Clinical features of dipeptidyl peptidase-4 inhibitor-associated bullous pemphigoid in Japan: A nationwide retrospective observational study

J Dermatol. 2022 Jul;49(7):697-702. doi: 10.1111/1346-8138.16394. Epub 2022 Apr 27.

Abstract

Many cases of bullous pemphigoid (BP) have been reported in patients taking dipeptidyl peptidase-4 inhibitors (DPP-4i), which are the most widely used antidiabetic drug for type 2 diabetes mellitus. However, no large-scale survey has been conducted in Japan. This retrospective study investigated the incidence, clinical presentation, and clinical course of DPP-4i-associated BP (DPP-4i-BP) using epidemiological data from a nationwide registry for BP. In 2016, 713 new BP patients at 94 dermatological institutes were registered, 243 (34.1%) with DPP-4i-BP and 461 (64.7%) with non-DPP-4i-BP. The male-to-female ratio was 1.9 and 0.84, respectively. Patients with DPP-4i-BP were predominantly male. Non-inflammatory BP was more common in DPP-4i-BP (33.3%) than in non-DPP-4i-BP (14.6%), while inflammatory BP was common in both. No specific subtype or difference in disease severity was evident in DPP-4i-BP. The most common gliptins administered to DPP-4i-BP patients were vildagliptin (37.2%) and linagliptin (23.8%). DPP-4i intake was discontinued in 79.9% of cases after diagnosis. Some DPP-4i-BP patients (17.6%) achieved spontaneous remission after discontinuing DPP-4i without requiring the use of systemic corticosteroids and/or adjuvant therapy. Mean duration to achieve disease control was 2.87 months. The odds ratio for non-inflammatory BP requiring systemic corticosteroids and/or adjuvant therapy was low (0.52), suggesting that remission was achieved easily with supportive care in that phenotype. Non-inflammatory and mild cases of DPP-4i-BP may resolve spontaneously with supportive care, including the discontinuation of DPP-4i and no oral corticosteroid therapy.

Keywords: bullous pemphigoid; dipeptidyl peptidase-4 inhibitor; non-inflammatory; spontaneous remission; vildagliptin.

Publication types

  • Observational Study

MeSH terms

  • Adrenal Cortex Hormones / therapeutic use
  • Diabetes Mellitus, Type 2* / drug therapy
  • Diabetes Mellitus, Type 2* / epidemiology
  • Dipeptidyl-Peptidase IV Inhibitors* / adverse effects
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / therapeutic use
  • Female
  • Humans
  • Hypoglycemic Agents / adverse effects
  • Japan / epidemiology
  • Male
  • Pemphigoid, Bullous* / chemically induced
  • Pemphigoid, Bullous* / drug therapy
  • Pemphigoid, Bullous* / epidemiology
  • Retrospective Studies

Substances

  • Adrenal Cortex Hormones
  • Dipeptidyl-Peptidase IV Inhibitors
  • Hypoglycemic Agents
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases