Thiopurine Methyltransferase Levels and Azathioprine Outcomes in Thai Patients with Cutaneous Autoimmune Diseases

Purit Pureesrisak,1,2 Oraya Kwangsukstid,1 Pinnaree Kattipathanapong,1 Tanawatt Kootiratrakarn,1 Chonlaphat Sukasem,3 Dumrong Mairiang,4,5 Wenika Channakorn,1 Daraka Phainupong,1 Mingkwan Suphannaphong1 1Institute of Dermatology, Bangkok, Thailand; 2Division of Dermatology, Department of Medicine, Rajavithi Hospital, College of Medicine, Rangsit University, Bangkok, Thailand; 3Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Bangkok, Thailand; 4Division of Dengue Hemorrhagic Fever Research, Research Department, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand; 5Molecular Biology of Dengue and Flaviviruses Research Team, National Center for Genetic, Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Pathum Thani, ThailandCorrespondence: Oraya Kwangsukstid, Institute of Dermatology, Bangkok, Thailand, Email [email protected]: Thiopurine methyltransferase (TPMT) is responsible for the inactivation of azathioprine, and is widely used to treat cutaneous autoimmune diseases. TPMT activity is inherited as an autosomal codominant trait and ranges from high to undetectable levels in different individuals. Low TPMT activity may result in a higher risk of adverse effects (AEs), whereas high TPMT activity may result in potential treatment failure.Objective: To assess TPMT levels in patients with cutaneous autoimmune diseases and evaluate the correlation between TPMT levels and AEs of azathioprine and clinical response in patients with pemphigus.Methods: A cross-sectional study was conducted in 300 patients with cutaneous autoimmune diseases. Blood samples were collected to identify TPMT levels by ELISA. In 10 patients with the lowest TPMT levels, subsequent PCR analysis for the TPMT genotype was performed.Results: Among 300 patients, pemphigus vulgaris was diagnosed in 93 (31%), lupus erythematosus in 93 (31%), pemphigus foliaceus in 39 (13%), bullous pemphigoid in 32 (10.7%), systemic sclerosis in 26 (8.7%), and other diseases in 17 (5.6%). The mean TPMT level was 84.9 ± 30.5 mU/mL. Alcohol consumption significantly correlated with lower TPMT levels (p = 0.005). TPMT levels were not correlated with AEs (p = 0.184). The TPMT genotype showed TPMT*1/*1 (wild-type) in all 10 patients with the lowest TPMT levels. In the pemphigus group, the TPMT level did not correlate with clinical response (p = 0.363).Conclusion: Alcohol consumption resulted in lower TPMT levels. TPMT levels did not correlate with clinical response in the pemphigus group and AEs. These findings provide real-world clinical insight in Thai patients, where routine TPMT screening is not universally implemented, highlighting the need for alternative predictors of azathioprine toxicity.Keywords: azathioprine, thiopurine methyltransferase, pharmacogenetics, pemphigus, autoimmune skin diseases