More Severe Erosive Phenotype Despite Lower Circulating Autoantibody Levels in Dipeptidyl Peptidase-4 Inhibitor (DPP4i)-Associated Bullous Pemphigoid: A Retrospective Cohort Study

Background The clinical and immunological profile of patients with dipeptidyl peptidase-4 inhibitor (DPP4i)-associated bullous pemphigoid (BP) is inconsistent in the current literature. Objectives The aims were to investigate the clinical and immunological features of patients with DPP4i-associated BP and to examine whether there are intraclass differences between different DPP4i agents. Methods A retrospective cohort study was conducted, including all consecutive patients diagnosed with BP throughout the years 2009-2019 in a tertiary referral center. Results The study encompassed 273 patients with BP (mean age at diagnosis 79.1 +/- 9.9 years), of whom 24 (8.8%) were associated with DPP4i. Sitagliptin was the prescribed agent for 17 patients (70.8%), and vildagliptin was prescribed in seven patients (29.2%). Relative to other patients with BP, patients with DPP4i-associated BP had more prominent truncal involvement (95.8% vs. 73.9%;P = 0.017), greater erosion/blister Bullous Pemphigoid Disease Area Index (BPDAI) subscore (29.8 +/- 17.4 vs. 20.6 +/- 14.4;P = 0.018), and lower levels of anti-BP180 NC16A (279.2 +/- 346.1 vs. 572.2 +/- 1352.0 U/ml;P = 0.009) and anti-BP230 (25.5 +/- 47.8 vs. 128.6 +/- 302.9 U/ml;P = 0.009) antibodies. Relative to patients with sitagliptin-associated BP, those with vildagliptin-associated BP had a lower seropositivity rate (57.1% vs. 94.1%,P = 0.031) and lower levels (96.7 +/- 139.0 vs. 354.5 +/- 376.5;P = 0.023) of anti-BP180 NC16A antibodies, and tended to present with higher erosion/blister BPDAI subscore (36.3 +/- 9.6 vs. 25.8 +/- 19.7;P = 0.095). Conclusions DPP4i-associated BP is characterized by a more severe blistering and erosive presentation despite lower levels of typically pathogenic antibodies.

Automated summary

Patients with DPP4i-associated BP exhibit a more severe blistering and erosive presentation despite lower levels of typically pathogenic antibodies.