LETTER
Case Reports and Causality
Fred I. Gilbert, Jr., MD
15 April 1994 | Volume 120 Issue 8 | Page 696
TO THE EDITOR:
The authors of the computer-generated case–control study of acute liver disease associated with certain antibiotics [1] correctly stated that "case reports and case series suffer from the absence of a control group, making any causal relations difficult to determine". It is also true that case–control studies done retrospectively from prospectively structured computer-stored data often do not permit the more creative insights that result from deeper analysis of individual cases.
However, it was an intensive study of a single case in 1961 [2] and a review of similar case reports that led to the conclusion that esterification at a particular site of the erythromycin molecule was responsible for the induction of cholestatic hepatitis; that erythromycin estolate, the ester of erythromycin base, was capable of inducing hepatitis on the basis of hypersensitivity rather than toxicity; and that the nonesterified erythromycin base lacked the capability of inducing hepatitis. Although this causal relation was difficult to determine by a full-time general internist, particularly more than 30 years ago, it did result in descriptive drug inserts by pharmaceutical companies that advocated caution regarding the possibility of erythromycin estolate-induced hepatitis. This relation is probably why the authors found no use of erythromycin estolate in their series.
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Author and Article Information
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Straub Clinic and Hospital; Hanalulu, HI 96813
1. Carson JL, Strom BL, Duff A, Gupta A, Shaw M, Lundin FE, et al. Acute liver disease associated with erythromycins, sulfonamides, and tetracyclines. Ann Intern Med. 1993; 119:576-83.
2. Gilbert F. Cholestatic hepatitis caused by esters of erythromycin and oleandomycin. JAMA. 1962; 182:1048-50.
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