Death from Hypersensitivity due to Phenylbutazone

Abstract

PHENYLBUTAZONE AND URIC ACID METABOLISM BEDI late from plasma uric acid readings before and after treatment the total loss of body uric acid and to correlate this calculation with the actual excess observed in the urine. Such a calculation is shown in Table VI. Case 4 is excluded, as measurements of actual body weight were not taken.Where more than one estimation of circulating uric acid was made before treatment the mean has been taken. Such calculations require certain assumptions which need not be discussed here. Nevertheless, if the falls in plasma levels were greater than could be accounted for by the excess excretion, clearly a consistent discrepancy would appear. In Cases 2 and 5 the discrepancy is small, and in Case 3 slightly more uric acid was excreted than can be accounted for by the fall in plasma levels.Only in Case 1 is there the sort of discrepancy which would be required to claim that the fall in plasma levels is greater than can be accounted for by the excess excretion. It was in this case, however, that an acute attack developed during the control period, with a rapid rise in blood levels. The excess excretion of uric acid during this period is more than enough to account for the change in total blood uric acid. Calculating the plasma volume as 0.051 body weight, and assuming that the fall is due to clearance by the kidneys, it would require an excess excretion of 243 mg. to reduce the level from 9.4 to 3 mg. per 100 ml. In the event 483 mg. was excreted in excess during the relevant period. ConclusionsThere are thus two possible effects exerted by phenylbutazone and influencing uric acid estimations: (1) uricosuric-while this is no more than a mild effect it is nevertheless sufficient to account for the observed fall in circulating urate levels; and (2) water retaining-this was sufficient to precipitate congestive heart failure in the one case in which a uricosuric effect was not observed.It is suggested that the variable preponderance of uricosuric and water-retaining effects would account for the variable findings. Much further evidence is required to establish still a third effect, on uric acid metabolism itself; and the fact that uric acid excretion may be increased when phenylbutazone is administered is against such a possibility. SummaryFour cases of gout and one control case were treated with phenylbutazone and the changes in plasma uric acid and urinary uric acid levels were studied.The findings suggest that phenylbutazone has no more than a slight uricosuric effect. This may be neutralized if considerable water retention occurs at the same time.No evidence was found that phenylbutazone has any direct effect on uric acid metabolism. Toxic effects of phenylbutazone have been described by a number of authors, and death has been ascribed mainly to agranulocytosis and to intestinal haemorrhage or perforation. A case is recorded in which death is attributed to a hypersensitivity reaction (in the course of phenylbutazone therapy). Case ReportThe patient was a man aged 73. Five years ago he b...

Foetal Defects Following Insulin Coma Therapy in Early Pregnancy

“…Bourne (1953) reported three patients in whom the lesion appeared obstructive, and\in another-not clinically jaundiced-granulomatous lesions were found in the portal tracts (O'Brien and Storey, 1954). In our patient the hepatitis appears to have been definitely toxic in nature.…”

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Giant-cell Granuloma of the Respiratory Tract (Wegener's Granulomatosis)

“…The initial lesion is that in the respiratory tract, a granulomatous inflammation spreading from the mucosa, but there is little doubt that subsequent thrombosis of small vessels contributes to the development of the large necrotic areas in nares, glottis, and lung. The widespread granulomata resemble those found in experimental serum sickness (Rich, 1942), "allergic granulomatosis " (Churg and Strauss, 1951), and many cases of fatal drug sensitivity (Waugh, 1952;O'Brien and Storey, 1954;Rasmussen, 1955;and others). The necrotizing vascular lesions are morphologically similar to those in polyarteritis nodosa of the " microscopic " variety (Davson et al, 1948), "hypersensitivity angiitis" (Zeek, 1952(Zeek, , 1953, and experimental hypersensitivity (Rich and Gregory, 1943;McKeown, 1947;Crawford and Nassim, 1951;Germuth et al, 1955;and others).…”

Megaloblastic Anaemia Induced by Phenylbutazone

“…Effects were seen particularly in the leucocytes and liver (Steinberg et al, 1953 ;Engleman et al, 1954), and fatal cases of generalized visceral involvement were found (O'Brien and Storey, 1954;MacCarthy and Jackson, 1955;Hodge and Lawrence, 1957)., In view of this, the drug was reintroduced at a lower dosage, 200 mg. daily.…”