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Australasian Journal of Dermatology (2002) 43, 175–178
Treatment of interdigital tinea pedis with 25% and 50% tea tree oil solution: A randomized, Andrew C Satchell,1 Anne Saurajen,1 Craig Bell2 and Ross StC Barnetson1
1Department of Dermatology, Royal Prince Alfred Hospital, Camperdown and 2Australian Tea Tree Oil Research Institute, Southern Cross University, Lismore, and Epidermophyton floccosum, and appears to be related to occlusive footwear.2 Tinea pedis occurs as one of four clinical variants: intertriginous, papulosquamous, vesicular Tea tree oil has been shown to have activity against and acute ulcerative.3 Chronic, intertriginous tinea pedis is dermatophytes in vitro. We have conducted a random- characterized by a scaling and fissuring of the lateral toe ized, controlled, double-blinded study to determine the webs caused by dermatophyte invasion of the stratum efficacy and safety of 25% and 50% tea tree oil in corneum; macerated, erosive infections may follow as a result the treatment of interdigital tinea pedis. One hundred of secondary overgrowth of commensal bacteria, including and fifty-eight patients with tinea pedis clinically and Micrococcaceae (usually staphylococci), aerobic coryneforms microscopy suggestive of a dermatophyte infection and Gram-negative organisms.4 Microscopy and culture of were randomized to receive either placebo, 25% or 50% skin scrapings are used to identify the relevant organism.
tea tree oil solution. Patients applied the solution twice The treatment of intertiginous tinea pedis includes daily to affected areas for 4 weeks and were reviewed measures aimed at reducing hyperhidrosis, such as talcum after 2 and 4 weeks of treatment. There was a marked powder and wearing open-toed shoes. Topical antibacterial clinical response seen in 68% of the 50% tea tree oil measures such as 25% acetic acid soaks and colourless group and 72% of the 25% tea tree oil group, compared Castellani’s paint (phenolated resorcinol) are helpful in to 39% in the placebo group. Mycological cure was treating macerated infections.5 Topical antifungal treatments assessed by culture of skin scrapings taken at baseline for interiginous tinea pedis include tolnaftate, the imidazoles and after 4 weeks of treatment. The mycological cure and terbinafine; short-term oral treatments include itracona- rate was 64% in the 50% tea tree oil group, compared zole 400 mg daily for 1 week and terbinafine 250 mg daily to 31% in the placebo group. Four (3.8%) patients applying tea tree oil developed moderate to severe Tea tree oil (melaleuca oil) is an essential oil extracted dermatitis that improved quickly on stopping the primarily from the leaves of Melaleuca alternifolia, a shrub- like tree native to northern New South Wales and southernQueensland. Tea tree oil has antimicrobial properties and has Key words: athlete’s foot, melaleuca oil, natural
been used as a natural remedy for a variety of skin complaints therapy.
for many years. During World War I, tea tree oil was includedin the first-aid kits of Australian troops to treat burns, bites,and infections. Tea tree oil is widely available in Australianpharmacies and natural therapy stores in various prepar- INTRODUCTION
ations, including antifungal gel 50 mg/g, acne gel 200 mg/g, Tinea pedis is a dermatophyte infection of the feet or toes antiseptic cream 50 mg/mL, antiseptic solution 15% and affecting 10% of the population at any given time.1 It is most 100%, head lice solution 10%, insect repellant 18.9 mg/mL and commonly caused by Trichophyton rubrum, T. mentagrophytes shampoo and conditioner. Clinical studies have suggested teatree oil is effective in treating tinea pedis,7 onychomycosis8trichomonal vaginitis,9 acne10 and dandruff.11 Correspondence: Professor RStC Barnetson, Department of Tea tree oil is a complex mixture of hydrocarbons Dermatology, Royal Prince Alfred Hospital, Camperdown NSW 2050, and terpenes, consisting of almost 100 substances, and Australia. Email: [email protected] the antimicrobial activity appears to be related to the Andrew C Satchell, MB BS. Anne Saurajen, MB BS. Craig Bell, PhD.
major component, terpinen-4–0 L,12 which accounts for Submitted 8 October 2001; accepted 3 January 2002.
one-third of the final volume of tea tree oil. The minimum inhibitory concentration of tea tree oil for T. rubrum is 1.0% Patients were randomized to receive either placebo (20% volume/volume and T. mentagrophytes 0.3–0.4% volume/ ethanol, 80% polyethylene glycol), or 25% or 50% tea tree oil mixed in ethanol and polyethylene glycol solution. They were The activity of tea tree oil against dermatophytes prompted instructed to wash their feet with soap and water, dry between our department to trial its use in tinea pedis. In an earlier study the toes and apply the solution to the affected areas twice daily of 104 patients randomly assigned to receive either 10% tea for 4 weeks. They were given advice about the wearing of open tree oil cream, tolnafate 1% cream or placebo, we found that footwear and requested not to use other antifungal treatments.
10% tea tree oil cream significantly improved the condition The patients were reviewed at weeks 2 and 4 of the treat- clinically, but the mycological cure rate, while improved, ment. At each visit an assessment was made of scaling and was not significantly greater than placebo.7 Therefore, it was inflammation by the investigator, and burning and itching considered that an increased concentration of tea tree oil by the patient. Each of these was graded as absent, mild, might be more effective in achieving mycological cure. At moderate, severe or very severe and given a corresponding high concentrations tea tree oil is not stable in a cream. In score of 0–4; the four scores added together to give the this study we have compared 25% and 50% tea tree oil with ‘clinical score’. Assessments were made without referring placebo in a randomized, double-blind study of patients with back to previous scores. A marked clinical response was considered to be a reduction of three or more in the clinicalscore to a final value less than three, or a final value of zero.
The mycological cure rate was determined from culture of skin scrapings taken at baseline and at the end of the 4-week The study was approved by the Ethics Review Committee of treatment period. ‘Effective cure’ was considered to be both a the Royal Prince Alfred Hospital in Sydney, Australia, and marked clinical response and mycological cure.
informed consent was obtained. One hundred and fifty-eight It was anticipated that at least one of the tea tree oil groups patients, aged 14 or older, with typical clinical features of would have a response rate of at least 60%, and it was assumed intertriginous tinea pedis were recruited by advertising in local there would be a 20% response rate in the placebo group. In newspapers. A skin scraping was taken for microscopy and order to be able to declare this difference as statistically differ- culture and only those with microscopy suggestive of a ent at the 0.025 level, it was determined that there should be dermatophyte infection were enrolled into the study. Patients 32 patients in each treatment group. It was also assumed, excluded from the study were those treated with systemic based on previous work by this department, that approxi- antifungals within the preceding 6 months or topical anti- mately 40% of patients who present with positive microscopy fungals within the preceding 7 days, and those with derma- will have a negative culture for dermatophyte infection. As the titis, immunosuppression or a history of hypersensitivity to tea culture takes approximately 2–4 weeks to grow, all patients with a positive microscopy were enrolled in the study, but only Mycologic response at the end of 4 weeks treatment Clinical response at the end of 4 weeks treatment those patients who later showed a positive culture for dermato- tree oil and three patients applying 50% tea tree oil, one of phytes were included in the evaluation. Thus, a sample of whom was withdrawn from the study. These dermatitis reac- 54 patients per treatment group was chosen to ensure at least tions responded quickly to stopping the study medication 32 patients with confirmed dermatophyte infections in each and topical corticosteroids were used in two patients. Stinging group. The significance of the differences between the 25% tea on application was reported in two patients applying 25% tea tree oil group, the 50% tea tree oil group and the placebo group tree oil and two patients applying placebo, and was described was assessed using the χ-squared test. P values of <0.05 were as mild, lasting for a few seconds. There were no serious DISCUSSION
There were 158 patients enrolled into the study, of whom 104 There has been increasing interest in the use of natural ther- (66%) were male and 54 (34%) were female. Their ages ranged apies. Tea tree oil is one such product and is already widely from 17 to 83, with a mean age of 41 years. There were available in Australia for the treatment of superficial infections 53 patients randomized to the placebo group, 54 to the 25% tea tree oil group and 51 to the 50% tea tree oil group. One clinical study performed by our group has already The three groups were similar in sex distribution, mean age, shown that 10% tea tree oil cream was effective in improving baseline clinical scores and skin scraping culture results the tinea clinically, although the mycological cure rate was not significantly better than placebo.7 In order to improve the All 158 enrolled into the study had typical clinical features mycological cure rate, we have used higher concentrations of tinea pedis, as well as microscopy suggestive of a dermato- (25% and 50%) of tea tree oil, prepared in solution rather than phyte infection. However, only 137 (86.7%) patients sub- as a cream because of the immiscibility of tea tree oil in sequently cultured a dermatophyte: 49 (92.5%) in the placebo group, 43 (79.6%) in the 25% tea tree oil group and 45 (88.2%) The study was conducted as a double-blind study, although of the 50% tea tree oil group. Of the 137 patients with a it could be argued that the study was single-blinded because confirmed dermatophyte infection, 120 (87.6%) completed the distinctive odour of tea tree oil identifies it to the patient.
the study. One patient in the 50% tea tree oil group was with- However, this information was not volunteered to the patients, drawn because of an adverse reaction and 16 patients were and it is not possible to distinguish between 25% and 50% tea lost to follow up: three (2.19%) in the placebo group, seven (5.11%) in the 25% tea tree oil group and six (4.38%) in the Of the 158 patients with clinically apparent tinea pedis and 50% tea tree oil group. The higher loss to follow up in the tea skin scrapings demonstrating fungal elements on microscopy, tree oil groups was not statistically significant (P > 0.05).
a dermatophyte was cultured in 137 (87%). This was higher Mycological cure could be determined for 114 of the 120 than expected based on previous work in this department.14 patients who completed the study: six patients (one placebo, Only those patients who remained in the study and had a three 25% and two 50% tea tree oil) did not have follow-up repeat skin scraping (114 patients) could be used to determine skin scrapings taken. Mycological cure was achieved in 18 the cure rate. The rate of loss was higher in the tea tree oil (55%) of the 25% tea tree oil group and 23 (64%) of the 50% groups, although this was not statistically significant. It would tea tree oil group, compared with 14 (31%) in the placebo be reasonable, then, to draw conclusions based on the results group (Table 2). The higher mycological cure rate in the tea of only those patients completing the study.
tree oil groups was statistically significant (P < 0.01).
Mycological cure rates of 55% and 64% in the 25% and 50% The number of patients with a marked improvement in the tea tree oil groups, respectively, are somewhat lower than clinical score (a final clinical score of zero or a reduction of those obtained for clotrimazole (90%) and terbinafine (90%) three or more to a final value less than three) was also signifi- in similarly designed studies.14 The mycological response cantly higher in the tea tree oil groups compared with placebo observed in the placebo group (31%) was not unexpected, (Table 3). Marked improvement in the clinical score was seen because all patients were asked to wash their feet with soap in 26 (72%) of the 25% tea tree oil group and 26 (68%) of the and water and dry between the toes before applying the 50% tea tree oil group, compared with 18 (39%) in the placebo solution, and were given advice about wearing open footwear.
group. This too was statistically significant (P < 0.005). The The effective cure rate, which required both a marked clinical severity score fell 68% and 66% in the 25% and 50% clinical improvement and mycological cure, was seen in tea tree oil groups, respectively, compared with 41% in the 48% of the 25% tea tree oil group and 50% of the 50% tea tree oil group; both significantly better than the placebo group Effective cure, defined as both mycological cure and marked (13%). Again, these rates are lower than for standard topical clinical response, was again higher in the tea tree oil groups: treatments. Three studies, each with a similar design to this 16 (48%) in the 25% tea tree oil group, 18 (50%) in the 50% one, have been reviewed.14 These studies compared clotri- tea tree oil group and 6 (13%) in the placebo group mazole with terbinafine and estimated that the average effective cure rate for subjects applying clotrimazole was All patients enrolled in the study, including those without 63% (95% confidence interval (CI) = 56–69%) and terbinafine dermatophyte infections, were included in the safety popu- lation. Dermatitis occurred in one patient applying 25% tea Dermatitis occurred in four (3.8%) patients treated with tea tree oil. It is unclear whether these were irritant or allergic Fitzpatrick’s Dermatology in General Medicine, Vol. 2, 5th edn. reactions. All reactions developed after 2 weeks and patch New York: McGraw-Hill, 1999; 2337–57.
testing was not done. While it has been reported that 25% tea 4. Leyden JL. Tinea pedis pathophysiology and treatment. J. Am. Acad. Dermatol. 1994; 31: S31–3.
tree oil is not an irritant,11 there is no published information 5. Smith EB. Topical antifungal drugs in the treatment of tinea pedis, regarding the irritancy of 50% tea tree oil.
tinea cruris, and tinea corporis. J. Am. Acad. Dermatol. 1993; 28:
Tea tree oil has been reported to cause allergic contact dermatitis, although there are only a few reports,16–18 despite 6. Tausch I, Decroix J, Gwiezdzinski Z, Urbanowski S, Baran E, its popularity and the fact that it is often applied to already Ziarkiewicz M, Levy G, Del Palacio A. Short-term itraconazole irritated or broken skin. Interestingly, in patch testing of 28 versus terbinafine in the treatment of tinea pedis or manus. normal volunteers, it was found that three volunteers reacted Int. J. Dermatol. 1998; 37: 140–2.
7. Tong MM, Altman PM, Barnetson RStC. Tea tree oil in the strongly to 25% tea tree oil, and all three patients subsequently treatment of tinea pedis. Australas. J. Dermatol. 1992; 33: 145–9.
reacted strongly to preparations containing sesquiterpenoid 8. Buck DS, Nidorf DM, Addino JG. Comparison of two topical fractions of the oil.18 This suggests allergic contact dermatitis preparations for the treatment of onychomycosis: Melaleuca is not uncommon. Reported allergens within tea tree oil alternifolia (tea tree) oil and clotrimazole. J. Fam. Prac. 1994; 38:
include monoterpenes such as terpinen-4-ol, D-limonene and α-terpinene, the sesquiterpenoid fraction and 1,8 cineol.
9. Pena EF. Melaleuca alternifolia oil, uses for trichomonal vaginitis and other vaginal infections. Obstet. Gynaecol. 1962; In summary, we have found in a large, randomized, 19: 793–5.
placebo-controlled study that both 25% and 50% tea tree oil 10. Bassett IB, Pannowitz DL, Barnetson RStC. A comparative study solutions are effective in treating tinea pedis, and that 25% tea of tea-tree oil versus benzoylperoxide in the treatment of acne.
tree oil is associated with fewer complications than 50% tea Med. J. Aust. 1990; 153: 455–8.
tree oil solution. We recommend that 25% tea tree oil be 11. Satchell AC, Saurajen A, Bell C, Barnetson RStC. Treatment of considered in those patients keen to use natural agents in dandruff with 5% tea tree oil shampoo. J. Am. Acad. Dermatol.
2002; 38: In press.
the treatment of tinea pedis, although 25% tea tree oil is less 12. Carson CF, Riley TV. Antimicrobial activity of the major com- effective than standard topical treatments.
ponents of the essential oil of Melaleuca alternifolia. J. Appl.
Bacteriol. 1995; 78: 264–9.
13. Griffin SG, Markham JL, Leach DN. An agar dilution method for ACKNOWLEDGEMENT
the determination of the minimum inhibitory concentration of
essential oils. J. Essent. Oil Res. 2000; 12: 249–55.
This research was funded by the Australian Tea Tree Oil 14. Patel A, Brookman SD, Bullen MU, Marley J, Ellis DH, Williams T, Barnetson RStC. Topical treatment of interdigital tinea pedis:
Terbinafine compared with clotrimazole. Austral. J. Dermatol.
1999; 40: 197–200.
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