L Appelt1, P Nenoff2, S Uhrlaß2, C Krüger2, P Kühn3, K Eichhorn4, S Buder5, S Beissert6, S Abraham6, R Aschoff6, A Bauer6. 1. Klinik und Poliklinik für Dermatologie, Universitätsklinikum Carl Gustav Carus, Technische Universität, Fetscherstr. 74, 01307, Dresden, Deutschland. linda.appelt@uniklinikum-dresden.de. 2. Labor für medizinische Mikrobiologie, Mölbis, Deutschland. 3. Praxis für Podologie Penelope Kühn, Rheinstr. 32, 56355, Nastätten, Deutschland. 4. Privatpraxis für Venen & Haut, München, Deutschland. 5. Konsiliarlabor für Gonokokken, Klinik für Dermatologie und Venerologie, Vivantes Klinikum Neukölln, Rudower Str. 48, 12351, Berlin, Deutschland. 6. Klinik und Poliklinik für Dermatologie, Universitätsklinikum Carl Gustav Carus, Technische Universität, Fetscherstr. 74, 01307, Dresden, Deutschland.
Abstract
BACKGROUND: In recent years, therapy-refractory courses of dermatophytoses have increasingly become the focus of attention. The most frequent pathogens are Trichophyton (T.) rubrum and T. mentagrophytes. In addition to local therapy, first-line treatment includes terbinafine, an allylamine antifungal agent that acts by inhibiting squalene epoxidase and thus interfering with ergosterol synthesis. In refractory cases, terbinafine resistance due to point mutation in the squalene epoxidase gene has been frequently detected. OBJECTIVES: The aim is to present specific aspects in the epidemiology of dermatophytoses with terbinafine resistance and to illustrate them on the basis of four patient cases including diagnostic procedures. MATERIALS AND METHODS: A review of handbook knowledge, a selective literature search, and a review of four patient cases were performed. RESULTS: Detection of the terbinafine resistance was performed by in vitro testing using the breakpoint method as well as sequencing of the Trichophyton isolate and detection of the point mutation with amino acid substitution at position L393F or F397L of squalene epoxidase. CONCLUSION: In refractory and recurrent dermatophytoses, terbinafine resistance should be considered, especially in T. mentagrophytes and T. rubrum, and in vitro resistance testing of the dermatophyte and point mutation analysis of squalene epoxidase (SQLE) should be performed. Therapeutically, intermittent administration of itraconazole in combination with antifungal local therapy is recommended. Nevertheless, a recurrent course is to be expected and long-term therapy with itraconazole is usually necessary.
BACKGROUND: In recent years, therapy-refractory courses of dermatophytoses have increasingly become the focus of attention. The most frequent pathogens are Trichophyton (T.) rubrum and T. mentagrophytes. In addition to local therapy, first-line treatment includes terbinafine, an allylamine antifungal agent that acts by inhibiting squalene epoxidase and thus interfering with ergosterol synthesis. In refractory cases, terbinafine resistance due to point mutation in the squalene epoxidase gene has been frequently detected. OBJECTIVES: The aim is to present specific aspects in the epidemiology of dermatophytoses with terbinafine resistance and to illustrate them on the basis of four patient cases including diagnostic procedures. MATERIALS AND METHODS: A review of handbook knowledge, a selective literature search, and a review of four patient cases were performed. RESULTS: Detection of the terbinafine resistance was performed by in vitro testing using the breakpoint method as well as sequencing of the Trichophyton isolate and detection of the point mutation with amino acid substitution at position L393F or F397L of squalene epoxidase. CONCLUSION: In refractory and recurrent dermatophytoses, terbinafine resistance should be considered, especially in T. mentagrophytes and T. rubrum, and in vitro resistance testing of the dermatophyte and point mutation analysis of squalene epoxidase (SQLE) should be performed. Therapeutically, intermittent administration of itraconazole in combination with antifungal local therapy is recommended. Nevertheless, a recurrent course is to be expected and long-term therapy with itraconazole is usually necessary.