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32 Athlete’s foot Fay Crawford Background Definition Athlete’s foot or tinea pedis is most frequently Aetiology The dermatophytes most frequently reported in clinical trials to be present on patients’ skin caused by dermatophyte (ringworm) invasion of at trial entry are Trichophyton rubrum, T. the skin of the feet. It usually manifests in one of three ways: interdigital skin appears macerated (white) and soggy; patches of skin on the foot may be affected by recurrent vesicular eruptions which make the skin itchy and red; and finally the soles of the feet, including the sides and heels can appear dry and scaly.1 mentagrophytes, Epidermophyton floccosum and T. interdigitale.4 Scaling, fissuring, pruritus and itching are some of the clinical features of fungal infections of the skin and it is these irritations that make the patient seek treatment. The natural history of the condition if untreated is a chronic, worsening infection which can lead to fissuring and breaks in the epidermis. Although the condition will not resolve spontaneously, some evidence from cure rates collected from people in the placebo arms of controlled trials suggests that improved foot hygiene alone may cure the infection in a proportion of people.5,6 Diagnosis The use of laboratory tests to diagnose the presence of dermatophyte infection is very important because athlete’s foot can be mistaken for other skin conditions. For example, Figure 32.1 Athlete’s foot interdigital maceration can look exactly like interdigital athlete’s foot, and juvenile chronic Incidence/prevalence Tinea infections are common. It has been estimated that 15% of the general population have a fungal infection of the feet.2 Gentles and Evans3 found the prevalence of athlete’s foot to dermatosis and bacterial infections such as erythrasma can also have a similar appearance to fungal infections on the skin of the feet. Aims of treatment be 21×5% in a sample of adult male swimmers, Treatment aims to reduce the signs and but the prevalence amongst adult females participating in the same survey was only 3×3%. symptoms such as itching and flaking of the skin, and ultimately to eradicate the infection. 436 Athlete’s foot The many creams available for the treatment of athlete’s foot differ in cost and availability. The fungi in the trial populations. The search found two systematic reviews, one of topical treatments azoles (for example miconazole, clotrimazole) for skin infections7 and the other of oral and allylamines (terbinafine, naftifine) are sold over the counter in pharmacies. Other creams (for example tolnaftate, undecenoic acid) are available in supermarkets. This last group is the cheapest of the topical preparations and the treatments for skin infections.4 The search also identified three RCTs not included in the reviews, which compared topical allylamines with topical azoles. allylamine creams are the most expensive. Generic drug names are used in the effectiveness analyses below. Martindale8 gives Oral drugs are sometimes used in the a complete list of brand names of antifungal management of chronic manifestations of drugs. athlete’s foot. Griseofulvin is the oldest and cheapest of the oral antifungal drugs but it must be taken for a long time. Newer azoles such as itraconazole, ketoconazole and fluconazole are effective in a much shorter time. The newest oral antifungal drugs are allylamines (terbinafine, naftifine). The allylamines (both topical and oral) are fungicidal whereas all other antifungal agents are fungistatic. Relevant outcomes The effects of treatment on these symptoms are measured in randomised controlled trials (RCTs) but microscopy and culture are usually the primary outcomes. Secondary outcomes are measured using a variety of signs and symptoms (redness, flaking, itching etc.). A reduction in QUESTIONS How effective are allylamine creams in the treatment of athlete’s foot? One systematic review7 found 12 RCTs comparing allylamines (terbinafine 1% cream or naftifine 1% gel) with placebo controls, used for 4 weeks. The two active preparations were similarly effective. A pooled analysis of data from seven trials (n = 683) comparing either naftifine or terbinafine with placebo controls produced a relative risk (RR) of 3×69 (95% confidence intervals (CI) 2×41 to 5×66). The allylamine creams, used twice daily for 4 weeks, are highly effective in the management of athlete’s foot. symptoms may be achieved quite quickly but the tenacity of tinea infections often means that complete cure takes a long time. How effective are azole creams in the treatment of athlete’s foot? Methods of search One systematic review7 found 14 RCTs Systematic reviews and RCTs were identified using a search strategy published elsewhere.7 comparing 4–6 weeks treatment with azole creams (1% clotrimazole, 1% tioconazole, 1% This was updated to September 2001 with a bifonazole, 1% econazole, 2% miconazole Medline and Embase search using the same strategy and supplemented by a search of the Cochrane Central Register of Controlled Trials (September 2001). The inclusion criterion for study selection was the nitrate with placebo controls. They were similarly effective. Treatment with 6 weeks of clotrimazole or tioconazole applied twice daily was evaluated in four trials (n = 434) (RR 1×85, CI 1×27 to 2×69). mycological confirmation of the presence of Shorter treatment times (4 weeks) with 437 Evidence-based Dermatology bifonazole, econazole nitrate or miconazole nitrate gave a RR of 2×25 (CI 1×44 to 3×52, n = 520). All the creams were similarly effective whether (n = 48),11 no difference in cure rate emerged at any time during the trial (RR at 1 week 0×99, CI 0×57 to 1×7). At 4 weeks there were 12/22 cures used for 4 or 6 weeks. Over-the-counter (54×6%) in the terbinafine group and 15/23 antifungal creams are very effective in the treatment of athlete’s foot when compared with placebo controls. How do allylamines creams compare with azole creams in curing athlete’s foot? One systematic review of topical treatments (search date December 1997) indicated slightly better mycological cure rates with the allylamines (terbinafine 1% and butenafine 1% creams) than with azoles (clotrimazole 1% and (65×2%) in the miconazole group (RR 0×83, CI 0×51 to 1×35). Schopoff et al.12 compared terbinafine cream used for 1 week with clotrimazole cream for 4 weeks in 429 people with interdigital tinea pedis and found no differences in the effectiveness at any time during the trial. Pooling the data from all three trials (n = 792) comparing 1 week of terbinafine cream with either 2% miconazole or 1% clotrimazole found miconazole 1% creams) used for 4 weeks (RR 1·1×95% CI 0×99 to 1×23). This analysis was based on data from 11 RCTs (n = 1554).7 The no statistical difference between these treatments (RR 1×15, CI 0×82 to 1×61). analysis showed the allylamines to cure 80% of cases of athlete’s foot, compared with a cure rate of 72% achieved with azole creams. The systematic review7 included one RCT9 which compared 1 week of terbinafine 1% cream with 4 weeks of clotrimazole 1% cream. There was no difference in the cure rates (n = 211) after 1 week of treatment but 6 weeks after the start of treatment the cure rate for terbinafine was significantly better than that of clotrimazole (RR 1×16, CI 1×06 to 1×27). Patel et al.10 found exactly the opposite effect in How effectively do creams that can be bought in the supermarket cure athlete’s foot? A systematic review7 found two three-arm trials comparing undecenoic acid with tolnaftate and placebo, another trial comparing undecenoic acid with placebo and no treatment, a fourth trial comparing undecenoic acid with placebo and a fifth trial comparing tolnaftate with tea-tree oil and placebo. Pooling the tolnaftate data from the arms of three trials that compared it with placebo indicates that tolnaftate is more effective than placebo against dermatophyte infections (RR 1×56; CI 1×05 to 2×31). Pooled data from four trials a smaller but similar trial (n = 104). They showed undecenoic acid to be more effective compared 1 week of terbinafine cream with 4 weeks of clotrimazole cream in people with interdigital tinea pedis. Terbinafine was found to more effective after 1 week (RR 1×51, CI 1×16 to 1×98) but there were no differences in effectiveness for outcomes assessed at later times. In the smallest of the trials, comparing 1 week of 1% terbinafine with 4 weeks of 2% miconazole than placebo in the management of athlete’s foot (RR 2×83, CI 1×91 to 4×19). Two trials of ciclopirox olamine 1% (which is not available in the UK) found it effective in treating athlete’s foot. In one placebo-controlled trial (n = 163) the RR was 6×85 (CI 3×10 to 15×15). A second small trial (n = 87) comparing ciclopirox olamine with clotrimazole found no statistical difference (RR 1×12, CI 0×90 to 1×38). 438 Athlete’s foot Are oral drugs more effective than topical compounds in the treatment of athlete’s foot? Only one small RCT (n = 137) has compared the efficacy of an oral drug with a cream in the management of interdigital athlete’s foot.13 Cure rates were similar in those treated for 1 week with oral terbinafine 250 mg/day and those using clotrimazole 1% cream twice daily for 4 weeks. The relapse rates among those who were cured differed significantly, however: 11/39 in the terbinafine group and 5/50 in the clotrimazole group relapsed after 3 months. What are the most effective oral drugs in the treatment of athlete’s foot? One systematic review4 found 10 RCTs that compared two antifungal drugs and two RCTs that compared oral antifungal drugs with placebos. The sample sizes in all trials were small (range 14–66). The review found four trials comparing oral terbinafine 250 mg/day with itraconazole 100 mg/day. One trial (n = 117) compared 2 weeks of terbinafine with 2 weeks of itraconazole and found a significant difference in favour of terbinafine (RR 1×5, CI 1×23 to 2×02). Three trials (n = 339) comparing 2 weeks of terbinafine with 4 weeks of itraconazole found no statistical differences in cure rates (RR 1×17, CI 0×94 to 1×46). The systematic review found two small trials that compared griseofulvin 500 mg/day with terbinafine 250 mg/day for 4 or 6 weeks. The pooled data from the two trials found terbinafine to be significantly more effective (RR 2×20, CI 1×45 to 3×32). The systematic review4 found similar low cure griseofulvin 1000 mg (57%). The cure rates with fluconazole 50 mg did not differ significantly from those with itraconazole 100 mg or ketoconazole 200 mg, but in both trials the cure rates were high (89–100%). Treatments were taken for 6 weeks in these trials. Drawbacks Topical antifungal compounds are well tolerated and are not associated with high rates of adverse events. One systematic review7 found that few trial reports gave details of adverse events and the few that were reported were not severe (for example itching, redness or burning). The systematic review of oral treatments for fungal infections of the skin4 noted that all 12 included trials reported side-effects. All drugs produced side-effects; the rate was lowest for fluconazole (11%) and highest for terbinafine (18%). Gastrointestinal effects and rashes were reported most frequently. Comment The evidence from one small trial13 shows that oral treatments are no more effective in the management of interdigital athlete’s foot than the creams. The same study also found higher relapse rates after oral treatments. Implications for practice All antifungal creams, whether over the counter or those available in supermarkets are effective in the treatment of athlete’s foot. Prescription-only antifungal creams produce slightly higher cure rates than all other creams. The available evidence indicates that the most cost-effective management strategy for athlete’s foot is an over-the-counter cream twice daily for 4 weeks, with prescription only cream reserved rates for ketoconazole 200 mg (53%) and for treatment failures.14 439 Evidence-based Dermatology There appears to be no therapeutic advantage in 3. Gentles JC, Evans EGV. Foot infections in swimming using an allylamine cream (terbinafine or baths. BMJ 1973;3:260–2. naftifine) for 1 week rather than an azole cream 4. Bell-Syer SEM, Hart R, Crawford F et al. A systematic for 4 weeks. The hypothesis that higher review of oral treatments for fungal infections of the skin of compliance rates are likely to be associated with shorter treatment times is often quoted but has not been tested.15 the feet. J Dermatol 2001;12:69–74. 5. Smith EB, Graham JL, Ulrich JA. Topical clotrimazole in tinea pedis. South Med J 1977;70:47–8. 6. Evans EGV, James IGV, Joshipura RC. Two week If no advantage is gained from treating treatment of tinea pedis with terbinafine a placebo interdigital athlete’s foot with oral antifungals, physicians should be cautious in prescribing oral drugs to manage moccasin type (infection over the sole of the foot). The belief that recalcitrant cases of athlete’s foot are more effectively controlled study. J Dermatol Treat 1991;2:95–7. 7. Crawford F, Bell Syer S, Hart R, Torgerson D, Young P, Russell I. Topical treatments for fungal infections of skin and nails of the foot. In: Cochrane Collaboration. Cochrane Library, Issue 1. Oxford: Update Software, 2002. managed with oral drugs has not been 8. Martindales. The Complete Drug Reference, 32nd ed. extensively tested. Key points London: Pharmaceutical Press, 1999. 9. Evans EGV, Dodman B, Williamson DM. Comparison of terbinafine and clotrimazole in treating tinea pedis. BMJ 1993;307:645–7. • Athlete’s foot is common and can be hard to cure. • Long-standing case of athlete’s foot should be confirmed using microscopy and culture laboratory tests. • All fungal creams are effective in treating athlete’s foot. There is evidence that different antifungal creams are associated with different cure rates; creams containing allylamines are the most effective in producting a cure followed by the azoles and undecenoic acid and tolnaftate. • There is some evidence to suggest that oral drugs (tablets) are no more effective than creams in producing a cure for athlete’s foot. 10. Patel A, Brookman SD, Bullen MU et al. Topical treatment of interdigital tinea pedis: terbinafine compared with clotrimazole. Australas J Dermatol 1999;40:197–200. 11. Leenutaphong V, Tangwiwat S, Muanprasat C, Niumpradit N, Spitaveesuawan R. Double-blind study of the efficacy of one week topical terbinafine cream compared to 4 weeks miconazole cream in patients with Tinea pedis. J Med Assoc Thailand 1999;82:1006–9. 12. Schopof R, Hettler O, Brautigam M et al. Efficacy and tolerability of 1% topical solution used for 1 week compared with 4 weeks clotrimazole 1% topical solution in the treatment of interdigital tinea pedis: a randomised controlled clinical trial. Mycoses 1999;42:415–20. 13. Barnetson R St, Marley J, Bullen M et al. Comparison of one week of oral terbinafine (250 mg/per day) with four weeks of treatment with clotrimazole 1% cream in References 1. Springett K, Merriman L. Assessment of the skin and its appendages. In: Merriman L, Tollafield D, eds. Assessment of the Lower Limb. Edinburgh: Churchill Livingstone, 1995. 2. Gupta AK, Saunder DN, Shear NH. Efficacy of antifungal agent Terbinafine in the treatment of superficial dermatophyte infections – an overview. Today Ther Trends 1995;13:9–20. interdigital tinea pedis. Br J Dermatol 1998;139:675–8. 14. Hart R, Bell-Syer S, Crawford F, Torgerson D, Young P, Russell I. Systematic review of topical treatments for fungal infections of the skin and nails of the feet. BMJ 1999;319:79–82. 15. Williams H. Pragmatic clinical trial is now needed. [Letters] BMJ 1999;319:1070. 440 ... - tailieumienphi.vn
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