2. Rheumatoid arthritis

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

Alternative Names
RA; Arthritis - rheumatoid

Causes, incidence, and risk factors

The cause of rheumatoid arthritis (RA) is unknown. It is considered 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. It usually occurs in people between 25 and 55. Women are affected more often than men.
The course and the severity of the illness can vary considerably. Infection, genes, and hormones may contribute to the disease.
RA usually affects joints on both sides of the body equally. Wrists, fingers, knees, feet, and ankles are the most commonly affected.

Symptoms
The disease usually begins gradually with fatigue, morning stiffness (lasting more than one hour), widespread muscle aches, loss of appetite, and 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 (synovium) 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 effect the wrist, knees, elbows, fingers, toes, ankle or neck. Additional symptoms include:

• Loss of appetite
• Low-grade fever
• Limited range of motion
• Deformities of hands and feet
• Round, painless nodules under the skin (usually a sign of more severe disease)
• Inflammation of the lung (pleurisy)
• Skin redness or inflammation
• Paleness
• Swollen glands
• Eye burning, itching, and discharge
• Numbness or tingling
• Anemia may occur due to failure of the bone marrow to produce enough new red cells.

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

Signs and tests

• Joint x-rays
• Rheumatoid factor test is positive in about 75% of people with symptoms
• Erythrocyte sedimentation rate is elevated
• CBC may show low hematocrit (anemia) or abnormal platelet counts
• C-reactive protein may be a positive indication for patients with no detectable rheumatoid factor
• Synovial fluid analysis

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

MEDICATIONS
Once a diagnosis is confirmed, the current standard of care (in addition to rest, strengthening exercises, and anti-inflammatory drugs) is aggressive therapy with disease-modifying anti-rheumatic drugs (DMARDs).
Methotrexate (Rheumatrex) is the most commonly used DMARD for rheumatoid arthritis. Others include leflunomide (Arava), gold thiomalate (Myochrysine), aurothioglucose (Solganal), or auranofin (Ridaura).
Anti-inflammatory agents used to treat RA include aspirin and non-steroidal anti-inflammatory drugs (NSAIDS), such as ibuprofen (Motrin, Advil), fenoprofen, indomethacin, and naproxen (Naprosyn). NSAIDS are commonly used to relieve joint pain and inflammation. Although NSAIDs work well, long-term use can cause stomach problems, such as ulcers and bleeding, and possible heart problems. In April 2005, the FDA asked drug manufacturers of NSAIDs to include a warning label on their product that alerts users of an increased risk for cardiovascular events and gastrointestinal bleeding.
COX-2 inhibitors 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. Rofecoxib (Vioxx) and valdecoxib (Bextra) have been withdrawn from the U.S. market following reports of heart attacks in patients taking the drugs. 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 duration possible. Patients should ask their doctor whether the drug is appropriate and safe for them.

Antimalarial medications such as hydroxychloroquine (Plaquenil) and sulfasalazine (Azulfidine) are also beneficial, usually in conjunction with methotrexate. It may be weeks or months before a patient sees any benefit from these medications. Because they are associated with toxic side effects, the patient must have frequent blood tests.
Tumor necrosis factor (TNF) inhibitors are a relatively new class of medicatsions used to treat autoimmune disease. They include etanercept (Enbrel), infliximab (Remicade), and adalimumab (Humira). Adalimumab and etanercept are injectable medications. Infliximab is given by IV.

Another relatively new medication is injectible anakinra (Kineret), which is a man-made protein that blocks the inflammatory protein interleukin-1. The drug is used to slow the progression of moderate to severe active RA in patients over 18 who have not responded to one or more of the DMARDs. Kineret can be used with other DMARDs or TNF inhibitors.
Other drugs that suppress the immune system, like azathioprine (Imuran) and cyclophosphamide (Cytoxan), are sometimes used in people who have failed other therapies. These medications are associated with toxic side effects and usually reserved for severe cases of RA.

Corticosteroids have been used to reduce inflammation in RA for more than 40 years. However, because of potential long-term side effects, corticosteroid use is usually limited to short courses and low doses where possible. Side effects may include bruising, psychosis, cataracts, weight gain, susceptibility to infections, diabetes, high blood pressure , and thinning of the bones (osteoporosis ). A number of medications can be administered with steroids to minimize osteoporosis.
Consult a health care provider before using any medication, including over-the-counter drugs.

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 sysnovectomy, 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 your hand and wrist, and teach you how to best protect and use your 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.

PROSORBA COLUMN
The Prosorba column is for the treatment of moderate to severe RA in adults with long-standing disease who have not responded to DMARDs. The device removes inflammatory antibodies from the blood. The procedure takes 2-3 hours, and must be done once a week for 12 weeks.
Studies have reported that RA slows down or stops getting worse in about one third to one half of the people who receive this treatment. Side effects include anemia, fatigue, fever, low blood pressure, and nausea. Some people have developed an infection from the tube used to remove the blood. Often there is a flare-up of joint pain for several days after the treatment.

Expectations (prognosis)
Regular blood or urine tests should be done to determine how well medications are working and if drugs are causing any side effects.
The course of RA differs from person to person. People with rheumatoid factor or subcutaneous nodules seem to have a more severe form of the disease. People who develop RA at younger ages also have a more rapidly progressive course.
Remission is most likely to occur in the first year. The probability decreases over time. By 10 to 15 years from diagnosis, about 20% of people have remission.
More than half (50 - 70%) of patients are able to work full-time.
After 15-20 years, 10% of patients are severely disabled, and unable to do simple daily living tasks such as washing, dressing, and eating.
The average life expectancy for a patient with RA may be shortened by 3 to 7 years. Those with severe forms of RA may die 10-15 years earlier than expected. However, as treatment for rheumatoid arthritis improves, severe disability and life-threatening complications appear to be decreasing.

Complications
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 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 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.
Fortunately, better therapies appear to be reducing the occurrence of these severe complications.

Prevention
Rheumatoid arthritis has no known prevention. However, it is often possible to prevent further damage of the joints with proper early treatment.
Because RA may cause eye complications, patients should be have regular eye exams.

References
US Food and Drug Administration. FDA Announces Series of Changes to the Class of Marketed Non-Steroidal Anti-Inflammatory Drugs (NSAIDs). Rockville, MD: National Press Office; April 7, 2005. Press Release P05-16.
US Food and Drug Administration. FDA Issues Public Health Advisory Recommending Limited Use of Cox-2 Inhibitors. Rockville, MD: National Press Office; December 23, 2004. Talk Paper T04-61.

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