What is the recommended treatment for a patient with onychomycosis of the nail?

Treatment of Onychomycosis

Oral terbinafine 250 mg once daily is the first-line treatment for dermatophyte onychomycosis (the most common type), given for 6 weeks for fingernails and 12 weeks for toenails, achieving cure rates of 70-90%. 1, 2

Mandatory Diagnostic Confirmation Before Treatment

• Never initiate treatment without mycological confirmation through KOH preparation with microscopy AND fungal culture, as incorrect diagnosis is the most common cause of treatment failure. 3, 1, 4, 2
• Obtain subungual debris from the most proximal part of the infection using a dental scraper, scraping material from beneath the nail and from the nail bed. 3
• Submit as much material as possible to the laboratory due to the relative paucity of fungal elements. 3
• Culture on Sabouraud's glucose agar should be incubated at 28°C for at least 3 weeks before declaring negative. 3

Treatment Algorithm by Causative Organism

For Dermatophyte Onychomycosis (Majority of Cases)

First-Line: Oral Terbinafine

• Terbinafine 250 mg once daily for 6 weeks (fingernails) or 12 weeks (toenails) is superior to all other agents both in vitro and in vivo. 1, 4, 2
• Cure rates: 80-90% for fingernails, 70-80% for toenails. 1
• Check baseline liver function tests (ALT and AST) before starting, especially in patients with history of excessive alcohol consumption, hepatitis, or other liver diseases. 1

Second-Line: Itraconazole

• Itraconazole 200 mg twice daily (400 mg/day) for 1 week per month—2 pulses for fingernails, 3 pulses for toenails. 1
• Alternative continuous dosing: 200 mg daily for 12 weeks for toenails. 4

Not Recommended: Griseofulvin

• Griseofulvin has lower efficacy (30-40% mycological cure) and higher relapse rates, and should not be used as first-line treatment. 1

For Candida Onychomycosis (Fingernails with Paronychia)

• Itraconazole is the most effective agent when the nail plate is invaded by Candida: 400 mg daily for 1 week per month, repeated for 2 months for fingernails and 3-4 pulses for toenails. 1
• Candida onychomycosis typically begins in the proximal nail plate with associated nail fold infection (paronychia), unlike dermatophyte infection. 3

For Non-Dermatophyte Mold Infections

• Suspect non-dermatophyte molds when previous antifungal treatment has failed on several occasions, direct microscopy is positive but no dermatophyte was isolated, and there is no associated skin infection. 3
• These infections often affect only one nail and typically occur in nails that have been previously diseased or traumatized. 3

Topical Therapy (Limited Role)

Topical treatment is inferior to systemic therapy except in very limited cases:

• Amorolfine 5% lacquer applied 1-2 times weekly for 6-12 months for superficial and distal onychomycosis without matrix involvement. 1, 4
• Ciclopirox 8% lacquer applied once daily for up to 48 weeks, only for mild to moderate onychomycosis of fingernails and toenails without lunula involvement. 1, 5
• Efinaconazole 10% solution and tavaborole 5% solution are FDA-approved alternatives with fewer adverse effects but lower cure rates than oral agents. 6, 7
• Topical therapy requires concurrent monthly removal of unattached, infected nail by a healthcare professional. 5

Special Population Considerations

Diabetic Patients

• Terbinafine is the agent of choice due to low risk of drug interactions and no hypoglycemia risk. 1, 4
• Onychomycosis is a significant predictor of foot ulcers and cellulitis in diabetic patients, making treatment particularly important to prevent serious complications. 1

Immunocompromised Patients (HIV, Transplant Recipients)

• Prefer terbinafine over itraconazole due to lower risk of drug interactions with antiretrovirals and immunosuppressive medications. 1, 4
• Prevalence of onychomycosis in HIV-positive patients is approximately 30%. 1
• Griseofulvin is the least effective oral antifungal in HIV-positive patients and should be avoided. 1

Pediatric Patients

• Terbinafine daily dosing based on weight: 62.5 mg/day for <20 kg, 125 mg/day for 20-40 kg, and 250 mg/day for >40 kg. 1
• Duration: 6 weeks for fingernails, 12 weeks for toenails. 1
• Cure rates are higher in the pediatric population than in adults. 1

Management of Treatment Failure (20-30% of Cases)

Common causes of failure:

• Poor adherence to treatment, poor drug absorption, immunosuppression, and dermatophyte resistance. 1
• Dermatophytoma subungual (a compact mass of fungi that prevents drug penetration) is a major cause of failure. 1, 4
• Nail thickness >2 mm, slow outgrowth, and severe onycholysis. 4

Strategies for therapeutic failure:

• Consider partial nail removal or mechanical debridement in cases of dermatophytoma subungual before or during antifungal therapy. 1, 4
• Switch to an alternative agent: if terbinafine was used, switch to itraconazole or vice versa. 1
• Reevaluate patients 3-6 months after initiating treatment to assess response. 1

Prevention of Recurrence

• Always wear protective footwear in communal bathing facilities, gyms, and hotel rooms to avoid re-exposure to T. rubrum. 1, 4
• Apply absorbent antifungal powders (miconazole, clotrimazole, or tolnaftate) to shoes and feet. 1, 4
• Wear cotton socks, keep nails short, avoid sharing toenail clippers, and discard old footwear. 1
• Disinfecting floors of communal bathing places is very difficult because fungal elements are protected in small pieces of keratin. 3

Critical Pitfalls to Avoid

• Do not treat based on clinical appearance alone without mycological confirmation—this is the most common cause of treatment failure in the UK. 3, 1, 4
• Do not expect complete clinical normalization even with mycological cure, as nails may have pre-existing dystrophy from trauma or non-fungal disease. 1
• Do not use concomitant systemic and topical antifungal agents, as no studies have determined whether this reduces effectiveness. 5
• Surgical avulsion followed by topical therapy, photodynamic therapy, and laser therapy are not recommended due to disappointing results or insufficient evidence. 4
• Toenails take around 12 months to grow out and fingernails about 6 months—treatment success cannot be assessed until complete nail regrowth occurs. 3