What is the best treatment option for a patient with nail mycosis (fungal infection of the nail)?

Treatment of Nail Mycosis (Onychomycosis)

Oral terbinafine 250 mg daily is the first-line treatment for dermatophyte onychomycosis (which causes 90-95% of cases), given for 6 weeks for fingernails and 12 weeks for toenails, achieving mycological cure rates of 70-79%. 1, 2

Diagnostic Confirmation Required Before Treatment

• Never initiate treatment without mycological confirmation through KOH microscopy and fungal culture 3
• Treatment based on clinical appearance alone is the most common cause of treatment failure 3
• Identifying the causative organism determines the optimal treatment choice 1

Treatment Algorithm by Causative Organism

For Dermatophyte Onychomycosis (90-95% of cases)

First-line: Oral Terbinafine

• Dosing: 250 mg once daily for 6 weeks (fingernails) or 12 weeks (toenails) 1, 3
• Mycological cure rates: 70-79% for toenails, 79% for fingernails 1, 2
• Clinical cure plus mycological cure: 38% for toenails, 59% for fingernails 2
• Superior to itraconazole both in vitro and in vivo 1, 3
• Continuous daily dosing is significantly more effective than pulse dosing (76.67% vs 26.67% cure rate) 4
• Drug persists in nails for 6+ months after treatment completion 5, 6

Baseline Monitoring:

• Obtain liver function tests (ALT, AST) and complete blood count before starting treatment, especially in patients with history of alcohol consumption, hepatitis, or liver disease 1, 3

Second-line: Oral Itraconazole

• Dosing: 200 mg twice daily (400 mg/day) for 1 week per month—2 pulses for fingernails, 3 pulses for toenails 1, 5
• Alternative continuous dosing: 200 mg daily for 12 weeks 1
• Mycological cure rates: 26-46% (lower than terbinafine) 1
• Must be taken with food and acidic beverages for optimal absorption 5
• Monitor hepatic function tests, especially with continuous therapy >1 month or concomitant hepatotoxic drugs 1, 5
• Contraindicated in heart failure and active liver disease 1, 5

Third-line: Oral Fluconazole

• Dosing: 150-450 mg once weekly for at least 6 months (toenails) or 3 months (fingernails) 1, 5
• Less effective than terbinafine or itraconazole but useful when others cannot be tolerated 1
• Fewer drug interactions than itraconazole 1, 5
• Once-weekly dosing may improve compliance 1

For Candida Onychomycosis

First-line: Oral Itraconazole

• Dosing: 400 mg daily for 1 week per month (pulse therapy)—minimum 4 weeks for fingernails, 12 weeks for toenails 1, 3
• Alternative: 200 mg daily continuously 1
• Cure rate: 92% (significantly superior to terbinafine's 40% for Candida) 1, 3
• Shorter treatment duration makes it more cost-effective and improves compliance 1

Second-line: Oral Fluconazole

• Dosing: 50 mg daily or 300 mg weekly 1
• Equally effective as itraconazole for Candida onychomycosis 1
• Use when itraconazole is contraindicated 1

Terbinafine for Candida:

• Requires prolonged treatment (48 weeks) for adequate efficacy 1
• Mycological cure: 70% for C. albicans, 85% for C. parapsilosis after 48 weeks 1
• Not recommended as first-line due to extended treatment duration 1

For Nondermatophyte Moulds

• Itraconazole has broader antimicrobial coverage than terbinafine for nondermatophyte moulds 1
• Aspergillus shows excellent susceptibility to itraconazole 1
• Scopulariopsis, Fusarium, and Acremonium show reduced susceptibility to most antifungals including terbinafine 1
• Consider newer triazoles (voriconazole, posaconazole) for recalcitrant infections 1

Special Population Considerations

Diabetic Patients

• Terbinafine is the agent of choice due to low risk of drug interactions and no hypoglycemia risk 3
• Onychomycosis is a significant predictor of foot ulcers and cellulitis in diabetics—treatment is particularly important 3

Immunocompromised Patients

• Terbinafine is preferred over itraconazole due to lower risk of drug interactions with antiretrovirals and immunosuppressive medications 3
• Griseofulvin should be avoided in HIV-positive patients (least effective) 3

Pediatric Patients (Age 1-12 years)

• Terbinafine dosing: 62.5 mg/day for <20 kg, 125 mg/day for 20-40 kg, 250 mg/day for >40 kg 3
• Duration: 6 weeks for fingernails, 12 weeks for toenails 3
• Itraconazole alternative: 5 mg/kg/day for 1 week per month—2 pulses for fingernails, 3 pulses for toenails 5
• Cure rates are higher in children than adults 3
• Baseline monitoring recommended as terbinafine is not licensed for pediatric onychomycosis 1

Elderly Patients

• Fluconazole 450 mg once weekly for at least 6 months is preferred when terbinafine is not tolerated 5
• Itraconazole may not be suitable due to contraindication in heart failure (more prevalent in elderly) and greater potential for drug interactions with statins 5

Adjunctive Topical Therapy

When to Consider:

• Mild to moderate infection without nail matrix involvement 3, 7
• As adjunct to systemic therapy to enhance cure rates 5
• Provides antimicrobial synergy and wider antifungal spectrum 5

Options:

• Amorolfine 5% lacquer: Apply once or twice weekly for 6-12 months 1, 3, 5
• Ciclopirox 8% lacquer: Apply once daily for up to 48 weeks 1, 3, 5, 7
• Ciclopirox shows 34% mycological cure vs 10% placebo, but only 8% complete clinical cure 5
• Topical therapy alone is inferior to systemic therapy except in very limited distal or superficial white onychomycosis 3
• Concomitant use of ciclopirox with systemic antifungals is not recommended per FDA labeling 7

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

Common Causes:

• Poor adherence to treatment 3
• Poor drug absorption 3
• Immunosuppression 3
• Dermatophyte resistance 3
• Dermatophytoma (compact fungal mass preventing drug penetration) 1, 3
• Thick nails (>2 mm), severe onycholysis, slow nail growth 1

Strategies:

• Consider partial nail removal or debridement in cases of dermatophytoma before retreatment 3
• Switch to alternative agent: if terbinafine failed, use itraconazole or vice versa 3
• Re-evaluate at 3-6 months after treatment initiation 1, 3
• Give further treatment if disease persists 1

Follow-up and Monitoring

• Re-evaluate patients 3-6 months after initiating treatment 1, 3
• Monitor for at least 48 weeks from start of treatment to identify potential relapse 5
• Mean time to overall success: approximately 10 months for toenails, 4 months for fingernails 2
• Clinical relapse rate approximately 15% at 6+ months after achieving clinical cure 2
• Up to 18 months required for complete toenail plate regrowth 1

Prevention of Recurrence

Essential Measures:

• Always wear protective footwear in communal bathing facilities, gyms, and hotel rooms 1, 3
• Apply absorbent antifungal powders (miconazole, clotrimazole, tolnaftate) in shoes and on feet 1, 3
• Wear cotton, absorbent socks 1, 3
• Keep nails as short as possible 1, 3
• Avoid sharing toenail clippers with family members 1, 3

Footwear Decontamination:

• Discard old and moldy footwear if possible 1, 5
• Alternative: Place naphthalene mothballs in shoes, seal in plastic bag for minimum 3 days to kill fungal arthroconidia 1, 5
• Apply antifungal powders inside shoes regularly after decontamination 1, 5
• Consider periodic spraying of terbinafine solution into shoes 1, 5
• Treat all infected family members simultaneously 1

Critical Drug Interactions and Adverse Effects

Terbinafine:

• Most common adverse effects: gastrointestinal (49%)—nausea, diarrhea, taste disturbance; dermatological (23%)—rash, pruritus, urticaria 1
• Rare but serious: Stevens-Johnson syndrome, toxic epidermal necrolysis, hepatotoxicity 1
• Permanent taste disturbance is very rare but patients must be warned 1
• Inhibits CYP2D6 (minimal drug interactions) 1, 6
• Can aggravate psoriasis and cause subacute lupus-like syndrome 1

Itraconazole:

• Common adverse effects: headache, gastrointestinal upset 1, 5
• Inhibits CYP3A4—significant interactions with statins, requiring dose adjustment 5
• Contraindicated in heart failure (negative inotropic effects) 1, 5
• Not recommended in active or chronic liver disease 1

Fluconazole:

• Common adverse effects: headache, skin rash, gastrointestinal complaints, insomnia 1
• Adverse effects leading to discontinuation: 20% at 150 mg/week, 58% at 300-450 mg/week 1
• Weaker CYP450 inhibitor than itraconazole—fewer drug interactions 1
• Dose adjustment required based on creatinine clearance 1

Common Pitfalls to Avoid

• Do not treat without mycological confirmation—this is the most common cause of treatment failure 3
• Do not expect complete clinical normalization even with mycological cure—nails may have pre-existing dystrophy from trauma or non-fungal disease 3
• Do not use pulse terbinafine dosing—continuous daily dosing is significantly more effective 4
• Do not use terbinafine as first-line for Candida onychomycosis—requires 48 weeks vs 12 weeks with itraconazole 1
• Do not ignore dermatophytoma—requires mechanical removal before antifungal therapy 5
• Do not forget to address footwear contamination—shoes contain large numbers of infective fungal elements 1