{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T12:22:19Z","timestamp":1782476539909,"version":"3.54.5"},"reference-count":26,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:00:00Z","timestamp":1778716800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>Metformin is a first-line therapy for type 2 diabetes mellitus and is generally considered to have a favorable safety and tolerability profile. Although rare, cutaneous adverse reactions to metformin are diverse, with erythema multiforme (EM) being particularly uncommon. We report the case of a 51-year-old man who developed generalized targetoid skin lesions with scaling and mild pruritus ten days after initiating metformin (500 mg twice daily) for newly diagnosed type 2 diabetes. He was also receiving aspirin and atorvastatin for an acute cerebral infarction (both previously used without allergic reactions). The rash completely resolved within two weeks after discontinuation of all oral medications. Aspirin and atorvastatin were safely reintroduced without recurrence, suggesting that metformin was the most likely causative agent. To the best of our knowledge, this is only the second report in the English-language literature specifically describing a metformin-associated erythema multiforme phenotype since the first case in 2004, with a causality assessment of \u201cprobable,\u201d further supporting that this drug can, on rare occasions, induce such a reaction. Moreover, this case liter provides a practical reference for drug discontinuation and differential diagnosis to identify the culprit agent in the setting of polypharmacy, thereby avoiding the unnecessary withdrawal of critical therapies due to misattribution.<\/jats:p>","DOI":"10.3389\/fendo.2026.1850545","type":"journal-article","created":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T14:40:36Z","timestamp":1778769636000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Probable metformin-associated erythema multiforme: a case report and practical reference to causality assessment"],"prefix":"10.3389","volume":"17","author":[{"given":"Long","family":"Luo","sequence":"first","affiliation":[{"name":"Department of Neurology, The Central Hospital of Xiangtan (The Affiliated Hospital of Hunan University)","place":["Xiangtan, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biao","family":"Teng","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Changde Hospital, Xiangya School of Medicine, Central South University (The First People\u2019s Hospital of Changde City)","place":["Changde, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-017-4336-x","article-title":"Metformin: clinical use in type 2 diabetes","volume":"9","author":"Sanchez-Rangel","year":"2017","journal-title":"Diabetologia"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.12116","article-title":"Metformin in dermatology: an overview","volume":"11","author":"Badr","year":"2013","journal-title":"J Eur Acad Dermatol Venereology: JEADV"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1097\/mjt.0000000000000292","article-title":"DRESS syndrome following metformin administration: a case report and review of the literature","volume":"6","author":"Voore","year":"2016","journal-title":"Am J Ther"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1097\/dad.0000000000000800","article-title":"Metformin-induced generalized fixed drug eruption with cutaneous hemophagocytosis","volume":"6","author":"Ram\u00edrez-Bellver","year":"2017","journal-title":"Am J Dermatopathology"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.77441","article-title":"Confirmation of metformin-induced acute generalized exanthematous pustulosis through a positive dechallenge-rechallenge test: a case report and review of cutaneous manifestations associated with metformin","volume":"1","author":"Alfalah","year":"2025","journal-title":"Cureus"},{"key":"B6","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1111\/j.1365-4632.2011.05348.x","article-title":"Clinical features, diagnosis, and treatment of erythema multiforme: a review for the practicing dermatologist","volume":"8","author":"Sokumbi","year":"2012","journal-title":"Int J Dermatol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1537","DOI":"10.1345\/aph.1E074","article-title":"Erythema multiforme from metformin","volume":"9","author":"Burger","year":"2004","journal-title":"Ann Pharmacother"},{"key":"B8","doi-asserted-by":"publisher","first-page":"107514","DOI":"10.1016\/j.vascn.2024.107514","article-title":"Inter-rater agreement between WHO- Uppsala Monitoring Centre system and Naranjo algorithm for causality assessment of adverse drug reactions","author":"More","year":"2024","journal-title":"J Pharmacol Toxicol Methods"},{"key":"B9","article-title":"Erythema multiforme: recognition and management","volume":"2","author":"Trayes","year":"2019","journal-title":"Am Family Physician"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1245","DOI":"10.3390\/life13061245","article-title":"Annular erythemas and purpuras","volume":"6","author":"Kluger","year":"2023","journal-title":"Life (Basel Switzerland)"},{"key":"B11","article-title":"Subacute cutaneous lupus erythematosus","volume":"14","author":"Jore","year":"1997","journal-title":"Tidsskrift For Den Norske Laegeforening: Tidsskrift For Praktisk Medicin Ny Raekke"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1007\/s40257-020-00505-3","article-title":"Fixed drug eruptions: an update, emphasizing the potentially lethal generalized bullous fixed drug eruption","volume":"3","author":"Patel","year":"2020","journal-title":"Am J Clin Dermatol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2019.02.057","article-title":"Triggers, clinical manifestations, and management of pediatric erythema multiforme: a systematic review","volume":"3","author":"Zoghaib","year":"2019","journal-title":"J Am Acad Dermatol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1177\/12034754231204295","article-title":"The mind body connection in dermatologic conditions: a literature review","volume":"6","author":"Mar","year":"2023","journal-title":"J Cutaneous Med Surg"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.12659\/ajcr.896424","article-title":"Metformin-induced fixed-drug eruption confirmed by multiple exposures","author":"Steber","year":"2016","journal-title":"Am J Case Rep"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.293.6545.483","article-title":"Leucocytoclastic vasculitis and pneumonitis induced by metformin","volume":"6545","author":"Klapholz","year":"1986","journal-title":"Br Med J (Clinical Res Ed)"},{"key":"B17","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1159\/000246152","article-title":"Lichen planus associated with metformin therapy","volume":"4","author":"Azzam","year":"1997","journal-title":"Dermatol (Basel Switzerland)"},{"key":"B18","doi-asserted-by":"publisher","first-page":"11","DOI":"10.5070\/d37cf866x9","article-title":"Psoriasiform drug eruption associated with metformin hydrochloride: a case report","volume":"3","author":"Koca","year":"2003","journal-title":"Dermatol Online J"},{"key":"B19","first-page":"1272","article-title":"Metformin-induced pseudoporphyria","volume":"11","author":"Lenfestey","year":"2012","journal-title":"J Drugs Dermatology: JDD"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1345\/aph.1H155","article-title":"Rare case of metformin-induced leukocytoclastic vasculitis","volume":"9","author":"Ben Salem","year":"2006","journal-title":"Ann Pharmacother"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.2165\/11593230-000000000-00000","article-title":"Metformin-induced leukocytoclastic vasculitis: a case report","volume":"1","author":"Czarnowicki","year":"2012","journal-title":"Am J Clin Dermatol"},{"key":"B22","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1186\/2050-6511-15-3","article-title":"Rosacea-like facial rash related to metformin administration in a young woman","author":"Mumoli","year":"2014","journal-title":"BMC Pharmacol Toxicol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.12890\/2019_001119","article-title":"Erythroderma and chronic lichenification due to metformin","volume":"6","author":"D\u00edaz","year":"2019","journal-title":"Eur J Case Rep Internal Med"},{"key":"B24","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.alit.2024.08.006","article-title":"Delayed drug hypersensitivity reactions: how p-i transforms pharmacology into immunology","volume":"1","author":"Pichler","year":"2025","journal-title":"Allergology International: Off J Japanese Soc Allergology"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.alit.2025.08.003","article-title":"Undressing DReSS as p-i mediated disease","volume":"2","author":"Pichler","year":"2026","journal-title":"Allergology International: Off J Japanese Soc Allergology"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.alit.2025.03.002","article-title":"Pharmacogenetic biomarkers associated with risk of developing severe drug eruptions and clinical implementation of HLA genetic testing","volume":"3","author":"Mushiroda","year":"2025","journal-title":"Allergology International: Off J Japanese Soc Allergology"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1850545\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T14:40:37Z","timestamp":1778769637000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1850545\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,14]]},"references-count":26,"alternative-id":["10.3389\/fendo.2026.1850545"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2026.1850545","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,14]]},"article-number":"1850545"}}