Immune checkpoint inhibitor-induced bullous pemphigoid: a systematic review of clinical characteristics and outcomes based on case reports.

Objective: Immune checkpoint inhibitor-induced bullous pemphigoid (ICI-BP) is a rare and complex cutaneous immune-related adverse event (cirAE) that often impacts the continuation of ICI therapy. Currently, there are no prospective clinical studies addressing the optimal management of BP alongside ICI continuation, with existing evidence largely derived from case reports or series. This study systematically analyzes published case reports and series to compile evidence regarding the management of ICI-BP and ICI rechallenge, aiming to inform clinical practice. Methods: A comprehensive search of the PubMed, Embase, and Web of Science Core Collection (WoS CC) databases was conducted from their inception to identify eligible case reports and series. Relevant data were extracted using a standardized form. A total of 116 cases from 89 publications were included in the analysis. Results: There was no discernible disparity in the final response rate between patients with mild and severe BP (p > 0.05); however, the percentage of severe patients undergoing escalation therapy was notably higher (p < 0.001). This suggests that employing an active treatment approach based on disease severity effectively ameliorated the potentially graver prognosis in severe cases. Following BP management, 18 patients underwent rechallenge with ICI therapy, with an overall low BP recurrence rate (22.2%), indicating that most patients tolerated the resumption well. Nevertheless, the majority of relapses transpired in patients with initial severe BP, with mucosal invasion, and those who restarted the original therapy, pointing to an elevated risk in this cohort. The 11 deceased patients constituted a high-risk subset distinguished by advanced age (median 74 years), a prevalence of melanoma, and severe BP. The duration from BP diagnosis to demise was briefer in this subset (median 3.7 months), with half of the patients succumbing within 4 months. Conclusion: ICI-BP is usually manageable through a stepwise therapeutic approach, and resuming ICI treatment after lesion remission is generally possible. Clinical decision-making must be tailored to the individual patient. Caution and careful monitoring are essential when reinitiating ICI in patients who initially presented with severe disease or mucosal involvement. For elderly patients, those with melanoma, and individuals experiencing severe BP, heightened vigilance is necessary concerning short-term prognostic risks. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD420251172315.