Gout

Gout is a disorder that results when a type of urate crystal accumulates in the joints because of high levels of uric acid in the blood (hyperuricemia), leading to painful attacks of joint inflammation.

Gout is more common in men than in women. It usually develops during middle age in men and any time after menopause in women. Drug treatment is generally effective. However, despite treatment, over time and after repeated attacks, joint motion may become progressively restricted by damage caused by deposits of urate crystals in the joints and tendons. Significant disability may result.

Kidney stones, primarily uric acid stones, develop in one fifth of the people who have gout. If left untreated, kidney stones may lead to infection and kidney damage.

Causes

Normally, uric acid is present in small amounts in the blood because of the breakdown of cells. Also, the body transforms substances in foods called purines into uric acid. Uric acid is usually excreted in the urine, keeping blood levels of uric acid normal.

Levels of uric acid may become abnormally high when the kidneys cannot eliminate enough uric acid in the urine. In most people, the cause is unknown. However, levels are especially likely to increase in people with kidney damage due to diseases such as diabetes and high blood pressure. Certain drugs (eg, thiazide diuretics) directly impair the kidneys' ability to eliminate uric acid, also causing levels of uric acid to rise. In some people, a disease such as leukemia causes excessive uric acid to be produced. The kidneys are overwhelmed by the large amount of uric acid and are unable to excrete it sufficiently.

When the levels of uric acid in the blood are high, urate crystals may form and accumulate in joints. Hard lumps of urate crystals (tophi) are first deposited in the joint lining (synovium) or cartilage or in bone near the joints and then under the skin around joints. Tophi can also develop in the kidney, under the skin on the ears, in the tough band extending from the calf muscles to the heel (Achilles tendon), or around the elbows. If untreated, tophi can burst and discharge chalky masses of urate crystals through the skin.

Regardless of the underlying cause of gout, a high-purine diet (which includes such foods as anchovies, asparagus, consommé, herring, meat gravies and broths, mushrooms, mussels, all organ meats, sardines, and sweetbreads) worsens matters. Alcohol ingestion makes things worse because alcohol both increases the production of uric acid and interferes with its elimination by the kidneys.

Symptoms

Painful gout attacks (acute gouty arthritis) can occur without warning. These attacks may be triggered by an injury, surgery, consumption of large quantities of alcohol or purine-rich food, fatigue, emotional stress, or illness. Typically, severe pain occurs suddenly in one or more joints, often at night. The pain becomes progressively worse and is often excruciating, particularly when the joint is moved or touched. Even a sheet or blanket touching a toe affected by gout can hurt. The joint becomes inflamed—it swells and feels warm, and the skin over the joint appears red or purplish, tight, and shiny. The joints most likely to be affected are those in the feet, particularly at the base of the big toe. Other joints commonly affected include those in the ankles, knees, wrists, and elbows. The joints of the spine, hips, and shoulders are rarely affected.

Other symptoms of an attack can include fever (which may reach 102° F), chills, a general feeling of illness, and a rapid heartbeat. The first few attacks usually affect only one joint and last for a few days. The symptoms gradually disappear, joint function returns, and no symptoms appear until the next attack. However, if the disorder progresses, untreated attacks last longer, occur more frequently, and affect several joints.

If kidney stones develop in the urinary tract (urolithiasis), excruciating pain may result.

Diagnosis

Doctors often diagnose gout on the basis of its distinctive symptoms and an examination of the affected joints. The diagnosis is confirmed when urate crystals are identified in a sample of a tophus or in joint fluid that has been removed with a needle (joint aspiration) and viewed under a microscope.

Other tests are sometimes performed to support the diagnosis and to provide additional information. They also help exclude other possible causes. A blood test may show a high level of uric acid in the blood, which supports the diagnosis. A blood test may also show a high white blood cell count due to the inflammation caused by the urate crystals. X-rays may show joint damage and the presence of tophi.

Treatment

The first step is to relieve the painful joint by controlling the inflammation with drugs.

Nonsteroidal anti-inflammatory drugs (NSAIDs), including the cyclooxygenase-2 (COX-2) inhibitors (coxibs), are often effective. NSAIDs must be used with caution in older people, however, because these drugs pose a higher risk of side effects, primarily bleeding in the digestive tract and kidney damage. One of the coxibs, rofecoxib (withdrawn from the market), appears to increase the risk of heart attack and stroke after long-term use. The risk with other coxibs is being studied. Because one recent study has shown a 2.5-fold increase in cardiovascular problems with another coxib, celecoxib, current FDA recommendations are to limit use of any coxib to people at high risk of gastrointestinal bleeding, who have a history of intolerance to other NSAIDs, or who are not doing well on other NSAIDs. Caution should be taken with use of coxibs for long periods or by people with risk factors for heart attack and stroke. Rarely, opioid analgesics, such as codeine, are needed. Colchicine, the traditional but no longer the most common first-step treatment, begins to ease joint pain after 12 hours. The pain is relieved within 36 to 48 hours. However, it tends to cause diarrhea. Corticosteroids, such as prednisone, are sometimes used to reduce joint inflammation in people who cannot tolerate the other drugs. Corticosteroids may also be injected into an inflamed joint to relieve pain.

In addition to drug therapy, the inflamed joint may be immobilized with a splint to help further reduce pain.

The second step is to avoid recurrences of gout attacks. Avoiding alcoholic beverages, losing weight, discontinuing drugs that cause elevated blood levels of uric acid, and eating smaller amounts of purine-rich foods may be all that is needed. Many people who have gout are overweight. As they gradually lose weight, their blood levels of uric acid often return to normal or near normal, and gout attacks cease. Most tophi on the ears, hands, elbows, or feet shrink slowly when the uric acid level falls sufficiently. However, extremely large tophi may have to be removed surgically. Uric acid stones in the urinary tract can be broken up and thereby washed out in the urine, with ultrasound directed at the stones from outside the body (extracorporeal shock wave lithotripsy).

Preventive daily drug treatment may be needed for people who experience repeated, severe attacks. Colchicine may be taken daily to prevent attacks or to greatly reduce their frequency. NSAIDs may also be taken daily, but continued use is not encouraged because of potential side effects. NSAIDs pose some risks for people who have kidney or liver disease. Preventing attacks does not prevent or heal existing joint damage caused by urate crystals, because the crystals remain in the joints.

Drugs that cause excretion of uric acid in the urine (uricosuric drugs), such as probenecid and sulfinpyrazone, can be used to lower the uric acid level in the blood (in people who have normal kidney function) by increasing the kidney's excretion of uric acid. Aspirin, even in low doses, blocks the effects of probenecid and sulfinpyrazone and thus should be avoided when a person is taking either of these drugs.

Although uricosuric drugs lower the level of uric acid in the blood, they can increase the concentration of uric acid in the urine; drinking plenty of fluids—at least 3 quarts a day—may help reduce the risk of uric acid stones developing in the urinary tract. Uricosuric drugs can cause a gout attack when they are first taken. Because low doses of colchicine or an NSAID can decrease this risk, one of these drugs is usually taken for a few months as well.

Allopurinol is another drug that is used to lower the level of uric acid in the blood. This drug blocks the production of uric acid in the body and is especially helpful for people who have a high level of uric acid in the blood as well as urate stones or impaired kidney function. However, allopurinol can cause stomach upset, a skin rash, a decreased white blood cell count, or liver damage. In addition, as with uricosuric drugs, allopurinol can cause a gout attack when it is first taken. To decrease this risk, a doctor may prescribe low-dose colchicine or an NSAID to be taken as well for a few months.

See the table Drugs Used for Gout.