{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T18:10:03Z","timestamp":1747678203154,"version":"3.40.5"},"reference-count":15,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,10,26]],"date-time":"2024-10-26T00:00:00Z","timestamp":1729900800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Dermatology"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Autoimmune blistering diseases (AIBDs), classified into pemphigus and pemphigoid, consist of relatively rare skin disorders caused by autoantibodies that target desmosomal and hemidesmosomal proteins, respectively. Although systemic corticosteroids are used as a first\u2010line treatment for AIBDs, azathioprine is frequently co\u2010administered as a steroid\u2010sparing agent. Azathioprine is metabolized into thioguanine nucleotides (TGNs) which are its major active metabolites. The enzyme nudix hydrolase 15 (NUDT15) plays a key role in regulating TGNs. Serious side effects of azathioprine, including leukopenia and alopecia, are known to be particularly problematic in individuals with <jats:italic>NUDT15<\/jats:italic> variants. The single\u2010nucleotide polymorphism c.415C &gt;T (p.Arg139Cys) is one of the most frequent <jats:italic>NUDT15<\/jats:italic> variants associated with severe thiopurine toxicity. Recently, we treated a case of pemphigus vulgaris in a patient with <jats:italic>NUDT15<\/jats:italic> variants in which the patient developed rapidly progressive diffuse hair loss and myelosuppression while receiving azathioprine. Previous reports on <jats:italic>NUDT15<\/jats:italic> polymorphisms mainly focused on patients with inflammatory bowel disease or hematological malignancies, and the prevalence of <jats:italic>NUDT15<\/jats:italic> polymorphisms remains unknown in AIBDs. This highlights the urgent need for research on <jats:italic>NUDT15<\/jats:italic> polymorphisms in AIBDs to achieve a better understanding of the genetic factors influencing adverse reactions to azathioprine. To clarify the prevalence of <jats:italic>NUDT15<\/jats:italic> variants in Japanese patients with AIBDs, we retrospectively reviewed the medical records of 78 patients with AIBDs (26 with bullous pemphigoid, 26 with pemphigus vulgaris, 17 with pemphigus foliaceus, and nine with other AIBDs) who had come to Hokkaido University Hospital between 2018 and 2023. The frequencies of <jats:italic>NUDT15<\/jats:italic> variants of Arg\/Arg, Arg\/Cys, and Cys\/Cys in these patients were approximately 72%, 23%, and 5%, respectively. Our findings indicate a prevalence of <jats:italic>NUDT15<\/jats:italic> variants in AIBD patients that is similar to the prevalences of previous studies on patients with other diseases. These results emphasize the importance of screening for <jats:italic>NUDT15<\/jats:italic> variants prior to initiating azathioprine treatment in Japanese patients with AIBDs.<\/jats:p>","DOI":"10.1111\/1346-8138.17515","type":"journal-article","created":{"date-parts":[[2024,10,26]],"date-time":"2024-10-26T07:24:27Z","timestamp":1729927467000},"page":"363-366","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A case of rapidly progressive hair loss due to azathioprine, and the prevalence of <scp>NUDT15<\/scp> variants among Japanese patients with autoimmune blistering diseases: A single\u2010center retrospective observational study"],"prefix":"10.1111","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0188-3717","authenticated-orcid":false,"given":"Sho","family":"Katayama","sequence":"first","affiliation":[{"name":"Department of Dermatology Faculty of Medicine and Graduate School of Medicine, Hokkaido University  Sapporo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kentaro","family":"Izumi","sequence":"additional","affiliation":[{"name":"Department of Dermatology Faculty of Medicine and Graduate School of Medicine, Hokkaido University  Sapporo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7931-949X","authenticated-orcid":false,"given":"Inkin","family":"Ujiie","sequence":"additional","affiliation":[{"name":"Department of Dermatology Faculty of Medicine and Graduate School of Medicine, Hokkaido University  Sapporo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3489-5418","authenticated-orcid":false,"given":"Hideyuki","family":"Ujiie","sequence":"additional","affiliation":[{"name":"Department of Dermatology Faculty of Medicine and Graduate School of Medicine, Hokkaido University  Sapporo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,10,26]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/1346-8138.14588"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2019.0709"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/1346-8138.16265"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-018-1486-7"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2017.04.041"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.15028"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1304"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-015-1142-4"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.5217\/ir.2017.15.3.328"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.13796"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/MIB.0000000000001148"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-018-4398-2"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2018.00460"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2019.00346"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1089\/gtmb.2018.0313"}],"container-title":["The Journal of Dermatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1346-8138.17515","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T17:30:00Z","timestamp":1747675800000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/1346-8138.17515"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,26]]},"references-count":15,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,2]]}},"alternative-id":["10.1111\/1346-8138.17515"],"URL":"https:\/\/doi.org\/10.1111\/1346-8138.17515","archive":["Portico"],"relation":{},"ISSN":["0385-2407","1346-8138"],"issn-type":[{"type":"print","value":"0385-2407"},{"type":"electronic","value":"1346-8138"}],"subject":[],"published":{"date-parts":[[2024,10,26]]},"assertion":[{"value":"2024-06-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-26","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}