Abstract
Tinea unguium caused by dermatophyte species are usually treated with oral antimycotic, terbinafine (TBF). To understand the mechanisms of improvement and recalcitrance of tinea unguium by oral TBF treatment, a method of quantifying dermatophyte viability in the nail was developed, and the viability of dermatophytes was analyzed in toenail lesions of 14 patients with KOH-positive tinea unguium treated with oral TBF 125 mg/day for up to 16 weeks. Mycological tests, including KOH examination and fungal culture, and targeted quantitative real-time PCR for internal transcribed spacer (ITS) region, including rRNA, were demonstrated at the initial visit and after 8 and 16 weeks of treatment. Assays in eight patients showed that average ITS DNA amount significantly decreased, to 44% at 8 weeks and 36% at 16 weeks compared with 100% at initial visit. No significant difference was observed between at 8 and 16 weeks, despite the TBF concentration in the nail supposedly more than 10-fold higher than the minimum fungicidal concentration for dermatophytes. This finding suggests the pathogenic dermatophytes in nail lesions could survive in a dormant form, such as arthroconidia, during oral TBF treatment. Both antimycotic activity and nail growth are important factors in treatment of tinea unguium.
Highlights
Onychomycosis is the most common nail disorder, with a mean prevalence of 11.4% (95% confidence interval: 9.1–13.6%) calculated from 21 previous reports [1]
The quantification ranges by Quantitative Real-Time PCR (qPCR) ranged from 101 to 107 conidia when DNA samples were extracted in the presence or absence of human nail
DNA is more stable than RNA, the number of internal transcribed spacer (ITS) DNA copies decreased markedly 48 h after adding 1 lg/mL TBF to germinating conidia, with the number of copies consistent with the number of colony-forming units (CFU) [13]
Summary
Onychomycosis is the most common nail disorder, with a mean prevalence of 11.4% (95% confidence interval: 9.1–13.6%) calculated from 21 previous reports [1]. The major pathogens of onychomycosis are dermatophyte species, a condition called tinea unguium, which produce arthroconidia from hyphae in some nail lesions [2]. Because the complete cure rate, defined both clinically as 100% cleaning of the toenail and mycologically as negative on KOH examination and fungal culture, reached 55% at week 72 for the patients treated with 250 mg/day TBF for 16 weeks. This rate was significantly higher than that of patients treated with 400 mg/day itraconazole for 1 week every 4 weeks for 16 weeks [7]
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