Autoimmune Skin Disease Pathogenesis: A Chronological Immune Cascade and Multi-Hit Model

This review explores the pathogenesis of autoimmune skin diseases using vitiligo as a model to establish a chronological framework of disease onset, progression, and recurrence. It introduces a "stochastic multi-hit model" where disease results from cumulative genetic and environmental factors breaching immunological checkpoints. The review details immune processes such as antigen exposure, T cell priming, and the formation of tertiary lymphoid structures. It also discusses inflammation resolution and recurrence driven by adaptive immunity and inflammatory memory. The framework is extended to other autoimmune skin diseases like alopecia areata, pemphigus vulgaris, and psoriasis, highlighting unexplored mechanistic gaps and offering new directions for research and clinical practice.