Genetic, immunological and clinical assessment of isolated chronic recalcitrant dermatophytosis: a prospective study

Background Chronic recalcitrant dermatophyte infection (CRDI) remains poorly understood, with limited research on its genetic, immunological and treatment aspects. Objectives To investigate the genetic and immunological profiles, clinical characteristics and treatment outcomes in otherwise healthy patients with CRDI. Methods This was a prospective study of patients with isolated superficial dermatophyte infections persisting for > 5 years and refractory to at least three oral antifungal agents. Whole-exome sequencing, interleukin (IL)-17 quantification and lymphocyte subset analysis were performed. Results Of 5910 patients with superficial cutaneous fungal infections, 11 (10 men; 91%) with a mean (SD) disease duration of 26.4 (8.7) years were included in this study. All patients presented with extensive dermatophytosis, involving a mean (SD) of 5.6 (1.4) skin and nail sites. Immune alterations were identified in 55% (n = 6/11) of the patients, including three with monogenic immunodeficiency mutations (CARD9 and FOXN1), one with acquired immunodeficiency (Good syndrome) and two with isolated IL-17 deficiencies. Most patients (n = 10/11) showed a partial clinical response to continuous oral antifungal therapy, while only one patient remained a complete responder after discontinuing treatment. Conclusions CRDI is a rare condition in patients with superficial cutaneous fungal infections. Genetic and immunological evaluation for immunodeficiency should be considered in patients with CRDI. Management may require prolonged or lifelong oral antifungal therapy.