Pasek, Jarosław MD, PhD; Stanek, Agata MD, PhD; Szyluk, Karol MD, PhD; Cieślar, Grzegorz MD, PhD
Advances in Skin & Wound Care: November 2022 – Volume 35 – Issue 11 – p 1-5
doi: 10.1097/01.ASW.0000874176.25479.2c
Abstract
Treatment with ozone therapy is of interest in many fields of medicine. In the field of angiology, ozone is used to treat infected wounds that are difficult to heal. In this case report, the authors report the introduction of innovative therapeutic equipment into clinical practice to accelerate the healing process of clinical wounds by the external application of ozone in various forms. They present positive results of the comprehensive treatment of a 52-year-old woman with an ulcer on her right lower leg, which formed after a previous orthopedic surgery. In addition to pharmacotherapy and compression therapy, local ozone therapy was applied. After 30 ozone therapy procedures, the ulcer healed completely, and the patient’s pain was significantly alleviated, as assessed by a visual analog scale (9.0 points before therapy vs 0.5 point after therapy). As a result, the patient’s quality of life improved, as assessed by the EuroQol scale (10 points before therapy vs 90 points after therapy).
The use of local ozone therapy can be an appropriate complement in the comprehensive treatment of chronic wounds. In the presented case, ozone therapy helped complete healing of the ulcer and significantly reduced the intensity of pain experienced, thus improving the patient’s quality of life.
ONLINE EXCLUSIVES
Ozone Therapy in the Comprehensive Treatment of Leg Ulcers: Case Report
Pasek, Jarosław MD, PhD; Stanek, Agata MD, PhD; Szyluk, Karol MD, PhD; Cieślar, Grzegorz MD, PhD Author Information
Advances in Skin & Wound Care: November 2022 – Volume 35 – Issue 11 – p 1-5
doi: 10.1097/01.ASW.0000874176.25479.2c
- Free
Abstract
Treatment with ozone therapy is of interest in many fields of medicine. In the field of angiology, ozone is used to treat infected wounds that are difficult to heal. In this case report, the authors report the introduction of innovative therapeutic equipment into clinical practice to accelerate the healing process of clinical wounds by the external application of ozone in various forms. They present positive results of the comprehensive treatment of a 52-year-old woman with an ulcer on her right lower leg, which formed after a previous orthopedic surgery. In addition to pharmacotherapy and compression therapy, local ozone therapy was applied. After 30 ozone therapy procedures, the ulcer healed completely, and the patient’s pain was significantly alleviated, as assessed by a visual analog scale (9.0 points before therapy vs 0.5 point after therapy). As a result, the patient’s quality of life improved, as assessed by the EuroQol scale (10 points before therapy vs 90 points after therapy).
The use of local ozone therapy can be an appropriate complement in the comprehensive treatment of chronic wounds. In the presented case, ozone therapy helped complete healing of the ulcer and significantly reduced the intensity of pain experienced, thus improving the patient’s quality of life.
INTRODUCTION
Chronic wounds occur in 2% of the population worldwide. In Poland, chronic wounds affect approximately 760,000 people, and the cost of treatment of such wounds amounts to almost 4 billion Polish zloty.1,2
In the lower extremities, chronic wounds are often ulcers of various etiologies and are associated with pain and reduced quality of life (QoL). Crural ulcers of the lower leg also reduce physical fitness, impede locomotion, and increase the risk of premature disability. In addition, the aesthetically unpleasant trophic changes and odor produced by necrotic tissues in chronic wounds may cause discomfort and a lack of self-acceptance in patients.3,4
The treatment of leg ulcers requires a comprehensive and interdisciplinary approach, as recommended by the TIME (Tissue, Infection and Inflammation control, Moisture, Edges) paradigm. The current approach of wound healing experts indicates the fundamental importance of the TIMERS (TIME, Repair, Social and individual related factors) paradigm.5
Ozone therapy is a physical procedure that is used in the treatment of leg ulcers of various etiologies. Ozone therapy using the active form of oxygen, ozone (O3), is most often applied topically in the form of dry baths. The oxygen-ozone mixture is applied to the lesion by means of the so-called “ozone shoe”6–8 in the following proportion: 5% ozone and 95% oxygen by volume.
Ozone applied to the area of the ulcer demonstrates a very strong bactericidal effect, the mechanism of which prevents bacterial strains from developing resistance. As a consequence of ozone’s decomposition, a diatomic oxygen molecule and active singlet oxygen are formed. The latter is a strong oxidant that damages the bacterial cell membrane by reacting with the polyunsaturated fatty acids; phospholipids; and proteins containing methionine, cysteine, and histidine. The oxidation of these compounds leads to changes in the permeability of cell membranes and to the secondary oxidation of proteins that are part of the enzymatic system in the cytoplasm, resulting in bactericidal properties. Because of these properties, ozone can successfully be used in the treatment of difficult chronic wounds, including infected wounds.9–11
CASE REPORT
This case report describes a 52-year-old woman with an ulceration of the lower leg that was treated with local ozone therapy. The patient came to the Clinical Department of Internal Diseases, Angiology, and Physical Medicine because of ulceration of her right leg that had persisted for 7 days. The interview and medical documentation showed that in May 2019 she underwent surgery because of a fracture in the right ankle joint. When the patient reported to the orthopedic ward to remove the metal anastomosis, she was not admitted because of the clinic’s COVID-19 procedures; the removal of the anastomosis was postponed and finally performed 3 months later. Seventeen months after the surgery, the skin in the area affected by the surgery ulcerated, and the patient was referred by her family doctor to the emergency angiologic clinic 7 days later.
On admission, physical examination revealed an infected ulcer in the distal part of the right lower leg with purulent discharge emitting an unpleasant odor and a visible inflammatory reaction around the ulcer (Figure 1). No evidence of osteomyelitis was present in the deep wound infection, and apart from edema due to the infection, no significant venous component was observed. The patient reported increased pain in the area of the ulcer (9.0 points on a visual analog scale) and difficulties in moving related to her inability to properly keep weight on the limb. The patient was also assessed for QoL using the EuroQol-5D-5L (European Quality of Life five-dimension, five-level) scale, which evaluates mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The patient scored 10 points on the scale (0 points = the worst QoL imaginable, 100 points = the best QoL imaginable).
Laboratory tests revealed leukocytosis of 13.1 G/L (reference range, 4.0–10.0 G/L) with a normal peripheral blood smear, mild macrocytic anemia (red blood cell count, 3.05 T/L [reference range, 4.0–5.2 T/L]; hemoglobin concentration, 10.5 g/dL [reference range, 12.0–16.0 g/dL]; mean red blood cell volume, 103.0 fL [reference range, 80.0–96.0 fL]; iron concentration, 67 μg/dL [reference range, 33.0–193.0 μg/dL]; and vitamin B12 concentration, 290.7 pmol/L [reference range, 145.0–637.0 pmol/L]), moderately elevated values of C-reactive protein inflammatory marker (56.1 g/L; reference range, 0–5.0 g/L), increased procalcitonin concentration (1.2 ng/mL; reference range, 0–0.5 ng/mL), and antibodies positive for anti-ds-DNA, as well as antinuclear antibodies (ANA 9). The ulcer swab was negative.
The patient was additionally treated for arterial hypertension and hypercholesterolemia. She did not have any other comorbidities affecting healing. The patient had a body mass index of 27.5 kg/m2 (moderate overweight). She smokes tobacco and consumes alcohol only occasionally.
During hospitalization, pharmacologic treatment was initiated, including comprehensive IV antibiotic therapy: amoxicillin (Augmentin) 2 × 1.2 g IV, clindamycin (Dalacin C) 2 × 300 mg IV, and metronidazole 2 × 500 mg IV; pentoxifylline (Polfilin Prol) 2 × 400 mg PO, sulodexide (Vesel Due-F) 2 × 250 units, and prednisone (Encorton) 30 mg PO. The treatment also included local ozone therapy using the ATO-3 apparatus (Metrum Cryoflex, Warsaw, Poland). The protocol of local ozone therapy was approved by the Local Bioethical Commission of the Medical University of Silesia in Katowice, Poland (permission no. KNW/0022/KB1/102/16). The patient signed a written informed consent for the publication of this report and granted permission for her photographs to be published.
During local ozone therapy, the lower leg of the patient placed in a plastic bag (the so-called “ozone shoe”) and exposed for 30 minutes to a gaseous oxygen-ozone mixture (5% ozone and 95% oxygen) with the concentration of 50 mg/mL. Treatment sessions took place every day, 5 days a week (no sessions on Saturdays or Sundays) in two series consisting of 15 treatment procedures each. There was a 3-week interval between the two treatment series to counter the potentially harmful long-term skin/tissue risk of ozone therapy. Because the local ozone therapy was applied to the tissue with the use of a plastic bag, the oxygen-ozone mixture was contained in a tightly closed space around the ulcer, preventing lung exposure and subsequent potential harmful effects in the form of lung fibrosis.
After each physical procedure, the wound was treated with a silver dressing (ALLEVYN Ag Adhesive; Smith+Nephew, Watford, UK) and local compression therapy with the use of a Codoban elastic bandage (TRICOMED, Łódź, Poland).
RESULTS
During treatment, gradual healing was observed, and the ulcer healed completely after 9 weeks (Figure 2). The patient also experienced gradual alleviation of pain until almost complete pain resolution was achieved (from 9.0 to 0.5 points on the visual analog scale). At the end of the ozone therapy cycle, tissue inflammation around the wound was reduced, and the patient subjectively assessed her QoL at the level of 90 points on the EuroQol-5D-5L scale.
Because leg ulceration recurs in almost 70% of patients, the patient had a check-up at the angiology clinic 6 months after completing treatment. Examination determined that the previously treated ulcer had healed fully, resulting in significantly improved aesthetics of the skin around the healed ulcer (Figure 3).
DISCUSSION
Treatment of leg ulcers is a frequent but difficult therapeutic problem. Thanks to the progress of modern physical medicine, devices for performing physical procedures can enable acceleration of the ulcer-healing process.3,6
Ozone treatment not only reduces infection by inhibiting bacterial cell activity, it also improves tissue metabolism by increasing oxygenation and reducing local inflammation. Under the influence of ozone, blood microcirculation is stimulated and tissue oxygenation increases, thus increasing the body’s natural defense system.9,12 The reported findings support that early and properly conducted ozone therapy as part of the comprehensive treatment of leg ulcers can result in a significant acceleration of healing with simultaneous relief of accompanying pain.8,10,13
One of the most important biological functions of ozone is the stimulation of the production of enzymes (eg, superoxide dismutase, catalase, and glutathione peroxidase) that work by eliminating free radicals. Ozone therapy also changes the structure and charge of the erythrocyte membrane: as a result of peroxidation of the lipids of the cell membrane, the erythrocyte membrane increases its elasticity and reduces the tendency for red blood corpuscles to adhere and result in a roll of erythrocytes. This makes it easier for erythrocytes to pass through narrowed blood vessels. All of the above mechanisms lead to improved blood flow in the blood vessels, improved oxygenation in hypoxic areas, and reduced symptoms of hypoxia. Moreover, after the use of ozone in the plasma, there is a significant increase in platelet-derived growth factor and transforming growth factor β1. The appearance of these cytokines may explain the accelerated healing of ulcers in patients.14–16
Another important action of ozone is the improvement of cellular metabolism by increasing the supply of oxygen to tissues, which accelerates granulation and thus wound healing.12,17 Ozone also induces the glycolysis process and the hexose pathway in erythrocytes, thereby increasing the concentration of 2,3-diphosphoglycerate, a compound responsible for increasing the amount of oxygen delivered to ischemic tissues.
In addition, ozone causes vasodilation, modified by the action of hydrogen peroxide, nitrous oxide, and cyclic guanosine monophosphate, and ozone therapy increases the level of glycolysis in erythrocytes. Because of this process, the concentration of 2,3-diphosphoglycerate increases, which causes an increased release of oxygen to the tissues. Ozone also leads to the activation of the Krebs cycle by enhancing the oxidative carboxylation process of pyruvate. The product of this reaction stimulates the production of ATP (adenosine triphosphate), a molecule that carries energy within cells.
Ozone significantly reduces the concentration of NADH (nicotinamide adenine dinucleotide) and supports the oxidation of cytochrome C. Because of these effects, tissue oxygenation and nutrient supplies are increased. In addition, the action of ozone activates fibroblasts and keratinocytes and stimulates the production of intracellular matrix and collagen, which helps to improve the effectiveness of the ulcer-healing process.9,10,15,18,19 Ozone also stimulates the synthesis of antioxidants, which, together with the reaction products of ozone (used in controlled doses) and polyunsaturated fatty acids, activate endothelial, interstitial, and blood cells, stimulating healing processes.4,16,20
Previous research has confirmed the efficacy of ozone treatment in wound healing. Kim et al12 applied topically ozonated olive oil to guinea pigs with artificially created acute wounds and found that the beneficial effect of this therapy related to the increased expression of platelet-derived growth factor, transforming growth factor β, and vascular endothelial growth factor. In another study, Roth et al18 demonstrated the bactericidal effectiveness of local ozone therapy in the case of two of the most common pathogenic bacteria: Pseudomonas aeruginosa and Staphylococcus epidermidis. Izadi et al,21 in turn, assessed the effectiveness of ozone therapy in 86 patients with chronic wounds. The authors showed that ozone therapy has a beneficial effect, not only on the process of chronic wound healing, but also on the QoL improvement of the treated patients. In another study, Kawecki et al22 assessed the effect of topical ozone therapy with the use of dry ozone baths on 32 patients with chronic wounds of various etiologies. They found that this method has a positive impact on the eradication of chronic wounds by reducing the number of colonies of Acinetobacter baumannii and Staphyloccus aureus.
Ozone therapy treatment is painless and does not require special preparations. It is estimated that in Europe the costs of treating and caring for patients with chronic wounds account for up to 5% of the budgets of European healthcare systems. Modern medicine is constantly looking for alternative, cost-effective methods to successfully treat chronic wounds.2,14 In the presented case history, the total cost of the therapy across all sessions, including ozone therapy procedures (€40), daily dressings with a specialized dressing (€103), elastic bandages for compression therapy (€8), and other dressing materials (€32) was approximately €183. Oxygen-ozone therapy is very cost-effective, and can reduce standard treatment costs by 25%.23
In terms of pharmacologic treatment of leg ulcers, many groups of drugs with different mechanisms of action have been used. The aim of pharmacological therapy is to ensure optimal conditions for the healing ulcers and inhibit the progressive fibrosis of the skin and subcutaneous fat tissue (lipodermatosclerosis). Another condition is the desire to reduce venous pressure, edema, and microcirculation disorders.4,14 Pentoxifylline is a frequently used drug for this purpose; its use significantly increases the number of ulcers that heal within 8 to 24 weeks.24,25
Kotz et al26 found that clinicians rated ALLEVYN Ag as satisfying or exceeding expectations in over 90% of patients with exuding chronic wounds. The condition of the wound tissue and surrounding skin improved, and there was a significant reduction in the level of exudate from initial to final assessment (P < .001). The evaluation showed that the dressing offered real benefits to patients and clinicians across multiple indications when used in conjunction with local protocols.26 In another study, Senejko et al27 evaluated the therapeutic efficacy of the active specialized medical dressing Atrauman Ag (HARTMANN, Heidenheim, Germany), which contains silver ions, and medicated paraffin gauze BACTIGRAS (Smith+Nephew) in the treatment of pressure injury. The researchers reported that average wound surface area significantly decreased in both research groups, and that the silver ion content supported curative effectiveness of the applied dressing.27
CONCLUSIONS
Ozone therapy can be a valuable supplement to classic pharmacologic treatment of chronic wounds, including leg ulcers. In many complicated cases it can prevent limb amputation.6,28 Although many studies have confirmed the beneficial effects of ozone therapy, its use in medicine is still considered controversial. More controlled, randomized clinical trials are needed to determine the effectiveness of this treatment and establish clinical criteria for its use.
The use of ozone therapy procedures can be an appropriate complement to the comprehensive treatment of patients with difficult to heal and infected wounds. In the presented case, the use of local ozone therapy resulted in complete ulcer healing and a significant reduction in the intensity of pain experienced, thus improving the patient’s QoL.
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