Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a disorder in which affected joints, usually including those of the hands and feet, are inflamed, resulting in swelling, pain, and, often, significant damage.

Typically, RA first appears between ages 25 and 50, although it may begin at any age. RA affects about 1% of the population worldwide and affects about 2 to 3 times more women than men.

In RA, damage to joints is usually gradual but may be relentless and can result in significant disability. Sometimes, however, RA is limited and becomes dormant (goes into remission) before significant damage occurs. The progression of RA depends on many factors, including a person's family history.

Most people with RA have mild anemia (an insufficient number of red blood cells). Rarely, the white blood cell count becomes abnormally low. When a person with RA has a low white blood cell count and an enlarged spleen, the disorder is called Felty's syndrome.

Causes

The cause of RA is unknown, although it is thought to be an autoimmune disease. The body's immune system attacks the connective tissue that lines joints (synovium) and can also attack connective tissue in many other parts of the body, such as the blood vessels and lungs. Eventually, the joints are damaged.

Symptoms

RA may be mild, with occasional flare-ups followed by long periods of remission, or may progress steadily, either slowly or rapidly. Rheumatoid arthritis may start suddenly, affecting many joints of the lower and upper extremity but especially the hand. More often, it starts gradually, affecting different joints at different times. Usually, the inflammation is symmetric, affecting the same joint on both sides of the body. Typically, toes, feet, wrists, elbows, ankles, and the small joints in the fingers become inflamed first.

Affected joints are usually painful and often stiff, especially just after awakening. Stiffness often lasts for at least several hours after awakening but may diminish with use of the joints. Some people feel tired and weak, especially in the early afternoon. A low-grade fever (around 100.4° F) may occur intermittently.

Affected joints are painful and red and tend to swell. They may become dislocated. Unless exercised, affected joints may freeze in one position. Swollen wrists can pinch a nerve and result in numbness or tingling due to carpal tunnel syndrome. Fluid-filled swellings called cysts may develop behind affected knees and rupture, causing pain and swelling in the lower legs. Hard bumps may develop under the skin, usually near pressure points, such as the back of the forearm near the elbow.

Rarely, RA affects parts of the body other than the joints. For example, blood vessels may become inflamed (vasculitis). Inflamed blood vessels lead to reduced blood supply to tissues and may result in nerve damage or leg sores (ulcers). The membranes that cover the lungs may become inflamed (pleuritis), as may the sac that surrounds the heart (pericarditis). Inflammation and scarring of the lungs can lead to chest pain or shortness of breath. Excessive dryness of the eyes or mouth (Sjögren's syndrome) or swollen lymph nodes may develop.

Diagnosis

A doctor diagnoses RA on the basis of the typical symptoms. Tests to support the diagnosis may include blood tests, an examination of a sample of joint fluid obtained with a needle (aspiration), and a biopsy (in which a tissue sample from a rheumatoid nodule is removed and examined under a microscope). Characteristic changes in the joints may be seen on x-rays.

In most affected people, the erythrocyte sedimentation rate (ESR) is increased. ESR is a test that measures the rate at which red blood cells settle to the bottom of a test tube containing blood. An increased ESR indicates active inflammation. A doctor may monitor the ESR when symptoms are mild to help determine whether RA is still active.

Many people with RA have distinctive antibodies in their blood. Antibodies are substances formed in the body to fight disease, but in the case of RA, they attack the body's own joint tissues. For instance, an antibody called rheumatoid factor is present in most people with RA. Usually, as the level of rheumatoid factor increases, the RA is more severe and the outlook is poorer. The level of rheumatoid factor may decrease when joints are less inflamed.

Treatment

Treatment of RA ranges from simple life-style modifications to specific drug and nondrug therapies.

Diet: Rarely, people experience symptom flare-ups after eating certain foods. If so, these foods should be avoided. A diet rich in fish and plant oils but low in red meat may slightly reduce inflammation.

Rest: Regular rest periods often help relieve pain in affected joints. Sometimes a short period of bed rest helps relieve a severe flare-up in its most active, painful stage. Rest is especially important when symptoms are severe. However, prolonged bed rest weakens muscles and reduces the ability to exercise and may lead to permanent loss of independence. Splints can be used to immobilize and rest one or several joints, but some systematic exercise of the joints is needed to prevent muscles from weakening and joints from freezing in place.

Drug therapy: Drugs used to treat RA fall into four categories: Nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen; corticosteroids, such as prednisone; disease-modifying anti-rheumatic drugs (DMARDs), such as methotrexate; and anti-cytokines, such as infliximab. Corticosteroids, DMARDs, and anti-cytokines are sometimes referred to as immunosuppressive drugs because they suppress certain functions of the immune system involved in the progression of RA.

Corticosteroids, DMARDs, and anti-cytokines not only relieve symptoms but also may slow the progression of RA.

Nondrug therapies: Nondrug therapies are used in addition to drugs to reduce joint inflammation. These therapies include exercise, physical or occupational therapy, and, sometimes, surgery.

Gentle exercise helps maintain motion in inflamed joints so that they do not freeze in one position. As the inflammation subsides, regular aerobic exercise can help improve function, although a person should not exercise to the point of fatigue. For many people, exercise in water may be easier.

Physical therapy can be especially useful when degree of movement (range of motion) in the joints has been severely reduced by pain and inflammation. Physical therapists sometimes use heat therapy, which may involve applying hot packs or infrared heat to joints. Heat therapy may also involve immersing small joints (such as those in the hands) in a paraffin bath and immersing specific body parts or the whole body from the neck down in warm water (usually about 85° F). Cold therapy (for example, with ice packs) is an alternative. Intensive exercises and, occasionally, splints may also be used to gradually extend the joint and help prevent deformities. Instruction may be given for performing exercises at home.

Occupational therapy for people who are disabled by RA can involve training in the use of several aids or devices that make it possible to accomplish daily tasks. For example, a device called a gripper enables a person to grasp an object without having to squeeze the hand forcefully. Walking can be made less painful by wearing specially modified shoes, which can be fitted by an orthotist.

Surgically replacing knee or hip joints is the most effective way of restoring mobility and function when RA is in an advanced stage and drug therapy has not helped sufficiently. Joints can also be removed or fused together, especially in the foot, to make walking less painful. The thumb can be fused to enable a person to grasp. Unstable vertebrae at the top of the neck can be fused to prevent them from compressing the spinal cord.

Outlook

In general, the long-term outlook is poor for people with long-standing, severe RA. Although treatment usually relieves symptoms, joint damage often continues, and at least 1 out of 10 people with RA eventually becomes severely disabled. In addition, people with active RA have higher rates of serious infections and cardiovascular disease compared with the general population. In rare cases, RA resolves without aggressive treatment.

See the table Some Drugs Used for Rheumatoid Arthritis.