Immune checkpoint inhibitors (ICIs) targeting PD-1, PD-L1, and CTLA-4 enhance antitumor immunity but can produce immune-related adverse events (irAEs). Cutaneous irAEs are among the most frequent and can range from mild eruptions to severe autoimmune bullous disorders (AIBDs). While bullous pemphigoid (BP) is the most commonly reported ICI-related AIBD, information on the broader spectrum of ICI-associated AIBDs and their management remains limited. Understanding these reactions is important because they may require oncologic treatment interruption and affect clinical outcomes.
The study aimed to comprehensively characterize ICI-associated autoimmune bullous disorders by describing patient demographics, oncologic diagnoses and immunotherapy agents, clinical presentation, histopathologic and immunofluorescence findings, therapeutic approaches, treatment responses, clinical outcomes, and mortality in a single-center cohort.
Investigators performed a retrospective chart review at a single institution using a text-based database search spanning 2011–2023. Adult patients aged 18 years or older with biopsy-confirmed AIBDs attributed to ICIs were included. Extracted data included demographic and oncologic variables, details of immunotherapy exposure, clinical features of the AIBD, histopathology, direct immunofluorescence findings, treatments administered, response to therapy, and mortality. The study design and time window reflect a review of clinical records; further methodological specifics beyond the chart review approach are not provided in the abstract.
Forty-four patients met inclusion criteria. The cohort was predominantly male (29/44, 65.9%) with a reported mean age of 70.4 years and an age range listed as 62–80 years. The most frequent underlying malignancies were lung carcinoma (12/44, 27.2%) and melanoma (9/44, 20.4%). Pembrolizumab was the most commonly implicated ICI (25/44, 56.8%).
Regarding diagnostic categorization, bullous pemphigoid (BP) represented most cases (36/44, 81.8%). Lichen planus pemphigoides (LPP) accounted for 6 cases (13.6%), and there was one case each of mucous membrane pemphigoid (MMP) and linear IgA bullous dermatosis (LABD).
Pruritus was reported in the majority of patients (the abstract states pruritus in 42 patients). The most commonly involved anatomic sites were the upper extremities (36/44, 81.8%), chest (34/44, 77.2%), and lower extremities (32/44, 72.2%).
Histopathologic evaluation of BP cases frequently demonstrated eosinophilic infiltration; eosinophilia was present in most BP cases where it was assessed (reported as 23/28 BP cases, 81.8%). Direct immunofluorescence patterns in BP most commonly showed linear deposition of IgG and C3 at the basement membrane zone. These clinicopathologic features are consistent with classic BP but were observed in the context of ICI exposure.
Therapeutic strategies varied but most patients received topical and/or systemic corticosteroids. Topical corticosteroids were used in 34/44 patients (77.2%), and systemic corticosteroids in 32/44 patients (72.7%). Antibiotic therapy with doxycycline was used in 22 patients (50%). Other systemic immunomodulatory therapies included rituximab (6/44, 13.6%), intravenous immunoglobulin (IVIG) (5/44, 11.3%), and single-case use of agents such as dapsone, mycophenolate mofetil, methotrexate, and colchicine (each reported in 1/44, 2.2%). Dupilumab was administered to four BP patients (4/44, 9.1%).
Regarding ICI management, 16 patients required at least temporary interruption of ICI therapy. Three cases categorized as Grade 3 in severity required permanent discontinuation of ICI treatment.
Clinical stabilization of the irAIBD was achieved in 24 patients (54.5%), and remission was reported in 16 patients (36.3%). One death (1/44, 2.2%) was attributed to sepsis in a patient with severe irAIBD. Overall, most patients were able to continue ICI therapy while undergoing management of their AIBD, though a subset required temporary or permanent treatment interruption.
This single-center retrospective review of 44 biopsy-confirmed ICI-associated AIBD cases over 2011–2023 highlights that these disorders, though uncommon, are clinically meaningful complications of immune checkpoint inhibitor therapy. The majority of cases were bullous pemphigoid, primarily occurring in older adults treated for lung cancer or melanoma, with pembrolizumab the most frequent associated agent. Management commonly involved topical and systemic corticosteroids, doxycycline, and a range of systemic immunomodulatory therapies; a small proportion received dupilumab. Most patients achieved stabilization or remission, and most continued ICI therapy during management, but a minority required temporary or permanent ICI discontinuation and one death from sepsis was reported. The findings emphasize the need for early recognition and multidisciplinary management of ICI-associated AIBDs.
Note: The abstract provides summary data but does not detail statistical methods, inclusion/exclusion criteria beyond biopsy confirmation and attribution to ICIs, or granular timelines between ICI exposure and AIBD onset; those specifics were not reported in the provided source abstract.