More Severe Erosive Phenotype Despite Lower Circulating Autoantibody Levels in Dipeptidyl Peptidase-4 Inhibitor (DPP4i)-
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ORIGINAL RESEARCH ARTICLE
More Severe Erosive Phenotype Despite Lower Circulating Autoantibody Levels in Dipeptidyl Peptidase‑4 Inhibitor (DPP4i)‑Associated Bullous Pemphigoid: A Retrospective Cohort Study Sascha Ständer1 · Enno Schmidt1,2 · Detlef Zillikens1 · Ralf J. Ludwig1,2 · Khalaf Kridin2
© The Author(s) 2020
Abstract 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 sitagliptinassociated 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.
1 Introduction Bullous pemphigoid (BP) is the most prevalent subepidermal autoimmune bullous disease in Western Europe and Northern America [1]. During the last 2 decades, a 1.9- to 4.3-fold rise in the incidence of BP was noted in France, Germany, and Israel, an epidemiological finding that has been attributed to multiple factors, including growing exposure to culprit medications [2]. Several lines of evidence Ralf J. Ludwig and Khalaf Kridin contributed equally. * Khalaf Kridin [email protected] 1
Department of Dermatology, University of Lübeck, Lübeck, Germany
Lübeck Institute of Experimental Dermatology, University of Lübeck, Ratzeburger Allee 160, 23562 Lübeck, Germany
2
Key Points Patients with dipeptidyl peptidase-4 inhibitor–associated bullous pemphigoid (BP) demonstrate lower levels of anti-BP180 NC16A autoantibodies and a more severe erosive phenotype. Patients with vildagliptin-associated BP had a lower seropositivity rate and lower levels of
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