Rheumatoid arthritis

Definition

Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting the joints, most often in the hands and feet. It results in swelling, stiffness, pain, and sometimes joint, bone, and cartilage destruction.

Description

Although the exact cause of RA is unknown, the disease belongs to a group of diseases called autoimmune disorders. In these disorders, the immune system, the function of which is to protect the body, produces antibodies that attack the soft tissues lining the joints and may also attack connective tissue in many other parts of the body, including the blood vessels and lungs. Eventually, the cartilage, bone, and ligaments of the joint deteriorate, causing deformity, instability, and scarring within the joint. The rate at which the joints deteriorate varies with the individual. A number of risk factors, including genetic predisposition, gender, and unspecified environmental factors, may put a person at risk for developing the disease as well as influence the pattern of the disease.

As with other forms of arthritis, RA involves inflammation of the joints. A membrane called the synovium lines each of the body's movable joints. In RA, white blood cells, which usually attack foreign invaders such as bacteria and viruses, move from the bloodstream into the synovium. There, these blood cells appear to play an important role in causing inflammation to the synovial membrane, a condition called synovitis. This inflammation results in the release of proteins that, over months or years, causes thickening of the synovium. These proteins

can also damage cartilage, bone, tendons, and ligaments. Gradually, the joint loses its shape and alignment, and eventually may be destroyed.

Genetic profile

Rheumatoid arthritis is a genetically complex disease. Studies in monozygotic (identical) and dizygotic (fraternal) twins indicate that genetic factors are involved in acquiring the susceptibility or tendency to RA rather than the disease itself. People with certain human leukocyte antigen (HLA) genes—specifically, the genetic marker called HLA-DR4 (the DR4 refers to the specific antigen)—are more likely to develop the disease than those without the genes. However, people without this antigen can develop the disease as well.

The HLA-DR4 marker is found in white blood cells and plays a role in helping the body distinguish between its own cells and foreign invaders. In addition, these genes also help predict the severity of the disease and how effectively the disease responds to treatment. The mechanism by which HLA alleles (HLA genetic variations) affect disease risk is still under investigation.

In one study, French scientists found 63 genes that appeared to be linked to the development of rheumatoid arthritis. The group studied and compared the expression of 5,200 genes in the synovial (joint) fluid of a group of patients with RA and another group with osteoarthritis. The researchers found 48 known and 15 unknown genes that were either overexpressed or underexpressed in RA patients compared with osteoarthritis patients. Two of the novel genes were located on chromosome 6, at the p21 region, which is an area already linked to inflammatory disease. Four other genes were located on the X chromosome. The French scientists hope their findings will lead to the identification of new pathways related to RA, as well as to new diagnostic and treatment options.

However, not all the genes associated with RA have been discovered, and more research is needed.

Demographics

Rheumatoid arthritis affects approximately 1% of the United States population. Although some people have a mild form of RA, 70% eventually develop chronic problems, and 15% have a severe crippling form of the disease.

The disease occurs in all races and countries. Although RA affects women two to three times more often than men, men tend to be affected more severely by it. The onset of RA most commonly occurs between the ages of 25 and 50, but children and adolescents as well as the elderly may be affected as well. When the disease occurs in children, it is referred to as juvenile RA.

Signs and symptoms

The course of RA varies with each individual. Some people may have mild symptoms, occasional flare-ups, and long periods without disease (remission), or disease that progresses steadily, either slowly or rapidly. The disease may begin suddenly, with many joints becoming inflamed simultaneously. Most often, however, RA begins subtly, gradually affecting different joints. Usually the inflammation is symmetric, with joints on both sides of the body affected. Typically, the small joints in the fingers, toes, hands, feet, wrists, elbows, and ankles become inflamed first. The inflamed joints are usually painful and often stiff, especially just after awakening (such stiffness generally lasts for at least 30 minutes and often much longer) or after prolonged inactivity. Some people feel tired and weak, especially in the early afternoon. In addition, RA may produce a low-grade fever.

Affected joints enlarge because of swelling of the soft tissue and can quickly become deformed. Joints may freeze in one position so that they cannot bend or open fully. The fingers may tend to dislocate from their normal position toward the little finger on each hand, causing tendons in the fingers to slip out of place.

Swollen wrists can pinch a nerve and result in numbness or tingling due to carpal tunnel syndrome. Cysts, which may develop behind affected knees, can rupture and cause pain and swelling in the lower legs. Up to 30% of people with RA have hard bumps (called rheumatoid nodules) just under the skin, usually near sites of pressure (such as the back of the forearm near the elbow).

In rare cases, RA causes an inflammation of blood vessels called vasculitis; this condition reduces the blood supply to tissues and may cause nerve damage or leg sores (ulcers) that may become infected. Inflammation of the membranes covering the lungs (pleura) or of the sac surrounding the heart (pericardium), or inflammation and scarring of the lungs can lead to chest pain and shortness of breath. Some people develop swollen lymph nodes, dry eyes or mouth, or red, painful eyes as a result of inflammation.

Diagnosis

In addition to the important characteristic pattern of symptoms, many tests may be used to support the diagnosis.

Laboratory tests may include rheumatoid factor, white blood cell count, a blood test for anemia, erythrocyte sedimentation rate (ESR, or sed rate), and C-reactive protein, which detects inflammation.

Many people with RA have certain characteristic antibodies in their blood, such as rheumatoid factor, which is present in 70% of people with RA. In addition to RA, rheumatoid factor occurs in several other diseases, such as hepatitis and other infections. Some people even have rheumatoid factor in their blood without any evidence of disease. A higher level of rheumatoid factor in the blood usually results in a more severe RA and a poorer prognosis. The rheumatoid factor level may decrease when joints are less inflamed.

Most people 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.

Nine out of 10 people with RA have an elevated sed rate, a test that measures the rate at which blood cells settle to the bottom of a test tube containing blood; an elevated sed rate suggests that active inflammation is present. The rate depends on certain proteins in the blood. However, this test alone cannot identify the cause of the inflammation. Doctors may monitor the sed rate when symptoms are mild to help determine whether the disease is still active.

A needle biopsy may be recommended. A needle biopsy is an examination of a joint fluid sample or of a tissue sample from rheumatoid nodules, both obtained by a needle.

Characteristic changes in the joints may be seen on x rays.

Treatment and management

Treatments for RA have improved in recent years. Although most treatments involve medications, in some cases, surgical procedures may be necessary.

Medications for rheumatoid arthritis can relieve its symptoms and slow or halt its progression. Nonsteroidal anti-inflammatory drugs (NSAIDs) help to alleviate both pain and inflammation, if taken on a regular basis. These drugs, which are available without a prescription, include aspirin, ibuprofen (Motrin, Advil), and naproxen (Aleve). These medications are available at higher dosages by prescription. Other NSAIDs available in prescription strength include ketoprofen (Oruvail), tolmetin (Tolectin), diclofenac (Arthrotec, Voltaren), nabumetone (Relafen), and indomethacin (Indocin).

Taking NSAIDs on a regular basis, however, can lead to adverse side effects, such as indigestion and stomach bleeding. Other potential harmful side effects may include damage to the liver and kidneys, ringing in the ears (tinnitus), fluid retention, and hypertension (high blood pressure).

Initially, it was thought that COX-2 inhibitors, another class of NSAIDS, was less damaging to the stomach than the traditional NSAIDS. Like other NSAIDs, COX-2 inhibitors, such as celecoxib (Celebrex), which is one of the few COX-2 inhibitors still on the market in the United States, suppress an enzyme called cyclooxygenase (COX) that is active in joint inflammation. It was believed that NSAIDs work against two versions of the COX enzyme present in the body: COX-1 and COX-2. However, there is increasing evidence to suggest that by suppressing COX-1, the enzyme responsible for protecting the stomach lining, NSAIDs may cause stomach and other problems. Unlike other NSAIDs, COX-2 inhibitors suppress only COX-2, the enzyme involved in inflammation.

Side effects of COX-2 inhibitors may include fluid retention and causing or exacerbating high blood pressure. Furthermore, this class of drugs has been linked to an increased risk of heart attack and stroke. These are reasons why Merck Pharmaceuticals chose to remove its COX-2 inhibitor rofecoxib (Vioxx) from the worldwide market in September 2004. About 1.3 million people in the United States and about 700,000 abroad were using the drug. In April 2005, the COX-2 inhibitor valdecoxib (Bextra) was voluntarily removed from the market by its manufacturer, Pfizer, at the request of the FDA, which stated that the potential risks of heart attack, stroke, and potentially life-threatening skin reactions were greater than its benefits. The FDA also announced new label requirements for both prescription and nonprescription NSAIDS. Prescription labels for COX-2 inhibitors like celecoxib were required to carry a "black box warning" stressing the life-threatening effects associated with the drug.

In December 2004, the FDA issued a Public Health Advisory recommending limited use of COX-2 inhibitors. The guidelines warn patients at high risk of gastrointestinal bleeding, those with a history of intolerance to certain NSAIDS. Individual patient risk for cardiovascular problems and other risks commonly associated with NSAIDS should be taken into account for each patient. Consumers are advised that all nonprescription pain relievers, including NSAIDS, should be used exactly as specified on the label. If NSAIDS are needed for more than 10 days, the FDA suggests that a doctor be consulted.

The FDA's actions differ from the recommendations of an FDA expert advisory panel, which, in February 2005, voted in favor of allowing COX-2 inhibitors celecoxib and valdecoxib to remain available. The panel also voted to allow rofecoxib back on the market, under strict conditions.

Corticosteroids, such as prednisone (Deltasone) and methylprednisolone (Medrol), reduce inflammation and pain and slow the progression of joint damage and destruction associated with RA. In the short term, corticosteroids alleviate pain significantly. When used for many months or years, however, these drugs tend to lose their efficacy and cause serious side effects that may include bruising, thinning of bones, cataracts, weight gain, and diabetes. Doctors often prescribe corticosteroids to alleviate acute symptoms, with the goal of gradually tapering off the medication when the patient's pain decreases.

Physicians prescribe disease-modifying antirheumatic drugs (DMARDs) to limit the amount of joint damage that occurs in RA. Taking these drugs during the early stages in the development of RA is especially important in an attempt to slow disease progression and save the joints and other tissues from permanent damage. Because many of these drugs act slowly, it may take weeks to months to detect any benefit. Typically, DMARDs are used in combination with an NSAID or a corticosteroid. Although the NSAID or corticosteroid alleviates any immediate symptoms and limits inflammation, the DMARD acts directly on the disease. Commonly used DMARDs include hydroxychloroquine (Plaquenil), the gold compound auranofin (Ridaura), sulfasalazine (Azulfidine), and minocycline (Dynacin, Minocin). Additional forms of DMARDs include immunosuppressants and tumor necrosis factor (TNF) blockers.

Immunosuppressants act to quiet the immune system, which is overactive in RA. In addition, some of these drugs attack and destroy cells associated with the disease. Some of the commonly used immunosuppressants include methotrexate (Rheumatrex), leflunomide (Arava), azathioprine (Imuran), cyclosporine (Neoral, Sandimmune), and cyclophosphamide (Cytoxan). These medications may have potentially serious adverse side effects, such as increased susceptibility to infection.

The TNFs are a class of DMARDs known as biologic response modifiers. Tumor necrosis factor is a cell protein, or cytokine, that acts as an inflammatory agent in RA. Anti-TNF medications, or TNF blockers, target or block this cytokine and can help reduce pain, morning stiffness, and tender or swollen joints, typically within one or two weeks after initiating treatment. There is evidence that TNF blockers may halt the progression of disease. Often these medications are taken in combination with the immunosuppressant methotrexate. The TNF blockers approved for treatment of RA include etanercept (Enbrel), infliximab (Remicade), and adalimumab (Humira). These medications should not be taken if active infection is present.

Interleukin-1 receptor antagonist (IL-1Ra) is another type of biologic response modifier and is an artificially created (recombinant) form of the naturally occurring interleukin-1 receptor antagonist. Interleukin-1 (IL-1) is a cell protein that promotes inflammation and occurs in excessive amounts in people with RA or other types of inflammatory arthritis. If IL-1 is prevented from binding to its receptor, the inflammatory response is decreased.

The first IL-1Ra approved by the FDA for use in individuals with moderate to severe RA who have not responded adequately to conventional DMARD therapy is anakinra (Kineret). This drug may be used alone or in combination with methotrexate. Anakinra is administered as a daily self-injection. Some potential side effects include injection-site reactions, decreased white blood cell counts, headache, and increased upper respiratory tract infections, especially in people with asthma or chronic obstructive pulmonary disease. If active infection is present, anakinra should not be used.

Some people with RA also experience symptoms of depression. The most common antidepressants used for RA pain and for sleep that is not restful are amitriptyline (Elavil), nortriptyline (Aventyl, Pamelor), and trazodone (Desyrel).

Although a combination of medication and self-care is the first course of action for RA, other methods are available in severe cases of the disease. The Prosorba column is a blood-filtering technique used to remove certain antibodies that contribute to pain and inflammation in the joints and muscles and is usually performed once a week for 12 weeks on an outpatient basis. Some of the side effects of this procedure include fatigue and a temporary increase in joint pain and swelling for the first few days after the treatment. The Prosorba column treatment is not recommended in combination with angiotensin-converting enzyme (ACE) inhibitors or if heart problems, high blood pressure, or blood-clotting problems are present.

Joint replacement surgery is an option chosen by many people with RA when less invasive methods or medications are not able to alleviate pain and deter joint destruction. When joints are severely damaged, joint replacement surgery can often help restore joint function, reduce pain, or correct a deformity. In some cases, the entire joint may need to be replaced with a metal, ceramic, or plastic prosthesis. Surgery may also involve tightening or loosening tendons, fusing bones to reduce pain, or removing a portion of a diseased bone to improve mobility. The inflamed joint lining may also require removal (synovectomy).

Prognosis

In rare cases, RA resolves spontaneously. However, at least one out of 10 people with RA eventually becomes severely disabled.

Resources

BOOKS

Schlotzhauer, Tammi L., and James L. McGuire. Living with Rheumatoid Arthritis. Baltimore, MD: Johns Hopkins University Press, 2003.

Zashin, Scott J., and Laurette Hesser. Arthritis without Pain: The Miracle of TNF Blockers. Bangor, ME: Sarah Allison Publishing, 2004–2005.

PERIODICALS

Drazen, J. M. "Cox-2 Inhibitors: A Lesson in Unexpected Problems." New England Journal of Medicine 352 (March 17, 2005): 1131–32.

Silman, A. J., and Jacqueline E. Pearson. "Epidemiology and Genetics of Rheumatoid Arthritis." Arthritis Research & Therapy 4 (Supplement 3) (May 9, 2002): S265–S272. Available online: <http://arthritis-research.com/content/4/S3/S265>.

Smolen, J. S. "The Science of Rheumatoid Arthritis: A Prelude." Arthritis Research & Therapy 7 (Supplement 2) (March 16, 2005): S1–S3.

WEBSITES

Arthritis Research & Therapy. (April 22, 2005.) <http://arthritis-research.com/>.

ORGANIZATIONS

American Academy of Orthopaedic Surgeons. P.O. Box 2058, Des Plaines, IL 60017. (800) 824-2263. (April 22, 2005.) <http://www.aaos.org>.

American College of Rheumatology. 1800 Century Place, Suite 250, Atlanta, GA 30345. (404) 633-3777. (April 22, 2005.) <http://www.rheumatology.org/index.asp?>.

Arthritis Foundation. 1330 West Peachtree Street, Atlanta, GA 30309. (800) 283-7800. (April 22, 2005.) <http://www.arthritis.org>.

National Institute of Arthritis and Musculoskeletal and Skin Diseases. National Institutes of Health. 1 AMS Circle, Bethesda, MD 20892-3675 (877) 226-4267. (April 22, 2005.) <http://www.niams.nih.gov>.

Genevieve T. Slomski, PhD

Rheumatoid Arthritis

Definition

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 healthcare 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.

KEY TERMS

Articular bones— Two or more bones connected to each other via a joint.

Joint— Structures holding two or more bones together.

Pauciarticular juvenile RA— Rheumatoid arthritis found in children that affects less than four joints.

Polyarticular juvenile RA— Rheumatoid arthritis found in children that affects more than four joints.

Synovial joint— A type of joint that allows articular bones to move.

Synovial membrane— The membrane that lines the inside of the articular capsule of a joint and produces a lubricating fluid called synovial fluid.

Resources

BOOKS

Arthritis Foundation. The Good Living with Rheumatoid Arthritis. New York: Longstreet Press Inc., 2000.

PERIODICALS

Case, J. P. "Old and New Drugs Used in Rheumatoid Arthritis: A Historical Perspective. Part 2: The Newer Drugs and Drug Strategies." American Journal of Therapeutics May-June 2001: 163-79.

Goekoop, Y. P., et al. "Combination Therapy in Rheumatoid Arthritis." Current Opinions in Rheumatology May 2001: 177-83.

Koivuniemi, R., and M. Leirisalo-Repo. "Juvenile Chronic Arthritis in Adult Life: A Study of Long-term Outcome in Patients with Juvenile Chronic Arthritis or Adult Rhuematoid Arthritis." Clinical Rheumatology 1999: 220-6.

Rheumatoid arthritis

Definition

Rheumatoid arthritis (RA) is a chronic disease causing inflammation and deformity of the joints. Other systemic problems throughout the body may also develop, including inflammation of blood vessels (vasculitis), the development of bumps (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 characteristics.

The joints are structures that hold two or more bones together. Synovial joints allow for movement between the bones being joined, the 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 called 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, 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 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 and 50. RA appears to run in families, although certain factors in the environment may also influence the development of the disease.

Causes & 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 and triggers the disease cycle in a person with a particular genetic makeup. In late 2001, researchers announced discovery of the genetic markers that predict increased risk of RA. The discovery should soon aid research into diagnosis and treatment of the disease. Recent research has also shown that several autoimmune diseases, including RA, share a common genetic link. In other words, patients with RA might share common genes with family members who have other autoimmune diseases like systemic lupus, multiple sclerosis , and others.

Many researchers are examining the possibility that exposure to an organism (a bacteria or virus) may be the first event in the development of RA. The body's normal response 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 antibodies, 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.

Reports in late 2001 suggest that certain stress hormones released during pregnancy may affect development of RA and other autoimmune diseases in women. Researchers have observed that women with autoimmune disorders will often show lessened symptoms during the third trimester of pregnancy. The symptoms then worsen in the year after pregnancy. Further, women appear to be at higher risk of developing new autoimmune disorders following pregnancy.

RA can begin very gradually or it can strike without warning. The first symptoms are pain , swelling, and stiffness in the joints. The most commonly involved joints include hands, feet, wrists, elbows, and ankles. The joints are typically 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 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. The hands and feet may also 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, an inflammation of the blood vessels, may interfere with blood circulation. This can result in irritated pits (ulcers) in the skin, gangrene , and interference with nerve functioning that causes numbness and tingling.

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, the 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 an autoantibody found in about 66% of patients with RA. However, it is also found in about 5% of all healthy people and in 10–20% of healthy people over the age of 65. Rheumatoid factor is also positive in a large number of other autoimmune diseases and other infectious diseases.

A long, thin needle can be inserted into a synovial joint to withdraw a sample of the synovial fluid for examination. In RA, this fluid has certain characteristics that indicate active inflammation. The fluid will be cloudy, relatively thinner than usual, with increased protein and decreased or normal glucose. It will also contain 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 other complications of the disease. Efforts are also made to provide relief from the symptoms and to maintain maximum flexibility and mobility of the joints.

A variety of alternative therapies have been recommended for patients with RA. Meditation , hypnosis, guided imagery, relaxation , and reflexology techniques have been used effectively to control pain. Acupressure and acupuncture have also been used for pain; work on the pressure points should be done daily in combination with other therapies. Bodywork can be soothing and is thought to improve and restore chemical balance within the body. A massage with rosemary and chamomile , or soaking in a warm bath with these essential oils , can provide extra relief. Stiff joints may also be loosened up with a warm sesame oil massage, followed by a hot shower to further heat the oil and allow entry into the pores. Movement therapies like yoga, t'ai chi , and qigong also help to loosen up the joints.

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 helpful, including turmeric (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 recommend 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.). The enzyme bromelain, found in pineapple juice has also been found to have significant anti-inflammatory effects.

RA, considered an autoimmune disorder, is often connected with food allergies or 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. Various yoga exercises done once a day can also assist in maintaining joint flexibility.

Allopathic treatment

Nonsteroidal anti-inflammatory agents and aspirin are used to decrease inflammation and to treat pain. 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, as well as other drugs called disease-modifying antirheumatic drugs. These include gold compounds, D-penicillamine, antimalarial drugs, and sulfasalazine. 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 healthcare professionals to carefully compare the risks associated with these medications to the benefits.

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. Another surgery used to stop pain in a stiff joint, such as the ankle, is the fusion of the affected bones together (arthrodesis, or artificial anklylosis).

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.

Resources

BOOKS

Aaseng, Nathan. Autoimmune Diseases. New York: F. Watts, 1995.

Lipsky, Peter E. "Rheumatoid Arthritis." Harrison's Principles of Internal Medicine. 14th ed. edited by Anthony S. Fauci, et al. New York: McGraw-Hill, 1998.

Schlotzhauer, M. Living with Rheumatoid Arthritis. Baltimore: Johns Hopkins University Press, 1993.

PERIODICALS

Akil, M., and R. S. Amos. "Rheumatoid Arthritis: Clinical Features and Diagnosis." British Medical Journal. 310 (March 4, 1995): 587+.

Gremillion, Richard B. and Ronald F. Van Vollenhoven. "Rheumatoid Arthritis: Designing and Implementing a Treatment Plan." Postgraduate Medicine. 103 (February 1998): 103+.

Moran, M. "Autoimmune Diseases Could Share Common Genetic Etiology." American Medical News. 44; no. 38: (October 8, 2001):38.

"Suspect Gene Mapped, May Lead to New Diagnostic Markers and Drug Targets." Immunotherapy Weekly. (December 26, 2001):24.

Vastag, Brian. "Autoimmune Disorders and Hormones." JAMA, Journal of the American Medical Association. 286, no. 19 (November 21, 2001):1.

Ross, Clare. "A Comparison of Osteoarthritis and Rheumatoid Arthritis: Diagnosis and Treatment." The Nurse Practitioner. 22 (September 1997): 20+.

ORGANIZATIONS

American College of Rheumatology. 60 Executive Park South, Suite 150, Atlanta, GA 30329. (404)633–1870. http://www.rheumatology.org. [email protected].

Arthritis Foundation. 1330 West Peachtree St., Atlanta, GA 30309. (404)872–7100. http://www.arthritis.org. [email protected].

Kathleen Wright

Teresa G. Odle

Rheumatoid Arthritis

Definition

Rheumatoid arthritis is an autoimmune disease that primarily damages the lining of joints.

Description

Rheumatoid arthritis (RA) is a disease mainly characterized by chronic inflammation of the tissue lining the joints (synovium). A joint is a point of connection between two bones that allows motion. For example, an elbow joint connects an arm to the forearm allowing motion of the arm, and a knee joint connects a thigh to the lower leg, allowing the straightening and bending of the knee. RA can affect almost any joint of the body, including those of the fingers, wrists, shoulders, elbows, hips, knees, ankles, feet, and neck. It can lead to long-term joint damage, resulting in chronic pain and disability. RA does not only affect joints. It is a systemic disease, because it can affect other organs in the body, such as the heart, muscles, blood vessels, nervous system, and eyes.

RA is also a progressive disease. The first stage of the disease is inflammation of the synovium of the affected joint, which causes pain, warmth, stiffness, redness and swelling around the joint that can last for hours. The arthritis usually begins in the small joints of the hands and the feet, spreading later to the larger joints. In the second stage, there is an overgrowth of connective tissue on the articular surface of the affected joint resulting in a thickening of the affected synovium (pannus). Finally, as part of the automimmune response, the inflamed cells release substances that start destroying bone and cartilage, causing joint deformity, more pain, and loss of function.

Demographics

According to the World Health Organization (WHO), RA is the most common chronic inflammatory joint disease. The incidence and prevalence of RA appear to have fallen in Europe, North America and Japan in the last 50 years. The prevalence of RA is estimated as relatively constant in many populations, at 0.5–1.0%, with low occurrences reported in populations from China and Japan. According to the Arthritis Foundation, approximately 1.3 million Americans are afflicted by RA. The disease can affect anyone, including children, but 70% of people with RA are women. RA onset usually occurs between 30 and 50 years of age. A high prevalence of RA has been reported in the Pima (5.3%) and in the Chippewa (6.8%) Indians. Older age and female gender are risk factors both for the development of RA and for a poor outcome.

Causes and symptoms

The cause of RA remains unknown, but most medical researchers believe that it is an autoimmune disease, meaning a disease characterized by the involvement of an inappropriate immune response that leads the body to attack the lining of its own joints. How this autoimmune response develops is not known, but it causes the inflammation that produces the pain, swelling, and stiffness associated with RA. Other research has proposed that susceptibility to RA may be genetic or environmental.

The symptoms of RA are the same as for all forms of arthritis and usually include morning stiffness, lasting joint pain, joint swelling, joint stiffness, tenderness or pain when touching a joint, difficulty using or moving a joint normally, and warmth and redness in a joint.

Diagnosis

The RA diagnosis may be difficult to establish, because there is no single test that can be performed to confirm RA. The diagnosis is based upon an individual's history of clinical symptoms and a complete physical examination. A specialized physician, often a rheumatologist , reviews all signs and symptoms experienced by a person, so as to rule out other joint diseases. This often requires various tests, which may include:

• Rheumatoid factor (RF) test: This test looks for distinctive antibodies released in the blood by people with RA to distinguish it from other forms of arthritis and other conditions that cause similar symptoms of joint pain, inflammation, and stiffness. In the early stages of RA, however, only one in five persons tests positive for rheumatoid factor.
• Antinuclear antibody (ANA) test: This test is performed to help screen for autoimmune disorders.A small percentage of healthy people, however, have a positive ANA.
• C-Reactive protein (CRP) test: The CRP test is used to evaluate how active the inflammation is. CRP tests are not specific enough to diagnose RA, but provide a general marker of infection and inflammation levels.

QUESTIONS TO ASK YOUR DOCTOR

• What kind of arthritis is RA?
• What causes RA?
• Are there any treatments for RA?
• What does the treatment involve?
• How effective is it?
• What are the risks?
• What are the side effects associated with RA medications?

Other tests, including x rays and magnetic resonance imaging (MRI), may be used to determine the cause of chronic back pain or examine internal organs that may be affected by RA.

Treatment

There is presently no cure for rheumatoid arthritis. In addition to pain and anti-inflammatory medicines, RA is treated with antirheumatic drugs, called “disease-modifying antirheumatic drugs”(DMARDs) that can slow the damage caused by RA. Rest is prescribed for severely inflamed joints, as using them can aggravate the inflammation. Regular rest periods can often relieve pain, with short periods of bed rest considered helpful to relieve a severe flare-up in its most painful stage.

Nutrition/Dietetic concerns

There is presently no scientific evidence showing conclusively that any particular foods may have a beneficial effect on joint inflammation, although some reports have proposed that oranges and some fish oils may reduce joint inflammation in some people with RA. A healthy, balanced diet aimed at maintaining a normal weight is important for people afflicted with RA, because excess weight increases stress on the weight-bearing joints, contributing to joint pain, stiffness and inflammation.

Therapy

Drug therapy prescribes medications that can help with the pain and swelling. Acetaminophen (Tylenol) is commonly used to ease RA pain. Some nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen (Motrin) and naproxen, are available over-the-counter. Stronger NSAIDs must be obtained by prescription. However, in 2005, the Food and Drug Administration (FDA) issued a warning about possible side effects of some NSAIDs. Disease modifying antirheumatic drugs (DMARDs) are a group of medications commonly prescribed to RA patients with more severe RA. They act by suppressing the body's autoimmune response, decreasing pain and inflammation, reducing joint damage, and preserving the structure and function of the joints. The type of DMARD prescribed depends on the stage and severity of RA. The possible side effects and expected benefits must also be weighed. Some common DMARDs include methotrexate (Rheumatrex), sulfasalazine (Azulfidine), hydroxychloroquine (Plaquenil), leflunomide (Arava) and cyclosporine (Sandimmune, Neoral). Corticosteroid medicines such as prednisone are among the most effective drugs for relieving inflammation quickly. They are used as a temporary measure to reduce dangerous flares of inflammation, until other drugs, such as DMARDs, take effect. Generally, the stronger medications have important side effects that must be taken into account when planning treatment.

RA patients can also undergo occupational therapy, where they are instructed on how to protect affected joints, and how to reduce strain on the joints during daily activities. For instance, special shoes and the use of a cane can help alleviate pain in the feet, knees, and hips when walking. Occupational therapy also seeks to restore abilities that may have been lost, and to suggest approaches to maintain independence and fitness.

The National Arthritis Foundation provides information on alternative and complementary therapies to RA treatment programs. People with RA may benefit from massage, acupuncture , acupressure , and various herbs and supplements.

KEY TERMS

Anorexia —An eating disorder characterized by markedly reduced appetite or total aversion to food.

Antibody —A protein produced by the body's immune system in response to a foreign substance.

Autoimmune disease —Disease characterized by the involvement of an inappropriate immune response that leads the body to attack its own cells and tissues.

Autoimmune response —A condition in which a person's immune system fails to recognize its own cells as being “self” and attacks its own body.

Disease-modifying antirheumatic drug (DMARD) —Medication belonging to a group of medications commonly used in patients with rheumatoid arthritis that acts by lowering the autoimmune response.

Immune system —The organs and cells that defends the body against infections and other diseases.

Immunosuppressant —Medication that can block the body's immune response.

Joint —The point of connection between two bones that allows motion.

Nonsteroidal anti-inflammatory drug (NSAID) —Medication that does not contain cortisone used to reduce the symptoms of the pain and inflammation of arthritis.

Pannus —Overgrowth of connective tissue on the articular surface of a joint.

Rheumatoid factor (RF) —An antibody present in the blood serum of many individuals affected by rheumatoid arthritis.

Synovial fluid —A lubricating fluid secreted by the synovial membrane.

Synovial membrane —A layer of connective tissue that lines the cavities of joints.

Synovium —A fibrous envelope that produces a fluid to help to reduce friction and wear in a joint.

Systemic disease —A disease that affects the entire body instead of a specific organ.

Prognosis

The course of RA varies from one individual to another, but in general, the long-term prognosis is poor. The irreversible destruction of joints usually begins within the first 2 years of disease onset in the majority of people with RA. Treatment can manage the pain and swelling caused by RA, and joint damage may even slow down or stop. Treatment can bring relief of symptoms to 75% of those afflicted. However, at least 1 of 10 people eventually becomes severely disabled, and the average life expectancy for a patient with RA may be shortened by 3–7 years.

Prevention

Because its cause is unknown, RA cannot be prevented. However, it is often possible to prevent further damage of the joints with early treatment and therapy.

Caregiver concerns

The prevalence of RA increases up to age 80 and represents an important cause of disability in elderly persons. In many senior patients, RA first starts during middle age. Some of these patients have secondary joint deformities and deterioration even though the inflammation may be inactive. In most patients of this age group, the arthritis is accompanied by mild or moderate generalized feelings of discomfort (malaise) and anorexia. Fever and night sweats are also occasionally reported. Elderly-onset rheumatoid arthritis (EORA), defined as RA with onset at age 60 years or over, differs slightly from RA. It is characterized by a more equal gender distribution, a higher frequency of acute systemic symptoms with involvement of the shoulder, a higher rate of disease progression, and, in later stages, more joint damage and functional disability. The efficacy and tolerability of medications is similar in both older and younger patient groups, but in the elderly, caution is required with the use of NSAIDs.

Resources

BOOKS

Felstiner, Mary. Out of Joint: A Private and Public Story of Arthritis. Winnipeg, MAN: Bison Books, 2007.

Foltz-Gray, Dorothy. The Arthritis Foundation's Guide to Good Living with Rheumatoid Arthritis. 3rd ed., Atlanta, GA: Arthritis Foundation, 2006.

McNeil, M. E. A. The First Year: Rheumatoid Arthritis: An Essential Guide for the Newly Diagnosed. Washington, DC: Marlowe & Company, 2005.

Shlotzhauer, Tammi L., and James L. McGuire. Living with Rheumatoid Arthritis. Baltimore, MD: Johns Hopkins University Press, 2003.

Yu, Winnie, and Harry D. Fisher. What To Do When The Doctor Says It's Rheumatoid Arthritis: Stop Your Pain, Become More Active, and Learn How to Talk to Your Doctors. Beverley, MA: Fair Winds Press, 2005.

PERIODICALS

Kerr, L. D. “Inflammatory arthropathy: a review of rheumatoid arthritis in older patients.” Geriatrics 59, no. 10 (October 2004): 32–35.

Lyyra, T. M., and R. L. Heikkinen. “Experienced health in older women with rheumatoid arthritis.” Journal of Women & Aging 18, no. 4 (2006): 67–81.

Schmajuk, G., et al. “Treatment of older adult patients diagnosed with rheumatoid arthritis: improved but not optimal.” Arthritis and Rheumatism 57, no. 6 (August 2007): 928–934.

Semanik, P., et al. “Physical activity behavior in older women with rheumatoid arthritis.” Arthritis and Rheumatism 51, no. 2 (April 2004): 246–252.

Tutuncu, Z., et al. Hedderwick. “Do patients with older-onset rheumatoid arthritis receive less aggressive treatment?” Annals of the Rheumatic Diseases 65, no. 9 (2006): 1226–1229.

OTHER

Arthritis Advice. National Institute on Aging, Age Page. (March 08, 2008) http://www.niapublications.org/agepages/arthritis.asp

Arthritis Drug Guide. Arthritis Foundation, Arthritis Today Health Magazine. (March 08, 2008) http://www.arthritis.org/drug-guide.php

Common Therapies to Consider. Arthritis Foundation, Alternatives Overview. (March 08, 2008) http://www.arthritis.org/common-therapies-to-consider.php

Do I have Arthritis? NIAMS, Health Information Page. http://www.niams.nih.gov/Health_Info/Arthritis/tengo_artritis.asp

51 Ways to Be Good to Your Joints—Lose Weight. Arthritis Foundation, Information Page. (March 08, 2008) http://www.arthritis.org/joints-weight.php

Living Well with a Rheumatic Disease. American College of Rheumatology, Information Page. (March 08, 2008) http://www.rheumatology.org/public/factsheets/livingwell.asp

Rheumatoid Arthritis. American Academy of Family Physicians, FamilyDoctor.org Information Page (March 08, 2008) http://familydoctor.org/online/famdocen/home/articles/876.printerview.html

Rheumatoid Arthritis. Arthritis Foundation, Disease Center Information Page. (March 08, 2008) http://www.arthritis.org/disease-center.php?disease_id=31

What Is Rheumatoid Arthritis? NIAMS, Health Information Page. (March 08, 2008) http://www.niams.nih.gov/Health_Info/Rheumatic_Disease/rheumatoid_arthritis_ff.asp

ORGANIZATIONS

American College of Rheumatology, 1800 Century Place, Suite 250, Atlanta, GA, 30345-4300, (404)633-3777, (404)633-1870, http://www.rheumatology.org.

Arthritis Foundation, P.O. Box 7669, Atlanta, GA, 30357-0669, (800)283-7800, http://www.arthritis.org.

National Institute of Arthritis and Musculoskeletal Diseases (NIAMS), 1 AMS Circle, Bethesda, MD, 20892-3675, (301)495-4484, (877)22-NIAMS, (301)718-6366, [email protected], http://www.niams.nih.gov.

Monique Laberge Ph.D.

Rheumatoid Arthritis

Definition

Rheumatoid arthritis is a chronic inflammatory autoimmune joint disease that causes pain, stiffness, swelling, and decreased movement in joints. Unchecked, it can lead to the eventual joint destruction.

Description

Rheumatoid arthritis is a painful disease that causes joints to swell and become stiff and restricts their range of motion. People of any age, including children, can get rheumatoid arthritis, but it most commonly appears in middle age. About three times more women than men develop rheumatoid arthritis. Between .03% and 1.5% of the population in the United States, or about 2.5 million people, have rheumatoid arthritis. The disease occurs in all ethnic groups worldwide.

Causes and symptoms

Although researchers are not sure of the exact cause of rheumatoid arthritis, they do know that it is an autoimmune disease in which immune system cells function incorrectly, leading them to attack the ligaments and joints of the body.

Symptoms vary from person to person and can mimic other bone and joint diseases such as osteoarthritis. For most people, the symptoms of rheumatoid arthritis appear gradually, although about one-third of individuals develop serious symptoms within a few months. In many people, symptoms tend to change from day to day, with periods of improvement followed by periods of worsening symptoms. In more serious cases, symptoms simply worsen progressively without periods of improvement. The wrists and hand joints are affected in more than 85% of individuals with rheumatoid arthritis. Usually if a joint on one side of the body is inflammed, the same joint on the other side will also be affected.

Signs and symptoms of rheumatoid arthritis include:

• sore, stiff, swollen, and warm joints
• involvement of multiple joints
• prolonged stiffness of over an hour in the morning
• general feelings of illness and fatigue, especially when joint pain has worsened
• chronic low fever
• appetite loss and weight loss
• anemia
• formation of rheumatoid nodules or bumps under the skin often around the elbow, spine, and fingers
• inflammation of the tear and salivary glands, causing dry eyes and mouth.

Diagnosis

Although a family physician can diagnose rheumatoid arthritis, a rheumatologist who specializes in bone and joint diseases usually is consulted. Rheumatoid arthritis is difficult to diagnose because symptoms are common to many other diseases. Diagnosis is made on the basis of medical history supplemented with x rays and blood tests. Diagnosis often involves ruling out other causes of joint distress.

The American Rheumatology Association designates that at least four of the following seven criteria must be present for at least six weeks to diagnose rheumatoid arthritis.

• morning joint stiffness lasting more than one hour
• pain simultaneously in three or more joint areas
• arthritis in the wrist or hand
• joint pain in symmetrical joint areas (e.g., both wrists, both knees)
• presence of rheumatoid nodules
• presence of serum rheumatoid factor, a protein found in blood
• x rays that show typical rheumatoid arthritis changes in the affected joints

X rays often appear normal until rheumatoid arthritis is quite advanced and serious joint damage has already occurred. Rheumatoid factor is an antibody or immune system protein. It is found in 80-90% of people with rheumatoid arthritis, but it is also found in about 30% of people who have no symptoms of the disease, so its presence is not a definitive diagnosis.

Treatment

There is no cure for rheumatoid arthritis. Treatment is divided into two categories: treatment of symptoms and treatment to stop or slow joint damage. Treatment to improve symptoms includes the use of various pain medications including nonsteroidal anti-inflammatory drugs (e.g., aspirin, ibuprophen, naproxen sodium) and analgesics (acetaminophen, tramadol), either alone or in combination with narcotic pain medications. Corticosteroids such as prednisone and cortisone are also used in the lowest effective dose to control pain and stiffiness. Also beneficial is exercise and physical therapy to increase strength and flexibility.

Drugs to stop or slow joint damage are collectively called disease-modifying antirheumatic drugs (DMARDs). These drugs, especially when given early in the course of the disease, interfere with the disease process in ways that slow or stop joint damage. DMARDs are often given in combination with drugs to improve symptoms. Some common DMARDs include methotrexate (Rheumatrex, Trexall), hydroxy-chloroquinine (Plaquenil), sulfasalazine (Azulfidine), leflunomide (Arava), D-pencillamine (Dpen, Cuprimine), azathioprine (Imuran), cyclosporine (Neoral, Sandimmune) and minocycline (Minocin, Dynacin). All these drugs have potentially serious side effects and may require regular blood or other tests.

Rheumatoid arthritis can also be treated with biologic response modifiers (BMRs). BMRs target specific proteins of the immune system that are involved in rheumatoid arthritis. Most BMRs are approved for use in adults only. The exception is etanercept (Enbrel), which is approved for individuals over age four. Other BMRs used to treat rheumatoid arthritis include infliximab (Remicade), anakinra (Kineret), and adalimumab (Humira). BMRs interfere with and may weaken the immune system. Individuals should not receive live-virus vaccinations while taking BMRs. Other side effects are also possible.

Many complementary and alternative cures are heavily advertised for rheumatoid arthritis. The National Center for Complementary and Alternative Medicine has investigated many of these alternative cures. Most do not provide any benefit to individuals with rheumatoid arthritis. Those complementary and alternative treatments that may have possible benefit include thunder god vine (Tripteryguim wilfordii, not available in the United States as of September 2005), gamma-linolenic acid (GLA), fish oil, glucosamine and chrondroitin (effective in animals, but unproven in humans), and mind-body stress reduction techniques. Individuals should not replace conventional treatment with alternative therapies, and before adding any herbal or other complementary treatments should consult their physician, as some complementary therapies may interfere with the conventional treatment and/or have serious side effects.

When treatment fails to control pain and joint damage, joint replacement surgery followed by guided rehabilitation may be necessary. Knee and hip replacement surgery are the most common types of surgery done on individuals with rheumatoid arthritis.

Prognosis

There is no cure for rheumatoid arthritis. The course of the disease is variable. Some people have the disease for only a year or two, and then it goes away on its own without joint damage. Many other people have periods when the disease is quiet and symptoms disappear, only to flare up again for unknown reasons. For some people the disease is continuous, chronic, and progressively worsens. It is estimated that rheumatoid arthritis reduces the lifespan of men by 7.5 years and of women by 3.5 years.

Health care team roles

A rheumatologist normally oversees the health care team treating an individual with rheumatoid arthritis. Nurses play an important role in patient education by teaching individuals with rheumatoid arthritis how to balance activity and rest. Physical therapists evaluate an individual's range of motion and teach appropriate exercises to promote joint mobility and muscle fitness and the appropriate use of heat and cold treatments. Physical therapists also have special equipment that can provide electrical stimulation to reduce pain and improve joint movement. Occupational therapists teach individuals how to move in ways that protect their joints and how to perform tasks of daily living in ways that reduce pain and stress on he joints. Both PT and OT are essential after surgery, but may also be helpful to individuals with advanced rheumatoid arthritis undergoing non-surgical treatments.

Prevention

Rheumatoid arthritis cannot be prevented. Early detection and treatment can help slow the disease. Clinical trials of new medications and complementary and alternative therapies for rheumatoid arthritis are ongoing. A list of clinical trials currently enrolling patients is available at www.clinicaltrials.gov.

KEY TERMS

Autoimmune disease— A disease in which the immune system of the body inappropriately attacks the body's own tissues.

Osteoarthritis— A noninflammatory wearing away of bone and cartilage most often associated with aging.

Resources

BOOKS

Haskell, Gretchen. Arthritis Foundation's Guide to Good Living with Rheumatoid Arthritis, 2nd ed. Atlanta, GA: Arthritis Foundation, 2005.

ORGANIZATIONS

American College of Rheumatology. 1800 Century Place, Suite 250 Atlanta, GA 30345-4300. (404) 633-3777. http://www.rheumatology.org.

Arthritis Foundation. P. O. Box 7669, Atlanta, GA 30357-0669. (800) 568-4045. http://www.arthritis.org.

National Institute of Arthritis and Musculoskeletal and Skin Disease Information Clearing House. National Institutes of Health, 1 Ames Circle, Bethesda, MD 20892-3675. (877) 226-4267 (toll free). http://www.niams.nih.gov.

OTHER

"Rheumatoid Arthritis." Arthritis Foundation. 2003. http://www.arthritis.org.

Ruderman, Eric. "Rheumatoid Arthritis." American College of Rheumatology, May 2004.

"Rheumatoid Arthritis and Complementary and Alternative Medicine." National Center for Complementary and Alternative Medicine. September 2005. http://nccam.nih.gov/health/RA.