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The diagnostic workup of cutaneous fungal infections is traditionally based on microscopic KOH preparations as well as culturing of the causative organism from sample material. Another possible option is the detection of fungal elements by dermatohistology. If performed correctly, these methods are generally suitable for the diagnosis of mycoses. However, the advent of personalized medicine and the tasks arising therefrom require new procedures marked by simplicity, specificity, and swiftness. The additional use of DNA-based molecular techniques further enhances sensitivity and diagnostic specificity, and reduces the diagnostic interval to 24-48 hours, compared to weeks required for conventional mycological methods. Given the steady evolution in the field of personalized medicine, simple analytical PCR-based systems are conceivable, which allow for instant diagnosis of dermatophytes in the dermatology office (point-of-care tests).

Die verschiedenen klinischen Manifestationsformen mukokutaner Mykosen zu erkennen und zu diagnostizieren sowie die entsprechende Therapie einzuleiten ist Teil des Praxisalltags eines jeden Dermatologen. Nur wenn Klinik, Diagnostik und Therapie in einer Hand liegen, ist gewahrleistet, dass die erhobenen Laborbefunde auch richtig eingeordnet und interpretiert werden. Nach dem Inkrafttreten der neuen Richtlinien zu Qualitatssicherung laboratoriumsmedizinischer Untersuchungen durch die Bundesarztekammer besteht nun vielerorts unter Dermatologen Unsicherheit, wie diese qualitatssichernden Masnahmen im Bereich der Mykologie umgesetzt werden konnen. Die Autoren mochten dem Leser hierzu Hilfestellung geben und hoffen, so dazu beizutragen, dass die mykologische Diagnostik auch in Zukunft beim praktisch tatigen Dermatologen verbleibt.

Chronic recalcitrant dermatophytoses, due to Trichophyton (T.) mentagrophytes Type VIII are on the rise in India and are noteworthy for their predominance. It would not be wrong to assume that travel and migration would be responsible for the spread of T. mentagrophytes Type VIII from India, with many strains resistant to terbinafine, to other parts of the world. From September 2016 until March 2020, a total of 29 strains of T. mentagrophytes Type VIII (India) were isolated. All patients were residents of Germany: 12 females, 15 males and the gender of the remaining two was not assignable. Patients originated from India (11), Pakistan (two), Bangladesh (one), Iraq (two), Bahrain (one), Libya (one) and other unspecified countries (10). At least two patients were German-born residents. Most samples (21) were collected in 2019 and 2020. All 29 T. mentagrophytes isolates were sequenced (internal transcribed spacer (ITS) and translation elongation factor 1-&alpha, gene (TEF1-&alpha, )). All were identified as genotype VIII (India) of T. mentagrophytes. In vitro resistance testing revealed 13/29 strains (45%) to be terbinafine-resistant with minimum inhibitory concentration (MIC) breakpoints &ge, 0.2 &micro, g/mL. The remaining 16 strains (55%) were terbinafine-sensitive. Point mutation analysis revealed that 10/13 resistant strains exhibited Phe397Leu amino acid substitution of squalene epoxidase (SQLE), indicative for in vitro resistance to terbinafine. Two resistant strains showed combined Phe397Leu and Ala448Thr amino acid substitutions, and one strain a single Leu393Phe amino acid substitution. Out of 16 terbinafine-sensitive strains, in eight Ala448Thr, and in one Ala448Thr +, new Val444 Ile amino acid substitutions were detected. Resistance to both itraconazole and voriconazole was observed in three out of 13 analyzed strains. Treatment included topical ciclopirox olamine plus topical miconazole or sertaconazole. Oral itraconazole 200 mg twice daily for four to eight weeks was found to be adequate. Terbinafine-resistant T. mentagrophytes Type VIII are being increasingly isolated. In Germany, transmission of T. mentagrophytes Type VIII from the Indian subcontinent to Europe should be viewed as a significant public health issue.

An alarming pan Indian increase in the incidence of superficial dermatophytosis has been noticed over the past 5-6 years. Recent studies have demonstrated emerging predominance of Trichophyton (T.) mentagrophytes as the causative organism in such cases. Interestingly, a distinct Indian genotype of T. mentagrophytes has been identified and recognised with the help of sequencing of the ITS region of the rDNA. That has, however, led to a basic confusion owing to the newly introduced taxonomy of dermatophytes in 2017. According to this most recently suggested classification and new taxonomy of dermatophytes, the former "T. mentagrophytes complex" is differentiated into T. mentagrophytes (zoophilic strains) and T. interdigitale (anthropophilic strains). We have noticed that in some recent studies the causative agent of the chronic, relapsing dermatophytosis outbreak in India has been described as T. interdigitale. In our opinion, it is very likely that these T. interdigitale strains isolated in Delhi and Chennai in India are indeed strains more closely related to the neotype of T. mentagrophytes and not strains of T. interdigitale. We therefore want to underscore the importance of a common nomenclature of species in accordance with the new taxonomy of dermatophytes. This would most likely facilitate better understanding of the issue amongst dermatologists and microbiologists in general. Mistaken identification of Trichophyton isolates not limited to India is very likely to occur due to the lack of appropriate molecular diagnosis which in turn is based on the already published data that presumably wrongly identify one species instead of the other.

Moulds and yeasts, so-called dimorphic fungi, cause a number of cutaneous infections. Transmission takes place via inoculation of the agents as a result of injury, e.g. following barefoot walking in semiarid to arid areas, or through haematogenous spread, mostly from the lung. Examples for inoculation mycoses are mycetomas caused by various fungi and bacteria, chromoblastomycoses due to melanized or brown-pigmented fungi and sporotrichosis due to Sporothrix schenckii, a ubiquitous occurring dimorphic fungus. Secondary cutaneous involvement after haematogenous transmission occurs in blastomycosis, coccidioidomycosis, cryptococcosis and histoplasmosis, frequently in immunosuppressed patients.

BACKGROUND Microsporum (M.) canis, whose source of infection is mostly cats, is still considered as the most frequently occurring zoophilic dermatophyte in Germany and Europe. In distinct areas of Germany, the zoophilic dermatophyte Trichophyton (T.) anamorph of Arthroderma (A.) benhamiae also presents a frequent and emerging causative agent of dermatophytoses. MATERIALS AND METHODS Over a period of 3 years, from March 2010 to March 2013, skin samples from scalp, face, trunk, and limbs were investigated using mycological cultivation and by polymerase chain reaction (PCR) for dermatophytes. Materials originated in particular from the German Free States Saxony and Thuringia, and from the Federal State Saxony-Anhalt, but also included samples submitted from around Germany. The cultural detection of dermatophytes was performed on Sabouraud's 4% glucose agar with and without cycloheximide. For dermatophyte DNA detection, a uniplex PCR-ELISA was used. RESULTS In all, 8464 samples from a total of 7680 patients were investigated. In 114 (1.5%) of 7680 patients, M. canis could be detected both by culture and/or PCR. M. canis was detected culturally in 100 samples, in 107 samples by PCR, in 91 samples both culturally and by PCR. For 12 patients, only cultural detection was done (without PCR). Also detected was tinea corporis due to M. canis in 59 patients, tinea capitis 8, tinea faciei 5, and tinea manus 2 patients. Of the patients, 45% were younger than 20 years, 42% were 20-49 years old, and 13% were 50 years or older. In comparison, T. anamorph of A. benhamiae was detectable by culture and/or PCR in 231 of 7680 patients (2.9%). M. canis was the second most common zoophilic dermatophyte. CONCLUSIONS M. canis is still a frequent zoophilic dermatophyte in Germany. Since a few years ago, a rise of infections due to T. anamorph of A. benhamiae has been observed in Germany and other European countries. At least in distinct regions of Germany, this zoophilic dermatophyte, which is transferred from guinea pigs to human beings, currently seems to be more frequent when compared to M. canis.

Zusammenfassung Die Behandlung der Dermatophytosen basiert auf dem klinischen Bild und dem mykologischen Erregernachweis. Die Onychomykose kann bei richtiger Indikationsstellung topisch mit antimykotischem Nagellack behandelt werden. Die atraumatische Nagelabrasion mit 40 % Harnstoff-Salbe hat einen gunstigen Einfluss auf die Heilung. Die kontinuierliche Behandlung der Onychomykose mit Terbinafin ist die wirksamste systemische Therapieform. Terbinafin oder Itraconazol sind die sichersten und wirksamsten Antimykotika zur Behandlung der Onychomykose im Kindesalter. Zur Lasertherapie der Onychomykose liegen bislang wenige Studien zur klinischen Wirksamkeit vor. Fur die Tinea capitis wird heute eine gezielte „Spezies-spezifische“ Therapie der Dermatophytosen des Kapillitiums empfohlen. Terbinafin, jedoch auch Itraconazol und Fluconazol sind wirksam bei Tinea capitis durch Trichophyton-Arten. Microsporum-Infektionen der Kopfhaut lassen sich am besten mit Griseofulvin behandeln, alternativ mit Itraconazol oder Fluconazol, Terbinafin ist weniger wirksam. Kutane intertriginose Candidosen werden mit Nystatin, aber auch mit Azolen oder Ciclopirox topisch antimykotisch behandelt. Die systemische Therapie erfolgt mit Fluconazol oder Itraconazol. Topische und systemisch applizierbare Antimykotika sind ebenburtige Therapieformen bei akuten Formen der vulvovaginalen Mykose. Mittel der Wahl zur Therapie der chronisch-rezidivierenden Vulvovaginalmykosen durch Candida albicans ist Fluconazol. Ketoconazol hat eine sehr gute Wirkung bei Pityriasis versicolor. Fur die systemische Behandlung bei ausgepragter grosflachiger Pityriasis versicolor ist Itraconazol das Mittel der Wahl.

Treatment of dermatophyte infections is based on the clinical picture and mycological detection of the causative pathogen. Based on the appropriate indication, onychomycosis can be treated topically using an antimycotic nail lacquer. Atraumatic nail abrasion with 40 % urea ointment has a beneficial effect on healing. Continuous treatment of onychomycosis with terbinafine represents the most effective systemic therapy. Terbinafine or itraconazole are the safest and most effective antimycotic agents for the treatment of onychomycosis in children. For laser therapy of onychomycosis, only a few studies on clinical efficacy are available. Regarding tinea capitis, targeted species-specific therapy of dermatophytosis of the scalp is currently recommended. Terbinafine, yet also itraconazole and fluconazole, are effective in tinea capitis caused by Trichophyton species. Microsporum infections of the scalp are preferably treated with griseofulvin, alternatively with itraconazole or fluconazole. Terbinafine is less effective. Candidal intertrigo are topically treated with nystatin, but azoles or ciclopirox olamine are also suitable candidates. Systemically, fluconazole or itraconazole are used. Topical and systemic antimycotics are equivalent forms of therapy in acute vulvovaginal mycosis. Fluconazole is the drug of choice in chronic recurrent vulvovaginal mycosis caused by Candida albicans. Ketoconazole shows very good efficacy in tinea versicolor. With respect to systemic treatment of severe and widespread tinea versicolor, itraconazole is the drug of choice.

Today, tropical and travel-related dermatomycoses must be increasingly anticipated to present in dermatological offices and clinics. Skin infections due to dermatophytes or other fungi may occur after a journey in countries with a high prevalence for the respective causative fungal pathogen, e.g., tinea corporis due to Trichophyton soudanense. Otherwise, more frequently, single infections and even localized outbreaks due to "exotic" or "imported" pathogens of dermatophytoses occur. These epidemics are observed in childcare facilities in Germany and in other European countries. Source of infection are immigrants from Africa and sometimes from Asian countries. Furthermore, African children, and sometimes also adults, are often only asymptomatic carriers of such anthropophilic dermatophytes. Outbreaks of dermatophyte infections with one and more affected children and also adult staff and teachers due to Trichophyton violaceum or Microsporum audouinii in kindergartens and schools are not a rarity these days. Further tropical and travel-associated dermatophytes are Trichophyton tonsurans, Trichophyton schoenleinii, and Trichophyton concentricum. Tinea capitis should be treated in a species-specific manner. Griseofulvin is the treatment of choice for infections due to Microsporum species. In contrast, tinea capitis due to Trichophyton species has to be treated by terbinafine, however, because the agent is not approved for children in Germany, only after receiving written consent of parents. Alternatives are fluconazole and itraconazole. Onset and aggravation of tinea pedis during travel has its origin in a preexisting neglected fungal infection of the feet. In the tropics, exacerbations and secondary bacterial complications of tinea pedis develop under distinctly promoting conditions.

Nannizzia praecox, formerly known as Microsporum praecox, is a geophilic dermatophyte. Up to now 31 cases of human tinea have been reported in the literature, most of them with an inflammatory course. Three recent cases diagnosed in Germany within 1 year suggest that the fungus might be a more common cause of human dermatophytosis than reported so far. This might be based on the fact that N. praecox is often found in an equine environment and that horse riding is becoming more popular recently.

Dermatophyte research has renewed interest because of changing human floras with changing socioeconomic conditions, and because of severe chronic infections in patients with congenital immune disorders. Main taxonomic traits at the generic level have changed considerably, and now fine-tuning at the species level with state-of-the-art technology has become urgent. Research on virulence factors focuses on secreted proteases now has support in genome data. It is speculated that most protease families are used for degrading hard keratin during nitrogen recycling in the environment, while others, such as Sub6 may have emerged as a result of ancestral gene duplication, and are likely to have specific roles during infection. Virulence may differ between mating partners of the same species and concepts of zoo- and anthropophily may require revision in some recently redefined species. Many of these questions benefit from international cooperation and exchange of materials. The aim of the ISHAM Working Group Dermatophytes aims to stimulate and coordinate international networking on these fungi.

Nucleic acid amplification techniques (NATs), such as PCR, are highly sensitive and specific methods that have become valuable supplements to culture and serology in the diagnosis of infectious disorders. However, especially when using formalin-fixed and paraffin-embedded tissue, these techniques are associated with both false-negative and false-positive results, a pitfall that is frequently misjudged. Representatives of the German Society of Hygiene and Microbiology (DGHM) and the German Society of Dermatology (DDG) therefore set out to develop a consensus - in the form of a review article - on the appropriate indications for NATs using paraffin-embedded tissue, its contraindications, and the key points to be considered in the pre- and post-analytical phase. Given that fresh, naive tissue is preferably to be used in the workup of a suspected infection, PCR analysis on paraffin sections represents an exception. The latter may be considered if an infection is suspected at a later point in time and fresh tissue has not been preserved or can no longer be obtained. Potential indications include confirmation of histologically suspected infections with Leishmania spp., Bartonella spp., Rickettsia spp., or in case of ecthyma contagiosum. Infections with, for example, mycobacteria or RNA viruses, on the other hand, are not considered useful indications for NATs using paraffin sections. In order to avoid misinterpretation of test results, it is essential that laboratory reports on NATs using paraffin-embedded tissue contain information on the indication/diagnostic circumstances, the required and chosen pre-analytical steps, the limitations of the method, and on diagnostic alternatives.

Nukleinsäure-Amplifikations-Techniken (NAT), wie die PCR, sind hochsensitiv sowie selektiv und stellen in der mikrobiologischen Diagnostik wertvolle Ergänzungen zur kulturellen Anzucht und Serologie dar. Sie bergen aber gerade bei formalinfixiertem und in Paraffin eingebettetem Gewebe ein Risiko für sowohl falsch negative als auch falsch positive Resultate, welches nicht immer richtig eingeschätzt wird. Daher haben Vertreter der Deutschen Gesellschaft für Hygiene und Mikrobiologie (DGHM) und der Deutschen Dermatologischen Gesellschaft (DDG) einen Konsensus in Form einer Übersichtsarbeit erarbeitet, wann eine NAT am Paraffinschnitt angezeigt und sinnvoll ist und welche Punkte dabei in der Präanalytik und Befundinterpretation beachtet werden müssen. Da bei Verdacht auf eine Infektion grundsätzlich Nativgewebe genutzt werden soll, ist die PCR am Paraffinschnitt ein Sonderfall, wenn beispielsweise bei erst nachträglichaufgekommenem Verdacht auf eine Infektion kein Nativmaterial zur Verfügung steht und nicht mehr gewonnen werden kann. Mögliche Indikationen sind der histologisch erhobene Verdacht auf eine Leishmaniose, eine Infektion durch Bartonellen oder Rickettsien, oder ein Ecthyma contagiosum. Nicht sinnvoll ist oder kritisch gesehen wird eine NAT am Paraffinschnitt zum Beispiel bei Infektionen mit Mykobakterien oder RNA-Viren. Die Konstellation für eine NAT aus Paraffingewebe sollte jeweils benannt werden, die erforderliche Prä-Analytik, die jeweiligen Grenzen des Verfahrens und die diagnostischen Alternativen bekannt sein. Der PCR-Befund sollte entsprechend kommentiert werden, um Fehleinschätzungen zu vermeiden.

The zoophilic dermatophyte Trichophyton verrucosum is the most important causative agent of bovine dermatophytosis. Additionally, it causes profound and poorly healing skin infections in humans indicating the high zoonotic potential. The objective of this study was to establish differentiation of T. verrucosum from other dermatophytes by mass spectrometry and to identify distinct features of the mass spectra. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was successful for identification of this pathogen only after extension of the database of the manufacturer with spectra from T. verrucosum strains, which were identified as such by sequencing of the internal transcribed spacer (ITS) region. MALDI-TOF MS analysis was conducted with 46 field isolates from cattle, two live vaccine strains, and 10 isolates from humans identified as T. verrucosum by sequence analysis of the ITS region. The results suggest a very good agreement of both methods. Comparison with the mass spectra of 68 strains of other keratinophilic fungi revealed that most T. verrucosum wild-type isolates showed a characteristic peak at 7950-7954 m/z, which was missing in the spectra of other keratinophilic fungi and the live vaccine strains. The spectra of T. verrucosum were most similar to the spectra of T. benhamiae, an emerging zoophilic dermatophyte. In summary, MALDI-TOF MS is a powerful and reliable tool to identify T. verrucosum.

Zusammenfassung Pilzinfektionen der Haut werden in Deutschland und weltweit am haufigsten durch Dermatophyten verursacht. Die Tinea pedis ist die haufigste Pilzinfektion in den Industriestaaten der westlichen Welt. Ausgehend von dieser Dermatophytose entwickelt sich eine Tinea unguium. Insbesondere bei alteren Patienten kommt es infolge Autoinokulation von der Tinea pedis et unguium zu Tinea-Formen der freien Haut. Die Tinea capitis tritt bei Erwachsenen selten auf. Dagegen gilt sie als haufigste Pilzinfektion im Kindesalter. Bei der antimykotischen Behandlung der Tinea unguium und der Tinea capitis kann ein Dermatophytid auftreten. Hefepilzinfektionen betreffen die Schleimhaut von Orointestinaltrakt und Genitalsystem. Die Candidose der Haut betrifft vorzugsweise die intertriginosen Regionen der Hautfalten. Dagegen ist die Pityriasis versicolor eine oberflachliche Pilzinfektion am Korperstamm. Schimmelpilzinfektionen sind selten und spielen fast nur bei der Onychomykose eine Rolle. Die Diagnostik von Dermatomykosen umfasst den mikroskopischen Pilznachweis mittels Kaliumhydroxid- bzw. alternativ fluoreszenzoptischem Blankophor-Praparat und den kulturellen Pilznachweis. Dem histologischen Pilznachweis mittels PAS-Farbung sollte aufgrund der hohen Empfindlichkeit insbesondere bei der Onychomykose-Diagnostik ein wesentlich hoherer Stellenwert zukommen. Mit der PCR, u. a. einem Dermatophyten-PCR-ELISA, lassen sich die Erreger direkt im klinischen Material spezifisch und hoch empfindlich nachweisen. Molekulare Methoden, auch die MALDI-TOF (matrix-assisted laser desorption ionization-time of flight)-Massenspektrometrie (MS) als Kulturbestatigungstest, erganzen die konventionelle mykologische Diagnostik.

Most fungal infections of the skin are caused by dermatophytes, both in Germany and globally. Tinea pedis is the most frequent fungal infection in Western industrial countries. Tinea pedis frequently leads to tinea unguium, while in the elderly, both may then spread causing tinea corporis. A variety of body sites may be affected, including tinea glutealis, tinea faciei and tinea capitis. The latter rarely occurs in adults, but is the most frequent fungal infection in childhood. Following antifungal treatment of tinea unguium and also tinea capitis a dermatophytid or hyperergic reaction to dermatophyte antigens may occur. Yeast infections affect the mucous membranes both of the gastro-intestinal system and the genital tract as candidiasis mostly due to Candida albicans. Cutaneous candidiasis affects predominantely the intertriginous regions such as groins and the inframammary area, but also the intertriginous space of fingers and toes. In contrast, pityriasis versicolor is a superficial epidermal fungal infection primarily on the the trunk. Mold infections are rare in dermatology; they play a role nearly exclusively in nondermatophyte-mold (NDM) onychomycosis. The diagnosis of dermatomycoses comprises the microscopic detection of fungi using the potassium hydroxide preparation or alternatively the fluorescence optical Blankophor preparation together with culture. The histological fungal detection with PAS staining possesses a high sensitivity, and it should play a more important role in particular for diagnosis of onychomycosis. Molecular biological methods, based on the amplification of fungal DNA with use of specific primers for the distinct causative agents are on the rise. With PCR, such as dermatophyte-PCR-ELISA, fungi can be detected directly in clinical material in a highly specific and sensitive manner without prior culture. Today, molecular methods, such as Matrix Assisted Laser Desorption/Ionization Time-Of-Flight Mass Spectrometry (MALDI TOF MS) as culture confirmation assay, complete the conventional mycological diagnostics.

Die Kopflaus kennt keine sozialen Unterschiede, hochkontagios kann sie sich in Kindergarten und Schulen rasch ausbreiten. Zunehmende Resistenzen gegenuber den gangigen Mitteln fuhren immer wieder zu Therapieversagen.

Bei Patienten, die sich in chemotherapeutischer Behandlung befinden, muss sowohl mit oberflachlichen als auch mit disseminierten tiefen Candidosen gerechnet werden. Dabei sind je nach Manifestation und Auspragung gezielte Masnahmen gefordert. Vor allem bei immunsupprimierten Patienten ist eine systemische antimykotische Behandlung unumganglich.

Zusammenfassung In Deutschland kommen seit einigen Jahren Infektionen durch den zoophilen Dermatophyten Trichophyton (T.) Spezies von Arthroderma benhamiae vor. Das Reservoir fur diesen neuen Erreger – ein emerging pathogen – uberlappt mit dem des zoophilen T. interdigitale. Insbesondere Meerschweinchen sind Carrier. T. Spezies von Arthroderma benhamiae verursacht eine entzundliche Tinea bei Kindern und Jugendlichen. Neben der Tinea capitis werden Tinea corporis und Tinea manus verursacht, vor allem jedoch die Tinea faciei. T. Spezies von Arthroderma benhamiae ist in Deutschland ein haufiger zoophiler Dermatophyt, in manchen Regionen haufiger als Microsporum canis. Die Identifizierung der Isolate mit gelb gefarbten Kolonien ist anhand makro- und mikroskopischer Merkmale moglich. Ein Teil der Isolate weist jedoch Koloniemerkmale auf, welche mit denen von T. interdigitale ubereinstimmen. Diese Stamme lassen sich nur mittels molekularer Methoden identifizieren. Mit einem PCR-ELISA oder real-time PCR kann der Dermatophyt direkt im klinischen Material nachgewiesen werden. Als Kulturbestatigungstest hat sich die Sequenzierung der internal transcribed spacer Region (ITS) der ribosomalen DNA bewahrt. Auch die matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI TOF MS) ist dafur geeignet. Die Behandlung von ausgedehnten Dermatophytosen durch T. Spezies von Arthroderma benhamiae, insbesondere der Tinea capitis, erfolgt mit oralen Antimykotika, am besten Terbinafin; Alternativen sind Fluconazol und Itraconazol.

The reason why the cutaneous form of sarcoidosis is well known in the literature is because of its spectrum of manifestations granting it the fame of a Great Imitator. The mystery shrouding the pathogenesis of this rare cutaneous disease is still there (in spite of the fundamental progress of the various diagnostic methods in current day medicine). The production of the morphological substrate – the epithelioid cell granuloma – which is considered to be characteristic of skin sarcoidosis, could, however, also be the end result of a reaction to i) various specific infectious agents such as Leishmaniasis cutis, coccidioidomycosis, etc., ii) certain residual bacterial or other mycobacterial antigens which, at the moment of setting the diagnosis are - by definition - non-infectious but still immunogenic, as well as iii) different tumor antigens in lesional tissue or other location. Often, differentiating between sarcodiosis and a sarcoid-like reaction, based on the updated criteria for cutaneous sarcoidosis, is problematic to downright impossible. A future characterization of the genetic signature of the two conditions, as well as the implementation of additional mandatory panels for i) the identification of certain infectious or ii) non-infectious but immunogenic and iii) tumor antigens in the epithelioid cell granuloma (or in another location in the organism), could be a considerable contribution to the process of differentiating between the two above-mentioned conditions. This will create conditions for greater accuracy when setting the subsequent therapeutic approaches.

In Germany, infections due to the zoophilic dermatophyte Trichophyton (T.) species of Arthroderma benhamiae are being more frequently diagnosed. The source of infection of this emerging pathogen overlaps with that of the zoophilic species T. interdigitale. The most common source are guinea pigs. T. species of Arthroderma benhamiae causes inflammatory dermatophytosis in children and adolescents. In addition to tinea capitis, it may cause both tinea corporis, tinea manus and frequently tinea faciei. In Germany, T. species of Arthroderma benhamiae is a frequent zoophilic dermatophyte, which in regions is probably more frequent than Microsporum canis. The mycological identification of the isolates with their yellow stained colonies is based on their macroscopic and microscopic features. However, some exhibit colony features consistent with those of T. interdigitale. These strains only can be identified unambiguously by means of molecular techniques. Using detection methods such as PCR-ELISA or real-time PCR, the dermatophyte can be identified directly from clinical material. Sequencing of the internal transcribed spacer region (ITS) of the ribosomal DNA has been approved as culture confirmation test for T. species of Arthroderma benhamiae. In addition, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI TOF MS) is useful. Widespread dermatophytosis due to T. species of Arthroderma benhamiae, in particular of tinea capitis, requires oral antifungal agents. Terbinafine is most effective, alternatives are fluconazole and itraconazole.

Hintergrund Kutane Fusarium-Infektionen treten sekundar infolge hamatogener Aussaat bei einer systemischen Infektion auf, oder sie sind primare kutane Infektionen nach traumatischer Inokulation.

Nagelpilz ist eine alte Krankheit. Bereits 1853 gelang dem Gottinger Medizinstudenten Georg Meissner die Entdeckung der pilzlichen Ursache der Erkrankung [1]. Rudolf Virchow nannte sie „Onychomykose“ [2]. Die Genialitat dieses Begriffes besteht darin, dass darunter alle infrage kommenden Erreger eingeschlossen werden konnen: Dermatophyten, Hefen und Schimmelpilze.

Infektionen der Finger- und Zehennagel werden am haufigsten durch Pilze verursacht, an erster Stelle durch Dermatophyten. Erreger der Tinea unguium sind in der Regel anthropophile Dermatophyten. Trichophyton rubrum ist in Deutschland und weltweit bei der Onychomykose nach wie vor der wichtigste Erreger. Hefepilze werden jedoch viel haufiger als vermutet bei Nagelpilzinfektionen – sowohl der Paronychie als auch einer Onychomykose – isoliert. Es handelt sich entweder um eine saprophytare Besiedlung der Nagel oder – gar nicht selten – auch um eine akute oder chronische Infektion des Nagelapparates. Wichtigste Erreger sind Candida parapsilosis und Candida guilliermondii, erst auf dem dritten Rang folgt Candida albicans. Onychomykosen durch Schimmelpilze oder sog. „non-dermatophyte molds“ (NDM) werden zunehmend nachgewiesen. Es handelt sich dabei teilweise um als sog. „emerging pathogen“ angesehene Erreger, an erster Stelle Fusarium-Arten, aber auch um seltene Schimmelpilze wie Onychocola canadensis. Bakterielle Infektionen der Nagel werden durch Gram-negative Bakterien, an erster Stelle Pseudomonas aeruginosa (erkennbar an der grunlich schwarzen Verfarbung der Nagel), aber auch durch Klebsiella spp. und durch Gram-positive Bakterien, z. B. Staphylococcus aureus, verursacht. Die Behandlung der Onychomykose erfolgt mit lokalen Antimykotika (Amorolfin, Ciclopirox), bei Befall von mehr als 50 % der Nagelplatte bzw. bei Befall von mehr als 3 von 10 Nageln systemisch mit Terbinafin (bei Dermatophyteninfektionen), Fluconazol (bei Hefepilzinfektionen) oder alternativ mit Itraconazol. Bei bakteriellen Infektionen kommen antiseptische (Octenidin), im Einzelfall auch antibiotische (Nadifloxacin, Gentamicin) Wirkstoffe zur Anwendung. Systemisch wird bei Pseudomonas-Infektionen des Nagelapparates mit Ciprofloxacin oder bei anderen Erregern entsprechend Antibiogramm zielgerichtet mit Antibiotika behandelt.

Hintergrund Im Jahr 1969 haben Kolipp und Hoffmann erstmals den Dermatophyten Trichophyton (T.) thuringiense isoliert. Seitdem ist diese geophile Dermatophyten-Spezies wahrscheinlich nicht wieder isoliert bzw. beschrieben worden – weder vom Tier noch vom Menschen. Erst jetzt ist T. thuringiense wieder gefunden worden, jedoch nicht bei einem Tier, sondern erstmals beim Menschen.

Summary Dermatomycoses are caused most commonly by dermatophytes. The anthropophilic dermatophyte Trichophyton rubrum is still the most frequent causative agent worldwide. Keratinolytic enzymes, e.g. hydrolases and keratinases, are important virulence factors of T. rubrum. Recently, the cysteine dioxygenase was found as new virulence factor. Predisposing host factors play a similarly important role for the development of dermatophytosis of the skin and nails. Chronic venous insufficiency, diabetes mellitus, disorders of cellular immunity, and genetic predisposition should be considered as risk factors for onychomycosis. A new alarming trend is the increasing number of cases of onychomycosis – mostly due to T. rubrum – in infancy. In Germany, tinea capitis is mostly caused by zoophilic dermatophytes, in particular Microsporum canis. New zoophilic fungi, primarily Trichophyton species of Arthroderma benhamiae, should be taken into differential diagnostic considerations of tinea capitis, tinea faciei, and tinea corporis. Source of infection are small household pets, particularly rodents, like guinea pigs. Anthropophilic dermatophytes may be introduced by families which immigrate from Africa or Asia to Europe. The anthropophilic dermatophytes T. violaceum, T. tonsurans (infections occurring in fighting sports clubs as “tinea gladiatorum capitis et corporis”) and M. audouinii are causing outbreaks of small epidemics of tinea corporis and tinea capitis in kindergartens and schools. Superficial infections of the skin and mucous membranes due to yeasts are caused by Candida species. Also common are infections due to the lipophilic yeast fungus Malassezia. Today, within the genus Malassezia more than 10 different species are known. Malassezia globosa seems to play the crucial role in pityriasis versicolor. Molds (also designated non-dermatophyte molds, NDM) are increasingly found as causative agents in onychomycosis. Besides Scopulariopsis brevicaulis, several species of Fusarium and Aspergillus are found.

Summary Miconazole is a broad-spectrum antifungal used in topical preparations. In the present investigation the minimal inhibitory concentration (MIC) of miconazole for eighty wild type strains of gram-positive and gram-negative bacteria isolated from infected skin lesions was assessed using a modified agar dilution test (adapted to CLSI, Clinical Laboratory Standards Institute). 14 ATCC reference strains served as controls. Miconazole was found efficacious against gram-positive aerobic bacteria (n=62 species), the MICs against Staphylococcus (S.) aureus, S. spp., Streptococcus spp. und Enterococcus spp. ranged between 0.78 and 6.25 μg/mL. Interestingly, there were no differences in susceptibility between methicillin-susceptible (MSSA, 3) methicillin-resistant (MRSA, 6) and fusidic acid-resistant (FRSA, 2) S. aureus isolates. Strains of Streptococcus pyogenes (A-streptococci) (8) were found to be slightly more sensitive (0.78-1.563 μg/mL), while for gram-negative bacteria, no efficacy was found within the concentrations tested (MIC >200 μg/mL). In conclusion, for the gram-positive aerobic bacteria the MICs of miconazole were found within a range which is much lower than the concentration of miconazole used in topical preparations (2%). Thus topically applied miconazole might be a therapeutic option in skin infections especially caused by gram-positive bacteria even by those strains which are resistant to antibiotics.

Since 2010 the FDA has approved laser systems as capable of producing a "temporary increase in clear nails" in patients with onychomycosis. Fungal eradication is probably mediated by heat in infrared laser systems; their efficacy has been confirmed thermographically, histologically and in electron microscopy. Another approach to decontaminate the nail organ is to disrupt fungi and spores by q-switched pulse applications. Recently specific combinations of wavelengths have been tested for their ability to disrupt the mitochondrial transmembrane potential at physiological temperatures by generating ATP and ROS. While clinically extremely high clearance rates of approximately 87.5-95.8 % have been reported, in-vitro investigations have failed to confirm the clearance. The variety of systems and advised parameters hampers a systematic evaluation. Recommendations for safe and practical treatment protocols, informed consent items, and combination with conventional treatment options are all areas of active work. Currently there is a lack of data concerning the long-term efficacy of laser therapy of onychomycosis; certified treatment protocols are needed.

Trichophyton (T.) species of Arthroderma (A.) benhamiae is a new emerging pathogen of dermatomycoses in children and adolescents. This zoophilic fungus seems to be more common than other zoophilic dermatophytes, e. g. Microsporum canis transmitted from cats to humans, zoophilic strains of T. interdigitale, and T. verrucosum as cause of ringworm of cattle. Trichophyton species of A. benhamiae is transmitted from guinea pigs (Cavia porcellus form. domestica) to human beings and causes highly inflammatory dermatomycoses both of the face and the scalp. When this dermatophyte produces purulent abscess-forming deep cutaneous infections of the scalp known as kerions, they are both a diagnostic and in particular a therapeutic challenge.

Approximately 2-13% of the world population suffers from onychomycosis. Recently, lasers have been introduced for treatment. However, no effect was found with in vitro laser irradiation of pathogens on agar plates. This study aimed to investigate the efficacy of laser irradiation against fungi using an alternative in vitro approach.Lasers of 808, 980 and 1064 nm were used to heat cell culture media and a nail clipping. Trichophyton rubrum. T. interdigitale. Microsporum gypseum. Candida albicans. C. parapsilosis, and C. guilliermondii species were subcultured and subjected to laser treatments (808/980 nm: 9-27 J/cm(2), 6 ms, 12 × 12 or 12 × 50 mm and 1064 nm: 50-240 J/cm(2), 90 ms, 5-10 mm). After irradiation, the fungal elements were transferred onto agar plates using conventional and Drigalski spatulas and were incubated for 6 days.The highest increase in temperature was found using a 980-nm laser with a pulse duration of 6 ms and a fluence of 27 J/cm(2). The histology work-up revealed a dissection of the nail plate from the nail bed tissue after laser irradiation. Growth inhibition was only found for C. guilliermondii and T. interdigitale. All other pathogens presented only reduced growth, and C. albicans growth was unaffected.This study demonstrates a clear thermal effect for linear scanning 980-nm and long-pulsed 1064-nm laser systems on either nail clippings or cell culture media. Complete pathogen growth impairment was achieved if temperatures were measured above 50 °C. The results for the 1064-nm system were almost comparable to 980 nm results.

Bei einer Chemotherapie von soliden urologischen Tumoren muss sowohl mit oberflachlichen als auch mit disseminierten tiefen Candidosen gerechnet werden. Abhangig von Manifestation und Auspragung sind gezielte Masnahmen gefordert. Vor allem bei immunsupprimierten Patienten ist eine systemische antimykotische Behandlung unumganglich.

Summary Background The prevalence of onychomycosis has increased steadily in the past decade. An accurate diagnosis at the outset is important for successful and cost-effective treatment of patients. However, current diagnostic tests for onychomycosis are not rapid, sensitive or specific. Objectives To develop a microsatellite-based polymerase chain reaction (PCR)-enzyme-linked immunosorbent assay (MS-ELISA) for the detection of Trichophyton rubrum, which is the most common aetiological agent of onychomycosis. Methods An archival set of 434 nail and skin specimens from 217 patients was included as the test sample in this study. We also compared MS-ELISA with an earlier published topoisomerase PCR-ELISA (TI-ELISA) using template DNA extracted by another method. Results The MS-ELISA detected the highest number of positive samples (69%) followed by direct microscopy (56%), TI-ELISA (44%) and fungal culture (30%). When an identical DNA extraction method was applied to 120 specimens, the MS-ELISA proved to be twice as sensitive as the TI-ELISA. Conclusions We have optimized a target gene and DNA extraction method for rapid detection of T. rubrum onychomycosis.

Onychomykosen sind weltweit im Anstieg begriffen. Vor einer antimykotischen Therapie steht die exakte Diagnostik, die derzeit mit den Routineverfahren Mikroskopie und mit kulturellem Erregernachweis erfolgt. Diese konventionellen mykologischen Methoden weisen jedoch Nachteile auf. Das mikroskopische Praparat ermoglicht keine Gattungs- oder Speziesidentifizierung, es werden lediglich avitale Pilzelemente nachgewiesen. Der Zeitaufwand fur die Pilzkultur ist hoch, beim kulturellen Nachweis besteht zudem eine betrachtliche subjektive Fehlermoglichkeit bei der Bestimmung der Pilzspezies. Uber einen Zeitraum von 3 Monaten wurden in einer chirurgischen Praxisklinik insgesamt 218 Patienten – alle wiesen disponierende Faktoren fur eine Nagel- und Fuspilzinfektion auf – mit Verdacht auf Tinea pedis und/oder Onychomykose in die prospektive Studie aufgenommen. Zusatzlich zur konventionellen Diagnostik der Nagelspane und Hautschuppen mittels Nativpraparat mit Blancophor® und Pilzkulturen wurde ein PCR (Polymerasekettenreaktion)-ELISA-Test zum Direktnachweis von Dermatophyten-DNS durchgefuhrt. Letzterer erlaubt aufgrund von spezifischen Primern, die gegen das Topoisomerase-II-Gen gerichtet sind, die Identifizierung von Trichophyton (T.) rubrum, T. interdigitale und Epidermophyton floccosum im klinischen Material. Kulturell waren bei 23,9 % der Patienten Dermatophyten nachweisbar (T. rubrum oder T. interdigitale). Mittels PCR-ELISA-Test konnte dagegen bei 29,9 % der Patienten Dermatophyten-DNS von entweder T. rubrum oder T. interdigitale nachgewiesen werden. Epidermophyton floccosum wurde weder kulturell noch mit PCR gefunden. Die PCR-ELISA-Technik zum Nachweis von Dermatophyten-DNS wies im Vergleich zur Kultur eine hohere diagnostische Sensitivitat (79,0 %) und diagnostische Spezifitat (85,5 %) auf. Der PCR-ELISA-Test ermoglicht eine schnelle und sehr spezifische sowie empfindliche Diagnostik einer Dermatophytose der Nagel und der Haut innerhalb von 24 (bis maximal 48) Stunden mit Identifizierung des Erregers bis zur Speziesebene.

Altogether 285 dermatophyte isolates of 21 different species - including both Trichophyton rubrum and T. interdigitale, but also eight additional Trichophyton species, Microsporum canis and seven other Microsporum species, as well as Epidermophyton floccosum and Arthroderma spp. - were analyzed using Matrix Assisted Laser Desorption Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS) and the AnagnosTec 'SARAMIS' (Spectral Archiving and Microbial Identification System) software. In addition, sequence analysis of the internal transcribed spacer (ITS) of the ribosomal DNA was performed for a high number of the tested strains. Sufficient agreement was found between the results obtained with standard identification methods and those with the MALDI-TOF MS for species identification of dermatophytes. A mass spectra database was constructed which contained the species identifications of all 285 isolates. The results were confirmed for 164 of the isolates by sequence analysis of the internal transcribed spacer (ITS) of the ribosomal DNA. Statistical analysis of all 285 dermatophyte strains showed that conventional identification matched the results of MALDI-TOF MS for 78.2% of the isolates tested. In the case of the 164 isolates for which the identifications were confirmed by PCR, the results of their conventional diagnosis and MALDI-TOF MS were in agreement for only 68.9 % (113 of 164 strains) of the test isolates. In contrast, there was agreement of 99.3 % or 98.8 % in the identifications obtained with PCR and MALDI-TOF MS techniques (283/285 or 162/164). The two exceptions were isolates that proved to be T. violaceum which could not be identified by the MALDI-TOF MS technique. In conclusion, the MALDI-TOF mass spectroscopy represents a fast and very specific method for species differentiation of dermatophytes grown in culture.

Dermatomykosen infolge Kontaktes zu Haus- und Nutztieren betreffen haufig Kinder und junge Erwachsene, hauptsachliche Erreger sind zoophile Dermatophyten. Die meist hochentzundlichen Dermatophytosen der freien Haut und Kopfhaut werden – wie seit Langem bekannt – durch Microsporum canis verursacht. Aufgrund fehlender Meldepflicht in Deutschland hat sich ein nahezu unbemerkter Erregerwandel vollzogen hin zu Infektionen durch zoophile Stamme von Trichophyton interdigitale (fruher Trichophyton mentagrophytes) sowie neuerdings auch zu Trichophyton species von Arthroderma benhamiae. Bei letzterem Dermatophyten handelt es sich um die anamorphe Spezies der teleomorphen Art Arthroderma benhamiae, der ursprunglich in Fernost (Japan) beschrieben worden ist. Infektionsquelle fur diese Hautpilze sind kleine Nagetiere (insbesondere Meerschweinchen), die von den Eltern der im Nachhinein von der Infektion betroffenen Kinder mit bester Absicht als Haustier in Zoohandlungen gekauft werden, ohne dass ihnen klar ist, dass damit gleichzeitig auch ein relevanter Infektionserreger erworben wird. Die Folge sind hochkontagiose Dermatophytosen, oft eine ausgepragte Tinea corporis, nicht selten eine Tinea capitis profunda bis hin zum Kerion Celsi. Weitere Dermatophyten, an die aktuell zu denken ist, sind Trichophyton verrucosum – der Erreger der Kalberflechte – sowie Trichophyton erinacei nach Igelkontakt. Nicht zu vergessen sind jedoch auch Hefepilze, vor allem Malassezia pachydermatis, einziger nichtlipophiler Vertreter der Gattung Malassezia, der vom Hund auf den Menschen ubertragen wird. Cryptococcus neoformans hat sein Erregerreservoir ebenfalls im Tier, konkret im Vogelkot, neben pulmonalen und Zentralnervensysteminfektionen sind sekundare, selten primare kutane Kryptokokkosen bei meist immunsupprimierten Patienten (HIV/Aids) eine mogliche Folge des Kontaktes zu diesen Tieren.

Tinea capitis is a dermatophyte infection common among prepubertal children in sub-Saharan Africa and mainly caused by Trichophyton and Microsporum species. Accurate identification is challenging as conventional methods like culture and microscopy are slow and mostly based on morphological characteristics, which make them less sensitive and specific. Modern molecular methods, like polymerase chain reaction (PCR) assays, are gaining acceptance and are quick as well as accurate. The aim of this study was to investigate the clinical patterns of tinea capitis and to accurately identify the most common causative dermatophytes affecting the scalps of children aged 1 to 16 years attending the Skin Clinic at Mbarara University of Science and Technology (MUST), Mbarara, Uganda, East Africa, using both conventional mycological methods and PCR-ELISA for detection of dermatophyte DNA. One hundred fifteen clinical samples from children from Western Uganda attending the MUST Skin Clinic with a clinical diagnosis of tinea capitis were analyzed. T. violaceum was identified as the most common causative agent, followed by M. audouinii, T. soudanense, and T. rubrum. The early identification of the causative agent of tinea capitis is a prerequisite for the effective management of the disease, the identification of probable source and the prevention of spreading. Children with tinea capitis in Western Uganda should be treated by systemic therapy rather than topical preparations to ensure high cure rates as the most common causative dermatophytes T. violaceum exhibits an endothrix rather than ectothrix invasion of the hair follicle.

Background Nail disorders can arise at any age. About half of all nail disorders are of infectious origin, 15% are due to inflammatory or metabolic conditions, and 5% are due to malignancies and pigment disturbances. The differential diagnosis of nail disorders is often an area of uncertainty. Methods This review is based on publications and guidelines retrieved by a selective search in PubMed, including Cochrane reviews, meta-analyses, and AWMF guidelines. Results Nail disorders are a common reason for derma - tologic consultation. They are assessed by clinical inspection, dermatoscopy, diagnostic imaging, microbiological (including mycological) testing, and histopathological examination. Some 10% of the overall population suffers from onychomycosis, with a point prevalence of around 15%. Bacterial infections of the nails are rarer than fungal colonization. High-risk groups for nail disorders include diabetics, dialysis patients, transplant recipients, and cancer patients. Malignant tumors of the nails are often not correctly diagnosed at first. For subungual melanoma, the mean time from the initial symptom to the correct diagnosis is approximately 2 years; this delay is partly responsible for the low 10-year survival rate of only 43%. Conclusion Evaluation of the nail organ is an important diagnostic instrument. Aside from onychomycosis, which is a common nail disorder, important differential diagnoses such as malignant diseases, drug side effects, and bacterial infections must be considered.