Abstract: Of the 364 records identified, 129 studies with 18,086 participants met the inclusion criteria. Half of the studies were judged at high risk of bias with the remainder judged at unclear risk. A wide range of different comparisons were evaluated across the 129 studies, 92 in total, with azoles accounting for the majority of the interventions. Treatment duration varied from one week to two months, but in most studies this was two to four weeks. The length of follow-up varied from one week to six months. Sixty-three studies contained no usable or retrievable data mainly due to the lack of separate data for different tinea infections. Mycological and clinical cure were assessed in the majority of studies, along with adverse effects. Less than half of the studies assessed disease relapse, and hardly any of them assessed duration until clinical cure, or participant-judged cure. The quality of the body of evidence was rated as low to very low for the different outcomes. Data for several outcomes for two individual treatments were pooled. Across five studies, significantly higher clinical cure rates were seen in participants treated with terbinafine compared to placebo (risk ratio (RR) 4.51, 95% confidence interval (CI) 3.10 to 6.56, number needed to treat (NNT) 3, 95% CI 2 to 4). The quality of evidence for this outcome was rated as low. Data for mycological cure for terbinafine could not be pooled due to substantial heterogeneity. Mycological cure rates favoured naftifine 1% compared to placebo across three studies (RR 2.38, 95% CI 1.80 to 3.14, NNT 3, 95% CI 2 to 4) with the quality of evidence rated as low. In one study, naftifine 1% was more effective than placebo in achieving clinical cure (RR 2.42, 95% CI 1.41 to 4.16, NNT 3, 95% CI 2 to 5) with the quality of evidence rated as low. Across two studies, mycological cure rates favoured clotrimazole 1% compared to placebo (RR 2.87, 95% CI 2.28 to 3.62, NNT 2, 95% CI 2 to 3). Data for several outcomes were pooled for three comparisons between different classes of treatment. There was no difference in mycological cure between azoles and benzylamines (RR 1.01, 95% CI 0.94 to 1.07). The quality of the evidence was rated as low for this comparison. Substantial heterogeneity precluded the pooling of data for mycological and clinical cure when comparing azoles and allylamines. Azoles were slightly less effective in achieving clinical cure compared to azole and steroid combination creams immediately at the end of treatment (RR 0.67, 95% CI 0.53 to 0.84, NNT 6, 95% CI 5 to 13), but there was no difference in mycological cure rate (RR 0.99, 95% CI 0.93 to 1.05). The quality of evidence for these two outcomes was rated as low for mycological cure and very low for clinical cure. All of the treatments that were examined appeared to be effective, but most comparisons were evaluated in single studies. There was no evidence for a difference in cure rates between tinea cruris and tinea corporis. Adverse effects were minimal - mainly irritation and burning; results were generally imprecise between active interventions and placebo, and between different classes of treatment. The pooled data suggest that the individual treatments terbinafine and naftifine are effective. Adverse effects were generally mild and reported infrequently. A substantial number of the studies were more than 20 years old and of unclear or high risk of bias; there is however, some evidence that other topical antifungal treatments also provide similar clinical and mycological cure rates, particularly azoles although most were evaluated in single studies.There is insufficient evidence to determine if Whitfield’s ointment, a widely used agent is effective. Although combinations of topical steroids and antifungals are not currently recommended in any clinical guidelines, relevant studies included in this review reported higher clinical cure rates with similar mycological cure rates at the end of treatment, but the quality of evidence for these outcomes was rated very low due to imprecision, indirectness and risk of bias. There was insufficient evidence to confidently assess relapse rates in the individual or combination treatments. Although there was little difference between different classes of treatment in achieving cure, some interventions may be more appealing as they require fewer applications and a shorter duration of treatment. Further, high quality, adequately powered trials focusing on patient-centred outcomes, such as patient satisfaction with treatment should be considered.

Plain-language summary: We included 129 studies published up to August 2013 which examined 18,086 people. Participants included men and women of any age, although most were between 18 to 70 years old. There was considerable variation in the reporting quality of the studies. A quarter were partially funded by pharmaceutical companies, and it was unclear what impact this may have had on reporting of the results. Most studies appeared to be conducted within dermatology outpatient clinics. A range of treatments were evaluated, mostly in single studies. Most treatments were applied once or twice daily for between two and four weeks. Mycological cure (disappearance of fungal infection); and clinical cure (absence of symptoms such as redness and itchiness); were assessed in the majority of studies, along with side effects. Less than half of the studies assessed disease recurrence and hardly any assessed the time to achieve clinical cure, or whether study participants considered they had been cured. Almost all treatments were effective at achieving both mycological and clinical cure, compared with placebo. We combined data for several outcomes in two individual treatments: terbinafine against placebo and naftifine against placebo. Both were shown to be effective treatments. We combined data on different groups of treatments. There was no difference in rate of mycological cure between azoles and benzylamines. Combinations of antifungal treatment with a topical corticosteroid achieved higher clinical cure rates, probably because the skin redness disappears sooner due to the effect of the corticosteroid. There was no evidence of any difference in the speed of resolution of fungal infection with these combination treatments. The overall quality of the evidence for the different outcomes was rated as low to very low. There is currently insufficient evidence to be able to decide if one particular treatment is better than any of the others. All the treatments we evaluated reported low rates of mild side effects. This review highlights the need for better quality studies on treatments for fungal skin infections. Despite the limitations of our main findings, it appears that most active treatments are effective and further research should concentrate on comparing active treatments, rather than comparisons with a placebo. Topical treatments that need to be used only once a day over a short period of time may be more appealing in practice. Some of the treatments examined in our review may not be readily available in-low income countries.