Topical 15 % Zinc Sulfate Solution Is an Effective Therapy for Feet Odor *

Background: Feet odor is a common sociomedical problem that affects the feet of human beings of different etiological factors. Multiple modalities of therapy have been used in the treatment of feet odor. Objective: To evaluate the efficacy and safety of topical 15% zinc sulfate solution in the treatment of feet odor. Patients and Methods: This single blind, placebo, controlled therapeutic study was conducted at the Department of Dermatology-Baghdad Teaching Hospital, from March 2010 to July 2011. A total of 108 (88 males and 20 females) patients with feet odor were enrolled and were divided into 2 groups: Group A: treated with 15% zinc sulfate solution. Group B: treated with distilled water as placebo control group. Full history and examination were carried out including all relevant points. Four scoring had been used to assess the severity of odor in patients with bared feet Score 0: no odor, Score 1: mild odor, Score 2: moderate odor and Score 3: severe odor. Zinc sulfate solution 15% was applied to sole and toe webs once daily for two weeks, three times per week for next two weeks and followed by single application weekly as maintenance after clearance of odor for two months. Patients were seen every two weeks to be examined and to score the odor again and to record side effects. Results: Group A: Fifty patients completed the study, their ages ranged from 8 68 (33 + 14.5) years, while the duration of the disease ranged from 1 180 (7.22 + 38.24) months. The complete clearance of feet odor after two weeks of therapy was 35 (70%) patients which was similar to two months maintenance therapy 35 (70%) and was highly statistically significant (p value = 0.0000001). Group B: Fifty patients received the placebo solution, their ages ranged from 16 75 (32.6 + 13.4) years, while the duration of the disease ranged from 1 180 (43.7 + 47.65) months. The complete clearance of feet odor was in 1 (2%) patient after two weeks therapy and after two months maintenance therapy. No side effects were recorded. Conclusions: Topical 15% zinc sulfate solution had an effective therapeutic and prophylactic action against feet odor.


Introduction
Feet odor is a common socio-medical problem, its etiopathogenesis is not well elucidated but there are multifactorial agents like sweating, bacterial, fungal infections, shoes and socks [1].
The most common type of bacteria of feet is Brevibacteria which is considered a major cause of feet odor because they ingest dead skin on the feet and, in the process, convert amino acid methionine into methanethiol, which has a sulfuric aroma and cheesy odor.Also Propionibacteria which thrive in the ducts of adolescent and adult sebaceous glands produce propionic acid as result of a breakdown product of amino acids, it has vinegar-like odor.Staphylococcus epidermidis also play a role in feet odor by degradation of leucine present in sweat and changed it to isovaleric acid, which give strong cheesy odor [2].
There are many systemic drugs like anticholinergic (glycopyrrolate) [3] and topical antibacterial drugs like erythromycin, clindamycin and benzoyl peroxide have been used in the treatment of feet odor [4].Also, topical anti-perspiration agents like aluminum salts and ionto-phoresis have been used as therapeutic measures [5,6].
For this reasons the present study was designed to evaluate the efficacy and safety of topical 15% zinc sulfate solution in the treatment of feet odor.

Patients and Methods
This single blind placebo controlled therapeutic trial using topical 15% zinc sulfate solution in the treatment of feet odor was carried out in Department of Dermatology and Venereology, Baghdad Teaching Hospital from March 2010 to July 2011.One hundred eight (88 males and 20 females) patients with feet odor were included in this work.All patients attending the Department of Dermatology and Venereology complained from feet odor were included regardless the age and sex.

Exclusion Criteria
Patients with feet odor with associated tinea pedis, patients had received any therapy for feet odor for last two months, patients with feet complication of diabetes mellitus or atherosclerosis, feet deformity, malformation and patients on immunosuppressive drugs were excluded.
Full history and examination was performed including: age, sex, marital status, residence, social status, job, history of feet odor and family history, duration, type, site, associated with axillary odor, palmoplanter hyperhidrosis, seasonal variations and aggravating factors.Also, history of type of socks, daily change and type of shoes were taken from all cases.
Formal consent was taken from each patient after and full explanation about the nature, course of treatment.The ethical approval was obtained from the Scientific Council of Dermatology and Venereology-Arab Board for Medical Specializations, Patients were instructed for cleaning and drying the feet and apply the solution to the sole and toe webs as follow: single daily for two weeks, three times per week for other two weeks then single application weekly as maintenance therapy for two months and at each visit the following scoring was done:

Scoring of feet odor (Sharquie's scoring):
Four scoring had been used to assess the severity of odor in patient with bared feet: Score 0: No odor.Score 1: Mild odor as it is smelt by patient only when he puts his finger in between toe webs and on his sole.
Score 2: Moderate odor as it is smelt by examining doctor in close contact with patient.
Score 3: Severe odor as the odor is smelt by surroundding people.
This score has been used for first time for such studies.Follow up of the patients was done every two weeks to assess the response to therapy, to do scoring of odor again and to record any side effects.

Preparation and Treatment Plan
Fifteen percent (W/V) zinc sulfate solution is prepared by dissolving 15 grams of zinc sulfate crystals (ZnSO 4 7H 2 O = 287.54,by Thomas Bekar India) in 100 ml of distilled water, and kept in clean container at the room temperature of hospital.Patients were asked to apply this preparation on their sole and toe webs using cotton applicator.
Statistical analysis was used in all parameters.Student's t test used for comparison of means by analysis of variance scoring and Chi Square used to compare the changes that result from the treatment.
P value of less than 0.05 is considered to be significant.

Results
Hundred patients completed the therapy, while 8 patients defaulted for unknown reasons.
Group A: Fifty patients 8 (16%) females and 42 (84%) males included in this group.Their ages ranged from 8 -68 years with a mean ± SD of 33 ± 14.5 years; while the duration of the disease ranged from 1 -180 months with a mean ± SD of 7.22 ± 38.24 months.
Seven (14%) patients had axillary odor in addition to feet odor while 8 (16%) patients had positive family history of feet odor.History of palmoplanter hyperhydrosis was found in 6 (12%) patients, while 44 (88%) patients had associated plantar hyperhydrosis.The quality of odor was cheesy in 33 (66%) patients and vinegar odor in 17 (34%) cases.Twenty one (42%) of patients had seasonal variation and was worse odor during summer time, while 15 (30%) cases had habit of drying of their feet after washing.
Scoring of feet odor before therapy was Score 1 in 21 (42%) patients, Score 2 11 (22%) patients and Score 3 18 (36%) patients (Table 2).Group B: Fifty-three patients with feet odors were included in this study.Fifty patients of feet odor had received the placebo solution (distilled water), consisted from 10 (20%) females and 40 (80%) males.Their ages ranged from 16 -75 years with a mean ± SD of 32.6 ± 13.4 years while the duration of the disease ranged from 1 -180 months with a mean ± SD of 43.7 ± 47.65 months.
The quality of odor was cheesy odor in 39 (78%) patients and vinegar odor in 11 (22%) patients.Twenty (40%) of patients had seasonal variation with worse odor during summer time.Twenty (40%) cases had habit drying of feet after washing.
So the response to two months maintenance therapy could be summarized as follow: 35 (70%) patients had complete clearance which was similar to that after 2 weeks therapy, 11 (22%) patients with partial clearance and 8 (16%) patients no change in odor (Table 4 & Figure 1) (Chi square = 74.60,degree of freedom = 2, p value = 0.0000001).
No side effects were recorded apart from slight irritation in the early course of treatment which did not require discontinuing the treatment Group B: Scoring of feet odor after 2 weeks of therapy with distilled water was: score 0 in 1 (2%) patient, score 1 in 22 (44%) patients, score 2 in 9 (18%) patients and score 3 in 18 (36%) patients (Table 3) (t test = 0.18) (p value = 0.67).
So the response to therapy after two months could be summarized as follow: 1 (2%) patient had complete clearance, 2 (4%) patients with partial clearance and 47 (94%) patients showed no change in odor (Tables 4-6 & Figure 1).

Discussion
There are many etiological factors involved in feet odor like wearing shoes, hyperhydrosis, maceration of skin, proliferation of bacteria and fungal infections.All these factors encourage bacteria species like Staphylococcus epidermidis, Propionibacteria and Brevibacteria to produce volatile short chain free fatty acid which gives characteristic odor like cheesy and vinegar [2].Feet odor is common problem among Iraqi population especially in summer time.This problem practically is seen among people wearing close shoes and specifically among army people.From our daily practice we noticed that feet odor has personal diathesis as some people produce odor while the others not and both of them wear closed shoes and this was confirmed by the present work as family history was positive in 20% of patients.
There are many therapies which had been used in controlling feet odor, but according to our practice none of these are satisfactory topical antibacterial like erythromycin, clindamycin and benzyl peroxide [4] and topical antiperspirant agents (aluminum salts and iontophoresis) [5,6].
The present work showed that zinc sulfate is an effecttive mode of therapy in treatment of feet odor as 70% of patients had complete clearance after two weeks.This 70% clearance continued after two months of maintenance therapy and this was related to once week application of zinc sulfate.This was in comparison with 2% complete clearance treated by placebo.
The mechanism of action of topical zinc sulfate is not well elucidated but most probably related to its multiple effects like antibacterial, antifungal and anti-perspirant actions.
To the best of our knowledge, this is first study carried out and showed that topical 15% zinc sulfate solution is an effective clearance of feet odor.
To keep the clearance of feet odor, we strongly advise patients to keep maintenance therapy through once application every week as shown in the present study.
Scoring of feet odor is difficult to be carried out but fortunately we invented a new scoring system that proved its practicality by the present work.
In conclusion, topical 15% zinc sulfate solution proved it's effectiveness in clearance of feet odor in 70% of patients and it had both therapeutic and prophylactic actions.

Figure 1 .
Figure 1.Clinical responses among patients with feet odor following 2 months after therapy in group A and group B.