Emergence and Treatment Challenges in Drug-Resistant Dermatophyte Infections

On the third day of Dermatology Week, Esther Freeman, MD, PhD, focused on the emergence and treatment challenges of drug-resistant dermatophyte infections, contextualizing them within lessons learned from recent global health crises such as the COVID-19 pandemic and the mpox outbreak. In her session she emphasized the role of dermatologists in identifying and managing emerging infections, highlighting the need for vigilance, updated diagnostic practices, and collaboration in outbreak responses.

She began with a retrospective on the COVID-19 pandemic, which underscored the importance of registries in capturing diverse clinical manifestations, including skin-related effects of both the virus and vaccines. She highlighted the creation of a dermatology-specific COVID-19 registry by the American Academy of Dermatology and the International League of Dermatological Societies as a model for data collection. This registry, which has expanded to include conditions like mpox and drug-resistant dermatophytes, exemplifies how dermatologists play a critical role in tracking and addressing health crises beyond traditional dermatologic diseases. She stressed that clinicians are called to adapt their practices, not only recognizing direct dermatologic presentations but also their broader implications in public health.

Moving into lessons from the mpox outbreak of 2022, she described its origins and transmission dynamics. Unlike COVID-19, mpox transmission was predominantly through direct contact with infectious lesions, body fluids, or contaminated objects. While respiratory droplet transmission was possible, it required prolonged close contact. The outbreak revealed atypical presentations, such as single or few localized lesions, especially in the genital and perioral regions. This marked a departure from the classical textbook descriptions of widespread rashes, suggesting evolving patterns of disease presentation. Mpox serves as a cautionary tale about the need to adapt to changing clinical manifestations during outbreaks.

Next, Dr Freeman turned to drug-resistant dermatophyte infections, with a particular focus on the newly emerged species Trichophyton indotineae. Previously classified as a subtype of Trichophyton mentagrophytes, this fungus has gained prominence for its widespread antifungal resistance, particularly to terbinafine, one of the most commonly used treatments. Initial reports of T. indotineae emerged from South Asia, with resistance rates as high as 71% in some studies. While traditionally a regional concern, cases have been identified globally, including in the United States, with the first documented instance occurring in March 2023.

She added that the rise of T. indotineae is attributed to genetic mutations that confer terbinafine resistance, notably in the squalene epoxidase gene. Clinically, infections caused by T. indotineae resemble typical dermatophyte infections but tend to be more extensive, persistent, and refractory to standard treatments. Patients may present with large annular plaques, well-demarcated borders, and significant scaling. These infections are often intensely pruritic and can rapidly spread to multiple body sites, including the face, trunk, and extremities. While nail infections (onychomycosis) are less commonly associated, they are not unheard of.

Dr Freeman emphasized the need for clinicians to maintain a high index of suspicion for resistant infections, particularly in cases that fail to respond to conventional therapies. Accurate diagnosis is essential, requiring laboratory confirmation through fungal culture or molecular testing to identify the species and determine resistance patterns. Current treatment strategies involve using alternative antifungal agents, such as itraconazole or voriconazole, although these too may face resistance challenges.

Broader public health concerns have been raised regarding the global spread of antifungal resistance. The World Health Organization has identified antimicrobial resistance, including that of fungi, as a top global health priority. The emergence of multi-drug-resistant pathogens like Candida auris has been cited alongside dermatophytes as evidence of this growing threat. Such resistance complicates treatment, increases health care costs, and poses risks to vulnerable populations, including immunocompromised patients.

To conclude her presentation, Dr Freeman called for improved surveillance, international collaboration, and public health initiatives to address the rising tide of drug-resistant infections. She encouraged clinicians to report cases, contribute to registries, and participate in research to enhance understanding and management. She reiterated the importance of adapting lessons from past outbreaks, such as COVID-19 and mpox, to strengthen preparedness and response efforts for emerging fungal threats like drug-resistant dermatophytes.

Reference
Freeman E. Antimicrobial-resistant tinea. Presented at: Dermatology Week; November 13–16, 2024; Virtual.