OZONE IN RHEUMATOLOGY: A REVIEW

Inflammatory and non-inflammatory rheumatic diseases including osteoarthritis, fibromyalgia, rheumatoid arthritis, systemic sclerosis and gout affect millions of people worldwide. These conditions frequently result in chronic pain and reduced ability to function. While pharmacological interventions remain the cornerstone of treatment, many patients either fail to achieve adequate symptom relief or experience treatment-related complications. This clinical reality has prompted renewed interest in complementary approaches as in ozone therapy. This narrative review critically appraises the available published data on the use of oxygen-ozone mixtures in treating various rheumatic conditions. Experimental studies suggest that ozone modulates inflammatory cascades by affecting cytokine networks (particularly interleukin IL-1β, IL-6, and tumor necrosis factor-α) and redox homeostasis. Randomised trials in knee osteoarthritis have reported rapid analgesic effects following intra-articular injection, though the durability of these effects beyond six months remains uncertain. Major autohemotherapy appears to be beneficial for patients with fibromyalgia, with improvements reported in terms of pain severity, fatigue, and sleep architecture. A growing body of evidence, including a recent randomised study demonstrating 92% healing rates, supports the use of ozone therapy for refractory digital ulcers in systemic sclerosis. Preliminary observations also suggest a synergistic benefit when ozone is combined with tocilizumab for lower extremity ulceration in this patient group. Data on the use of ozone in the treatment of rheumatoid arthritis and gout are more limited, but are mechanistically plausible. Across indications, the safety profile appears favourable, with transient and minor adverse events predominating. Nevertheless, protocol heterogeneity and the absence of standardised guidelines pose significant challenges to clinical translation. This review discusses the available evidence, the underlying mechanisms, and the methodological gaps that require attention in subsequent investigations.