Ozone in chronic leg ulcers (Part one)

As we mentioned in the first article about ozone therapy, one of the main indications is the treatment of hard-to-heal wounds, where the most common is chronic leg ulcer (CLU).

Chronic leg ulcer is defined as any wound below the knee that does not heal within a 6-week period. It is a common pathology affecting about 1% of the population and up to 3% of people over 65 years old. CLU has a significant impact on the person's quality of life as well as on the cost of the healthcare system.

Healthcare financial reports estimate that 1% of annual healthcare budgets in European countries go towards the treatment of leg ulcers. In the USA, patients with CLU are estimated to be over 6 million with a financial impact of about 2 billion Euros. In Italy, about 2 million people have CLU.

Regardless of etiology, CLU leads to tissue inflammation as a result of inadequate blood supply, resulting in tissue anoxia, edema, induration, and extravasation of serum, cytokines, and blood elements. The final step of this pathophysiological cascade are structural changes in the surrounding tissues and cell death.

The healing process

Regardless of the etiology (venous stasis, trauma, diabetes), an ulceration represents a breach in the epithelial layer covering the skin so that the underlying tissue is exposed and damaged. The physiological response is the activation of the healing process with the interaction of platelets, collagen, and exposed extracellular substances. Although the healing process is a continuum that begins immediately after damage, conventionally it is divided into 4 phases: inflammatory, migratory, proliferative, and remodeling.

If the metabolic demands of the damaged tissue are not met properly, the healing cascade is interrupted in the inflammatory phase, and the lesion becomes chronic.

A chronic lesion is characterized by an increase in the concentration of vasoactive substances such as histamine, bradykinin, serotonin, PAF (platelet activating factor), TNF (tumor necrosis factor), growth cell factors, ADP (adenosine diphosphate), arachidonic acid derivatives (prostacyclin, thromboxane, leukotrienes), interleukin, etc. Chronic inflammation is also responsible for the persistence of platelets and the activation of the coagulation cascade, vascular permeability, edema, capillary compression, hypoperfusion, etc.

Local ischemia is a critical factor that hinders the healing process because it perpetuates hypoxia, low pH, high concentration of lactic acid, and lipid peroxidation. Oxidative metabolites such as free radicals and other ROS dramatically increase in areas with chronic hypoxia and become major factors for the chronicity of the lesion.

Under physiological conditions, the synthesis of ROS (reactive oxygen species) is balanced by the scavenging activity of endogenous antioxidant mechanisms of agents like superoxide dismutase, catalase, albumin, etc. When this equilibrium is disrupted, the toxic effect of ROS clinically manifests in various forms up to permanent tissue damage.

How does ozone affect CLU?

Locally, ozone has a bactericidal, wound-cleaning, and wound-healing effect.

Systemically, ozone regulates the body's antioxidant mechanisms, accelerates the cleansing process of free radicals, detoxifies the body, activates endogenous protective enzymes, improves tissue oxygenation and the rheological properties of the blood, and mobilizes cellular and humoral immunity.

Ozone therapy is applied alongside conventional treatment, including wound care. It practically combines ozone bagging with MAHT (major autohemotherapy), microinjections of ozone around the wound, injection of biologically active points, etc.

From the international journal of ozone therapy (INTERNATIONAL JOURNAL OF OZONE THERAPY) I have excerpted two articles that present spectacular results of ozone therapy with one of its forms: MAHT or ozone bagging. If these forms were combined with each other (alongside conventional treatment) the results would be even better, and the time and cost of treatment would be significantly reduced.

The above-mentioned articles present many cases. Let's look at some of them.

Case 1. A 57-year-old man; non-smoker, non-alcoholic. He had no other accompanying diseases. Two years ago he started suffering from deep ulcers in both legs with progressive worsening. The patient was visited by several specialists including a dermatologist, internist, allergologist, plastic surgeon, and vascular surgeon. Allergic, vascular, and autoimmune diseases were ruled out. Ultimately, a diagnosis of vasculitis of unknown origin was made.

Even cortisone treatment had no effect. The pain was unmanageable despite major and minor analgesics. The patient's quality of life was quite poor as a result of continuous pain and extreme limitation of movement.

An epidural catheter was placed where bupivacaine (25 mg/day) and morphine (3 mg/day) were administered. The pain was managed, but the lesion worsened and became infected. As an extreme measure, the surgeon considered bilateral amputation of the legs. As a last chance, MAHT was started. After 62 treatments, the left leg healed completely, while the right one after 120 sessions of MAHT (Fig.1).

Right leg	Left leg
Result