[Cytolytic hepatitis during treatment with phenothiazines: apropos of a case]

In contrast to the well known chlorpromazine-induced cholestatic hepatitis, we report the case of a schizophrenic patient who presents a cytolytic hepatitis, without any prior hepatic disease. Mr G. was first hospitalized for depressive symptomatology. A pseudo-nevrotic schizophrenia was diagnosed. Pretherapeutic clinical and biological data were normal. A treatment with chlorpromazine 400 mg/day was given. At day 8, the patient was still anxious and began to be agitated. An increase to 500 mg/day of chlorpromazine posology and an addition of haloperidol 200 mg/day was implemented. At day 10, the following clinical symptoms appeared: 38.6 degrees C fever; headache; myalgia; epigastralgia and hypocondrium pain. Biological hepatitis disturbances (ALAT, 984 U/L; ASAT, 414 U/L) and hypereosinophilia with normal white cell count were found. Clinical and biological investigations were normal. Blood-culture, A, B, C hepatitis, HIV and CMV serologies were negative. Neuroleptic treatment was discontinued. Evolution to normality of the disturbances and biological data suggested a cytolytic hepatitis. Mr G... remained treated with flupentixol without side-effects. Phenothiazine-induced cholestatis is frequent, mild, and recovers spontaneously. The biological mechanism is supposed to be immunologic. Prevalence of biological hepatic disturbances is 10 to 20% with chlorpromazine in long-term treatment. More often, symptomatology is the same; jaundice, pruritus, abdominal pain, fever. Although pharmacological data suggest for a cytotoxic activity of phenothiazines, cytolytic hepatitis is poorly described. Maximum range of transaminase blood level reported in previous studies is about 400 U/l. This level is not clearly correlated with hepatic cell lysis. Few cases of hepatic necrosis have been reported. In all cases, preexistent hepatic injuries were observed. Chlorpromazine-induced cytolytic hepatitis is uncommon and cholestatic hepatitis mild. Biological hepatic parameters investigations remain necessary during neuroleptic treatment.