Dipeptidyl Peptidase-4 Inhibitor-Associated Bullous Pemphigoid in an Elderly Woman With Type 2 Diabetes Mellitus: A Case Report

Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering disease and predominantly affects older adults. In recent years, dipeptidyl peptidase-4 inhibitors (DPP-4i), widely prescribed for type 2 diabetes mellitus, have emerged as important pharmacologic triggers of BP. DPP-4 inhibitors as a class have been associated with BP, with the strongest evidence reported for vildagliptin, although cases involving linagliptin have also been documented. Linagliptin has also been increasingly recognized as a potential trigger of drug-associated disease. We report the case of an 81-year-old woman with long-standing type 2 diabetes mellitus treated with metformin and linagliptin who developed a generalized pruritic vesiculobullous eruption. Dermatologic examination demonstrated multiple tense bullae, erosions, crusted plaques, and post-inflammatory hyperpigmented lesions involving the trunk, extremities, and intertriginous regions. Histopathologic examination revealed a subepidermal blister with prominent eosinophilic infiltration. Direct immunofluorescence demonstrated linear C3 and IgG deposition along the basement membrane zone, while indirect immunofluorescence localized immunoreactants to the roof of the split, confirming the diagnosis of BP. The temporal association with linagliptin exposure and the absence of alternative triggers supported the diagnosis of DPP-4 inhibitor-associated BP. Linagliptin was discontinued, and treatment with prednisone was initiated, resulting in progressive improvement and complete cessation of new blister formation at follow-up. This case highlights the importance of recognizing medication-induced BP in older diabetic patients and reviews current evidence regarding the epidemiology, pathogenesis, clinical presentation, diagnosis, and management of DPP-4 inhibitor-associated BP.