Research in practice: Immune checkpoint inhibitor related autoimmune bullous dermatosis

Summary
Immune checkpoint receptors and ligands such as cytotoxic T lymphocyte antigen‐4 (CTLA‐4), programmed death‐1 (PD‐1) and ligand‐1 (PD‐L1) are widely expressed on immune and non‐immune cells and fine tune the activation level of immune cells, thus, enabling, preventing, or terminating immune responses. Blockade of CTLA‐4, PD‐1 or PD‐L1 by checkpoint inhibitors (CIs), unleashing immune responses, has become a mainstay in the treatment of diverse types of cancer. The induction of autoinflammatory, yet unspecific tissue damage in diverse organs is called an immune related adverse event (irAE), a class side‐effect of CIs and may require the discontinuation of immunotherapy. Among frequent skin rashes, CIs targeting the PD‐L1/PD‐1 axis can elicit the IgG autoantibody‐ and granulocyte‐driven bullous pemphigoid (BP) in about 0.3% to 0.6% of treated patients. Pathogenesis of BP requires a complex cellular inflammatory response after anti‐BP180 autoantibody binding to the dermal epidermal junction. The prevalence of autoantibodies against BP180 in healthy blood donors of approximately 0.52% equals the prevalence of irBP among treated cancer patients, underlining the potential relevance of the PD‐1 mediated regulation of tissue inflammation for spontaneous BP. If skin rashes appear during CI therapy, biopsies should be taken and examined by histopathological and direct immunofluorescence microscopy.