Treatments for Onychomycosis: A Bibliometric Analysis.

Introduction: Oral antifungals were the earliest treatments to receive approval for the management of onychomycosis and have a long-standing record to support their efficacy. Topical antifungals and device-based treatments have been explored and some implemented in more recent years as alternatives to traditional oral antifungals. The present bibliometric analysis summarizes trends in publication frequency for onychomycosis treatment modalities over time and characterizes their body of literature in terms of types of studies available and relative level of evidence. Methods: A comprehensive literature search was performed using Web of Science and SCOPUS databases. Results: Covering all publications from 1970 to present day, our search identified oral therapeutics n = 295 articles (n = 63 randomized control trials [RCTs]), topical therapeutics n = 358 articles (n = 72 RCTs), and device-based treatments n = 158 articles (n = 37 RCTs). Spikes in research activity surround FDA approval of therapeutics for each treatment modality. Research activity within the last decade has focused on topical and device-based treatments. Evidence for efficacy of device-based treatments is lacking from relatively few high-quality RCTs. Conclusion: With growing concern for non-dermatophyte mold onychomycosis and terbinafine resistance, researchers should validate the efficacy and safety of device-based treatments with high-quality studies.

Concealing Meets Healing in the Treatment of Toenail Onychomycosis: A Review of Concurrent Nail Polish Use with Topical Efinaconazole 10% Solution.

Objective: Patients with onychomycosis may use nail polish to camouflage affected nails, despite potential interactions between nail polish use and topical onychomycosis treatments. Our objective was to review available data on nail polish use concurrent with topical efinaconazole 10% solution for the treatment of onychomycosis. Methods: We conducted a PubMed search and narrative review of data on effects of nail polish on penetration of efinaconazole and clinical studies of efinaconazole in the treatment of toenail onychomycosis concurrent with nail polish use, including results of an investigator-initiated study of gel nail polish pedicures. Results: In vitro, penetration of efinaconazole through cadaverous nails coated with traditional nail polish was similar to penetration through uncoated nails. In a 52-week clinical study, efinaconazole treatment was associated with similar improvements in onychomycosis severity and clear toenail growth between participants who used traditional nail polish and those who did not use nail polish. In a second clinical study, participants received efinaconazole treatment concurrent with monthly gel nail polish pedicures. After 6 months, 100% of participants tested negative for fungal infection and all experienced visible improvements in treated toenails. Efinaconazole application was associated with degradation of traditional nail polish texture/appearance. In contrast, efinaconazole did not affect the duration, quality, or texture of gel polish. Limitations: Only four small studies have assessed nail penetration and efficacy of efinaconazole 10% solution with concurrent nail polish use. Conclusion: Efinaconazole 10% solution demonstrated efficacy in the treatment of toenail onychomycosis among participants concurrently using toenail polish, with no visible impact on gel-polished nails.

A case of refractory onychomycosis caused by Kloeckera apiculata: Successful treatment with itraconazole.

Here, we present the case of an otherwise healthy patient, without risk factors, who developed a refractory case of onychomycosis caused by Kloeckera apiculata, an uncommon human pathogen. The diagnosis was ultimately confirmed by fungal nail plate culture, histopathology, and PCR. Whereas prior treatments with topical 5 % tavaborole solution, oral terbinafine, and oral fluconazole were ineffective, complete clinical and mycological cure was achieved with a 3-month course of oral itraconazole.

Efficacy of Amorolfine in Onychomycosis Treatment: A Mixed-Effects Models and Multivariate Logistic Regression Analysis.

BACKGROUND: Onychomycosis (OM) is a common nail infection treated with amorolfine hydrochloride nail lacquer in China. Monitoring drug concentrations and using dermoscopy to evaluate treatment efficacy may provide new insights. OBJECTIVE: The study aims to analyse amorolfine concentrations in nails with mild to moderate OM, assess treatment outcomes using dermoscopy and explore factors influencing drug concentrations and efficacy. METHODS: Patients with mild to moderate OM confirmed by fungal microscopy were enrolled. Amorolfine nail lacquer was applied twice weekly for 36 weeks. Monthly nail samples measured amorolfine concentrations using liquid chromatography. Dermoscopy was performed before and after treatment to evaluate responses. Mixed-effects models and logistic regression analysed factors affecting drug concentrations and outcomes. RESULTS: Ninety-seven nails were included. Amorolfine concentrations increased over time, with higher levels in females, fingernails, 2nd-5th digits and superficial white OM (p < 0.05). Age was a risk factor, while drug concentration and OM type were protective for clinical efficacy (p < 0.05). Peak concentration correlated with clinical (r = 0.487, p = 0.000) and mycological (r = 0.433, p = 0.000) responses. Dermoscopic features improved significantly in successful cases (p < 0.05). LIMITATIONS: In the assessment of fungal efficacy, only fungal microscopy was used, and fungal cultures were not performed. The study was limited by a small sample size and the lack of a longer follow-up to assess relapse. CONCLUSION: Amorolfine concentrations vary with patient and nail characteristics, influencing efficacy. Dermoscopy is valuable for monitoring OM treatment.

New Sources of Resistance to Terbinafine Revealed and Squalene Epoxidase Modelled in the Dermatophyte Fungus Trichophyton interdigitale From Australia.

BACKGROUND: Terbinafine is widely used to treat onychomycosis caused by dermatophyte fungi. Terbinafine resistance in recent years is causing concern. Resistance has so far been associated with single-nucleotide substitutions in the DNA sequence of the enzyme squalene epoxidase (SQLE) but how this affects SQLE functionality is not understood. OBJECTIVES: The aim of this study was to understand newly discovered resistance in two Australian strains of Trichophyton interdigitale. PATIENTS/METHODS: Resistance to terbinafine was tested in four newly isolated strains. Three-dimensional SQLE models were prepared to investigate how the structure of their SQLE affected the binding of terbinafine. RESULTS: This study found the first Australian occurrences of terbinafine resistance in two T. interdigitale strains. Both strains had novel deletion mutations in erg1 and frameshifts during translation. Three-dimensional models had smaller SQLE proteins and open reading frames as well as fewer C-terminal α-helices than susceptible strains. In susceptible strains, the lipophilic tail of terbinafine was predicted to dock stably into a hydrophobic pocket in SQLE lined by over 20 hydrophobic amino acids. In resistant strains, molecular dynamics simulations showed that terbinafine docking was unstable and so terbinafine did not block squalene metabolism and ultimately ergosterol production. The resistant reference strain ATCC MYA-4438 T. rubrum showed a single erg1 mutation that resulted in frameshift during translation, leading to C-terminal helix deletion. CONCLUSIONS: Modelling their effects on their SQLE proteins will aid in the design of potential new treatments for these novel resistant strains, which pose clinical problems in treating dermatophyte infections with terbinafine.

Nailfold capillaroscopy for diagnosis of onychodystrophies: A prospective cross-sectional study.

BACKGROUND: Nail diseases are often associated with significant physical and psychosocial burden, but diagnosis is challenging due to nonspecific clinical and histological findings. Nailfold capillaroscopy has been studied for the diagnosis of systemic diseases, but studies on nail diseases are lacking. OBJECTIVE: The objectives of our study were to characterize and compare capillary changes in a set of nail conditions versus controls, between nail groups, and based on demographic/clinical criteria. METHODS: This was a prospective cross-sectional study of patients with nail psoriasis, onychomycosis, idiopathic onycholysis, brittle nail syndrome, nail lichen planus, retronychia, other nail conditions, and no nail findings (controls) undergoing capillaroscopy imaging/analysis. RESULTS: Nail psoriasis versus control patients demonstrated decreased capillary length/density and increased abnormal capillaries, with higher frequency in older, male patients. Onychomycosis was associated with increased meandering capillaries compared with controls, nail psoriasis, and nail lichen planus. Retronychia is associated with increased disorganized polymorphic capillaries compared with controls and onychomycosis. LIMITATIONS: Limitations include a small sample size for certain nail conditions and small numbers of nail psoriasis patients with psoriatic arthritis. CONCLUSION: Our findings highlight nailfold capillaroscopy as a potentially quick, cost-effective, and noninvasive imaging modality, as an adjunct for diagnosis and treatment initiation for patients with onychodystrophies.

Pediatric dermatophyte onychomycosis: a review.

Recent studies have reported an increase in pediatric onychomycosis prevalence worldwide, suggesting that this population may be increasingly affected by the infection. A summary of the epidemiological impact, antifungal treatment options, special considerations for at-risk subpopulations, and methods to prevent infection and recurrence are discussed. A systematic review of available epidemiological studies found the worldwide prevalence of culture-confirmed pediatric toenail onychomycosis to be 0.33%, with no significant increases in prevalence over time. A systematic review of studies investigating the efficacy of various antifungals in treating pediatric onychomycosis found high cure rates and low frequency of adverse events with systemic itraconazole and terbinafine; however, the studies are few, dated, and lack impact because of small sample sizes. Comparatively, clinical trials implementing FDA-approved topical antifungal treatments report slightly reduced cure rates with larger sample sizes. Patients with immunity-altering conditions, such as Down's syndrome, or those immunosuppressed because of chemotherapy or HIV/AIDS are at a greater risk of onychomycosis infection and require special consideration with treatment. Proper sanitization and hygiene practices are necessary to reduce the risk of acquiring infection. Early diagnosis and treatment of onychomycosis in children, as well as any affected close contacts, are crucial in reducing the impact of the disease.

Diagnostic Accuracy of Dermatoscopy Versus Microbiological Culture and Polymerase Chain Reaction in the Diagnosis of Onychomycosis: A Cross-Sectional Study.

BACKGROUND: Several clinical signs in dermatoscopy are very characteristic of onychomycosis and can be a quick complement for the diagnosis of onychomycosis. OBJECTIVES: The aim of this study was to evaluate the diagnostic accuracy of dermatoscopy compared to microbiological culture and polymerase chain reaction (PCR), as well as the clinical signs associated with onychomycosis. METHODS: The clinical signs of 125 patients were assessed cross-sectionally using dermatoscopy, and a positive or negative result was assigned. A sample was then taken for PCR and microbiological culture. RESULTS: Of the 125 patients, 69.6% (87/125) had positive results when both laboratory tests were combined. When they were not combined, the prevalence was lower at 48% (60/125) with PCR and at 43.2% (54/125) with culture. Furthermore, 76.8% (96/125) were classified as positive with dermatoscopy with a sensitivity of 1, a specificity of 0.76, positive predictive value of 0.91 and negative predictive value of 1 (with 95% confidence intervals). Of the 96 dermatoscopy-positive samples, 36 were negative with PCR (p < 0.001), 42 were negative with culture (p < 0.001) and nine were negative when both tests were combined (p < 0.001). Clinical signs that were significantly associated with the presence of onychomycosis were subungual hyperkeratosis (dermatoscopy: p = 0.004, odds ratio (OR) = 2.438; PCR + microbiological culture: p = 0.004, OR = 3.221), subungual detritus (p = 0.033, OR = 3.01, only with dermatoscopy) and dermatophytoma (dermatoscopy: p = 0.049, OR = 3.02; PCR + microbiological culture: p = 0.022, OR = 2.40). CONCLUSIONS: The results suggest that dermatoscopy is a good tool for the diagnosis of onychomycosis but should be used as a complementary test or for screening patients to be sampled for laboratory testing. The combination of the three tests can lead to a reduction of false-positive and false-negative clinical and laboratory results. This allows for early diagnosis and specific treatment based on test results.

Extended Use of Topical Efinaconazole Remains Safe and Can Provide Continuing Benefits for Dermatophyte Toenail Onychomycosis.

INTRODUCTION: Efinaconazole 10% topical solution labeling for onychomycosis describes phase III trials of 12 months of treatment; the slow growth of onychomycotic nails suggests a longer treatment period may increase efficacy. We present here the first evaluation of extended use of efinaconazole 10% topical solution for up to 24 months. MATERIALS AND METHODS: Enrolled patients (n = 101) had one target great toenail with mild to moderate distal lateral subungual onychomycosis and applied efinaconazole 10% topical solution to all affected toenails once daily for 18 months (EFN18) or 24 months (EFN24). Efficacy and safety were evaluated at each visit by visual review and mycology sampling. RESULTS: Regarding the target toenail for patients treated for 24 months (EFN24), mycological cure (negative microscopy and culture) was 66.0% at Month 12, increasing to 71.7% at Month 24; effective cure (mycological cure and ≤10% affected nail) was 13.2% at Month 12, rising to 22.6% at Month 24. Mild to moderate application site reactions (symptoms of erythema/scaling) were the only efinaconazole-related reactions, in eight patients (7.9%). No systemic efinaconazole events or drug interactions were found. Patients aged 70 years or more had similar efficacy to younger patients at all time periods and did not show any increased treatment risks. Thinner nails exhibited better clearance versus thicker nails. A higher proportion of patients with Trichophyton mentagrophytes complex infection experienced application site reactions (35.7%), and a higher effective cure was found at Month 24 versus T. rubrum patients. CONCLUSION: There is a trend of increasing mycological cure and effective cure beyond Month 12 to Month 24, without an increased safety risk. The enrolled population in this trial was significantly older than in the phase III trials, with a greater degree of onychomycosis severity; however, increased age did not appear to reduce the chance of efficacy to Month 24 in this study. Our data suggest that lack of ability to clear nail dystrophy remains a significant problem for patients, rather than any lack of efinaconazole action over long-term treatment periods.

Epidemiology of Onychomycosis in the United States Characterized Using Molecular Methods, 2015-2024.

Onychomycosis is a recalcitrant fungal infection of the nail unit that can lead to secondary infections and foot complications. Accurate pathogen identification by confirmatory testing is recommended to improve treatment outcomes. In this study, we reviewed the records of 710,541 patients whose nail specimens were sent to a single molecular diagnostic laboratory between 2015 and 2024. PCR testing revealed a more comprehensive spectrum of pathogens than previously reported, which was corroborated by the demonstration of fungal invasion on histopathology. Consistent with our current understanding, the T. rubrum complex (54.3%) are among the most common pathogens; however, a significant portion of mycology-confirmed diagnoses were caused by the T. mentagrophytes complex (6.5%), Aspergillus (7.0%) and Fusarium (4.5%). Females were significantly more likely to be infected with non-dermatophytes molds (NDMs; OR: 2.0), including Aspergillus (OR: 3.3) and Fusarium (OR: 2.0), and yeasts (OR: 1.5), including Candida albicans (OR: 2.0) and C. parapsilosis (OR 1.6), than males. The T. mentagrophytes complex became more prevalent with age, and conversely the T. rubrum complex became less prevalent with age. Patients aged ≥65 years also demonstrated a higher likelihood of contracting onychomycosis caused by NDMs (OR: 1.6), including Aspergillus (OR: 2.2), Acremonium (OR: 3.5), Scopulariopsis (OR: 2.9), Neoscytalidium (OR: 3.8), and yeasts (OR: 1.8), including C. albicans (OR: 1.9) and C. parapsilosis (OR: 1.7), than young adults. NDMs (e.g., Aspergillus and Fusarium) and yeasts were, overall, more likely to cause superficial onychomycosis and less likely to cause dystrophic onychomycosis than dermatophytes. With regards to subungual onychomycosis, Aspergillus, Scopulariopsis and Neoscytalidium had a similar likelihood as dermatophytes. The advent of molecular diagnostics enabling a timely and accurate pathogen identification can better inform healthcare providers of appropriate treatment selections and develop evidence-based recommendations.

Monocentric evaluation of the Novaplex dermatophyte multiplex qPCR assay in the diagnosis of dermatophytoses.

Superficial fungal infections caused by dermatophytes are a prevalent global health concern. Rapid and accurate diagnosis of these pathogens through molecular tools would offer a substantial advantage for early detection and effective treatment. The conventional fungal culture presents inherent limitations, including extended result delivery delay and variable sensitivity. This study aimed to evaluate the performance of the multiplex real-time PCR Novaplex dermatophyte assay (Seegene) in comparison to traditional mycological methods including direct examination and culture. A total of 312 nail, skin, and scalp samples collected from patients with suspected superficial fungal infections for mycological diagnosis were retrospectively subjected to the Novaplex dermatophyte assay. Overall, 170 (54.6%) and 186 (59.6%) samples tested positive for dermatophyte culture and dermatophyte PCR, respectively. The concordance between PCR and culture for dermatophyte detection was 87.2%. There were 158 culture-positive/PCR-positive samples, 12 culture-positive/PCR-negative samples, and 28 culture-negative/PCR-positive samples. The sensitivity of PCR against culture varied according to the dermatophyte target, ranging from 90.5% (Trichophyton mentagrophytes/interdigitale/benhamiae), 91.2% (Trichophyton rubrum), to 100% (Microsporum spp. and Trichophyton tonsurans). When considering the final diagnosis using composite criteria, the sensitivity and specificity for the diagnosis of dermatophytosis were 92.9% and 96.6% for PCR, 86.7% and 100% for culture, and 95.4% and 92.2% for direct examination and culture combined, respectively. The Seegene Novaplex dermatophyte assay is an easy-to-use automated one-step extraction-PCR system that offers satisfactory performance for routine diagnosis of dermatophytoses in clinical laboratories, particularly in non-specialized centers. However, it cannot fully replace conventional mycology due to its inability to detect mold infections and to identify dermatophytes at the species level.

Reactive oxygen species-inducing itraconazole and its anti-biofilm activity against resistant Candida parapsilosis sensu lato biofilm cells isolated from patients with recalcitrant onychomycosis.

Candida parapsilosis was introduced as the second most responsible for nail involvement. The colonization of biotic and abiotic surfaces by Candida spp. can result in the formation of biofilms, which possess a high level of resistance to typical antifungal agents. Since Candida spp. can produce biofilm mass on the surface of the nails, dermatologists should consider appropriate antifungals to eliminate both the planktonic and biofilm cells. The aim of this research was to determine the antifungal efficacy of itraconazole against C. parapsilosis sensu lato biofilm formations, in addition to its static effects. Ten C. parapsilosis sensu lato isolates were enrolled in this study. The use of itraconazole results in the accumulation of reactive oxygen species (ROS) during treatment. In order to verify the correlation between ROS and itraconazole-induced cell death, the viability of cells was analyzed by administering the ROS scavenger Ascorbic acid. The apoptotic features of itraconazole were analyzed using the Annexin V-FITC method. Based on current data, it was found that the generation of intracellular stresses by itraconazole is not observed in cells upon ROS inhibition, emphasizing the importance of intracellular ROS in the apoptotic mechanism of itraconazole. Targeting the oxidative defense system is a powerful point to use ROS-inducing antifungals as a superior choice for more effective therapies in case of recalcitrant onychomycosis.

Understanding Global Access to Topical Onychomycosis Therapy: A Systematic Review and Meta-Analysis.

INTRODUCTION: Equal access to medicines is crucial to ensuring public health, but access is difficult to measure, especially for infections where changes in infective species make treatment choices highly dynamic. This study investigated if the combination of infection prevalence with medicine efficacy and regulatory availability could access medicines access of topical onychomycosis medicines. METHODS: Two databases, PubMed and Web of Science, were used to identify relevant information published between 1990 and 2019. For the meta-analysis, human onychomycosis investigations using PCR analysis were included. Reviewers independently selected eligible articles, extracted data and assessed the study quality. A random-effects meta-analysis model with a Freeman-Tukey transformation was employed to the PCR data. For the meta-analysis, the global infection trends and regional differences in the infective organisms were determined. RESULTS: Of the 26 studies analysed, the PCR analysis in 18 studies confirmed onychomycosis in about half of the visually suspected cases (55%, CI 43%-67%). Across all 26 studies dermatophytes were the most prevalent infective organism (57%, CI 37%-76%), but a sub-group analysis showed yeasts predominated in females (31%, CI 0%-84%) (p < 0.0001), in fingernail infections (42%, CI 21%-65%) (p < 0.0001) and in arid countries (p < 0.0001). Combining these results with medicine efficacy data showed that residents from 83 of the 92 countries assessed (90%) could not access the most efficacious topical product, and 22% could not access any broad-spectrum agents. Countries in Africa had the poorest access to topical onychomycosis medicines. CONCLUSION: This study identified that access to effective topical products for onychomycosis is a global problem. This issue appeared to be due to under-representation of candida infections in pivotal clinical studies of topical onychomycosis products. A head-to-head multicentre study for topical efinaconazole or a novel broad spectrum topical agent is needed to help resolve these access problems. PROTOCOL REGISTRATION: PROSPERO-CRD42023464744.

A Clinico-Histopathological Study of Nail Dermatoses in a Tertiary Care Hospital.

Introduction Nail disorders account for an important component of all dermatological conditions. Nail abnormalities can result from local pathology or systemic diseases. Pathologies can lead to pain and impaired fine touch and are aesthetically distressing. Clinical assessment of nail pathologies is seldom accurate; moreover, the limited available investigative modalities make it difficult to correctly diagnose the disorders. Nail biopsies provide crucial histological information, especially for nail-limited dermatoses, though they are infrequently used and technically challenging. Proper biopsy techniques are vital to avoid complications like nail dystrophy and to ensure accurate diagnoses and effective treatments. Materials and methods A cross-sectional and observational study was conducted in the Dermatology Department of a tertiary care hospital in Maharashtra from November 2022 to July 2024, involving 51 patients aged 8-80 years with undiagnosed nail dermatoses. Patients with bleeding disorders, anesthesia allergies, and peripheral vascular diseases were excluded. Ethical clearance and written consent were obtained. In the case of pediatrics, patients' parental consent was obtained. Observation and results The age of the patients ranged from eight to 74 years, with a mean age of 38.04 years. The most affected age groups were 20-29 and 30-39 years old. Nineteen (37%) were manual laborers, followed by 10 (20%) students and nine (18%) professional workers. Symptoms lasted from one month to eight years, with a mean duration of 16.65 months. The most common dermatoses diagnosed clinically were as follows: 18 (35.3%) were onychomycosis, 16 (31.4%) were psoriasis, and eight (15.7%) were lichen planus. However, on histopathology, 20 (37.2%) were onychomycosis, followed by 16 (31.4%) of psoriasis, and eight (15.7%) were lichen planus. Conclusion This study highlights the critical role of nail biopsies in diagnosing nail disorders, particularly among middle-aged males who were manual laborers by occupation. It underscores the importance of combining clinical and histopathological approaches to accurately diagnose and manage, advocating for continued research and collaboration to improve patient outcomes.

Transungual Penetration and Antifungal Activity of Prescription and Over-the-Counter Topical Antifungals: Ex Vivo Comparison.

INTRODUCTION: Topical antifungals for toenail onychomycosis must penetrate the nail to deliver an inhibitory concentration of free drug to the site of infection. In two ex vivo experiments, we tested the ability of topical antifungals to inhibit growth of Trichophyton rubrum and Trichophyton mentagrophytes, the most common causative fungi in toenail onychomycosis. METHODS: Seven topical antifungals were tested: three U.S. Food and Drug Administration-approved products indicated for onychomycosis (ciclopirox 8% lacquer; efinaconazole 10% solution; tavaborole 5% solution) and four over-the-counter (OTC) products for fungal infections (tolnaftate 1% and/or undecylenic acid 25% solutions). The ability to inhibit fungal growth was tested in the presence and absence of keratin. Products were applied either to human cadaverous nails or keratin-free cellulose disks prior to placement on an agar plate (radius: 85 mm) seeded with a clinical isolate of T. rubrum or T. mentagrophytes. After incubation, the zone of inhibition (ZI), defined as the radius of the area of no fungal growth, was recorded. RESULTS: In the nail penetration assay, average ZIs for efinaconazole (T. rubrum: 82.1 mm; T. mentagrophytes: 63.8 mm) were significantly greater than those for tavaborole (63.5 mm; 39.1 mm), ciclopirox (7.4 mm; 3.6 mm) and all OTC products (range: 10.5-34.2 mm against both species; all P < 0.001). In the cellulose disk diffusion assay, efinaconazole and tavaborole demonstrated maximal antifungal activity against both species (ZIs = 85 mm); average ZIs against T. rubrum and T. mentagrophytes were smaller for ciclopirox (59.0 and 55.7 mm, respectively) and OTC products (range: 31.2-57.8 mm and 25.7-47.7 mm, respectively). CONCLUSIONS: Among all antifungals tested, the ability to penetrate human toenails to inhibit growth of both T. rubrum and T. mentagrophytes was greatest for efinaconazole, followed by tavaborole. These results indicate superior transungual penetration of efinaconazole compared to the other antifungals, suggesting lower keratin binding in the nail.

Systemic absorption and safety of topical terbinafine hydrochloride 10% solution (MOB015B): a phase 1 maximal usage trial in patients with moderate-to-severe onychomycosis.

Topical antifungals may be considered to treat onychomycosis with minimal risk of systemic side effects. In this study, we assess the safety, tolerability, systemic exposure, and pharmacokinetic characteristics of topical terbinafine hydrochloride 10% solution (MOB015B) in adults with moderate-to-severe onychomycosis. Clinically and mycologically confirmed patients with toenail onychomycosis (N = 20) were enrolled in this single-center, open-label study . Each patient had ≥50% involvement of both great toenails and at least four additional toenails affected. MOB015B was applied once daily to all toenails for 28 days. Blood was drawn on days 1, 14, and 28. Plasma concentrations of MOB015B after the first dose were quantifiable in all subjects by 24 h. Steady-state levels in plasma were reached by day 28. The mean systemic exposure on day 28 of 0.72 ng/mL for maximum plasma concentration (Cmax) was approximately 2,000 times lower than the mean plasma level of 1.39 µg/mL seen after oral administration of 250 mg terbinafine for 28 days. Adverse events (five patients), such as headache (n = 3), seasonal allergy (n = 1), and neck pain (n = 1), were considered unrelated to MOB015B; no application site reactions or study discontinuations due to an adverse event were observed. MOB015B applied to all affected toenails under maximal usage conditions for 28 days demonstrated very low levels of terbinafine in plasma (Cmax <1 ng/mL after 28 days), consistent with a favorable safety and tolerability profile. CLINICAL TRIALS: This study is registered with ClinicalTrials.gov as NCT03244280.

Differential diagnosis of pigmented nail lesions.

The diagnosis of pigmented nail lesions is a concern for both general practitioners and dermatologists, due to the possibility of indicating nail melanoma. The origin of the dark pigmentation can be either melanocytic or non-melanocytic (fungi, bacteria, or blood), and clinical evaluation alone may not be sufficient for differentiation, requiring additional exams. Onychoscopy provides valuable information prior to biopsy. The causes of nail pigmentation will be described to aid in the differential diagnosis.

Gallic acid loaded self-nano emulsifying hydrogel-based drug delivery system against onychomycosis.

Aim: To developed and investigate gallic acid (GA) loaded self-nanoemulsifying drug delivery systems (SNEDDS) for treating onychomycosis via transungual route. Materials & methods: The SNEDDS were prepared by direct dispersion technique and were evaluated for characteristics parameters using Fourier transform infrared, differential scanning calorimetry, confocal microscopy, transmission electron microscopy and zeta sizer. Furthermore, the safety of prepared formulation was evaluated via Hen's egg test-chorioallantoic membrane study and stability was confirmed using different parameters. Also, its effectiveness was evaluated against fungal strain Trichophyton mentagrophytes. Results: The SNEDDS displayed a particle size of 199.8 ± 4.21 nm and a zeta potential; of -22.75 ± 2.09 mV. Drug release study illustrated a sustained release pattern with a release of 70.34 ± 0.20% over a period of 24 h. The penetration across the nail plate was found to be 1.59 ± 0.002 µg/mg and 0.97 ± 0.001 µg/mg for GA loaded SNEDDS and GA solution respectively. An irritation score of 0.52 ± 0.005 and 3.84 ± 0.001 was reported for GA loaded SNEDDS hydrogel and GA solution, indicating a decrease in the drug's irritation potential from slightly irritating to non irritating due to its entrapment within the SNEDDS. Conclusion: GA loaded SNEDDS has potential to address limitations of conventional treatments, enhancing the drug's efficacy and reducing the likelihood of resistance in the treatment of Onychomycosis.

[Box: see text].

Analysis of clinical characteristics of terbinafine-induced subacute cutaneous lupus erythematosus.

INTRODUCTION: Terbinafine may cause subacute cutaneous lupus erythematosus (SCLE), and we aimed to analyze its clinical characteristics. METHODS: We collected literature on terbinafine-induced SCLE from 1997 to 2023 for retrospective analysis. Thirty-seven patients (33 females and 4 males) were included. RESULTS: The patients have a median age of 49.5 years (range 18-79) and onset time of 5 weeks (range 1-12). SCLE is mainly manifested as annular erythematous (83.3%), scaly erythematous (44.4%), and maculopapular erythematous (13.9%). Mainly, histopathological manifestations are lymphocytic infiltrate (55.6%), hyperkeratosis (38.9%) and keratinocyte necrosis (38.9%). Positive immunological parameters mainly include antinuclear antibody (100.0%), anti-Ro/SSA antibody (94.1%), and anti-La/SSB antibody (72.2%). Past medical history usually includes photosensitivity (33.3%), inflammatory disease (33.33%), and lupus erythematosus (12.1%). Symptoms are completely resolved within a median time of 35 days (range 7-84) after discontinuation of terbinafine and treatment with topical corticosteroids, systemic corticosteroids, hydroxychloroquine, and immunosuppressant. No recurrence was observed within 12 months (range 1.5-48) of follow-up. CONCLUSION: These results suggest that terbinafine-induced SCLE should be comprehensively diagnosed based on clinical symptoms, histopathological manifestations, immunological parameters, and past medical history. Terbinafine should be immediately discontinued when SCLE occurs, while systemic and topical corticosteroids combined with hydroxychloroquine may be an effective treatment.

Lower Limb Chronic Ischaemia Presenting Exclusively as Fungal Toenail Infection: Case Report and Brief Literature Review.

BACKGROUND/AIM: Chronic lower limb ischaemia is a peripheral arterial disease (PAD) which is typically instigated by atherosclerotic plaques in the peripheral vasculature. This article reports on a unique case of chronic ischaemia in the lower limb, presenting in a distinctive manner as a fungal toenail infection. CASE REPORT: An 82-year-old frail woman with multimorbidity presented with toenail symptoms in her right foot. While initial examination had shown onychomycosis, further investigation was unexpectedly consistent with chronic ischaemia in the lower limb. We explored the clinical presentation, diagnostic challenges encountered, and the subsequent management of this unique manifestation in the context of the patient's multimorbidity. CONCLUSION: This case report highlights the need to consider chronic limb ischemia as a differential diagnosis in toenail infections when no alternative causes or predisposing factors are identified.