The Role of Reactive Oxygen Species in the Pathogenesis of Alopecia Areata: A Systematic Review and Meta-Analysis

Background: Alopecia areata (AA) is a T-cell-mediated autoimmune disease that significantly impacts patient quality of life. The breakdown of hair follicle immune privilege underlies AA pathogenesis. However, the precise mechanism of this breakdown remains unclear. This study investigates the potential role of reactive oxygen species in AA pathogenesis. Summary: A systematic review and meta- analysis were conducted on observational studies and randomized controlled trials from 2000 to 2024. Studies included AA patients and measured oxidative stress index (OSI), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), or paraoxonase-1 (PON1). Extracted data were analyzed using the Cochrane risk-of- bias tool and random-effects models. The review included 21 studies with 743 AA patients. OSI was elevated in AA patients (effect size = 1.58, 95% CI: 0.31-2.68, p = 0.00068). MDA levels were also elevated (effect size = 1.60, 95% CI: 0.43-2.6, p = 0.00023), while SOD (effect size = -0.97, 95% CI: -1.65 to -0.30, p = 0.00066) and GSH-Px (effect size = -1.41, 95% CI: -2.28 to -0.53, p = 0.00068) activities were reduced. PON1 levels showed no significant difference (effect size = -3.56, 95% CI: -8.63 to 1.51, p = 0.051). Key Messages: The elevated OSI and MDA, and decreased antioxidant activity in AA patients suggest a substantial role for reactive oxygen species and oxidative stress in AA pathogenesis, highlighting oxidative stress as a potential target for therapeutic intervention. These results underscore the importance of oxidative stress in AA and support further research into antioxidant-based therapies.