Abstract
Background
Operational and training requirements of soldiers necessitate prolonged use of occlusive footwear which makes them susceptible to Tinea pedis and affects their performance. This study assesses copper oxide–impregnated socks as a treatment modality in soldiers with Tinea pedis.
Methods
Three hundred serving soldiers with Tinea pedis were randomly divided in two groups of 150 cases each. One group was supplied with 02 pairs of polyester copper oxide–impregnated socks and the second group was treated with oral terbinafine 250mg /day for two weeks and topical terbinafine twice a day for three weeks. Five end points viz. scaling, erythema, fissuring, vesicular eruptions and itching were monitored using the visual analogue score (VAS) weekly for 03 weeks.
Results
Copper oxide socks helped in reducing all the end points as assessed by VAS. The group treated with terbinafine showed better response; however test socks were as efficacious as oral and topical terbinafine in controlling fissuring and vesiculation. Safety profile of the copper impregnated socks was comparable with the conventional treatment.
Conclusion
Copper-impregnated socks are effective and safe in treating Tinea pedis. They may also have prophylactic role in tinea pedis in susceptible serving soldiers deployed at remote locations in different terrain and weather conditions.
Keywords: Tinea pedis, Soldiers, Copper oxide, Socks
Introduction
Tinea pedis, also known as Hong Kong foot or athlete's foot, is a fungal infection that affects millions of people worldwide and is a major public health concern.1 It is a common infection in soldiers who are required to wear shoes for prolonged periods of time and are exposed to unhygienic environment, thereby affecting their operational performance. Approximately 15% of the population has a podiatric fungal infection at any given time, and over 70% have suffered from it at some point in their lives.2
The diagnosis of tinea pedis is often based on the clinician's assessment as there are no uniform global quantitative criteria defining the severity. There are both specific and non-specific anti-fungal agents available for treatment. Non-specific agents include Gentian violet, zinc pyrithione, 25% sodium thiosulphate with salicylic acid and aluminium chloride while specific agents include various systemic and topical anti-fungals like azoles and allylamines.3
Development of resistance, adverse effects, lack of compliance and comorbidities hinders the success of many anti-fungal treatments.2 Thus, newer treatment modalities are being tried, one of which is copper-embedded fabrics. Copper is a trace element, which plays a key role in many physiological processes in different tissues4,5 including angiogenesis and wound healing.6, 7, 8 Additionally, copper has very potent anti-fungal, anti-bacterial and anti-viral properties.9 In contrast, human skin is not susceptible to copper, and the risks of adverse effects are extremely low.10,11
Terbinafine is extremely well tolerated in any pharmaceutical preparation and also has been found to have a high efficacy in the treatment of tinea pedis. Terbinafine also has an added advantage of less duration required for the treatment of tinea pedis compared with other anti-fungal agents.12
The present study aims to assess the efficacy of copper-oxide impregnated socks on soldiers suffering from tinea pedis and compare with the conventional therapy of topical and systemic anti-fungal therapy.
Materials and methods
Study design
Randomized control trial on topical and systemic treatment modalities for tinea pedis, which includes a novel treatment modality in one arm and existing effective therapeutic modality in the other arm.
Study period
Three years – from September 2013 to September 2016.
Study place
Out-Patient Department (OPD) of Department of Dermatology of a tertiary care hospital.
Sample size
The study is a non-inferior variant of RCT where all participants were divided equally into two groups, and the two treatment modalities were administered to equal number of patients, randomized and analysed. The researcher specified the null and alternate hypothesis and taking into consideration the primary outcome measures, which includes response rates of standard treatment and new treatment, standard normal deviate, clinically acceptable margins and standard deviation, a sample size of 300 with 150 in each arm was deduced.
Ethical approval
We obtained the necessary approval to conduct this study from the Institutional Ethics Committee. The participants were explained about the purpose of the study and assured about the confidentiality of the information. Informed consent of the patient was taken prior to enrolment in the study.
Inclusion criteria
Three-hundred patients with tinea pedis (diagnosis clinical and also confirmed by KOH-mount microscopy and fungal culture) presenting to the Dermatology OPD at a large tertiary care hospital over a period of 3 years, i.e. September 2013 to September 2016, were included in the study.
Exclusion criteria
Amongst various topical and systemic anti-fungals used for treatment of tinea pedis, terbinafine and itraconazole remain in the stratum corneum of skin and the appendages for a maximum period of 4 weeks. Hence, patients who had already been on treatment with oral/topical medications for the same condition in the past 1 month were excluded from the study.
Methodology
Simple randomization was done using computer-generated sequence, and patients were divided into two groups of 150 each. The first group was provided with two pairs of copper-oxide impregnated socks to be worn for maximum possible time of the day (group 1). The patients in the second group were treated with oral terbinafine 250 mg/day for 2 weeks and topical terbinafine twice a day for 3 weeks (group 2).
Pre- and post-trial questionnaires were given to all patients to assess the degree of discomfort, itching and malodour. Serial photographs were taken, and four primary endpoints i.e. scaling, erythema, fissuring and vesicular eruptions were assessed along the Visual Analogue Score (VAS) [Table 1] both by patient and an independent dermatologist every week for 3 weeks. The data were maintained prospectively in a computerized database, which was further analysed using appropriate statistical techniques. Side effects, if any, due to copper-oxide impregnated test socks or with oral or topical terbinafine were documented.
Table 1.
Visual Analogue Score (VAS).
| Improvement | Score |
|---|---|
| Very much improved (76–100%) | 4 |
| Much improved (51–75%) | 3 |
| Moderately improved (26–50%) | 2 |
| Little improved (1–25%) | 1 |
| No improvement | 0 |
All the statistical analysis was performed using SPSS version 20. The clinical profile of patients was analysed by chi-square test for qualitative variables. Student t-test was performed for comparison of quantitative variables. Five percent probability level was considered as statistically significant i.e., p < 0.05.
Results
A total of 300 patients were studied (150 in each group). There was a male preponderance in the study (91% in group 1 and 95% in the group 2). Seventy-nine percent of group 1 and eighty-eight percent of group 2 had a positive fungal culture. Clinical description and site in both the groups are shown in Fig. 1, Fig. 2, respectively. Other associated symptoms of 70% of group 1 and 92% of group 2 had itching before treatment.
Fig. 1.
Group-wise distribution of clinical symptoms.
Fig. 2.
Site wise distribution of tenia lesions.
Improvement in scaling, erythema, fissuring, vesicular eruptions and itching/burning as well as improvement in average VAS (inclusive of all four outcome measures) by patient as well as dermatologist for both the groups after a period of 3 weeks are represented in Table 2, Table 3, respectively.
Table 2.
Visual Analogue Score (VAS) observed by dermatologist at week -03.
| VAS Score |
Total | p-value | |||||||
|---|---|---|---|---|---|---|---|---|---|
| 0 | 1 | 2 | 3 | 4 | |||||
| Group | Group 1 | Count | 33.0 | 21.0 | 37.0 | 47.0 | 12.0 | 150.0 | <0.001 |
| % of total | 22% | 14% | 25% | 31% | 8% | 100% | |||
| Group 2 | Count | 13.0 | 6.0 | 29.0 | 99.0 | 3.0 | 150.0 | ||
| % of total | 9% | 4% | 19% | 66% | 2% | 100% | |||
| Total | Count | 46.0 | 27.0 | 66.0 | 146.0 | 15.0 | 300.0% | ||
| % of total | 15.5% | 9.0% | 22.0% | 48.5% | 5.0% | 100.0% | |||
Table 3.
Visual Analogue Score (VAS) observed by patient at week 3.
| VAS Score |
Total | p-value | |||||||
|---|---|---|---|---|---|---|---|---|---|
| 0 | 1 | 2 | 3 | 4 | |||||
| Group | Group 1 | Count | 30.0 | 29.0 | 36.0 | 46.0 | 9.0 | 150.0 | <0.001 |
| % of total | 20% | 19% | 24% | 31% | 6% | 100% | |||
| Group 2 | Count | 12.0 | 6.0 | 34.0 | 96.0 | 2.0 | 150.0 | ||
| % of total | 8% | 4% | 23% | 64% | 1% | 100% | |||
| Total | Count | 42.0 | 35.0 | 70.0 | 142.0 | 11.0 | 300.0% | ||
| % of total | 14.0% | 11.5% | 23.5% | 47.5% | 3.5% | 100.0% | |||
Both the groups reported significant improvement in scaling, erythema, fissuring, vesicular eruptions and itching along with VAS. The improvement rates were better in the terbinafine group (group 2) for scaling, erythema and itching; however, the results were comparable for vesiculation and fissuring (difference was not statistically significant).
Study took into consideration the site of lesions i.e. intertriginous, dorsum of feet and soles. Bullous lesions were present in a total of 45 patients. Bullous lesions generally responded sub-optimally to the treatment in both the groups.
Three patients in group 1 reported to have side effects in the form of worsening of vesiculation, whereas in group 2 one patient developed nausea and vomiting due to oral terbinafine. The difference between the two groups in terms of side effect profile was statistically insignificant (p = 0.568) as represented in Table 4.
Table 4.
Group-wise distribution of side effects.
| Side effects |
Total | p-value | ||||
|---|---|---|---|---|---|---|
| No | Yes | |||||
| Group | Group 1 | Count | 145.0 | 5.0 | 150.0.0 | 0.005 |
| % of total | 97% | 3% | 100.0% | |||
| Group 2 | Count | 148.0 | 2.0 | 150.0 | ||
| % of total | 99% | 1% | 100.0% | |||
| Total | Count | 293.0 | 7.0 | 300.0 | ||
| % of total | 98.0% | 2% | 100.0% | |||
Discussion
Tinea pedis or athlete's foot is a very common entity affecting millions of individuals worldwide and is a major public health concern caused by dermatophytes. Trichophyton rubrum, Trichophyton interdigitale and Epidermophyton floccosum form the major group of organisms that cause tinea pedis. Adults are more commonly affected with a mean age of 15 years, and males are more commonly affected than females with a ratio of 2.26:1.1,2Amongst various predisposing factors, tight and prolonged use of shoes or socks and plantar hyperhidrosis are important, and the bacterial flora especially diphtheroids contribute to the infection. Four main clinical variants of tinea pedis are known, which are intertriginous, hyperkeratotic, bullous and ulcerative.1,2 Intertriginous tinea pedis is the commonest variant caused by T. interdigitale, but all four variants can be caused by any of the dermatophyte species. A soft corn in the fourth toe usually leads to chronic web space infection. Hyperkeratotic variant is commonly associated with toe nail onychomycosis and colloquially known as ‘moccasin foot’. Bullous and ulcerative variants are more common in immunocompromised patient with super added bacterial infection. Owing to their relatively asymptomatic nature, tinea pedis can be chronic and recalcitrant to treatment.4
Various topical and oral anti-fungals are used for treatment of tinea pedis amongst which itraconazole and terbinafine are most effective with lowest recurrence rates. Griseofulvin is effective but is sub-optimal. Topical azoles and allylamines are effective when combined with oral medications. Supportive treatments like potassium permanganate soaks, oral and topical antibiotics and removal of soft corns are essential in a few cases. The drawbacks in managing tinea pedis are antifungal drug resistance, adverse effects of drugs, lack of compliance and high rates of re-infections.3,5,7 Bonifaz et al in their study on recurrent tinea pedis found 10.46% of patients were at risk for re-infection by having contact with their socks. Usage of therapeutic properties of copper is a novel means of managing tinea pedis and the study attempts to evade a common predisposing factor like socks by impregnation of copper.5,6,8
Copper is a trace element, which has a key role in various physiological processes in humans with potent antifungal, antibacterial, antiviral, anti-inflammatory and angiogenetic properties. Early usage of copper as a therapeutic agent was used by Romans and Egyptians, which have now come into being in modern medicine since the early part of this century. It is hypothesized that copper has multiple mechanisms of action, which include alteration of tertiary structure of proteins, lipid peroxidation, deactivation of vital microbial enzymes and acceleration of superoxide-mediated damage. Therapeutic effects of copper were studied in 2016 study at the ICU where linen and floor tiles were impregnated with it in Massachusetts, and the hospital acquired infections by multi-drug-resistant organisms were significantly low in that setting. Subsequently, copper was used in manufacturing wound dressings, anti-viral masks and acaricidal beddings. The employability of copper in treating tinea pedis was a serendipity when 33 Chilean miners were trapped for 65 days and copper socks donning miners had no residual tinea pedis after 38 days. Studies conducted by Zatcoff et al, in 2008 and Guigillo et al, in 2012 emphasized effectiveness of copper-impregnated socks in treating tinea pedis with significant improvement in erythema, scaling and itching. Moreover, these studies mention that the concentration of elemental copper is not high enough to cause systemic absorption and adverse effects, and it accumulates in the epidermis and dermis predominantly. This makes copper a relatively safe drug when used topically as compared to other anti-fungals. Moreover, the content of copper remains unchanged even after 75 washings making its employability in fabrics ideal.7,8
Soldiers of Indian armed forces are routinely affected by tinea pedis to the extent that it is regarded as an occupational dermatosis instead of affection by chance. Longer periods of shoe-bound predisposition in long route patrols, exercises and training activities makes tinea pedis a chronic infection amongst soldiers and a potential hindrance in disposal of their duties. Lack of accessibility to oral and topical anti-fungals in remote terrains for longer periods makes it even more difficult to treat chronic fungal infections in armed forces personnel. A simple yet effective technique like impregnation of an anti-fungal like copper into socks of soldiers can be an apt solution to this chronic debilitating problem.9,10As copper is known to prevent hospital acquired infections, it can be used as a prophylactic measure for prevention of tinea pedis amongst serving soldiers by providing them with copper-impregnated socks.10,12
In the present study, the efficacy of copper-impregnated socks was analysed in comparison with the conventional therapy of topical and systemic anti-fungal therapy. Improvement was noted with copper oxide socks in all the endpoints i.e. scaling (44%), erythema (11%), fissuring (25%) and vesicular eruptions (63%) within 3 weeks. This was a significant improvement considering that the socks were used as a monotherapy. Hence, we recommend usage of copper socks for minimum 3 weeks for treatment or till the clearance of lesions. Fig. 3.
Fig. 3.
Clinical improvement following use of copper-oxide impregnated socks.
The results are consistent with the findings of various other studies. As per a study conducted by Gargiulo et al the tinea pedis infection was assessed by fissuring, scaling, erythema and/or vesicular eruptions after treatment with copper oxide socks before and after treatment. Statistical analysis revealed a significant reduction in the severity of all the endpoints analysed (p < 0.05).13
As per a study conducted by Shi et al, the short combination therapy with oral and topical terbinafine was found more effective than just topical.14 Current study observed similar improvements in the control group using terbinafine as high recovery grades and improvements in all the endpoints.
The improvement in two groups, in terms of fissuring and vesiculation was comparable, implying that copper socks are as efficacious as oral and topical terbinafine in controlling the above-mentioned signs. Copper-impregnated socks were also found to be comparable with terbinafine in terms of side effects.
Factors determining the efficacy of copper-oxide impregnated socks include patient's adherence to use of the socks, the active ingredient dosage, and the severity of the condition.14, 15, 16, 17
Advantages of the study
Novelty of this study is to use one of the most important risk factors for chronicity of tinea pedis i.e. socks and revert it into therapeutic/prophylactic advantage. The study is very ergonomic in its approach and can be used in a large scale. It also validates the fact that the use of copper-impregnated socks is equally effective as oral terbinafine with hardly any adverse effects.
Limitations
The study was conducted in an urban tertiary care hospital and patients of the nearby locality were recruited. Hence, effect of variables such as environmental factors (terrain, climate, humidity, temperature etc.) Lifestyle and protective clothing on the outcome of copper socks as a therapy for tinea pedis is yet to be ascertained. Also, soldiers of Indian navy and air force operate under different microenvironments compared with army personnel; hence, the efficacy needs to be validated in varied environment by further large-scale multicentric studies. Patients in both the groups were followed up for 3 weeks, longer follow-up would have further strengthened the study.
Further scope of study
Large-scale studies will further validate our findings and pave way for prophylactic use as well. Also, cost-to-benefit analysis of conventional woollen socks versus copper-oxide impregnated polyester socks need to be studied giving due cognizance to cost of consultation/medicines/hospitalization and intangible parameters such as loss of manhours and hindrance to operational and training efficiency of the combatants.
Conclusion
This study paves the way for use of copper-impregnated fabrics in tinea pedis. It can be inferred that copper-impregnated socks alone are effective and safe in treating tinea pedis as an alternate to oral and topical medication; further, it can also be logically extrapolated to have a prophylactic role. However, larger studies are needed in various climatic conditions and terrains like forests, mountains, coastal areas, ships and deserts for ascertaining the therapeutic and prophylactic roles.
Disclosure of competing interest
The authors have none to declare.
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