Alopecia Areata: A Comprehensive Review of Pathogenesis, Diagnosis, and Emerging Therapeutics

Abstract

Alopecia areata (AA) is a common, immune-mediated, non-scarring alopecia characterized by unpredictable hair loss and substantial psychosocial burden. Once considered a hair-restricted disorder, AA is now recognized as a systemic disease arising from complex interactions between genetic susceptibility, immune dysregulation, environmental triggers, intrinsic hair follicle vulnerabilities. Central to disease pathogenesis is the collapse of hair follicle, driven predominantly by cytotoxic CD8⁺NKG2D⁺ T cells within a Th1-skewed cytokine milieu dominated by interferon-γ and interleukin-15. Genome-wide association studies have identified multiple susceptibility loci, including HLA class II genes and immune regulatory pathways, while emerging evidence implicates hair-shaft–specific genes, oxidative stress regulators, and epigenetic modifiers, underscoring disease heterogeneity beyond classical autoimmunity. Environmental factors such as smoking, sleep disturbance, psychological stress, and microbiome dysbiosis, further modulate disease risk and severity. Advances in Trichoscopy have refined non-invasive diagnosis and disease monitoring, while therapeutic strategies have expanded from conventional corticosteroids to targeted Janus kinase inhibitors, representing a paradigm shift in disease management. However, challenges related to long-term safety, relapse, accessibility, and cost still remain. This review integrates current insights into AA pathogenesis, diagnostics, and emerging therapies, emphasizing the need for personalized, multidisciplinary, and translational approaches to improve long-term outcomes and quality of life.