Dipeptidyl peptidase-4 inhibitors-associated bullous pemphigoid: A retrospective study of 168 pemphigoid and 9,304 diabetes mellitus patients

J Diabetes Investig. 2019 Mar;10(2):392-398. doi: 10.1111/jdi.12877. Epub 2018 Jul 25.

Abstract

Aims/introduction: Bullous pemphigoid (BP) might be drug-induced. The present study evaluated the relationship between BP and dipeptidyl peptidase-4 inhibitors (DPP4Is).

Materials and methods: We recruited patients diagnosed with BP at Ogaki Municipal Hospital from 1 December 2009 through 31 December 2017. We retrospectively collected data from medical records and divided patients into two groups based on whether they received DPP4Is. Additionally, we determined the incidence of BP in patients who were first prescribed DPP4Is at our hospital during the study period.

Results: Of 168 patients diagnosed with BP, 133 (79.1%) were positive for anti-BP180NC16a antibody. A total of 32 (19.0%) patients had been prescribed a DPP4I, 21 of whom (65.6%) were positive for anti-BP180NC16a antibody; this rate was lower than that in patients not receiving a DPP4I (82.3%; P = 0.0360). A total of 16 patients with type 2 diabetes mellitus had not been prescribed a DPP4I; only one (6.3%) was positive for anti-BP180NC16a antibody (P = 0.0339). During the study period, 9,304 patients were prescribed DPP4Is, eight of whom developed BP; six (75.0%) had non-inflammatory BP, and five of the six (83.3%) were negative for anti-BP180NC16a antibody.

Conclusions: The positive rate of anti-BP180NC16a antibody was lower in BP patients with DPP4I than without DPP4I, regardless of type 2 diabetes mellitus. The antibody titer was low in both the overall and type 2 diabetes mellitus populations. The prevalence of BP in 9,304 patients receiving DPP4Is was 0.0859%, which is higher than that in the general population. As DPP4Is are common diabetes treatments, we must be aware of the risk of BP.

Keywords: Bullous pemphigoid; Dipeptidyl peptidase-4 inhibitors; Drug side-effect.

Publication types

  • Observational Study

MeSH terms

  • Aged
  • Biomarkers / analysis
  • Blood Glucose / analysis
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Dipeptidyl-Peptidase IV Inhibitors / adverse effects*
  • Female
  • Follow-Up Studies
  • Glycated Hemoglobin / analysis
  • Humans
  • Incidence
  • Japan / epidemiology
  • Male
  • Pemphigoid, Bullous / chemically induced*
  • Pemphigoid, Bullous / epidemiology*
  • Prognosis
  • Retrospective Studies

Substances

  • Biomarkers
  • Blood Glucose
  • Dipeptidyl-Peptidase IV Inhibitors
  • Glycated Hemoglobin A
  • hemoglobin A1c protein, human