What is the recommended treatment for onychomycosis of the toe nail in an otherwise healthy adult?

Treatment of Toenail Onychomycosis

Oral terbinafine 250 mg daily for 12 weeks is the first-line treatment for toenail onychomycosis in otherwise healthy adults, achieving mycological cure rates of approximately 73% at 48 weeks post-treatment. 1

Diagnostic Confirmation Required Before Treatment

• Never initiate treatment without mycological confirmation through microscopy with potassium hydroxide (KOH) and fungal culture, as incorrect diagnosis is the most common cause of treatment failure 1, 2
• Dermatophytes (primarily Trichophyton rubrum) cause approximately 90% of toenail onychomycosis cases 3
• Non-dermatophyte molds account for about 5% of UK cases and 20% of North American cases 4

First-Line Systemic Treatment

Oral terbinafine 250 mg once daily for 12 weeks continuously is the gold standard for dermatophyte toenail infections, offering superior mycological and clinical cure rates compared to all other systemic agents 1, 2

Key advantages of terbinafine:

• Achieves 70-80% cure rates for toenails 2
• Low risk of drug interactions, making it particularly preferred in diabetic patients 1
• Preferred in immunocompromised patients due to reduced antiretroviral drug interactions 1, 2
• No hypoglycemia risk 2

Monitoring requirements:

• Check liver function tests (ALT and AST) before starting treatment, especially in patients with excessive alcohol consumption, hepatitis, or other liver diseases 2
• Monitor for reversible taste disturbance and idiosyncratic liver reactions 1

Second-Line Systemic Treatment

Itraconazole is recommended as second-line therapy when terbinafine fails or is contraindicated 1, 2

Dosing options:

• Continuous therapy: 200 mg daily for 12 weeks 1
• Pulse therapy: 400 mg daily for 1 week per month for 3 pulses (better compliance but slightly lower efficacy) 1, 2

Critical contraindication:

• Itraconazole is absolutely contraindicated in heart failure due to negative inotropic effects 1

Special indication:

• Itraconazole is more effective than terbinafine for non-dermatophyte mold infections (e.g., Scopulariopsis), achieving approximately 88% cure rates 1
• Itraconazole is the most effective agent when Candida invades the nail plate 2

Topical Therapy (Limited Role)

Topical agents should be reserved for mild-to-moderate disease affecting only the distal nail without lunula involvement or when systemic therapy is contraindicated 1

FDA-approved topical options:

• Efinaconazole 10% solution (FDA-approved for T. rubrum and T. mentagrophytes): achieves mycological cure rates approaching 50% with complete cure in 15% after 48 weeks 1, 5
• Amorolfine 5% nail lacquer: applied 1-2 times weekly for 6-12 months, shows approximately 50% efficacy when only distal nail portions are infected 1, 2
• Ciclopirox 8% lacquer: applied once daily for up to 48 weeks 2

Topical treatment is inferior to systemic therapy except in very limited cases of distal or superficial white onychomycosis 2

Factors Predicting Treatment Failure

The following factors significantly reduce treatment success and must be addressed before initiating therapy 1:

• Nail thickness >2 mm 1
• Severe onycholysis 1
• Dermatophytomas (dense hyphal masses in the subungual space) 1

Management of dermatophytomas:

• Dermatophytomas require mechanical removal before antifungal therapy can be effective, followed by systemic antifungal treatment 1
• Consider partial nail removal in cases of subungual dermatophytoma 2

Managing Treatment Failure (20-30% of Cases)

When treatment fails, consider 2:

1. Poor adherence to the 12-week regimen
2. Poor drug absorption
3. Presence of dermatophytoma requiring mechanical removal
4. Resistance of the dermatophyte
5. Immunosuppression

Strategy for therapeutic failure:

• Switch to an alternative agent: if terbinafine was used, switch to itraconazole (or vice versa) 2
• Consider partial nail removal for dermatophytomas 1, 2

Combination Therapy for Enhanced Outcomes

Adding a topical antifungal (e.g., amorolfine or ciclopirox lacquer) to systemic treatment creates antimicrobial synergy, broadens the spectrum of activity, improves overall cure rates, and helps suppress the emergence of resistant fungal strains 1

Timeline Expectations and Follow-Up

• Full toenail regrowth requires up to 18 months due to slow growth patterns 1
• Reevaluate patients 3-6 months after initiating treatment 2
• Therapeutic success is confirmed when the newly grown nail plate is free of fungal elements 1
• Do not expect complete clinical normalization even with mycological cure, as nails may have pre-existing dystrophy from trauma or non-fungal disease 2

Prevention of Recurrence (40-70% Recurrence Rate)

Post-treatment prophylaxis is essential given the high recurrence rate 1:

• Wear protective footwear in public bathing facilities, gyms, and hotel rooms where T. rubrum is commonly found 1, 2
• Apply antifungal powders (miconazole, clotrimazole, or tolnaftate) inside shoes and on feet 1, 2
• Discard old footwear or decontaminate shoes with naphthalene mothballs for three days 1
• Treat all infected household members simultaneously to decrease recurrence 1
• Keep nails short and avoid sharing toenail clippers 2
• Wear cotton socks 2

Special Populations

Diabetic patients:

• Terbinafine is the preferred treatment due to low risk of drug interactions and no hypoglycemia risk 1, 2
• Onychomycosis is a significant predictor of foot ulcers and cellulitis in diabetic patients, making treatment particularly important 2

Immunocompromised patients:

• Terbinafine or fluconazole are preferred due to reduced antiretroviral drug interactions 1
• Prevalence of onychomycosis in HIV-positive patients is approximately 30% 2
• Avoid griseofulvin, which is the least effective oral antifungal in HIV-positive patients 2

Pediatric patients:

• Both terbinafine and itraconazole are first-line options 2
• Dosing: 62.5 mg/day for <20 kg, 125 mg/day for 20-40 kg, and 250 mg/day for >40 kg, for 12 weeks for toenails 2
• Children experience higher cure rates (approximately 94-100%) and faster therapeutic response compared with adults 1

Critical Pitfalls to Avoid

• Never treat based on clinical appearance alone without mycological confirmation—this is the most common cause of treatment failure 2
• Do not use Nd:YAG laser as standard treatment; the British Association of Dermatologists explicitly recommends against it due to insufficient evidence (strength of recommendation D, level of evidence 3) 1
• Avoid cutting nails too short, as this is a common predisposing factor; trim nails straight and not too short 6
• Do not overlook dermatophytomas, which prevent drug penetration and require mechanical removal before antifungal therapy 1