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

Abstract

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.

Risk Factors for Psoriasis Flares: A Narrative Review

“…Among them, immune checkpoint inhibitors (ICIs) are often responsible for immune-related cutaneous adverse events that can also manifest themselves with the appearance of de novo psoriasis or with the reactivation of a pre-existing psoriasis. 65 ICIs commonly include Cytotoxic T-Lymphocyte Antigen-4 (CTLA-4) inhibitors (Ipilimumab), programmed cell death 1 (PD-1) inhibitors (Nivolumab, Pembrolizumab, and Cemiplimab), and programmed cell death ligand 1 (PD-L1) inhibitors (Atezolizumab, Durvalumab and Avelumab). ICIs have been utilized successfully in patients with metastatic melanoma, renal cell carcinoma, head and neck cancers and non-small lung cancer.…”

Pemphigus vulgaris as an immune-related adverse event in recurrent metastatic esophageal squamous cell carcinoma treated with ipilimumab plus nivolumab: a case report and literature review

“…The timing of PV-irAE onset from the first ICI dose varied and symptoms were relatively mild. Notably, PV-irAE could be controlled with topical steroids, and had less effect on the prognosis compared to PNP and BP associated with ICI ( 9 , 16 , 18 ). If PV-irAE is severe, oral prednisone is a treatment option ( 12 ).…”

“…According to a literature review and our experience, if patients develop blisters during ICI treatment, treating physicians should be mindful of the possible development of cutaneous irAEs. Collaboration between oncologists and dermatologists should be encouraged to manage the development of blistering diseases ( 16 ). Dermatologists should also consider performing a skin biopsy to avoid wasting time and inappropriate treatments.…”

“…Of note, the differential diagnosis of PNP and PV is often complicated. Both PNP and PV are rare autoimmune diseases evoked by the production of autoantibodies due to B-cell hyperactivation ( 14 – 16 ). Noting clinical features and conducting serological examinations are helpful for a differential diagnosis.…”

From Molecular Insights to Clinical Perspectives in Drug-Associated Bullous Pemphigoid

“…Immune checkpoint proteins prevent the immune system from recognizing and eliminating cancer cells. Consequently, the use of immune checkpoint inhibitors (ICI) disrupts the tumoral evasion mechanisms, resulting in the increased activation of the immune system against the tumor [121].…”