Skin toxicities related to Bruton tyrosine kinase inhibitors: an updated review

Introduction: Bruton's tyrosine kinase inhibitors (BTKi) have transformed the management of B-cell malignancies by selectively targeting signaling pathways essential for malignant B-cell survival, thereby reducing the systemic toxicity of conventional chemotherapy. However, with their expanding use, cutaneous adverse events are increasingly recognized as clinically relevant complications that may affect quality of life and treatment adherence. Areas covered: This review provides an updated overview of first- and second-generation BTKi, including ibrutinib, acalabrutinib, zanubrutinib, and pirtobrutinib, with a specific focus on dermatologic toxicities. A comprehensive literature search was conducted using PubMed, Embase, and Scopus, covering publications up to February 2025. Clinical studies, case series, and case reports describing skin-related adverse events associated with BTKi therapy were reviewed. Expert opinion: Cutaneous toxicities related to BTKi are often underrecognized but clinically significant, ranging from xerosis and bruising to lichenoid eruptions and vasculitis. First-generation agents, particularly ibrutinib, are associated with a broader spectrum of dermatologic adverse events, whereas newer BTKi show improved selectivity and potentially reduced skin toxicity. Early recognition, standardized dermatologic evaluation, and proactive multidisciplinary management are essential to minimize patient discomfort, preserve quality of life, and prevent unnecessary treatment discontinuation.