Chlorpropamide-induced granulomas. A probable hypersensitivity reaction in liver and bone marrow

Abstract

Anicteric hepatitis, associated with fever and exfoliative dermatitis, developed in a diabetic patient two weeks after intake of a long-acting sulfonylurea, chlorpropamide (Diabinese). Granulomas showing heavy infiltration with eosinophils were found in the liver and bone marrow. These were interpreted as manifestations of an allergic reaction. The clinical signs, abnormal laboratory findings, and hepatic lesions subsided spontaneously on withdrawal of the drug. Bone marrow changes, however, persisted seven months after cessation of the drug. To our knowledge, this is the first report of a patient with liver and bone marrow inflammation characterized by granulomas with eosinophilic infiltration following intake of chlorpropamide.

Hepatotoxicity of Drugs Used for Treatment of Obesity and Its Comorbidities

“…Furthermore, an interesting pathological study that compared autopsy findings of dialysis patients who used intraperitoneal insulin to controls who used intraperitoneal dialysis without insulin showed subcapsular steatosis and/or steatonecrosis only in the insulin-using group. 24 Since then, several 29,32,119,120 Glibenclamide/glyburide Oral sulfonylurea Cholestasis, hepatitis, liver failure [33][34][35][36]121 Tolbutamide Oral sulfonylurea Hepatitis, jaundice 122,123…”

“…The incidence of reported toxicity for the sulfonylureas is 1%, 29 and is felt to be caused by hypersensitivity to the sulfa moiety. [29][30][31][32] The most common liver abnormality is cholestasis. 31,33,34 Granulomatous hepatitis has also been reported with glyburide and chlorpropamide, and has been shown to improve on liver biopsy after discontinuation of the sulfonylurea.…”

“…31,33,34 Granulomatous hepatitis has also been reported with glyburide and chlorpropamide, and has been shown to improve on liver biopsy after discontinuation of the sulfonylurea. 32,35 Significant cytotoxic injury (transaminase elevations above ten times normal with consistent pathology) has been reported within 1 to 2 months of instituting glyburide. 36 Tolazamide has been implicated in one case of chronic liver disease, where cholestasis persisted for 4 months after discontinuation of the drug, and biopsy showed bridging fibrosis.…”

Diagnosis of Hepatic Granulomas: A Review1

“…Drug rechallenge has almost never been carried out. Only a handful of predominantly single case studies are available and of these phenylbutazone (Ishak et al 1977), sulphonamide (Espiritu et al 1967), chlorpropamide (Rigberg et al 1976), allopurinol (Medline et al 1978), hydralazine (Jori & Peschle 1973), halothane (Dordal et al 1970) and quinidine (Geltner et al 1976) fulfil the criteria. However, McMaster & Hennigar (1981) have suggested that many cases of drug-induced hepatic granulomas are probably being missed, for they concluded that 28 cases in their own retrospective survey of 95 patients were probably (14 cases) or possibly (14 cases) related to drugs.…”