In 2020, Trichophyton indotineae was recognized as a distinct species within the TMTI complex after characterization of the highly terbinafine-resistant genotype VIII¹. Since 2018, an epidemic-like increase in recalcitrant dermatophytosis has been documented in India, which was largely attributed to the inappropriate use of topical steroid-antifungal combinations and incomplete antifungal therapy^2,3. Following its initial description, T. indotineae has been reported across Asia, the Middle East, Europe, and North America^4-7. By 2024-2025, confirmed cases of T. indotineae had also emerged in Taiwan and Thailand^8,9.

In Korea, clinicians have increasingly suspected terbinafine-resistant dermatophytosis. However, to date, no infections had been molecularly confirmed as T. indotineae. Herein, we report two such cases and discuss their clinical course, laboratory confirmation, and implications for local transmission and antifungal stewardship.

A 36-year-old man presented with multiple pruritic plaques involving the trunk, buttocks, and legs that had persisted for more than one year. The eruption began as small erythema- tous annular plaques on the thighs and gradually expanded, forming large confluent scaly plaques (Fig. 1, A1 and A2). The patient had been treated with topical terbinafine preparation and oral terbinafine (200-375 mg/day) for three months with- out improvement. In fact, the lesions became more extensive. Subsequently, he received oral itraconazole (200 mg/day) irregularly for about five months. However, this regimen only led to brief periods of partial improvement. For severe itching, he intermittently received short courses of oral methylpredni- solone and used topical antifungal-corticosteroid combination creams (clotrimazole-hydrocortisone, econazole-triamcinolone acetonide, and isoconazole nitrate-diflucortolone valerate), but the eruption progressively worsened. The patient had no history of overseas travel.

Several months after his eruption began, his Korean partner developed similar pruritic annular plaques, raising suspicion of household transmission. A 29-year-old woman presented with large coalescent annular plaques on her right ankle and lower leg, accompanied by intense pruritus and excoriations (Fig. 1, B1). She had taken oral terbinafine (250 mg/day) for three months without significant response. Subsequent treat- ment with oral itraconazole (200 mg/day) for five months, together with the same topical antifungal-corticosteroid com- bination creams as case 1 and intermittent short courses of oral methyl-prednisolone, produced only transient relief. Moreover, the affected area slowly enlarged during this period. The patient also denied any travel abroad.

In both patients, the lack of response to an apparently adequate course of oral terbinafine raised strong suspicion for terbinafine-resistant dermatophytosis. Irregular itracona- zole therapy combined with the intermittent use of cortico- steroids did not induce remission. Therefore, all topical and systemic corticosteroids were discontinued, and itraconazole was switched to another generic formulation and administered at 200 mg/day under close supervision. Both patients steadily improved with strict adherence to this regimen. After five months, case 2 showed complete clinical and mycological remission, whereas case 1 showed near-complete clearance with only faint residual scaling on the buttocks and thighs (Fig. 1, A3, A4, and B2). Follow-up cultures were negative in both cases, although a few hyphae were still detectable on direct KOH examination in case 1.

Figure 1. Clinical features and treatment response in two Korean patients with dermatophytosis caused by Trichophyton indotineae. (A1 and A2) Before adequate treatment, case 1 showed extensive annular and polycyclic erythematous plaques with scaly active borders on the trunk, buttocks, and thighs, which were partly modified by intermittent potent topical corticosteroids. (A3 and A4) Near-complete clearance with faint post inflammatory hyperpigmentation at five months after corticosteroid withdrawal and continuous oral itraconazole; (B1) Before adequate treatment, case 2 showed coalescent annular plaques with peripheral scale on the right lower leg and ankle. (B2) Complete clinical remission after supervised itraconazole therapy and discontinuation of steroid-containing topical preparations

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Direct KOH examination of skin scraps from both patients revealed branching septate hyphae. Meanwhile, cultures on Sabouraud dextrose agar and potato dextrose cornmeal agar with Tween 80, incubated at 25-30℃, produced colonies within 10 days. The colonies were white to gray in color, fluffy, and somewhat cottony with yellow-brown reverse pigmentation (Fig. 2, A and B).

Microscopic examination revealed numerous pyriform microconidia arranged in grape-like clusters, spiral hyphae, and frequent macroconidia, which are features compatible with the TMTI complex (Fig. 2, C and D). Urease test on Christensen's urea agar remained negative after 14 days, whereas T. mentagrophytes and T. interdigitale controls typic- ally became positive within one week (Fig. 2, E). The negative urease reaction supported T. indotineae as the presumptive species.

Figure 2. Mycological findings of Trichophyton indotineae isolates from the two patients. (A and B) Colonies on potato dextrose cornmeal agar with Tween 80 after 14 days at 25-30℃, showing white to gray cottony surfaces compatible with the T. mentagrophytes / T. interdigitale complex; (C and D) Lactophenol cotton blue mounts (×400) with numerous pyriform microconidia in grape-like clusters, spiral hyphae, and macroconidia; (E) Urease test on Christensen's urea agar after 14 days; Both clinical isolates remain urease-negative, whereas the T. interdigitale control is urease-positive, supporting identification of T. indotineae.

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DNA sequencing of the internal transcribed spacer (ITS) region showed 100% identity with the T. indotineae type strains NUBS19006 (NR_173767) and NUBS19007 (LC- 508728). Meanwhile, squalene epoxidase (SQLE) gene se- quencing identified a c.1179A>T substitution at codon 393, resulting in the L393F amino acid change.

Antifungal susceptibility testing was performed according to the CLSI M38-A3 protocol. The minimum inhibitory con- centrations (MICs) are summarized in Table 1. Both isolates demonstrated high-level resistance to terbinafine (MIC values >10 μg/mL) while remaining susceptible to itraconazole and posaconazole.

These two cases represent the first molecularly confirmed T. indotineae infections acquired in Korea. The lack of travel history in both patients and the occurrence of a similar eruption in a household contact of case 1 suggest that an imported terbinafine-resistant strain may now be circulating domestically, as has been observed in other regions^5,6,9.

Morphologic differentiation among members of the TMTI complex is difficult and often unreliable¹⁰. In our patients, the colony morphology and microscopic findings were compatible with the TMTI complex, but not distinctive for T. indotineae. The negative urease tests raised suspicion, whereas definitive identification required ITS sequencing. This finding highlights the need for access to molecular tools and updated matrix-assisted laser desorption/ionization time-of-flight databases or species-specific polymerase chain reaction assays, where available^7,11.

Terbinafine resistance in T. indotineae has been associated with structural alterations in SQLE that reduce terbinafine binding while preserving enzyme function. The F397L sub- stitution is most frequently reported worldwide, followed by L393F, with other substitutions being less commonly described^7,10,12. Our isolates carried L393F and showed high terbinafine MICs, consistent with these reports.

Clinicians should consider T. indotineae when patients present with large, scaly plaques involving the trunk and groin while sparing the feet and nails, and fail to respond to a 4~6-week course of appropriately dosed terbinafine^3,13,14. A negative urease test in a TMTI-complex isolate further raises suspicion for this species¹⁰. In such cases, mycological con- firmation, including culture, molecular identification, and antifungal susceptibility testing, is important for patient man- agement and surveillance^7,11.

Itraconazole is generally effective against T. indotineae. However, clinical outcomes may be compromised by irregular intake, suboptimal formulations, or concurrent corticosteroid use^14,15. In our patients, in vitro susceptibility testing suggested that itraconazole remained active, and clinical failure appeared to be driven primarily by irregular dosing, concomitant use of systemic and topical corticosteroids, and possibly formulation-dependent differences among itraconazole generics. Both patients showed gradual but sustained improvement under supervised itraconazole monotherapy at 200 mg/day with complete withdrawal of corticosteroids, resulting in near-complete clearance with minimal residual scaling and low-level residual hyphae on KOH in case 1 and complete clinical and mycological remission in case 2. Because therapeutic drug monitoring was not performed, our experience cannot be taken as proof of superiority of one generic over another. However, the temporal association suggests that formulation-dependent bioavailability and consistent intake may play a clinically relevant role in real-world practice¹⁵.

For symptom control, patients with severe pruritus are often prescribed with short courses of topical or systemic cortico- steroids. However, in active dermatophytosis, corticosteroids can modify lesion morphology, delay diagnosis, and prolong the disease course^2,3,13. During antifungal therapy, symptom- atic relief should primarily rely on nonsteroidal measures, including oral antihistamines, emollients, and cooling agents. If corticosteroids are considered unavoidable, they should be used at the lowest effective potency and for the shortest possible duration under close follow-up.

From a public health standpoint, the emergence of T. indotineae in Korea highlights the need for coordinated anti- fungal resistance surveillance. In Europe, reference laboratory networks and standardized susceptibility testing have enabled earlier recognition of resistant dermatophytes^4,16. However, antifungal susceptibility testing is rarely performed in routine practice in Korea, largely because it is not reimbursed. The inclusion of such testing within insurance coverage, together with national guidelines recommending when to test, would facilitate systematic monitoring of MIC trends and SQLE mutations. Ongoing data collection will be essential for up- dating treatment recommendations and supporting antifungal stewardship.

This report is limited by the small number of patients, lack of therapeutic drug monitoring for itraconazole, and absence of confirmatory testing in household contacts. Moreover, although case 2 achieved complete clinical and mycological cure, case 1 still showed minimal residual scaling and a few hyphae on KOH at the last follow-up. Therefore, longer observation is needed to confirm durable mycological cure. Our statement that these are the first molecularly confirmed T. indotineae cases in Korea is based on extensive searches of domestic and international literature and conference abstracts available at the time of writing. However, unpublished or unrecognized cases may exist.

T. indotineae has now been identified as a terbinafine-resistant dermatophyte causing extensive tinea corporis and cruris in Korea. This species should be suspected when large, intensely pruritic plaques on the trunk and groin persist des- pite standard terbinafine therapy and when urease-negative isolates of the TMTI complex are recovered. Corticosteroid withdrawal, use of adequately dosed itraconazole, and access to molecular identification and antifungal susceptibility testing will be crucial to treat and limit the spread of T. indotineae.