Bullous Pemphigoid Induced by Whole Breast Radiation in the Setting of Concurrent Pembrolizumab: A Case Report and Review of the Literature.

Bullous pemphigoid (BP) is a rare autoimmune blistering disorder increasingly recognized as an immune-related adverse event associated with programmed cell death protein 1 inhibitors, with limited data describing its occurrence in the setting of concurrent radiation therapy (RT). We report a case of a 50-year-old woman with stage IIIB triple-negative breast cancer treated with neoadjuvant chemoimmunotherapy followed by mastectomy and adjuvant pembrolizumab who developed BP during postmastectomy RT with regional nodal irradiation. After 7 fractions, she developed bullous lesions initially outside the radiation field, with subsequent progression to involve both irradiated and nonirradiated skin as well as mucocutaneous surfaces. Biopsy demonstrated subepidermal vesicular dermatosis consistent with BP, later confirmed on repeat biopsy with direct immunofluorescence. RT and pembrolizumab were held, and she was treated with systemic corticosteroids and steroid-sparing therapy, although her course was prolonged and relapsing, ultimately requiring permanent discontinuation of immunotherapy. This presentation, including early onset during RT and distribution beyond the treatment field, supports a synergistic interaction between RT and programmed cell death protein 1 inhibition, potentially mediated by enhanced antigen presentation and loss of immune tolerance. Because combined-modality therapy becomes more common, clinicians should maintain a high index of suspicion for immune-mediated toxicity, particularly when findings are atypical for radiation dermatitis, to facilitate prompt diagnosis and multidisciplinary management.