Bruton Tyrosine Kinase Inhibitors in Immune-Mediated Skin Diseases: Current Evidence and Future Directions

Bruton tyrosine kinase (BTK) is a central signaling molecule that links the B-cell receptor (BCR), Fc receptors, and Toll-like receptors (TLRs). By coordinating signaling in B cells, mast cells, macrophages, and other immune cells, BTK occupies an important position in cutaneous immune responses. BTK inhibitors (BTKis) can inhibit B-cell and Fc-receptor-dependent effector-cell signaling, providing a mechanistic rationale for several immune-mediated skin diseases. However, these cellular effects should not be equated with suppression of established autoantibody production or durable disease modification. This review summarizes the biological functions of BTK and critically evaluates clinical and translational evidence in chronic spontaneous urticaria (CSU), atopic dermatitis (AD), pemphigus, psoriasis, and hidradenitis suppurativa (HS). Evidence is strongest for short-term symptom control in CSU cases. Clinical value remains uncertain in pemphigus and HS, rilzabrutinib did not meet its primary AD efficacy endpoint and topical atuzabrutinib showed no exploratory efficacy benefit, and psoriasis evidence is preclinical. Priorities include prospective validation of predictive biomarkers, disease-specific confirmatory trials, agent- and setting-specific safety assessments, and long-term and real-world follow-up.