What is the recommended treatment for Tinea unguium (Fungal Nail Infection)?

Treatment of Tinea Unguium (Onychomycosis)

Oral terbinafine 250 mg daily is the first-line treatment for tinea unguium: 6 weeks for fingernails and 12 weeks for toenails. 1, 2

Diagnostic Confirmation Required Before Treatment

• Obtain laboratory confirmation via KOH preparation, fungal culture, or nail biopsy before initiating therapy to confirm dermatophyte infection, as this is mandated by FDA labeling and guidelines 2
• Specimens should be collected via scalpel scraping or nail clipping from the affected nail plate 1

First-Line Systemic Treatment: Terbinafine

Terbinafine is the oral antifungal of choice with the highest strength of recommendation (Grade A, Level 1+ evidence) 1

Dosing Regimen

• Fingernail onychomycosis: 250 mg once daily for 6 weeks 2
• Toenail onychomycosis: 250 mg once daily for 12 weeks 2
• Optimal clinical effect occurs months after treatment completion due to the time required for healthy nail outgrowth 2

Why Terbinafine is Preferred

• Only oral fungicidal antimycotic available, with potent activity against dermatophytes, particularly T. rubrum and T. mentagrophytes 1
• Persists in nail tissue for 6 months after treatment completion due to long half-life 1
• Superior efficacy compared to older agents like griseofulvin, which achieves only 30-40% mycological cure rates for toenails 1
• More than 70% oral absorption, unaffected by food intake 1

Alternative Systemic Agents

Itraconazole (Second-Line)

• Pulse therapy: 200 mg twice daily for 1 week per month 1
• Fingernails: 2 pulses (2 months total) 1
• Toenails: 3-4 pulses (3-4 months total) 1
• Contraindicated in congestive heart failure due to negative inotropic effects 1
• Significant drug interactions via CYP3A4 inhibition, particularly with antiretrovirals, warfarin, certain antihistamines, and statins 1, 3

Fluconazole (Third-Line)

• Less commonly used due to limited comparative efficacy data and higher cost 3
• Reserved for Candida-associated onychomycosis where azoles are preferred over terbinafine 1

Griseofulvin (No Longer Recommended)

• Not recommended as first-line due to low efficacy (30-40% cure rates), long treatment duration (12-18 months for toenails), and availability of superior alternatives 1

Topical Therapy Considerations

Topical monotherapy is generally inadequate for onychomycosis but may be considered in specific circumstances:

• Amorolfine 5% nail lacquer applied once or twice weekly for up to 48 weeks on toenails 1
• Ciclopirox 8% lacquer applied daily for up to 48 weeks, though cure rates are lower than amorolfine (34% vs. 10% placebo for mycological cure) 1
• Efinaconazole 10% solution applied daily achieves approximately 50% mycological cure and 15% complete cure after 48 weeks 1
• Topical therapy alone is appropriate only for mild-to-moderate infections involving <50% of nail plate, distal disease, or when oral therapy is contraindicated 1, 4
• Combination topical plus systemic therapy may improve cure rates through antimicrobial synergy and broader antifungal spectrum 1

Special Population Considerations

Diabetic Patients

• Terbinafine is the preferred agent due to low risk of drug interactions and hypoglycemia 1
• Onychomycosis is a significant predictor for diabetic foot ulcers, making treatment particularly important 1
• Itraconazole should be avoided given higher prevalence of cardiac disease in diabetics 1

Immunocompromised Patients (HIV, Transplant Recipients)

• Terbinafine and fluconazole are preferred over itraconazole due to lower risk of drug interactions with antiretrovirals and immunosuppressants 1
• Most infections remain T. rubrum even in immunocompromised hosts 1

Pediatric Patients

• Pulse itraconazole 5 mg/kg/day for 1 week per month: 2 months for fingernails, 3 months for toenails 1
• Daily terbinafine based on weight: <20 kg: 62.5 mg/day; 20-40 kg: 125 mg/day; >40 kg: 250 mg/day 1
• Treatment duration: 6 weeks for fingernails, 12 weeks for toenails 1
• Higher cure rates and faster response than adults due to thinner, faster-growing nail plates 1

Critical Monitoring and Safety Considerations

Hepatotoxicity Monitoring (Terbinafine)

• Obtain baseline liver function tests before initiating therapy 2
• Discontinue immediately if biochemical or clinical evidence of liver injury develops 2
• Warn patients to report persistent nausea, anorexia, fatigue, vomiting, right upper abdominal pain, jaundice, dark urine, or pale stools 2
• Cases of liver failure requiring transplant or resulting in death have occurred, though rare 2

Other Terbinafine Warnings

• Taste disturbance (including complete loss) can be severe, prolonged (>1 year), or permanent—discontinue if this occurs 2
• Smell disturbance (including complete loss) may be prolonged or permanent—discontinue if this occurs 2
• Severe neutropenia reported—discontinue if neutrophil count ≤1,000 cells/mm³ 2
• Stevens-Johnson syndrome, toxic epidermal necrolysis, and DRESS syndrome reported—discontinue if signs of severe cutaneous reactions occur 2

Treatment Failure Management

When to Suspect Treatment Failure

• Dermatophytomas (dense white lesions of tightly packed hyphae) are resistant to antifungal treatment without prior mechanical removal 1
• Pathogenic dermatophytes can survive in dormant forms (arthroconidia) during oral terbinafine treatment despite adequate drug concentrations 5

Approach to Treatment Failure

• Assess compliance, drug absorption, organism sensitivity, and potential reinfection sources 1
• If clinical improvement with persistent positive mycology: continue current therapy for additional 2-4 weeks 6, 7
• If no clinical improvement: switch to alternative agent (e.g., itraconazole if on terbinafine) 6, 7
• Consider mechanical debridement or removal of dermatophytomas before continuing antifungal therapy 1

Prevention of Recurrence

• Screen and treat all household contacts, as >50% may be affected with anthropophilic species like T. tonsurans 6, 3
• Clean all fomites (hairbrushes, combs, towels) with disinfectant or 2% sodium hypochlorite solution 6, 3
• Treat concurrent tinea pedis to prevent reinfection of nails 1
• Mycological cure, not just clinical response, is the definitive treatment endpoint—follow-up with repeat mycology until clearance documented 6, 7, 3

Common Pitfalls to Avoid

• Never start treatment without mycological confirmation, as clinical appearance alone is insufficient 2
• Do not use topical therapy alone for moderate-to-severe disease (>50% nail involvement or >3 nails affected) 4
• Avoid itraconazole in patients with heart failure or those on multiple interacting medications 1, 3
• Do not expect immediate clinical cure—up to 18 months may be required for complete nail plate outgrowth after mycological cure 1
• Surgical avulsion followed by topical therapy has shown disappointing results in randomized trials and is not recommended 1