Analysis of the Clinical Characteristics of Dipeptidyl Peptidase-4 Inhibitor-Induced Bullous Pemphigoid

Ann Pharmacother. 2022 Feb;56(2):205-212. doi: 10.1177/10600280211022722. Epub 2021 Jun 9.

Abstract

Objective: To analyze and discuss the clinical characteristics of dipeptidyl peptidase-4 inhibitor (DPP4i)-induced bullous pemphigoid (BP).

Data sources: We collected case reports of DPP4i-induced BP by searching databases from 2006 to mid-May 2021, as a retrospective analysis.

Study selection and data extraction: Relevant case reports and case analyses of DPP4i-induced BP were included.

Data synthesis: The median time of symptom onset was 9 months (range 0.5-59 months). BP most often occurred in patients receiving vildagliptin (52.63%) followed by linagliptin (27.19%) and sitagliptin (17.54%). Tense bullae and blisters (85.51%) and erythema (82.61%) on the extremities and trunk were the most common presenting symptoms. In total, 64.06% of BP patients were anti-BP180 autoantibody positive, 58.97% were BP180NC16a autoantibody positive, and 31.25% were anti-BP230 autoantibody positive. Skin biopsy revealed subepidermal bulla eosinophil infiltration in 93.85% of BP patients, lymphocyte infiltration in 56.93%, and neutrophil infiltration in 44.62%. Direct immunofluorescence was positive in 98.94% of BP patients with linear deposition of IgG (97.80%) and/or complement C3 (98.94%) along the basement membrane zone. Indirect immunofluorescence was positive in 87.88% of BP patients. Complete remission of BP was achieved in 83.64% of patients on DPP4i withdrawal and after 4 months (range 0.13-72 months) of follow-up.

Relevance to patient care and clinical practice: This review analyzes and discusses the clinical characteristics of DPP4i-induced BP and provides a reference for the safe and reasonable clinical application of DPP4i.

Conclusions: DPP4i drugs are related to the occurrence of BP in diabetic patients, especially elderly men taking vildagliptin.

Keywords: BP180; BP230; bullous pemphigoid; dipeptidyl peptidase-4 inhibitors; gliptin; pharmacovigilance.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aged
  • Autoantibodies
  • Dipeptidyl-Peptidase IV Inhibitors* / adverse effects
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
  • Humans
  • Male
  • Pemphigoid, Bullous* / chemically induced
  • Pemphigoid, Bullous* / diagnosis
  • Pemphigoid, Bullous* / drug therapy
  • Retrospective Studies
  • Vildagliptin

Substances

  • Autoantibodies
  • Dipeptidyl-Peptidase IV Inhibitors
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
  • Vildagliptin