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Journal of the American Academy of... May 2024
Tinea pedis, peripheral vascular disease, and male gender are associated with higher odds of onychomycosis in a retrospective case-control study of 1257 onychodystrophy patients.
PubMed: 38754629
DOI: 10.1016/j.jaad.2024.05.016 -
Journal of the American Podiatric... 2024Dermatophytoma, also described as a longitudinal streak/spike, is a form of onychomycosis that presents as yellow/white streaks or patches in the subungual space, with... (Review)
Review
BACKGROUND
Dermatophytoma, also described as a longitudinal streak/spike, is a form of onychomycosis that presents as yellow/white streaks or patches in the subungual space, with dense fungal masses encased in biofilm. This scoping review of the literature was conducted to address a general lack of information about the epidemiology, pathophysiology, and treatment of dermatophytomas in onychomycosis.
METHODS
A search was performed in the PubMed and Embase databases for the terms "longitudinal spike" or "dermatophytoma." Outcomes of interest were definition, prevalence, methods used for diagnosis, treatments, and treatment efficacy. Inclusion and exclusion of search results required agreement between two independent reviewers.
RESULTS
Of a total of 51 records, 37 were included. Two reports provided the first unique definitions/clinical features of dermatophytomas. Overall, many descriptions were found, but one conclusive definition was lacking. Prevalence data were limited and inconsistent. The most frequently mentioned diagnostic techniques were clinical assessment, potassium hydroxide/microscopy, and fungal culture/mycology. Oral terbinafine and topical efinaconazole 10% were the most frequently mentioned treatments, followed by topical luliconazole 5% and other oral treatments (itraconazole, fluconazole, fosravuconazole). In studies with five or more patients without nail excision, cure rates were highest with efinaconazole 10%, which ranged from 41% to 100% depending on the clinical and/or mycologic assessment evaluated. Other drugs with greater than or equal to 50% cure rates were topical luliconazole 5% (50%), oral fosravuconazole (57%), and oral terbinafine (67%). In studies that combined oral terbinafine treatment with nail excision using surgical or chemical (40% urea) methods, cure rates ranged from 50% to 100%.
CONCLUSIONS
There is little published information regarding dermatophytomas in onychomycosis. More clinical research and physician education are needed. Although dermatophytomas have historically been considered difficult to treat, the efficacy data gathered in this scoping review have demonstrated that newer topical treatments are effective, as are oral antifungals in combination with chemical or surgical methods.
Topics: Humans; Onychomycosis; Antifungal Agents; Prevalence; Foot Dermatoses; Tinea; Female; Male
PubMed: 38753536
DOI: 10.7547/22-161 -
Mycoses May 2024
PubMed: 38721657
DOI: 10.1111/myc.13731 -
Journal of the European Academy of... May 2024Dermoscopy of the nail unit (onychoscopy) is a method which allows for non-invasive observation of the nail structures, increasing the accuracy of clinical diagnosis.... (Review)
Review
Dermoscopy of the nail unit (onychoscopy) is a method which allows for non-invasive observation of the nail structures, increasing the accuracy of clinical diagnosis. Currently, it is used in evaluation of both inflammatory and neoplastic conditions of the nail unit. However, in contrast to the skin, the anatomy of the nail unit prevents direct observation of nail bed or nail matrix structure during classic onychoscopy. Intra-operative onychoscopy is a variant of the technique which uses direct visualization of the nail unit structures after nail plate avulsion. The aim of this systematic review was to summarize the current state of knowledge on intra-operative onychoscopy. The MEDLINE, EMBASE and Cochrane databases were systematically searched in January 2024. All types of study designs assessing intra-operative dermoscopy of the nail unit were included in this study. The risk of bias in included studies was assessed using the Joanna Briggs Institute critical appraisal tools. The qualitative synthesis of 19 studies totalling a number of 218 cases in 217 patients included the following entities: melanoma, nevus, hypermelanosis (melanocytic activation), melanocytic hyperplasia, melanophages accumulation, squamous cell carcinoma, glomus tumour, lichen planus, onychomatricoma, onychomycosis and subungual exostosis. The main limitation of the study was a relatively low number of identified studies, most with low levels of evidence. Intra-operative onychoscopy does not replace histologic examination, though it may be useful in determining the modality of surgical diagnostic procedures.
PubMed: 38717320
DOI: 10.1111/jdv.20078 -
Infectious Diseases and Therapy Jun 2024Amorolfine 5% lacquer is an established topical treatment for fungal infection of the nails. The success of topical therapy for onychomycosis depends on whether the...
Penetration Profile of Terbinafine Compared to Amorolfine in Mycotic Human Toenails Quantified by Matrix-Assisted Laser Desorption Ionization-Fourier Transform Ion Cyclotron Resonance Imaging.
INTRODUCTION
Amorolfine 5% lacquer is an established topical treatment for fungal infection of the nails. The success of topical therapy for onychomycosis depends on whether the permeated drug concentration in the deep nail bed is retained above the effective antifungal minimum inhibitory concentration (MIC). We compared the penetration profile of amorolfine and a new topical formula of terbinafine in human mycotic toenails using matrix-assisted laser desorption ionization mass spectrometry imaging-Fourier transform ion cyclotron resonance (MALDI-FTICR) imaging.
METHODS
Amorolfine 5% lacquer and terbinafine 7.8% lacquer were applied to mycotic nails (n = 17); nail sections were prepared, and MALDI-FTICR analysis was performed. Based on the MICs of amorolfine and terbinafine needed to kill 90% (MIC) of Trichophyton rubrum, the fold differences between the MIC and the antifungal concentrations in the nails (the multiplicity of the MIC) were calculated overall and for the keratin-unbound fractions.
RESULTS
Both amorolfine and terbinafine penetrated the entire thickness of the nail. The mean concentration across the entire nail section 3 h following terbinafine treatment was 1414 μg/g of tissue (equivalent to 4.9 mM) compared with 780 μg/g (2.5 mM) following amorolfine treatment (not significantly different; p = 0.878). The median multiplicity of the MIC was significantly higher in amorolfine- than terbinafine-treated nails overall (191 vs. 48; p = 0.010) and for the keratin-unbound fractions only (7.4 vs. 0.8; p = 0.002).
CONCLUSION
In this ex vivo study, MALDI-FTICR demonstrated that, although amorolfine 5% and terbinafine 7.8% had similar distribution profiles, both penetrating from the surface to the nail bed, the concentration of amorolfine in the nail was significantly higher than that of terbinafine relative to their respective MIC values. Clinical studies are required to determine whether these effects translate to a clinical difference in treatment success.
PubMed: 38713301
DOI: 10.1007/s40121-024-00979-2 -
Infectious Diseases and Therapy Jun 2024Onychomycosis is a fungal infection of the nails that can be challenging to treat. Here, matrix-assisted laser desorption ionization-Fourier transform ion cyclotron...
Penetration Profiles of Four Topical Antifungals in Mycotic Human Toenails Quantified by Matrix-Assisted Laser Desorption Ionization-Fourier Transform Ion Cyclotron Resonance Imaging.
INTRODUCTION
Onychomycosis is a fungal infection of the nails that can be challenging to treat. Here, matrix-assisted laser desorption ionization-Fourier transform ion cyclotron resonance (MALDI-FTICR) imaging was applied to the quantitative analysis of the penetration profile of the antifungal compound, amorolfine, in human mycotic toenails. The amorolfine profile was compared with those of three other antifungals, ciclopirox, naftifine, and tioconazole.
METHODS
Antifungal compounds (amorolfine 5% lacquer, ciclopirox 8% lacquer, naftifine 1% solution, and tioconazole 28% solution) were applied to mycotic nails (n = 42). Nail sections were prepared, and MALDI-FTICR analysis was performed on the sections at a spatial resolution of 70 μm to compare the distribution profiles. Based on the minimum inhibitory concentrations of the four test compounds needed to kill 90% (MIC) of the fungal organism, Trichophyton rubrum, the fold differences between the MIC and the antifungal concentrations in the nails (termed the multiplicity of the MIC) were calculated for each.
RESULTS
The penetration profiles indicated higher concentrations of amorolfine and ciclopirox in the deeper layers of the nails 3 h after treatment, compared with naftifine and tioconazole. The mean concentrations across the entire nail sections at 3 h were significantly different among the four antifungals: amorolfine, 2.46 mM; ciclopirox, 0.95 mM; naftifine, 0.63 mM; and tioconazole, 1.36 mM (p = 0.016; n = 8 per compound). The median multiplicity of the MIC at 3 h was 191-fold for amorolfine, tenfold for ciclopirox, 52-fold for naftifine, and 208-fold for tioconazole.
CONCLUSION
In this study, MALDI-FTICR was successfully applied to the quantitative analysis of antifungal distribution in human mycotic nails. The findings suggest that amorolfine penetrates deeper layers of the nail and accumulates at concentrations far exceeding the MIC needed to exert antimycotic activity.
PubMed: 38704491
DOI: 10.1007/s40121-024-00978-3 -
BMJ Open May 2024To evaluate the efficacy of topical miconazole or amorolfine compared to placebo for mild to moderately severe onychomycosis. (Randomized Controlled Trial)
Randomized Controlled Trial
How effective is topical miconazole or amorolfine for mild to moderately severe onychomycosis in primary care: the Onycho Trial - a randomised double-blind placebo-controlled trial.
OBJECTIVES
To evaluate the efficacy of topical miconazole or amorolfine compared to placebo for mild to moderately severe onychomycosis.
DESIGN
Randomised, double-blind, placebo-controlled trial, with computer-generated treatment allocation at a 1:1:1 ratio.
SETTING
Primary care, recruitment from February 2020 to August 2022.
PARTICIPANTS
193 patients with suspected mild to moderately severe onychomycosis were recruited via general practices and from the general public, 111 of whom met the study criteria. The mean age of participants was 51 (SD 13.1), 51% were female and onychomycosis was moderately severe (mean OSI 12.1 (SD 8.0)).
INTERVENTIONS
Once-daily miconazole 20 mg/g or once-weekly amorolfine 5% nail lacquer solution was compared with placebo (denatonium benzoate solution).
MAIN OUTCOME MEASURES
Complete, clinical and mycological cure at 6 months. Secondary outcomes were clinical improvement, symptom burden, quality of life, adverse effects, compliance, patient-perceived improvement and treatment acceptability.
RESULTS
Based on intention-to-treat analysis, none of the participants receiving miconazole or amorolfine reached complete cure compared with two in the placebo group (OR not estimable (n.e.), p=0.493 and OR n.e., p=0.240, respectively). There was no evidence of a significant difference between groups regarding clinical cure (OR n.e., p=0.493 and OR 0.47, 95% CI 0.04 to 5.45, p=0.615) while miconazole and amorolfine were less effective than placebo at reaching both mycological cure (OR 0.25, 95% CI 0.06 to 0.98, p=0.037 and OR 0.23, 95% CI 0.06 to 0.92, p=0.029, respectively) and clinical improvement (OR 0.26, 95% CI 0.08 to 0.91, p=0.028 and OR 0.25, 95% CI 0.07 to 0.85, p=0.021, respectively). There was no evidence of a significant difference in disease burden, quality of life, adverse reactions, compliance, patient-perceived improvement or treatment acceptability.
CONCLUSIONS
Topical miconazole and amorolfine were not effective in achieving a complete, clinical or mycological cure of mild to moderately severe onychomycosis, nor did they significantly alleviate the severity or symptom burden. These treatments should, therefore, not be advised as monotherapy to treat onychomycosis.
TRIAL REGISTRATION NUMBER
WHO ICTRP NL8193.
Topics: Humans; Miconazole; Onychomycosis; Female; Double-Blind Method; Male; Middle Aged; Antifungal Agents; Administration, Topical; Treatment Outcome; Adult; Primary Health Care; Quality of Life; Aged; Severity of Illness Index; Morpholines
PubMed: 38702077
DOI: 10.1136/bmjopen-2023-081914 -
The Journal of Dermatology May 2024Onychomycosis is a chronic and intractable disease whose prevalence increases during aging. In elderly patients, if onychomycosis is left untreated and progresses to a...
Onychomycosis is a chronic and intractable disease whose prevalence increases during aging. In elderly patients, if onychomycosis is left untreated and progresses to a severe stage it may cause functional decline of the lower limbs due to foot pain. This could lead to a decline in activities of daily living and secondary impairment such as cognitive decline. Thus, the treatment of onychomycosis in elderly patients is important. We have previously shown that fosravuconazole is relatively safe and effective for onychomycosis in elderly patients. In the present study, we continued the follow-up study and investigated the efficacy of re-administration of fosravuconazole in patients with recurrent onychomycosis. One hundred and twenty-five patients aged ≥65 years who had been initially diagnosed with onychomycosis at our hospital's dermatology department, and who had responded well to fosravuconazole at 48 weeks after the initial treatment, were followed up until 144 weeks after the start of the initial treatment. Patients who experienced a recurrence within 24 weeks after the start of the follow-up were assigned to the short-term recurrence group, and those who experienced a recurrence after 24 weeks were assigned to the long-term recurrence group. All patients in both groups were re-treated with fosravuconazole to evaluate its efficacy. The short-term and long-term recurrence groups consisted of 17 (14.3%) and 10 (8.4%) patients, respectively. There were no significant differences in mean age and sex ratio between the two groups. There were no serious adverse effects in either group, and the toenail opacity ratio was significantly reduced after 12 weeks of re-treatment in both groups. The short-term and long-term recurrence groups were significantly more likely to have wedge-shaped onychomycosis and total dystrophic onychomycosis, respectively. The results suggest that re-administration of fosravuconazole is safe and as effective as the first administration for elderly patients with recurrent onychomycosis. This study was registered at UMIN-CTR (UMIN000053516).
PubMed: 38700273
DOI: 10.1111/1346-8138.17254 -
Dermatology (Basel, Switzerland) May 2024Super-bioavailable itraconazole (SB ITZ) overcomes the limitations of conventional itraconazole (CITZ) such as interindividual variability and reduced bioavailability....
Super-bioavailable itraconazole (SB ITZ) overcomes the limitations of conventional itraconazole (CITZ) such as interindividual variability and reduced bioavailability. It has been approved for systemic mycoses in Australia and Europe as 50 mg and the USA as 65 mg and in India as 50 mg, 65 mg, 100 mg, and 130 mg. However, data on the ideal dose and duration of SB ITZ treatment in managing dermatophytosis are insufficient. This consensus discusses the suitability, dosage, duration of treatment, and relevance of using SB ITZ in managing dermatophytosis in different clinical scenarios. Sixteen dermatologists (>15 years of experience in the field and ≥2 years clinical experience with SB ITZ), formed the expert panel. A modified Delphi technique was employed, and a consensus was reached if the concordance in response was >75%. A total of 26 consensus statements were developed. The preferred dose of SB ITZ is 130 mg once daily and if not tolerated, 65 mg twice daily. The preferred duration for treating naïve dermatophytosis is 4-6 weeks and that for recalcitrant dermatophytosis is 6-8 weeks. Moreover, cure rates for dermatophytosis are a little better with SB ITZ than with CITZ with a similar safety profile as of CITZ. Better patient compliance and efficacy are associated with SB ITZ than with CITZ, even in patients with comorbidities and special needs such as patients with diabetes, extensive lesions, corticosteroid abuse, adolescents, and those on multiple drugs. Expert clinicians reported that the overall clinical experience with SB ITZ was better than that with CITZ.
PubMed: 38697027
DOI: 10.1159/000538080 -
Journal of Fungi (Basel, Switzerland) Apr 2024While typically exhibiting characteristic features, fungal infections can sometimes present in an unusual context, having improbable localization (eyelid, face, or... (Review)
Review
While typically exhibiting characteristic features, fungal infections can sometimes present in an unusual context, having improbable localization (eyelid, face, or joint); mimicking other skin diseases such as eczema, psoriasis, or mycosis fungoides; and appearing with unexpected color, shape, or distribution. The emergence of such a challenging clinical picture is attributed to the complex interplay of host characteristics (hygiene and aging population), environment (climate change), advances in medical procedures, and agent factors (fungal resistance and species emergence). We aim to provide a better understanding of unusual epidemiological contexts and atypical manifestations of fungal superficial diseases, knowing that there is no pre-established clinical guide for these conditions. Thus, a literature examination was performed to provide a comprehensive analysis on rare and atypical superficial mycosis as well as an update on certain fungal clinical manifestations and their significance. The research and standard data extraction were performed using PubMed, Medline, Scopus, and EMBASE databases, and a total of 222 articles were identified. This review covers published research findings for the past six months.
PubMed: 38667966
DOI: 10.3390/jof10040295