A case series of immune checkpoint inhibitor-induced bullous pemphigoid successfully treated with dupilumab and evidence for the BP180 midportion epitope as a preferential autoantigenic target

Bullous pemphigoid (BP) is the most common autoimmune bullous disease and represents a recognized cutaneous immune-related adverse event associated with immune checkpoint inhibitors (ICIs). Management of ICI-induced BP is challenging, as conventional systemic corticosteroids may interfere with antitumor immunity, highlighting the need for effective steroid-sparing therapies. We report a case series of four elderly male patients who developed BP during treatment with ICIs and were successfully managed with dupilumab, an interleukin-4 receptor alpha antagonist. The median age was 72 years, and BP onset occurred a median of 26 weeks after ICI initiation; nivolumab was the trigger drug in all cases. Diagnosis was established through clinical features, histopathology, direct immunofluorescence, and serological detection of IgG antibodies against BP180, including midportion epitopes in some patients. All patients obtained a sustained clinical remission on dupilumab, with a four-year follow-up showing no treatment-related adverse events, no BP relapse despite continued ICI therapy, and no cancer progression. Our findings support the use of dupilumab as a safe and effective steroid-sparing treatment for ICI-induced BP and suggest that non-NC16A BP180 epitopes may aid diagnosis in selected cases.