Occurrence of three cases of carcinoma in individuals with Crohn's disease treated with metronidazole.

Controversy exists regarding the safety of metronidazole. Experimental studies have suggested both a carcinogenic and mutagenic effect in animals. In women treated with metronidazole for trichomoniasis which involves low dosages and short time periods, no carcinogenic effect was noted. Metronidazole is also used in the treatment of Crohn's disease which involves larger dosages over longer periods of time. The authors have recently encountered three individuals with Crohn's disease who were treated with large doses of metronidazole and who developed a malignancy [breast (two) and cholangiocarcinoma] at a rather young age (32, 31, and 27 years, respectively). Whereas this association based on three cases is not per se incriminatory or even suggestive, nevertheless, the cases are unusual and we urge prospective and long-term follow-up studies on individuals being treated with large doses of metronidazole over prolonged periods of time. Metronidazole (Flagyl) was introduced into The United States in the 1960's for the treatment of trichomoniasis (1). The conditions for which this drug is indicated and has been used have expanded to include such diverse entities as amebiasis (2), brain abscess (3), and Crohn's disease (4). A controversy exists regarding the safety of this drug (5, 6). Experimental studies have shown that metronidazole is both carcinogenic and mutagenic (7-9). However, a recent study (10) cited lack of evidence for a carcinogenic effect with the use of metronidazole in women treated for trichomoniasis. In the past 1 1/2 years we have encountered three unusual cases involving individuals who were treated with large doses of metronidazole for Crohn's disease and who developed a malignant neoplasm at a relatively young age. The features of these three cases are the subject of this report.