Degenerative Diseases - Arthritis
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The word "arthritis" literally means joint inflammation, and it is applied to more than one hundred related diseases known as rheumatic diseases. When a joint—the point where two bones meet—becomes inflamed, swelling, redness, pain, and loss of motion occur. In the most serious forms of the disease, the loss of motion can be physically disabling.
Normally, inflammation is the body's response to an injury or a disease. It causes pain, redness, swelling, and warmth in the inflamed body part. Once the injury is healed or the disease is cured, the inflammation stops. In arthritis, however, the inflammation does not subside. Instead, it becomes part of the problem, damaging healthy tissues. This generates more inflammation and more damage, and the painful cycle continues. The damage can change the shape of bones and other tissues of the joints, making movement difficult and painful.
Types of Arthritis
More than one hundred types of arthritis have been identified, but four major types affect large numbers of Americans:
- Osteoarthritis—The most common type of arthritis, osteoarthritis generally affects people as they grow older. Sometimes called degenerative arthritis, it causes the breakdown of bones and cartilage (connective tissue attached to bones) and usually causes pain and stiffness in the fingers, knees, feet, hips, and back. The National Institutes of Health (NIH) estimates that osteoarthritis affects about twenty-one million Americans, usually after age forty-five.
- Fibromyalgia—Fibromyalgia affects the muscles and connective tissues and causes widespread pain, fatigue, sleep problems, and stiffness. Fibromyalgia also causes "tender points" that are more sensitive to pain than other areas of the body. According to the National Fibromyalgia Association, ten million Americans, mostly women, have this condition.
- Rheumatoid arthritis—Rheumatoid arthritis is caused by a flaw in the body's immune system that results in inflammation and swelling in joint linings, followed by damage to bone and cartilage in the hands, wrists, feet, knees, ankles, shoulders, or elbows. The Arthritis Foundation, a not-for-profit research and advocacy organization (http://www.arthritis.org/), reports that in the United States more than two million people, mostly women, have this form of arthritis.
- Gout—Gout is an inflammation caused by an accumulation of a natural substance, uric acid, in the joint, usually the big toe, knee, or wrist. The uric acid forms crystals in the affected joint, causing severe pain and swelling. According to the Arthritis Foundation, gout affects more men than women and occurs in about two million Americans.
Other Inflammatory and Autoimmune Disorders
Another less common, but potentially life-threatening, form of rheumatic disease is systemic lupus erythematosus (known as SLE or lupus), an inflammatory autoimmune disease (the immune system mistakenly attacks the body's own tissues) that attacks skin, joints, blood, and kidneys. SLE occurs more frequently among women than men, and three times as many African-American women are diagnosed with SLE than white women. The Arthritis Foundation reports that at least 239,000 Americans have lupus, with women affected from eight to ten times more often than men. Generally diagnosed in people age fifteen to forty-five years, the symptoms of SLE include the following:
- Painful or swollen joints, muscle pain, and fatigue
- Fever, weight loss, hair loss, and skin rashes
- Cold, pale, or blue fingers, also known as Raynaud's phenomenon
- Swollen legs or glands
- Nephritis (inflammation of the kidneys)
- Pleuritis (inflammation of the lungs) that may produce chest pain or increase the risk of developing pneumonia
- Myocarditis, endocarditis, or pericarditis (inflammation of the heart valves and the membrane around the heart, respectively) and vasculitis (inflammation of blood vessels)
As with other inflammatory and autoimmune disorders, each patient experiences the disease differently. SLE symptoms ranging from mild to severe flare up and subside throughout the course of illness. Some patients with SLE also experience headaches, vision disturbances, strokes, or behavior changes as a result of the effects of the disease on the central nervous system.
No cure exists for SLE, and treatment aims to relieve symptoms and reduce the potential for organ damage and complications. Most patients receive corticosteroid hormones, such as prednisone and dexamethasone, which rapidly reduce inflammation. Patients with SLE also are treated with nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen (Motrin, Advil), naproxen (Naprosyn, Aleve), and indomethacin (Indocin), along with other drugs to combat pain, swelling, and fever. Drugs originally used to treat malaria (antimalarials, such as Plaquenil) also are used to treat the fatigue, joint pain, rashes, and pleuritis resulting from SLE.
Many chronic degenerative diseases, especially autoimmune diseases, are thought to occur when a genetically susceptible individual encounters an environmental trigger. For example, some researchers believe that viruses may be the environmental triggers for diseases such as lupus and scleroderma, an illness in which skin and internal organs thicken and harden.
Prevalence of Arthritis
Arthritis is a very common problem. In 2005 the CDC reported that more than forty-six million Americans had been diagnosed with arthritis, another twenty-three million suffer chronic joint symptoms but have not yet been diagnosed, and more than seven million are disabled by the disease. By 2030 the total number is expected to increase to nearly sixty-five million Americans suffering from some form of arthritis. (See Figure 6.1.)
Arthritis is the leading cause of disability among Americans older than age fifteen. Rheumatic and musculoskeletal disorders are the most frequently reported causes of impairment in the adult population, the leading causes of limitation of mobility, and the second-leading causes of activity restriction. Arthritis and other musculoskeletal diseases are responsible for considerable limitation of activity and disability among American workers. Figure 6.2 shows that arthritis or other musculoskeletal diseases account for the greatest proportion of activity limitation among adults of all ages. The Arthritis Foundation observes that arthritis is a more frequent cause of activity limitation than heart disease, cancer, or diabetes. Lost wages, medical bills, and other costs to the U.S. economy resulting from the effects of arthritis amount to more than $86.2 billion annually ("Support 5% Increase for NIH Arthritis Research Funding," Arthritis Foundation, February 20, 2006, http://www.arthritis.org/advocacy/priorities/priorities_2006research.asp).
About half of all people older than age sixty-five will experience some form of arthritis in their lifetimes. Although some think of it as only an older person's disease, nearly three of five arthritis sufferers are younger than age sixty-five, and about 30% of people between the ages of forty-five and sixty-four—28.4% of women and 37.3% of men—have arthritis. It also can affect children. According to the Arthritis Foundation, an estimated three hundred thousand children and teenagers suffer from arthritis. Of these, approximately fifty thousand have juvenile rheumatoid arthritis, a potentially crippling disease that eventually destroys the joints ("Arthritis Prevalence: A Nation in Pain," Arthritis Foundation, 2005, http://www.arthritis.org/conditions/Fact_Sheets/Arthritis_Prev_Fact_Sheet.asp).
In all age groups, women have a slightly higher likelihood of developing arthritis, and as they age, women have an increasingly higher prevalence of arthritis than men do, 24.3% versus 17.1%. According to the Arthritis Foundation, if prevalence rates remain about the same, the number of affected persons age sixty-five and older will nearly double to 41.1 million by 2030.
Developments in Arthritis Research
As researchers learn more about inflammation and the body's immune system, they come closer to finding new drugs designed to relieve the pain of arthritis and to block the degenerative process of these diseases. Researchers are investigating ways to improve treatment by using the body's own biologic response modifiers (products that modify immune responses). They expect that these substances can be used to control the destructive processes of autoimmune diseases (in which the immune system attacks one's own cells) without weakening the whole immune system. One thing researchers know for sure is that the sooner arthritis is treated, the better.
Medications used to help relieve the symptoms of joint pain, stiffness, and swelling include NSAIDs, aspirin, analgesics, and corticosteroids. These drugs may be used in combination. Among recent advances are more effective pain-relief drugs with fewer adverse side effects than those already on the market. One of the problems with NSAIDs, the most widely used class of drugs for osteoarthritis, is the potential to irritate the stomach and cause ulcers.
Disease-modifying antirheumatic drugs (DMARDs) help reduce joint inflammation. They are generally effective but take as long as three or four months to produce benefits, so they must be started as early as possible to help prevent joint deformities and disability later in life. Doctors often prescribe an additional medication, such as a corticosteroid or an NSAID, to help control pain and inflammation while the DMARD starts to work.
DMARDs include low doses of methotrexate, leflu-nomide, penicillamine, sulfasalazine, auranofin (also known as oral gold), gold sodium thiomalate (also known as injectable gold), minocycline, azathioprine, hydroxy-chloroquine sulfate (and other antimalarials), cyclospor-ine, and biologic agents. DMARDs are used most often for rheumatoid arthritis, but some DMARDs also can be used for juvenile rheumatoid arthritis, ankylosing spon-dylitis, psoriatic arthritis, and lupus.
Other therapies also are available. For instance, patients with moderate to severe rheumatoid arthritis who have not responded well to DMARDs may try Prosorba therapy. This involves drawing blood, separating plasma from red blood cells, and treating plasma through a Prosorba column (a cylinder the size of a soup can that holds a sand-like substance coated with protein A, a molecule that binds antibodies). Treated plasma then is rejoined with red blood cells and returned to the body. Treatments are given in twelve weekly sessions that last about 2.5 hours each. It may take as long as sixteen weeks for patients to feel the benefits of the therapy.
Investigators are studying how joints respond to different types of stresses. This may help in developing more effective exercises or new self-help devices. Researchers have found that regular exercise, weight control, and other self-care measures considerably reduce the incidence and effects of the disease.
Setbacks in Arthritis Drug Treatment
In 1999 two new drugs, celecoxib, sold as Celebrex, and rofecoxib, sold as Vioxx, were marketed to physicians and directly to consumers as potent painkillers for arthritis sufferers. The drugs, called COX-2 inhibitors, are NSAIDs and were heralded as superior to conventional NSAIDs because they provided the same pain-relieving effects as aspirin and NSAIDs but with less chance of causing ulcers and intestinal bleeding. Almost immediately after their introduction, the drugs joined the ranks of the nation's best-selling prescription pharmaceuticals.
In November 2002 the first reports of increased heart disease among patients taking Vioxx were issued, and in April 2002 the U.S. Food and Drug Administration (FDA) required Merck, the pharmaceutical company that makes Vioxx, to inform the public about the potential for increased risk of heart attack and stroke. The same year, a third COX-2 inhibitor, called Bextra, was introduced by the drug company Pfizer.
When a study released in September 2004 revealed that patients taking Vioxx were twice as likely to suffer from stroke and heart attack as nonusers, Merck withdrew the product, which had annual sales of $2.5 billion, from the market (David J. Graham et al, "Risk of Acute Myocardial Infarction and Sudden Cardiac Death in Patients Treated with COX-2 Selective and Non-Selective NSAIDs," October 2005, http://www.fda.gov/cder/drug/infopage/vioxx/vioxxgraham.pdf). Less than three months later the FDA asked Pfizer to add a "black-box" warning to the Bextra labels alerting doctors and consumers to the increased risk of heart attack and stroke. (A "black-box" warning is the strongest form of warning the FDA can request.) One week later, on December 17, 2004, the National Cancer Institute terminated a colon polyp study due to an increased cardiovascular risk in Celebrex users, and the NIH halted a study of Alzheimer's disease because it suggested that the NSAID naproxen (Naprosyn) also increased risk for heart attack or stroke. At the close of 2004 the FDA formally exhorted limited and cautious use of COX-2 inhibitors and traditional NSAIDs.
In February 2005 the FDA reversed its determination about naproxen, stating that it was not associated with increased cardiovascular risk. The FDA also recommended that COX-2 drugs remain on the market. By April 2005 the FDA asked Pfizer to take Bextra off the market, and manufacturers of over-the-counter and prescription NSAIDs, as well as Celebrex, were asked to change their labels to reflect the increased risk.
Since its withdrawal from the market, nearly ten thousand Vioxx-related lawsuits have been filed against Merck by former Vioxx users or their survivors, alleging harm from the widely marketed drug. Merck lost its first lawsuit—a product liability case—in Texas in the summer of 2005. On August 19, 2005, Merck was found to be negligent in the death of a fifty-nine-year-old marathoner, and his widow was awarded $253 million. The amount will likely be substantially reduced under Texas law that limits awards. Merck, however, won its second case in New Jersey. The jury found that Merck did not fail to warn consumers about the safety of Vioxx, was not guilty of fraud, did not misrepresent the risks of heart attack and stroke when marketing it to physicians, and did not conceal information about the drug (Aaron Smith, "Big Win for Merck in Vioxx 2," CNN/Money.com, November 3, 2005, http://money.cnn.com/2005/11/03/news/fortune500/merck_humeston/index.htm).
The majority of the Vioxx suits have been filed in state court in New Jersey, Merck's home state, or in federal court. The first federal Vioxx trial, Plunkett v. Merck, ended in a hung jury on December 13, 2005, in a federal court in Houston, Texas. An estimated twenty million people took the once-popular painkiller, and Merck faces billions of dollars in potential payouts arising from pending state and federal lawsuits ("Next Vioxx Cases Scheduled for Spring," Associated Press, Forbes.com, January 13, 2006). By May 2006 six Vioxx lawsuits had reached settlements, and Merck had lost three (Linda A. Johnson, "Update 4: Study—Vioxx Risks Started within Months," Associated Press, Forbes.com, May 19, 2006).