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Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with severe consequences on quality of life. One aspect of this is that HS has been linked to an increased risk of infertility, but as data is still limited, it is not known if the association reflects causality. We performed a cross-sectional study of 161 female participants included at Zealand University Hospital, Roskilde, Denmark. Data regarding basic demographics, infertility, pregnancies, sexual function, and known factors with impact on fertility was collected. Logistic regressions were performed to analyze the association between HS and infertility, adjusting for factors that influence fertility. The study population consisted of 55 patients with HS, 55 patients with other dermatological diseases (ODD), and 51 healthy controls (HC). The HS group had a higher BMI, lower sexual function, and a higher tobacco use. We found no significant difference between the three groups in terms of whether they had children, the number of children they had, infertility, or whether they had received fertility treatments. The logistic analyses found no correlation between HS and infertility, and adjusting for factors affecting infertility did not alter this result. This study did not find a significant difference in infertility between patients with HS compared to those with ODD or HC. This result was not affected by adjustments for other factors known to influence fertility. Interestingly, the lower sexual function in the HS group did not appear to influence their desire or ability to conceive., (© 2024. The Author(s).)

Background: Tinea pedis is one of the most prevalent superficial fungal infections. Initial antifungal treatment is often acquired over-the-counter (OTC) without previous consultation with a physician., Objective: Lately, increasing antifungal terbinafine resistance has been documented in Denmark and globally and it is therefore of interest to assess how Danish pharmacies advise customers with tinea pedis., Methods: One hundred Danish pharmacies were randomly selected and an employee interviewed from each. A structured question guide was followed, with the possibility to add further comments., Results: Interviews of 94 pharmacies were conducted. Six pharmacies never replied. Terbinafine as standard dose or cutaneous solution terbinafine one time application (Lamisil Once (R)) were recommended by 99% of the pharmacy employees as first-line treatment. The customer was advised to seek medical attention when tinea pedis was recurring (93%), or when treatment duration was > 2 weeks (77%). The majority (88%) of the pharmacy employees had no knowledge about antifungal resistance., Conclusion: Only few pharmacy employees were aware of the current problem of antifungal resistance and the majority advised costumers to initiate treatment using OTC topical terbinafine. The problem of emerging antifungal resistance requires attention in order to provide customers with tinea pedis effective treatment and prevent further societal spread of resistance to antifungals., (© 2024 The Author(s). Mycoses published by Wiley‐VCH GmbH.)

Background: Nakaseomyces glabratus (N. glabratus) formerly known as Candida glabrata (C. glabrata), is an endogenous opportunistic pathogen, which is generally located in the gastrointestinal tract but can spread in immunocompromised patients. N. glabratus is the second most common pathogen that causes candidemia in several countries. N. glabratus virulence factors may increase antifungal resistance and reduce the number of available treatment options. High resistance to azoles and increasing resistance to echinocandins have been previously reported in N. glabratus., Objective: To establish the distribution of N. glabratus isolates in Europe and its drug susceptibility/resistance in each country over the last 7 years., Methods: The search was performed across three databases: PubMed, Scopus and Scielo, using the MeSH terms: "Candida glabrata", "Nakaseomyces glabratus", "Europe", "resistance" and "Epidemiology" exclusively in English. All available information from January 2002 to December 2022 was included, excluding reviews, meta-analyses and book chapters., Results: Fifty-seven articles with information on antifungal susceptibility in Europe were retrieved and analysed with a total of 15,400 reported C. glabrata isolates. Remarkably, nations that presented the maximum number of cases during the study period included the United Kingdom (n = 7241, 47.02%), France (n = 3190, 20.71%), Spain (n = 900, 5.84%), Hungary (n = 745, 4.84%) and Italy (n = 486, 3.16%). C. glabrata isolates presented resistance to azoles [voriconazole (n = 2225, 14.45%), fluconazole (n = 1612, 10.47%), itraconazole (n = 337, 2.19%) and clotrimazole (n = 89, 0.58%)], increased resistance to echinocandins, especially to anidulafungin (n = 138, 0.89%), and high sensitivity to amphotericin B., Conclusion: The number of candidemia cases associated with triazole-resistant N. glabratus isolates have been increasing in Europe. Therefore, echinocandins and amphotericin B can be considered optional empirical treatments; however, antifungal susceptibility testing is required to determine the best therapeutic options., (© 2024 The Author(s). Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

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., (© 2024 The Author(s). Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Background: Microsporum audouinii has resurged recently. Infections with the dermatophyte are difficult to treat, which raises the question if we treat M. audouinii infections with the most effective antifungal (AF) agent., Objectives: The aims of this study was to investigate an outbreak of tinea capitis (TC) in Denmark, address the challenges in outbreak management and to conduct two reviews regarding previous outbreaks and minimal inhibitory concentration (MIC)., Methods: We used Wood's light, culture, direct microscopy, and PCR for screening and antifungal susceptibility testing (AFST) for treatment optimization. We performed two reviews to explore M. audouinii outbreaks and MIC values using broth microdilution method., Results: Of 73 screened individuals, 10 had confirmed M. audouinii infections. Clinical resistance to griseofulvin was observed in 4 (66%) cases. While previous outbreaks showed high griseofulvin efficacy, our study favoured terbinafine, fluconazole and itraconazole in our hard-to-treat cases. AFST guided the choice of AF. Through the literature search, we identified five M. audouinii outbreaks, where differences in management included the use of Wood's light and prophylactic topical AF therapy. Terbinafine MIC values from the literature ranged from 0.002 to 0.125 mg/L., Conclusion: Use of Wood's light and preventive measurements were important for limiting infection. The literature lacked MIC data for griseofulvin against M. audouinii, but indicated sensitivity for terbinafine. The clinical efficacy for M. audouinii treatment was contradictory favouring both terbinafine and griseofulvin. AFST could have a key role in the treatment of difficult cases, but lack of standardisation of AFST and MIC breakpoints limits its usefulness., (© 2024 The Author(s). Mycoses published by Wiley‐VCH GmbH.)

Acne fulminans (AF) is a rare, serious, sudden-onset and long-lasting skin disease that causes scarring of face and body. Standard treatment with combined long-term isotretinoin and prednisolone is not always sufficient and has a well-known propensity for adverse effects leaving an unmet need for improved therapy. Case reports suggest that tumor necrosis factor (TNF)-α inhibitors may play a role in the management of AF. In a 3-year retrospective data collection from two dermatology centers and literature review of clinical cases of acne fulminans treated with anti-TNF-α therapy, three clinical cases and twelve literature cases were identified. A total of five different TNF-α inhibitors have been tested, with adalimumab being the most commonly used. Clinical response was seen after 1 month in 2/3 (67%) clinical cases and 5/12 (42%) literature cases, respectively, and treatment was successful in 2/3 (67%) and 11/12 (92%) after a median 3-7 months. All reported adverse effects were mild and reversible. Anti-TNF-α treatment may provide rapid improvement in patients with AF when initial treatment with isotretinoin and prednisolone fails. However, randomized controlled trials are lacking, and exact dosage and timing need to be explored before clinical implementation., (© 2023 The Authors. Journal der Deutschen Dermatologischen Gesellschaft published by Wiley-VCH GmbH on behalf of Deutsche Dermatologische Gesellschaft.)

Introduction: Data concerning the global burden of hidradenitis suppurativa (HS) are limited. Reported prevalence estimates vary between 0.0003% and 4.1%, and data from various geographical regions are still to be collected. Previously reported prevalences have been limited by the methodological approach and source of data. This has resulted in great heterogeneity as prevalence data from physician-diagnosed cases poorly match those of self-reported apparent HS disease., Methods: The Global Hidradenitis Suppurativa Atlas (GHiSA) introduces an innovative approach to determine the global prevalence of HS. This approach involves using a previously validated questionnaire to screen apparently healthy adults accompanying a patient to a non-dermatological outpatient clinic visit in a hospital or a private/family medicine clinic. The screening questionnaire (i.e., the index test) is combined with a subsequent physician-based in-person validation (i.e., the reference standard) of the participants who screen positive. Approximately ten percent of the screen-negative participants are also clinically assessed to verify the diagnostic precision of the test. The local prevalence (pi) will be estimated from each country that submits the number of patients who are HS positive according to the index test and clinical examination (n), and the corresponding total number of observations (N)., Conclusion: The GHiSA Global Prevalence studies are currently running simultaneously in 58 countries across six continents (Africa, Europe, Australia, North America, South America, and Asia). The goal of the combined global proportion is the generation of a single summary (i.e., proportional meta-analysis), which will be done after a logit transformation and synthesized using a random-effects model. The novel standardization of the Global Prevalence Studies conducted through GHiSA enables direct international comparisons, which were previously not possible due to substantial heterogeneity in past HS prevalence studies., (© 2024 S. Karger AG, Basel.)

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease associated with psychiatric comorbidity. Attention deficit hyperactivity disorder (ADHD) is a mental disorder associated with systemic and skin inflammation such as psoriasis and atopic dermatitis. Whether HS symptoms are associated with ADHD symptoms remains unexplored. Thus, the aim of this study was to explore the possible association between HS and ADHD. Participants in the Danish Blood Donor Study (DBDS) were included in this cross-sectional study during 2015-2017. The participants provided questionnaire data on screening items of HS, ADHD symptoms (ASRS-score), and depressive symptoms, smoking and body mass index (BMI). A logistic regression with HS symptoms as a binary outcome predicted by ADHD adjusted for age, sex, smoking, BMI, and depression was conducted to investigate the association between HS and ADHD. A total of 52,909 Danish blood donors were included in the study. Of these were 1004/52,909 (1.9%) considered participants with HS. Of the participants with HS, 74/996 (7.4%) screened positive of ADHD symptoms, while only 1786/51,129 (3.5%) of the participants without HS screened positive of ADHD. Adjusted for confounders, ADHD was positively associated with HS, odds ratio 1.85 (95% confidence interval: 1.43-2.37). Psychiatric comorbidity of HS is not limited to depression and anxiety. This study shows a positive association between HS and ADHD. Further research on the biological mechanisms behind this association is warranted., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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), CO 2 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). CO 2 laser was used for surgery with a success rate ranging from 70.7% to 96.7%. CO 2 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., Competing Interests: Declaration of Competing Interest Zealand University Hospital is a member of the European Reference Network on Rare and Undiagnosed Skin Disorders and the European Hidradenitis Suppurativa Foundation. DML Saunte received honoraria as a consultant for advisory board meetings by AbbVie, Janssen, Sanofi, Leo Pharma, Novartis, UCB and as a speaker and/or received grants from the following companies: Abbvie, Janssen, Novartis, Sanofi, Jamjoom Pharma and Leo Pharma during the last three years. She is a primary investigator for Moberg. GBE Jemec has received honoraria from AbbVie, Chemocentryx, Coloplast, Incyte, Inflarx, Novartis, Pierre Fabre and UCB for participation on advisory boards, and grants from Abbvie, Astra-Zeneca, Inflarx, Janssen-Cilag, Leo Pharma, Novartis, Regeneron and Sanofi, for participation as an investigator, and received speaker honoraria from AbbVie, Boehringer-Ingelheim, Galderma and MSD. He has also received unrestricted departmental grants from Abbvie, Leo Pharma and Novartis., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Malassezia is a lipophilic yeast that is a part of the human mycobiome. Malassezia folliculitis appears when the benign colonization of the hair follicles, by the Malassezia yeasts, becomes symptomatic with pruritic papules and pustules. Although Malassezia folliculitis is common in hospital departments, diagnosing and treating it varies among dermatologists and countries. The European Academy of Dermatology and Venereology Mycology Task Force Malassezia folliculitis working group has, therefore, sought to develop these recommendations for the diagnosis and management of Malassezia folliculitis. Recommendations comprise methods for diagnosing Malassezia folliculitis, required positive findings before starting therapies and specific treatment algorithms for individuals who are immunocompetent, immunocompromised or who have compromised liver function. In conclusion, this study provides a clinical strategy for diagnosing and managing Malassezia folliculitis., (© 2023 European Academy of Dermatology and Venereology.)

An abscess is a collection of pus forming a cavity in the tissue, for example, the skin. They are generally perceived as the result of infection but infection is not mandatory for the diagnosis. Skin abscesses may occur independently (primary) or be part of other diseases such as the recurrent inflammatory skin disease hidradenitis suppurativa (HS). HS is noninfectious but nevertheless abscesses are a common differential diagnosis. The purpose of this study is to review the microbiome of bacteria positive primary skin abscesses in order to explore the reported microbiota. EMBASE, MEDLINER, and COCHRANE LIBRABRY were searched on 9th of October 2021 for microbiome, skin, and abscesses. Studies with more than 10 patients reporting the microbiome in human skin-abscesses were included and studies with abscess microbiota sampled from HS patients, microbiota not sampled from skin-abscesses, missing information on microbiome data, sampling bias, studies in other language than English or Danish, reviews and meta-analyses were excluded. In total 11 studies were included for further analysis. S. aureus is likely to dominate the microbiome of bacteria positive primary skin abscesses in contrast to the polymicrobial microbiome of HS., (© 2023 Scandinavian Societies for Pathology, Medical Microbiology and Immunology.)

Background: The human leukocyte antigen system (HLA) is divided into two classes involved in antigen presentation: class I presenting intracellular antigens and class II presenting extracellular antigens. While susceptibility to infections is correlated with the HLA system, data on associations between HLA genotypes and Malassezia-related skin diseases (MRSD) are lacking. Thus, the objective of this study was to investigate associations between HLA alleles and MRSD., Materials and Methods: Participants in The Danish Blood Donor Study (2010-2018) provided questionnaire data on life style, anthropometric measures, and registry data on filled prescriptions. Genotyping was done using Illumina Infinium Global Screening Array, and HLA alleles were imputed using the HIBAG algorithm. Cases and controls were defined using filled prescriptions on topical ketoconazole 2% as a proxy of MRSD. Logistic regressions assessed associations between HLA alleles and MRSD adjusted for confounders and Bonferroni corrected for multiple tests., Results: A total of 9455 participants were considered MRSD cases and 24,144 participants as controls. We identified four risk alleles B*57:01, OR 1.19 (95% CI: 1.09-1.31), C*01:02, OR 1.19 (95% CI: 1.08-1.32), C*06:02, OR 1.14 (95% CI: 1.08-1.22), and DRB1*01:01, OR 1.10 (95% CI: 1.04-1.17), and two protective alleles, DQB1*02:01, OR 0.89 (95% CI: 0.85-0.94), and DRB1*03:01, OR 0.89 (95% CI: 0.85-0.94)., Conclusion: Five novel associations between HLA alleles and MRSD were identified in our cohort, and one previous association was confirmed. Future studies should assess the correlation between Malassezia antigens and antigen-binding properties of the associated HLA alleles., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Onychomycosis is a common disease with a significant negative impact on quality of life. While the disease is usually manageable in general practice, a proportion of patients need specialist treatment in academic hospital clinics. However, it is an unknown question whether the incidence in those needing specialist treatments is changing. Furthermore, the comorbidity burden in this patient population severely affected by onychomycosis has never been characterized. We conducted a retrospective study on patients treated for onychomycosis in Danish hospitals from 1994 to 2018. The cohort was observed for 24 years, and the data comprise 7.2 million Danes and their hospital diagnoses. A disease trajectory algorithm was used to examine the comorbidity burden in the cohort. A total of 2,271 patients received hospital treatment for onychomycosis during the time period, of which 1358 (59.8%) were men. The data show an increase in the incidence of hospital-treated cases since 2012 and that the most common comorbidities in this patient population include cardiovascular disease, alcohol-related diagnoses, and diabetes. One explanation of the increase in specialist treatment may include a general increase in patients with decreased resilience to fungal disease. This lack of resilience may both include an increasing elderly population with atherosclerosis, diabetes, and immunosuppression but also a potential increase in patients treated with immunosuppressive agents. Another possible explanation may include a shift in patient expectations in the case of treatment failure. Thus, patients may have an increasing demand for specialist treatment. While our data document an increase in the number of patients in need of specialist treatment for onychomycosis, we suggest future research to examine the general incidence of onychomycosis but also whether this increase in an apparently recalcitrant disease may be attributed to increased antifungal resistance, more specialist treatment options, or increased attention to dermatomycoses.

Background: An increase in the number of recurrent and recalcitrant dermatophytoses calls for a tool to guide the clinician to correlate in vitro minimum inhibitory concentration (MIC) data, antifungal treatment with clinical outcomes. This systematic review aims to explore a possible correlation between one aspect of this, previous antifungal exposure, and clinical outcomes. Methods: A systematic literature search for articles on previous antifungal treatment, treatment outcome, susceptibility methods used, organism (genus/species), and MIC values was conducted. Results: A total of 720 records were identified of which 19 articles met the inclusion criteria. Forty percent of the cases had contact with or travel to India, 28% originated from or had traveled to other countries where treatment unresponsive tinea infections had been reported. Tinea corporis was the most common clinical presentation and the species involved were Trichophyton ( T. ) indotineae and T. rubrum , followed by T. mentagrophyte / interdigitale complex and T. tonsurans . Nearly all patients had previously been exposed to one or more antifungals. The studies were too heterogeneous to perform a statistical analysis to test if previous antifungal exposure was related to resistance. Conclusions: Only a few studies were identified, which had both sufficient and robust data on in vitro susceptibility testing and clinical treatment failure. Further research on the value of susceptibility testing to improve clinical practice in the management of dermatophyte infections is needed.

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., (© 2022 The Authors. Pediatric Dermatology published by Wiley Periodicals LLC.)

Background: Treatment of tinea pedis and onychomycosis is complicated by high rates of reinfection and the emergence of terbinafine-resistant strains of Trichophyton spp. Effective disinfection of contaminated socks is an important measure. Appropriate washing reduces the risk of reinfection and is paramount in treating tinea pedis and onychomycosis., Objectives: The aim of this study was to describe the effect of commonplace disinfection methods using socks pieces inoculated with terbinafine-resistant or terbinafine-susceptible isolates of Trichophyton spp., Methods: Sock pieces were inoculated with seven terbinafine-resistant isolates of Trichophyton spp. with known mutations in the SQLE-gene (T. rubrum (n = 3), T. interdigitale (n = 1) and T. indotineae (n = 3)) and six terbinafine-susceptible isolates of Trichophyton spp. (T. rubrum (n = 3) and T. interdigitale (n = 3)). Methods of disinfection included soaking in a quaternary ammonium (QAC) detergent (0.5, 2 and 24 h), freezing at -20°C (0.5, 12 and 24 h), domestic and steam washing (both at 40°C with detergent). Sock pieces were cultured for 4 weeks following disinfection. The primary end point was no growth at the end of week 4., Results: Soaking in a QAC-detergent for 24 h procured at disinfectant rate of 100% (13/13), whilst soaking in 0.5 and 2 h had a disinfectant rate of 46.2% (6/13) and 84.6% (11/13), respectively. Domestic washing (40°C with detergent) produced a disinfectant rate of 7.7% (1/13). Freezing at -20°C (0.5, 12 and 24 h) and steam washing (40°C with detergent) had no disinfectant properties., Conclusions: Soaking in a QAC-detergent for 24 h effectively disinfected sock pieces contaminated with dermatophytes., (© 2022 Wiley-VCH GmbH.)

Terbinafine resistance in Trichophyton species has emerged and appears to be increasing. A new EUCAST susceptibility testing method and tentative ECOFFs were recently proposed for Trichophyton . Terbinafine resistance and target gene mutations were detected in 16 Danish isolates in 2013-2018. In this study, samples/isolates submitted for dermatophyte susceptibility testing 2019-2020 were examined. Species identification (ITS sequencing for T. mentagrophytes/T. interdigitale species complex (SC) isolates), EUCAST MICs and squalene epoxidase (SQLE) profiles were obtained. Sixty-three isolates from 59 patients were included. T. rubrum accounted for 81% and T. mentagrophytes/T. interdigitale SC for 19%. Approximately 60% of T. rubrum and T. mentagrophytes/interdigitale SC isolates were terbinafine non-wildtype and/or had known/novel SQLE mutations with possible implications for terbinafine MICs. All infections with terbinafine-resistant T. mentagrophytes/interdigitale SC isolates were caused by Trichophyton indotineae . Compared to 2013-2018, the number of patients with terbinafine-resistant Trichophyton isolates increased. For T. rubrum , this is partly explained by an increase in number of requests for susceptibility testing. Terbinafine-resistant T. indotineae was first detected in 2018, but accounted for 19% of resistance (4 of 21 patients) in 2020. In conclusion, terbinafine resistance is an emerging problem in Denmark. Population based studies are warranted and susceptibility testing is highly relevant in non-responding cases.

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., (© 2021 S. Karger AG, Basel.)

Tinea capitis is a fungal infection mostly affecting children. Epidemiology is changing over time due to migration, and it has been estimated that up to 40% of children from certain developing countries are affected. The mechanism of transmission is still unclear although asymptomatic carriage seems to have an influence in establishing persistent reservoirs that can cause or fuel epidemics. Screening and prophylactic treatment of close contacts of tinea capitis patients are therefore recommended by several international guidelines, but vaguely and not consistent. The treatments involved can be expensive, hard to integrate in everyday life, have well-known side effects and some are not approved for the treatment of children. The aim of this review was to clarify the evidence behind treatment of human asymptomatic carriers of tinea capitis. Databases were searched for the 'tinea capitis', 'carriers' and 'treatment'. Inclusion criteria were clinical trials, observational and interventional studies including case series (10+ cases) and case reports in English, Danish, Swedish, Norwegian and French. Reviews, guidelines, unclear reports and in vitro trials were excluded. A systematic review identified 10 studies with low to moderate evidence levels. The topical treatments ketoconazole, povidone-iodine, miconazole and the systemic antifungals terbinafine and itraconazole have all shown significant effects in the mycological eradication of fungal conidia. General prophylactic hygienic measures may have a benefit. The scientific evidence behind the treatment of asymptomatic carriage of scalp dermatophytes is sparse and not of high quality. Yet, both topical and systemic antifungal agents show treatment efficacy. Considering the possible adverse effects, topical agents are preferable, but with necessary attention to the compliance of asymptomatic contacts with treatment., (© 2021 European Academy of Dermatology and Venereology.)

Background: Hidradenitis suppurativa (HS) is a painful chronic, recurrent inflammatory skin disease with great impact on health-related quality of life (HRQOL). Recently, Hidradenitis SuppuraTiva cORe outcomes set International Collaboration (HISTORIC) established HRQOL as a core domain set for HS clinical trials and developed the Hidradenitis Suppurativa Quality of Life (HiSQOL) as a validated outcome measurement instrument., Objectives: To provide further convergent validity of HiSQOL by comparing it to Dermatology Life Quality Index (DLQI) and Pictorial Representation of Illness and Self Measure-Revised 2 (PRISM-R2)., Methods: In this cross-sectional study, 103 participants completed HiSQOL, PRISM-R2 and DLQI. PRISM-R2 is an instrument designed to measure suffering and reports the two measures, Illness Perception Measure (IPM) and Self-Illness Separation (SIS). Correlation analyses were performed including a sub-analysis for a subgroup of patients with high scores in the HS-specific domains of HiSQOL., Results: A very strong correlation was found between HiSQOL and DLQI (ρ = 0.93, P < 2.2 × 10 -16 , (95% CI: 0.89;0.95)), and moderately strong correlations were found between HiSQOL and SIS (ρ = -0.73, P < 2.2 × 10 -16 , (95% CI: -0.81; -0.62)) and DLQI and SIS (ρ = -0.70, P < 2.2 × 10 -16 , (95% CI: -0.79; -0.59)). IPM was positively associated with HiSQOL and DLQI and negatively with SIS., Conclusions: HiSQOL is a valid measure of quality of life for HS patients, and we suggest that HiSQOL can be used as a measure of suffering as well., (© 2021 European Academy of Dermatology and Venereology.)

Background: Dermatophytosis is a world-wide distributed common infection. Antifungal drug resistance in dermatophytosis used to be rare, but unfortunately the current Indian epidemic of atypical widespread recalcitrant and terbinafine-resistant dermatophytosis is spreading and has sporadically been reported in Europe., Objectives: To explore the occurrence of clinical and mycological proven antifungal drug resistance in dermatophytes in Europe., Methods: A standardized questionnaire was distributed through the EADV Task Force of Mycology network to dermatologists in Europe., Results: Representatives from 20 countries completed the questionnaires of which 17 (85 %) had observed clinical and/or mycological confirmed antifungal resistance, two countries published cases of antifungal resistance and one country had no known cases., Conclusions: This pilot study confirms that both clinical and mycological antifungal resistance exist in Europe., (© 2021 European Academy of Dermatology and Venereology.)

Background: Hidradenitis suppurativa (HS) is not a well-studied or easily treated disease. Genetic information is essential for advances in the understanding and treatment of HS. This study aims to examine mutations in the gamma-secretase complex, the Notch signalling pathway and to perform a Mendelian analysis of genetic variants that segregated with disease in a full exome sequencing of 11 families with HS., Method: Whole-exome sequencing and Mendelian analysis of 11 families with HS from Denmark. Patients with a clinical diagnosis of active HS and a positive family history of HS were recruited. Consenting family members were enrolled and examined for HS as well. We included 11 families, with a total of 51 participants, 24 with HS and 27 without. Whole-exome sequencing using HiSeq platform as paired-end 2 × 150 bases was used., Results: We found mutations in the Notch pathway for all families. We found mutations in the PSENEN and APH1B of the gamma-secretase genes. We also report 161 variants of unknown significance that segregated with the disease within these families., Conclusions: We did not find causative mutation for each family in this study, supporting the theory that HS is rarely caused by single-gene mutations. We suggest that future genetic studies should be focused on genome-wide association with thousands of cases, as this technique is better suited for suspected polygenic diseases., (© 2020 European Academy of Dermatology and Venereology.)

Background: Atopic dermatitis (AD) patients have an altered skin bacterial community, with an abundance of Staphylococcus aureus associated with flares, highlighting that microbial organisms may be important for disease exacerbation. Despite strong evidence of association between bacterial skin colonisation and AD, very limited knowledge regarding the eukaryotic microbial community, including fungi and ectoparasites, in AD exists. In this study, we compared the skin and nasal eukaryotic microbial community between adult AD patients (n = 55) and non-AD healthy controls (n = 45) using targeted 18S rRNA amplicon sequencing. Analysis was based on the presence or absence of eukaryotic microorganisms., Results: The cutaneous composition of the eukaryotic microbial community and the alpha-diversity differed significantly between AD patients and non-AD individuals, with increased species richness on AD skin. Alpha-diversity and beta-diversity were similar on lesional and non-lesional skin of patients. The ectoparasite Demodex folliculorum and the yeast Geotrichum candidum were significantly more prevalent on the skin of AD patients. The prevalence of D. folliculorum on lesional skin was greater among patients recently treated with topical corticosteroid. Malassezia was one of the most frequently detected genera at all sites, with M. globosa and M. restricta being the most prevalent. M. restricta was under represented in the anterior nares of AD patients as compared to the non-AD control population., Conclusion: Significant differences in the eukaryotic microbial communities were found between AD patients and non-AD individuals, with the most striking finding being the significantly overrepresentation of D. folliculorum on AD skin. Whether D. folliculorum can contribute to skin inflammation in AD needs further investigation.

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., (Copyright © 2020. Published by Elsevier B.V.)

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., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Tinea capitis (TC) is a fungal infection of the hair and scalp. It mainly affects children, and treatment requires an extensive regimen including oral therapy, antifungal creams, and shampoo, as well as disinfection of fomites, bed linen, and clothes. Family members to patients with TC need prophylactic treatment to limit spread of the infection. Adherence to therapy in TC is time consuming, and the disease may cause psychosocial impairment to the caregivers. In this study, we performed interviews with parents to children with TC to identify factors related to treatment adherence and psychosocial implications from the parent's perspective. The interviews were performed and recorded at a dermatology outpatient clinic in Roskilde, Denmark (2018-2019). A total of 11 families agreed to participate in the study. The families had one to four affected children (age range: 1-14 years). We found that the key factors affecting adherence were the level of cooperation between the child and their parent, lack of symptoms in family members, and language barrier. The psychosocial well-being of parents was negatively affected due to fear of stigma and the time spent on treatment. Our study emphasizes the need for proper treatment instructions and psychosocial support of the parents by healthcare professionals., (© 2020 Wiley Periodicals LLC.)

Background: The possible connection between hidradenitis suppurativa (HS) patients undergoing surgery and higher complications/recurrences has been implied, but inconsistent results reported., Objective: To assess the complication and recurrence rates for HS patients undergoing surgery and to evaluate whether known HS comorbidities and habits (smoking, obesity and diabetes) have an effect on the complication and recurrence rates., Materials and Methods: A systematic review was conducted by 2 reviewers. PubMed and Embase were searched using a predefined search string created in collaboration between the authors and a librarian on January 23, 2019., Results: Of the 271 references in the original search, 54 relevant articles were identified. This systematic review indicates an overall mean complication rate of 24% and a mean recurrence rate of 20.1% for HS patients undergoing surgery., Conclusion: No significant association between the known surgical risk factors and surgical complications-or recurrence rates in this patient group was found. This review revealed a lack of quality and quantity data in studying the complications/recurrences. The heterogeneity of the studies created limitations, and the presented mean complication/recurrence rates should be interpreted with the consequences thereof. It elucidates the need for better studies and a necessity for a standardized definition of postsurgical HS recurrence.

Superficial fungal infections have been known for hundreds of years. During the 20th century new diagnostic methods were developed and the taxonomy changed several times, which, unfortunately, resulted in many fungi having several names (synonyms). The taxonomy is important, as species-specific identification guides clinicians when choosing the most appropriate antifungal agent, and provides an indication of the source of infection (anthropophilic, zoophilic or geophilic). Traditional diagnostic tests (direct microscopy, culture and histopathology) are still widely used, but molecular-based methods, such as PCR, have many advantages, and increasingly supplement or replace conventional methods. Molecular-based methods provide detection of different genus/species spectra. This paper describes recent changes in dermatophyte taxonomy, and reviews the currently available diagnostics tools, focusing mainly on commercially available PCR test systems.

Yeasts of the genus, Malassezia , formerly known as Pityrosporum , are lipophilic yeasts, which are a part of the normal skin flora (microbiome). Malassezia colonize the human skin after birth and must therefore, as commensals, be normally tolerated by the human immune system. The Malassezia yeasts also have a pathogenic potential where they can, under appropriate conditions, invade the stratum corneum and interact with the host immune system, both directly but also through chemical mediators. The species distribution on the skin and the pathogenetic potential of the yeast varies between different Malassezia related diseases such as head and neck dermatitis, seborrheic dermatitis, pityriasis versicolor, and Malassezia folliculitis. The diagnostic methods used to confirm the presence of Malassezia yeasts include direct microcopy, culture based methods (often a combination of morphological features of the isolate combined with biochemical test), molecular based methods such as Polymerase Chain Reaction techniques, and Matrix Assisted Laser Desorption/Ionization-Time Of Flight mass spectrometry and the chemical imprint method Raman spectroscopy. Skin diseases caused by Malassezia are usually treated with antifungal therapy and if there are associated inflammatory skin mechanisms this is often supplemented by anti-inflammatory therapy. The aim of this paper is to provide an overview of Malassezia related skin disease, diagnostic methods and treatment options., (Copyright © 2020 Saunte, Gaitanis and Hay.)

Onychomycosis is the most common cause of nail changes accounting for about half of all nail diseases. It is important to diagnose the fungal pathogen to prescribe adequate treatment, but as genus- and species-specific diagnostic tests can be time consuming and expensive, it is crucial to obtain representative tissue during nail scrapings. Optical coherence tomography (OCT) is a non-invasive imaging tool enabling real-time imaging of skin and tissue. Pilot studies using OCT have described morphological characteristics of onychomycosis, though diagnostic criteria of onychomycosis and other nail diseases are lacking. The aim of this study is to investigate the applicability of OCT to detect and localize fungal elements in nails with clinical signs of onychomycosis. OCT scans and nail scrapings were performed on all participants and only confirmed cases of onychomycosis were included in the data analysis. All scans were analyzed, and a set of morphological criteria based on known literature and deviations from healthy nail morphology were suggested. The suggested morphological features were: hyperreflective lines divided into sharply and diffusely demarcated; hyperreflective dots divided into singular and clustered patterns; irregular surface, divided into mild, moderate and severe degree; dark bands and disturbed architecture. The suggested OCT morphology is a refinement of previous studies, and though OCT cannot replace genus- or species-specific identification, it could be a useful assistance tool to increase diagnostic sensitivity of nail scrapings and laboratory tests as well as for monitoring treatment response.

Cutaneous candidiasis is a common skin disease, and several treatments have been investigated within the last fifty years. Yet, systematic reviews are lacking, and evidence-based topical and systemic treatment strategies remain unclear. Thus, the aim of this review was to summarize efficacy and adverse effects of topical and oral therapies for cutaneous candidiasis in all age groups. Two individual researchers searched PubMed and EMBASE for 'cutaneous candidiasis' and 'cutaneous candidiasis treatment', 'intertrigo', 'diaper dermatitis' and 'cheilitis'. Searches were limited to 'English language', 'clinical trials' and 'human subjects', and prospective clinical trials published in abstracts or articles were included. In total, 149 studies were identified, of which 44 were eligible, comprising 41 studies of 19 topical therapies and four studies of three systemic therapies for cutaneous candidiasis. Topical therapies were investigated in infants, children, adolescents, adults and elderly, while studies of systemic therapies were limited to adolescents and adults. Clotrimazole, nystatin and miconazole were the most studied topical drugs and demonstrated similar efficacy with complete cure rates of 73%-100%. Single-drug therapy was as effective as combinations of antifungal, antibacterial and topical corticosteroid. Four studies investigated systemic therapy, and oral fluconazole demonstrated similar efficacy to oral ketoconazole and topical clotrimazole. Limitations to this review were mainly that heterogeneity of studies hindered meta-analyses. In conclusions, clotrimazole, nystatin and miconazole were the most studied topical drugs and demonstrated equal good efficacy and mild adverse effects similar to combinations of antifungal, antibacterial and topical corticosteroids. Oral fluconazole was as effective as topical clotrimazole and is the only commercially available evidence-based option for systemic treatment of cutaneous candidiasis., (© 2019 European Academy of Dermatology and Venereology.)

In recent years, cases involving terbinafine-resistant Trichophyton isolates have been reported increasingly, particularly in India. We present 14 cases of terbinafine treatment failure in Trichophyton -infected Danish patients due to acquired resistance. Patients infected with Trichophyton rubrum ( n  = 12) or Trichophyton interdigitale ( n  = 2) with elevated terbinafine MICs during 2013-2018 were included. Antifungal susceptibility testing (AFST) was performed following a modified EUCAST E.Def 9.3.1 method (5 days of incubation) with or without cycloheximide and chloramphenicol (CC) supplementation of the growth medium. The squalene epoxidase (SE) target gene was sequenced, and 3-dimensional enzyme homology modeling was performed. Most patients (12/14 [86%]) were male. The mean age was 53.5 years (range, 11 to 77 years). The mean duration of infections was 4.8 years at the time of resistance detection. Prior systemic terbinafine treatment was documented for all patients, and topical therapy for 62% (information was missing in one case). Overall, nine isolates (64%) displayed high terbinafine resistance (MICs, 4 to >8 mg/liter), while two (14%) displayed moderate (MICs, 1 to 2 mg/liter) and three (21%) displayed low (MICs, 0.125 to 0.25 mg/liter) terbinafine resistance compared with control isolates. MICs generated with or without CC supplementation were similar, but CC prevented contamination. Known and novel SE amino acid substitutions (F397L, L393F, L393S, F415S, H440Y F484Y, and I121M V237I) were detected in resistant but not control isolates. Three-dimensional homology modeling suggested a role of the novel I121M and V237I alterations. Terbinafine resistance has been detected in Denmark using a modified EUCAST method, which facilitated susceptibility testing of dermatophytes. Action is needed for this emerging public health problem., (Copyright © 2019 American Society for Microbiology.)

The zoophilic dermatophyte Trichophyton benhamiae has received attention due to increasing infections in human in recent years. Trichophyton benhamiae has been found on asymptomatic rodents from pet shops in several countries posing a potential risk for transmission to humans. The aim of this study was to determine the prevalence of positive dermatophyte cultures from rodents in Danish pet shops in order to clarify the magnitude of potential sources of zoophilic infections and to prevent further spread. Specimen sampling was performed in 17 Danish pet shops using the brush technique (MacKenzie technique). After incubation, cultures were sent to ITS DNA sequencing for molecular species identification. Pet shop employees were asked to fulfil a five-question survey regarding purchase and procedures of diseased animals. A total of 98 animals were sampled (N = 32 rabbits, N = 32 guinea pigs and N = 34 hamsters). Trichophyton benhamiae was found in 14/98 samples (14%); 12/32 guinea pigs (38%) were positive with T benhamiae, 2/34 (6%) hamsters and 0/32 rabbits (0%). We found that hamsters and particularly guinea pigs from Danish pet shops are common asymptomatic carriers of the dermatophyte T benhamiae. Although a larger study is warranted to test this postulate, and it raises the question if infection control measures should be implemented in pet shops., (© 2019 Blackwell Verlag GmbH.)

Background: Superficial fungal infections are common. It is important to confirm the clinical diagnosis by mycological laboratory methods before initiating systemic antifungal treatment, especially as antifungal sensitivity and in vitro susceptibility may differ between different genera and species. For many years, the gold standard for diagnosis of superficial fungal infections has been direct fungal detection in the clinical specimen (microscopy) supplemented by culturing. Lately, newer molecular based methods for fungal identification have been developed., Objective: This study was initiated to focus on the current usage of mycological diagnostics for superficial fungal infections by dermatologists. It was designed to investigate whether it was necessary to differentiate between initial diagnostic tests and those used at treatment follow-up in specific superficial fungal infections., Methods: An online questionnaire was distributed among members of the EADV mycology Task Force and other dermatologists with a special interest in mycology and nail disease., Results: The survey was distributed to 62 dermatologists of whom 38 (61%) completed the whole survey, 7 (11%) partially completed and 17 (27%) did not respond. Nearly, all respondents (82-100%) said that ideally they would use the result of direct microscopy (or histology) combined with a genus/species directed treatment of onychomycosis, dermatophytosis, Candida- and Malassezia-related infections. The majority of the dermatologists used a combination of clinical assessment and direct microscopy for treatment assessment and the viability of the fungus was considered more important at this visit than when initiating the treatment. Molecular based methods were not available for all responders., Conclusion: The available diagnostic methods are heterogeneous and their usage differs between different practices as well as between countries. The survey confirmed that dermatologists find it important to make a mycological diagnosis, particularly prior to starting oral antifungal treatment in order to confirm the diagnose and target the therapy according to genus and species., (© 2018 European Academy of Dermatology and Venereology.)