Autoimmune bullous dermatoses in cancer patients treated by immunotherapy: a literature review and Italian multicentric experience

• Published in: Frontiers in medicine Vol. 10; p. 1208418
• Main Authors: Merli, Martina, Accorinti, Martina, Romagnuolo, Maurizio, Marzano, Angelo, Di Zenzo, Giovanni, Moro, Francesco, Antiga, Emiliano, Maglie, Roberto, Cozzani, Emanuele, Parodi, Aurora, Gasparini, Giulia, Sollena, Pietro, De Simone, Clara, Caproni, Marzia, Pisano, Luigi, Fattore, Davide, Balestri, Riccardo, Sena, Paolo, Vezzoli, Pamela, Teoli, Miriam, Ardigò, Marco, Vassallo, Camilla, Michelerio, Andrea, Satta, Rosanna Rita, Dika, Emi, Melotti, Barbara, Ribero, Simone, Quaglino, Pietro
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 20.07.2023
• Subjects: anti PD-1; anti PD-L1; bullous pemphigoid; cutaneous irAE; immunotherapy; lichen planus pemphigoides; Medicine; anti PD-1; bullous pemphigoid; anti PD-L1; pemphigus; mucous membrane pemphigoid; immunotherapy; lichen planus pemphigoides; cutaneous irAE
• ISSN: 2296-858X; 2296-858X
• DOI: 10.3389/fmed.2023.1208418

Cutaneous immune-related adverse events are frequently associated with immune checkpoint inhibitors (ICIs) administration in cancer patients. In fact, these monoclonal antibodies bind the cytotoxic T-lymphocyte antigen-4 and programmed cell death-1/ligand 1 leading to a non-specific activation of the immune system against both tumoral cells and self-antigens. The skin is the most frequently affected organ system appearing involved especially by inflammatory manifestations such as maculopapular, lichenoid, psoriatic, and eczematous eruptions. Although less common, ICI-induced autoimmune blistering diseases have also been reported, with an estimated overall incidence of less than 5%. Bullous pemphigoid-like eruption is the predominant phenotype, while lichen planus pemphigoides, pemphigus vulgaris, and mucous membrane pemphigoid have been described anecdotally. Overall, they have a wide range of clinical presentations and often overlap with each other leading to a delayed diagnosis. Achieving adequate control of skin toxicity in these cases often requires immunosuppressive systemic therapies and/or interruption of ICI treatment, presenting a therapeutic challenge in the context of cancer management. In this study, we present a case series from Italy based on a multicenter, retrospective, observational study, which included 45 patients treated with ICIs who developed ICI-induced bullous pemphigoid. In addition, we performed a comprehensive review to identify the cases reported in the literature on ICI-induced autoimmune bullous diseases. Several theories seeking their underlying pathogenesis have been reported and this work aims to better understand what is known so far on this issue.