Dipeptidyl Peptidase-4 Inhibitor Associated Bullous Pemphigoid with Anti-full-length BP180 and BP230 Antibodies

Abstract

A 69-year-old womanwas referred to us for erythema and bullae onthe upper extremities and the back that appeared a month before. Oral antibiotics prescribed by a local dermatologist under the putative diagnosis of infectious impetigo were ineffective. Physical examination revealed erosions,crusts, and pigmentation associated with faint erythema, and tense bullae on the back and upper extremities. Skinbiopsy revealed subepidermal bullae with regenerated epidermis. The direct immunofluorescence of the skin sample disclosed linear deposition of C3 at the dermo-epidermal junction. Chemiluminescent enzyme immunoassay (CLEIA) for BP180 NC16A, desmoglein-1, and desmoglein-3, and enzyme-linked immunosorbent assay (ELISA) for BP230 showed negative results ; however, ELISA for the full-length BP180 triplet was positive. Immunoblotting using human epidermal extracts as substrate uncovered positivity at 230 kDa BP230. The patient had been taking oral dipeptidyl peptidase-4 (DPP-4) inhibitors for 4.5 years (linagliptin for 2 years and then teneligliptin for 2.5 years). Oral prednisolone (15 mg/day) and minocycline (50 mg/day) were started, and teneligliptin was stopped nine days later. As the eruption showed remarkable improvement, the prednisolone was tapered off at day 50 after the first visit. No recurrence of bullous disorder was observed. The DPP-4 inhibitor-associated bullous pemphigoid (DPP-4i-BP) is reported to be relatively mild, often negative for anti-BP180 NC16A autoantibodies in CLEIA/ELISA,and sometimes positive for the full-length BP180 triplet. In addition, anti-BP230 antibodies were positive only by immunoblotting. Previous studies reported that the anti-BP230 antibodies may be associated with blistering in mice and human ; thus, further study is required to elucidate the role of anti-BP230 antibodies in DPP-4i-BP. Skin Research, 21 : 34-38, 2022