An international survey of recalcitrant and recurrent tinea of the glabrous skin-A potential indicator of antifungal resistance.

BACKGROUND: There has been a global rise in cases of dermatophytosis and, in particular, recalcitrant and recurrent cases on tinea of the glabrous skin. This phenomenon, particularly prevalent in India, has been linked to the concerning rise of antifungal resistance. The challenge is amplified by a dearth of comprehensive, international data to understand the global scope and characteristics of such cases. OBJECTIVES: This study aims to collate international insights, focusing on areas outside Europe (as this was previously published), to map the extent and characteristics of clinical and, where possible, laboratory confirmed tinea of the glabrous skin through an online survey administered to dermatologists globally. METHODS: An online survey was distributed from February 2022 to July 2023 and captured data on respondents' experience of recalcitrant and recurrent tinea of the glabrous skin over the preceding 3 years. RESULTS: A total of 260 responses were received spreads across 36 countries, excluding Europe. In total, 91.7% reported seeing cases of recalcitrant or recurrent tinea of the glabrous skin over the preceding 3 years. Common anatomical sites affected were the trunk and groin. T. mentagrophytes and T. rubrum were the predominant species implicated, and there were low rates of laboratory confirmed dermatophyte resistance. CONCLUSIONS: The high rates of reported recalcitrant and recurrent tinea of the glabrous skin underscore an urgent need for global collaborative efforts and enhanced diagnostic measures. The findings advocate for the establishment of a standardized global disease registry, regulation of over-the-counter antifungal and steroid combinations, correlation of clinical suspicion with laboratory confirmed drug resistance and exploration of alternative therapeutic strategies to mitigate the burgeoning challenge of dermatophyte resistance.

Laser and intense pulsed light in the treatment of hidradenitis suppurativa.

Treatment of hidradenitis suppurativa (HS) requires a combination of medical, surgical, and lifestyle interventions. Intense pulsed light (IPL) and lasers have been reported to be useful. The aim of this review is to find the evidence supporting IPL and laser treatment of HS and to provide guidance for the management of specific HS lesions. We searched PubMed and Web of Science for "laser" and "hidradenitis suppurativa" on April 6, 2022. Inclusion criteria were >10 patients, reported follow-up, English language, and human subjects with a diagnosis of HS. A total of 724 articles were screened, but only 17 studies qualified for inclusion (IPL (n = 4), Nd:YAG (n = 6), CO2 laser (n = 6), and intralesional treatment (n = 2). The majority of the studies had a low (n = 10) or moderate (n = 7) evidence level. Treatment effect was noticed in studies using IPL and Nd:YAG (hair reduction). CO2 laser was used for surgery with a success rate ranging from 70.7% to 96.7%. CO2 laser is useful for surgery of stationary HS lesions, but it is difficult to draw a conclusion on the use of IPL and Nd:YAG (hair reduction) as the studies were too heterogeneous to perform a meta-analysis.

Systematic review of the prevalence of onychomycosis in children.

Onychomycosis is one of the most common nail diseases in adults but is described as infrequent in children. Data are, however, scattered and diverse. Studies have nevertheless suggested that the prevalence of onychomycosis is increasing in children lately and the aim of this review was therefore to examine this problem. Two authors individually searched PubMed, Embase, and Cochrane Library for articles on epidemiology and prevalence of onychomycosis in children. The literature search was conducted in accordance per PRISMA guidelines. In total 1042 articles were identified of which 23 were eligible for inclusion. One of the articles presented two studies and a total of 24 studies were therefore included. Seventeen studies presented data of the prevalence of onychomycosis in children in the general population and seven studies among children visiting a dermatological and pediatric department or clinic. The prevalence ranged from 0% to 7.66% with an overall discrete increase of 0.66% during the period 1972 to 2014 in population studies (not statistically significant). This review supports a trend towards an increased prevalence of onychomycosis in children, albeit based on a paucity of studies. The data suggests an increasing prevalence of onychomycosis with age, and co-infection with tinea pedis (reported in 25% of the studies). The most common pathogen reported was Trichophyton rubrum and onychomycosis was more prevalent in toenails compared to fingernails. The general characteristics of onychomycosis in children are thus similar to those described in adults.

The Emerging Terbinafine-Resistant Trichophyton Epidemic: What Is the Role of Antifungal Susceptibility Testing?

BACKGROUND: Dermatophytosis is commonly encountered in the dermatological clinics. The main aetiological agents in dermatophytosis of skin and nails in humans are Trichophyton (T.) rubrum, T. mentagrophytes and T. interdigitale (former T. mentagrophytes-complex). Terbinafine therapy is usually effective in eradicating infections due to these species by inhibiting their squalene epoxidase (SQLE) enzyme, but increasing numbers of clinically resistant cases and mutations in the SQLE gene have been documented recently. Resistance to antimycotics is phenotypically determined by antifungal susceptibility testing (AFST). However, AFST is not routinely performed for dermatophytes and no breakpoints classifying isolates as susceptible or resistant are available, making it difficult to interpret the clinical impact of a minimal inhibitory concentration (MIC). SUMMARY: PubMed was systematically searched for terbinafine susceptibility testing of dermatophytes on October 20, 2020, by two individual researchers. The inclusion criteria were in vitro terbinafine susceptibility testing of Trichophyton (T.) rubrum, T. mentagrophytes and T. interdigitale with the broth microdilution technique. The exclusion criteria were non-English written papers. Outcomes were reported as MIC range, geometric mean, modal MIC and MIC50 and MIC90 in which 50 or 90% of isolates were inhibited, respectively. The reported MICs ranged from <0.001 to >64 mg/L. The huge variation in MIC is partly explained by the heterogeneity of the Trichophyton isolates, where some originated from routine specimens (wild types) whereas others came from non-responding patients with a known SQLE gene mutation. Another reason for the great variation in MIC is the use of different AFST methods where MIC values are not directly comparable. High MICs were reported particularly in isolates with SQLE gene mutation. The following SQLE alterations were reported: F397L, L393F, L393S, H440Y, F393I, F393V, F415I, F415S, F415V, S443P, A448T, L335F/A448T, S395P/A448T, L393S/A448T, Q408L/A448T, F397L/A448T, I121M/V237I and H440Y/F484Y in terbinafine-resistant isolates.

Photodynamic therapy: A treatment option for terbinafine resistant Trichophyton species.

BACKGROUND: Terbinafine is a first-line agent against Trichophyton-infections. However, treatment failure and resistance due to squalene epoxidase (SQLE) alterations are increasingly being reported. Photodynamic therapy (PDT) is based on combining a photosensitizer, light and oxygen to create photo-activated reactive oxygen species. It has demonstrated in vitro and in vivo activity against various microorganisms including dermatophytes. We investigated if PDT is equally effective against terbinafine resistant and susceptible strains. METHODS: Minimum inhibitory concentrations (MIC) of methylene blue (MB)-PDT against wildtype and resistant Trichophyton rubrum and Trichophyton interdigitale were determined in duplicate in microtitre plates following EUCAST E.Def 11.0 reference methodology. Included mutants harboured F397L, L393F, L393S, F415S or F397I SQLE-alterations. Illumination with red diode light was performed after <3 min, 30 min and 3 h of incubation, respectively, and plates were cultured at 25 °C for 5 days. Geometric mean MICs and MIC ranges were calculated for each isolate. RESULTS: MB-PDT led to complete inhibition of all isolates at geometric mean concentrations of 1-16 mg/L. Efficacy was independent of incubation time prior to illumination, terbinafine susceptibility (MICs ≤0.004-4 mg/L) and presence of SQLE mutations. However, the MB-PDT MIC was slightly elevated (MB: 2-8 mg/L and 8-16 mg/L) in isolates from two pigmented cultures of Trichophyton interdigitale (one wildtype and one harbouring L393F) with a darker color when compared to unpigmented cultures (MB: 0.5-4 mg/L). CONCLUSION: Terbinafine resistant and susceptible strains are equally susceptible to MB-PDT. Lower efficacy was observed against dark coloured isolates which we speculate may be due to melanisation interfering with photo-activation due to preferential light absorption.

Photodynamic therapy treatment of superficial fungal infections: A systematic review.

BACKGROUND: Fungal infections in skin, hair and nails affect up to 25 % of the global population. Conventional antifungal treatment is effective but due to resistance, treatment failure, drug interactions, and treatment related toxicity, there is a need for alternative treatments. Photodynamic therapy (PDT) has shown antimicrobial properties and is used increasingly for fungal infections. This review investigates the reported efficacy and side effects of PDT of superficial mycoses. METHODS: Pubmed and Embase were searched 26-01-2020 for "superficial fungal infections" and "photodynamic therapy" in "Human subjects" using a predefined search string. Criteria for inclusion were: clinical trials and cases involving PDT-treated patients with primary fungal infections in skin, hair and nails. Criteria for exclusion were: languages other than English, animal models, in vitro trials, secondary fungal infections, reviews and guidelines. RESULTS: 541 records were identified and 34 papers fulfilled the criteria. PDT of onychomycosis (n = 380 patients) found treatment with methylene blue (MB) photosensitizer (PS) more efficacious with complete cure rates of 70 %-80 % than 5-aminolevulinic acid (ALA)-PDT (mycological cure rates of 17 %-57 %) and methyl aminolevulinate (MAL)-PDT (mycological cure rate of 32 %). Other PDT-treated fungal diseases included (n = 55): foot infections (n = 19), tinea cruris (n = 10), scalp infections (n = 2), Malassezia infections (n = 9) and subcutaneous fungal infections (n = 15) achieved promising effect. CONCLUSION: PDT-treatment of superficial mycoses can be efficacious as salvage therapy. In the light of increasing resistance and few licensed treatment alternatives, larger randomized controlled trials investigations and optimization of the PDT-treatment protocol are warranted to evaluate PDT's potential as a future antifungal treatment.

Evidence-based Danish guidelines for the treatment of Malassezia-related skin diseases.

Internationally approved guidelines for the diagnosis and management of Malassezia-related skin diseases are lacking. Therefore, a panel of experts consisting of dermatologists and a microbiologist under the auspices of the Danish Society of Dermatology undertook a data review and compiled guidelines for the diagnostic procedures and management of pityriasis versicolor, seborrhoeic dermatitis and Malassezia folliculitis. Main recommendations in most cases of pityriasis versicolor and seborrhoeic dermatitis include topical treatment which has been shown to be sufficient. As first choice, treatment should be based on topical antifungal medication. A short course of topical corticosteroid or topical calcineurin inhibitors has an anti-inflammatory effect in seborrhoeic dermatitis. Systemic antifungal therapy may be indicated for widespread lesions or lesions refractory to topical treatment. Maintenance therapy is often necessary to prevent relapses. In the treatment of Malassezia folliculitis systemic antifungal treatment is probably more effective than topical treatment but a combination may be favourable.

Prevalence of toe nail onychomycosis in diabetic patients.

Onychomycosis among diabetic patients has been reported in some studies to be of high prevalence. This study aimed to investigate the prevalence of onychomycosis among diabetic patients at a Danish University Hospital. Clinical and mycological examinations were performed on type 1 and 2 diabetic patients from in- and out-patient clinics. A total of 271 patients were enrolled, 72% males, mean age 61.3 years, 26% of the patients had diabetes type 1. The prevalence of toe nail onychomycosis (positive culture and/or microscopy) was 22% (n = 59) of which 55 cases were caused by dermatophytes (93%) and 4 cases by yeasts (7%). A correlation was found between onychomycosis and age (p =0.02) and severity of nail changes (p <0.001), respectively. However, no significant correlation was found to gender, type of diabetes, lower extremity arterial disease, neuropathy, toe amputation or oedema. Onychomycosis occurred with a high prevalence in diabetic patients, especially among older patients and those with severe nail changes.