The old and new concepts of acute gouty arthritis.

Abstract

CUTE GOUTY ARTHRITIS was regarded by Garrod in 1876 as an inA flammatory reaction to crystals of sodium urate that had been deposited in and about the joint. He further concluded that a local deposition of sodium urate occurred during the acute attack.l Much of his evidence for such a concept was tenuous by modern concepts and failure of investigators during subsequent years to obtain experimental evidence in support of his hypothesis gradually led to its abandonment. In the past two decades most investigators have denied a role for sodium urate in the pathogenesis of the acute attack of gouty arthritis although there has been no firm evidence for such a denial. The reported failure of injected sodium urate to give rise to an inflammatory response,2 as well as the generally painless development of gouty tophi, have constituted the central argument against Garrods hypothesis. In like manner, the failure of intravenously injected solutions of sodium urate to produce an acute arthritis, as well as the relative infrequency with which gout is seen in other clinical conditions associated with hyperuricemia, such as chronic nephritis and certain malignancies, have constituted further arguments against a direct role for uric acid in acute gout.3 Additional evidence has been marshalled in a seeming paradox whereby uricosuric drugs are of no benefit in the treatment of the acute attack of gouty arthritis and their use may even result in an exacerbation of the acute atta~k.~ By contrast, colchicine, which has no known effect on urate metabolism or excretion, is of remarkable therapeutic effectiveness in this disease. A multitude of proposals have been made to account for acute gouty arthritis. An abnormality in endocrine function, originally proposed by Wolfson, was not substantiated. A vascular abnormality was proposed to account for the propensity for involvement of the first metatarsophalangeal joint. Allergy and hypersensitivity have also been proposed.; The possibility that a defect in intermediary purine metabolism might give rise to the acute arthritis has been explored with the observation by Weissman and Gutman of an increased excretion of 8-hydroxy-7-methyl-guanine during acute attacks of gouty arthritis and a decreased excretion of 6-succinoaminopurine during an acute attack.6 An increased excretion of pseudouridine has also recently been noted among gouty subjects. The possibility that acute gouty arthritis might be related to hyperuricemia only by proximity of genes along the chromosome has also been ~onsidered.~ Evidence from a variety of types of investigations and observations in recent years has prompted the re-investigation of Garrods original hypothesis for the genesis of acute gouty arthritis. Reports of acute gouty arthritis developing in individuals with no pre-existing hyperuricemia or family history of gout, in whom a hyperuricemia had been produced by administration of