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The Journal of Dermatological Treatment Feb 2022Toenail fungal infections account for half of all nail disease cases, and a highly negative impact on patient quality of life. Our aim was to compare the efficacy and... (Meta-Analysis)
Meta-Analysis
AIM
Toenail fungal infections account for half of all nail disease cases, and a highly negative impact on patient quality of life. Our aim was to compare the efficacy and safety of commercially available oral antifungals for onychomycosis.
METHODS
A systematic review was performed in PubMed and Scopus. Randomized controlled trials evaluating the effect of oral antifungals on mycological cure, discontinuation and adverse events were included. Network meta-analyses were built for each outcome. Results were reported as odds ratios (OR) with 95% credibility intervals (CrI). Ranking probabilities were calculated by surface under the cumulative ranking analysis (SUCRA).
RESULTS
We included 40 trials ( = 9568). Albaconazole 400 mg (OR 0.02 [95% CrI 0.01-0.07] placebo), followed by posaconazole 200-400 mg and terbinafine 250-350 mg were considered the best therapies (SUCRA probabilities over 75%). For the networks of discontinuation and individual adverse events, few significant differences among treatments were observed, but itraconazole 400 mg was considered the safest drug (SUCRA around 25%). Albaconazole 400 mg, posaconazole 200-400 mg, and terbinafine 250-350 mg were the most effective therapies for onychomycosis, while itraconazole 400 mg was the safest.
CONCLUSION
The profile of albaconazole and posaconazole compared to current first-line therapies should be further investigated in well-designed trials.
Topics: Antifungal Agents; Foot Dermatoses; Humans; Itraconazole; Nails; Network Meta-Analysis; Onychomycosis; Quality of Life; Treatment Outcome
PubMed: 32043906
DOI: 10.1080/09546634.2020.1729336 -
Journal of the European Academy of... Jul 2014Nail diseases are often annoying for the patient and diagnostically challenging for dermatologists. New imaging techniques are of high interest in the diagnosis of nail... (Review)
Review
Nail diseases are often annoying for the patient and diagnostically challenging for dermatologists. New imaging techniques are of high interest in the diagnosis of nail disorders to reduce the number of nail biopsies. Confocal microscopy is a high-resolution emerging imaging technique that can be used to explore the entire body surface, including skin, mucosa, hair and nails. A systematic review of the literature concerning the use of confocal microscopy for the study of either healthy or pathological nail has been performed to evaluate the current use of this technique and possible future applications. Confocal microscopy is particularly suitable for nails because it allows a non-invasive in vivo examination of this sensitive body area, and nail plate transparency permits to image up to the nail bed with an easy identification of corneocytes. Confocal microscopy can play a role in the diagnosis of onychomycosis and melanonichia, and in the study of drug penetration through the nail plate. It could be used in the future as a non-invasive procedure for the investigation of different nail diseases, such as psoriasis and lichen planus. Further application could be the intra-operative ex vivo examination of nail specimens to outline tumour margins to assist surgery.
Topics: Diagnosis, Differential; Diagnostic Imaging; Humans; Microscopy, Confocal; Nail Diseases; Nails; Onychomycosis
PubMed: 24320009
DOI: 10.1111/jdv.12330 -
Dermatology Online Journal Nov 2013Urea is an organic compound that has been used clinically for dermatological diseases for more than a century. Urea is a potent emollient and keratolytic agent, making... (Review)
Review
INTRODUCTION
Urea is an organic compound that has been used clinically for dermatological diseases for more than a century. Urea is a potent emollient and keratolytic agent, making urea an effective monotherapy for conditions associated with dry and scaly skin. A systematic review of the literature is needed to provide clinicians with evidence-based applications of urea in the treatment of dermatological diseases.
METHODS
A PubMed search was conducted using the term "urea" combined with "skin," "ichthyosis," "psoriasis," "xerosis," "emollient," "onychomycosis," "dermatitis," and "avulsion." A total of 81 publications met inclusion criteria and were evaluated. Treatment indication(s), test agents, number of subjects, treatment protocols, results, and side effects were recorded.
RESULTS
Effective treatment with urea has been reported for the following conditions: ichthyosis, xerosis, atopic dermatitis/eczema, contact dermatitis, radiation induced dermatitis, psoriasis/seborrheic dermatitis, onychomycosis, tinea pedis, keratosis, pruritus, and dystrophic nails. Furthermore, urea has been used with other medications as a penetration enhancing agent. Mild irritation is the most common adverse event, proving urea to be a safe and tolerable topical drug without systemic toxicity.
DISCUSSION/CONCLUSION
Urea is a safe, effective dermatologic therapy with wide-ranging clinical utility and minimal, non-systemic side effects. In order to optimize patient care, dermatologists should be well informed with regards to urea's indications and efficacy.
Topics: Dermatologic Agents; Humans; Skin Diseases; Urea
PubMed: 24314769
DOI: No ID Found -
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 -
American Journal of Therapeutics 2019Onychomycoses are fungal nail infections affecting predominantly toenails, and mainly caused by dermatophyte fungi, molds and some Candida species. Nail infections can...
BACKGROUND
Onychomycoses are fungal nail infections affecting predominantly toenails, and mainly caused by dermatophyte fungi, molds and some Candida species. Nail infections can be mild with purely cosmetic implications, but they can also negatively influence quality of life. The deep-seated nature of fungi within the nail plate, prolonged treatment, poor patient adherence, frequent recurrences, and development of resistance to various antimicrobial agents make onychomycosis difficult to successfully treat.
AREAS OF UNCERTAINTY
When and how should clinicians prescribe systemic and topical antifungal drugs for onychomycosis?
DATA SOURCES
A narrative review was undertaken of the current literature identified in Medline, Scopus, CINAHL, the Cochrane library, and Google Scholar.
RESULTS
Treatment is often lengthy and requires persistence and patient education. Definitive mycological diagnosis, and an individualized evaluation of risks and benefits of different treatments are imperative before initiating therapy. The choice of treatment can be influenced by the age and general health of the patient, the causative organism, the number of affected nails, and the extent of nail involvement. Oral antifungals offer greater likelihood of a cure than topicals, but oral therapy carries greater risks and requires closer monitoring. Oral terbinafine is the treatment of choice, followed by itraconazole pulse regimen. The newly approved topical agents, efinaconazole and tavaborole, were superior to placebo in clinical trials and appear to produce slightly improved mycological cure rates compared to previous topicals, but further direct comparisons are needed.
CONCLUSIONS
The treatment of onychomycosis can be challenging, as most therapeutic options are lengthy, expensive and potentially unsuccessful.
Topics: Administration, Oral; Administration, Topical; Antifungal Agents; Clinical Trials as Topic; Humans; Medication Adherence; Onychomycosis; Patient Education as Topic; Quality of Life; Recurrence; Time Factors; Treatment Outcome
PubMed: 31082864
DOI: 10.1097/MJT.0000000000000696 -
Journal of Cutaneous Medicine and... 2015Onychomycosis is a difficult-to-treat infection whose current treatment paradigm relies primarily on oral antifungals. The emergence of new topical drugs broadens the... (Review)
Review
BACKGROUND
Onychomycosis is a difficult-to-treat infection whose current treatment paradigm relies primarily on oral antifungals. The emergence of new topical drugs broadens the therapeutic options and prompts a re-evaluation of the current Canadian treatment strategy.
OBJECTIVE
To define a patient-centred Canadian treatment strategy for onychomycosis.
METHODS
An expert panel of doctors who treat onychomycosis was convened. A systematic review of the literature on treatments for onychomycosis was conducted. Based on the results, a survey was designed to determine a consensus treatment system.
RESULTS
First-line therapy should be selected based on nail plate involvement, with terbinafine for severe onychomycosis (>60% involvement), terbinafine or efinaconazole for moderate onychomycosis (20%-60% involvement), and efinaconazole for mild onychomycosis (<20% involvement). Comorbidities, patient preference and adherence, or nail thickness may result in the use of alternative oral or topical antifungals.
CONCLUSION
These guidelines allow healthcare providers and patients to make informed choices about preventing and treating onychomycosis.
Topics: Antifungal Agents; Canada; Consensus; Critical Pathways; Humans; Nails; Onychomycosis; Practice Guidelines as Topic; Toes
PubMed: 25857439
DOI: 10.1177/1203475415581310 -
Journal of the European Academy of... Jun 2015Onychomycosis is a fungal infection of the nail and is the most common nail affliction in the general population. Certain patient populations are at greater risk of... (Review)
Review
Onychomycosis is a fungal infection of the nail and is the most common nail affliction in the general population. Certain patient populations are at greater risk of infection and the prevalence of onychomycosis reported in the literature has yet to be summarized across these at-risk groups. We performed a systematic review of the literature and calculated pooled prevalence estimates of onychomycosis in at-risk patient populations. The prevalence of dermatophyte toenail onychomycosis was as follows: general population 3.22% (3.07, 3.38), children 0.14% (0.11, 0.18), the elderly 10.28% (8.63, 12.18), diabetic patients 8.75% (7.48, 10.21), psoriatic patients 10.22% (8.61, 12.09), HIV positive patients 10.40% (8.02, 13.38), dialysis patients 11.93% (7.11, 19.35) and renal transplant patients 5.17% (1.77, 14.14). Dialysis patients had the highest prevalence of onychomycosis caused by dermatophytes, elderly individuals had the highest prevalence of onychomycosis caused by yeasts (6.07%; 95% CI = 3.58, 10.11) and psoriatic patients had the highest prevalence of onychomycosis caused by non-dermatophyte moulds (2.49%; 95% CI = 1.74, 3.55). An increased prevalence of onychomycosis in certain patient populations may be attributed to impaired immunity, reduced peripheral circulation and alterations to the nail plate which render these patients more susceptible to infection.
Topics: Age Factors; Arthrodermataceae; Diabetes Mellitus; Foot Dermatoses; HIV Infections; Humans; Kidney Transplantation; Onychomycosis; Prevalence; Psoriasis; Renal Dialysis; Risk Factors; Yeasts
PubMed: 25413984
DOI: 10.1111/jdv.12873 -
Future Microbiology Feb 2008Terbinafine is the only systemic allylamine antifungal currently available. Its mechanism of action is unique and sets it apart from other agents. Although it is... (Review)
Review
Terbinafine is the only systemic allylamine antifungal currently available. Its mechanism of action is unique and sets it apart from other agents. Although it is primarily used for dermatophyte infections, such as onychomycosis and tinea pedis, terbinafine has broad in vitro activity against a variety of non-dermatophyte fungal pathogens, including Candida spp. and many molds. In addition, synergistic activity is noted with other antifungals, notably triazoles. Multiple case reports exist of its use for unusual and refractory fungal infections, but no systematic review is available. We review the current literature with regard to in vitro data and clinical experience with terbinafine in the treatment of rare and refractory mycoses.
Topics: Animals; Antifungal Agents; Candida; Dermatomycoses; Drug Resistance, Fungal; Humans; Mycoses; Naphthalenes; Terbinafine; Treatment Outcome; Triazoles
PubMed: 18230029
DOI: 10.2217/17460913.3.1.9 -
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 -
Photodiagnosis and Photodynamic Therapy Sep 2020Fungal infections in skin, hair and nails affect up to 25 % of the global population. Conventional antifungal treatment is effective but due to resistance, treatment... (Review)
Review
BACKGROUND
Fungal infections in skin, hair and nails affect up to 25 % of the global population. Conventional antifungal treatment is effective but due to resistance, treatment failure, drug interactions, and treatment related toxicity, there is a need for alternative treatments. Photodynamic therapy (PDT) has shown antimicrobial properties and is used increasingly for fungal infections. This review investigates the reported efficacy and side effects of PDT of superficial mycoses.
METHODS
Pubmed and Embase were searched 26-01-2020 for "superficial fungal infections" and "photodynamic therapy" in "Human subjects" using a predefined search string. Criteria for inclusion were: clinical trials and cases involving PDT-treated patients with primary fungal infections in skin, hair and nails. Criteria for exclusion were: languages other than English, animal models, in vitro trials, secondary fungal infections, reviews and guidelines.
RESULTS
541 records were identified and 34 papers fulfilled the criteria. PDT of onychomycosis (n = 380 patients) found treatment with methylene blue (MB) photosensitizer (PS) more efficacious with complete cure rates of 70 %-80 % than 5-aminolevulinic acid (ALA)-PDT (mycological cure rates of 17 %-57 %) and methyl aminolevulinate (MAL)-PDT (mycological cure rate of 32 %). Other PDT-treated fungal diseases included (n = 55): foot infections (n = 19), tinea cruris (n = 10), scalp infections (n = 2), Malassezia infections (n = 9) and subcutaneous fungal infections (n = 15) achieved promising effect.
CONCLUSION
PDT-treatment of superficial mycoses can be efficacious as salvage therapy. In the light of increasing resistance and few licensed treatment alternatives, larger randomized controlled trials investigations and optimization of the PDT-treatment protocol are warranted to evaluate PDT's potential as a future antifungal treatment.
Topics: Aminolevulinic Acid; Dermatomycoses; Humans; Methylene Blue; Onychomycosis; Photochemotherapy; Photosensitizing Agents
PubMed: 32339671
DOI: 10.1016/j.pdpdt.2020.101774