S1 Guideline onychomycosis

Onychomycosis is a fungal infection of the fingernails and toenails. In Europe, tinea unguium is mainly caused by dermatophytes. The diagnostic workup comprises microscopic examination, culture and/or molecular testing (nail scrapings). Local treatment with antifungal nail polish is recommended for mild or moderate nail infections. In case of moderate to severe onychomycosis, oral treatment is recommended (in the absence of contraindications). Treatment should consist of topical and systemic agents. The aim of this update of the German S1 guideline is to simplify the selection and implementation of appropriate diagnostics and treatment. The guideline was based on current international guidelines and the results of a literature review conducted by the experts of the guideline committee. This multidisciplinary committee consisted of representatives from the German Society of Dermatology (DDG), the German‐Speaking Mycological Society (DMykG), the Association of German Dermatologists (BVDD), the German Society for Hygiene and Microbiology (DGHM), the German Society of Pediatric and Adolescent Medicine (DGKJ), the Working Group for Pediatric Dermatology (APD) and the German Society for Pediatric Infectious Diseases (DGPI). The Division of Evidence‐based Medicine (dEBM) provided methodological assistance. The guideline was approved by the participating medical societies following a comprehensive internal and external review

Molekulare Systematik und Evolution der Spezies der Familie Arthrodermataceae (Dermatophyten)

Dermatophyten sind keratinophile Pilze, d.h. sie besiedeln und infizieren die Haut und ihre Anhangsgebilde (Haare, Nägel) bei Mensch und Tier. Die derzeit häufigsten durch Dermatophyten hervorgerufenen Infektionen sind die Onychomykose, Tinea pedis, Tinea capitis und Tinea corporis. Da Antimykotika nicht bei alle Erregern von Dermatophytosen gleich wirksam sind, sollte im Vordergrund einer Behandlung zunächst die korrekte Erregerdifferenzierung stehen. Konventionell erfolgt diese Differenzierung über morphologische Merkmale wie Form und Farbe der auf dem Nährmedium gewachsenen Pilzkolonie, charakteristische mikromorphologische Elemente (Konidien) und biochemische Eigenschaften. Diese Merkmale werden jedoch oftmals nicht exprimiert. Damit ist in diesen Fällen keine Speziesdiagnose möglich. Eine zuverlässige Diagnostik sollte zudem das natürliche Klassifizierungssystem direkt reflektieren. Die Studien zur molekularen Biodiversität innerhalb der Dermatophyten sollten deshalb zur Klärung evolutionärer, taxonomischer und populationsgenetischer Zusammenhänge bei den verschiedenen Spezies der Gattungen Arthroderma, Trichophyton, Microsporum und Epidermophyten beitragen und helfen, geeignete DNA-Marker für die Anwendung in der medizinischen Diagnostik zu finden und einzusetzen. Dazu wurden verschiedene Methoden und Zielsequenzen genutzt, wie die Sequezierung der internal transcribed spacer (ITS) Region der ribosomalen DNA, das PCR-Fingerprinting, single strand conformation polymorphism (SSCP) und amplified fragment length polymorphism (AFLP)-Analyse. Es wurden weit über 200 Stämme, die bisher ca. 100 verschiedenen Taxa zuzuordnen waren, analysiert. Die molekularen Studien zeigen, dass die phylogenetisch ältesten Dermatophytenspezies geophil sind und sich die wärmeliebenden, zoophilen Arten erst später durch Koevolution mit warmblütigen Tieren entwickelt haben. Die anthropophilen scheinen dagegen erst mit Entstehung des Menschen evolviert und demzufolge am jüngsten zu sein. Damit kann man ihre geringe Biodiversität und ihr verändertes pathogenetisches Verhalten erklären. Es konnte gezeigt werden, dass die molekularen Phylogenie der Spezies besser mit ihrer Ökologie und dem Krankheitsbild als mit morphologischen Eigenschaften übereinstimmt und dass etliche Dermatophytenspezies überklassifiziert sind. Aus diesem Grunde wurde eine neue Systematik vorgeschlagen. Für den Nachweis des häufigsten Erreger, Trichophyton rubrum wurde eine Gensonde entwickelt, die in der medizinischen Diagnostik einsetzbar ist.Dermatophytes are keratinophilic fungi which colonise and infect skin, hair and nails of man and animals. The most common infections caused by dermatophytes are onychomycosis, tinea pedis, tinea capitis and tinea corporis. Antimycotics may have different spectra of activity even in related dermatophyte species. Therefore a correct species identification is necessary before onset of antifungal therapy. Conventionally, the identification of dermatophytes is performed by the use of morphological features, such as shape and colour of the colony, micromorphological characteristics (conidia) and biochemical properties. However, these characters may not be expressed and then identification down to the species level is frequently impossible. Reliable diagnostics directly reflects the natural system. Studies of biodiversity in dermatophytes should therefore focus on elucidation of the connection of evolution, taxonomy and population genetics of the species of the genera Arthroderma, Trichophyton, Microsporum and Epidermophyten and thus contribute to development of stable DNA markers to be applied in routine diagnostics. Several methods and targets were applied such as sequencing of the internal transcribed spacer region (ITS) of the ribosomal DNA, PCR fingerprinting, single strand conformation polymor phism (SSCP) and amplified fragment length polymorphism (AFLP) analysis. More than 200 strains belonging to about 100 dermatophyte taxa were analysed. Phylogenetically, the molecular data show the oldest dermatophyte species to be geophilic and subsequently co-evolved as zoophilic dermatophytes with warm blooded animals. In contrast, the anthropophilic dermatophytes are much younger as they evolved in association with humans. This hypothesis is supported by their low biodiversity and changing pathogenicity. The molecular data show correspondence between phylogeny of species and their ecology and clinical picture, rather than with morphological features. Many dermatophyte species were shown to be overclassified. A new systematic system was proposed. For the identification of Trichophyton rubrum, the most common dermatophyte species, an oligonucleotide probe was developed which is applicable in medical routine diagnostics

A Hundred Years of Diagnosing Superficial Fungal Infections:Where Do We Come From, Where Are We Now and Where Would We Like To Go?

Superficial fungal infections have been known for hundreds of years. During the 20(th) 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

Trichophyton eboreum sp. nov. Isolated from Human Skin

An unusual dermatophyte was isolated from the plantar scales of a human immunodeficiency virus-positive man with tinea pedis. Morphology, physiology, and molecular data provided evidence to support the new species Trichophyton eboreum. This dermatophyte is characterized by rapid growth on common mycological media, a flat powdery off-white colony, formation of clavate microconidia, smooth- and thin-walled cylindrical or club-shaped macroconidia with two to nine cells, the presence of hook-shaped hyphae, the production of cleistothecium-like structures and spiral hyphae in older cultures, positive hair perforation, the absence of pigmentation on potato glucose agar, the absence of a requirement for vitamins, a weak positive urease reaction, no growth at 37°C, resistance to 5% NaCl, resistance to fluconazole, good growth on human epidermal keratin, and the production of various enzymes on different media by the API-ZYM test. More than 5% divergence from any known species of dermatophyte was revealed by sequence analysis of the internal transcribed spacer of the rRNA gene

German-Wide Analysis of the Prevalence and the Propagation Factors of the Zoonotic Dermatophyte Trichophyton benhamiae

For about 10 years, a new variant of the pathogen Trichophyton (T.) benhamiae has appeared in Germany, characterized by a previously unobserved culture phenotype with a strong yellow reverse. A few studies suggest that this new variety is now the most common zoophilic dermatophyte in Germany. The guinea pig is the main carrier. Exact prevalence measurements are not yet available. Thus, the aim of our ongoing study was to collect data on the frequency and geographic distribution of the pathogen and its phenotypes (white and yellow) in humans and guinea pigs throughout Germany. Our former studies have already shown that animals from large breeding farms are particularly heavily affected. In contrast to this, 21 small, private breedings were sampled and husbandry conditions recorded. This placed us in a position to identify propagation factors and to give recommendations for containment. For animals from private breedings, we detected T. benhamiae with a prevalence of 55.4%, which is a reduction of nearly 40% compared with animals from large breeding farms. As risk factors, we identified the type of husbandry and the contact to other breedings. Furthermore, certain animal races, like Rex guinea pigs and races with long hair in combination with curls were predestined for colonization with T. benhamiae due to their phenotypic coat characteristics. A prevalence for infections with T. benhamiae of 36.2% has been determined for symptomatic pet guinea pigs suspected of having dermatophytosis and is comparable to the study of Kraemer et al. showing a prevalence of 34.9% in 2009 in Germany. The prevalence in humans is stable with about 2-3% comparing the data of 2010-2013 and 2018 in Thuringia. The new type of T. benhamiae was by far the most frequent cause in all settings

Polyphasic Discrimination of Trichophyton tonsurans and T. equinum from Humans and Horses

The anthropophilic dermatophyte Trichophyton tonsurans and its zoophilic counterpart T. equinum are phylogenetically closely related. The barcoding marker rDNA internal transcribed spacer (ITS) shows limited variation between these two species. In the current study, we combined molecular approaches with phenotypic data to determine the species boundaries between T. tonsurans (n = 52) and T. equinum (n = 15) strains originating from humans (n = 40), horses (n = 26), and a mouse (n = 1). Culture characteristics and physiology on Trichophyton agar media 1 and 5 were evaluated. Multi-locus sequencing involving ITS, partial large rDNA subunit (LSU), β-tubulin (TUB), 60S ribosomal protein (RPB), and translation elongation factor-3 (TEF3) genes, and the mating-type (MAT) locus was performed. Amplified fragment length polymorphism data were added. None of the test results showed complete mutual correspondence. With the exception of strains from New Zealand, strains of equine origin required niacin for growth, whereas most strains from human origin did not show this dependence. It is concluded that T. tonsurans and T. equinum incompletely diverged from a common lineage relatively recently. MAT1-1 and MAT1-2 are the main distinguishing genes between the two species

<i>Trichophyton indotineae</i>—An Emerging Pathogen Causing Recalcitrant Dermatophytoses in India and Worldwide—A Multidimensional Perspective

Trichophyton (T.) indotineae is a newly identified dermatophyte species that has been found in a near-epidemic form on the Indian subcontinent. There is evidence of its spread from the Indian subcontinent to a number of countries worldwide. The fungus is identical to genotype VIII within the T. mentagrophytes/T. interdigitale species complex, which was described in 2019 by sequencing the Internal Transcribed Spacer (ITS) region of ribosomal DNA of the dermatophyte. More than 10 ITS genotypes of T. interdigitale and T. mentagrophytes can now be identified. T. indotineae causes inflammatory and itchy, often widespread, dermatophytosis affecting the groins, gluteal region, trunk, and face. Patients of all ages and genders are affected. The new species has largely displaced other previously prevalent dermatophytes on the Indian subcontinent. T. indotineae has become a problematic dermatophyte due to its predominantly in vitro genetic resistance to terbinafine owing to point mutations of the squalene epoxidase gene. It also displays in vivo resistance to terbinafine. The most efficacious drug currently available for this terbinafine-resistant dermatophytoses, based on sound evidence, is itraconazole