Sodium salicylate and probenecid in the treatment of chronic gout; assessment of their relative effects in lowering serum uric acid levels.

Very little is known about the aetiology of acute attacks of gout or the mode of action of colchicine in relieving them. Their relationship to high serum uric acid levels and urate deposition is obscure, for maintaining serum levels at normal together with a negative urate balance does not prevent their occurrence. Fortunately the vast majority of acute attacks readily respond to colchicine in proper dosage, and the few exceptions may be treated with phenylbutazone ("Butazolidin"). Unlike the acute variety, chronic gout appears to be closely related to high serum and tissue fluid uric acid levels with supersaturation and deposition of urates in various tissues, especially joint structures and bursae. Uric acid deposition induces a chronic inflammatory reaction, and increasing size of the deposits leads to progressive and even total destruction of the affected joints. Urate deposition is often confirmed by the presence of tophi, but even in their absence it may be inferred by isotopic uric acid dilution studies. Such studies have shown that the miscible pool of uric acid in normal adults ranges from 731 to 1,341 mg. (Benedict, Forsham, and Stetten, 1949; Geren, Bendich, Bodansky, and Brown, 1950; Bishop, Garner, and Talbott, 1951). In gouty persons the miscible pool is greatly increased and may be as high as 30,000 mg. (Benedict and others, 1950). This enormous increase cannot be accounted for by uric acid in solution and must indicate the presence of solid phase urate which has taken part in dilution of the isotope. The patient with chronic gout complains of increasing stiffness, pain, and deformity of one or more joints, symptoms which are unaffected by colchicine and which ultimately give rise to severe crippling and invalidism. Until 1950, it had not been found possible to maintain the serum uric acid at normal levels, and the progress of chronic gouty changes had never been arrested. Since 1950,