Mycology – an update. Part 1: Dermatomycoses: Causative agents, epidemiology and pathogenesis

Authors


  • Conflict of interest None.

  • Trichophyton rubrum is the most common dermatophyte in Germany and worldwide.

  • The prevalence of fungal nail infections in certain risk groups, e.g., diabetics and psoriasis patients, is higher than in the general population.

  • Yeasts – primarily Candida albicans – cause candidiasis affecting the skin and mucous membranes.

  • Malassezia-related superficial skin infections, primarily pityriasis versicolor, are very common.

  • Non-dermatophyte molds (NDM) are increasingly found to be the cause of onychomycosis of the toenails.

  • The most common pathogens identified in children and adolescents are zoophilic dermatophytes.

  • The target structures for Trichophyton rubrum 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 more than 90%.

  • T. rubrum infections are increasingly occurring at other sites on the body than previously reported.

  • Tinea pedis and onychomycosis are caused by the anthropophilic dermatophytes T. rubrum, T. interdigitale and Epidermophyton floccosum.

  • As a rule, a healthy nail is not susceptible to fungal infection.

  • Predisposing factors for tinea pedis et unguium include circulatory disorders affecting the lower extremities as well as metabolic disorders such as diabetes mellitus.

  • In treatment-refractory onychomycosis, keratinization disorders affecting the skin and nails are more common than previously thought.

  • 27% of psoriasis patients who have nail changes have onychomycosis involving the toenails.

  • Disorders of cellular immunity are among the predisposing factors for dermatophytosis.

  • Diabetics have a higher risk of tinea pedis and onychomycosis.

  • Onychomycosis is now considered to be a predictor of diabetic foot syndrome.

  • Onychomycosis is significantly more common if the feet were not washed on a daily basis.

  • Diabetics who are using hemodialysis have about an 88% higher probability of onychomycosis than non-diabetics.

  • A family history of disease is considered to be a risk factor in onychomycosis

  • Autosomal dominant inheritance of a susceptibility factor promotes the development of distal subungual onychomycosis due to Trichophyton rubrum.

  • Ashkenazi Jews are protected from onychomycosis by the human leukocyte antigen DR4 (HLA-DR4).

  • 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 destroy the complex protein, keratin, found in the nails and epidermis via keratinase.

  • Due to the high level of enzyme activity at normal body temperature and skin pH levels, dermatophytes (e.g., Trichophyton spp.) are well-suited to the skin's surface in human beings.

  • Thus, the pathogen reservoir of T. rubrum, as an anthropophilic dermatophyte, is only found on the person himself or in his home.

  • Along with the keratinases, cysteine dioxygenase and a sulfite efflux pump are also responsible for keratin degradation.

  • Proteolytic enzymes, such as hydrolase (keratinases, nucleases) and cysteine dioxygenase, allow keratin degradation by dermatophytes. They are considered virulence factors.

  • A comparative genomic analysis of T. rubrum and closely-related dermatophyte species studied the candidate genes which are responsible for infection. The dermatophyte species exhibited various biological behaviors related to host specificity, reproductive behavior, and disease course.

  • Although fungal nail infections are not life-threatening, they can significantly impair the patient's quality of life.

  • The most common problems affecting the patients' attitude toward life were issues concerning cutting the nails, cosmetically disturbing disfigurement, and ill-fitting shoes.

  • 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.

  • Onychomycosis was found to lead to a similar level of stigmatization as psoriasis vulgaris.

  • Along with cats, especially rodents (e.g., guinea pigs) are a source of infection and transmission of dermatophytes.

  • Because these diseases are not notifiable in Germany, there has been a nearly invisible shift in pathogens toward infections by Trichophyton species of Arthroderma benhamiae.

  • T. interdigitale – previously known as T. mentagrophytes – is now the second most common dermatophyte in Germany.

  • The anthropophilic strains of T. interdigitale tend to cause tinea unguium and tinea pedis, and, less often, tinea corporis.

  • 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.

  • Nearly all other anthropophilic and zoophilic varieties of Trichophyton mentagrophytes are now taxonomically classified under the new species Trichophyton interdigitale.

  • In Germany, there has been a virtually unnoticed increase in A. benhamiae.

  • Trichophyton species of Arthroderma benhamiae can cause tinea with severe inflammation in children/adolescents and immunosuppressed patients.

  • In terms of mycological diagnosis, T. species of A. benhamiae may be confused with M. canis, T. interdigitale, T. erinacei, or T. soudanense.

  • The most reliable method of identification of A. benhamiae is direct molecular biological detection in skin flakes using polymerase chain reaction (PCR-Elisa).

  • 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.

  • In Italy, 100% of stray cats are carriers of M. canis.

  • Humans can become infected by direct contact with sick animals, healthy carriers, or by contact with contaminated dust, brushes, or clothing.

  • Trichophyton verrucosum is becoming increasingly common due to low vaccination rates of livestock (calves).

  • Calves and cows are the infection source, transmitting disease mainly to children and adolescents who are vacationing on a farm.

  • 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).

  • According to the German Ordinance on Occupational Disease (Berufskrankheitenverordnung [BeKV]), any suspected professional acquired T. verrucosum infection must be reported.

  • T. erinacei – an emerging pathogen – is transmitted as a zoophilic dermatophyte from hedgehogs to people.

  • Non-endangered hedgehogs imported from Africa are the pathogen reservoir for tinea forms with severe inflammation due to Trichophyton erinacei in humans.

  • 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.”

  • In recent years, Microsporum audouinii has again been isolated in Germany. This highly contagious dermatophyte was brought there from Africa by immigrating families and has caused small epidemics.

  • Contact with soil can lead to infection with the geophilic dermatophyte M. gypseum

  • In the United States, T. tonsurans is the most common pathogen in tinea capitis in children and adults (especially among African Americans and Hispanics).

  • Outbreaks of tinea corporis et capitis gladiatorum due to T. tonsurans (which is associated with wrestling mats) routinely occur in children and adolescents who participate in wrestling.

  • T. violaceum is an anthropophilic “exotic” dermatophyte that occurs in tropical regions, especially Sub-Saharan Africa (Figure ).

  • In Germany, Trichophyton violaceum infections overwhelmingly affect immigrants from Africa and people with whom they have had contact.

  • In terms of molecular genetics, T. soudanense is identical to T. violaceum; the phenotypes of the pathogens differ significantly, however.

  • In 1839 Robert Remak and Johann Lukas Schönlein discovered the pathogen that was responsible for a fungal skin infection which later became known as T. schönleinii.

  • In Germany, T. schoenleinii occurs only very rarely, as a sporadic infection.

  • The anthropophilic dermatophyte Epidermophyton floccosum is rarely isolated. It mainly affects the skin (tinea pedis, tinea inguinalis), but may affect the nails. It does not affect the hair.

  • Malassezia 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.

  • In recent years, along with M. furfur and M. pachydermatis (non-lipophilic, transmitted by dogs), a large number of new species have been described.

  • The most commonly identified causative fungus in pityriasis versicolor is M. globosa.

  • There have been increasing reports of non-dermatophyte molds (NDM) causing onychomycosis.

  • Distinguishing between molds as relevant pathogens in onychomycosis and mere colonization is a diagnostic challenge.

  • Pathogens in NDM onychomycoisis include Scopulariopsis brevicaulis, along with Fusarium and Aspergillus species and other rare molds.

  • 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.

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.

Ancillary