Why are dermatophytoses (fungal infections) chronic and persistent?

Why Dermatophytoses are Chronic and Persistent

Dermatophytoses are chronic and persistent due to the complex interaction between fungal virulence factors, host immune responses, and environmental factors that allow fungi to evade elimination and establish long-term infection in the nail apparatus and skin.

Pathophysiological Mechanisms of Persistence

Fungal Factors Contributing to Chronicity

• Dermatophytes possess keratolytic properties that allow them to invade and break up the nail plate, creating a protected environment for continued growth 1
• In distal and lateral subungual onychomycosis (DLSO), the most common form of dermatophyte nail infection, fungi spread proximally along the nail bed in a relentless progression until reaching the posterior nail fold 1
• Fungi can persist in nail debris and keratin for extended periods, serving as a reservoir for reinfection 1
• The development of drug-resistant strains, particularly against terbinafine, contributes to treatment failure and persistent infection 2

Host Factors Contributing to Chronicity

• Genetic predisposition plays a significant role in susceptibility to dermatophytosis, with some forms of onychomycosis following an autosomal dominant pattern of inheritance 3
• Increasing age is a major risk factor, with prevalence reaching 20% in those over 60 years and up to 50% in those over 70 years 3
• Immunosuppression significantly increases the risk of developing persistent dermatophytosis, particularly proximal subungual onychomycosis (PSO) 1
• Peripheral vascular disease and diabetes mellitus impair circulation and immune response to the infection site, allowing fungi to establish persistent infection 1, 4

Anatomical Factors Contributing to Chronicity

• The compact structure of the nail plate acts as a barrier to drug penetration, with topical drug concentration dropping by 1000 times from the outer to inner surface 1
• The hydrophilic nature of the nail plate prevents absorption of most lipophilic antifungal molecules with high molecular weights 1
• The slow growth rate of nails (toenails take approximately 12 months to grow out completely, fingernails about 6 months) contributes to the persistence of infection 1

Clinical Manifestations of Chronicity

Patterns of Chronic Dermatophytosis

• Distal and lateral subungual onychomycosis (DLSO) is the most common pattern, affecting the hyponychium initially and spreading proximally along the nail bed 1
• Superficial white onychomycosis (SWO) affects the surface of the nail plate rather than the nail bed, with a flaky appearance 1
• Proximal subungual onychomycosis (PSO) is uncommon but often associated with immunosuppression and may indicate underlying disease 1
• Total dystrophic onychomycosis represents an advanced stage where the nail plate is almost completely destroyed 5

Candidal Onychomycosis

• Chronic paronychia with secondary nail dystrophy occurs in patients with wet occupations, where the cuticle becomes detached from the nail plate, allowing microorganisms to enter the subcuticular space 1
• Distal nail infection with Candida is uncommon and nearly always associated with Raynaud phenomenon or vascular insufficiency 1
• Chronic mucocutaneous candidiasis leads to gross thickening and hyperkeratosis of the nail plate, often with frequent relapses 1

Treatment Challenges Contributing to Chronicity

Pharmacological Challenges

• Treatment requires long duration (6-12 months for toenails, 6 months for fingernails) due to the slow growth rate of nails 1, 5
• The hard keratin and compact structure of the nail plate limit drug penetration, making topical treatments less effective for extensive infections 1
• Antifungal resistance, particularly against terbinafine, is increasingly reported and contributes to treatment failure 2

Clinical Management Challenges

• Inadequate treatment duration is a common cause of recurrence, as treatment must continue until the infected nail has grown out completely 1
• Misdiagnosis is common, with approximately 50% of nail dystrophies being fungal in origin, leading to inappropriate treatment 1
• Failure to address concurrent skin infections (e.g., tinea pedis) can lead to reinfection of treated nails 1
• Comorbidities such as diabetes and immunosuppression complicate management and increase the risk of treatment failure 3, 4

Prevention of Recurrence

• Treatment of all concurrent fungal infections, particularly tinea pedis, is essential to prevent reinfection 1
• Addressing underlying risk factors such as peripheral vascular disease, diabetes, and immunosuppression is crucial for long-term management 1, 4
• For Candida paronychia, avoiding prolonged water exposure and maintaining proper hand hygiene can prevent recurrence 1
• In chronic mucocutaneous candidiasis, high-dose therapy for extended periods may be necessary, but this can lead to the development of drug-resistant strains 1