S1 Guideline onychomycosis.

Onychomycosis is a fungal infection of the fingernails and toenails. In Europe, tinea unguium is mainly caused by dermatophytes. The diagnostic workup comprises microscopic examination, culture and/or molecular testing (nail scrapings). Local treatment with antifungal nail polish is recommended for mild or moderate nail infections. In case of moderate to severe onychomycosis, oral treatment is recommended (in the absence of contraindications). Treatment should consist of topical and systemic agents. The aim of this update of the German S1 guideline is to simplify the selection and implementation of appropriate diagnostics and treatment. The guideline was based on current international guidelines and the results of a literature review conducted by the experts of the guideline committee. This multidisciplinary committee consisted of representatives from the German Society of Dermatology (DDG), the German-Speaking Mycological Society (DMykG), the Association of German Dermatologists (BVDD), the German Society for Hygiene and Microbiology (DGHM), the German Society of Pediatric and Adolescent Medicine (DGKJ), the Working Group for Pediatric Dermatology (APD) and the German Society for Pediatric Infectious Diseases (DGPI). The Division of Evidence-based Medicine (dEBM) provided methodological assistance. The guideline was approved by the participating medical societies following a comprehensive internal and external review.

A multicentre, randomised, parallel-group, double-blind, vehicle-controlled and open-label, active-controlled study (versus amorolfine 5%), to evaluate the efficacy and safety of terbinafine 10% nail lacquer in the treatment of onychomycosis.

BACKGROUND: Onychomycosis is a difficult-to-treat fungal nail infection whose treatment can involve systemic or topical antifungal approaches. OBJECTIVES: To assess the efficacy and safety of terbinafine 10% nail lacquer in distal-lateral subungual onychomycosis (DLSO). PATIENTS/METHODS: Patients with mild-to-moderate DLSO were randomised (3:3:1) to receive double-blind topical terbinafine 10% (n = 406) or its vehicle (n = 410) administered once daily for 4 weeks and then once weekly for 44 weeks, or open-label topical amorolfine 5% (n = 137) for 48 weeks, with a 12-week follow-up period. The primary efficacy endpoint, complete cure rate at Week 60, was a composite of negative potassium hydroxide (KOH) microscopy, negative culture for dermatophytes and no residual clinical involvement of the target big toenail. RESULTS: Complete cure rates at Week 60 in the terbinafine, vehicle and amorolfine groups were 5.67%, 2.20% and 2.92%, respectively (odds ratio (OR) vs vehicle = 2.68; 95% confidence intervals (CI): 1.22-5.86; p = .0138). Statistically significant differences in responder (negative KOH and negative culture and ≤10% residual clinical involvement) and mycological cure rates (negative KOH and negative culture) at Week 60 were obtained between terbinafine and vehicle. Terbinafine was well-tolerated with no systemic adverse reactions identified; the most common topical adverse reactions were erythema and skin irritation. CONCLUSIONS: Terbinafine 10% nail lacquer was an effective treatment for mild-to-moderate onychomycosis improving both clinical and mycological criteria compared with vehicle. Furthermore, there may be some benefits compared to the currently available topical agent, amorolfine 5%. Treatment was well-tolerated and safe.

Race reporting and representation in onychomycosis clinical trials: A systematic review.

BACKGROUND: Onychomycosis is the most common nail disease seen in clinical practice. Inclusion of diverse groups in onychomycosis clinical trials subjects is necessary to generalise efficacy data. OBJECTIVES: We aimed to systematically review race and ethnicity reporting and representation, as well as, treatment outcomes in onychomycosis clinical trials. METHODS: A PubMed search for onychomycosis clinical trials was performed in August 2020. Primary clinical trial data were included and post hoc analyses were excluded. Categorical variables were compared using chi-squared and Fisher's exact tests. Statistical significance was set at p < .05. Photos in articles were categorised by Fitzpatrick skin type. RESULTS: Only 32/182 (17.5%) trials reported on race and/or ethnicity and only one trial compared treatment efficacy in different subgroups. Darker skin colours were infrequently depicted in articles. Topical treatment, location with ≥1 US-based site, industry funding type and publication date after 2000 were significantly associated with reporting of racial/ethnic data (p < .05 for all comparisons). LIMITATIONS: Demographics on excluded subjects and methods of recruitment were not available. Assigning Fitzpatrick skin type is inherently subjective. CONCLUSIONS: This study highlights a need for consistent reporting of races and ethnicities of onychomycosis clinical trial participants with subgroup analyses of treatment efficacies.

Onychomycosis: Clinical overview and diagnosis.

Onychomycosis is a fungal nail infection caused by dermatophytes, nondermatophytes, and yeast, and is the most common nail disorder seen in clinical practice. It is an important problem because it may cause local pain, paresthesias, difficulties performing activities of daily life, and impair social interactions. In this continuing medical education series we review the epidemiology, risk factors, and clinical presentation of onychomycosis and demonstrate current and emerging diagnostic strategies.

Onychomycosis: Treatment and prevention of recurrence.

Onychomycosis is a fungal nail infection caused by dermatophytes, nondermatophytes, and yeast, and is the most common nail disorder seen in clinical practice. It is an important problem because it may cause local pain, paresthesias, difficulties performing activities of daily living, and impair social interactions. The epidemiology, risk factors, and clinical presentation and diagnosis of onychomycosis were discussed in the first article in this continuing medical education series. In this article, we review the prognosis and response to onychomycosis treatment, medications for onychomycosis that have been approved by the US Food and Drug Administration, and off-label therapies and devices. Methods to prevent onychomycosis recurrences and emerging therapies are also described.

Onychomycosis: Old and New.

Onychomycosis is a common chronic fungal infection of the nail that causes discoloration and/or thickening of the nail plate. Oral agents are generally preferred, except in the case of mild toenail infection limited to the distal nail plate. Terbinafine and itraconazole are the only approved oral therapies, and fluconazole is commonly utilized off-label. Cure rates with these therapies are limited, and resistance to terbinafine is starting to develop worldwide. In this review, we aim to review current oral treatment options for onychomycosis, as well as novel oral drugs that may have promising results in the treatment of onychomycosis.

Therapeutic treatment strategies for the management of onychomycosis: a patent perspective.

INTRODUCTION: Onychomycosis, a multifactorial fungal infection of the nails, shows a global prevalence of about 5.5% and is responsible for 50% of all nail infections. To develop effective management strategies, it is necessary to understand the etiology, pathophysiology, and risk factors of onychomycosis. Oral route of drug delivery is one of the routes utilized to deliver anti-fungal agents, but, has its own limitations like longer duration of treatment, increased adverse effects, and potential for drug interaction. The ungual route has received greater attention due to its localized, non- invasive action and improved patient compliance. AREAS COVERED: This review comprehensively discusses conventional onychomycosis therapies and patented novel drug delivery systems for the management of onychomycosis including chemical permeation enhancers, non-particulate drug delivery systems, penetration enhancing devices etc., Databases such as PubMed, ResearchGate, and Google Patents were searched by using the keywords onychomycosis and trans-ungual drug delivery. EXPERT OPINION: Enormous research has been conducted and is still ongoing to find the best possible novel drug delivery system for onychomycosis management. Approaches like incorporation of herbal constituents in nano-formulations, inkjet printing, laser devices, iontophoretic techniques, etc. can be employed to make safe and effective drug delivery systems which are regulatory compliant.

A clinical study for the treatment of onychomycosis patients using a novel ROS producing onychomycosis treatment when compared against 5% amorolfine topical lacquer to reduce the visible size of infected toenails.

BACKGROUND: Onychomycosis affects approximately 5% of the population worldwide without satisfactory treatment options regarding efficacy and safety. The aim of this first in human study was to compare the safety and efficacy of the novel compound Mycosinate® against an approved toenail lacquer containing 5% Amorolfine. DESIGN: A randomized, single-blinded, controlled parallel group study with allocation concealment was carried out. METHODS: Thirty-eight participants either used the novel compound Mycosinate® or an approved toenail lacquer containing 5% Amorolfine for topical application in their own homes. Outcome measures included a) % change in area of clear visible toenail, b) mycological cure rate and c) safety assessments. RESULTS: Statically significant differences for % change in area of clear visible toenail (p<0.05) of 39.8, 40.0 and 70.7 in favour of Mycosinate® were noted at time points 6 weeks, 12 weeks, and 6 months respectively when compared to Amorolfine. No statistically significant differences were noted for mycological cure rates. No adverse events, serious adverse events or deaths occurred for either treatment. CONCLUSION: Mycosinate® is a promising novel topical onychomycosis treatment with high rates of efficacy and excellent safety profile. Further clinical trials are warranted. (EU Clinical Trials Register 2018/000294/78).

Diagnostic accuracy of dermoscopy for onychomycosis: A systematic review.

Background: Dermoscopy is a non-invasive adjuvant diagnostic tool that allows clinicians to visualize microscopic features of cutaneous disorders. Recent studies have demonstrated that dermoscopy can be used to diagnose onychomycosis. We performed this systematic review to identify the characteristic dermoscopic features of onychomycosis and understand their diagnostic utility. Methods: We searched the Medline, Embase, Scopus, and Cochrane databases from conception until May 2021. Studies on the dermoscopic features of onychomycosis were screened. The exclusion criteria were as follows: fewer than 5 cases of onychomycosis, review articles, and studies including onychomycosis cases that were not mycologically verified. Studies on fungal melanonychia were analyzed separately. We adhered to the MOOSE guidelines. Independent data extraction was performed. Data were pooled using a random effects model to account for study heterogeneity. The primary outcome was the diagnostic accuracy of the dermoscopic features of onychomycosis. This was determined by pooling the sensitivity and specificity values of the dermoscopic features identified during the systematic review using the DerSimonian-Laird method. Meta-DiSc version 1.4 and Review Manager 5.4.1 were used to calculate these values. Results: We analyzed 19 articles on 1693 cases of onychomycosis and 5 articles on 148 cases of fungal melanonychia. Commonly reported dermoscopic features of onychomycosis were spikes or spiked pattern (509, 30.1%), jagged or spiked edges or jagged edge with spikes (188, 11.1%), jagged proximal edge (175, 10.3%), subungual hyperkeratosis (131, 7.7%), ruins appearance, aspect or pattern (573, 33.8%), and longitudinal striae (929, 54.9%). Commonly reported features of fungal melanonychia included multicolor (101, 68.2%), non-longitudinal homogenous pigmentation (75, 50.7%) and longitudinal white or yellow streaks (52, 31.5%). Conclusion: This study highlights the commonly identified dermoscopic features of onychomycosis. Recognizing such characteristic dermoscopic features of onychomycosis can assist clinicians diagnose onychomycosis by the bedside.

Updated Perspectives on the Diagnosis and Management of Onychomycosis.

Onychomycosis is the most common nail disease encountered in clinical practice and can cause pain, difficulty with ambulation, and psycho-social problems. A thorough history and physical examination, including dermoscopy, should be performed for each patient presenting with nail findings suggestive of onychomycosis. Several approaches are available for definitive diagnostic testing, including potassium hydroxide and microscopy, fungal culture, histopathology, polymerase chain reaction, or a combination of techniques. Confirmatory testing should be performed for each patient prior to initiating any antifungal therapies. There are several different therapeutic options available, including oral and topical medications as well as device-based treatments. Oral antifungals are generally recommended for moderate to severe onychomycosis and have higher cure rates, while topical antifungals are recommended for mild to moderate disease and have more favorable safety profiles. Oral terbinafine, itraconazole, and griseofulvin and topical ciclopirox 8% nail lacquer, efinaconazole 10% solution, and tavaborole 5% solution are approved by the Food and Drug Administration for treatment of onychomycosis in the United States and amorolfine 5% nail lacquer is approved in Europe. Laser treatment is approved in the United States for temporary increases in clear nail, but clinical results are suboptimal. Oral fluconazole is not approved in the United States for onychomycosis treatment, but is frequently used off-label with good efficacy. Several novel oral, topical, and over-the-counter therapies are currently under investigation. Physicians should consider the disease severity, infecting pathogen, medication safety, efficacy and cost, and patient age, comorbidities, medication history, and likelihood of compliance when determining management plans. Onychomycosis is a chronic disease with high recurrence rates and patients should be counseled on an appropriate plan to minimize recurrence risk following effective antifungal therapy.

Combination Therapy Should Be Reserved as Second-Line Treatment of Onychomycosis: A Systematic Review of Onychomycosis Clinical Trials.

Onychomycosis is the most common nail disease encountered in clinical practice. Its importance extends well beyond aesthetics, often causing pain, difficulty with ambulation and performing daily activities, and impairing quality of life. Many patients fail to achieve cure with antifungal monotherapy and recurrences are common. Combination therapy has therefore gained considerable interest, given the potential for drug synergy and prevention of antifungal resistance, but it has not been well studied. A systematic review of onychomycosis medication only, as well as medication and procedural (laser, debridement, photodynamic therapy), clinical or randomized controlled trials evaluating combination vs. monotherapies was performed. After exclusions, 30 studies were included in the final analysis. There were conflicting results for medication-only trials, with some showing significant benefit of combination therapy over monotherapy, however, trials were not robustly designed and lacked sufficient follow-up. Procedural studies also lacked long-term follow-up, and failed to demonstrate efficacy in some severe onychomycosis cases. Considering the high cure rates demonstrated in pivotal antifungal monotherapy trials, and conflicting results, costs, and safety concerns associated with combination therapy, we recommend that combination therapy be reserved as second-line treatment options in patients with poor prognostic factors or for those who failed monotherapy for onychomycosis.

Efficacy of Propolis Gel on Mature Biofilm Formed by Neocosmospora keratoplastica Isolated from Onychomycosis.

This article describes Neocosmospora keratoplastica as an etiological onychomycosis agent. Ex vivo studies were initially performed to demonstrate the ability of this species to grow and form a well-organized characteristic biofilm on sterilized healthy nails. Based on the history of excellent results, both for antifungal and antibiofilm, of propolis resin gum, we evaluated its activity using artificially formed biofilm. In vitro, the minimal biofilm eradication concentration of the propolis extract (PE) was 375 µg of total polyphenol content (TPC) per mL, while for the propolis gel (PG) it was 450 µg of TPC per mL. In biofilm exposed to the propolis products, a decrease in hyphae and conidia was evident, accompanied by a disorganization of the extracellular matrix. Additionally, this low concentration of PE was able to significantly reduce the number of colony-forming units and the metabolic activity. Furthermore, the treatment of a 15-year nail infection due to N. keratoplastica was carried out exclusively using a topical treatment with a gel containing propolis (30%) with a daily dosage. This treatment achieved complete remission of the onychomycosis in 12 months. It is important to point out that some inconveniences previously reported by other patients treated with propolis extract were eliminated, increasing adherence to treatment.

Retrospective analysis of adverse events with systemic onychomycosis medications reported to the United States Food and Drug Administration.

BACKGROUND: Onychomycosis is the most common nail condition and when left untreated, has esthetic, physical and emotional-social sequelae. OBJECTIVE: To classify the most common adverse reactions with the oral onychomycosis medications terbinafine, itraconazole, and off-label fluconazole. METHODS: The United States Food and Drug Administration Adverse Event Reporting (FAERS) database was analyzed for common adverse reactions with terbinafine, itraconazole, and off-label fluconazole. Transaminase elevations reported with terbinafine usage were further subdivided by the age group. Google Trends was used to examine public interest in these medications and compare yearly data with adverse events in the FAERS database. RESULTS: The most common adverse reaction with terbinafine was taste disturbance and the most common adverse events with itraconazole and fluconazole were drug interactions. Transaminase elevations associated with terbinafine were extremely rare in the pediatric population. Increased Google searches for all three medications were also associated with increased reporting of adverse events in the FAERS database. CONCLUSION: Patients should be counseled that taste disturbance with terbinafine is the most common adverse event. Concomitant medications must be reviewed carefully before prescribing itraconazole or fluconazole since drug interactions are relatively common. Public interest in onychomycosis has increased in recent years, potentially explaining increased prescribing of oral onychomycosis medications and increased reporting to FAERS.

Deferring Nail Mycological Sampling during the COVID-19 Pandemic: Recommendations from a Multidisciplinary Panel of Nail Specialists.

Onychomycosis is the most common nail condition seen in clinical practice, with significant impact on quality of life. Clinical examination alone is insufficient for accurate diagnosis, but mycological confirmation can be challenging during the COVID-19 pandemic. In this letter, a multidisciplinary panel of dermatologists, a podiatrist, dermatopathologists, and a mycologist, discuss considerations for mycological sampling during the pandemic.

Pharmacotherapy for onychomycosis: new and emerging treatments.

INTRODUCTION: Onychomycosis is the most common nail disorder seen in clinical practice. It is not merely an aesthetic disorder and may cause significant disability and affect the quality of life. There are no strict guidelines for onychomycosis therapy. Therefore, medical management is individualized based on drug efficacy, taken together with clinical presentation, infecting organism, co-morbidities, concomitant medications, and patient preferences. AREAS COVERED: This review provides a clinically oriented critical perspective on the pathophysiology of onychomycosis, infecting organisms, and prognostic factors, and how these play a role in choosing optimal pharmacotherapy. Clinical and pharmacological considerations are described in explaining the optimal medical management of onychomycosis. EXPERT OPINION: Onychomycosis is a common nail disorder with significant burden; yet, there are only six Food and Drug Administration approved medical therapies for this indication. When therapy is applied to specific patients, the options become even more limited. In addition, mycological and complete cure rates of systemic medications have not yet approached 100%, and cure rates for topicals are much lower. Further insight into the pathophysiology of the disease focusing on the fungal life cycle and understanding biofilms will likely lead to more optimal cure rates, decreasing morbidity and enhancing the overall quality life of the affected individuals.

Psychosocial perception of adults with onychomycosis: a blinded, controlled comparison of 1,017 adult Hong Kong residents with or without onychomycosis.

BACKGROUND: A survey was conducted amongst 1,017 Hong Kong residents ages 18 and over to determine their knowledge of fungal nail infections (onychomycosis) and the psychosocial impact of the disease on the relationships, social lives and careers of sufferers. METHODS: The Fungal Nail Perception Survey was conducted by email and online between May 29th and June 10th, 2013. Participants were shown three photographs of people with and without onychomycosis of the toenails. Respondents were asked ten questions (repeated for each picture) to ascertain their perceptions of the people in the pictures. Questions were related to perceptions around the ability of sufferers and non-sufferers to form relationships with others, social activities of sufferers and non-sufferers, perceptions of the effect of the disease on the potential for career success, and awareness of fungal nail disease and health. The sub-population who themselves suffered from onychomycosis were asked about self-perception as well as their perception of others with onychomycosis. RESULTS: Compared with non-sufferers, survey respondents perceived those with onychomycosis as less likely to be able to form good relationships. They also indicated that they would be more likely to exclude sufferers than non-sufferers from social activities and that they would be more likely to feel uncomfortable when sitting or standing beside an infected person than beside an uninfected person. Respondents perceived people with onychomycosis to be less able to perform well in their chosen career than with someone without onychomycosis. Interestingly, those respondents who themselves were infected felt socially excluded, upset and embarrassed by their infection. CONCLUSIONS: Onychomycosis may lead to stigmatization and social exclusion. Misconceptions of onychomycosis are high and education about the disease needs to be improved. Early recognition and treatment of the disease is essential to avoid complications and improve treatment outcomes, which would lead to reduced psychosocial impact on those with fungal nail infections.