Dermatophytosis human

Definition

Dermatophytes are a unique group of fungi that infect keratinous tissue and are able to invade the hair, skin, and nails of a living host. This closely related group of organisms can be categorized into one of three genera: Trichophyton, Microsporum, and Epidermophyton. Species within these genera that do not invade keratinous tissue are by definition excluded from the dermatophytes. As with a number of fungi, dermatophytes may exhibit two phases in their life cycle: the anamorph state [imperfect or asexual phase] that is the state isolated in the laboratory, and the teleomorph state [perfect or sexual phase]. The teleomorphs for all dermatophyte species have not yet been identified, but the generic name for both Trichophyton and Microsporum is Arthroderma [the obsolete name Nannizzia has been found to be identical].1-3

AGENTS

Dermatophytes are a closely related homogeneous clade of keratinophilic filamentous fungi36 that are associated with the stratum corneum of the skin, as well as hair and nails on the living host. They possess similar appearance, physiology, antigenicity, growth requirements, infectivity, and pathology. These fungi are classified in the anamorphic genera Epidermophyton, Keratinomyces, Microsporum, and Trichophyton. Some dermatophytes may reproduce sexually when the opposite mating types are crossed with each other. The single ascomycete genus Arthroderma accommodates the known sexual forms of all of the dermatophytes.7

Even though the term dermatophytosis refers to an infection caused by a dermatophyte, not all dermatophytes may cause infection. The fungus colonizes the stratum corneum and then grows in a radial manner without penetrating viable tissue. Invasion of hair, which is nonliving tissue, is an example of colonization. If the fungus enters viable tissue and continues to grow, then infection is present. Majocchi's granuloma [a nodular perifolliculitis due to dermatophytes] and pseudomycetoma are examples of fungal invasion of viable tissue. Colonization or infection may result in disease if there is structural or functional harm. These may be evident as damaged or destroyed hair and nails, hyperhidrosis, pruritus, inflammation, or alopecia. Contamination, the presence of nonreplicating dermatophytes on keratinized tissue, does not occur.

In addition to dermatophytes, other species of fungi that do not colonize or invade the stratum corneum, hair, and nails on the living host are classified in the same anamorphic genera owing to their similar microscopic and colonial characteristics. Some of these species may break down keratin in substrates such as feathers and hooves, but these are no longer on the living host. These keratinophilic species are not dermatophytes. The term dermatomycosis8 is parallel to dermatophytosis, but differs in that it encompasses colonization and infection of keratinized tissue by fungi not classified in the genera Epidermophyton, Keratinomyces, Microsporum, and Trichophyton. In addition, when their sexual forms are known, they are classified in genera other than Arthroderma.

The Agents

Dermatophytes are a closely related homogeneous clade of keratinophilic filamentous fungi36 and are associated with the stratum corneum of the skin, as well as hair and nails on the living host. They possess similar appearance, physiology, antigenicity, growth requirements, infectivity, and pathology. These fungi are classified in the anamorphic genera Epidermophyton, Microsporum, and Trichophyton. Some dermatophytes may reproduce sexually when the opposite mating types are crossed with each other. The single ascomycete genus Arthroderma accommodates the known sexual forms of all of the dermatophytes.7

Even though the term dermatophytosis refers to an infection caused by a dermatophyte, not all dermatophytes may cause infection. The fungus colonizes the stratum corneum and then grows in a radial manner without penetrating viable tissue. Invasion of hair, which is nonliving tissue, is an example of colonization. If the fungus enters viable tissue and continues to grow, then infection is present. Colonization or infection may result in disease if there is structural or functional harm. These may be evident as damaged or destroyed hair and nails, hyperhidrosis, pruritus, inflammation, or alopecia. Contamination, the presence of nonreplicating dermatophytes on keratinized tissue, does not occur.

In addition to dermatophytes, other species of fungi that do not colonize or invade the stratum corneum, hair, and nails on the living host are classified in the same anamorphic genera owing to their similar microscopic and colonial characteristics. Some of these species may break down keratin in substrates such as feathers and hooves; however, these keratinophilic species are not dermatophytes. The term dermatomycosis8 differs in that it encompasses colonization and infection of keratinized tissue by fungi not classified in the genera Epidermophyton, Microsporum, and Trichophyton. In addition, when their sexual forms are known, they are classified in genera other than Arthroderma.

Pathogenicity

Dermatophytes normally infect only the keratinized stratum corneum of the epithelial skin layers.1 They are restricted to the stratum corneum by cellular immune components. An indication of the relative importance of lymphocytes in host defense is seen in HIV infection, in which helper T-cell counts below 100cells/mL correlate with a marked increase in onychomycosis, including the unusual proximal white form.

Dermatophytes differ in their host interactions.1 Anthropophilic dermatophytes, specific to human disease, are distinguished from zoophilic dermatophytes, which have specific animal associations but may be transmitted to humans, and from geophilic dermatophytes, which are occasionally pathogenic to humans or animals but primarily grow on decaying keratinous material. Infection of humans by zoophilic dermatophytes usually elicits a pronounced inflammatory response. Such inflamed lesions may resolve spontaneously, unlike the often chronic lesions of anthropophilic dermatophytoses.

The common anthropophilic dermatophytes include lower body dermatophytes associated with sites other than the scalp, and dermatophytes strongly adapted for tinea capitis, less commonly causing other tineas. Trichophyton rubrum, T. mentagrophytes complex and Epidermophyton floccosum are the common lower body species.1 Tinea capitis dermatophytes consist of two major groups distinguished by their colonization of hair.

Tinea capitis agents primarily cause new infections in children, and may cause dramatic outbreaks.1 Microsporum audouinii infections spontaneously resolve at 1519 years of age, but most endothrix agents cause lifelong asymptomatic infections in some adult carriers.2 New anthropophilic tinea capitis infections are usually acquired via shared headgear, bedding or grooming and haircutting instruments. Adults who acquire new infections caused by endothrix species usually have intimate contact with infected children. Anthropophilic lower body dermatophytoses are often acquired via the feet, either from family members or in communal aquatic or exercise facilities. After infecting the feet, these fungi may go on to infect other body sites.

Zoophilic dermatophytes usually cause tinea corporis or tinea capitis in humans.1 They may be transmitted directly from infected animals or from fomites, such as fence posts in farm yards. Microsporum canis may cause limited outbreaks among humans before virulence is attenuated.

C. albicans is often acquired in the birth canal or in infancy from caregivers.1 Generally, an individual harbors only one or two strains. Cutaneous candidosis is predisposed to by warm, moist conditions with abrasion, especially in the diaper rash of infancy but also in adult occupations that involve wet hands. In the latter cases, paronychia or interdigital erosion frequently results. Intertriginous candidosis occurs in moist body folds and is exacerbated by diabetes mellitus or obesity. Chronic mucocutaneous candidosis [CMC], in which skin and mucosa are extensively colonized by C. albicans, results from inherited defects in cellular immunity1 [see also Chapter 78].

Malassezia spp. are also generally acquired as commensal surface flora in early infancy. They primarily use fatty acids secreted by the skin. Corticosteroid use, Cushing's disease, malnutrition and immunosuppression may contribute to an increased frequency of tinea versicolor.

2.1 Dermatophytosis

Dermatophytes are the causative agents of dermatophytosis [tinea]. They are the group of parasitizing filamentous fungi that are able to infect the keratinized tissues such as the stratum corneum of the epidermis, nails and hairs.810 Dermatophytes induce a dermal inflammatory response which leads to erythema and scaling, which cause intense itching.7 The pathogenesis of tinea include many steps, beginning with the contact of infective spores with the skin, adherence to the superficial cells, invasion of keratin layers by the secretion of the keratinases and induction of inflammation.6 Keratinases degrade the hard keratin into components of low molecular weight which can be utilized by dermatophytes.11 Dermatophytes are subcategorized into different groups. On the basis of their microscopic characteristics they are classified into Trichophyton species, Epidermophyton species, and Microsporum species. According to their normal habitats, they are classified as anthropophilic species, causing infections only in humans, zoophilic species, primarily pathogenic for different animals, and geophilic species, dwelling in the soil.

Dermatophytes are the most common fungi causing superficial skin infections; a frequently isolated pathogen worldwide is Trichophyton [T.] rubrum.1416

Pathogenesis

Dermatophytes prefer to invade keratinized surfaces. In animals, dermatophytosis manifests as a contagious pruritic dermatologic disease resulting in round focal areas of alopecia, ringworm. In humans, dermatophytosis is referred to as tinea and can result in several clinical syndromes such as tinea pedis [athlete's foot], tinea capitis [ringworm of the scalp], tinea corporis [ringworm of the body], or onychomycosis [nail-associated disease]. A thorough description of variation in clinical presentation has been reviewed elsewhere. The infective stage of dermatophytosis is an arthrospore formed by segmentation of fungal hyphae. The arthrospores become associated with host skin after they are encountered in the environment or after touching an infected animal or human. After adhering to keratinocytes, if the arthrospores successfully evade host immunity, they adhere, germinate, and grow resulting in the characteristic ringworm lesion. The intense pruritus associated with infection was associated with dermatophyte serine proteases through protease-activated receptor 2 rather than mast cell degranulation.

Because most dermatophyte infections are self-limiting, current research efforts are directed toward understanding mechanisms by which the fungus attaches to and invades skin. Trichophyton adhesion appears to rely on recognition of mannose and galactose residues on the surface of the arthrospore; the specific adhesins involved in this processes have yet to be identified. Morphologically, Trichophyton extends fibrils into the stratum corneum, but the composition of these structures is unknown. M. canis was shown to produce a subtilisin protease Sub3 and a dipeptidyl peptidase DppvIV, which are involved in adherence. Dermatophyte attachment is an active area of research that will be accelerated by recent developments of models for adherence to animal skin such as reconstructed feline epidermis.

Dermatophytes capitalize on defects or microabrasions in the skin to establish infection, but they also possess mechanisms for keratinolysis that are required for pathogenesis. Keratinolysis is a stepwise process that involves several enzymatic steps beginning with the reduction of keratin and resulting in amino acid monomers. Although a universal invasion enzyme has not been identified, virulence is correlated with fungal keratinolytic activity. Dermatophytes secrete sulfite via efflux pumps, disrupting disulfide bonds and weakening tightly woven keratinized tissue, rendering it susceptible to subsequent enzymatic attack. Subtilisins [Sub4] and fungalysins [Mep3 and Mep4] degrade large proteins, further degraded by DppvV and IV. Host inflammatory factors also contribute to the invasive capability of dermatophytes. In Trichophyton infections, increased β-defensin 2 expression resulted in epidermal proliferation. While proliferation may remove dermatophytes that cannot be accessed by phagocytes in the stratum corneum, this proliferation may also be associated with increased permeability and loss of keratin integrity. While several fungal factors contributing to skin invasion have been described, the host factors contributing to susceptibility and invasion need further investigation.

Presence of dermatophyte antigen in the stratum corneum promotes production of IL-8 by keratinocytes, recruiting neutrophils. Macrophages recognize dermatophytes through lectin receptors dectin-1 and dectin-2. IFN-γ-producing T lymphocytes, eliciting a delayed-type hypersensitivity response, were associated with lesion resolution. Athymic animals are not able to clear infection.