Recent Findings in Onychomycosis and Their Application for Appropriate Treatment

Area of Science:

• Medical Mycology
• Dermatology
• Infectious Diseases

Background:

• Onychomycosis is a common nail infection, predominantly caused by Trichophyton rubrum and Trichophyton interdigitale.
• Understanding fungal virulence factors is crucial for effective treatment of nail infections.

Purpose of the Study:

• To investigate the key proteases involved in nail invasion by dermatophytes.
• To re-evaluate the role of in vitro cultured proteases as virulence factors in onychomycosis.
• To highlight the importance of accurate fungal identification for refractory cases.

Main Methods:

• Analysis of fungal proteases secreted during in vivo nail infection.
• Comparison of in vivo secreted proteases with those obtained from in vitro keratin digestion.
• Review of treatment outcomes for onychomycosis caused by various fungi.

Main Results:

• Subtilisin Sub6 was identified as the primary protease secreted by Trichophyton species during nail infection, not detectable under in vitro conditions.
• Proteases abundant in vitro keratin digestion were largely absent in infected nails, invalidating their role as primary virulence factors.
• Non-dermatophyte molds like Fusarium and Aspergillus are resistant to standard terbinafine/itraconazole treatments.
• Topical amphotericin B is effective for refractory cases.
• Terbinafine resistance in Trichophyton, often due to squalene epoxidase mutations, necessitates alternative treatments like azoles.

Conclusions:

• The primary virulence factors of Trichophyton in onychomycosis are proteases secreted during infection, not those cultured in vitro.
• Accurate identification of the causative agent is essential for selecting appropriate antifungal therapy, especially in treatment-resistant onychomycosis.
• Emerging terbinafine resistance in Trichophyton infections requires consideration of alternative treatments such as azole-based therapies.