ARTHRITIS AND INFLAMMATION

Arthritis literally means an inflammation of a joint and is a blanket term for a number of ailments with differing significance, various causes, and diverse symptoms. Such conditions are usually characterized by pain when moving or putting weight on the joint. Inflammation (pain, heat, redness, and swelling) may or may not be present.

Pain, stiffness, swelling, or tenderness in any joint, or in the neck or lower back, that lasts longer than six weeks warrants a trip to the doctor to determine the cause of the problem. A long delay in seeking help may result in irreversible damage to joints.

You should seek medical attention for pain in a joint immediately if:

• joint pain or swelling is very sudden and intense;
• joint pain follows an injury (you may have a fracture near the joint); or
• joint problems are accompanied by a fever above 100 degrees Farenheit (38 degrees Centigrade).

At least 31.6 million Americans suffer from some form of arthritis. The three most common types are rheumatoid arthritis, osteoarthritis, and gout. Each has a different cause, treatment, and probable outcome.

Rheumatoid Arthritis

Rheumatoid arthritis is an inflammation of the joints caused by disturbances in the body’s immune system (which defends it against disease) and can occur at any age. Its victims are more likely to be female and include infants, teenagers, and middle-aged and older adults. It is often characterized by morning stiffness, along with pain and swelling in the joints of fingers, ankles, knees, wrists, and elbows, which improves as the day goes on. The distribution of affected joints is usually symmetrical; that is, if your right wrist is afflicted, your left wrist will probably be afflicted as well.

Treatment

There is no cure for rheumatoid arthritis, but the inflammation may be controlled under medical supervision. Drug therapy draws from two broad categories: the anti-inflammatory drugs and the antirheumatic drugs.

Anti-inflammatory Drugs

Anti-inflammatory drugs can be further divided into nonsteroidal and steroidal drugs. Nonsteroidal anti-inflammatory drugs (NSAIDs) work by inhibiting formation of chemicals in the body that cause pain, fever, and inflammation. NSAIDs can be either salicylate, such as aspirin, or nonsalicylate, such as ibuprofen (MOTRIN, ADVIL, NUPRIN, MEDIPRIN).

The amount of aspirin required to reduce the inflammation of arthritis, however, approaches levels at which a small proportion of people may experience undesirable adverse effects. (High-dose aspirin therapy should never be started without medical supervision to determine the correct dose and to achieve the most therapeutic effect with the fewest adverse effects.)

Aspirin works when it is present in the bloodstream at a certain level, which varies among users. Effective blood levels of aspirin range between 15 and 30 milligrams per deciliter (tenth of a liter of blood). To achieve this level, between 9 and 23 regular aspirin tablets (325 milligrams) must be taken daily (3.0 to 7.5 grams of aspirin).[1] If you are taking aspirin, the level of the drug in your blood should be monitored periodically to prevent toxicity (poisoning). Signs of aspirin toxicity include ringing in the ears, rapid breathing (hyperventilation), mental confusion, shortness of breath, swelling of feet or lower legs (edema), dizziness, headache, nausea or vomiting, sweating, and thirst. These symptoms should be reported to your doctor immediately.

All prescription NSAIDs for rheumatoid arthritis are much more expensive than aspirin, have significant adverse effects, and are no more effective than aspirin. Like aspirin, other NSAIDs may also cause gastrointestinal bleeding or impair kidney function. If you have had an allergic reaction or stomach problems after taking aspirin, however, another NSAID may be better tolerated. Read the information on individual NSAIDs for recommendations and adverse effects. Then discuss these choices with your doctor.

Selective COX-2 inhibitor NSAID drugs

Even before the FDA approved the first two of these drugs, celecoxib (CELEBREX) and rofecoxib (VIOXX), they were widely touted and promoted as the saviors for people who had developed ulcers and other serious gastrointestinal complications from the older NSAIDs. However, two large clinical studies of approximately one-year duration did not support removal of the standard NSAID warning of the risk of serious gastrointestinal events from the celecoxib (CELEBREX) and rofecoxib (VIOXX) labels. These large studies did not show an advantage in overall safety (as measured by the total number of deaths, serious adverse events, and discontinuations and hospitalizations due to adverse events) favoring the selective COX-2 inhibitors compared to the other, older NSAIDs tested.

Further, one large study found a four- to fivefold increase in heart attacks in people using rofecoxib (VIOXX) compared to people using the older NSAID naproxen. The increase in heart attacks was also accompanied by an increase in other thrombotic (blood-clotting) adverse effects such as strokes and clots in the legs as well as problems with high blood pressure in the rofecoxib group compared to those taking naproxen.[2]

A cardiovascular risk warning has been added to the professional product labeling for rofecoxib (VIOXX) and should also be added to celecoxib’s labeling, since there is some concern from a recent review that this risk may be a property of other COX-2 inhibitors such as celexocib in addition to rofecoxib. The authors of this study concluded that “the use of selective COX-2 inhibitors might lead to increased cardiovascular events.”[3]

In addition to the concern for increased cardiovascular risk with the COX-2 inhibitors, studies have been published concerning other adverse effects of these drugs, which can inhibit the body’s ability to acutely respond to stress. Examples include the heart’s ability to respond to heat stress[4] and the healing of a surgical wound,[5] an ulcer,[6] or a ligament injury.[7]

The other type of anti-inflammatory drugs, steroids, are very important hormones that have two functions: controlling inflammation and regulating vital body functions. They are not generally recommended first for treatment of rheumatoid arthritis. Steroids may be useful, however, for older adults who cannot take or do not respond to an NSAID. They can be locally injected into a joint if a specific joint is causing considerable pain. Whenever possible, steroids are to be avoided because they are associated with numerous adverse effects, including an increased risk of developing the bone-weakening disease osteoporosis (which is more likely to affect thin, small-boned white women).

Disease-Modifying Anti-Rheumatic Drugs (DMARDs)

In contrast to the anti-inflammatory drugs just described, the DMARDs not only relieve symptoms but may also slow or even modify the rheumatic disease process itself.

Until recently, most doctors reserved the use of DMARDs for patients who failed to respond to other therapies. Now, many physicians use DMARDs earlier and more aggressively in the hope of slowing disease progression and damage to joints. One of the first, still widely prescribed DMARDs, methotrexate (TREXALL), is often recommended as the first drug to be used in this category for patients with moderate to severe rheumatoid arthritis. There are four newer DMARDs, all of which are biologically based immune response modifiers: adalimumab (HUMIRA), anakinra (KINERET), etanercept (ENBREL), and infliximab (REMICADE). In many patients, three of these drugs can cause a dramatic improvement in symptoms by blocking the action of a naturally occurring protein called tumor necrosis factor (TNF), believed to play a role in joint inflammation and damage. Elevated levels of TNF are found in the joint fluid of rheumatoid arthritis patients. The drug anakinra apparently works by blocking the receptor for interleukin-1 (IL-1), another naturally occurring protein that has a role in increasing joint inflammation and damage.

As with many drugs with dramatic benefits, these drugs can also pose serious risks by interfering with the body’s immune mechanisms for fighting infectious diseases. Thus, it is required that information about increased risks of such diseases are tuberculosis (especially with infliximab) and other infections are included in the warnings for these drugs. As discussed in the monographs for these drugs, if you think you are getting any infection, notify your doctor immediately. For three of the four drugs (etanercept, infliximab, and adalimumab), if you experience the symptoms of heart failure, fatigue, difficulty breathing, swelling (especially in the legs and ankles), or rapid or “galloping” heartbeats, immediately notify your doctor.

Regardless of the drug therapy chosen by you and your doctor, an exercise program and physical therapy should be designed within the limits of pain. This will help to strengthen muscular action and maintain or improve range of motion in the joints. Inflammation also occurs in other rheumatologic diseases such as ankylosing spondylitis, scleroderma, temporal arteritis, and polymalgia rheumatica. Therapy follows the same general anti-inflammatory guidelines that are used to treat rheumatoid arthritis.

Osteoarthritis

Osteoarthritis is the most common type of arthritis and is usually related to the aging of the joint or prior injury. Often a mild condition, it may cause no symptoms or only occasional joint pain and stiffness. Most of the time osteoarthritis is not crippling, although a few people experience considerable pain and disability. It occasionally progresses to a point at which walking is difficult. Osteoarthritis frequently occurs in the finger joints, where it causes knobby bumps, and the spine, where it induces bone-like growths. These, however, do not commonly cause serious problems.

Osteoarthritis can often be treated without medical supervision.

Unlike rheumatoid arthritis, osteoarthritis is a degenerative joint disease that does not always have inflammation as a symptom. Obesity (being excessively overweight) aggravates the wear and tear on the inside surface of the joint. Not surprisingly, the most severe form of osteoarthritis is the type that affects the joints that bear the body’s weight, such as the hips and the knees. A marked improvement is often seen after weight loss and an exercise program that helps to preserve full range of movement in the affected joints.

Treatment

Unlike rheumatoid arthritis, which requires high doses of aspirin to reduce inflammation, two 325 milligram tablets four times a day is often sufficient to control osteoarthritic pain in adults. Other pain relievers, including acetaminophen, are recommended for the person who cannot take aspirin. Be aware that in contrast to aspirin, acetaminophen relieves pain, but it is not effective in reducing inflammation. Therefore, we do not recommend the use of acetaminophen for the treatment of arthritis unless it is clear that you have osteoarthritis, which does not have a significant amount of inflammation.

Topical (skin) preparations marketed for treating arthritis (external salicylate-containing painkillers, such as Aspercreme and Myoflex) have no place in arthritis treatment. Salicylates (including aspirin) exert their effect on joints by absorption into the bloodstream. This is best done by swallowing tablets, not by applying cream.

Exercise should put an affected joint through its full range of motion. Swimming and walking are particularly good for this. You can start immediately and gradually improve your strength and flexibility. Under medical supervision, severe osteoarthritis is sometimes treated with physical therapy, orthopedic devices, and, in extreme cases, surgery.

Gout

Gout is related to the formation of uric acid crystals in the joints. White blood cells respond to the crystals by releasing certain enzymes into the joint space. The release of these enzymes causes the intense pain and inflammation of an acute attack of gout. The big toe is a common location of gouty pain. Medical treatment by a professional is required, and is usually sought, as the pain typically comes on suddenly and is often severe.

Treatment

Gout therapy can be divided into treatment of acute (sudden) attacks and prevention of uric acid crystal formation. Colchicine relieves an acute attack by inhibiting the white blood cell response. NSAIDs are also effective for treating an acute attack but require 12 to 24 hours before their onset of action. If you suffer from frequent attacks, or if your uric acid blood levels remain high between attacks, your doctor may prescribe either allopurinol or probenecid to reduce the uric acid in your body. Allopurinol decreases the amount of uric acid produced by the body. Probenecid increases the amount of uric acid that is eliminated by the body.

People who have gout should not use aspirin and other salicylates. Be aware that over-the-counter (nonprescription) products that contain aspirin cause retention of uric acid and may result in a worsening of gouty arthritis. Aspirin also reduces the effectiveness of several antigout medications, for example, probenecid.

Infectious Arthritis

Infectious arthritis occurs when a joint is invaded by bacteria, causing it to become red, hot, and swollen. It may be difficult to distinguish this type of arthritis from other types, as it frequently occurs in patients with other kinds of arthritis.

Treatment

This type of infection is almost always accompanied by fever and requires antibiotics, as directed by a physician, as soon as possible; otherwise the joint may be destroyed by the infectious process. No nonprescription preparations are appropriate as the sole treatment for infectious arthritis.