Trichophyton indotineae-An Emerging Pathogen Causing Recalcitrant Dermatophytoses in India and Worldwide-A Multidimensional Perspective

Abstract

Trichophyton (T.) indotineae is a newly identified dermatophyte species that has been found in a near-epidemic form on the Indian subcontinent. There is evidence of its spread from the Indian subcontinent to a number of countries worldwide. The fungus is identical to genotype VIII within the T. mentagrophytes/T. interdigitale species complex, which was described in 2019 by sequencing the Internal Transcribed Spacer (ITS) region of ribosomal DNA of the dermatophyte. More than 10 ITS genotypes of T. interdigitale and T. mentagrophytes can now be identified. T. indotineae causes inflammatory and itchy, often widespread, dermatophytosis affecting the groins, gluteal region, trunk, and face. Patients of all ages and genders are affected. The new species has largely displaced other previously prevalent dermatophytes on the Indian subcontinent. T. indotineae has become a problematic dermatophyte due to its predominantly in vitro genetic resistance to terbinafine owing to point mutations of the squalene epoxidase gene. It also displays in vivo resistance to terbinafine. The most efficacious drug currently available for this terbinafine-resistant dermatophytoses, based on sound evidence, is itraconazole.

Keywords: ITS sequencing; Itraconazole; Trichophyton mentagrophytes; anthropophilic; antifungal; dermatophytoses; terbinafine resistance; tinea corporis; tinea cruris; tinea faciei.

Figure 1

Tinea corporis generalisata in an Indian patient. The itchy erythematosquamous plaques converge over a large area and are sharply limited to the unaffected skin of the environment. Differential diagnosis includes psoriasis vulgaris, microbial eczema, or seborrheic eczema. The diagnosis can be confirmed by detection of the dermatophyte Trichophyton mentagrophytes genotype VIII or Trichophyton indotineae from skin scales. (Dr Bhavesh Devani, Drashti Skin & Eye Care Hospital-Cosmetic Laser & Hair Care Center, Rajkot, Gujarat, India).

Figure 2

Tinea cruris and tinea genitalis in a 24-year-old patient by Trichophyton indotineae. (Dr. Lars Köhler, dermatologist, Mainz, Germany).

Figure 3

The phylogenetic analysis of the T. mentagrophytes/T. interdigitale complex based on the sequencing of the ITS regions of the rDNA. The calculations are based on the maximum likelihood method and the Tamura–Nei model from [26]. The phylogenetic family tree shows the distinction between the previously known genotypes of T. interdigitale and T. mentagrophytes, based on the sequencing of the ITS regions of rDNA genes. Genotypes I and II of the anthropophilic species T. interdigitale are found in the upper part of the dendrogram. Within the species T. mentagrophytes there are a total of 11 different genotypes—III, III*, IV, V, VII, IX, XXV, XXVI, XXVII, and XXVIII—including T. mentagrophytes ITS VIII (T. indotineae). The so-called mixed type or intermediate genotype (II*) is located between the clusters of T. interdigitale and T. mentagrophytes. The phylogenetic family tree was rooted with Trichophyton quinckeanum. Labeling after transmission.

Figure 4

Temporal course and changes in taxonomy and nomenclature of Trichophyton mentagrophytes and Trichophyton interdigitale. The earlier zoophilic and anthropophilic variants are grouped into species over time. Within the new species, more than ten different genotypes can be distinguished. Among these, Trichophyton mentagrophytes ITS genotype VIII represents a clinically significant “clonal offshots” and is now considered as the independent species Trichophyton indotineae. In addition, there are Trichophyton interdigitale (anthropophilic), Trichophyton mentagrophytes (zoophilic), Trichophyton erinacei (zoophilic), Trichophyton quinckeanum (zoophilic), and Trichophyton benhamiae (zoophilic).

Figure 5

Trichophyton indotineae: colony growth, isolated from dandruff of a 27-year-old patient with tinea corporis. The patient comes from Bangladesh but lives and works in Germany. Growth on Sabouraud 4% glucose agar without cycloheximide additive. (a) Fast-growing, peripherally white, medial beige to light brown pigmented flat and granular colonies; (b) detailed view of colonies of the same isolate with impressive granular aspect of the thallus; (c) the reverse of the colonies is pigmented in light brown to yellowish.

Figure 6

Trichophyton indotineae. Microscopic features of an isolate from tinea corporis and tinea genitalis of the mons pubis of a 24-year-old female from Bangladesh living in Germany. (a) Small and big round and oval microconidia together with spindle shaped septate macroconidia; (b) spiral hyphae.

Figure 7

Widespread tinea generalisata (erythroderma-like) due to merging of multiple large plaques of tinea corporis in a healthy immunocompetent man in India. History of using over 100 units (tubes) of fixed-dose combination creams (FDC) containing clobetasol propionate, clotrimazole/miconazole, and gentamicin/neomycin, in addition to erratic use of topical and oral antifungal drugs, for over a year.

Figure 8

Multiple recurrent plaques of tinea corporis et cruris in a young woman applying FDCs containing the same drugs as those used for over a year by the man in Figure 7. While the plaques have partially resolved on the trunk, she is developing new lesions, including one lesion of ‘tinea pseudoimbricata’ on the right thigh with concentric circles. Some lesions of ‘tinea recidivans’ show evidence of new appearance of active inflammatory margins in healed plaques of tinea. More interestingly, and unusual for a record from a Western dermatologist, are the striking striae albae and patchy hypopigmentation, both due to the misuse of FDCs containing clobetasol propionate, itraconazole, and irrational antibiotics for several months.

Figure 9

Terbinafine-resistant strain of Trichophyton indotineae. Isolate of a 41-year-old Indian male with tinea corporis. The susceptibility testing of this strain to terbinafine by agar dilution test yielded a minimum inhibitory concentration >0.5 μg/mL (breakpoint 0.2 μg/mL) corresponding to in vitro resistance to terbinafine. The left panel shows growing of the T. indotineae strain at terbinafine concentration 0.1, 0.2, and 0.5 µg/mL. The right panel shows growth of the dermatophyte at 0.2 µg/mL; however, growth was suppressed at terbinafine concentration of 8 and 16 µg/mL. The mutation analysis of the gene of squalene epoxidase revealed amino acid substitution in position F397L and thus proved terbinafine resistance.