Abstract
Psoriasis, a chronic immune-mediated inflammatory skin disease, is driven by keratinocyte hyperproliferation and dysregulated cytokine activity (e.g., TNF-α, IL-17, IL-23), significantly impacting quality of life. Standard treatments, including topical corticosteroids, phototherapy, and biologics, are effective but often limited by relapses, adverse effects, and high costs. Ozone therapy, an investigational approach utilizing ozone’s oxidative and immunomodulatory properties, has emerged as a potential alternative or adjunctive treatment. This review synthesizes evidence on ozone therapy’s mechanistic actions, clinical efficacy, and comparative effectiveness versus standard treatments in psoriasis. Mechanistically, ozone therapy suppresses the TLR2/NF-κB pathway, reduces pro-inflammatory cytokines (IL-17, IL-22, TNF-α), inhibits Th17 cell activation, and promotes keratinocyte differentiation via Tp63/KRT10 upregulation. It also enhances immunometabolic regulation by increasing PPAR-γ expression and improving lipid profiles. Clinically, small-scale trials demonstrate that topical ozonated oil and autohemotherapy reduce Psoriasis Area and Severity Index (PASI) scores and alleviate symptoms like erythema and pruritus, with efficacy comparable to topical corticosteroids in mild-to-moderate psoriasis. Safety profiles are favorable, with only mild, transient local irritation reported. However, comparative data with biologics are absent, and evidence is limited by small sample sizes, short study durations, and lack of long-term outcomes. While ozone therapy shows promise as an adjunctive treatment for mild-to-moderate psoriasis, large-scale, randomized controlled trials with extended follow-up and direct comparisons to biologics are needed to establish its therapeutic role.