title: Thiopurine S-methyltransferase genotypic analysis in autoimmune bullous diseases.
abstract: Thiopurine S-methyltransferase (TPMT) activity is inversely related to the risk of developing severe hematopoietic toxicity in patients treated with azathioprine. The aim of this study was to evaluate the usefulness of TPMT genotyping in severe cases of autoimmune bullous diseases treated with azathioprine. A retrospective study of TPMT genotyping was performed in patients with autoimmune bullous diseases hospitalized in a single centre between 1999 and 2006 and susceptible of being treated by azathioprine. Among 75 patients tested, 70 (93%) had a high TPMT activity and 5 (7%) an intermediate activity. TPMT genotyping was performed in 33/34 patients currently treated with azathioprine. Haematopoietic side-effects (usually moderate) were observed in 12/34 patients treated with a mean dosage of 2.7 mg/kg/day and occurred, despite a high predicted TPMT activity. No myelotoxicity was observed in the two patients with intermediate predicted TPMT activity (mean dosage: 1.7 mg/kg/day), who obtained a clinically complete remission. Although strongly recommended before azathioprine treatment, predicting TPMT activity appears only marginally helpful in patients with autoimmune bullous diseases, mainly for adjusting the azathioprine dosage. In addition, a normal TPMT genotyping is not a guarantee against the occurrence of haematological side-effects.
authors.affiliation: Department of Dermatology, Hôpital Robert-Debré, Centre Hospitalier de Reims, avenue du Général Koenig, 51092 Reims Cedex, France.
authors.forename: Maud
authors.initials: M
authors.lastname: Bezier
authors.forename: Ziad
authors.initials: Z
authors.lastname: Reguiai
authors.forename: Fabien
authors.initials: F
authors.lastname: Vitry
authors.forename: Franck
authors.initials: F
authors.lastname: Broly
authors.forename: Philippe
authors.initials: P
authors.lastname: Bernard
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001327:Autoimmune Diseases / Q000201:enzymology / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008780:Methyltransferases / Q000235:genetics*; D008875:Middle Aged; D012189:Retrospective Studies; D012872:Skin Diseases, Vesiculobullous / Q000201:enzymology / Q000235:genetics*
chemical_list: D008780:Methyltransferases; C022745:thiopurine methyltransferase