usually strikes adults between the ages of thirty and forty, and the incidence of clinical illness is greatest among those aged forty to sixty years. Up until now, even with appropriate drug therapy, up to 7% of patients are disabled to some extent five years after disease onset, and 50% are too disabled to work ten years after disease onset.

The symptoms of RA can show an abrupt onset (10% of cases), but more often the disease has a slow and insidious course. The gradual development of symmetric polyarthritis of the small joints in the hands and feet is common, although some patients develop arthritis of one or more large joints. Fever may be present; weight loss and fatigue are common.

In severe RA parts of the body other than the joints may become involved. Nodules may develop under the skin and in the lungs, which may become inflamed causing shortness of breath. Usually the eyes become inflamed and tear secretion is affected, making the eyes feel sore and dry. Muscles may atrophy as a result of disuse, adding to the general feeling of weakness. Anemia is present quite frequently, further aggravating fatigue. Very rarely, the heart and blood vessels become affected.

The primary goal in treating RA is to control inflammatory activity in order to prevent subsequent joint damage. Early intervention is generally the best approach to any acute or chronic disease in which progression is expected.

Traditional treatment strategies have been based on a therapeutic "pyramid" with a base of patient education, exercise, -physical therapy, followed by sequential medications. Initially nonsteroidal anti-inflammatory drugs (NSAIDS) were used as an initial attempt to control inflammation. Physicians very often avoided the use of cortico steroids or so called disease modifying antirheumatic drugs (DMARDS) because of their perceived potential toxicities and because the long term severity of RA was under-estimated. DMARDS were initiated only after evidence of joint damage. It wasn't recognized until recently that most patients with RA experienced much poorer long term outcomes than previously had been thought. Therefore, most rheumatologists now advocate more aggressive treatment early in the disease course with DMARDS, aiming for true remission in patients who have no damage.

DMARDS in prominent use at this time, including sulfasalazine (Azulfidine), hydroxychloroquine (Plaquenil), and methotrexate (Rheumatrex), and now more recently Etanercept (Enbrel), and Leflunomide (Arava), have much less severe overall toxicities than traditional DMARDS such as injectable gold, penicillamine, and azathioprine (Imuran).

Glucocorticoids (steroids) have long been recognized to have disease modifying capabilities. But their use was severely discouraged because of severe toxicities associated with high doses over long periods. Over the past two decades, however, evidence has emerged that prednisone in low doses of 7.5 mg. or less may be taken over long periods as an effective and well tolerated therapy. Glucocorticoids, usually long term, low dose prednisone, usually in combination with a DMARDS, are taken in about 75% of RA patients.

From the above mentioned DMARDS, methotrexate in particular is both more effective and less toxic than the traditional DMARDS. It remains to be seen where the two newer agents Leflunomide (Arava) and Etanercept (Enbrel) will fit and compare to methotrexate on a long term basis; although both of these agents in clinical trials have shown to be at least as effective as methotrexate in controlling the symptoms of the disease.

People with RA may respond differently to different drugs, and there is no single regime that is best for all patients. Today most rheumatologists regard treatment with NSAIDS alone as inadequate for most patients with RA. Hydroxychloroquine, methotrexate, and/or low dose prednisone treatment often is begun within the first six months of therapy, if not sooner. To this armamentarium we can now add Leflunomide (Arava) and Etanercept (Enbrel).

In addition, combination therapies with multiple DMARDS are increasingly used to control rheumatoid arthritis. The complex dysregulations of inflammatory markers and immune function in RA may require multiple drugs to address different stages of these dysregulations; a very close analogy to treating most cancers. Ongoing drug treatment for an indefinite period is required in the immune dysregulation of RA. Most clinicians therefore tend to combine therapy indefinitely, although cautious attempts at reducing dosage and even withdrawal are reasonable in some patients over the years. Although drug-free remission is generally not currently possible, complete suppression of inflammation is a reasonable goal at this time.

The advice provided on this website is intended to be general in nature and should not be relied upon for specific treatment. If you need personal medical attention please contact your physician.

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