Diagnosis and Treatment of Gouty Arthritis JOHN H. TALBOTT, M.D., Buffalo. New York AN ADEQUATE UNDERSTANDING of the approach to the * The characteristic phenomena of acute gouty diagnosis of a clinical entity and an effective regi- arthritis are'acute arthritis in a middle-aged men of therapy should be based upon accepted con- male, associated with serum uric acid above 6 cepts of normal and abnormal function. Diseases mg. per 100 cc. and a satisfactory response to that are identified as metabolic disturbances serve as coichicine. Roentgenographically observable good examples. Although gout is not the example par changes do not occur early. excellence, a clinical discussion of this dyscrasia In recent years uric acid metabolism has may be developed from accepted physiological and been studied by means of isotope techniques biochemical phenomena. utilizing labeled substances. Uric acid is ex- The clinical finding of acute arthritis associated creted in relatively constant amounts by humans with the cardinal signs of inflammation in a male and is little affected by variations in dietary should suggest gout as one possibility. If it is pres- intake, except for purine or nucleic acid sub- ent the amount of uric acid in the serum will be stances. Persons with gout have a greater total above 6 mg. per 100 cc., and if -a "full course" of amount of uric acid and a lower turnover than colchicine is administered, the acute articular symp- normal persons. toms should subside. These items-a characteristic In the treatment of acute affacks of gout col- clinical picture, an elevation of serum urate and a chicine is still the most practical single drug, satisfactory response to colchicine-constitute the even though its pharmacologic action remains triad of acute gouty arthritis. Elaboration and ex- unknown. tension of these phenomena will constitute the basis Benemid (probenecid) is a powerful urico- of this discussion. suric agent of /ow toxicity which has been sub- The initial attack of acute gouty arthritis usually jected to extensive clinical trial for three years. appears in the middle decades of life but it may ap- It causes inhibition of the resorption of urate pear as early as the first decade or as late as the from the glomerular filtrate; the site of action eighth. The disease affects males predominantly; is believed to be the tubular cells. The author's fewer than five per cent of patients are females. So usual dose is 2 gm. a day. This has caused a infrequently does the disease occur in females that lowering of the uric acid in the serum and an a clinician must exercise unusual acumen in making increase in the urinary output. a diagnosis of gout in a female if subcutaneous tophi have not developed. About two-thirds of a series of patients observed by the author had a fam- gical operation, meteorologic changes, emotional ily history positive for gout. This datum frequently turmoil, one of several drugs which include a mer- is helpful in diagnosis during the earlier years of the curial diuretic and antibiotics, particularly penicillin disease if stigmata of the well-developed case of and the vitamin B preparations administered paren- gout are lacking. Acute attacks are likely to affect terally, have been so implicated. The suddenness in the metatarsal-phalangeal joint of the great toe, but onset and the severity of pain in a previously asymp- they may involve any joint or joints in the upper tomatic male are typical. Complete restoration of or lower extremities. If the central joints of the body function may be expected if chronic deforming ar- are afflicted, tophaceous deposits usually have de- ticular changes are absent. veloped and the diagnosis is not in doubt. Observation of a concentration of uric acid in the Acute gouty arthritis may appear following the serum is of considerable help in diagnosis if properly impact of one of several precipitating agents or it determined, but may be misleading in selected in- may appear spontaneously. An acute infection, a sur- stances. The determination in the routine biochem- From the Department of Medicine, University of Buffalo School ical laboratory is more difficult than several of other of Medicine and the Buffalo General Hospital. The researches reported upon herein were supported in part by a routine procedures. Uricosuric agents such as so- grant-in-aid from the National Institutes of Health, Bethesda, Md. dium salicylate, cinchophen, corticotropin (ACTH) Guest Speaker's Address: Part of a Panel Discussion on Gout and Arthritis presented before the Section on General Medicine at and Butazoliding are anti-arthritic agents that may the 82nd Annual Session of the California Medical Association, Los Angeles, May 24-28, 1953. depress an elevated urate concentration and cause 220 CALIFORNIA MEDICINE confusion. Known uricosuric agents should be omit- concept of renal function was widely accepted. At ted for at least 48 hours if diagnostic information is the moment it is believed that uric acid appears in sought regarding the concentration of uric acid in glomerular filtrate in essentially the same concentra- the serum. tion as it exists in a protein-free filtrate of plasma. The response to a "full course" of colchicine is The glomerular filtrate is acted upon by the tubular highly specific. No other disease of the joints re- cells and approximately 90 per cent of the urate is sponds so well to this drug. The other anti-arthritic resorbed and only 10 per cent is excreted in bladder drugs which include sodium salicylate, corticotropin urine. and Butazolidin are endowed with limited diagnostic If expressed in functional terms, the urate clear- capacity. A "full course" of colchicine will be de- ance is approximately 10 cc. per minute. This implies scribed later. that the quantity of uric acid contained in 10 cc. of Conditions other than gout which may be asso- plasma is excreted from the body in this unit of ciated with increased concentration of serum urate time. This may be compared in a controlled experi- include acute febrile illness, renal insufficiency, leu- ment with the clearance of water of 2 cc. per minute kemia and selected other blood dyscrasis. It is note- and the clearance of urea of 65 cc. per minute. If worthy that increased concentration of uric acid in 10 per cent of uric acid that appears in glomerular the serum occurs relatively often in non-arthritic filtrate is excreted and 90 per cent is resorbed, it relatives of gouty patients. Furthermore, in a series might be in the realm of possibility to alter this pro- of "normal" persons a small proportion may show portion by interfering with tubular resorption. The an increased concentration of serum urate that is not uricosuric agents noted above are believed to act in explained satisfactorily. The determination of serum this manner. Furthermore, it has been demonstrated urate in a multiphasic screening project as a public that when the sugar content of the blood is high- health effort is to be encouraged. 400 mg. per 100 cc. or greater-the tubules are sat- Roentgenographic evidence of articular disease is urated and working maximally in resorbing glucose not an early finding in patients with gout. A decade from glomerular filtrate and the excretion of urate or more may elapse following the initial attack of is enhanced. It has been postulated that in such cir- acute gouty arthritis before the characteristic roent- cumstances the resorption of glucose takes prece- genographic changes are present. Not infrequently dence over resorption of urate and for a time the in a mild case of gout no changes will be noted in tubules do not extract the usual amount of uric acid. unmagnified images throughout the natural life of In recent years another phase of uric acid metabo- the patient. With the development of a satisfactory lism has been approached through the use of iso- technique for magnified roentgenography, character- topes, radioactive and heavy isotopes alike. Selected istic changes may be detected in some patients at an studies in humans and in animals utilizing labeled earlier stage of the disease. substances have shed considerable light upon the Circumstantial evidence suggestive of gout in- precursors of uric acid. It has been known for some cludes low grade albuminuria, hypertension, large time that uric acid is the end-product of nitrogenous vessel sclerosis and urate calculi. It is not believed substances of amino acid and pyrimidin origin. that coronary sclerosis in the absence of articular Most other mammals convert uric acid to allantoin gout is intimately related to the metabolic dyscrasia. and excrete only small amounts of uric acid. Birds of uric in the and reptiles excrete uric acid as the end-product The increased concentration of acid of or amino serum reflects a similar concentration in the syno- nitrogenous substances whether purine vial fluid and probably other interstitial fluids except acid origin. those associated with the central nervous system. The Uric acid is excreted in relatively constant mechanism by which increased concentration of uric amounts by humans and is little affected by varia- acid in body fluids is brought about is not known tions in dietary intake except for purine or nucleic but certain presumptions have been advanced. There acid substances. At least 300 mg. of nitrogenous are at least three reasonable possibilities to account urate is excreted daily on a purine-free diet with an for the increased concentration: Decreased destruc- adequate caloric intake.1" It is generally accepted tion, impaired excretion or increased formation. that mammals are capable of synthesizing purines There is meager evidence only that gouty patients as well as of converting purines to uric acid. It has are deficient in uricolytic enzymes.