Abstract
Introduction
Around 15% to 30% of people are likely to have athlete's foot at any one time. The infection can spread to other parts of the body and to other people.
Methods and outcomes
We conducted a systematic overview, aiming to answer the following clinical question: What are the effects of oral treatments for athlete's foot? We searched: Medline, Embase, The Cochrane Library, and other important databases up to September 2014 (BMJ Clinical Evidence overviews are updated periodically; please check our website for the most up-to-date version of this overview).
Results
At this update, searching of electronic databases retrieved 335 studies. After deduplication and removal of conference abstracts, 210 records were screened for inclusion in the overview. Appraisal of titles and abstracts led to the exclusion of 162 studies and the further review of 48 full publications. Of the 48 full articles evaluated, one systematic review was included. We performed a GRADE evaluation for six PICO combinations.
Conclusions
In this systematic overview, we categorised the efficacy for one intervention based on information relating to the effectiveness and safety of oral antifungals versus placebo and different oral antifungals versus each other.
Key Points
Fungal infection of the feet (athlete's foot or tinea pedis) can cause white and soggy skin between the toes, dry and flaky soles, or reddening and blistering of the skin all over the foot.
Around 15% to 30% of people are likely to have athlete's foot at any one time.
The infection can spread to other parts of the body and to other people.
Current consensus is that athlete’s foot should usually be treated with a topical antifungal as the primary treatment. Oral antifungal therapy is reserved for people with chronic or extensive disease, or where application of a topical agent is not feasible.
Appropriate follow-up duration and education on proper foot hygiene are also important components in providing effective therapy.
We searched for evidence of effectiveness of oral antifungals for athlete's foot from RCTs and systematic reviews of RCTs.
We found no RCTs undertaken in children, or longer-term studies.
Most trials were published more than 20 years ago, and some may have been too small to detect a clinically important difference.
We found one systematic review with two small RCTs that compared oral antifungals with placebo in adults.
Oral terbinafine and oral itraconazole seem to be more effective than placebo at increasing mycological cure in adults at 8 to 9 weeks in patients with moccasin-type athlete's foot.
We found no RCTs on the effectiveness of other oral antifungals versus placebo or on associated adverse effects. We found no RCTs undertaken in children, and no longer-term studies.
We found seven RCTs undertaken in adults that compared different oral antifungals with each other.
Oral terbinafine may be more effective than griseofulvin at improving mycological cure at 4 to 8 weeks in adults with athlete’s foot, although we don’t know whether these drugs differ in effectiveness at decreasing recurrence beyond 12 weeks from start of treatment. Griseofulvin may not be available widely.
We don’t know whether terbinafine and itraconazole differ in effectiveness at increasing mycological cure at 4 to 8 weeks or at decreasing recurrence of infection at 16 weeks in adults with athlete’s foot.
We don’t know whether itraconazole and fluconazole differ in effectiveness at increasing mycological cure at 10 weeks.
We found no RCTs of sufficient quality on the effects of other oral antifungals versus each other.
Clinical context
General background
Athlete's foot (tinea pedis) is not life-threatening in people with normal immunity; however, in some people, it can cause persistent symptoms and the infection can spread to other parts of the body, as well as to other people. Current consensus is that tinea pedis should usually be treated with a topical antifungal as primary treatment, while oral antifungal therapy is reserved for patients with chronic or extensive disease or where application of a topical agent is not feasible.
Focus of the review
The evidence that topical antifungal agents are effective treatments for athlete’s foot appears to be stable, so for this overview we decided to re-focus our research question on oral treatments instead. Oral therapy is usually used for chronic conditions or when topical treatment has failed.
Comments on evidence
There are several problems with the evidence, including the fact that, for most of the RCTs, the method of randomisation, allocation concealment, and blinding were not described. Most RCTs were published more than 15 to 20 years ago, or else the number of participants included was too small to find a clinically important difference between groups. We found no RCTs in children, and none with long-term follow-up. We have not considered the effectiveness and safety of co-treatment of antifungals with other agents, such as astringents, which may be used together in practice. Often, included trials received funding or support from pharmaceutical companies, did not report funding, or had co-authors who were employees of a pharmaceutical company.
Search and appraisal summary
The literature search was carried out in September 2014. For more information on the electronic databases searched and criteria applied during assessment of studies for potential relevance to the overview, please see the Methods section. Searching of electronic databases retrieved 335 studies. After deduplication and removal of conference abstracts, 210 records were screened for inclusion in the overview. Appraisal of titles and abstracts led to the exclusion of 162 studies and the further review of 48 full publications. Of the 48 full articles evaluated, one systematic review was included.
Additional information
Appropriate follow-up duration and education on proper foot hygiene are also important components in providing effective therapy.
About this condition
Definition
Athlete's foot (tinea pedis) is a cutaneous fungal infection caused by dermatophyte infection. It is characterised by itching, flaking, and fissuring of the skin. Athlete's foot presents in two readily distinguishable clinical forms: acute (with self-limited, intermittent, and recurrent attacks) and chronic, which usually persists indefinitely if untreated. It may manifest in three ways: the skin between the toes may appear macerated (white) and soggy (interdigital tinea pedis); the soles of the feet may become dry and scaly (plantar type tinea pedis, also know as 'moccasin foot'); and the skin all over the foot may become red, and vesicular eruptions may appear (vesicular [bullous] type). It is conventional in dermatology to refer to fungal skin infections as superficial in order to distinguish them from systemic fungal infections.
Incidence/ Prevalence
Epidemiological studies have produced various estimates of the prevalence of athlete's foot. Studies are usually conducted in populations of people who attend dermatology clinics, sports centres, or swimming pools, or who are in the military. UK estimates suggest that athlete's foot is present in about 15% of the general population. A population-based study conducted in 1148 children in Israel found the prevalence among children to be 30%. More recently, an observational study of 1568 people referred for foot inflammatory pathologies in a dermatology clinic in Italy found the prevalence of positive microscopy or culture-proven tinea pedis to be 15%.
Aetiology/ Risk factors
Swimming-pool users and industrial workers may be at increased risk of fungal foot infection. However, one survey identified fungal foot infection in only 9% of swimmers, with the highest prevalence (20%) being in men aged 16 years and older.
Prognosis
Fungal infections of the foot are not life-threatening in people with normal immune status, but in some people they cause persistent itching and, ultimately, fissuring. Some people are apparently unaware of persistent infection. The infection can spread to other parts of the body and to other individuals. Current consensus is that tinea pedis should usually be treated with a topical antifungal as primary treatment, while oral antifungal therapy is reserved for patients with chronic or extensive disease or where application of a topical is not feasible.
Aims of intervention
To control symptoms and prevent recurrence, with minimal adverse effects.
Outcomes
Mycological cure rates rates of fungal eradication, shown by negative microscopy and culture, and resolution of clinical signs and symptoms at follow-up. We have chosen mycological cure as a primary outcome because clinical cure is not reported consistently in superficial mycology trials. Microscopy and culture results are the most frequently used efficacy outcomes in athlete's foot research. However, like many other diagnostic tests, microscopy and culture are not absolutely accurate. Recurrence Having achieved a cure of the condition 12 weeks after the start of the intervention; adverse effects.
Methods
Search strategy BMJ Clinical Evidence search and appraisal September 2014. Databases used to identify studies for this systematic overview include: Medline 1966 to September 2014, Embase 1980 to September 2014, The Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Clinical Trials 2014, Issue 9 (1966 to date of issue), the Database of Abstracts of Reviews of Effects (DARE), and Health Technology Assessment (HTA) database. Inclusion criteria Study design criteria for inclusion in this overview were systematic reviews and RCTs published in English, at least single-blinded, and containing 20 or more individuals. There was no minimum length of follow-up and no maximum loss to follow-up. We excluded all studies described as 'open', 'open label', or not blinded unless blinding was impossible. BMJ Clinical Evidence does not necessarily report every study found (e.g., every systematic review). Rather, we report the most recent, relevant, and comprehensive studies identified through an agreed process involving our evidence team, editorial team, and expert contributors. Evidence evaluation A systematic literature search was conducted by our evidence team, who then assessed titles and abstracts, and finally selected articles for full text appraisal against inclusion and exclusion criteria agreed a priori with our expert contributor. In consultation with the expert contributor, studies were selected for inclusion and all data relevant to this overview extracted into the benefits and harms section of the overview. In addition, information that did not meet our predefined criteria for inclusion in the benefits and harms section, may have been reported in the 'Further information on studies' or 'Comment' sections. Adverse effects All serious adverse effects, or those adverse effects reported as statistically significant, were included in the harms section of the overview. Pre-specified adverse effects identified as being clinically important were also reported, even if the results were not statistically significant. Although BMJ Clinical Evidence presents data on selected adverse effects reported in included studies, it is not meant to be, and cannot be, a comprehensive list of all adverse effects, contraindications, or interactions of included drugs or interventions. A reliable national or local drug database must be consulted for this information. Comment and Clinical guide sections In the Comment section of each intervention, our expert contributors may have provided additional comment and analysis of the evidence, which may include additional studies (over and above those identified via our systematic search) by way of background data or supporting information. As BMJ Clinical Evidence does not systematically search for studies reported in the Comment section, we cannot guarantee the completeness of the studies listed there or the robustness of methods. Our expert contributors add clinical context and interpretation to the Clinical guide sections where appropriate. Structural changes this update At this update, we have removed the following previously reported question: What are the effects of topical treatments for athlete’s foot? We have added the following question: What are the effects of oral treatments for athlete’s foot? Data and quality To aid readability of the numerical data in our overviews, we round many percentages to the nearest whole number. Readers should be aware of this when relating percentages to summary statistics such as relative risks (RRs) and odds ratios (ORs). BMJ Clinical Evidence does not report all methodological details of included studies. Rather, it reports by exception any methodological issue or more general issue which may affect the weight a reader may put on an individual study, or the generalisability of the result. These issues may be reflected in the overall GRADE analysis. We have performed a GRADE evaluation of the quality of evidence for interventions included in this review (see table). The categorisation of the quality of the evidence (high, moderate, low, or very low) reflects the quality of evidence available for our chosen outcomes in our defined populations of interest. These categorisations are not necessarily a reflection of the overall methodological quality of any individual study, because the Clinical Evidence population and outcome of choice may represent only a small subset of the total outcomes reported, and population included, in any individual trial. For further details of how we perform the GRADE evaluation and the scoring system we use, please see our website (www.clinicalevidence.com).
Table.
GRADE Evaluation of interventions for Athlete's foot: oral antifungals.
| Important outcomes | Adverse effects, Mycological cure rates, Recurrence | ||||||||
| Studies (Participants) | Outcome | Comparison | Type of evidence | Quality | Consistency | Directness | Effect size | GRADE | Comment |
| What are the effects of oral treatments for athlete's foot? | |||||||||
| 2 (113) | Mycological cure rates | Oral antifungals versus placebo | 4 | –2 | 0 | –1 | +2 | Moderate | Quality points deducted for weak methods and sparse data; effect size points added for RR >5; directness point deducted for small number of comparators |
| At least 3 (at least 222) | Mycological cure rates | Oral allylamines versus oral azoles | 4 | –1 | –1 | 0 | 0 | Low | Quality point deducted for weak methods; consistency point deducted for statistical heterogeneity between RCTs |
| 1 (129) | Recurrence | Oral allylamines versus oral azoles | 4 | –3 | 0 | 0 | 0 | Very low | Quality points deducted for weak methods, sparse data, and incomplete reporting of results |
| 1 (35) | Mycological cure rates | Oral azoles versus each other | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and weak methods |
| 2 (71) | Mycological cure rates | Oral griseofulvin versus oral allylamines | 4 | –3 | 0 | 0 | +1 | Low | Quality points deducted for sparse data, weak methods, incomplete outcome data, and loss to follow-up; effect size point added for RR >2 |
| 1 (28) | Recurrence | Oral griseofulvin versus oral allylamines | 4 | –3 | 0 | 0 | 0 | Very low | Quality points deducted for weak methods, sparse data, and incomplete reporting of results |
We initially allocate 4 points to evidence from RCTs, and 2 points to evidence from observational studies. To attain the final GRADE score for a given comparison, points are deducted or added from this initial score based on preset criteria relating to the categories of quality, directness, consistency, and effect size. Quality: based on issues affecting methodological rigour (e.g., incomplete reporting of results, quasi-randomisation, sparse data [<200 people in the analysis]). Consistency: based on similarity of results across studies. Directness: based on generalisability of population or outcomes. Effect size: based on magnitude of effect as measured by statistics such as relative risk, odds ratio, or hazard ratio.
Glossary
- Low-quality evidence
Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
- Moderate-quality evidence
Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
- Very low-quality evidence
Any estimate of effect is very uncertain.
Disclaimer
The information contained in this publication is intended for medical professionals. Categories presented in Clinical Evidence indicate a judgement about the strength of the evidence available to our contributors prior to publication and the relevant importance of benefit and harms. We rely on our contributors to confirm the accuracy of the information presented and to adhere to describe accepted practices. Readers should be aware that professionals in the field may have different opinions. Because of this and regular advances in medical research we strongly recommend that readers' independently verify specified treatments and drugs including manufacturers' guidance. Also, the categories do not indicate whether a particular treatment is generally appropriate or whether it is suitable for a particular individual. Ultimately it is the readers' responsibility to make their own professional judgements, so to appropriately advise and treat their patients. To the fullest extent permitted by law, BMJ Publishing Group Limited and its editors are not responsible for any losses, injury or damage caused to any person or property (including under contract, by negligence, products liability or otherwise) whether they be direct or indirect, special, incidental or consequential, resulting from the application of the information in this publication.
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