Table of Contents

m211 Trichophyton ment. var interdigitale Scientific Information Summary Allergen Epidemiology Environmental Characteristics Route of Exposure Clinical Relevance Molecular Aspects Compiled By

Whole Allergen

m211 Trichophyton ment. var interdigitale

m211 Trichophyton ment. var interdigitale Scientific Information

Type:

Whole Allergen

Display Name:

Trichophyton ment. var interdigitale

Route of Exposure:

Contact or Inhalation

Family:

Arthrodermataceae

Species:

Interdigitale

Latin Name:

Trichophyton interdigitale (previously T.mentagrophytes var. interdigitale)

Summary

Trichophyton mentagrophytes var. goetzii and Trichophyton mentagrophytes var. interdigitale have recently been reclassified as the same species, T. interdigitale. T. interdigitale is, along with T. rubrum, the most common cause of dermatophytosis in humans, a highly prevalent infectious disease. T. interdigitalis causes tinea pedis and onychomycosis predominantly. Trichophyton allergens have been implicated in the pathogenicity of both atopic and allergic airway disease. The route of exposure has not been elucidated. Three T. interdigitalis allergens are currently recognized.

Allergen

Nature

Trichophyton interdigitale (previously classified as T. mentagrophytes var. interdigitale) is a dermatophyte fungus and the second most common cause of dermatophytosis in humans, after T. rubrum. Dermatophyte fungi are filamentous and keratinophilic. The differentiation of the various species belonging to the T. mentagrophytes complex, including T. interdigitale, has historically been challenging, as identification through morphology and physiological characteristics was unreliable (1-3).

The T. mentagrophytes complex fungi have previously been classified according to host specificities, either anthropophilic (including T. mentagrophytes var. interdigitale and T. mentagrophytes var. goetzii) or zoophilic (including T. mentagrophytes var. granulosum in rodents and T. mentagrophytes var. quinckeanum in mice). However, the emergence of molecular analysis has resulted in a re-ordering of the classification of the T. mentagrophytes complex. T. mentagrophytes now is a synonym only for the zoophilic T. mentagrophytes var. quinckeanum. Whereas T. mentagrophytes var. interdigitale and T. mentagrophytes var. goetzii, as well as T. mentagrophytes var. nodulare and T. mentagrophytes var. granulosum are now all considered a single species, T. interdigitale, due to being genetically indistinguishable. Different strains of T. interdigitale can be either anthropophilic or zoophilic (2, 4). This reclassification has been formally adopted. From a human clinical perspective, T. interdigtale is the cause of non-inflammatory tinea pedis and unguium, whilst T. mentagrophytes is isolated from cases of tinea corporis, tinea cruris, tinea capitis and tinea faciei (5, 6).

It is possible to distinguish the anthropophilic and zoophilic strains of T. interdigitale morphologically. A difference in the quantity of conidiophores and conidia has been described. The zoophilic strains produce more conidia, resulting in a granular appearance to the colonies with a beige hue. Whereas the anthropophilic strains have a reduced number of conidia and a cottony appearance (4). This difference in clinical, epidemiological and virulence properties between the granular and downy strains has been recognized for over 60 years (7). Sequence analysis of the internal transcribed spacer region of ribosomal DNA is the gold standard for differentiation of dermatophyte species and can be obtained directly from hair, skin or nail samples (4). Correct species identification is essential to select the most effective antimycotic therapy (2).

T. mentagrophytes var interdigitalis is a pathogenic fungus that causes dermatophytosis in humans and animals and is considered a zoonosis. It is predominantly found in cases of tinea pedis and onychomycosis, where a prevalence of between 1.5–55.4% has been reported (8). Furthermore, a T. interdigitale (mentagrophytes) syndrome has been described, characterized as a chronic dermatophytosis that is distinct from other forms of tenia (4). Drug resistance of some strains of T. interdigitale has been reported. One recent study from India described a resistance rate to terbinafine of 32% amongst 63 T. interdigitale isolates (9, 10).

Taxonomy

*Taxonomic tree of Trichophyton* (Fukutomi & Taniguchi, 2015)**
Domain	Eukaryote
Kingdom	Fungi
Phylum	Ascomycota
Subphylum	Pezizomycotine
Class	Eurotiomycetes
Order	Onygenales
Family	Arthrodermataceae
Genus	Trichophyton

*Taxonomic tree of Trichophyton* (Fukutomi & Taniguchi, 2015)**

Since the reclassification of the T. mentagrophytes complex into T. interdigitale and T.mentagrophytes, the differentiation of these species remains challenging and is achieved by sequencing the Internal Transcribed Spacer (ITS) region of the rDNA. ITS analysis has identified 9 different genotypes of T.interdigitale and T.mentagrophytes, which are associated with geographic origin. ITS Type I and ITS Type II are T. interdigitale genotypes and ITS type III – IX are T. mentagrophytes. It suspected that the challenges in distinguishing these dermatophyte infections resulted in their being used interchangeably in the literature (6, 11).

Epidemiology

Worldwide distribution

Trichophyton mentagrophytes and T. rubrum are the most common pathogens associated with onychomycosis (1). However, some geographical variation is reported; in Libya, the most common cause of onychomycosis in women is yeasts of the genus Candida, whereas in men, it is T. violaceum, T. rubrum, T. mentagrophytes and Microsporum canis (12).

The epidemiology of anthropophilic T. interdigitale strains are similar to that of T rubrum. T. interdigitale is the cause of 4–8% of infections in Europe (4). An analysis of Trichophyton spp. contaminating nail dust from salons in different regions of Australia found that T. interdigitale was the most prevalent dermatophyte (13). Thought to be associated with the widespread abuse of topical steroid-containing creams, the underlying cause is widely reported as T. interdigitale. ITS analysis, however, has shown it is T. mentagrophytes (11).

A link between allergic skin disease and dermatophyte infection has been proposed. One study found a 79% prevalence of sensitization to Trichophyton spp. amongst patients with concurrent allergic skin disease and dermatophyte infection termed atopic-chronic dermatophytosis syndrome (Thammahong et al., 2020). This observation supports the findings of a controlled prospective trial from China, which found that 84.9% of patients with chronic urticaria and dermatophytosis were sensitized (as determined by skin prick test) to T. mentagrophytes (14).

Environmental Characteristics

Living environment

Trichophyton spp. are found at very low levels in either indoor or outdoor environments, despite the high prevalence of dermatophytosis in the general population (15). Colonization of the skin is thought to occur through direct contact with infected dander in the environment, and typically busy communal areas of swimming pools or gyms (7, 12).

Route of Exposure

Main

The primary route of exposure to Trichophyton spp. is not fully understood. Sensitization to Trichophyton-specific allergen is common in patients with clinical dermatophytosis, suggesting hypersensitivity is due to transdermal contact with the allergen (15). However, there is evidence that Trichophyton hypersensitivity may also play a role in late-onset asthma and allergic rhinitis and that route of exposure may be inhalation, particularly in those patients with no concurrent dermatophytosis (15). Alternatively, Trichophyton spp. allergens may elicit hypersensitivity through a yet-to-be described mechanism (16).

Clinical Relevance

Trichophyton spp. allergens have been implicated in the pathogenesis of atopic dermatitis, late-onset asthma and allergic rhinitis (7). Trichophyton-specific allergens have been shown to have the unusual capacity to induce either immediate- (ITH) or delayed- (DTH) type hypersensitivity. In some patients, both immune responses are induced (12). The type of immune response induced is strongly associated with the clinical profile of dermatophyte disease. Whereas DTH is associated with acute inflammatory dermatophytosis with resolution, ITH results in persistent low-grade infection. It is proposed this is a dysregulated immune response and the mechanism for the association between chronic dermatophytosis and clinical hypersensitivity. This is supported by evidence of monosensitivity to dermatophyte antigens in patients with ”intrinsic” asthma (12). Furthermore, sensitization to Trichophyton spp. allergens is a possible risk factor for more severe disease amongst patients with asthma (15, 16). T. mentagrophytes has also been implicated as an allergen in a small subgroup of patients with cholinergic urticaria (17).

Molecular Aspects

Allergenic molecules

Table adapted from (18)

Allergen name	Protein group (if known)	Size (kDa)
Tri me 2 (Zhang)	Vacuolated Serine protease, Major allergen	29
Tri me 4 (Zhang)	Alkaline Serine protease, Dipeptidyl peptidase	84
Art va 4	Dipeptidyl peptidase	-

Allergen name

Protein group (if known)

Size (kDa)

Tri me 2 (Zhang)

Vacuolated Serine protease, Major allergen

Tri me 4

(Zhang)

Alkaline Serine protease, Dipeptidyl peptidase

Art va 4

Dipeptidyl peptidase

Allergen name	Protein group (if known)	Size (kDa)

The WHO-IUIS Allergen Nomenclature Sub-Committee recognizes two T. mentagrophytes-specific allergens, Tri me 2 and Tri me 4, which can be considered relevant to T. interdigitale after reclassification. Also, as there are strains of T. interdigitale which belong to the teleomorph species Arthroderma vanbreuseghemii (Nenoff et al., 2007), it could be proposed that Art va 4 is a third T. interdigitale – specific allergen. Additionally, several proteases secreted by T. mentagrophytes have been characterized that invade the epidermal barrier, including substilins and fungalysins. This includes a T. mentagrophytes keratinase, Sub 6, which has been identified as the major allergen Tri r2 from T. rubrum (8).

Cross-reactivity

A study found that a significant number of patients with allergic bronchopulmonary aspergillosis and Aspergillus-sensitized asthma were sensitized to T. mentagrophytes var. goetzii, indicating the possibility that patients are erroneously diagnosed with sensitivity to Aspergillosis spp. allergens (Muthu et al., 2021). Furthermore, a study from China has demonstrated sensitization to T. mentagrophytes (as well as E. flocculosum and T. rubrum) in T. rubrum culture-positive patients, indicating cross-reactivity between the three dermatophytes (14).

Compiled By

Author: RubyDuke Communications

Reviewer: Dr. Christian Fischer

Last reviewed:January 2022

References

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