Onychomycosis as a Chronic Superficial Fungal Infection: "Why is it so Hard to Clear?"

Abstract

Onychomycosis is a fungal infection of the nail unit. Compared to other superficial dermatophytoses of the skin and hair, onychomycosis is associated with a chronic course and frequent recurrence. Originally, structural characteristics of the nail, such as poor vascular supply and thick layers of hard keratin, were thought to be limiting factors for efficient drug delivery, resulting in prolonged treatment. However, recent research reveals the following crucial mechanisms contributing to the chronicity of nail dermatophytosis: innate characteristics of Trichophyton rubrum, formation of dormant spores called arthroconidia, physical and immunologic characteristics of the nail apparatus, and alteration of the defense system of the host. T. rubrum, the most common causative fungal pathogen for onychomycosis, acquires selective immune tolerance toward the host's defense system. Transformation into dormant phases, such as arthroconidia, creates greater resistance to antifungal medication and nonnutritive environments. The anatomical and biological structures of the nail allow immune evasion, increase infection susceptibility, and promote biofilm formation. Key regulators of the host's innate and adaptive immune systems are downregulated as infection persists, and age-associated immunomodulation aggravates the process.