Importance Enzyme-linked immunosorbent assay (ELISA) and/or chemiluminescent enzyme immunoassay (CLEIA) for BP180 noncollagenous 16A (NC16A) extracellular domain is a sensitive diagnostic tool for bullous pemphigoid (BP). However, some patients with BP have negative results for these assays. Objective To elucidate the clinical and immunological features of patients with BP without antibodies that react to BP180 NC16A. Design, Setting, and Participants This retrospective case series study included 152 patients who were diagnosed with BP and followed up at the Kurume University Hospital in Japan from 2007 to 2016. The diagnosis was made using clinical, histological, and immunological findings. Main Outcomes and Measures Clinical and immunological features of patients with BP who had negative results for BP180 NC16A using ELISA and/or CLEIA. Results Of the 152 patients, 69 (45.4%) were men and 83 (54.6%) were women. The mean (SD) age of participants was 75.2 (14.4) years. Of the 152 patients with BP, 14 (9.2%) had negative results for BP180 NC16A on ELISA and/or CLEIA; most of these patients exhibited no erythema and had relatively mild phenotypes. Two (14%) of the 14 patients had positive results for intact BP180 in epidermal extracts, 10 (71%) had positive results for a 120-kD fragment of BP180 (LAD-1) and 3 (21%) had positive results for BP180 C-terminal domain. Seven (50%) patients tested positive in BP230 ELISA. Five (36%) patients did not require oral prednisolone treatment, whereas the others required a dose of prednisolone at less than 30 mg per day. Three (21%) patients were administered a dipeptidyl peptidase-4 inhibitor (DPP4i) before disease onset. This ratio was not significantly higher than that in patients with BP who tested positive for BP180 NC16A ELISA and/or CLEIA (19 [14%] of 138 patients). Our follow-up study (mean [SD], 31.9 [33.2] weeks; range, 0-108 weeks) revealed that patients with BP tested negative for BP180 NC16A ELISA and/or CLEIA during the later stages of the disease. Conclusions and Relevance This study indicates that patients with BP negative for BP180 NC16A ELISA and/or CLEIA had milder phenotypes, fewer erythemas, and required less extensive treatments.
