Dermatomycoses may be divided according to the responsible pathogen into dermatophyte, yeast, and mold infections. Fungi on the skin, or dermatophytes, are the cause of dermatophytosis, also referred to as tinea (ringworm). The most common dermatophyte in Germany, and probably the world, is Trichophyton rubrum. Fungal nail infections, or onychomycosis, are very common disorders in industrialized nations . The prevalence of fungal nail infections among certain risk groups, e.g., diabetics, is higher than in the general population; it is also higher in patients with disorders of keratinization affecting the skin and nails, e.g., psoriasis patients. The clinical diagnosis is often difficult, given that nail disorders due to other causes must be ruled out. A new epidemiological development is the increase in onychomycoses, usually due to T. rubrum, in children .
Yeasts – primarily Candida albicans – cause candidiasis of the skin and mucous membranes, also known as thrush. Although the term “thrush” (sponge) is still frequently used, it is considered obsolete. Malassezia-related superficial skin infections, primarily pityriasis versicolor, are very common; Malassezia folliculitis is less so. The lipophilic yeasts belonging to the Malassezia species are also associated with seborrheic and atopic eczema. Molds rarely cause cutaneous infections. Occasionally, secondary (hematogenic) skin infections can occur in immunosuppressed patients, e.g., with leukemia and after stem cell transplantation; primary skin infections due to molds are even rarer (e.g., due to Aspergillus fumigatus). Yet, non-dermatophyte molds (NDM) are considered emerging pathogens in onychomycosis of the toenails.
The most common pathogens among children and adolescents are zoophilic dermatophytes. The sources of infection are house pets and, less often farm animals. In Germany – probably due to immigration and greater urban densities compared to Austria – anthropophilic dermatophytes are becoming more common. Anthropophilic dermatophytes which are isolated in pediatric patients include T. tonsurans (associated with wrestling mats) and – becoming more common in kindergartens and schools – Microsporum audouinii. The latter fungus is from Africa and is transmitted, directly or indirectly, by immigrating families. A problem is chronic hyperkeratotic infections, which often involve pus and abscesses formation, on the scalp (e.g., tinea capitis profunda). These may be caused by well-known (M. canis) and “new” (T. species von Arthroderma benhamiae) zoophilic pathogens. Only rapid mycological diagnosis, also with molecular biological techniques for dermatophyte DNA detection, and immediate systemic antifungal treatment can prevent scarring of the scalp or pseudopelade of Brocq.
Trichophyton rubrum – the most common dermatophyte
T. rubrum continues to be the most common dermatophyte in the world with the highest incidence in Europe (Figure 1). Trichophyton is derived from the Greek words “θριχóς” “hair” and “ϕυτóν” “plant”; “rubrum” (Latin for red) refers to the red-brown pigmentation found in the fungal culture on the underside of the colony of the white thallus. Yet unlike most other dermatophytes, T. rubrum (“red hairy plant”), only rarely affects the hair and hair roots. Its target structures are the stratum corneum of the epidermis and the nail keratin. The percentage of the anthropophilic fungus T. rubrum among the dermatophytes causing tinea unguium is 91% in Germany . T. rubrum and T. interdigitale (previously known as T. mentagrophytes) are also responsible for about 90% of all cases of dermatophytosis in Poland. The same figures have been reported in Great Britain and Sweden . In Poland, the most common forms of fungal skin infections, irrespective of causative dermatophytes, are tinea unguium pedum (42.2%) and tinea pedis (41.4%); tinea corporis (5,6%), tinea manuum (4.1%), tinea unguium manuum (3.0%), tinea capitis (2.4%), and tinea cruris (1.3%) are much less common .
Along with tinea pedis and tinea unguium, T. rubrum infections are increasingly occurring at other sites on the body than previously reported . An example is tinea faciei due to T. rubrum after autoinoculation with tinea pedis et unguium of the lower extremities . Tinea capitis due to T. rubrum is unusual.
Dermatophyte transmission in the home
The pathogen reservoir for tinea pedis and onychomycosis are anthropophilic dermatophytes, i.e., T. rubrum and T. interdigitale (only anthropophilic strains) and Epidermophyton floccosum (Table 1). The most common source of infection is the bath; and transmission among family members is the most common route. Spread may be horizontal, e.g., between spouses, or vertical between the generations. The latter, for instance, between a father or grandfather and (grand-) child, is much more common than horizontal spread. Other sources of infection are showers in fitness studios, changing rooms at public pools, mats in sports facilities (wrestling or martial arts facilities, tropical baths, and hotels and mosques) .
|Epidermophyton floccosum||Increasingly rare in Germany, infections of feet, toenails, and groin|
|Microsporum audouinii||Mainly in Sub-Saharan African|
|Microsporum ferrugineum||Mainly found in Asia, rarely in Africa or Eastern Europe|
|Trichophyton concentricum||Limited to Southeast Asia, cause of tinea imbricata (“Tokelau”) as cockade-like fungal infection|
|Trichophyton interdigitale (anthropophilic strains)||Second most common dermatophyte in Germany|
|Trichophyton megninii||Very rare in Germany; tinea pedis, tinea manuum, tinea unguium, tinea barbae|
|Trichophyton rubrum||Most common dermatophyte in the world, tinea unguium, tinea pedis et corporis, rarely invades hair and hair roots|
|Trichophyton rubrum var. raubischekii||Variant of T. rubrum, found nearly only in Africa; recent isolated reports in Germany, Turkey, Spain, and Asia (Japan)|
|Trichophyton schoenleinii||Favus pathogen, rare in Europe|
|Trichophyton tonsurans||Tinea capitis pathogen in America; in Germany tinea gladiatorum occurs in martial arts participants|
|Trichophyton violaceum||Most important dermatophyte in Africa|
|Trichophyton soudanense||Found in Africa; genotypically, but not phenotypically, identical to T. violaceum|
|Trichophyton vanbreuseghemii||Very rarely isolated from humans (skin) or soil|
Molecular epidemiology and transmission of Trichophyton rubrum in the home
The results of a recent study done in the United States confirmed the transmission of dermatophytes within homes in which individual family members had tinea pedis or onychomycosis. The dermatophytes were detected using molecular biological methods with polymerase chain reaction (PCR). The primer used was the internal transcribed spacer (ITS) region (ITS1 und ITS4). For stem cell differentiation, a ribosomal-DNA-specific probe (containing ITS1, 5.8S ribosomal DNA and ITS2) was used to detect restriction fragment length polymorphism (RFLP). In 50 households, 18 family members had multiple infections . T. rubrum was the most common dermatophyte, followed by T. mentagrophytes (T. interdigitale) and Epidermophyton floccosum. Sixteen T. rubrum strains were found in 8 households with multiple infections. Certain T. rubrum strains had a significantly higher tendency toward spreading; there was also an association with a history of tinea pedis and onychomycosis, with plantar scaling, and nail plate discoloration.
Pathogenesis of dermatophytosis
Predisposing host factors for dermatophyte infections
Predisposing host factors allow tinea pedis and onychomycosis to occur. As a rule, a healthy nail is not susceptible to fungal infection. Among predisposing factors for tinea pedis et unguium are circulatory disorders affecting the lower extremities as well as metabolic disorders such as diabetes mellitus (Table 2).
▸ Circulatory disorders (chronic venous insufficiency, peripheral arterial circulatory disorder)
▸ Lymphedema in the lower extremities
▸ Malalignment of the feet including hallux valgus, hammer toe
▸ Toenail deformities/onychodystrophy
▸ Psoriasis vulgaris and psoriasis unguium
▸ Ichthyosis vulgaris
▸ Diabetes mellitus
▸ Nail and nail bed microtrauma due to sporting activities (track and field, jogging, marathon running, soccer)
▸ Strong perspiration/hyperhidrosis pedum
▸ Immunosuppression (HIV/AIDS)
▸ Patients with trisomy 21
Psoriasis vulgaris and onychomycosis
In treatment-refractory onychomycosis, keratinization disorders affecting the skin and nails are more common than previously thought. Most patients have undetected psoriasis vulgaris and psoriasis unguium; atopic eczema and ichthyosis vulgaris are also related to more pronounced keratinization, which is a predisposing factor in dermatophyte infections. Twenty-seven percent of patients with psoriasis who have nail changes have onychomycosis involving the toenails . The findings of in vitro studies show that scale taken from patients with psoriasis can promote the growth of dermatophytes, yeasts, and molds .
In patients with psoriasis vulgaris, there is a significantly higher rate of Candida colonization of the toenails . Kaçar and colleagues  studied patients with onychomycosis, 168 of whom had concomitant psoriasis and 164 who did not. Using fungal tests, onychomycosis was diagnosed in 22 patients with psoriasis (13.1%) and in 13 controls (7.9%). In the psoriasis group, primarily dermatophytes were found to be the pathogens in onychomycosis; in the control group, it was mainly molds. Dermatophytes were isolated significantly more often in psoriasis patients than in the control group.
In one study with patients in Bulgaria and Greece on the prevalence of fungal nail infections in psoriasis vulgaris, out of 228 patients with nail changes and psoriasis vulgaris, 62% had a positive fungal culture . In 67% of these patients, a dermatophyte was isolated; in 24% a yeast was found; and in 6%, a mold was identified. The incidence of onychomycosis in psoriatic patients was higher.
Ichthyosis as a predisposing disease for dermatophytosis due to Trichophyton rubrum
A 10-month old child with congenital lamellar ichthyosis had a treatment-refractory T. rubrum infection. Tests revealed a high total IgE and specific IgE to T. rubrum. Ichthyosis, a keratinization disorder affecting the epidermis is a risk factor for chronic dermatophytosis; both the excessive amounts of keratin as well as the barrier defect are predisposing factors. A type IV immune response (delayed type of hypersensitivity) to T. rubrum promotes healing of tinea. Immediate hypersensitivity and IgE do not protect against tinea; chronic infection may be expected.
Cellular immunity as a predisposing factor for dermatophytosis
The host-specific side of dermatophyte infections, that is, the cellular immune response, has been studied in patients with severe dermatophytosis due to T. rubrum. Immunophenotyping showed no differences between affected patients and controls. In the control group, a lymphocyte proliferation test showed significantly higher stimulation rates of lymphocytes to American pokeweed mitogen, Candida spp., and T. rubrum extract with the main fungal epitope (TriR2). Cytokine analysis showed a significant difference between the groups only for IFN-γ, after stimulation by PHA and TriR2.
Diabetes mellitus and onychomycosis
Diabetics have a higher risk of tinea pedis and onychomycosis. Compared to patients with gastroesophageal reflux, they have a much higher risk of bacterial and fungal infections (odds ratios of 5.95 and 2.66) . Onychomycosis is now considered to be a predictor of diabetic foot syndrome . Diabetics with onychomycosis have a 1.6 times greater risk of having a diabetic foot ulcer .
In a prospective study , the prevalence of onychomycosis in diabetics (type II) was 22%; most infections were due to dermatophytes, and only in four patients were yeasts identified. In another study, 383 out of 1,245 Taiwanese patients with diabetes mellitus were reported to have onychomycosis, which corresponds to a prevalence of 30.76% . Older age, being male, metabolic syndrome, being overweight, elevated triglyceride levels, and poor control of blood sugar levels (elevated HbA1c) were associated with onychomycosis.
The results of one study found that, out of 95 patients with type I diabetes in Germany (average duration of disease: 35.8 years), 82.1% had changes affecting the feet that were suggestive of mycosis; in 84.6%, fungal infection was confirmed by a plain specimen and mycological culture . Twenty-eight patients had a fungal nail infection, and another 28 had both cutaneous and nail infections.
In a cross-sectional study conducted in Japan, 51.3% of patients with diabetes had onychomycosis of the toenails . Nail thickness was significantly correlated with an elevated HbA1c value. Onychomycosis was significantly more common if the feet were not washed on a daily basis.
Onychomycosis in patients with diabetes and chronic hemodialysis
Out of 100 patients who were on chronic hemodialysis, 39% had onychomycosis . The most common pathogens were dermatophytes (ca. 70%), Candida spp. (15%), and non-dermatophyte molds (NDM; 15%). T. interdigitale was the most common pathogen, followed by Candida spp. and T. rubrum. The risk of onychomycosis increased with every year of life by around 1.9%. Diabetics who are using hemodialysis have about an 88% higher probability of onychomycosis than non-diabetics.
Genetic predisposition for onychomycosis
A family history of disease is considered to be a risk factor in onychomycosis. Genetic factors – such as autosomal dominant inheritance of susceptibility to distal subungual onychomycosis due to T. rubrum – promote the development of onychomycosis . This often leads to the vertical transmission of onychomycosis between family members.
Faergemann and colleagues  have shown that the high prevalence of onychomycosis in certain families is apparently the result of intra-family transmission (and predisposition?). Family members who married into the family are less likely to have onychomycosis, yet their children do have a high prevalence of onychomycosis, which supports the suggestion of autosomal dominant inheritance.
Ashkenazi Jews are protected from onychomycosis by the human leukocyte antigen DR4 (HLA-DR4) . HLA-DR6 has been identified by one study in 7 out of 21 Mexican mestizos with onychomycosis (33%) and in 45% of controls . Six patients (29%) and 3 controls (7%) had children with a nail infection. Thirteen of the patients (62%) with onychomycosis, and 12 of the controls (29%), had a first-degree relative who also had onychomycosis. Among Mexican mestizos, the HLA-DR6 antigen has been found to be a protective factor. In people who have a first-degree relative with onychomycosis, there is a significantly elevated risk of onychomycosis; this supports the hypothesis of genetically determined susceptibility for onychomycosis.
Virulence factors of dermatophytes
Although various factors related to the potential host create the conditions for dermatophytosis (predisposition), dermatophyte virulence factors must also be present for a cutaneous infection to occur. The target structure for infection and dermatophyte proliferation in the stratum corneum of the epidermis is the hard, firm cytokeratin found in the skin, hair, and nails. Dermatophytes degrade these complex proteins via keratinase. A recent study measured the keratolytic activity of T. rubrum, T. interdigitale, M. canis, and M. gypseum using spectrophotometry. At temperatures of 30–40°C, and in a slightly alkaline milieu (pH: 7.0–8.0), Trichophyton spp. produced the highest keratinase activity . The high level of enzyme activity of Trichophyton spp. at normal body temperatures and pH levels of the skin is presumably responsible for the adaptation of certain dermatophytes to the surface of human skin. This is referred to as “anthropozation.” Thus, the pathogen reservoir of T. rubrum, as an anthropophilic dermatophyte, is only found on the person himself or in his home. The infection pathways for dermatophytes are thus either direct (rarely, via skin contact from one person to another) or indirect (most common, from walking barefoot on surfaces that have been contaminated with infectious material from the skin, floors, rugs, etc.).
Adherence, hydrolase activity, and cysteine dioxygenase of dermatophytes
The adherence of dermatophytes to the epithelial tissue of the host, which contains keratin, is mediated by mannan glycoproteins in the cell wall of the fungus . Maturation of the arthroconidia produces hyphae, which are able to penetrate the deeper layers of the skin tissue. Other factors include the nutritive medium for the fungus, host-pathogen interactions (signals), transport proteins, synthesis of structural proteins in the fungus and secretion of proteolytic enzymes, predominantly hydrolase (keratinase, nuclease). The hydrolase activity is inhibited by disulfide bridges, which link epidermal keratins. These disulfide bonds must be broken by cysteine dioxygenase to set the process of keratinolysis in motion.
Keratin degradation is caused by keratinase, cysteine dioxygenase, and a sulfite efflux pump . A recent hypothesis suggests that keratin breakdown is facilitated by secretion of the reducing compound, sulfite, which can break the keratin-stabilizing cysteine bonds. A working group led by Peter Staib at the Leibniz Institute in Jena found that dermatophytes can form sulfite from cysteine found in the environment. At higher concentrations, cysteine has a toxic effect on microorganisms as well as human beings. Sulfite formation from cysteine is due to the effect of the key enzyme cysteine dioxygenase Cdo1 and is supported by the sulfite efflux pump Ssu1. Because keratin is rich in cysteine, the cysteine transformation and sulfite efflux pump appear to contribute to cysteine and sulfite tolerance and to keratin degradation.
Marker candidate genes for the dermatophyte virulence
To understand the pathogenesis of dermatophytosis, knowledge of genes and the proteins they code (or enzymes) is essential. A comparative genomic analysis of T. rubrum and closely-related dermatophyte species (T. tonsurans, T. equinum, M. canis and M. gypseum) focused on the candidate genes which are responsible for infection . The dermatophyte species demonstrated various biological behaviors related to host specificity, reproductive behavior, and disease course. Although the genome of the various dermatophytes is relatively uniform, there are genetic segments which do not seem to be present in other pathogenic fungi that cause disease in humans. According to the authors of the aforementioned molecular biological study, the dermatophyte genome contains gene families of the LysM domains, which are needed to bind chitin and carbohydrates. Other genes code fungus-specific gene kinases and pseudokinases, which may competitively inhibit phosphorylation; this can have an effect on cellular signal transduction. Still other genes code enzymes that synthesize secondary metabolites. In addition, the dermatophytes contain genes for various classes of proteases which enable fungal growth as a result of keratin degradation.
Impaired quality of life due to fungal nail infections
Although fungal nail infections are not life-threatening, they can significantly impair the quality of life of those affected . The influence of onychomycosis on quality of life was recently described in a Polish study on 140 patients . Not only women, but patients in general who had onychomycosis of the toenails for more than two years, had a poorer disease-specific quality of life. The most common problems affecting the patients' attitude toward life were cutting the nails, cosmetically disturbing disfigurement, and ill-fitting shoes. An important aspect was the concern among patients that the infection would spread to other nails or to other people. Industrial workers and craftsmen, i.e., blue collar workers, reported greater impairment as a result of the nail infection than did white collar workers.
Stigmatization due to onychomycosis
Szepietowski and Reich  found that patients with onychomycosis have lacking self-esteem as well as a feeling of shame, along with a decreased willingness to participate in social activities, and a fear of transmitting the infection to others. This study was also conducted in Poland, with 1,684 onychomycosis patients, and reported an average score of stigmatization of 5.3 points (range: 0–17 points). Patients felt the greatest impairment if their disease was considered to be contagious; this was followed by the feeling that other people would stare at their nails; in third place was a feeling of unattractiveness. Women reported significantly more often that they felt unattractive, and that others were looking at their nails. Onychomycosis was found to lead to a similar level of stigmatization as psoriasis vulgaris. Antifungal treatment improved not only physical symptoms but also emotional well-being and quality of life.
House pets as a pathogen reservoir for dermatomycosis
Children and adolescents are often affected by zoophilic dermatophytosis as a result of direct transmission from animals or due to an outbreak in the family or school/daycare. Along with cats, especially rodents (e.g., guinea pigs) are a source of infection and transmission of dermatophytes. There are no current data on infection rates of small animals with dermatophytes (T. interdigitale, Trichophyton species of Arthroderma benhamiae, M. canis) in Germany.
The frequently inflammatory dermatophytoses on bare skin, and especially the scalp, are often caused by M. canis. Because these diseases are not notifiable in Germany, there has been a nearly invisible shift in pathogens toward infections by zoophilic strains of T. interdigitale (previously known as T. mentagrophytes) as well as Trichophyton species of Arthroderma benhamiae (Table 3). The latter are an anamorphic species of the teleomorphic genus Arthroderma benhamiae, which originally was reported in the Far East (Japan). The source of infection for these skin fungi are small rodents (especially guinea pigs).
|Microsporum bullosum||Horses, donkeys|
|Microsporum canis||Cats, rarely dogs (usually in South America)|
|Microsporum gallinae||Chickens (very rarely transmitted to humans)|
|Microsporum nanum||Pigs, cows|
|Microsporum persicolor||Moles, other rodents, e.g., mice|
|Trichophyton equinum||Horses, morphology strongly resembles T. tonsurans|
|Trichophyton interdigitale (zoophilic strains)||Rodents (e.g., guinea pigs, golden hamsters, rats, mice, chinchillas), rabbits, dwarf rabbits, ferrets|
|Trichophyton mentagrophytes||Mice and camels (almost never in Germany, only in Middle East)|
|Trichophyton simii||Monkeys, chickens, guinea pigs, shrews|
|Trichophyton species of Arthroderma benhamiae||Guinea pigs, other small rodents|
|Trichophyton verrucosum||Calves, cows, other farm animals (e.g., horses, pigs, dogs, and cats)|
Trichophyton interdigitale – anthropophilic and zoophilic dermatophyte
T. interdigitale – previously known as T. mentagrophytes – is now the second most common dermatophyte in Germany . Within the species, a distinction is made between anthropophilic and zoophilic strains. The anthropophilic strains of T. interdigitale tend to cause tinea unguium and tinea pedis, and, less often, tinea corporis  (Figure 2).
Originally, a distinction was made within the T. mentagrophytes complex between diverse anthropophilic varieties or subspecies. Along with T. mentagrophytes var. interdigitale, there were T. mentagrophytes var. nodulare (also known as T. krajdenii) and T. mentagrophytes var. goetzii. Zoophilic varieties included T. mentagrophytes var. granulosum (corresponding to T. mentagrophytes var. asteroides), the reservoir of which were rodents (e.g., dwarf rabbits, guinea pigs, rats), as well as T. mentagrophytes var. erinacei (hedgehog) and T. mentagrophytes var. quinckeanum (mice and camels) [38, 39].
On the basis of molecular biological analyses of dermatophyte DNA, we now know that T. mentagrophytes, as a separate species, corresponds to the former zoophilic variety T. mentagrophytes var. quinckeanum. This dermatophyte is the pathogen responsible for mouse favus and is found only among camels and mice in Arab countries, not in Germany or the rest of Europe [8, 40].
Nearly all other anthropophilic and zoophilic varieties of T. mentagrophytes are genetically identical; the new taxonomic classification is under the new species T. interdigitale. This greatly simplifies the mycological diagnosis in the laboratory and clinical practice.
Tinea barbae is considered a classic infection that is caused by T. mentagrophytes (first described by David Gruby in 1842) . In the 19th century, it was probably always a zoophilic infection. The term “mentagrophytes” referred to the location (the Latin word “mentum” means chin). The current designation, T. interdigitale, is illogical since the disease occurs on the head or trunk, as in tinea capitis and tinea corporis due to zoophilic strains of this dermatophyte species. Yet one should be aware of it. More commonly, T. interdigitale (anthropophilic strains) causes tinea pedis or tinea unguium. In fungal infections affecting the interdigital spaces between the toes, this term is certainly plausible. The new taxonomic division of dermatophytes is now internationally established. Thus, for modern dermatomycology in Germany the new taxa should be used.
Trichophyton species of Arthroderma benhamiae
In Germany, there has been a virtually unnoticed increase in A. benhamiae. These strains are not the teleomorphic, or perfect form of the dermatophyte, but rather the imperfect form. Thus, these should preferably be referred as Trichophyton species (anamorphic) of Arthroderma benhamiae (Figure 3a, b). Reliable pathogen detection and identification requires molecular testing methods. The epidemiology of dermatophyte distribution in Germany is currently being corrected. The pathogen reservoir of Trichophyton species of A. benhamiae corresponds to the zoophilic T. interdigitale isolates. The reservoir consists of small rodents, mainly guinea pigs (which are usually only carriers, but may have a manifest infection). T. species of A. benhamiae, similar to the zoophilic strains of T. interdigitale, can cause tinea with severe inflammation in children/adolescents and immunosuppressed patients .
The first reports of A. benhamiae infection came from Japan  where A. benhamiae was reported in 2002 as a dermatophyte pathogen in humans. Isolates were taken from two patients with tinea corporis and one isolate from a rabbit, which was the source of infection . The differentiation was based on the sequencing of the chitin synthase 1 (CHS1) gene as well as cross-breeding studies. In 1998, A. benhamiae had already been isolated from a rabbit in Japan.
Shiraki and colleagues  reported on tinea corporis due to A. benhamiae with atypical clinical features in a patient who worked at a pet shop. The authors suggested that A. benhamiae was probably widespread in Japan.
Even with a bright yellow reverse side of the colony, the differentiation is problematical, and confusion with M. canis, T. interdigitale and T. erinacei, and possibly even T. soudanense is conceivable. The most reliable method of identification of A. benhamiae is direct molecular biological detection in skin flakes using polymerase chain reaction (PCR-Elisa). A matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) may be used to confirm the results of culture.
Microsporum canis – cause of tinea capitis and tinea corporis after contact with cats
The source of M. canis infection is cats. Contact usually occurs during vacation in Southern Europe (Spain, Italy, Greece), Southeast Europe (Balkans, including Bulgaria), or North Africa (Tunisia, Morocco), rather than in Germany. According to one study, in central Italy, 13% of cats living in private households (100 animals) were carriers of M. canis; the pathogen was identified in 100% of stray cats (Figure 4). Adult cats are often asymptomatic carriers  and should be considered infectious. A mangy coat or other signs of fungal infection (hair loss, bare areas, increased scaling, erosions, and crusts) may be seen in young animals and immunosuppressed cats.
Poor hygiene is considered a risk factor for M. canis infection in cats. Endemic disease may affect cats in “cat hotels” or animal shelters . The infectious arthrospores from the fur of the cats end up in the environment where they may remain virulent for a year. Humans can become infected by direct contact with sick animals, healthy carriers, or by contact with contaminated dust, brushes, or clothing.
Trichophyton verrucosum – the responsible pathogen in trichophytosis
T. verrucosum is a dermatophyte which was all but forgotten until recently when it was identified again as a causative pathogen in various infections (trichophytosis). The pathogen used to only be found among agricultural workers. To reduce costs, nowadays livestock are often not vaccinated against T. verrucosum. Calves and cows are the infection source, transmitting disease mainly to children and adolescents who are vacationing on a farm. Indirect transmission via contact with contaminated materials (wooden stalls, saddles, and other pieces of riding equipment) is also possible. In addition to calves and cows, T. verrucosum also sometimes colonizes on or infects other farm animals (Table 3) . Papini and colleagues  found T. verrucosum in all 20 farms that were studied in Central Italy; 25–100% of calves were infected.
The suspicion of work-related T. verrucosum infection, in accordance with no. 3102 of the German Ordinance on Occupational Disease (Berufskrankheitenverordnung [BeKV]) a notifiable disease (dermatologist's report). Veterinarians as well as students of veterinary medicine may also be infected .
There was also a rare report on T. verrucosum in a cattle farm worker who presumably inoculated herself accidentally with the live vaccine while vaccinating calves .
Trichophyton erinacei – transmission from hedgehog to person
T. erinacei – an emerging pathogen – is transmitted as a zoophilic dermatophyte from hedgehogs to people. The source of infection is the Central European hedgehog, which is an endangered species and may not be kept as a pet. Contact may occur when caring for injured or hypothermic animals at “hedgehog stations”. At present, non-endangered hedgehogs are being imported and are available for sale in commercial pet stores. These are the African white-bellied or dwarf hedgehog (African pygmy hedgehog, Atelerix albiventris) as well as the Egyptian long-eared hedgehog (Hemiechinus auritus) . In Würzburg, Germany, there has been a report of a 29-year-old woman with tinea manus due to T. erinacei. The isolate was identified using molecular biological methods with sequencing of the ITS1 region of ribosomal DNA. The source of infection was a pet African white-bellied hedgehog (Atelerix albiventris). Long-term, combination topical and systemic antifungal therapy was needed to treat the erosive, severely inflamed lesions.
M. audouinii, an anthropophilic, highly contagious dermatophyte, is the pathogen responsible for classic microsporia. During the 18th and 19th centuries, infection was considered a characteristic childhood disease of the scalp; it had an epidemic character and was referred to as an “orphanage disease.” Up until the 1950s, M. audouinii was widespread in schools. Hence the name “orphanage disease.” After the late 1950s, this pathogen, which causes tinea capitis, was no longer identified in Germany for several decades, probably due to the availability of an effective treatment (griseofulvin).
Yet, in the last two or three years, the fungus has experienced a renaissance. Immigrating families and their children have brought it from Africa to Germany, where it is endemic in kindergartens and schools. The pattern of hair root invasion by M. audouinii is endothrix-ectothrix. The spores surround the hair in a mosaic-like arrangement; the hair loses its elasticity and breaks. Lesions fluoresce green on Wood light examination .
In Africa, south of the Sahara (e.g., Uganda), M. audouinii is the second most common dermatophyte infecting children and adolescents, after T. violaceum. In Nigeria, M. audouinii has also been reported in second place among elementary school children, after T. mentagrophytes, and before T. verrucosum.
There are current reports of outbreaks occurring in Munich, Wittlich (Rhineland-Palatinate), Berlin, and Hanover in childcare centers and kindergartens; in Munich and Hanover in particular, the infection was so widespread that the Department of Health and the Environment became involved [56, 57]. The infection is primarily transmitted through human-to-human contact. At the same time, there was an outbreak in Switzerland of M. audouinii infections . Neither terbinafine nor fluconazole had an effect on the tinea capitis. Two children healed only after switching to griseofulvin, and a third had to be treated with itraconazole. In order to identify asymptomatic carriers of the anthropophilic dermatophytes, the children's families, as well as three classes had to take part in a screening test with the toothbrush technique. Three family members and five classmates were found to be carriers of M. audouinii. All of them were treated in order to prevent re-infection. The family members were treated with oral griseofulvin and the classmates with ketoconazole shampoo.
Contact with soil can lead to infection with the geophilic dermatophyte M. gypseum (Table 4, Figure 5). Infection of exposed areas of the skin can occur when children play outdoors or on the floor (e.g., tinea manus) . Soil contact is also the trigger in tinea manus, as seen among allotment or professional gardeners. In the latter, similar to T. verrucosum, in accordance with no. 3102 of the German Ordinance on Occupational Disease (Berufskrankheitenverordnung [BeKV]), the infection is notifiable (dermatologist's report).
|Microsporum cookei||Rarely causes dermatomycosis in humans; occurs in animals, e.g., dogs, monkeys, squirrels|
|Microsporum fulvum||Morphology barely distinguishable from M. gypseum, causes infections in humans and animals|
|Microsporum gypseum||Most common geophilic dermatophyte, usually in tinea manus, but also isolated in tinea capitis, after contact with soil, e.g., gardening|
|Microsporum racemosum||Rare, causes tinea corporis and tinea unguium|
|Trichophyton ajelloi||Colonizes skin and nail material, tends to not be pathogenic|
|Trichophyton flavescens||Found in birds, not pathogenic to humans|
|Trichophyton gloriae||Very rare, still unknown whether or not pathogenic to humans|
|Trichophyton phaseoliforme||Found worldwide, usually not pathogenic to humans or animals|
|Trichophyton terrestre||Sporadically isolated in Germany, colonizes skin and nail material, considered non-pathogenic|
|Trichophyton thuringiense||Reported in rodents (mice and moles), one report in a human being (toenail), but probably apathogenic|
T. tonsurans is a ubiquitous anthropophilic dermatophyte with a particularly high prevalence in Mexico and other Latin American countries (Figure 6). In the United States, T. tonsurans is the most common pathogen in tinea capitis in children and adults (especially among African Americans and Hispanics) . T. tonsurans is on the rise in Europe, especially in Great Britain , but it is also becoming more common in Germany . In Germany there are routine outbreaks of tinea corporis et capitis gladiatorum due to T. tonsurans among wrestlers, usually children and adolescents.
One study has investigated whether specific genetic factors influence the susceptibility to T. tonsurans or protection against it, examining 40 children with whole genome genotyping to identify a variety of genes . Twenty-three genes seem likely to have mechanistic role in skin infection by the dermatophytes. In 21 genes, there were significant differences in the infection rates among children. This formed the basis for a risk index. The genes were involved, for instance, in leukocyte activation and migration, the integrity and new formation of the extracellular matrix, the differentiation of epidermal cells, and wound healing as well as cutaneous permeability.
Trichophyton violaceum and Trichophyton soudanense
T. violaceum is an anthropophilic “exotic” dermatophyte that occurs in tropical regions, especially Sub-Saharan Africa (Figure 7). Infections in Germany have been reported in immigrants from African countries . In West Scotland, Great Britain, T. violaceum is reportedly the most common dermatophyte causing tinea capitis, followed by T. tonsurans. Almost all patients are children from families from Africa and Pakistan who have applied for asylum in Great Britain.
In terms of molecular genetics, T. soudanense is identical to T. violaceum; the phenotypes of the pathogens differ significantly, however. The pathogens also differ in regard to geography: T. soudanense is primarily found in Nigeria. In the 1950s, it was assumed that T. soudanense would never infect Caucasians (“white skin”), although this is now known to be untrue .
Favus caused by Trichophyton schoenleinii
Favus may be caused by T. schoenleinii, an anthropophilic dermatophyte which was very widespread during the 19th century in Germany; today it is found only in Northern Africa and Asia Minor (Iran, Turkey). T. schoenleinii causes a specific type of tinea capitis in which scutulae – saucer-shaped yellow crusts, sometimes with hair projecting through them – cover the entire scalp. In 1839, Robert Remak and Johann Lukas Schönlein described the pathogen, which was later called T. schönleinii or. T. schoenleinii, as the causative organism in an infectious skin disorder known as favus. Up until then, given the familial incidence of infection, the disorder was believed to be hereditary .
In Germany, T. schoenleinii occurs only very rarely, as a sporadic infection . In Rumania, tinea corporis bullosa without scalp involvement due to T. schoenleinii was recently diagnosed in a 41-year-old woman . Onychomycosis caused by T. schoenleinii, as recently reported in Poland, is very rare .
This anthropophilic dermatophyte primarily affects the skin (tinea pedis, tinea inguinalis), but can also invade the nails; there is no hair involvement  (Figure 8). In the literature, the pathogen is reportedly the fourth most common dermatophyte. In our own studies, it is much less common than other dermatophytes; it is usually found in tinea unguium.
Malassezia (M.) – previously known as Pityrosporum ovale or orbiculare – is a lipophilic yeast that is part of the physiological skin flora. A facultative pathogenic yeast, Malassezia is opportunistic. It can cause pityriasis versicolor, Malassezia-related folliculitis in immunosuppressed patients, and occasionally onychomycosis. Malassezia also plays a role as a trigger factor in the inflammatory reaction in seborrheic dermatitis, dandruff, and atopic eczema, [72-74]. In recent years, along with M. furfur and M. pachydermatis (non-lipophilic, transmitted by dogs), a large number of new species have been described. These include M. sympodialis, M. globosa, M. restricta, M. obtusa, M. slooffiae, M. dermatis, M. japonica, M. yamatoensis, M. nana (from cats and cows), and, recently M. cuniculi sp. nov. (from rabbit skin) [75, 76].
The most commonly identified causative fungus in pityriasis versicolor is M. globosa. There have been several studies on the prevalence of Malassezia species in pityriasis versicolor. Chaudhary and colleagues  have shown M. globosa to be the most common species in India, followed by M. sympodialis, M. furfur, M. obtusa, and M. restricta. In Argentina, M. sympodialis and M. globosa have been shown to be the most common species in pityriasis versicolor, followed by M. furfur in third place . A molecular biological study done in Giessen, Germany, has supported the pathogenicity of M. globosa in pityriasis versicolor  using a comparative analysis of different expression of genes in tryptophan-dependent pigment synthesis in M. furfur with the gene sequences in M. globosa. The results of the study showed that M. globosa has homology with most of genes which are expressed during pigment synthesis in M. furfur, supporting the pathogenetic role of this Malassezia species.
Onychomycosis due to non-dermatophyte molds (NDM)
There have been increasing reports of non-dermatophyte molds (NDM) causing onychomycosis. In addition to known fungi, such as Scopulariopsis brevicaulis, there are also Fusarium species and, rarely, other molds such as Onychocola canadensis, Aspergillus fumigatus, Aspergillus ochraceopetaliformis, Acremonium spp., Neoscytalidium dimidiatum (previously known as Hendersonula toruloidea), Arthrographis kalrae, and Chaetomium spp. (along with Trichophyton interdigitale) as the causative pathogens in onychomycosis. Yet molds are often merely due to contamination, that is, they grow saprophytically on nails with pathological changes (onychodystrophy). Distinguishing between molds as relevant pathogens in onychomycosis and mere colonization is a diagnostic challenge. The following criteria should therefore be used for diagnosing onychomycosis due to mold: positive KOH (or Blancophor dye) test, three-month-long consecutive isolation of the same mold from culture, and lacking detection of a dermatophyte. Shemer and colleagues  have proposed the following criteria as an alternative for diagnosing a nail infection due to NDM. If NDM are identified, a further study of three separate nail specimens, taken simultaneously, should be performed. Only after there has been pathogen identification in all cultures is the infection confirmed, and targeted treatment may commence. Gupta and colleagues  have now re-defined six main criteria for diagnosis of onychomycosis due to NDM: microscopic detection of NDM in a nail specimen (KOH preparation), cultural isolation of the pathogen, repeated isolation from culture, colony density, lacking detection of a dermatophyte, and histology. At least three of these criteria should be present. Microscopic detection of fungi in the KOH preparation and isolation of the pathogen from culture are essential for ruling out mere contamination.