Rheumatoid arthritis (RA) is a long-term disease that leads to inflammation of the joints and surrounding tissues. It can also affect other organs.

The cause of RA is unknown. It is considered an autoimmune disease. The body's immune system normally fights off foreign substances, like viruses. But in an autoimmune disease, the immune system confuses healthy tissue for foreign substances. As a result, the body attacks itself.

RA can occur at any age. Women are affected more often than men.

RA usually affects joints on both sides of the body equally. Wrists, fingers, knees, feet, and ankles are the most commonly affected. The course and the severity of the illness can vary considerably. Infection, genes, and hormones may contribute to the disease.

The disease usually begins gradually with:

• Fatigue
• Loss of appetite
• Morning stiffness (lasting more than 1 hour)
• Widespread muscle aches
• Weakness

Eventually, joint pain appears. When the joint is not used for a while, it can become warm, tender, and stiff. When the lining of the joint becomes inflamed, it gives off more fluid and the joint becomes swollen. Joint pain is often felt on both sides of the body, and may affect the fingers, wrists, elbows, shoulders, hips, knees, ankles, toes, and neck.

Additional symptoms include:

• Anemia due to failure of the bone marrow to produce enough new red blood cells
• Eye burning, itching, and discharge
• Hand and feet deformities
• Limited range of motion
• Low-grade fever
• Lung inflammation (pleurisy)
• Nodules under the skin (usually a sign of more severe disease)
• Numbness or tingling
• Paleness
• Skin redness or inflammation
• Swollen glands

Joint destruction may occur within 1-2 years after the appearance of the disease.

A specific blood test is available for diagnosing RA and distinguishing it from other types of arthritis. It is called the anti-CCP antibody test. Other tests that may be done include:

• Complete blood count
• C-reactive protein
• Erythrocyte sedimentation rate
• Joint ultrasound or MRI
• Joint x-rays
• Rheumatoid factor test (positive in about 75% of people with symptoms)
• Synovial fluid analysis

RA usually requires lifelong treatment, including medications, physical therapy, exercise, education, and possibly surgery. Early, aggressive treatment for RA can delay joint destruction.

MEDICATIONS

Disease modifying antirheumatic drugs (DMARDs): These drugs are the current standard of care for RA, in addition to rest, strengthening exercises, and anti-inflammatory drugs. Methotrexate (Rheumatrex) is the most commonly used DMARD for rheumatoid arthritis. Leflunomide (Arava) may be substituted for methotrexate. These drugs are associated with toxic side effects, so you will need frequent blood tests when taking them.

Anti-inflammatory medications: These include aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen. Although NSAIDs work well, long-term use can cause stomach problems, such as ulcers and bleeding, and possible heart problems. NSAID packaging now carries a warning label to alert users of an increased risk for cardiovascular events (such as heart attack or stroke) and gastrointestinal bleeding.

Antimalarial medications: This group of medicines includes hydroxychloroquine (Plaquenil) and sulfasalazine (Azulfidine), and is usually used in combination with methotrexate. It may be weeks or months before you see any benefit from these medications.

Corticosteroids: These medications work very well to reduce joint swelling and inflammation. Because of potential long-term side effects, however, corticosteroids should be taken only for a short time and in low doses when possible.

Cyclooxygenase-2 (COX-2) inhibitors: These drugs block an inflammation-promoting enzyme called COX-2. This class of drugs was initially believed to work as well as traditional NSAIDs, but with fewer stomach problems. However, numerous reports of heart attacks and stroke have prompted the FDA to re-evaluate the risks and benefits of the COX-2s. Celecoxib (Celebrex) is still available, but labeled with strong warnings and a recommendation that it be prescribed at the lowest possible dose for the shortest possible duration. Talk to your doctor about whether COX-2s are right for you.

BIOLOGIC AGENTS:

Specific white blood cell modulators: These treatments effectively control inflammation. They include:

• Orencia (abatacept) - Given under the skin (subcutaneously) or into a vein (intravenously) once a month. Reduces the number of T-cells (a type of white blood cell).
• Rituxan (rituximab) - Given under the skin or into a vein twice a year. Reduces the number of B-cells (a types of white blood cell).

Tumor necrosis factor (TNF) inhibitors: This class of medications block a protein in the body involved in creating inflammation. They are given under the skin or directly into a vein. They include:

• adalimumab (Humira)
• etanercept (Enbrel)
• infliximab (Remicade)

SURGERY

Occasionally, surgery is needed to correct severely affected joints. Surgeries can relieve joint pain, correct deformities, and modestly improve joint function.

The most successful surgeries are those performed on the knees and hips. The first surgical treatment is a synovectomy, which is the removal of the joint lining (synovium).

A later alternative is total joint replacement with a joint prosthesis. In extreme cases, total knee or hip replacement can mean the difference between being totally dependent on others and having an independent life at home.

PHYSICAL THERAPY

Range-of-motion exercises and individualized exercise programs prescribed by a physical therapist can delay the loss of joint function.

Joint protection techniques, heat and cold treatments, and splints or orthotic devices to support and align joints may be very helpful.

Sometimes therapists will use special machines to apply deep heat or electrical stimulation to reduce pain and improve joint mobility.

Occupational therapists can construct splints for the hand and wrist, and teach how to best protect and use joints when they are affected by arthritis. They also show people how to better cope with day-to-day tasks at work and at home, despite limitations caused by RA.

Frequent rest periods between activities, as well as 8 to 10 hours of sleep per night, are recommended.

For additional information and resources, see arthritis support group.

Regular blood or urine tests should be done to determine how well medications are working and if drugs are causing any side effects.

RA differs from person to person. People with rheumatoid factor, the anti-CCP antibody, or subcutaneous nodules seem to have a more severe form of the disease. People who develop RA at younger ages also seem to get worse more quickly.

Many people with RA work full-time. However, after many years, about 10% of those with RA are severely disabled, and unable to do simple daily living tasks such as washing, dressing, and eating.

In the past, the average life expectancy for a patient with RA could be shortened by 3-7 years. Those with severe forms of RA would often die 10-15 years earlier than expected. However, as treatment for rheumatoid arthritis has improved, severe disability and life-threatening complications have decreased considerably and many people live relatively normal lives.

Rheumatoid arthritis is not solely a disease of joint destruction. It can involve almost all organs.

A life-threatening joint complication can occur when the cervical spine (neck bones) becomes unstable as a result of RA.

Rheumatoid vasculitis (inflammation of the blood vessels) is a serious, potentially life-threatening complication of RA. It can lead to skin ulcerations and infections, bleeding stomach ulcers, and nerve problems that cause pain, numbness, or tingling. Vasculitis may also affect the brain, nerves, and heart, which can cause stroke, heart attack, or heart failure.

RA may cause the the outer lining of the heart to swell (pericarditis) and cause heart complications. Inflammation of the heart muscle, called myocarditis, can also develop. Both of these conditions can lead to congestive heart failure.

The treatments for RA can also cause serious side effects. If you experience any side effects, immediately tell your health care provider.

Call your health care provider if you think you have symptoms of rheumatoid arthritis.

Rheumatoid arthritis has no known prevention. However, it is often possible to prevent further damage of the joints with proper early treatment.

Stop smoking. Research shows that the risk of developing RA is nearly double for current smokers compared with non-smokers.

Because RA may cause eye complications, patients should be have regular eye exams.

Harris ED Jr., Budd RC, Genovese MC, Firestein GS, Sargent JS, eds. Kelley's Textbook of Rheumatology. 7th ed. Philadelphia, Pa: Saunders Elsevier; 2005

Smolen JS, Aletaha D, Koeller M, Weisman MH, Emery P. New therapies for treatment of rheumatoid arthritis. Lancet. 2007;370(9602):1861-74.