Bullous pemphigoid associated with vildagliptin in an elderly adult with diabetes mellitus. First case in Peru
DOI:
https://doi.org/10.17843/rpmesp.2025.421.13871Keywords:
Bullous Pemphigoid, Dipeptidyl-Peptidase IV Inhibitors, Vildagliptin, Drug-Related Side Effects and Adverse Reactions, Case ReportsAbstract
Vildagliptin, a dipeptidyl peptidase-4 inhibitor (DPP-4i) used in the treatment of type 2 diabetes mellitus (DM2), stands out for its safety in older adults. However, it is associated with adverse reactions, such
as bullous pemphigoid (BP), although no cases have been documented in Peru to date. We report the case of a 76-year-old male patient with hypertension and DM2 who started treatment with vildagliptin
and metformin. After one month, he presented pruritic, bullous and ulcerated skin lesions, leading to the diagnosis of BP. BP, associated with DPP-4i, mainly affects older adults, manifesting on average about 9 months after the start of treatment. Its diagnosis is based on clinical criteria, histopathology and immunofluorescence. Treatment includes discontinuation of the drug and the use of corticosteroids. Vildagliptin, although safe and effective, can cause BP, which requires timely diagnosis and treatment due to its high mortality.
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References
Mulvihill EE, Drucker DJ. Pharmacology, physiology, and mechanisms of action of dipeptidyl peptidase-4 inhibitors. Endocr Rev. 2014;35(6):992–1019. doi: 10.1210/er.2014-1035.
Hayashi T, Murayama H, Shinfuku Y, Taniguchi T, Tsumiyama I, Oyama N. Safety and efficacy of vildagliptin: 52-week post-marketing surveillance of Japanese patients with type 2 diabetes in combination with other oral antidiabetics and insulin. Expert Opin Pharmacother. 2020 Jan;21(1):121–30. doi: 10.1080/14656566.2019.
Mathieu C, Kozlovski P, Paldánius PM, Foley JE, Modgill V, Evans M, et al. Clinical Safety and Tolerability of Vildagliptin - Insights from Randomised Trials, Observational Studies and Post-marketing Surveillance. Eur Endocrinol. 2017;13(2):68–72. doi: 10.17925/EE.2017.13.02.68.
Yang W, Cai X, Zhang S, Han X, Ji L. Dipeptidyl peptidase-4 inhibitor treatment and the risk of bullous pemphigoid and skin-related adverse events: A systematic review and meta-analysis of randomized controlled trials. Diabetes Metab Res Rev. 2021;37(3):e3391. doi: 10.1002/dmrr.3391.
Silverii GA, Dicembrini I, Nreu B, Montereggi C, Mannucci E, Monami M. Bullous pemphigoid and dipeptidyl peptidase-4 inhibitors: a meta-analysis of randomized controlled trials. Endocrine. 2020;69(3):504–7. doi: 10.1007/s12020-020-02272-x.
Phan K, Charlton O, Smith SD. Dipeptidyl peptidase-4 inhibitors and bullous pemphigoid: A systematic review and adjusted meta-analysis. Australas J Dermatol. 2020;61(1):e15–21. doi: 10.1111/ajd.13100.
Chouchane K, Di Zenzo G, Pitocco D, Calabrese L, De Simone C. Bullous pemphigoid in diabetic patients treated by gliptins: the other side of the coin. J Transl Med. 2021;19:520. doi: 10.1186/s12967-021-03192-8.
Leisti P, Pankakoski A, Jokelainen J, Huilaja L, Panelius J, Tasanen K, et al. Type 2 Diabetes and its Treatment with Linagliptin are both Associated with Elevated Mortality in Bullous Pemphigoid. Acta Derm Venereol. 2024;104:40645. doi: 10.2340/actadv.v104.40645.
Arai M, Shirakawa J, Konishi H, Sagawa N, Terauchi Y. Bullous Pemphigoid and Dipeptidyl Peptidase 4 Inhibitors: A Disproportionality Analysis Based on the Japanese Adverse Drug Event Report Database. Diabetes Care. 2018;41(9):e130–2. doi: 10.2337/dc18-0210.
Carnovale C, Mazhar F, Arzenton E, Moretti U, Pozzi M, Mosini G, et al. Bullous pemphigoid induced by dipeptidyl peptidase-4 (DPP-4) inhibitors: a pharmacovigilance-pharmacodynamic/pharmacokinetic assessment through an analysis of the vigibase®. Expert Opin Drug Saf. 2019;18(11):1099–108. doi: 10.1080/14740338.2019.1668373.
Béné J, Moulis G, Bennani I, Auffret M, Coupe P, Babai S, et al. Bullous pemphigoid and dipeptidyl peptidase IV inhibitors: a case-noncase study in the French Pharmacovigilance Database. Br J Dermatol. 2016;175(2):296–301. doi: 10.1111/bjd.14601.
Molina-Guarneros JA, Sainz-Gil M, Sanz-Fadrique R, García P, Rodríguez-Jiménez P, Navarro-García E, et al. Bullous pemphigoid associated with the use of dipeptidil peptidase-4 inhibitors: analysis from studies based on pharmacovigilance databases. Int J Clin Pharm. 2020;42(2):713–20. doi: 10.1007/s11096-020-01003-6.
Jedlowski PM, Jedlowski MF, Fazel MT. DPP-4 Inhibitors and Increased Reporting Odds of Bullous Pemphigoid: A Pharmacovigilance Study of the FDA Adverse Event Reporting System (FAERS) from 2006 to 2020. Am J Clin Dermatol. 2021;22(6):891–900. doi: 10.1007/s40257-021-00625-4.
Tasanen K, Varpuluoma O, Nishie W. Dipeptidyl Peptidase-4 Inhibitor-Associated Bullous Pemphigoid. Front Immunol. 2019;10:1238. doi: 10.3389/fimmu.2019.01238.
Sun L, Wang C, Wu C, Zhou Y, Wang C. Analysis of the Clinical Characteristics of Dipeptidyl Peptidase-4 Inhibitor-Induced Bullous Pemphigoid. Ann Pharmacother. 2022;56(2):205–12. doi: 10.1177/10600280211022722.
Kridin K, Shihade W, Bergman R. Mortality in Patients with Bullous Pemphigoid: A Retrospective Cohort Study, Systematic Review and Meta-analysis. Acta Derm Venereol. 2019;99(1):72–7. doi: 10.2340/00015555-2930.
Bağcı IS, Horváth ON, Ruzicka T, Sárdy M. Bullous pemphigoid. Autoimmun Rev. 2017 May;16(5):445–55. doi: 10.1016/j.autrev.2017.03.010.
Mai Y, Nishie W, Izumi K, Shimizu H. Preferential Reactivity of Dipeptidyl Peptidase-IV Inhibitor-Associated Bullous Pemphigoid Autoantibodies to the Processed Extracellular Domains of BP180. Front Immunol. 2019 May 29;10:1224. doi: 10.3389/fimmu.2019.01224.
Roy A, Sahoo J, Narayanan N, Merugu C, Kamalanathan S, Naik D. Dipeptidyl peptidase-4 inhibitor-induced autoimmune diseases: Current evidence. World J Diabetes. 2021;12(9):1426–41. doi: 10.4239/wjd.v12.i9.1426.
Hertl M, Eming R, Veldman C. T cell control in autoimmune bullous skin disorders. J Clin Invest. 2006;116(5):1159–66. doi: 10.1172/JCI28547.
Okazaki A, Miyagawa S, Yamashina Y, Kitamura W, Shirai T. Polymorphisms of HLA-DR and -DQ Genes in Japanese Patients with Bullous Pemphigoid. J Dermatol. 2000;27(3):149–56. doi: 10.1111/j.1346-8138.2000.tb02141.x.
Hirose M, Schilf P, Benoit S, Eming R, Gläser R, Homey B, et al. Polymorphisms in the mitochondrially encoded ATP synthase 8 gene are associated with susceptibility to bullous pemphigoid in the German
population. Exp Dermatol. 2015;24(9):715–7. doi: 10.1111/exd.12732.
Rychlik-Sych M, Barańska M, Wojtczak A, Skrętkowicz J, Żebrowska A, Waszczykowska E. The impact of the CYP2D6 gene polymorphism on the risk of pemphigoid. Int J Dermatol. 2015;54(12):1396–401. doi: 10.1111/ijd.12967.
Weisenseel P, Martin S, Partscht K, Messer G, Prinz JC. Relevance of the low-affinity type of the Fcγ-receptor IIIa-polymorphism in bullous pemphigoid. Arch Dermatol Res. 2007;299(3):163–4. doi: 10.1007/s00403-007-0755-8.
Eming R, Sticherling M, Hofmann SC, Hunzelmann N, Kern JS, Kramer H, et al. S2k guidelines for the treatment of pemphigus vulgaris/foliaceus and bullous pemphigoid. JDDG J Dtsch Dermatol Ges. 2015;13(8):833–44. doi: 10.1111/ddg.12606.
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Copyright (c) 2025 Juan Eduardo Quiroz-Aldave, Janet Ángeles-Zavaleta, María del Carmen Durand-Vásquez, José Paz-Ibarra, Janneth Y. Quispe-Meza, Marcio Concepción-Zavaleta; Cristian D. Armas; Luis Concepción-Urteaga
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