Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes inflammation and deformity of the joints. Other problems throughout the body (systemic problems) may also develop, including inflammation of blood vessels (vasculitis), the development of bumps (called rheumatoid nodules) in various parts of the body, lung disease, blood disorders, and weakening of the bones (osteoporosis).

Description

The skeletal system of the body is made up of different types of strong, fibrous tissue called connective tissue. Bone, cartilage, ligaments, and tendons are all forms of connective tissue that have different compositions and different characteristics.

The joints are structures that hold two or more bones together. Some joints (synovial joints) allow for movement between the bones being joined (articulating bones). The simplest synovial joint involves two bones, separated by a slight gap called the joint cavity. The ends of each articular bone are covered by a layer of cartilage. Both articular bones and the joint cavity are surrounded by a tough tissue called the articular capsule. The articular capsule has two components, the fibrous membrane on the outside and the synovial membrane (or synovium) on the inside. The fibrous membrane may include tough bands of tissue called ligaments, which are responsible for providing support to the joints. The synovial membrane has special cells and many tiny blood vessels (capillaries). This membrane produces a supply of synovial fluid that fills the joint cavity, lubricates it, and helps the articular bones move smoothly about the joint.

In rheumatoid arthritis (RA), the synovial membrane becomes severely inflamed. Usually thin and delicate, the synovium becomes thick and stiff, with numerous infoldings on its surface. The membrane is invaded by white blood cells, which produce a variety of destructive chemicals. The cartilage along the articular surfaces of the bones may be attacked and destroyed, and the bone, articular capsule, and ligaments may begin to wear away (erode). These processes severely interfere with movement in the joint.

RA exists all over the world and affects men and women of all races. In the United States alone, about two million people suffer from the disease. Women are three times more likely than men to have RA. About 80% of people with RA are diagnosed between the ages of 35-50. RA appears to run in families, although certain factors in the environment may also influence the development of the disease.

Causes and symptoms

The underlying event that promotes RA in a person is unknown. Given the known genetic factors involved in RA, some researchers have suggested that an outside event occurs that triggers the disease cycle in a person with a particular genetic makeup.

Many researchers are examining the possibility that exposure to an organism (like a bacteria or virus) may be the first event in the development of RA. The body's normal response to such an organism is to produce cells that can attack and kill the organism, protecting the body from the foreign invader. In an autoimmune disease like RA, this immune cycle spins out of control. The body produces misdirected immune cells, which accidentally identify parts of the person's body as foreign. These immune cells then produce a variety of chemicals that injure and destroy parts of the body.

RA can begin very gradually, or it can strike quickly. The first symptoms are pain, swelling, and stiffness in the joints. The most commonly involved joints include hands, feet, wrists, elbows, and ankles, although other joints may also be involved. The joints are affected in a symmetrical fashion. This means that if the right wrist is involved, the left wrist is also involved. Patients frequently experience painful joint stiffness when they first get up in the morning, lasting for perhaps an hour. Over time, the joints become deformed. The joints may be difficult to straighten, and affected fingers and toes may be permanently bent (flexed). The hands and feet may curve outward in an abnormal way.

Many patients also notice increased fatigue, loss of appetite, weight loss, and sometimes fever. Rheumatoid nodules are bumps that appear under the skin around the joints and on the top of the arms and legs. These nodules can also occur in the tissue covering the outside of the lungs and lining the chest cavity (pleura), and in the tissue covering the brain and spinal cord (meninges). Lung involvement may cause shortness of breath and is seen more in men. Vasculitis (inflammation of the blood vessels) may interfere with blood circulation. This can result in irritated pits (ulcers) in the skin, tissue death (gangrene), and interference with nerve functioning that causes numbness and tingling.

Juvenile RA is a chronic inflammatory disease that affects the joints of children less than 16 years old. It is estimated to affect as many as 250,000 children in the United States alone. Most children with juvenile RA have arthritis when the illness starts, which affects multiple joints in 50% of these children, and only one joint in 30%. In all, 20% of the children affected by juvenile RA have the acute systemic form of the disease, which is characterized by fever, joint inflammation, rash, liver disease, and gastrointestinal disease.

Two periods of childhood are associated with an increased incidence of onset of juvenile RA. The first is from one to three years of age, and the second, from eight to 12 years. When more than four joints are affected, the disease is described as being polyarticular. If less than four joints are affected, the disease is known as pauciarticular juvenile RA, and this particular manifestation falls into two categories. The first occurs in girls aged one to four years old, and the onset of joint involvement is in the knees, ankles, or elbows. The second form occurs in boys aged eight years and older, and involves the larger joints, such as those of the hips and legs.

Diagnosis

There are no tests available that can absolutely diagnose RA. Instead, a number of tests exist that can suggest the diagnosis of RA. Blood tests include a special test of red blood cells (called erythrocyte sedimentation rate), which is positive in nearly 100% of patients with RA. However, this test is also positive in a variety of other diseases. Tests for anemia are usually positive in patients with RA, but can also be positive in many other unrelated diseases. Rheumatoid factor is another diagnostic test that measures the presence and amounts of rheumatoid factor in the blood. Rheumatoid factor is an autoantibody found in about 80% of patients with RA. It is often not very specific however, because it is found in about 5% of all healthy people and in 10-20% of healthy people over the age of 65. In addition, rheumatoid factor is also positive in a large number of other autoimmune diseases and other infectious diseases, including systemic lupus erythematosus, bacterial endocarditis, malaria, and syphilis. In addition, young people who have a process called juvenile rheumatoid arthritis often have no rheumatoid factor present in their blood.

Finally, the clinician may examine the synovial fluid, by inserting a thin needle into a synovial joint. In RA, this fluid has certain characteristics that indicate active inflammation. The fluid is cloudy, with increased protein and decreased or normal glucose. It also contains a higher than normal number of white blood cells. While these findings suggest inflammatory arthritis, they are not specific to RA.

Treatment

There is no cure available for RA. However, treatment is available to combat the inflammation in order to prevent destruction of the joints, and to prevent other complications of the disease. Efforts are also made to maintain flexibility and mobility of the joints.

The "first line" agents for the treatment of RA include nonsteroidal anti-inflammatory agents (NSAIDs) and aspirin, which are used to decrease inflammation and to treat pain. The NSAIDs include naproxen (Naprosyn), ibuprofen (Advil, Medipren, Motrin), and etodolac (Lodine). While these medications can be helpful, they do not interrupt the progress of the disease. Low-dose steroid medications can be helpful at both managing symptoms and slowing the progress of RA. Disease-modifying antirheumatic drugs, including gold compounds, D-penicillamine, certain antimalarial-like drugs, and sulfasalazine (Azulfadine) are also often the first agents clinicians use to treat RA, but in patients with the aggressive destructive type of RA, more slow-acting medications are needed. Methotrexate, azathioprine, and cyclophosphamide are all drugs that suppress the immune system and can decrease inflammation. All of the drugs listed have significant toxic side effects, which require health-care professionals to carefully compare the risks associated with these medications versus the benefits.

Recently, several categories of drugs have been explored and developed for the treatment of RA. The first is a category of agents known as biological response modifiers. These work to reduce joint inflammation by blocking a substance called tumor necrosis factor (TNF). TNF is a protein that triggers inflammation during the body's normal immune responses. When TNF production is not regulated, the excess TNF can cause inflammation. Three agents in this class have become "second line" drugs for the treatment of RA. These are etanercept (Enbrel), leflunamide (Arava), and infliximab (Remicade), and they are recommended for patients in whom other medications have not been effective. Etanercept is approved by the FDA but is not recommended for patients with active infection. It is given twice weekly via subcutaneous injections by either the patient or a health care professional. Because this agent is so new, long-term side effects have not been fully studied. Infliximab is given intravenously once every eight weeks, and is approved for combined use with methotrexate to combat RA.

The cyclo-oxygenase-2 (COX-2) inhibitors are another category of drugs used to treat RA. Like the traditional NSAIDs, the COX-2 inhibitors work to block COX-2, which is an enzyme that stimulates inflammatory responses in the body. Unlike the NSAIDs, the COX-2 inhibitors do not carry a high risk of gastrointestinal ulcers and bleeding, because they do not inhibit COX-1, which is the enzyme that protects the stomach lining. These new agents include celecoxib (Celebrex) and rofecoxib (Vioxx). Celecoxib has been approved by the FDA for the treatment of RA and osteoarthritis, and is taken once or twice daily by mouth. Rofecoxib is approved for RA and osteoarthritis, and for acute pain caused by primary dysmenorrhea and surgery.

Total bed rest is sometimes prescribed during the very active, painful phases of RA. Splints may be used to support and rest painful joints. Later, after inflammation has somewhat subsided, physical therapists may provide a careful exercise regimen in an attempt to maintain the maximum degree of flexibility and mobility. Joint replacement surgery, particularly for the knee and the hip joints, is sometimes recommended when these joints have been severely damaged.

Alternative treatment

A variety of alternative therapies has been recommended for patients with RA. Meditation, hypnosis, guided imagery, and relaxation techniques have been used effectively to control pain. Acupressure and acupuncture have also been used for pain. Bodywork can be soothing, decreasing stress and tension, and is thought to improve/restore chemical balance within the body.

A multitude of nutritional supplements can be useful for RA. Fish oils, the enzymes bromelain and pancreatin, and the antioxidants (vitamins A, C, and E, selenium, and zinc) are the primary supplements to consider.

Many herbs also are useful in the treatment of RA. Anti-inflammatory herbs may be very helpful, including tumeric (Curcuma longa), ginger (Zingiber officinale), feverfew (Chrysanthemum parthenium), devil's claw (Harpagophytum procumbens), Chinese thoroughwax (Bupleuri falcatum), and licorice (Glycyrrhiza glabra). Lobelia (Lobelia inflata) and cramp bark (Vibernum opulus) can be applied topically to the affected joints.

Homeopathic practitioners recommended Rhus toxicondendron and Bryonia (Bryonia alba) for acute prescriptions, but constitutional treatment, generally used for chronic problems like RA, is more often recommended. Yoga has been used for RA patients to promote relaxation, relieve stress, and improve flexibility. Nutritionists suggest that a vegetarian diet low in animal products and sugar may help to decrease both inflammation and pain from RA. Beneficial foods for patients with RA include cold water fish (mackerel, herring, salmon, and sardines) and flavonoid-rich berries (cherries, blueberries, hawthorn berries, blackberries, etc.).

RA, considered an autoimmune disorder, is often connected with food allergies/intolerances. An elimination/challenge diet can help to decrease symptoms of RA as well as identify the foods that should be eliminated to prevent flare-ups and recurrences. Hydrotherapy can help to greatly reduce pain and inflammation. Moist heat is more effective than dry heat, and cold packs are useful during acute flare-ups.

Prognosis

About 15% of all RA patients will have symptoms for a short period of time and will ultimately get better, leaving them with no long-term problems. A number of factors are considered to suggest the likelihood of a worse prognosis. These include:

• race and gender (female and Caucasian).
• more than 20 joints involved.
• extremely high erythrocyte sedimentation rate.
• extremely high levels of rheumatoid factor.
• consistent, lasting inflammation.
• evidence of erosion of bone, joint, or cartilage on x rays.
• poverty.
• older age at diagnosis.
• rheumatoid nodules.
• other coexisting diseases.
• certain genetic characteristics, diagnosable through testing.

Patients with RA have a shorter life span, averaging a decrease of three to seven years of life. Patients sometimes die when very severe disease, infection, and gastrointestinal bleeding occur. Complications due to the side effects of some of the more potent drugs used to treat RA are also factors in these deaths.

Prevention

There is no known way to prevent the development of RA. The most that can be hoped for is to prevent or slow its progress.