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The Cochrane Database of Systematic... Jan 2020Onychomycosis refers to fungal infections of the nail apparatus that may cause pain, discomfort, and disfigurement. This is an update of a Cochrane Review published in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Onychomycosis refers to fungal infections of the nail apparatus that may cause pain, discomfort, and disfigurement. This is an update of a Cochrane Review published in 2007; a substantial amount of new research warrants a review exclusively on toenails.
OBJECTIVES
To assess the clinical and mycological effects of topical drugs and device-based therapies for toenail onychomycosis.
SEARCH METHODS
We searched the following databases up to May 2019: the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase and LILACS. We also searched five trials registers, and checked the reference lists of included and excluded studies for further references to relevant randomised controlled trials.
SELECTION CRITERIA
Randomised controlled trials of topical and device-based therapies for onychomycosis in participants with toenail onychomycosis, confirmed by positive cultures, direct microscopy, or histological nail examination. Eligible comparators were placebo, vehicle, no treatment, or an active topical or device-based treatment.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. Primary outcomes were complete cure rate (normal-looking nail plus fungus elimination, determined with laboratory methods) and number of participants reporting treatment-related adverse events.
MAIN RESULTS
We included 56 studies (12,501 participants, average age: 27 to 68 years), with mainly mild-to-moderate onychomycosis without matrix involvement (where reported). Participants had more than one toenail affected. Most studies lasted 48 to 52 weeks; 23% reported disease duration (variable). Thirty-five studies specifically examined dermatophyte-caused onychomycosis. Forty-three studies were carried out in outpatient settings. Most studies assessed topical treatments, 9% devices, and 11% both. We rated three studies at low risk of bias across all domains. The most common high-risk domain was performance bias. We present results for key comparisons, where treatment duration was 36 or 48 weeks, and clinical outcomes were measured at 40 to 52 weeks. Based on two studies (460 participants), compared with vehicle, ciclopirox 8% lacquer may be more effective in achieving complete cure (risk ratio (RR) 9.29, 95% confidence interval (CI) 1.72 to 50.14; low-quality evidence) and is probably more effective in achieving mycological cure (RR 3.15, 95% CI 1.93 to 5.12; moderate-quality evidence). Ciclopirox lacquer may lead to increased adverse events, commonly application reactions, rashes, and nail alteration (e.g. colour, shape). However, the 95% CI indicates that ciclopirox lacquer may actually make little or no difference (RR 1.61, 95% CI 0.89 to 2.92; low-quality evidence). Efinaconazole 10% solution is more effective than vehicle in achieving complete cure (RR 3.54, 95% CI 2.24 to 5.60; 3 studies, 1716 participants) and clinical cure (RR 3.07, 95% CI 2.08 to 4.53; 2 studies, 1655 participants) (both high-quality evidence) and is probably more effective in achieving mycological cure (RR 2.31, 95% CI 1.08 to 4.94; 3 studies, 1716 participants; moderate-quality evidence). Risk of adverse events (such as dermatitis and vesicles) was slightly higher with efinaconazole (RR 1.10, 95% CI 1.01 to 1.20; 3 studies, 1701 participants; high-quality evidence). No other key comparison measured clinical cure. Based on two studies, compared with vehicle, tavaborole 5% solution is probably more effective in achieving complete cure (RR 7.40, 95% CI 2.71 to 20.24; 1198 participants), but probably has a higher risk of adverse events (application site reactions were most commonly reported) (RR 3.82, 95% CI 1.65 to 8.85; 1186 participants (both moderate-quality evidence)). Tavaborole improves mycological cure (RR 3.40, 95% CI 2.34 to 4.93; 1198 participants; high-quality evidence). Moderate-quality evidence from two studies (490 participants) indicates that P-3051 (ciclopirox 8% hydrolacquer) is probably more effective than the comparators ciclopirox 8% lacquer or amorolfine 5% in achieving complete cure (RR 2.43, 95% CI 1.32 to 4.48), but there is probably little or no difference between the treatments in achieving mycological cure (RR 1.08, 95% CI 0.85 to 1.37). We found no difference in the risk of adverse events (RR 0.60, 95% CI 0.19 to 1.92; 2 studies, 487 participants; low-quality evidence). The most common events were erythema, rash, and burning. Three studies (112 participants) compared 1064-nm Nd:YAG laser to no treatment or sham treatment. We are uncertain if there is a difference in adverse events (very low-quality evidence) (two studies; 85 participants). There may be little or no difference in mycological cure at 52 weeks (RR 1.04, 95% CI 0.59 to 1.85; 2 studies, 85 participants; low-quality evidence). Complete cure was not measured. One study (293 participants) compared luliconazole 5% solution to vehicle. We are uncertain whether luliconazole leads to higher rates of complete cure (very low-quality evidence). Low-quality evidence indicates there may be little or no difference in adverse events (RR 1.02, 95% CI 0.90 to 1.16) and there may be increased mycological cure with luliconazole; however, the 95% CI indicates that luliconazole may make little or no difference to mycological cure (RR 1.39, 95% CI 0.98 to 1.97). Commonly-reported adverse events were dry skin, paronychia, eczema, and hyperkeratosis, which improved or resolved post-treatment.
AUTHORS' CONCLUSIONS
Assessing complete cure, high-quality evidence supports the effectiveness of efinaconazole, moderate-quality evidence supports P-3051 (ciclopirox 8% hydrolacquer) and tavaborole, and low-quality evidence supports ciclopirox 8% lacquer. We are uncertain whether luliconazole 5% solution leads to complete cure (very low-quality evidence); this outcome was not measured by the 1064-nm Nd:YAG laser comparison. Although evidence supports topical treatments, complete cure rates with topical treatments are relatively low. We are uncertain if 1064-nm Nd:YAG laser increases adverse events compared with no treatment or sham treatment (very low-quality evidence). Low-quality evidence indicates that there is no difference in adverse events between P-3051 (ciclopirox hydrolacquer), luliconazole 5% solution, and their comparators. Ciclopirox 8% lacquer may increase adverse events (low-quality evidence). High- to moderate-quality evidence suggests increased adverse events with efinaconazole 10% solution or tavaborole 5% solution. We downgraded evidence for heterogeneity, lack of blinding, and small sample sizes. There is uncertainty about the effectiveness of device-based treatments, which were under-represented; 80% of studies assessed topical treatments, but we were unable to evaluate all of the currently relevant topical treatments. Future studies of topical and device-based therapies should be blinded, with patient-centred outcomes and an adequate sample size. They should specify the causative organism and directly compare treatments.
Topics: Administration, Topical; Adult; Aged; Antifungal Agents; Female; Humans; Male; Middle Aged; Onychomycosis; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 31978269
DOI: 10.1002/14651858.CD012093.pub2 -
Annales de Dermatologie Et de... Jan 2020There are few studies focusing on ungual lesions in patients with lupus erythematosus (LE). The aim of this study is to describe the type and the prevalence of ungual...
INTRODUCTION
There are few studies focusing on ungual lesions in patients with lupus erythematosus (LE). The aim of this study is to describe the type and the prevalence of ungual lesions among LE patients.
PATIENTS AND METHODS
A systematic literature review with analysis of individual data was performed by searching the MEDLINE database for scientific articles using the keywords "lupus erythematosus" and "nail".
RESULTS
Two-hundred and eighty-seven cases were collated including 55.1% women, with an average age of 32.2±11 years. The most common ungual or peri-ungual lesions were longitudinal ridging (83 patients, 28.9%), peri-ungual erythema (62 patients, 21.6%), onycholysis (60 patients, 20.9%), melanonychia (34 patients, 11.8%) and dyschromia (33 patients, 11.5%). An association between the presence of onycholysis and peri-ungual erythema and disease activity was noted [respectively 33 (38.8%) and 26 (30.6%) patients out of 85 with active disease versus 3 (5.8%) and 4 (7.7%) patients out of 52 with non-active disease, P<0.001 and P=0.018]. Screening for fungal infection was performed in one third of the cases, with proven onychomycosis in 34.7% of cases.
DISCUSSION
Ungual lesions are not specific and do not permit diagnosis of LE. They can in fact occur in other diseases such as connective tissue disorders. However, their diagnosis is important because they may be the presenting sign in LE, and certain of them may be associated with more active disease. Onychomycosis is frequently a confounding factor in such immunocompromised patients.
Topics: Adolescent; Adult; Aged; Child; Female; Humans; Lupus Erythematosus, Systemic; Male; Middle Aged; Nail Diseases; Onychomycosis; Young Adult
PubMed: 31812364
DOI: 10.1016/j.annder.2019.10.027 -
Current Microbiology Apr 2020To present an overview of the existing epidemiological evidence regarding the occurrence of tinea gladiatorum in wrestlers and dermatophyte contamination in wrestling... (Meta-Analysis)
Meta-Analysis
To present an overview of the existing epidemiological evidence regarding the occurrence of tinea gladiatorum in wrestlers and dermatophyte contamination in wrestling halls, five electronic databases including "PubMed," "Scopus," "Google Scholar," "Science Direct," and "Web of Science" were searched from inception to 30 December 2018. Studies focusing on epidemiology of dermatophytosis among wrestlers and on the presence of dermatophytes in wrestler hall were included. Data from 13 studies, 4818 wrestlers, and 391 wrestling mat samples from Turkey, Iran, and the USA (including a separate dataset for Alaska) were included. The prevalence of tinea gladiatorum in wrestlers varied from 2.4 to 90.62%, with the overall prevalence of 34.29% (95% CI 20.33-48.25). The prevalence of dermatophytes in wrestling halls varied from 0 to 56%, with the overall prevalence of 5% (95% CI 4‒7). The most frequent causative agent was Trichophyton tonsurans (875/951; 92%). The most common clinical feature of dermatophytosis among wrestlers was tinea corporis (62.2%). Meta-analysis indicated significant heterogeneity of all included studies (Q = 3204.72, P < 0.001, I = 99.6%). The publication bias evaluated using Egger's test was negligible (P = 0.033). The current systematic review and meta-analysis are limited by the relatively low number of published studies on tinea gladiatorum and its prevalence among wrestlers. In Conclusion, the analysis revealed a relatively high prevalence of tinea gladiatorum among wrestlers, with a paucity of evidence on dermatophytes in wrestling halls.
Topics: Arthrodermataceae; Athletes; Dermatomycoses; Humans; Iran; Prevalence; Skin; Sports and Recreational Facilities; Tinea; Wrestling
PubMed: 31773190
DOI: 10.1007/s00284-019-01816-3 -
Medicine Nov 2019Laser systems are a common treatment choice for onychomycosis. They exert their effects on inhibiting the growth of the fungus by selective photothermolysis but efficacy... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Laser systems are a common treatment choice for onychomycosis. They exert their effects on inhibiting the growth of the fungus by selective photothermolysis but efficacy is dependent on the specific type of apparatus used. To systematically review the available published literature on the curative effects and safety of laser treatment for onychomycosis.
METHODS
Databases including PubMed, web of science, China National Knowledge Internet (CNKI), WanFang Database and VIP were searched systematically to identify relevant articles published up to July 2018. Potentially relevant articles were sourced, assessed against eligibility criteria by 2 researchers independently and data were extracted from included studies. A meta-analysis was performed using R software.
RESULTS
Thirty-five articles involving 1723 patients and 4278 infected nails were included. Meta-analysis of data extracted from these studies revealed that: the overall mycological cure rate was 63.0% (95%CI 0.53-0.73); the mycological cure rate associated with the 1064-nm Nd: YAG laser was 63.0% (95%CI 0.51-0.74); and that of CO2 lasers was 74.0% (95%CI 0.37-0.98). The published data indicate that laser treatment is relatively safe, but can cause tolerable pain and occasionally lead to bleeding after treatment.
CONCLUSION
Laser treatment of onychomycosis is effective and safe. The cumulative cure rate of laser treatment was significantly higher for CO2 lasers than other types of laser. Laser practitioners should be made aware of potential adverse effects such as pain and bleeding.
Topics: Humans; Lasers, Gas; Lasers, Solid-State; Low-Level Light Therapy; Nails; Onychomycosis; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 31770202
DOI: 10.1097/MD.0000000000017948 -
Journal of the European Academy of... Mar 2020Onychomycosis is a chronic, fungal infection of the nails. Complete cure remains challenging, but oral antifungal medications have been successful in managing the fungus... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
Onychomycosis is a chronic, fungal infection of the nails. Complete cure remains challenging, but oral antifungal medications have been successful in managing the fungus for a significant proportion of patients. Treatment with these drugs can be continuous or intermittent, albeit the evidence on their relative efficacies remains unclear.
OBJECTIVE
To determine the relative effectiveness and safety of pulse versus continuous administration, of three common oral therapies for dermatophyte onychomycosis, by conducting multiple-treatment meta-analysis.
METHODS
This systematic review and network meta-analysis compared the efficacy (as per mycological cure) and adverse event rates of three oral antifungal medications in the treatment of dermatophyte toenail onychomycosis, namely terbinafine, itraconazole and fluconazole. A total of 30 studies were included in the systematic review, while 22 were included in the network meta-analysis.
RESULTS
The likelihood of mycological cure was not significantly different between continuous and pulse regimens for each of terbinafine and itraconazole. Use of continuous terbinafine for 24 weeks - but not 12 weeks - was significantly more likely to result in mycological cure than continuous itraconazole for 12 weeks or weekly fluconazole for 9-12 months. Rank probabilities demonstrated that 24-week continuous treatment of terbinafine was the most effective. There were no significant differences in the likelihood of adverse events between any continuous and pulse regimens of terbinafine, itraconazole and fluconazole. Drug treatments were similar to placebo in terms of their likelihood of producing adverse events.
CONCLUSION
More knowledge about the fungal life cycle and drugs' pharmacokinetics in nail and plasma could further explain the relative efficacy and safety of the pulse and continuous treatment regimens. Our results indicate that in the treatment of dermatophyte toenail onychomycosis, the continuous and pulse regimens for terbinafine and itraconazole have similar efficacies and rates of adverse events.
Topics: Administration, Oral; Antifungal Agents; Fluconazole; Humans; Itraconazole; Onychomycosis; Terbinafine; Treatment Outcome
PubMed: 31746067
DOI: 10.1111/jdv.16101 -
Journal de Mycologie Medicale Sep 2019Onychomycosis or fungal nail infection is one of the most common fungal infections. Nearly 50% of all nail disorders are caused by fungi. This systematic review and... (Meta-Analysis)
Meta-Analysis
Onychomycosis or fungal nail infection is one of the most common fungal infections. Nearly 50% of all nail disorders are caused by fungi. This systematic review and meta-analysis was conducted to determine the prevalence of onychomycosis across Iran. We searched English and Persian databases for studies reporting the epidemiologic features of onychomycosis in Iranian people from January 2000 to December 2018. Literature search revealed 307 studies, of which 24 studies met the eligibility criteria. In order to identifying the existence of publication bias among studies, funnel plots were used. The results of the meta-analysis were visualized as a forest plot representing the prevalence estimates of each study. Heterogeneity was also analyzed using the I, Chi, and Tau statistics. A high level of I and Chi was obtained among studies, which provides evidence of notable heterogeneity between studies. The results of current study revealed that the highest prevalence of onychomycosis was related to Mazandaran and Tehran provinces, respectively. As in the literature hypothesized shift in etiologic agents from yeasts to dermatophytes or molds could not be confirmed. Females were affected more frequently than males and in both sexes the highest incidence of infection occurrence was at the ages of >50 years. It seems the highest prevalence of onychomycosis in Mazandaran and Tehran provinces is due to the concentration of specialist doctors and research centers in these two provinces compared with others which leads to more detection and more care of the disease. Therefore, further educational strategies in order to accurate diagnosis in other provinces is necessary to reduce the risk of onychomycosis in Iran.
Topics: Age Factors; Arthrodermataceae; Dermatomycoses; Female; Geography; Humans; Iran; Male; Onychomycosis; Prevalence; Risk Factors; Sex Factors; Yeasts
PubMed: 31285126
DOI: 10.1016/j.mycmed.2019.05.004 -
Lasers in Medical Science Oct 2019Laser therapy for onychomycosis is emerging but its efficacy remains unestablished. To examine current evidence on efficacy of laser treatment of onychomycosis. A... (Meta-Analysis)
Meta-Analysis
Laser therapy for onychomycosis is emerging but its efficacy remains unestablished. To examine current evidence on efficacy of laser treatment of onychomycosis. A systematic review and one-arm meta-analysis, including all prospective clinical trials, identified on PubMed, Cochrane Library, and EMBASE databases. Trials with participants as unit of analysis (UOA), n = 13, were analyzed separately from trials with nails as UOA, n = 7. Summary proportions and 95% confidence intervals (95% CI) were calculated. Outcomes were mycological cure, clinical improvement, or complete cure. Twenty-two prospective trials (four randomized controlled trials and 18 uncontrolled trials) with a total of 755 participants were analyzed. Summary proportions with 95% CI for participants as UOA were mycological cure 70.4%, 95% CI 52.2-83.8%; clinical improvement 67.2%, 95% CI 43.2-84.7%; and complete cure 7.2%, 95% CI 1.9-23.5%. High statistical heterogeneity was detected (mycological cure I = 88%, P < 0.01; clinical improvement I = 69%, P < 0.01; complete cure I = 60%, P = 0.11). The current level of evidence is limited and with high heterogeneity, making it difficult to assess the true efficacy of laser treatment for onychomycosis. Larger randomized controlled trials with well-defined methodology are warranted.
Topics: Humans; Laser Therapy; Nails; Onychomycosis; Outcome Assessment, Health Care; Prospective Studies; Treatment Outcome
PubMed: 31254131
DOI: 10.1007/s10103-019-02802-8 -
The British Journal of Dermatology Feb 2020Onychomycosis is a fungal infection of the nail caused by dermatophytes, yeasts and nondermatophyte moulds that accounts for approximately 50% of all nail-related... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Onychomycosis is a fungal infection of the nail caused by dermatophytes, yeasts and nondermatophyte moulds that accounts for approximately 50% of all nail-related disease.
OBJECTIVES
This study aims to assess the effectiveness and safety of monotherapy and combination treatments for toenail onychomycosis using a network meta-analysis (NMA).
METHODS
Quality of evidence was assessed using Cochrane-compliant rules and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Efficacy and safety outcomes were compared using a random-effects NMA to estimate pooled odds ratios (ORs) of direct and indirect comparisons among oral and topical treatments (PROSPERO 2015: CRD42018086912). There were not enough eligible combination and device-based therapy trials to include in the NMA.
RESULTS
Of 77 randomized controlled trials, 26 were included in the ORs (8136 patients). There were no significant inconsistencies between the direct and indirect evidence. Relative effects show that the odds of mycological cure with continuous terbinafine 250 mg or continuous itraconazole 200 mg are significantly greater than topical treatments. Fluconazole, pulse regimens of terbinafine and itraconazole, and topical treatments did not differ significantly in the odds of achieving mycological cure. The ORs of adverse events occurring with oral or topical treatments were not significantly different from each other. For mycological cure, evidence was of moderate or high quality while evidence ranged from very low to high quality for adverse events.
CONCLUSIONS
Our review suggests that oral and topical treatments for toenail onychomycosis are safe and effective in producing mycological cure. What's already known about this topic? Topical treatments traditionally have lower success rates than oral treatments. Oral treatments have the advantage of shorter treatment durations, but also present challenges in cases of drug-drug interactions or immunosuppression. A network meta-analysis (NMA) gathers data from indirect evidence to gain confidence about all treatment comparisons and allows for estimation of comparative effects that have not been investigated in head-to-head randomized clinical trials (RCTs). What does this study add? This NMA of efficacy and safety includes all RCTs of oral, topical, combination and device-based treatments for toenail onychomycosis, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement for NMA. The odds of achieving mycological cure with continuous terbinafine 250 mg or continuous itraconazole 200 mg were significantly greater than topical treatments. Fluconazole, pulse regimens of terbinafine and itraconazole, and topical treatments did not differ significantly in the odds of achieving mycological cure.
Topics: Antifungal Agents; Foot Dermatoses; Humans; Itraconazole; Nails; Naphthalenes; Network Meta-Analysis; Onychomycosis; Treatment Outcome
PubMed: 31120134
DOI: 10.1111/bjd.18155 -
Medical Mycology Jan 2020Published case fatality in blastomycosis patients ranges between 4% and 78%. This study aimed to assess mortality associated with blastomycosis and identify its... (Meta-Analysis)
Meta-Analysis
Published case fatality in blastomycosis patients ranges between 4% and 78%. This study aimed to assess mortality associated with blastomycosis and identify its associated risk factors. We conducted a systematic review of publications related to Blastomyces dermatitidis available in PubMed and Scopus databases. Studies that reported data on blastomycosis mortality and that were published from inception through February 2018 were assessed and included in the analysis. Using the R meta package, a random-effect model meta-analysis was used to calculate pooled and stratified estimates of case-fatality proportions and risk ratios. Of 1553 publications, we included 20 studies reporting on a total of 2820 cases of blastomycosis between 1970 and 2014 and three case series reports with 10, 21, and 36 patients. The mean or median ages ranged from 28 to 59 years. Mortality was defined as attributable mortality caused by blastomycosis in 13 studies. Among 14 studies with a standard error ≤0.05, the overall pooled mortality was 6.6% (95% confidence interval [CI], 4.9-8.2) with 57% heterogeneity. The mortality rate was 37% (95% CI, 23-51) in immunocompromised patients and 75% (95% CI, 53-96) in patients who developed an acute respiratory distress syndrome (ARDS) (n = 3 studies each). ARDS was the only identified risk factor in general patients (risk ratio = 10.2). The overall mortality was significantly higher in studies involving immunocompromised patients and ARDS patients. Our analysis showed considerable heterogeneity among studies. Inconsistent mortality definitions may have contributed to the observed heterogeneity. Further research is needed to assess potential risk factors for mortality.
Topics: Antifungal Agents; Blastomyces; Blastomycosis; Humans; Immunocompromised Host; Odds Ratio; Respiratory Distress Syndrome
PubMed: 31111911
DOI: 10.1093/mmy/myz048 -
The Journal of Dermatological Treatment Dec 2019Although labeling changes and market withdrawal have been implemented for oral ketoconazole (KTZ) due to serious adverse effects (AEs), topical KTZ is generally thought...
Although labeling changes and market withdrawal have been implemented for oral ketoconazole (KTZ) due to serious adverse effects (AEs), topical KTZ is generally thought to be effective and safe for the treatment of superficial fungal infections. New dermatologic indications for the use of topical KTZ have arisen such as onychomycosis, blepharitis, and hair loss. This article aims to review the literature on topical KTZ's efficacy and AEs, as well as provide an overview on current insights regarding its mechanism of action and upcoming developments. A PubMed search was done to include randomized controlled trials (RCTs) focusing on the use of topical KTZ in human subjects. Forty studies with 4566 patients were included in this review. Topical KTZ is clinically effective for the treatment of -related conditions such as seborrheic dermatitis (SD) and pityriasis versicolor (PV) with a reported efficacy of 63-90% and 71-89%, respectively. Topical KTZ demonstrates high clinical efficacy for -related conditions. More efficacious alternatives are now available for and . Although topical KTZ is safe, clinicians should be aware that allergic contact dermatitis may occur. Further studies should be completed to investigate the use of topical KTZ for hair loss and inflammatory dermatoses.
Topics: Administration, Topical; Alopecia; Antifungal Agents; Dermatitis, Seborrheic; Humans; Ketoconazole; Malassezia; Randomized Controlled Trials as Topic; Tinea Versicolor; Treatment Outcome
PubMed: 30668185
DOI: 10.1080/09546634.2019.1573309