Gout, complex disease caused by the faulty metabolism of uric acid produced in the body by breakdown of purine, a molecule found throughout all tissues and in many foods. Excessive production of uric acid or insufficient elimination of uric acid from the body by the kidneys can lead to hyperuricemia, or elevated levels of uric acid in the blood. This condition may be accompanied by the formation of crystals of uric acid in connective tissue and/or the joint space between bones. The accumulation of such crystals in the joint space can give rise to inflammation and bouts of intense pain that are the hallmark of gout.
Gout rarely affects children and young adults. It most frequently develops in adult men, especially between ages 40 and 50; it rarely strikes women before menopause. Some people may inherit a predisposition to gout; up to 20 to 25 percent of cases involve a family history of the disorder. Factors that appear to raise the risk of developing hyperuricemia or gout or may aggravate the disorder in some individuals include overweight, high alcohol consumption, excessive consumption of foods rich in purines, exposure to lead in the environment, use of certain drugs (such as diuretics, nicotinic acid, cyclosporine, and levodopa), and certain health conditions (such as untreated high blood hypertension, diabetes, high blood levels of fat and cholesterol in the blood, and arteriosclerosis).
The initial stage of the disease is marked by high blood levels of uric acid, although no symptoms appear. The buildup of uric acid crystals in joint spaces provides the basis for acute gout. Acute attacks are characterized by severe pain in the joints, most often in the big toe, but sometimes in the ankle, heel, knee, hip, shoulder, wrist, fingers, or elbow. The attack usually begins abruptly; the joint typically becomes swollen, red, inflamed, warm, and extremely tender. Untreated attacks last from a few days to a week or more. The interval between acute attacks–months or years in early stages of the disease–tends to decrease with time. Left untreated, gout may after several years progress to the advanced stage known as chronic tophacious gout. In this condition crystals of uric acid lodge as deposits of white, chalky material, or tophi, in soft body tissues and in and about the joints, where they may cause destruction of bone and bursitis. Large and deforming deposits may, after many years, settle in the outer margins of the ears, a characteristic feature of the disease. Chronic gout may also cause kidney damage, a condition called gouty nephropathy. In some people the accumulation of uric acid crystals in the kidneys leads to the formation of uric acid stones.
Treatment objectives include prevention of acute attacks, relief of the pain associated with acute attacks, avoidance of the formation of tophi and kidney stones, and prevention of gout-related disability. Acute attacks are commonly treated with orally administered nonsteroidal anti-inflammatory drugs (NSAIDs), such as indomethacin and naproxen, or with corticosteroids, given orally or injected into the affected joint or a muscle. An additional option is the alkaloid drug colchicine, which, however, may cause gastrointestinal problems in some individuals. Dietary restrictions may help reduce the severity of gout attacks; many doctors, for example, recommend limiting consumption of high-protein foods (such as meat, poultry, and fish), which can raise the level of uric acid in the blood. Chronic gout is usually treated by agents that promote excretion of uric acid, such as probenecid, and agents that inhibit production of uric acid, such as allopurinol. In some cases drug therapy proves insufficient, and it may be desirable to use surgical means to remove tophi and repair the affected joint.
Gout is sometimes confused with another inflammatory disorder–calcium pyrophosphate dihydrate deposition disease, acute attacks of which are often called pseudogout. Gout and pseudogout attacks may be characterized by similar symptoms, but their causes are different. Pseudogout results from deposits of calcium pyrophosphate dihydrate crystals, which weaken cartilage. The knees are a common site of severe attacks. Other joints that may be affected by pseudogout attacks include the wrists, shoulders, ankles, elbows, and hands.