C Sachs1, M Tebacher-Alt2, M Mark3, B Cribier1, D Lipsker4. 1. Clinique dermatologique, université de Strasbourg, hôpitaux universitaires de Strasbourg, 1, place de l'Hôpital, 67091 Strasbourg cedex, France. 2. Service de pharmacovigilance, université de Strasbourg, hôpitaux universitaires de Strasbourg, 1, place de l'Hôpital, 67091 Strasbourg cedex, France. 3. Service de biologie du développement et de la reproduction, université de Strasbourg, hôpitaux universitaires de Strasbourg, 1, place de l'Hôpital, 67091 Strasbourg cedex, France. 4. Clinique dermatologique, université de Strasbourg, hôpitaux universitaires de Strasbourg, 1, place de l'Hôpital, 67091 Strasbourg cedex, France. Electronic address: dan.lipsker@chru-strasbourg.fr.
Abstract
BACKGROUND: Aplasia cutis congenita (ACC) following in utero exposure to antithyroid drugs such as methimazole/carbimazole (MTZ/CMZ) has been reported since 1972. Though currently included in MTZ/CMZ embryopathy, it remains poorly characterized and is little discussed. Having seen two cases within a short period of time, we carried out a literature review and searched the French pharmacovigilance database for notification of cases. PATIENTS AND METHODS: We performed a search of the literature in the Medline database using the following keywords: "aplasia cutis congenita", "birth skin defects", "pregnancy" and "drug". All articles reporting cases of ACC following in utero exposure to antithyroid drugs were included. All cases of ACC under antithyroid drugs reported to French pharmacovigilance centres were analysed. RESULTS: Three hundred and sixty-eight articles were retrieved and 31 were analysed, including a further 4, mentioned in selected articles, giving 59 cases of ACC under MTZ/CMZ reported in the literature and having an intrinsic accountability score of plausible or dubious. ACC was typically isolated, single, small in size, and localised on the median scalp area. Exposure occurred in the first weeks of gestation. There were 6 familial cases involving siblings. Ten ACC and MTZ/CMZ cases were reported to pharmacovigilance centres in France. DISCUSSION: Practitioners should be aware of ACC following MTZ/CMZ exposure in utero, whether it occurs in isolation or not. It is likely a teratogenic effect of MTZ/CMZ enhanced by a genetic predisposition.
BACKGROUND:Aplasia cutis congenita (ACC) following in utero exposure to antithyroid drugs such as methimazole/carbimazole (MTZ/CMZ) has been reported since 1972. Though currently included in MTZ/CMZembryopathy, it remains poorly characterized and is little discussed. Having seen two cases within a short period of time, we carried out a literature review and searched the French pharmacovigilance database for notification of cases. PATIENTS AND METHODS: We performed a search of the literature in the Medline database using the following keywords: "aplasia cutis congenita", "birth skin defects", "pregnancy" and "drug". All articles reporting cases of ACC following in utero exposure to antithyroid drugs were included. All cases of ACC under antithyroid drugs reported to French pharmacovigilance centres were analysed. RESULTS: Three hundred and sixty-eight articles were retrieved and 31 were analysed, including a further 4, mentioned in selected articles, giving 59 cases of ACC under MTZ/CMZ reported in the literature and having an intrinsic accountability score of plausible or dubious. ACC was typically isolated, single, small in size, and localised on the median scalp area. Exposure occurred in the first weeks of gestation. There were 6 familial cases involving siblings. Ten ACC and MTZ/CMZ cases were reported to pharmacovigilance centres in France. DISCUSSION: Practitioners should be aware of ACC following MTZ/CMZ exposure in utero, whether it occurs in isolation or not. It is likely a teratogenic effect of MTZ/CMZ enhanced by a genetic predisposition.