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Alireza Firooz, MD; Nargess Ghandi, MD; Zahra Hallaji, MD; Cheyda Chams-Davatchi, MD; Mahin Valikhani, MD; Mozhgan Karbakhsh Davari, MD

Arch Dermatol. 2008;144(9):1143-1147.

Objective  To evaluate the relationship between thiopurine methyltransferase (TPMT) activity and the safety and efficacy of azathioprine sodium in the treatment of pemphigus vulgaris.

Design  Cross-sectional study.

Setting  Referral university hospital for autoimmune blistering diseases.

Participants  One hundred thirty-nine patients with pemphigus vulgaris treated with azathioprine.

Intervention  The TPMT activity in red blood cells was measured using high-performance liquid chromatography.

Main Outcome Measure  Severe adverse effects were defined as those judged serious enough that azathioprine therapy be discontinued in 139 patients treated with azathioprine. To evaluate the relationship of clinical response and TPMT concentration in 52 patients who had been treated with a combination of prednisolone and azathioprine only for at least 1 year were included in the study, and the clinical response was considered favorable if there was no recurrence of pemphigus vulgaris in the first year of treatment.

Results  The median activity of TPMT was 44.7 ng/mL/h (interquartile range, 28.7 ng/mL/h). Eleven patients (7.9%) had low TPMT activity (TPMT-HL), 127 patients (91.4%) had normal TPMT activity (TPMT-HH), and 1 patient (0.7%) had supranormal enzyme activity; TPMT activity was noted in all patients. Serious adverse effects occurred in 14 patients (10.1%). There was no relationship between development of adverse effects and TPMT activity (P = .29). Eleven patients with low TMPT activity had been treated with azathioprine for a mean (SD) of 10.2 (4.1) months. Only 1 patient exhibited serious adverse effects. The TPMT enzyme activity was not different in 28 patients with unfavorable clinical response compared with 24 patients with favorable clinical response (P = .09).

Conclusion  Larger prospective studies are needed to determine the clinical relevance of TPMT activity and to determine accurate azathioprine dosing guidelines based on TPMT activity.

Author Affiliations: Center for Research & Training in Skin Diseases & Leprosy (Dr Firooz) and Departments of Dermatology, Razi Skin Hospital (Drs Ghandi, Hallaji, Chams-Davatchi, and Valikhani) and Social Medicine (Dr Karbakhsh Davari), Tehran University of Medical Sciences, Tehran, Iran.

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