Management of Athlete's foot with topical Zinc Sulphate (15%) Solution versus Clotrimazole (1%) Solution

Background : Athlete's foot (tinea pedis) is by far the commonest fungal infections of the integument in the developed world that usually begins between the toes. Multiple drugs were used for the treatment of athlete's foot and including both; topical and systemic agents.Zinc sulphate has been used as topical antifungal agent. Objective: Comparison the efficacy of 15% zinc sulphate solution topically in the management of tinea pedis with topical clotrimazole solution. Patients and Methods: A therapeutic, single blind, comparative, study of Zinc Sulphate solution (15%) in the management of tinea pedis in comparison with clotrimazole solution (both topically), that conducted in the Unit of Dermatology and Venereology ,Baquba Teaching Hospital, extended from March 2020-July 2021 . Fifty patients, 31 males and 19 females with tinea pedis were registered in this study. Divided to 2 groups of patients included in the study:


Introduction
Athlete's foot or tinea pedis is one of the commonest fungi that infect the skin in the humans being.Also its common superficial fungal infection in developed countries.The most frequent dermatophytes that cause it Trichophyton rubrum(the most common and the most stubborn).T. mentagrophytes var.interdigitale and less by Epidermophyton floccosum,and the most cases are caused by that one of three organisms.The infected individual acts as a carrier, since when the infection occur, the organism may lasting as long as in the host [1].
Athlete's foot is more common in the adult than in children and more in males than women.The infection with tinea pedis occurs by the contact directly with arthroconidia (that produced by the filaments of dermatophyt), wearing of the tightly-fitting shoes also enhance the infection and it's spreading (spores in occlusive footwear encourage relapses) [2].The sharing of wash places, like the swimming pools, gymnasia, changing rooms of sports clubs and the public showers predisposes to infection [3].Athlete's foot considered as chronic fungul infection that often with remission with treatment and relapse thereafter, so the management is consider usually not so easy.There are many systemic drugs and include; terbinafin,,, itraconazole, and fluconazole.Topical antifungal medications like, allylamine, azole, ciclopirox, tolnaftate and undecenoic acid have been used in the treatment of Athlete's feet [4].Many of the drugs are used as antifungal drugs (azoles group and allylamines) that used currently in general practice for treatment of Athlete's foot have been shown to be less than satisfaction in eliminating the disease, even with good compliance from the treated patient.Azoles group that act as 14α-demethylase inhibitor of fungi and prevent the synthesis of the ergosterol; however, azoles group also inhibit the cytochrome P450 enzymes of mammalian.Allylamines prevent the formation of squalene epoxidase, that enzyme is crucial for the formation the cell membrane of the fungi, and have no effect on the mammalian cytochrome P450-dependent enzymes [5,6].
Odor in the Athlete's feet which is a common socio-medical issue, that could be caused either by the fungi of tinea pedis itself or by the associate microorganism like Brevibacteria( most one impotant for feet odor), as these microorganisms take the dead corneocytes on the feet and produce a cheesy odor and the sulfuric aroma, by the process that produce methanethiol from an amino acid (methionine).While Propionibacteria which present in the sebaceous glands ducts of the adolescent and adult it has vinegar-like odor as a result of propionic acid which result from the breakdown product of amino acids.Another microorganism that contributes to the feet odor is the Staphylococcus epidermidis that produce isovaleric acid by the degradation of the leucine that present in the sweat and give a strong cheesy odor [7,8].
Zinc is an important micronutient that is an essential component for more than 300 metalloenzymes that involved in a variety in metabolic pathways and cellular functions, that include the antioxidant enzymes, superoxide dismutase and affects their stability, conformity, and activity [9].Zinc sulphate was effective in the treatment of many skin diseases, where it used in the topical, intralesional or systemic formula , like acne vulgaris [10], recurrent oral aphthus [11] , cutanous leishmaniasis [12,13],many form of viral warts like plane warts [14],other viral infections [15,16], Tinea versicolor [17],and dermatophytes fungal infections [18].The action of zinc sulphate by the different mechanism of action that may be as antioxidant, immunomodulator, antiviral, anti-fungal , astringent, while it is cytotoxic in high concentration [19].
So, objective of the study is to compare the efficacy of topical 15% zinc sulphate solution in the managment of Athlete's feet in versus the topical clotrimazole solution.

Study protocol
The single-blind, comparative therapeutic study using topical 15% zinc sulphate solution with 1% clotrimazole solution for the management of tinea pedis was executed in the Unit of Dermatology, BaqubaTeaching Hospital between March 2020-July 2021.Fifty patients, 31 males and 19 females with tinea pedis were involved in this work.

Study design
The chief compliant is the tinea pedis (interdigital type) in all patients that attending to the Unit of Dermatology were only included regardless the age and sex.Full history were including: age of patients, sex, marital status, residence, social status, job, and history of the disease itself, including the duration, complaint of the patient, duration, associated with odor, family history, any seasonal variations and what is the aggravating factors.A socks type that been used, frequency of changes per day and type of the shoes also asked to all patients.In addition to history of drug intake that associated with sweating including aspirin, fluoxetin and insulin.
The assessment of severity of the disease in all cases was performed including :clinical examination to the lesion, and address the site, any changing in color , presence any of the dry scales, wet scales ,maceration , erythema and skin scraping test .Also the associated feet odor was assessed and scored.Evaluation of the patients was done every two weeks for one month and follow up was carried out.Photo for all lesions of the patients were taken by a digital camera (Sony:Cyber shoot with resolution 9 mega pixels), as a first visit(baseline) and then every other 14 days, in the same circumstances (place with fixed illumination and distance).

Study population
Exclusion criteria: patients were received no therapy for tinea pedis in the last two months prior the study.Patients with diabetes mellitus or atherosclerosis that may cause complications in the feet; deformity and malformation of the feet and immunosuppressant conditions were also excluded from the study.

Preparations
Fifteen percent of the zinc sulphate solution 15% (W/V) was produced by thawing zinc sulphate crystals (ZnSO4 7H2O=287.54It is manufactured by: Thomas Bekar India), 15

Results
Group A: Twenty five patients 16 (64%) males, 9 (36%) females involved in this group, with ages ranged from 27-73 and a mean± SD of 47.8±12.18years.While the disease duration ranged between 1-120 and a mean± SD of 43±46.61months.Also repeated foot washing ranged from 2-10 with a mean± SD of 5.24±2.66times/day.Twenty four (96%) patients had a feet odor and the manner of feet odor was cheesy odor in 20 (80%) patients and vinegar odor in 4 (16%) cases while 8 (32%) patients had itching.17 (68%) of cases presented with seasonal variation with tinea pedis that worsened during the summer time, while 16(64%) of patients had associated with plantar hyperhydrosis.While 10 (40%) cases madet drying of foot after the washing as a habit while others were not.
Group B: Twenty five patients presented with tinea pedis were involved in this study, 10(40%) females and 15 (60%) males.The ages were ranged from 24-65 with a mean± SD of 43.2±11.83years, and the disease duration were ranged from 1-180 months, and the mean± SD of 30.24±44.9 months.Also repeated foot washing ranged from 1-10 and the mean± SD of 4.84±2.15times/day.
Twenty (80%) of patients had feet odor and also the tinea pedis, while 8 (32%) patients reported a positive family history of tinea pedis, itching was found in 9 (36%) patients.The quality of odor was cheesy odor in 20 (80%) patients and vinegar odor in 2 (8%) patients.While 12 (48%) of caseshad history of variation around the seasons with worse odor during the summer time, and 19(76%) of patients had associated with plantar hyperhidrosis,and 12 (48%) patients had drying habit to the feet after washing while others were not.
The clinical response in that patients have the difference between two weeks and four weeks and was significant (chi square 7.14 P value =0.03).
The clinical response was also significant (chi square 20.12 P value =0.000043) in that patients between two weeks and four weeks of treatment.
Side effects of treatment were mild which included itching and burning sensation in 1(4%) patient.These side effects did not require discontinuation of the medicine.
There was no significant difference statistically in two weeks (chi square 5.37 P value =0.07) in the comparison between group A and B ,but was slightly significant at four weeks (chi square 6.65, P value =0.04).

Discussion
Athlete's foot considers the commonest form of dermatophyt skin infection in the North America, United Kingdom, and probably throughout the developed world [20].It is common in adults than more in children, but may also occur in children younger age 6years or more [21].The chance for presenting with tinea pedis in adult males probably about 20%, while among women to become chronically infected with tinea pedis only about 5% [ 21].It is a common problem seen among males and housewives, in Iraqi patients it accounted about (4.3%), with a mean age of 29 years and ranged from 17-53 years [22].
Three species of fungi are together responsible for the vast majority of cases of Athlete's foot throughout the world, Trichophyton rubrum, Trichophyton mentagrophytes var.interdigit ale, and also Epidermophyton floccose.The Trichophyton rubrum is consider the most common pathogen that associated with stubborn and chronic Athlete's foot [1].
Trauma, with the excessive moisture, and occlusive shoes, and also the frequent usage of public showers and pools these factors that might contribute to increase risk of infection: [23].
There are generale measurement in treatment of tinea pedis like wash of feet daily with drying thoroughly, avoid tight footwear, especially in the summer and avoid walking barefoot in the public areas, wear cotton socks and change them frequently and also wearing the plastic shoes or other of the footwear that do not allow sweat to be evaporate easily best to be avoided [24].
Feet odor is common sociomedical problem among males and it's etiology and pathogenesis is not well understood but there are multifactorial agents that play a role like weather,sweating,with bacterial, and fungal ORIGINAL RESEARCH Published: 5 2 December 2023 Doi: 10.26505/DJM.25027470402infections, wearing closed shoes and socks [7].The study showed that zinc sulfate was good agent in clearance of feet odor and probably work through its antibacterial and antifungal actions.
Zinc is an essential trace element that has direct anti-dermatophytes action in vivo and vitro [25] ,and had been shown to be an effective remedy in the treatment of pityriasis versicolor,Sharquie et al observed complete clinical and mycological clearance after 3 weeks treatment with 15% of zinc sulphate in the treatment of tinea versicolor [17]

Conclusions
Topical solution of 15% zinc sulphate was an effective treatment for tinea pedis and clearance of feet odor.

Recommendations
Our knowledgement To be better, the study that carried out and were observe the Zinc sulphate is an effective mode of treatment that used in the management of tinea pedis as 40% of patients had complete clearance but it was less superior than clotrimazole solution which gave76% clearance rate.
To increase the effectiveness of topical zinc sulphate a higher concentration like 25% is recommended [26].

Source of funding:
The current study was funded by our charges with no any other funding sources elsewhere.actinic keratosis.J cutenous and anesthetic surgery 2012;1(5).
grams in 100 ml of Distilled Water, and kept in cleaned container at the room temperature of hospital and Clotrimazole(1% )solution is obtained from MEDICO LABS _SYRIA.Clinical response score No clearance: -If there is no any response while clinically examine and no change in scoring of feet odor.Partial clearance: -If there is some clinical improvement,like change of wet scales into dry scales, abscence in scales and change in feet odor.Complete clearance: -There is complete clearance of rash and odor Scoring of feet odor The scoring system had been used to assess the patients with bared feet and any odor and to evaluate the odor intensity in that case and involve four points: Score 0: No any odor.Score1: mild; the odor is smell only when the patient's finger put between the toe webs of his sole.Score2: Moderate; when the doctor in close to the patient can smell the odor.Score 3: Severe; the surrounding people can smell the odor.
Figure (1B): Same patient above after one month of 15% topical zinc sulfate solution application ,and other superficial fungal infection [18].Sharquie et al in a single blinded placebo controlled therapeutic trial studied the efficacy of 15% zinc sulphate solution for the treatment of foot odor [27].
It done by Excell 2010, SPSS version 20 statistical program.P_value is considered significant when less than 0.05, It done by Excell 2010, SPSS version 20 statistical program.