Gliptin-Induced Bullous Pemphigoid: Are Statins and Angiotensin Receptor Blockers the Cause?

Recently, dipeptidyl peptidase 4 inhibitors (DPP4i), a group of drugs used for the treatment of diabetes mellitus, have been associated with an increased risk of bullous pemphigoid (BP). Several studies previously found clinical and laboratory differences between patients with gliptin-induced BP and conventional BP, and some authors accept DPP4i-induced BP as a separate entity. In this retrospective study, we aimed to compare clinical and laboratory characteristics, comorbidities, and medications used simultaneously with gliptins in these two groups of BP.

Patients with the diagnosis of BP hospitalized in our clinic between 2010 and 2023 were included in this retrospective cross-sectional study. Demographic, clinical, laboratory data, comorbidities, and additional medications were recorded for each patient. Patients were divided into DPP4i-associated and conventional BP groups, and the data were compared between the two groups.

A total of 105 patients with BP, of which 11 were DPP4i-associated, were included. There was no statistically significant difference in age, age at onset, gender distribution, lesion distribution, histopathological, and laboratory findings between the two groups. The median use of DPP4i before BP onset was 3 months (1-12). Disease and follow-up duration were shorter in the gliptin-associated group. DPP4i-induced patients had a higher frequency of severe disease and presentation with a prebullous phase. Cardiovascular disorders, hypertension, hyperlipidemia, the use of angiotensin receptor blockers (ARB), and statins were significantly higher in the gliptin-using patients.

This is one of the first studies to compare demographic, clinical, and laboratory characteristics of patients with gliptin-induced and conventional BP. Our results suggest gliptin-associated BP may present with more severe disease. Hyperlipidemia, ARB, and statin use may be associated with DPP4i-induced BP. Although larger studies are warranted to confirm this association, we believe these findings should be kept in mind while choosing patients to treat with gliptins.