Non-invasive Ozone Therapy Shows Effectiveness in Treating Digital Ulcers

Non-invasive, local treatment of digital ulcers with ozone for 20 days showed clinical effectiveness in systemic sclerosis patients, according to a new study.

The study, “Non-invasive Oxygen-Ozone Therapy in Treating Digital Ulcers of Patients with Systemic Sclerosis,” was published in the journal Acta Reumatológica Portuguesa, and was conducted by researchers at Asyut University and Suez Canal University, in Egypt.

Systemic sclerosis (SSc), or systemic scleroderma, is a chronic autoimmune disease that affects connective tissue (the tissue that supports and holds other tissues or organs together), and is characterized by excessive production of collagen protein, leading to fibrosis of the skin and internal organs.

Excessive collagen deposition can also narrow small blood vessels in the fingers and toes, resulting in Raynaud’s phenomenon, a condition where the fingers and toes feel numb, prickly and frigid in response to cold temperatures or stress.

Recurrent Raynaud’s phenomenon, poor peripheral circulation, and microtrauma can result in the development of digital ulcers (DUs), which can have a significant negative impact on a person’s quality of life. DUs are estimated to affect half of patients with SSc, and can be difficult to manage.

Ozone is considered an oxidant and disinfectant, with antiviral and bactericidal properties. Ozone has also been shown to help in wound healing, including diabetic foot ulcers; however, the mechanism through which ozone achieves healing in chronic wounds is not well-understood.

Researchers investigated the potential effectiveness of ozone therapy in the treatment of SSc DUs.

The study involved 50 female SSc patients with DUs (mean age 40.93 years; mean duration of Raynaud’s manifestation 8.13 years). Patients were divided into two groups: 25 were treated with a calcium channel blocker (Epilat 40 mg/day) and ozone for 20 days; the other 25  (control group) were treated with the calcium channel blocker only. Calcium channel blockers are a type of vasodilator therapy.

Ozone treatment was non-invasive and involved covering the ulcerated area with a special bag connected by a tube to an ozone generator. The treatment was administered 30 minutes a day for 20 days.

At the end of the treatment period, investigators saw a significantly greater reduction in wound size in patients treated with both ozone and the calcium channel blocker (wound size of 0.75 millimeters), compared to patients treated with the calcium channel blocker alone (2.44 millimeters).

In addition, the effective healing rate — defined as a visible reduction in ulcer size (less than half the initial size, more than half, or complete healing) — was significantly greater in ozone-treated patients (24 of 25, or 96%, showed evidence of healing) than those treated with the calcium channel blocker alone (11 of 25, or xx44%).

Researchers also found that patients treated with ozone “showed greater improvement in clinical characteristics, including number of Raynaud’s attacks/day, duration of Raynaud’s attack, and ulcer pain in comparison to the control group,” they said.

Using biopsies of ulcer borders and surrounding skin, the team also measured the levels of vascular endothelial growth factor (VEGF; a protein that stimulates the formation of blood vessels), and autoantibodies against the endothelin-1 type A receptor (ETAR). SSc patients often have autoantibodies against ETAR; these bind to the receptor in blood vessels, either inducing local inflammation and fibrosis, or activating it and mimicking the effects of endothelin (constricting blood vessels).

Results showed that after 20 days of treatment, levels of VEGF were significantly increased in ozone-treated patients; this could be beneficial, as it would enhance the formation of new blood vessels and improve blood circulation in the affected area. In contrast, the levels of autoantibodies against ETAR were significantly lower in these patients, which would reduce harmful inflammatory or vasoconstrictive effects.

The team acknowledged some limitations of the study, including the small sample size, the fact that both patients and clinicians knew what treatment was being administered, and the lack of an additional control group with patients subjected to the same procedure as ozone-treated patients but without receiving ozone (placebo group).

Nonetheless, based on the results, the team concluded that “ozone therapy may be a beneficial tool in the treatment of DUs in SSc patients, where it promotes wound healing through a potential induction of VEGF and downregulation of ETAR at sites of the ulcers.”