What is the treatment for toenail discoloration suspected to be caused by a fungal infection?

Treatment of Toenail Discoloration from Suspected Fungal Infection

For suspected fungal toenail infection (onychomycosis), oral terbinafine 250 mg daily for 12 weeks is the first-line treatment and is superior to all other options, but mycological confirmation should be obtained before starting therapy. 1

Diagnostic Confirmation Required Before Treatment

Never treat based on clinical appearance alone - approximately 50% of nail dystrophies are non-fungal. 1 Laboratory confirmation is essential because:

• Obtain nail specimens by cutting the affected nail as far back as possible through the entire thickness, including any crumbly material from discolored or dystrophic areas. 1
• Preferred diagnostic methods include potassium hydroxide (KOH) preparation with confirmatory fungal culture, periodic acid-Schiff stain, or polymerase chain reaction (PCR). 2
• Culture and microscopy yield results in 2-6 weeks, while real-time PCR provides results in less than 2 days with higher detection rates. 1

Key Differential Diagnoses to Exclude

• Bacterial infection (especially Pseudomonas aeruginosa) causes green or black nail discoloration, not the cream-colored changes typical of fungal infection. 1
• Candida infection typically begins proximally with paronychia (nail fold inflammation), unlike dermatophyte infection which starts distally. 1
• Non-infectious causes include psoriasis, trauma, lichen planus, and subungual melanoma - these don't produce the soft, friable nail surface characteristic of fungal infection. 1

First-Line Treatment: Oral Terbinafine

Terbinafine 250 mg once daily for 12 weeks for toenails (6 weeks for fingernails) is the preferred treatment with the highest cure rates. 1, 3

Why Terbinafine is Superior

• High-quality evidence demonstrates terbinafine achieves better clinical cure (RR 0.82) and mycological cure (RR 0.77) compared to azoles. 4
• Fungicidal action (not just fungistatic) through inhibition of squalene epoxidase, with effects persisting 6 months after treatment completion. 1
• Optimal clinical effect appears months after treatment cessation due to the time required for healthy nail outgrowth (up to 18 months for complete toenail replacement). 1, 3

Monitoring and Safety

• Baseline liver function tests and complete blood count are required before starting treatment. 1
• Monitor for hepatotoxicity - patients must report persistent nausea, anorexia, fatigue, vomiting, right upper abdominal pain, jaundice, dark urine, or pale stools immediately. 3
• Common adverse effects include headache, taste disturbance, and gastrointestinal upset, but serious adverse events occur in only 0.04% of patients. 1
• Taste and smell disturbances can be severe and prolonged (>1 year) or permanent; discontinue if these occur. 3

Alternative Oral Treatments

Itraconazole (Co-First-Line for Dermatophytes)

Itraconazole 200 mg daily for 12 weeks continuously OR pulse therapy 400 mg daily for 1 week per month (3 pulses for toenails). 1

• Equally effective as first-line for dermatophyte onychomycosis but generally less preferred than terbinafine. 1
• Contraindicated in heart failure; requires monitoring of hepatic function tests. 1
• Take with food for optimal absorption in acidic pH. 1

Fluconazole (Second-Line Alternative)

Fluconazole 150-450 mg weekly for at least 6 months for toenail infections. 1

• Useful alternative when terbinafine or itraconazole cannot be tolerated. 1
• Requires baseline and periodic monitoring of liver function tests and blood counts. 1

Griseofulvin (Not Recommended)

Griseofulvin has lower efficacy (30-40% mycological cure) and higher relapse rates compared to terbinafine and azoles, requiring 12-18 months of treatment for toenails. 1

• Only use when other drugs are unavailable or contraindicated. 1
• Low-quality evidence shows terbinafine is more effective (RR 0.32 for clinical cure, RR 0.64 for mycological cure). 4

Topical Treatments (For Mild to Moderate Disease)

Topical therapy is less effective than oral agents but has fewer adverse effects and drug interactions. 2

When to Consider Topical Therapy

• Mild to moderate onychomycosis affecting less than 50% of the nail plate. 5
• Fewer than 3 nails affected. 5
• Patients who cannot tolerate oral therapy due to drug interactions or contraindications. 2

Topical Options

• Efinaconazole 10% solution applied once daily achieves approximately 50% mycological cure and 15% complete cure after 48 weeks. 1
• Ciclopirox 8% lacquer has lower cure rates than efinaconazole. 1
• Tavaborole 5% solution is another option with fewer adverse effects than oral agents. 2

Adjunctive Measures Critical for Success

Mechanical Debridement

Nail trimming and debridement used concurrently with pharmacologic therapy improve treatment response. 2

• Remove dermatophytomas (dense white lesions of tightly packed hyphae beneath the nail) mechanically, as these are resistant to antifungal treatment alone. 1
• Surgical avulsion is not recommended based on disappointing randomized controlled trial results. 1

Prevention of Recurrence (25-70% Recurrence Rate)

• Always wear protective footwear in public bathing facilities, gyms, hotel rooms, and changing rooms where T. rubrum is commonly found. 1
• Apply antifungal powders (miconazole, clotrimazole, or tolnaftate) in shoes and on feet. 1
• Disinfect or discard old footwear - place naphthalene mothballs in shoes sealed in plastic bags for minimum 3 days to kill fungal arthroconidia. 1
• Keep nails short and avoid sharing nail clippers with family members. 1
• Treat all infected family members simultaneously as both onychomycosis and tinea pedis are contagious. 1

Treatment Failure Considerations

If treatment fails despite adequate therapy:

• Suspect non-dermatophyte molds when previous antifungal treatment has failed multiple times, direct microscopy is positive but no dermatophyte isolated, and no associated skin infection present. 1
• Check for dermatophytoma presence requiring mechanical removal. 1
• Assess nail thickness (>2 mm), slow outgrowth, and severe onycholysis as contributors to treatment failure. 1
• Re-confirm diagnosis with repeat mycological testing. 1