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1.
Article in English | MEDLINE | ID: mdl-38753536

ABSTRACT

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.


Subject(s)
Antifungal Agents , Onychomycosis , Humans , Onychomycosis/diagnosis , Onychomycosis/epidemiology , Onychomycosis/therapy , Onychomycosis/drug therapy , Antifungal Agents/therapeutic use , Prevalence , Foot Dermatoses/diagnosis , Foot Dermatoses/therapy , Foot Dermatoses/epidemiology , Foot Dermatoses/microbiology , Tinea/diagnosis , Tinea/therapy , Tinea/epidemiology , Tinea/drug therapy , Female , Male
2.
BMJ Open ; 14(5): e081914, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38702077

ABSTRACT

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.


Subject(s)
Administration, Topical , Antifungal Agents , Miconazole , Morpholines , Onychomycosis , Humans , Miconazole/administration & dosage , Miconazole/therapeutic use , Onychomycosis/drug therapy , Female , Double-Blind Method , Male , Middle Aged , Antifungal Agents/administration & dosage , Antifungal Agents/therapeutic use , Treatment Outcome , Adult , Primary Health Care , Quality of Life , Aged , Severity of Illness Index
3.
Mycoses ; 67(4): e13725, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38606891

ABSTRACT

BACKGROUND: Onychomycosis is a chronic nail disorder commonly seen by healthcare providers; toenail involvement in particular presents a treatment challenge. OBJECTIVE: To provide an updated estimate on the prevalence of toenail onychomycosis. METHODS: We conducted a literature search using PubMed, Embase and Web of Science. Studies reporting mycology-confirmed diagnoses were included and stratified into (a) populations-based studies, and studies that included (b) clinically un-suspected and (c) clinically suspected patients. RESULTS: A total of 108 studies were included. Based on studies that examined clinically un-suspected patients (i.e., with or without clinical features suggestive of onychomycosis), the pooled prevalence rate of toenail onychomycosis caused by dermatophytes was 4% (95% CI: 3-5) among the general population; special populations with a heightened risk include knee osteoarthritis patients (RR: 14.6 [95% CI: 13.0-16.5]), chronic venous disease patients (RR: 5.6 [95% CI: 3.7-8.1]), renal transplant patients (RR: 4.7 [95% CI: 3.3-6.5]), geriatric patients (RR: 4.7 [95% CI: 4.4-4.9]), HIV-positive patients (RR: 3.7 [95% CI: 2.9-4.7]), lupus erythematosus patients (RR: 3.1 [95% CI: 1.2-6.3]), diabetic patients (RR: 2.8 [95% CI: 2.4-3.3]) and hemodialysis patients (RR: 2.8 [95% CI: 1.9-4.0]). The prevalence of onychomycosis in clinically suspected patients was significantly higher likely due to sampling bias. A high degree of variability was found in a limited number of population-based studies indicating that certain pockets of the population may be more predisposed to onychomycosis. The diagnosis of non-dermatophyte mould onychomycosis requires repeat sampling to rule out contaminants or commensal organisms; a significant difference was found between studies that performed single sampling versus repeat sampling. The advent of PCR diagnosis results in improved detection rates for dermatophytes compared to culture. CONCLUSION: Onychomycosis is an underrecognized healthcare burden. Further population-based studies using standardized PCR methods are warranted.


Subject(s)
Diabetes Mellitus , Kidney Transplantation , Onychomycosis , Humans , Aged , Onychomycosis/epidemiology , Onychomycosis/drug therapy , Prevalence , Nails , Diabetes Mellitus/epidemiology
4.
Eur J Dermatol ; 34(1): 51-54, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38557458

ABSTRACT

Onychomycosis is the most frequent nail disorder, but unfortunately, curative treatment is still a challenge, and commonly the infection recurs. A widely disseminated system to accurately assess and classify the severity of this disease, such as the MASI score for melasma or PASI for psoriasis, is lacking in the literature. In 2011, Carney et al. established and successfully validated the Onychomycosis Severity Index (OSI), proving it to be a simple and reproducible tool. To validate the Onychomycosis Severity Index in a Brazilian population. Four experienced dermatologists were taught how to use the OSI system, and then evaluated photographs of 24 nails. There was no consultation between the dermatologists, and the results were evaluated by an impartial third party. A statistically significant (p<0.001) high degree of agreement was observed between the evaluators and overall OSI score (mild, moderate or severe) as well as its subcategories (area of involvement, proximity to the nail matrix and presence of dermatophytoma or hyperkeratosis). OSI is a very useful tool to improve the clinical assessment of onychomycosis and support clinical trial inclusion criteria (p<0.001). It also provides important prognostic data and allows for a better follow-up of treatment efficacy.


Subject(s)
Nail Diseases , Onychomycosis , Humans , Antifungal Agents/therapeutic use , Brazil , Nail Diseases/drug therapy , Nails , Onychomycosis/diagnosis , Onychomycosis/drug therapy , Treatment Outcome , Clinical Trials as Topic
5.
Mycoses ; 67(4): e13721, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38570912

ABSTRACT

BACKGROUND: Psoriatic patients may experience the coexistence of onychomycosis (OM). However, the evaluation of OM in psoriatics has been hindered by potential clinical differences from OM in non-psoriatics. OBJECTIVE: To assess and compare dermoscopic features between toenail OM in psoriatic and in non-psoriatic patients. PATIENTS AND METHODS: Between September 2020 and September 2023, dermoscopy was conducted on 183 affected toenails by OM in psoriatics and 232 affected toenails by OM in non-psoriatics in two centres. The dermoscopic characteristics were compared using the Chi-squared test. RESULTS: Among toenail OM cases in psoriatic subjects, the most prevalent dermoscopic features included pitting (147/183, 80.33%) and subungual hyperkeratosis (118/183, 64.48%). Conversely, toenail OM in non-psoriatics was characterized by subungual hyperkeratosis (175/232, 75.43%) and nail spikes (139/232, 59.91%). Comparative analysis revealed a significantly higher occurrence of pitting (80.33% vs. 15.96%, p < .001), periungual telangiectasis (22.40% vs. 4.74%, p < .001), oil patches (12.57% vs. 0.43%,p < .001) and transverse grooves (43.72% vs. 28.45%,p < .01) in toenail OM in psoriatics. Furthermore, toenail OM in psoriatics exhibited a significantly lower frequency of yellow structureless area (13.11% vs. 42.67%, p < .001), nail spikes (43.17% vs. 59.91%, p < .01), ruin appearance of sulphur nugget (8.20% vs. 31.03%, p < .001), dotted/blocky haemorrhage (6.01% vs. 20.69%,p < .001) and partial onycholysis (32.79% vs. 46.98%, p < .01). CONCLUSIONS: Dermoscopic features of toenail OM in psoriatic and non-psoriatic patients exhibit notable differences. OM in psoriatics shows a higher frequency of pitting and periungual telangiectasis, while a lower frequency of yellow structureless areas and nail spikes under dermoscopy.


Subject(s)
Keratosis , Nail Diseases , Onychomycosis , Telangiectasis , Humans , Onychomycosis/epidemiology , Onychomycosis/complications , Nails , Prospective Studies , Keratosis/complications , Telangiectasis/complications
6.
BMJ Open ; 14(4): e076441, 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38658014

ABSTRACT

INTRODUCTION: Diabetic foot ulcers are feared complications of diabetes mellitus (DM), requiring extensive treatment and hospital admissions, ultimately leading to amputation and increased mortality. Different factors contribute to the development of foot ulcers and related complications. Onychomycosis, being more prevalent in patients with diabetes, could be an important risk factor for developing ulcers and related infections. However, the association between onychomycosis and diabetic complications has not been well studied in primary care. RESEARCH DESIGN AND METHODS: To determine the impact of onychomycosis on ulcer development and related complications in patients with diabetes in primary care, a longitudinal cohort study was carried out using routine care data from the Extramural Leiden University Medical Center Academic Network. Survival analyses were performed through Cox proportional hazards models with time-dependent covariates. RESULTS: Data from 48 212 patients with a mean age of 58 at diagnosis of DM, predominantly type 2 (87.8%), were analysed over a median follow-up of 10.3 years. 5.7% of patients developed an ulcer. Onychomycosis significantly increased the risk of ulcer development (HR 1.37, 95% CI 1.13 to 1.66), not affected by antimycotic treatment, nor after adjusting for confounders (HR 1.23, 95% CI 1.01 to 1.49). The same was found for surgical interventions (HR 1.54, 95% CI 1.35 to 1.75) and skin infections (HR 1.48, CI 95% 1.28 to 1.72), again not affected by treatment and significant after adjusting for confounders (HR 1.32, 95% CI 1.16 to 1.51 and HR 1.27, 95% CI 1.10 to 1.48, respectively). CONCLUSIONS: Onychomycosis significantly increased the risk of ulcer development in patients with DM in primary care, independently of other risk factors. In addition, onychomycosis increased the risk of surgeries and infectious complications. These results underscore the importance of giving sufficient attention to onychomycosis in primary care and corresponding guidelines. Early identification of onychomycosis during screening and routine care provides a good opportunity for timely recognition of increased ulcer risk.


Subject(s)
Diabetic Foot , Onychomycosis , Humans , Onychomycosis/epidemiology , Onychomycosis/complications , Female , Male , Middle Aged , Longitudinal Studies , Netherlands/epidemiology , Diabetic Foot/epidemiology , Aged , Risk Factors , General Practice/statistics & numerical data , Diabetes Mellitus, Type 2/complications , Proportional Hazards Models , Adult , Primary Health Care/statistics & numerical data
8.
Expert Opin Pharmacother ; 25(5): 511-519, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38623728

ABSTRACT

INTRODUCTION: The reports of resistance to antifungal agents used for treating onychomycosis and other superficial fungal infections are increasing. This rise in antifungal resistance poses a public health challenge that requires attention. AREAS COVERED: This review explores the prevalence of dermatophytes and the current relationship between dermatophyte species, their minimum inhibitory concentrations (MICs) for terbinafine (an allylamine) and itraconazole (an azole), and various mutations prevalent in these species. The most frequently isolated dermatophyte associated with resistance in patients with onychomycosis and dermatophytosis was T. mentagrophytes. However, T. indotineae emerged as the most prevalent isolate with mutations in the SQLE gene, exhibiting the highest MIC of 8 µg/ml for terbinafine and MICs of 8 µg/ml and ≥ 32 µg/ml for itraconazole.Overall, the most prevalent SQLE mutations were Phe397Leu, Leu393Phe, Ala448Thr, Phe397Leu/Ala448Thr, and Lys276Asn/Leu415Phe (relatively recent). EXPERT OPINION: Managing dermatophyte infections requires a personalized approach. A detailed history should be obtained including details of travel, home and occupational exposure, and clinical examination of the skin, nails and other body systems. Relevant testing includes mycological examination (traditional and molecular). Additional testing, where available, includes MIC evaluation and detection of SQLE mutations. In case of suspected terbinafine resistance, itraconazole or voriconazole (less commonly) should be considered.


Subject(s)
Antifungal Agents , Arthrodermataceae , Drug Resistance, Fungal , Microbial Sensitivity Tests , Mutation , Terbinafine , Tinea , Antifungal Agents/pharmacology , Antifungal Agents/therapeutic use , Humans , Drug Resistance, Fungal/genetics , Tinea/drug therapy , Tinea/microbiology , Arthrodermataceae/drug effects , Arthrodermataceae/genetics , Terbinafine/pharmacology , Terbinafine/therapeutic use , Itraconazole/pharmacology , Itraconazole/therapeutic use , Onychomycosis/drug therapy , Onychomycosis/microbiology
9.
Photodiagnosis Photodyn Ther ; 46: 104045, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38479606

ABSTRACT

Onychomycosis, a fungal infection affecting the nail, is characterized by discoloration and thickening of the nail plate and is the most prevalent nail infection globally. We present a case of onychomycosis caused by Trichosporon asahii, a less common etiology. Notably, the patient was successfully treated with a non-traditional antibacterial approach, photodynamic therapy, which has been infrequently documented in the literature for such infections.


Subject(s)
Aminolevulinic Acid , Onychomycosis , Photochemotherapy , Photosensitizing Agents , Humans , Onychomycosis/drug therapy , Onychomycosis/microbiology , Photochemotherapy/methods , Photosensitizing Agents/therapeutic use , Aminolevulinic Acid/therapeutic use , Male , Trichosporon , Trichosporonosis/drug therapy , Middle Aged , Female , Basidiomycota
13.
J Drugs Dermatol ; 23(2): 110-112, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38306131

ABSTRACT

Good adherence to treatment is necessary for the successful treatment of onychomycosis and requires that an appropriate amount of medication be prescribed. Most prescriptions for efinaconazole 10% solution, a topical azole antifungal, are for 4 mL per month but there are no data on patient factors or disease characteristics that impact how much medication is needed. Data from two phase 3 studies of efinaconazole 10% solution for the treatment of toenail onychomycosis were pooled and analyzed to determine monthly medication usage based on the number of affected toenails, percent involvement of the target toenail, body mass index (BMI), and sex. Participants with two or more affected nails required, on average, >4 mL of efinaconazole per month, with increasing amounts needed based on the number of nails with onychomycosis (mean: 4.39 mL for 2 nails; 6.36 mL for 6 nails). In contrast, usage was not greatly impacted by target toenail involvement, BMI, or sex. Together, these data indicate that the number of affected nails should be the major consideration when determining the monthly efinaconazole quantity to prescribe. J Drugs Dermatol. 2024;23(2):110-112.    doi:10.36849/JDD.7676.


Subject(s)
Foot Dermatoses , Onychomycosis , Humans , Onychomycosis/diagnosis , Onychomycosis/drug therapy , Onychomycosis/microbiology , Nails , Administration, Topical , Triazoles/therapeutic use , Antifungal Agents , Foot Dermatoses/diagnosis , Foot Dermatoses/drug therapy , Foot Dermatoses/microbiology
14.
Regul Toxicol Pharmacol ; 148: 105588, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38423269

ABSTRACT

All cosmetics products, including nail care products, must be evaluated for their safety. The assessment of systemic exposure is a key component of the safety assessment. However, data on the exposure, especially via ungual route (nail plate) are limited. Based on the physicochemical properties of human nails and permeability data of topical onychomycosis drugs, the nail plate is considered a good barrier to chemicals. We examine factors impacting penetration of nail care ingredients through the nail plate, including properties of the nails of the ingredients and formulations. The molecular weight, vapor pressure, logP, water solubility, and keratin binding, as well as formulations properties e.g., polymerization of acrylate monomers are considered important factors affecting penetration. To estimate systemic exposure of nail care ingredients through the nail plate, a standardized framework is applied that quantifies the impacts of these properties on penetration with an adjustment factor for each of these influencing properties. All the adjustment factors are then consolidated to derive an integrated adjustment factor which can be used for calculation of the systemic exposure dose for the ingredient. Several case studies are presented to reflect how this framework can be used in the exposure assessment for nail cosmetic products.


Subject(s)
Cosmetics , Onychomycosis , Humans , Nails , Administration, Topical , Onychomycosis/drug therapy , Onychomycosis/metabolism , Drug Compounding , Permeability , Cosmetics/metabolism , Antifungal Agents
15.
J Mycol Med ; 34(1): 101464, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38367460

ABSTRACT

INTRODUCTION: The cases of dermatophytosis are increasing and they are associated with a higher number of therapeutic failures leading the doctor to prescribe combinations of antifungals as therapy. The objective was to evaluate the interaction of terbinafine and ciclopirox, the most commonly antifungals used in the clinic, in dermatophyte isolates. METHODOLOGY: The minimum inhibitory concentrations (MIC) of ciclopirox and terbinafine were determined by the broth microdilution method according CLSI and the checkerboard assay was used to evaluate the interaction between the antifungal agents. RESULTS: For terbinafine the mic50 was 0.125 ug/mL and mic90 was 0.250 ug/mL. For ciclopirox the values were 2.0 ug/mL for mic50 and 4.0 ug/mL for mic90. No synergistic interaction was observed for the dermatophyte isolates tested. CONCLUSION: These results suggest that the use of terbinafine in combination with ciclopirox, which is widely used in the clinic, may not be a good choice for the treatment of onychomycosis.


Subject(s)
Antifungal Agents , Onychomycosis , Humans , Terbinafine/pharmacology , Terbinafine/therapeutic use , Ciclopirox/therapeutic use , Antifungal Agents/pharmacology , Antifungal Agents/therapeutic use , Naphthalenes/pharmacology , Naphthalenes/therapeutic use , Onychomycosis/drug therapy , Onychomycosis/microbiology , Microbial Sensitivity Tests
16.
Mycoses ; 67(3): e13710, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38414346

ABSTRACT

BACKGROUND: Onychomycoses are difficult-to-treat fungal infections with high relapse rates. Combining oral and topical antifungal drugs is associated with higher success rates. Additive or synergistic modes of action are expected to enhance treatment success rates. OBJECTIVES: Investigation of the combined effects of antifungal drugs in vitro with different modes of action and application on clinical isolates from mycotic nails. METHODS: Isolates of Trichophyton rubrum, Trichophyton interdigitale and Scopulariopsis brevicaulis were collected from infected toenail specimens of patients with onychomycosis. Susceptibility testing was performed in 96-well polystyrene plates using a standard stepwise microdilution protocol. Additive or synergistic activity at varying concentrations was investigated by the checkerboard method. RESULTS: Combining terbinafine with amorolfine tended to be more effective than terbinafine in conjunction with ciclopirox. In most combinations, additive effects were observed. Synergy was detected in combinations with involving amorolfine in S. brevicaulis. These additive and synergistic interactions indicate that combined therapy with topical amorolfine and oral terbinafine is justified. Sublimation of amorolfine (and terbinafine) may enhance the penetration in and through the nail plate, and support treatment efficacy. CONCLUSIONS: These in vitro results support the notion that combining oral terbinafine and topical amorolfine is beneficial to patients with onychomycosis, particularly if the pathogen is a non-dermatophyte fungus such as S. brevicaulis.


Subject(s)
Morpholines , Onychomycosis , Humans , Terbinafine/pharmacology , Terbinafine/therapeutic use , Onychomycosis/drug therapy , Onychomycosis/microbiology , Ciclopirox/pharmacology , Ciclopirox/therapeutic use , Antifungal Agents/therapeutic use , Naphthalenes
17.
J Dermatol ; 51(4): 526-531, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38279193

ABSTRACT

Onychomycosis can be treated with topical and oral medications. However, it is important to appropriately select these medications according to the type and severity of the disease and ensure treatment is continued for the recommended duration. In Japan, treatment options for onychomycosis have increased in recent years. Moreover, in 2019, the guidelines for dermatomycosis treatment were revised. In this study, we conducted a receipt survey to clarify the actual treatment status of onychomycosis cases as indicated by the continuation rates of prescribed treatment drugs, together with a web-based survey to ascertain the prescribing policy of dermatologists regarding drugs for onychomycosis treatment. In agreement with past surveys, this receipt survey showed that the prescription continuation rate for oral medications was higher than that for topical medications. The 1-year prescription continuation rate for topical onychomycosis medications was found to be low (<10%). The web-based survey showed that the percentage of physicians who prescribed oral medications as their first choice increased by approximately 10% for each disease type, compared with the results of the previous survey conducted around 7 years ago. However, the study also confirmed that topical drugs are still prescribed for some disease types for which oral drugs are better suited. To ensure complete cure without patient drop-out, oral drugs with a high probability of achieving complete cure and a high continuation rate should be prescribed for patients with onychomycosis.


Subject(s)
Foot Dermatoses , Onychomycosis , Humans , Onychomycosis/drug therapy , Antifungal Agents/therapeutic use , Dermatologists , Administration, Oral , Internet , Administration, Topical , Foot Dermatoses/drug therapy
18.
Mycopathologia ; 189(1): 14, 2024 Jan 24.
Article in English | MEDLINE | ID: mdl-38265566

ABSTRACT

The two fungal species Trichophyton rubrum and Trichophyton violaceum are common pathogens on human, infecting keratinized tissue of the outer body parts. Both species are belonging to the "Trichophyton rubrum complex" and share very high similarity in the genome. Secreted proteinases, key factors for keratin degradation, are nearly identical. Contrary, the ecological niches are differing. Trichophyton rubrum preferably infects skin and nails, whereas T. violaceum preferably infects the scalp. We postulate, that differences in the protease expression contribute to differences in ecological preferences. We analyzed the expression profiles of all 22 endoprotease genes, 12 subtilisins (S8A), 5 deuterolysins (M35) and 5 fungalysins (M36), for both species. To compare the influence of the keratin source, we designed experiments with human nail keratin, sheep wool keratin and keratin free cultivation media. Samples were taken at 12 h, 24 h, 48 h and 96 h post incubation in keratin medium. The expression of the proteases is higher in wool-keratin medium compared to human nail medium, with the exception of MEP4 and SUB6. Expression in the keratin-free medium is lowest. The expression profiles of the two species are remarkable different. The expression of MEP1, MEP3, SUB5, SUB11 and SUB12 are higher in T. rubrum compared to T. violaceum. MEP2, NpIIc, NpIIe, SUB1, SUB3, SUB4, SUB7 and SUB8 are higher expressed in T. violaceum compared to T. rubrum. The differences of the protease expression in the two species may expalin the differences in the ecological niches. Further analysis are necessary to verify the hypothesis.Please check and conform the edit made in title.Here I thinke the species of strains shouldnt be capital, and the right expression should be,  "Expression Profiles of Protease in Onychomycosis-Related Pathogenic Trichophyton rubrum and Tinea Capitis-Related Pathogenic Trichophyton violaceum"Author names: Please confirm if the author names are presented accurately and in the correct se-quence (given name, middle name/initial, family name). Author 1 Given name: [Jingjing] Last name [Chen], Author 2 Given name: [Yangmin] Last name [Gao], Author 3 Given name: [Shuzhen] Last name [Xiong], Author 4 Given name: [Ping] Last name [Zhan]. Also, kindly confirm the details in the metadata are correct.YesPlease check and confirm the inserted city and country are correctly identified for affiliation 3.Please change the affiliations, Affiliation 2: ²Jiangxi Provincial Clinical Research Center for Skin Diseases, Dermatology Hospital of Jiangxi Province,The Affiliated Dermatology Hospital of Nanchang University, Nanchang, 330200, Jiangxi; Affiliation 3: 3Institute of Clinical Medicine, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College,Nanchang 330001, Jiangxi. Thanks a lot!


Subject(s)
Arthrodermataceae , Onychomycosis , Tinea Capitis , Sheep , Animals , Humans , Peptide Hydrolases , Keratins
19.
Dermatologie (Heidelb) ; 75(1): 48-54, 2024 Jan.
Article in German | MEDLINE | ID: mdl-38189829

ABSTRACT

In the course of globalization, migration and global warming, we are increasingly confronted with pathogens that do not occur naturally in our latitudes or appear in a different form. We know keratinophilic dermatophytes as the cause of tinea pedis, onychomycosis and also tinea corporis and capitis. Transmission usually occurs via domestic or farm animals and via autoinoculation. In recent years dermatophytes have gained additional importance as a possible sexually transmitted disease between immunocompetent persons. For the first time, dermatophytosis was described as a sexually transmitted infection in travelers who developed pronounced pubogenital or anogenital tinea after travelling in Southeast Asia, including Thailand, mostly after intensive sexual contact. Molecular and cultural analyses have identified Trichophyton (T.) mentagrophytes ITS (internal transcribed spacer) genotype VII as the main pathogen. Although this dermatophyte genotypically belongs to the zoophilic complex, direct (sexual) and occasionally indirect human-to-human contact with infected persons is suspected to be the current route of transmission. The infection can lead to inflammatory and purulent dermatophytosis, causing a high level of suffering. In this respect, a rapid and reliable diagnosis is essential in order to be able to initiate targeted treatment. The discovery of infection pathways and the awareness of the need to take rare diseases into account in our everyday lives will increasingly accompany us over the next few years and present us with new challenges, particularly in terms of prevention and treatment.


Subject(s)
Arthrodermataceae , Onychomycosis , Animals , Humans , Trichophyton/genetics , Genotype
20.
Colloids Surf B Biointerfaces ; 234: 113718, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38176335

ABSTRACT

Luliconazole-loaded microemulgels containing different permeation enhancers were formulated for transungual drug delivery for the management of onychomycosis, onychomycosis, which affects nails. The physicochemical properties like droplet size, zeta potential, pH, viscosity, spreadability, extrudability, oil binding capacity, drug content, and microscopic study were evaluated. The Pseudo-ternary phase diagram was constructed for the formulation of microemulsions (MEs) by keeping the Km ratio constant at 3:1 and characterized for clarity, mean droplet size, zeta potential, viscosity, pH, transmittance, refractive index, and stability. The ME mean droplet size and zeta potential were found in the range of 38.78 to 171.4 nm, and 0.00 to - 6.6 mV, respectively. Prepared MEs were converted into microemulgel by adding a 2.5% gelling agent (Carbapol 934) in the external phase, and a drug release study was conducted. Formulation E3 showed better drug release and was chosen as the control. Four different penetration enhancers were added separately within E3 and further evaluated for pH, viscosity, spreadability, extrudability, oil binding capacity, drug content, microscopic study, Compatibility study, XRD, and DSC. A favorable docking score was observed between luliconazole and Lanosterol 14-alpha-demethylase. In-vitro cumulative drug release at the end of 24 h from E3-SS, containing sodium sulfide as a penetration enhancer, was found to be 94.70% and was 2 times more than the control formulation. Ex-vivo transungual permeation studies through cutting nail clippings were found to be in the range of 28.18 - 36.52 µg/mm2. The microemulgels tagged as E3, E3-SS, and E3-SL showed a significant zone of inhibition against Candida albicans and Aspergillus fumigatus as compared to the marketed formulation.


Subject(s)
Imidazoles , Onychomycosis , Humans , Onychomycosis/drug therapy , Onychomycosis/metabolism , Administration, Topical , Chemistry, Pharmaceutical , Nails/metabolism , Antifungal Agents/chemistry
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