Toenail Onychomycosis Research Articles

In vivo Guinea Pig Model Study for Evaluating Antifungal Effect of a Dual-Diode Laser with Wavelengths of 405 Nm and 635 Nm on Dermatophytosis.

Various laser- and light-based devices have been introduced as complementary or alternative treatment modalities for dermatophytosis, particularly for finger or toenail onychomycosis. This study aimed to comparatively evaluate the antifungal effects of 405-nm and 635-nm dual-band diode lasers using an in vivo guinea pig model of dermatophytosis. A guinea pig model was developed by the repetitive application of fungal spore preparations to the back skin of guinea pigs. Dual-diode laser treatment was delivered to the guinea pig skin at a power of 24 mW at a wavelength of 405 nm and 18 mW at 635 nm for 12 min. The treatments were administered three times weekly for 2 weeks, and a mycological study was performed. Mycological studies using scraped samples obtained from treatment groups A (N = 8) and B (N = 8) after dual-diode laser treatment revealed that seven of eight (87.5%) samples in each group had negative results for direct potassium hydroxide microscopy and fungal culture studies. Skin specimens from each infected laser-untreated guinea pig exhibited spongiotic psoriasiform epidermis with parakeratosis. Meanwhile, skin specimens from infected laser-treated guinea pigs in groups A and B demonstrated thinner epidermal thickness than those from infected untreated controls but thicker than those from uninfected treated controls without noticeable inflammatory cell infiltration in the dermis. The guinea pig dermatophytosis model can be used to comparatively evaluate the efficacy and safety of various treatment modalities, including dual-diode lasers, for superficial fungal skin infection.

Relative impact of traditional vs. newer oral antifungals for dermatophyte toenail onychomycosis: a network meta-analysis study.

There is a paucity of evidence regarding the relative therapeutic efficacy of treatments for onychomycosis. We determined the relative efficacy of monotherapies for dermatophyte toenail onychomycosis with Bayesian network meta-analyses (NMAs). We searched PubMed, Scopus, EMBASE (Ovid) and CINAHL to identify studies that investigated the efficacy of monotherapy with oral antifungals for dermatophyte toenail onychomycosis in adults. In this paper, 'regimen' corresponds to a given agent and its dosage. The relative effects and surface under the cumulative ranking curve (SUCRA) values of the various regimens were estimated; evidence quality was assessed at the study level and across networks. Data from 21 studies were used. Our two efficacy-related endpoints were: (i) mycological and (ii) complete cure at 1 year; safety--related endpoints were: (i) 1-year count of any adverse event (AE), (ii) 1-year odds of discontinuation due to any AE, (iii) 1-year odds of discontinuation due to liver issues. Thirty-five regimens were identified; the newer agents among these included posaconazole and oteseconazole. We compared the efficacy of newer regimens with traditional ones like 'terbinafine 250 mg daily for 12 weeks' and 'itraconazole 200 mg daily for 12 weeks. We found that an agent's dosage was associated with its efficacy; for example, the 1-year odds of mycological cure with terbinafine 250 mg daily for 24 weeks (SUCRA = 92.4%) were significantly greater than those of terbinafine 250 mg daily for 12 weeks (SUCRA = 66.3%) (odds ratio 2.62, 95% credible interval 1.57-4.54). We also found that booster regimens can increase efficacy. Our results showed that some triazoles could be more effective than terbinafine. This is the first NMA study of monotherapeutic antifungals - and their various dosages - for dermatophyte toenail onychomycosis. Our findings could provide guidance for the selection of the most appropriate antifungal agent, especially amid the growing concerns about terbinafine resistance.

Detection of Squalene Epoxidase Mutations in United States Patients with Onychomycosis: Implications for Management

Resistance to oral terbinafine, the most commonly used antifungal to treat dermatophytosis and onychomycosis worldwide, is being increasingly reported. In this study, we aimed to investigate the species distribution and prevalence of squalene epoxidase mutations among toenail dermatophyte isolates. Samples from 15,683 patients suspected of onychomycosis visiting the offices of dermatologists and podiatrists in the United States were analyzed. Clinical information was reviewed, and dermatophyte species with or without squalene epoxidase mutations were detected using multiplex real-time PCRs. The frequency of dermatophytes was 37.6%; of isolates belonging to the Trichophyton genus, 88.3% were the T.rubrum complex, and 11.2% were the T.mentagrophytes complex. Individuals aged >70 years exhibited higher infection rates for the T.mentagrophytes complex. The overall mutation rate among Trichophyton spp. was 3.7%, with a higher mutation rate detected in the T.mentagrophytes complex (4.3 vs. 3.6%). Commonly detected mutations were T1189C/Phe397Leu (34.5%), T1306C/Phe415Ser (16.0%), and C1191A/Phe397Leu (11.0%). Squalene epoxidase gene mutations associated with decreased terbinafine susceptibility have been identified in United States patients with toenail onychomycosis. Physicians should be aware of the risk factors for resistance development and engage in antifungal stewardship practices such as directed diagnosis and treatment of dermatophytosis and onychomycosis.

A Case Study of Onychomycosis Caused by Aspergillus Fumigatus

Onychomycosis is known as a nail fungal infection brought on by dermatophytes, yeast, and non-dermatophyte mold. According to epidemiological investigations, Aspergillus fumigatus has been identified as an egregious fungal cause of toenail onychomycosis. Here, we present a case of A. fumigatus-related multiple toenail infections in a 47-year-old woman in good health. The causing agent was determined to be A. fumigatus based on the culture's macroscopic and microscopic features. Keywords: Aspergillus fumigatus, toenail & Onychomycosis

Treatment of Onychomycosis with Homoeopathic Medicine-An Evidence-Based Case Report

Onychomycosis commonly known as nail fungal infection is caused by various types of fungi. It usually affects the toenails but fingernails can also be involved. Homeopathy is an alternative medical practice involving highly diluted substances to stimulate the bodys natural healing processes. A 35-year-old woman presented with discoloration brittleness and thickening of her great right toenail. Following a comprehensive case assessment a prescription of Sepia 200 was given to be taken as needed during the homoeopathic treatment period. The administration of individuaized homoeopathic medicine resulted in a remarkable improvement in the case. Onychomycosis of the great right toenail was treated with an individualized approach of homoeopathic medicine resulting in reduced nail discolorationwith the Sepia 200.

PCR28 Utility Values Derived From Canadian Adults With Toenail Onychomycosis With and Without Comorbid Diabetes Mellitus: A Study Using the Health Utilities Index®

Toenail onychomycosis (fungal infection) affects nearly 7% of Canadians. Symptoms are progressive and include nail discolouration, disfiguration, and pain. The presence of type I/II diabetes mellitus is associated with both an increased risk of onychomycosis infection and of experiencing complications secondary to onychomycosis. Onychomycosis, with and without diabetes, may impact overall health status and associated utility estimates; however, such estimates are lacking. This study sought to estimate utility values associated with toenail onychomycosis, among adult patients with or without comorbid diabetes, in Canada.

PCR146 Preferences for Toenail Onychomycosis Treatments Among Canadians With and Without Diabetes Mellitus: A Discrete Choice Experiment

Toenail onychomycosis (fungal infection) affects approximately 7% of Canadians. Comorbid diabetes may increase risk of infection and associated complications. Treatments include topical therapies and oral agents with varying modes of administration, efficacy, and safety profiles. The objective was to understand patient preferences regarding onychomycosis treatment features and how preferences vary among those with and without diabetes.

Metagenomics of Toenail Onychomycosis in Three Victorian Regions of Australia.

Onychomycosis is a fungal disease of the nail that is found worldwide and is difficult to diagnose accurately. This study used metagenomics to investigate the microbiology of 18 clinically diagnosed mycotic nails and two normal nails for fungi and bacteria using the ITS2 and 16S loci. Four mycotic nails were from Bass Coast, six from Melbourne Metropolitan and eight from Shepparton, Victoria, Australia. The mycotic nails were photographed and metagenomically analysed. The ITS2 sequences for T. rubrum and T. interdigitale/mentagrophytes averaged over 90% of hits in 14/18 nails. The high abundance of sequences of a single dermatophyte, compared to all other fungi in a single nail, made it the most likely infecting agents (MLIA). Trichophyton rubrum and T. interdigitale/mentagrophytes were found in Bass Coast and Shepparton while only T. interdigitale/mentagrophytes was found in Melbourne. Two nails with T. interdigitale/mentagrophytes mixed with high abundance non-dermatophyte moulds (NDMs) (Aspergillus versicolor, Acremonium sclerotigenum) were also observed. The two control nails contained chiefly Fusarium oxysporum and Malassezia slooffiae. For bacteria, Staphylococcus epidermidis was in every nail and was the most abundant, including the control nails, with an overall mean rate of 66.01%. Rothia koreensis, Corynebacterium tuberculostearicum, and Brevibacterium sediminis also featured.

Urea versus fractional Er:YAG laser pretreatment of methylene blue photodynamic therapy in the treatment of moderate toenail onychomycosis: short- and medium-term effects

Keratolytic properties of urea 40% have long time used for the treatment of onychomycosis. Fractional ablative lasers enhance the delivery of topically applied photosensitizers improving photodynamic therapy (PDT) efficacy. The aim of this study was to compare the short- and medium-term efficacy of a pretreatment with urea 40% and fractional Er:YAG (Fr Er:YAG) laser radiation before PDT mediated by methylene blue (MB) for moderate toenail onychomycosis. Twenty-first-toe toenails were randomized to receive either urea 40% (Group I) or Fr Er:YAG laser (Group II) pretreatment and 9 sessions of MB/PDT over the course of 16 weeks. At baseline, 28- and 40-week follow-ups, clinical efficacy was assessed by digital photographs [allowing determination of the onychomycosis severity index (OSI)], whereas mycological efficacy was assessed by histological examination and fungal culture. Details of the side effects and patients’ satisfaction were also recorded. In both groups, a significant decrease in OSI values was observed at the 28-week follow-up and a slight rebound at the 40-week follow-up. The percentage of nail involvement decreased significantly in both groups at the 28-week follow-up, to continue declining gently in Group I at 40 weeks, in contrast to the rebound observed during this period in Group II. The mycological cure rate was 20% and 30% at 28-week follow-up and 70% and 40% at 40-week follow-up, in Group I and II, respectively. Patients reported being fairly satisfied, and no side effects were detected in any groups. Although both pretreatments favor the action of PDT for the treatment of onychomycosis, the use of urea at 40% is more effective in the medium term.

Prevalence of Onychomycosis in Diabetic Patients: A Case-Control Study Performed at University Hospital Policlinico in Catania.

Diabetes is characterized by an increased rate of serum glucose due to defects in insulin secretion, insulin action or both conditions. Glucose excesses can lead to extended cellular damage, with the consequence of several infectious and non-infectious skin disorders. The aim of the present study was to evaluate the toenail onychomycosis incidence in diabetic patients and healthy ones. The non-interventional, retrospective study was performed at the mycology laboratory of the University hospital “Policlinico-San Marco” in Catania, Italy, for over one year. Nail clippings were collected to perform microscopic and cultural exams, which allowed for the identification of fungal aetiological agents. A total of 715 patients (47 diabetic and 668 non-diabetic patients) were enrolled. In diabetic patients, dermatophytes were the most common cultural isolates (50%), followed by yeasts and moulds in 30.8% and 19.2%, respectively. In non-diabetic patients, the distribution of dermatophytes, yeasts and non-dermatophytic moulds was 67.4%, 5.3% and 27.3%, respectively. According to our results, diabetic patients are more predisposed to nail fungal infection. Our data suggest that dermatological follow-ups should always be performed for diabetic patients. All skin and nail disorders should be carefully monitored to perform a diagnostic confirmation and correct management of diabetic patients.

Epidemiology of Onychomycosis in Chinese Mainland: A 30-year Retrospective Study.

Onychomycosis was a common nail disease caused by dermatophytes, yeasts or molds. The prevalence of onychomycosis varied in different counties and it was necessary to understand the epidemiology in China. This study was conducted to investigate the epidemiology of onychomycosis in Chinese mainland in the past 30years. A 30-year systemic review was carried out by searching publications investigating the prevalence of onychomycosis in Chinese mainland from 1991 to 2020. A total of 90 articles involving more than 40,000 onychomycosis patients were enrolled in this study. The ratio of males to females was 1:1.32. Fingernail onychomycosis was found in 36.12% cases, toenail onychomycosis in 48.31%, and both fingernail and toenail onychomycosis in 15.57%. The most common clinical type of onychomycosis was distal lateral subungual onychomycosis (60.99%), followed by total dystrophic onychomycosis (18.91%), proximal subungual onychomycosis (10.19%) and superficial white onychomycosis (9.92%). Dermatophytes (60.59%) were the most frequently isolated pathogens, followed by yeasts (30.09%), molds (7.91%) and mixed infection (1.41%). The primary pathogens in dermatophytes, yeasts and molds were Trichophyton rubrum (49.93%), Candida albicans (10.99%) and Aspergillus (3.11%), respectively. Additionally, dermatophytes were more commonly affected males than females (63.69% vs. 51.57%), and mostly involved in toenail onychomycosis (75.63%). The infection of yeasts was higher in females than males (40.97% vs. 29.52%), often causing onychomycosis in fingernail than toenail (41.03% vs. 17.08%), and it was more common in warm and humid southern regions than northern area (34.07% vs. 24.41%). The proportion of the causative agents changed over time, dermatophytes, especially T. rubrum had always been the predominant pathogen, followed by yeasts and molds. The distribution of fungal pathogens varied among clinical types, gender, infection sites and geography gender.

Therapeutic Recommendations for the Treatment of Toenail Onychomycosis in the US

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Acitretin: Could it be a new therapeutic player in the field of onychomycosis?

Onychomycosis represents a therapeutic challenge. The complete cure rate with itraconazole pulse therapy remains unsatisfactory implying the need for an effective therapeutic regimen. Given the successful treatment of recurrent dermatophytosis with isotretinoin and itraconazole, we investigated the therapeutic use of acitretin in onychomycosis. To evaluate and compare the efficacy of combined itraconazole and acitretin versus monotherapy with each in onychomycosis. The study included 135 adult patients with finger- and/or toenail onychomycosis. They were equally subdivided into 3 groups: itraconazole pulse therapy, acitretin and combined itraconazole/acitretin therapy. The drugs were administered for 3months. Evaluation of severity was done by onychomycosis severity index score. Potassium hydroxide microscopy and culture were performed at baseline and at the end of the study. Mycological and complete cure of onychomycosis was observed in 51.1% and 20% of the itraconazole group, 28.9% and 28.9% of the acitretin group, and 80% and 53.3% of the combined group. There was a statistically significant difference between groups in favour of the combined itraconazole/acitretin therapy (P≤.05). Small sample and short therapy duration. Acitretin could be a powerful therapeutic player in the field of onychomycosis, with greater efficacy when combined with itraconazole.

Review of the alternative therapies for onychomycosis and superficial fungal infections: posaconazole, fosravuconazole, voriconazole, oteseconazole.

Terbinafine and itraconazole are the most commonly used oral antifungals to treat onychomycosis and superficial dermatomycoses. Recently, poor response to oral terbinafine has been reported. We have summarized the most appropriate dosing regimens of posaconazole, fosravuconazole, voriconazole, and oteseconazole (VT-1161) to treat onychomycosis and superficial fungal infections. A structured search on PubMed and Google Scholar was conducted. Additionally, the bibliographies of selected articles were searched to identify relevant records. The number of records identified from the searches was 463, with 50 articles meeting the inclusion criteria for review. None of the new azoles are US FDA approved for onychomycosis treatment; however, an increasing number of studies have evaluated these agents. The efficacies (complete cure and mycologic cure) of the antifungal agents for dermatophyte great toenail onychomycosis treatment are terbinafine 250 mg/day × 12 weeks (Phase III trial) (38%, 70%), itraconazole 200 mg/day × 12 weeks (Phase III trial) (14%, 54%), posaconazole 200 mg/day × 24 weeks (Phase IIB) (54.1%, 70.3%), fosravuconazole 100 mg/day ravuconazole equivalent × 12 weeks (Phase III) (59.4%, 82.0%), and oteseconazole 300 mg/day loading dose × 2 weeks (Phase II), followed by 300 mg/week × 10 weeks (maintenance dose) (45%, 70%). Guidelines for monitoring are also presented.

Therapeutic Recommendations for the Treatment of Toenail Onychomycosis in the US

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Total Dystrophic Onychomycosis Successfully Treated with Efinaconazole Topical Solution in Times of COVID: A Case Study

Toenail onychomycosis is a common condition that is equally challenging for podiatrists and patients. This case study documents a 26-year-old woman with bilateral total dystrophic onychomycosis of at least 5 years' duration. She had previously failed to respond to treatment with ciclopirox nail lacquer 8% and, despite hiding her condition with nail polish, was suffering from embarrassment, distress, and low self-esteem. At initial consultation, 100% of both great toenails was affected. After discussion of all treatment options, the patient opted for topical efinaconazole 10% solution, once daily for 48 weeks. Significant improvement was noted at the first (4-week) assessment period. This improvement was maintained through each subsequent virtual consultation, and complete cure was seen at a 30-week follow-up visit. To the author's knowledge, this is the first published report on the use of efinaconazole in total dystrophic onychomycosis. It suggests that the product may be effective in patients with even the most severe and treatment-recalcitrant disease, who are unwilling or unable to tolerate systemic antifungal therapy.

Therapeutic Recommendations for the Treatment of Toenail Onychomycosis in the US.

Onychomycosis affects around 14% of individuals in North America and Europe and is undertreated. Treatment is challenging as toenail growth can take 12–18 months, the nail plate may prevent drug penetration, and disease recurrence is common. National guidelines/consensus documents on onychomycosis diagnosis and treatment were last published more than 5 years ago and updated medical guidance is needed. This document aims to provide recommendations for the diagnosis and pharmaceutical treatment of toenail onychomycosis following a roundtable discussion with a panel of dermatologists, podiatrists, and a microbiologist specializing in nail disease. There was a general consensus on several topics regarding onychomycosis diagnosis, confirmatory laboratory testing, and medications. Onychomycosis should be assessed clinically and confirmed with microscopy, histology, and/or culture. Terbinafine is the primary choice for oral treatment and efinaconazole 10% for topical treatment. Efinaconazole can also be considered for off-label use for maintenance to prevent recurrences. For optimal outcomes, patients should be counseled regarding treatment expectations as well as follow-up care and maintenance post-treatment. This article provides important updates to previous guidelines/consensus documents to assist dermatologists and podiatrists in the diagnosis and treatment of toenail onychomycosis. J Drugs Dermatol. 2021;20(10):1076-1084. doi:10.36849/JDD.6291.

Combination of a triple wavelength (650 nm, 810 nm, and 915 nm) class IV laser system and local mechanical abrasion in the treatment of chronic toenail onychomycosis: an uncontrolled prospective pilot study.

BackgroundToenail onychomycosis is a frequent fungal infection that is difficult to treat, especially in elderly patients. Diverse local and systemic antifungal treatments are available with variable results. Recently, different laser systems have been proposed for the treatment of onychomycosis, among them a class IV laser system adopting three different wavelengths, that is, 650, 810, and 915 nm (K‐Laser Cube 3TM).ObjectivesThis prospective pilot study aims to clarify the clinical, histopathologic, and cultural mycological efficacy of the combination of a triple wavelength laser system and local mechanical abrasion in the treatment of toenail onychomycosis.MethodsEight treatment sessions were performed involving a mechanical drill of the friable nail material followed by the laser treatment with four 2‐minute cycles per nail with a median power of 3 W providing 240 J each. Clinical exam, mycological culture, and histopathology with PAS staining of nail clips were performed at the beginning and the end of the treatment period.ResultsNine patients with 16 clinically involved nails were included in this study (median age: 55.6). Clinical improvement was noted in eight patients (89%) at the end of the treatment cycles. Initial positive cultures could be reduced from six (67%) to two (22%), P = 0.07, while histopathologic examination by PAS staining remained invariable positive in all patients (100%).ConclusionDespite clinical improvement, the combination of this laser treatment and mechanical abrasion could not reduce the fungal infection rate in affected toenails. Additional local or systemic antimycotic agents should be combined in order to avoid expected clinical recurrences.

The Efficacy of Phototherapy for the Treatment of Onychomycosis: An Observational Study

(1) Background: Onychomycosis accounts for 50% of nail pathologies and is a therapeutic challenge due to an increase in resistance to antifungal agents. This study aimed to explore the effectiveness of 1064 nm diode laser irradiation for the treatment of Onychomycosis and establish a new set of laser parameters for effective and safe treatment; (2) Methods: An exploratory, single-blinded study was conducted on forty-five patients with toenail Onychomycosis. Digital images and nail clippings were taken for Periodic Acid-Schiff (PAS) staining and fungal microscopy and culture (MC&S). Group 1 received 5% topical Amorolfine lacquer to apply to affected nails. Group 2 received 1064 nm diode laser treatment at 10 mW/s, hallux 790 J/cm2 and lesser digits 390 J/cm2 (standard treatment). Group 3 received 1064 nm diode laser treatment at 10 mW/s, hallux 1 100 J/cm2 and lesser digits 500 J/cm2 (new treatment parameters). After laser treatment, nail temperatures were taken with a surface thermometer; (3) Results: PAS staining was more sensitive in identifying Onychomycosis (91.1%), compared to Fungal Microscopy (44.4%). Comparing treatment requirements over a period of 24 weeks, there was a statistical significance, p ≤ 0.01 (**), for standard laser treatment and, p ≤ 0.001 (***), for new laser parameter treatment, indicating treatment needed over time decreased. No adverse effects were noted with new laser therapy. An 86.7% visual improvement was noted in Group 3 after 24 weeks; (4) Conclusions: Phototherapy, or photo thermolysis, was the best treatment option for Onychomycosis. A new protocol for the standardization of laser irradiation with the possible inclusion into the Scoring Clinical Index for Onychomycosis treatment plan, was proposed.

Onychomycosis in older adults: The age and associated factors affecting the complete cure rate.

Limited studies exist on the factors associated with a complete cure of onychomycosis in older adults. To determine the age and factors associated with a complete cure among older adults diagnosed with toenail onychomycosis. A retrospective cohort study was conducted of 95 older adult patients (aged ≥ 60 years) diagnosed with toenail onychomycosis between January 2016 and December 2017. Demographic data, mycological findings, treatments and durations to a complete cure were reviewed. The complete cure rates of the patients aged < 70 years and ≥70 years were 67.4% and 44.9%, respectively (P = 0.027). Patients aged ≥ 70 years were significantly higher in male gender, had higher history of smoking, peripheral arterial disease, impaired renal function, antihypertensive drug and amorolfine nail lacquer usage, and polypharmacy. A multivariate analysis revealed that being aged ≥70 years and having a nail thickness >2 mm were associated with failure to achieve a complete cure. The median times to a complete cure for older adults aged <70 years and ≥70 years were 20 months and 47 months, respectively (P = 0.007). An age ≥ 70 years was related to a lower cure rate and delays in achieving a complete cure. A nail thickness > 2 mm was a poor prognostic factor for a complete cure. Moreover, very old adults were more likely to suffer side effects arising from the use of systemic antifungal medications.