erythromycin-estolate and Drug-Hypersensitivity

Primary cultures of rat hepatocytes were exposed to several concentrations of erythromycin estolate (EE). Hepatotoxicity was evaluated using lactate dehydrogenase (LDH) leakage and morphometric analysis of representative populations of cells examined optically. Results of the two techniques provided parallel information: cells exposed to the higher concentrations of EE had significantly greater LDH release and higher percentages of morphologically damaged cells. Planimetric analysis of a second set of hepatocytes showed increasing swelling of cells with increasing concentration of EE. Severe cellular swelling preceded disintegration, as hepatocytes became progressively more damaged by EE.

Topics: Animals; Cells, Cultured; Dose-Response Relationship, Drug; Drug Hypersensitivity; Erythromycin; Erythromycin Estolate; L-Lactate Dehydrogenase; Liver; Rats; Rats, Inbred Strains

A combined cholestatic and hepatocellular injury occurred in nine patients, following therapy with erythromycin estolate (EE) or other erythromycin derivatives. Eight of the nine patients developed jaundice within three weeks after initiation of treatment; pain was one of the main symptoms in five patients while fever and itching were noted in four patients. Symptoms and signs subsided and abnormal tests of liver function returned to normal after withdrawal of the drug. The major histologic finding was cholestasis, but the majority of cases also had evidence of hepatocellular injury of variable severity; one biopsy specimen showed centrilobular necrosis. Ultrastructural findings in one case included changes related to cholestasis as well as hepatocellular injury with striking mitochondrial abnormalities. Our data are compared with those of the literature, with special reference to morphologic features.

Topics: Adolescent; Adult; Cholestasis; Drug Hypersensitivity; Erythromycin; Erythromycin Estolate; Female; Histocytochemistry; Humans; Jaundice; Liver; Male; Microscopy, Electron; Middle Aged; Mitochondria, Liver; Necrosis; Racial Groups; Time Factors

A 53-year-old housewife who had developed severe cholestatic hepatitis following the administration of erythromycin estolate therapy two-and-a-half years previously, was studied by an in vitro "challenge" test in which peripheral venous lymphocytes were cultured in the presence of erythromycin estolate, erythromycin stearate and erythromycin base. Evidence of blastogenesis was observed in response to erythromycin estolate, but not to erythromycin stearate of erythromycin base. This test thus provided evidence that the patient was "sensitized" to erythromycin estolate without exposing her to the risk of in vivo challenge. Furthermore, in contrast to previous studies, the findings provide evidence that erythromycin estolate jaundice is mediated by immunological mechanisms.

Topics: Drug Hypersensitivity; Erythromycin; Erythromycin Estolate; Female; Humans; Jaundice; Lymphocyte Activation; Middle Aged

Topics: Alkaline Phosphatase; Bilirubin; Chemical and Drug Induced Liver Injury; Clinical Enzyme Tests; Drug Hypersensitivity; Erythromycin; Erythromycin Estolate; Hepatitis A; Jaundice; Liver Diseases; Liver Function Tests; Sodium Dodecyl Sulfate; Toxicology; Transaminases

Topics: Abdominal Pain; Cholestasis, Intrahepatic; Drug Hypersensitivity; Erythromycin; Erythromycin Estolate; Humans; Jaundice