Topical ozone and chronic wounds: improper use of therapeutic tools may delay wound healing.

Dear Editor,

We present a patient with multiple non-healing lower extremity ulcers, and further discuss the inappropriate use of topical ozone therapy and the need for a comprehensive approach to wound management. A 40-year-old male patient, with diabetes mellitus and coronary artery disease of two years’ duration, applied to our hyperbaric and wound care center for multiple non-healing necrotic ulcers over his legs [Figure 1]. Ulcers occurred around his ankles three months ago and spread proximally thereafter, despite topical antibiotic therapy and gauze dressings delivered at a local hospital. Sunk into despair, he was attracted from flyers advertising ozone therapy for chronic wounds. Thus, during the following four weeks, he received several topical ozone therapy sessions, which yielded no further significant signs of improvement. Eventually, he was suggested bilateral lower extremity amputation by a surgeon. On physical examination, he had multiple, necrotic, and infected deep ulcers in variable sizes reaching tendons in some areas [Figure 1]. The ulcers had sharp edges and erythema around. He had significant bilateral edema on his lower extremities due to heart failure. He showed high levels of inflammatory markers [WBC: 22.400/ μl, C-reactive protein (CRP): 49 mg/L, erythrocyte sedimentation rate (ESR): 92 mm/h] and wound culture grew Escherichia coli. Pathology of the lesions revealed leukocytoclastic vasculitis. We hospitalized the patient and undertook a holistic approach comprising aggressive anti-edema treatment, culture-driven intravenous antibiotic regimen, and comprehensive daily wound care, including debridement of necrotic tissues and management of exudates. The multidisciplinary approach resolved his lesions rapidly, and the wound size and depth showed significant reduction. We discharged the patient after one-month care and continued follow-up as an outpatient for an additional four weeks. All ulcers of both legs almost totally epithelized in 8 weeks [Figure 2]. The patient was lost to follow-up after this time.

Figure 1

He had multiple, necrotic, and infected deep ulcers on both legs

Figure 2

Almost all ulcers of both legs epithelized in 8 weeks

Ozone therapy is administered for a wide spectrum of disorders ranging from diabetes to rheumatoid arthritis and from Alzheimer's disease to HIV. Although recent studies highlight the mechanism of action of ozone, improper use and toxicity of ozone therapy is still a concern. Ozone is a reactive gas and may be toxic if not used in therapeutic doses. Medical ozone therapy uses a gas mixture of ozone and oxygen, which never contains less than 95% oxygen.[1] There are several routes of ozone application. These include autohemotherapy, intramuscular, intra-articular, and paravertebral injections, rectal or vaginal insufflations, and topical ozone application.

A number of studies suggest that ozone therapy may have a role in the treatment of chronic wounds. Martinez-Sanchez et al. used three different routes of ozone application concurrently in diabetic patients with chronic wounds and compared the results with matched controls.[2] Patients in the ozone therapy group were treated by rectal ozone insufflations, topical ozone, and wound dressings with ozonized sunflower oil. Although the number of patients with complete healing was similar in both groups, ozone therapy increased the healing rate of wounds and reduced the hospitalization time.[2] Wainstein et al. used topical ozone therapy in addition to standard therapy in diabetic wounds.[3] Although the intention-to-treat analysis failed to show any benefit, the per-protocol analysis revealed that topical ozone therapy might confer clinical benefit when added to conventional treatment in diabetic wounds smaller than 5 cm2.[3]

Yet, the treatment of problem wounds accompanying multiple comorbidities, such as the one described here, presents a considerable therapeutic challenge and requires a multidisciplinary approach. The standard of care for treating chronic ulcers has been well established, and early and appropriate treatment is the cornerstone of treatment because even superficial wounds may, in time, progress to the subcutaneous tissues, muscles, tendons, or bones. Focusing on the so-called “advanced wound healing modalities” may sometimes result in an unintentional neglect of principles of wound care, and hence may lead to incurable wounds, which may ultimately require foot amputation.

Our case is a representative of improper wound management and improper implementation of ozone therapy, which although caused no direct harm to the patient, failed to heal the wounds. Once comprehensive wound care management policies targeting underlying factors were applied in our department, all ulcers responded well and showed a significant step towards healing.

This case report highlights two major issues. First, the role of ozone therapy is still poorly defined in the management of foot ulcers and should be used with caution. Randomized controlled studies are necessary to validate its beneficial effects (if any) and to define those patients who can be expected to derive the maximum benefit from ozone therapy. Second, adjunctive therapies should only be applied when conventional treatments fail to heal the wound.