Resistance and Recalcitrance in Dermatophytosis: Mechanistic and Clinical Considerations for Keratinized Tissues.

Dermatophytosis remains one of the most prevalent superficial fungal infections worldwide and is increasingly encountered as a persistent or difficult-to-treat syndrome. A major clinical problem is that apparent treatment failure is often attributed to antifungal resistance, although many cases are instead driven by diagnostic uncertainty, corticosteroid-modified disease, reinfection, inadequate exposure, poor adherence, and limited drug delivery within keratinized tissues. This narrative review was developed to clarify the distinction between true antifungal resistance and clinical recalcitrance, with particular attention to terbinafine-resistant Trichophyton species, Trichophyton indotineae, tinea incognito, onychomycosis, dermatophytoma, and high-barrier skin and nail infections. We synthesized peer-reviewed literature and guideline-level evidence addressing epidemiology, molecular mechanisms of resistance, clinical phenotypes of recalcitrance, diagnostic escalation, therapeutic decision-making, and antifungal delivery in keratinized tissues. The review contributes a dermatology-centered conceptual framework in which persistent dermatophytosis is interpreted through both microbiological resistance and modifiable recalcitrance drivers. This approach emphasizes confirmation of fungal disease when indicated, phenotypic and anatomic classification, avoidance of inappropriate corticosteroid combinations, optimization of dose, duration, vehicle, and adherence, measures to improve drug access and reduce protected fungal burden in high-barrier disease, and prevention of reinfection from reservoirs. The proposed framework may support more rational antifungal use and reduce unnecessary escalation; however, it is based on narrative synthesis rather than a systematic review or prospective validation. Additional studies are needed to determine how such structured clinical approaches affect clinical outcomes, relapse rates, antifungal exposure, and resistance emergence in real-world dermatology practice.