GOUT DE WITT STETTEN, JR., M.D., Ph.D.* Gout, a disease peculiar to man, has afflicted the species since the dawn ofhistory and before. Among the earliest diseases to have been clearly described , it is also one ofthe first for which a specific remedy, still widely employed, was discovered. In part because ofthe exquisite pain which it produces, in part because ofits apparent association with men ofunusual accomplishment, gout has attracted, over the millennia, more than its legitimate share ofattention in both medical and literary history. The pain ofacute gouty arthritis has been variously described by many ofits victims , but perhaps the most frequently quoted word picture is due to the early nineteenth-century cleric and wit, Sydney Smith: "When I have gout, I feel as ifI am walking on my eyeballs." Despite the many years of observation and experimentation, despite its chemical and therapeutic peculiarities which might be expected to serve as guideposts and to simplify the problem, the origin ofgout and a satisfactory explanation ofits signs and symptoms still elude us. The earliest clear description ofgout is attributed to Hippocrates (about 500 B.c.), who segregated this disease from the welter ofarthritic diseases, the afflictions ofthejoints. Gout is far and away the earliest ofthe arthritides to be defined clinically. Among the characteristics which Hippocrates recognized was the high degree ofassociation with the male. Various modern authors have reported that 87-100 per cent of gout occurs in men, almost always commencing after puberty. When encountered in women, the disease generally is detected only after the menopause. A familial predisposition to gout has been recognized from early times, but even today it is not clear whether this predisposition is transmitted by a single dominant gene or by the cumulative action ofseveral genes. Both the male pre- * National Institute ofArthritis and Metabolic Diseases, Bethesda 14, Maryland. I85 ponderance and the familial nature of gout have found their place in our folklore: Lazy Tom withjacket blue, Stole his fadier's gouty shoe. The worst harm that Dad can wish him, Is his gouty shoe may fit him. Thus wrote Mother Goose in the sole reference to disease ofany kind in her verse. Gout is today recognized as being made up of two component parts. There is, onthe one hand, a recurrent acute arthritis and, onthe other hand, a chronic defect in metabolism which is manifested by hyperuricemia—an elevation above normal levels in the concentration ofuric acid in the blood. Great difficulty has been encountered in attempting to bridge the gap between these two aspects of the disease, and we shall therefore consider them separately. The onset ofclinical gout is an acute inflammation, with swelling, redness, local warmth, extreme pain, and exquisite tenderness of the soft tissues about one or more joints. Severaljoints may be involved simultaneously or serially, such as thejoints ofthe fingers, wrists, elbows, knees, ankles, and feet, but quite characteristically sooner or later the great toe is affected. Whereas the attack generally commences abrupdy, many older gouty patients learn to anticipate an acute attack by one or another prodrome, but the descriptions of these are not consistent. Descriptions ofthe pain ofacute gout are, however, consistent in regard to its severity. The vibration caused by a visitor walking in the room or the weight of the bed sheet on the affected extremity are all but unendurable. Clinical signs generally associated with infection may be present, but no infection can be demonstrated. Even if untreated, the acute arthritis of gout may subside after 1-6 weeks, leaving the patient completely free ofany residual disability. Months or even years may intervene between acute attacks. Various factors have been described which seem to precipitate attacks of acute gouty arthritis. These include skeletal fracture or other injury, surgical procedure, emotional stress, dietary indiscretion, or excessive alcoholic indulgence. To interrupt an acute attack, the physician has relied upon one drug of choice for the last fourteen centuries. The extract of Colchicum autumnale, the meadow saffron—containing what is now recognized as the alkaloid colchicine—has long been the sheet anchor oftherapy. It was introduced into the treatment of gout by Alexander of Tralles 186 DeWitt Stetten, Jr. ¦ Gout Perspectives in Biology and Medicine...