A new mutation in the SQLE gene of Trichophyton mentagrophytes associated to terbinafine resistance in a couple with disseminated tinea corporis.

Trichophyton is the most common dermatophyte genus responsible for tinea corporis and topical treatment with terbinafine is effective for limited disease but extensive disease required systemic therapy. Failure of terbinafine therapy in patients infected with T. rubrum or T. mentagrophytes is associated with mutations in the gene encoding squalene epoxidase, the terbinafine target. We report two cases of tinea corporis resistant to systemic terbinafine in a 60-year-old man and his wife, a 51 year-old-woman. Both patients had multiple diffuse erythematous annular scaly plaques and T. mentagrophytes was isolated in culture. Systemic treatment with terbinafine in combination with topical terbinafine and then topical ketoconazole failed to improve the disease after 8 weeks. The broth microdilution tests performed to evaluate the antifungal sensitivity of the T. mentagrophytes isolate revealed a high MIC for terbinafine but a low MIC for posaconazole and itraconazole. An A1223T point mutation leading to a Q408L substitution was identified by DNA sequencing the SQLE gene of the isolate. Itraconazole 200mg daily was then introduced but stopped because of elevated liver transaminases in the man. Finally, complete healing was achieved only six months later for both patients and required a 3 and 2-week regimen of itraconazole with topical eberconazole in the man and woman respectively. We believe that a close monitoring and antifungal susceptibility tests should now be done more systematically in dermatophytic infections that do not respond to conventional treatment as terbinafine resistant strains are likely to spread worlwide.