Type:
Whole Allergen
Whole Allergen
m205 Trichophyton rubrum
m205 Trichophyton rubrum Scientific Information
Display Name:
Trichophyton rubrum
Route of Exposure:
Contact
Family:
Arthrodermataceae
Species:
rubrum
Latin Name:
Trichophyton spp.
Summary
Trichophyton rubrum is the most common cause of dermatophytosis in humans and is found worldwide. It is likely that 70% of humans will have clinical dermatophytosis in their lifetime. Hypersensitivity to dermatophyte molds has been implicated in the pathogenesis of intrinsic, late onset asthma, although the route of allergen exposure is yet to be defined. Trichophyton sensitization is associated with more severe allergic respiratory disease and improvement of clinical hypersensitivity has been achieved with antifungal treatment. Two T. rubrum allergens are described, with evidence of cross-reactivity with other molds.
Allergen
Nature
Trichophyton rubrum is a keratinophilic, filamentous fungus and is a common cause of dermatophytosis, or tinea, the fourth most prevalent human disease (1). T. rubrum forms fluffy, white colonies on the surface, with brown tinges on the reverse. This is likely due to higher metabolic activity resulting in increased ammonia production and elevated pH (2).
T. rubrum is the most prevalent species of dermatophyte fungi, which includes the genera Trichophyton, Microsporum and Epidermophyton (1). It isolated from 50–80% of dermatophyte cases, which take predominantly the tinea pedis and onychomycosis form (3). The dermophyte molds have the ability to invade hair, skin and nails (1), which is achieved by excreting digestive proteases and sulphites to degrade hard keratin (4). Dermatophytosis is considered a major public health problem in some parts of the world (5).
Dermatophytes are classified as anthropophilic, zoophilic or geophilic, a reference to their ecological niche. Nevertheless, dermatophytes from all groups can cause disease in humans (1). However, T. rubrum infection of non-human species is rare (6). Dermatophytosis is generally considered a superficial skin disease and easily treated, although it can cause deep dermatoses in immunocompromised hosts (1).
A significant shift in the global epidemiology of dermatophytosis has been observed in the last 70 years. In the 1920s, T rubrum was infrequently isolated. However, since World War II, it has become the most common dermatophyte in Germany (7). It is also the dermatophyte most commonly isolated from foot mycoses in Africa (8). This epidemiological shift has been attributed to shifting socioeconomic patterns, increasing population and lifestyle changes (increased use of communal gyms and pools, use of synthetic footwear) (5).
Taxonomy
Taxonomic tree of Trichophyton Rubrum (9) |
|
|---|---|
Domain |
Eukaryote |
Kingdom |
Fungi |
Phylum |
Ascomycota |
Subphylum |
Pezizomycotine (10) |
Class |
Eurotiomycetes |
Order |
Onygenales |
Family |
Arthrodermataceae |
Genus |
Trichophyton |
Taxonomic tree of Trichophyton Rubrum (9) |
|---|
Epidemiology
Worldwide distribution
Dermatophytosis is common worldwide and Trichophyton rubrum is the most common dermatophyte in developed countries (8). An estimated 70% of the world’s population are thought develop dermatophytosis at some point in their lifetime (6). Men are more frequently affected than women (5).
The prevalence of sensitization to Trichophyton spp. in patients with allergic skin disease and dermatophyte infection (atopic-chronic dermatophytosis syndrome) was 79% in one study (11). A similar phenomenon was described in patients with chronic urticaria and dermatophyte infection (12), where 75.5% of patients were sensitized to T. rubrum, a significantly greater prevalence than in the control patient groups.
Environmental Characteristics
Living environment
In contrast to other pathogenic fungi, and despite the high prevalence in the general population, Trichophyton spp. are found at very low levels in the indoor or outdoor environment (Fukutomi & Taniguchi, 2015). Skin colonization is thought to occur through direct contact with infected dander in the environment, such as communal areas of swimming pools or gyms (5, 6). Hygiene standards are considered an important factor in the spread of dermatophytes (4).
Route of Exposure
Main
The primary route exposure to the T. rubrum allergen is not yet defined. Trichophyton-specific IgE can be found in patients with dermatophytosis, whether they have atopic disease or not. However, inhaled exposure is still implied for sensitized patients with asthma or rhinoconjunctivitis but without demonstrable dermatophytosis (10). Host- fungal interactions outside the classical sensitization process may also be at play (13).
Secondary
Occupational exposure risk to airborne T. rubrum has been described for nail technicians and podiatrists through inhalation of nail dust (5, 10). A high prevalence of allergen-specific IgE (31%) and sensitization to Trichophyton (16.5%) has been described in this at-risk demographic. However, the incidence of clinically apparent allergy in this group is not known (5).
Clinical Relevance
Trichophyton rubrum allergens can cause either immediate- (IH) or delayed-type hypersensitivity (DTH) reaction in sensitized patients. In some patients, both types of reactions are observed (5). DTH is associated with acute, severe inflammatory dermatophytosis with resolution of the infection. Conversely, an IH reaction is associated with chronic dermatophytosis with low-grade inflammation and is possibly a prerequisite for persistent infection. It has been proposed that dermatophyte induced IH reaction is a marker for immune dysregulation and is the mechanism for the association between chronic dermatophytosis and clinical atopy. Furthermore, monosensitivity to Trichophyton spp. has been described in patients presenting with “intrinsic” asthma, which can be severe (5).
This association has been supported by a placebo-controlled trial where an improvement in allergic-airway symptoms was observed in patients with late-onset asthma and tinea who were treated with oral fluconazole (10).
Molecular Aspects
Allergenic molecules
Table adapted from Allergome.org (14)
Allergen name |
Protein group (if known) |
Size (kDa) |
|---|---|---|
Tri r 2 (Sub6) |
Serine protease, Major allergen |
29 |
Tri r 4 |
Serine protease, Dipeptidyl peptidase |
84 |
Allergen name |
Protein group (if known) |
Size (kDa) |
|---|
Two allergens specific to T. rubrum are recognized as allergens by the WHO/IUIS Allergen Nomenclature Sub-committee: Tri r 2 and Tri r 4. Both are enzymatic homologues (Woodfolk, 2005) and are part of the constituent keratolytic fungal secretions (3, 4).
Tri r 2 is the serine subtilisin protease Sub 6. Encoded by the SUB6 genomic loci (Shi et al., 2015), one of seven genes encoding serine proteases (15). Tri r 2 is able to elicit both IH and DTH reactions. A major allergen, Sub 6, is likely to have a specific role in the T. rubrum infection process (4).
Tri r 4 is a dipeptidyl-peptidase (DPPIV) and has been less well-described. It is thought its pathogenicity lies in its ability to increase vascular permeability, based on the known action of DPPIV (5). It is observed to have similar activities to Aspergillus fumigatus orthologues (4).
Cross-reactivity
Zhang and colleagues have demonstrated cross-reactivity in sensitized patients of T. rubrum with two other dermatophytes (T. mentagrophytes and Epidermophyton floccosum). However, none was reported with the more phylogenetically distant Candida albicans (12). Furthermore, comparative genome analysis of T. rubrum with four other dermatophyte molds shows that most genes are conserved across the five species (1). Furthermore, the allergen Pen c 1 has significant amino acid sequence homology with Tr r 2, suggesting cross-reactivity amongst mold genera may be important in the pathophysiology of asthma where sensitization to molds is prevalent (5).
Compiled By
Author: RubyDuke Communications
Reviewer: Dr. Christian Fischer
Last reviewed:January 2022
References
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- Su H, Packeu A, Ahmed SA, Al-Hatmi AMS, Blechert O, İlkit M, et al. Species Distinction in the Trichophyton rubrum Complex. J Clin Microbiol. 2019;57(9).
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- Gräser Y, Monod M, Bouchara JP, Dukik K, Nenoff P, Kargl A, et al. New insights in dermatophyte research. Med Mycol. 2018;56(suppl_1):2-9.
- Woodfolk JA. Allergy and Dermatophytes. Clinical Microbiology Reviews. 2005;18(1):30-43.
- Ilkit M, Durdu M. Tinea pedis: the etiology and global epidemiology of a common fungal infection. Crit Rev Microbiol. 2015;41(3):374-88.
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- Life Co. Trichophyton rubrum (Castell.) Sabour., 1911 2021 [cited 2021 16.12.21]. Available from: http://www.catalogueoflife.org/annual-checklist/2019/details/species/id/f25bb86d3333904be643faeb7697fa3d
- Fukutomi Y, Taniguchi M. Sensitization to fungal allergens: Resolved and unresolved issues. Allergol Int. 2015;64(4):321-31.
- Thammahong A, Kiatsurayanon C, Edwards SW, Rerknimitr P, Chiewchengchol D. The clinical significance of fungi in atopic dermatitis. International Journal of Dermatology. 2020;59(8):926-35.
- Zhang M, Liu F, Liu H, Shen Y, Kong Q, Sang H. Sensitization and cross-reactions of dermatophyte and Candida albicans allergens in patients with chronic urticaria. Int J Dermatol. 2016;55(10):1138-42.
- Goldman DL, Huffnagle GB. Potential contribution of fungal infection and colonization to the development of allergy. Med Mycol. 2009;47(5):445-56.
- allergome. Tric rubrum 2021 [cited 2021 16.12.21]. Available from: http://www.allergome.org/script/search_step2.php.
- Jousson O, Léchenne B, Bontems O, Mignon B, Reichard U, Barblan J, et al. Secreted subtilisin gene family in Trichophyton rubrum. Gene. 2004;339:79-88..
