Bullous pemphigoid associated with dipeptidyl peptidase-4 inhibitors. A case series and analysis of cases reported in the Spanish pharmacovigilance database

Int J Dermatol. 2020 Feb;59(2):197-206. doi: 10.1111/ijd.14658. Epub 2019 Oct 12.

Abstract

Background: Bullous pemphigoid (BP) has been associated with dipeptidyl peptidase-4 inhibitors (DPP4i). Clinical features, outcomes, and risk of BP for new DPP4i (linagliptin, saxagliptin, and alopgliptin) are not well established. Comparison of risk of BP appearance for DPP4i and other oral antidiabetic drugs (OADs) such as sodium glucose cotransporter 2 inhibitors has not been studied to date.

Objectives: To describe the prevalence, sociodemographic, clinical, and histopathological characteristics, and outcome after drug withdrawal in DPP-4i-associated BP cases from our hospital. To review all Spanish spontaneous notifications of BP where DPP4i or OADs were included as suspected drugs and calculate the reporting odds ratios (RORs).

Methods: A retrospective observational study was performed examining the association between DDP4i and BP. Clinical features and RORs were analyzed. Data from the Spanish Pharmacovigilance System (SEFV) are included.

Results: In our center, 28 of 89 patients with BP (31.5%) were under DPP4i treatment; 53.6% were male, and mean age was 80.8 years. BP debuted the first year after DPP4i in 57.2%. BP control was achieved within 3.7 months after drug withdrawal. Regarding SEFV, 22 of 972 spontaneous notifications were related to BP and DPP4i. RORs were superior for DPP4i compared to other OADs. Vildagliptin had the highest ROR.

Conclusions: We present the largest DPP4i-induced BP case series in a single center, with a detailed study of the sociodemographic, clinical, and histopathological characteristics of each patient, and their treatment and outcome. Vildagliptin had the highest risk. DPP4i-associated BP does not seem to have specific clinical characteristics.

Publication types

  • Observational Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Databases, Factual
  • Dipeptidyl-Peptidase IV Inhibitors / adverse effects*
  • Female
  • Humans
  • Linagliptin / adverse effects
  • Male
  • Middle Aged
  • Pemphigoid, Bullous / blood
  • Pemphigoid, Bullous / chemically induced*
  • Pemphigoid, Bullous / pathology
  • Pharmacovigilance
  • Retrospective Studies
  • Sitagliptin Phosphate / adverse effects
  • Sodium-Glucose Transporter 2 Inhibitors / adverse effects
  • Spain
  • Vildagliptin / adverse effects

Substances

  • Dipeptidyl-Peptidase IV Inhibitors
  • Sodium-Glucose Transporter 2 Inhibitors
  • Linagliptin
  • Vildagliptin
  • Sitagliptin Phosphate