Update on dermatological toxicities of immune checkpoint inhibitors

The use of immune checkpoint inhibitors (ICIs) has emerged as a transformative approach in the treatment of various malignancies. ICIs target immune regulatory pathways-specifically cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed death-1 (PD-1), and programmed death-ligand 1 (PD-L1)-to reinvigorate anti-tumor immune responses. However, these therapies can induce immune-related adverse events (irAEs) due to systemic immune activation and loss of tolerance. Among the most common irAEs are those affecting the skin, manifesting as a spectrum of cutaneous autoimmune reactions. These range from self-limiting reactions (i.e. eczema-like reactions, psoriasis, lichenoid reactions, vitiligo) to severe and potentially life-threatening conditions such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), or autoimmune blistering diseases. Cutaneous irAEs can significantly affect a patient's quality of life and may necessitate dose adjustments or permanent discontinuation of life-prolonging therapies. Importantly, some skin toxicities may correlate with favorable anti-tumor responses. This article comprehensively reviews epidemiology, pathophysiology, clinical presentations, including rare and emerging patterns, diagnostic strategies, management protocols, and future directions in the understanding and treatment of cutaneous irAEs induced by immunotherapy.