What is the recommended diagnostic work‑up and first‑line treatment for onychomycosis in an adult patient?

Diagnostic Work-Up and First-Line Treatment for Onychomycosis

Obtain mycological confirmation with potassium hydroxide (KOH) preparation and fungal culture before initiating any systemic antifungal therapy, then treat with oral terbinafine 250 mg daily for 12 weeks for toenails or 6 weeks for fingernails. 1, 2

Diagnostic Work-Up

Confirmatory testing is mandatory before treatment because only approximately 50% of nail dystrophies are actually fungal infections. 3, 4, 5

Specimen Collection Technique

• Cut the affected nail as far back as possible through the entire thickness, including any crumbly material 3
• For superficial white onychomycosis, take nail scrapings with a curette 3
• Collect material from any discolored, dystrophic, or brittle parts of the nail 3
• Sterilize nail drills, scalpels, and nail elevators between patients 3

Laboratory Testing Options

• KOH preparation with confirmatory fungal culture is the preferred diagnostic approach 5, 6
• Periodic acid-Schiff (PAS) stain of nail clippings provides histopathologic confirmation 5
• Polymerase chain reaction (PCR) testing offers rapid results when available 5, 7

Differential Diagnosis to Exclude

• Psoriasis (typically shows nail pitting and oil-drop discoloration) 3
• Bacterial infection, particularly Pseudomonas aeruginosa (causes green or black discoloration) 3
• Chronic trauma, onycholysis, onychogryphosis 3
• Lichen planus (associated with nail thinning and dorsal pterygium) 3
• Subungual malignant melanoma 3

First-Line Treatment: Oral Terbinafine

Terbinafine 250 mg once daily is the gold standard first-line systemic therapy, achieving mycological cure rates of approximately 73% at 48 weeks post-treatment for toenail infections. 1, 2

Dosing Regimen

• Toenail onychomycosis: 250 mg daily for 12 weeks 1, 2
• Fingernail onychomycosis: 250 mg daily for 6 weeks 1
• Severe infections with extensive involvement: extend to 16 weeks 1

Pre-Treatment Monitoring

• Obtain baseline liver function tests (ALT, AST) and complete blood count 1, 8
• Baseline monitoring is particularly important in patients with history of heavy alcohol consumption, hepatitis, or pre-existing liver disease 8

Contraindications

• Active or chronic liver disease 8
• Renal impairment (creatinine clearance ≤50 mL/min) 8
• Pregnancy 3

Common Adverse Effects

• Gastrointestinal disturbances (nausea, diarrhea) occur in 49% of reported side effects 8
• Reversible taste disturbance affects approximately 1 in 400 patients 1, 8
• Dermatological reactions (rash, pruritus, urticaria) occur in 23% of cases 8
• Rare but serious: Stevens-Johnson syndrome, toxic epidermal necrolysis, idiosyncratic hepatotoxicity 8

Drug Interactions

• Rifampicin reduces terbinafine plasma levels 3
• Cimetidine increases terbinafine levels 3
• Monitor patients taking CYP2D6-metabolized drugs (tricyclic antidepressants, SSRIs, beta blockers, tamoxifen) 5

Ongoing Monitoring During Treatment

• For low-risk patients with normal baseline tests, routine periodic monitoring is not required unless treatment extends beyond one month 8
• Monitor hepatic function tests in high-risk patients or those on concurrent hepatotoxic medications 8
• Discontinue immediately if biochemical liver injury or clinical hepatotoxicity develops 8

Second-Line Treatment: Itraconazole

When terbinafine is contraindicated or not tolerated, use itraconazole 200 mg daily for 12 weeks continuously, or pulse therapy at 400 mg daily for 1 week per month for 3 pulses. 1, 9

Administration Requirements

• Must be taken with food and acidic beverages for optimal absorption 1, 9
• Baseline and periodic hepatic function monitoring required 1, 9

Critical Contraindications

• Heart failure (due to negative inotropic effects) 3, 1
• Pregnancy 3
• Concurrent use with terfenadine, astemizole, sertindole, midazolam, or cisapride 3

Important Drug Interactions

• Increases levels of warfarin, digoxin, ciclosporin, and simvastatin (raising myopathy risk) 3, 9
• Dose adjustments or close monitoring required with these medications 9

Third-Line Treatment: Fluconazole

Fluconazole 150-450 mg once weekly for at least 6 months is reserved for patients who cannot tolerate terbinafine or itraconazole. 1, 9

• Baseline liver function tests and complete blood count required 1, 9
• Monitor hepatic function during high-dose or prolonged therapy 9
• Requires 50% dose reduction when GFR <45 mL/min 8

Adjunctive Topical Therapy

Adding topical antifungals to systemic therapy creates antimicrobial synergy and improves overall cure rates. 1

• Amorolfine 5% lacquer: apply once or twice weekly for 6-12 months 1, 9
• Ciclopirox 8% lacquer: apply once daily for up to 48 weeks 1, 9
• Topical monotherapy should be reserved for mild-to-moderate disease affecting only the distal nail without lunula involvement 1

Special Clinical Scenarios

Candida Onychomycosis

Itraconazole is the preferred agent for Candida nail infections, achieving 92% cure rates versus only 40% with terbinafine. 1, 9

Nondermatophyte Mold Infections

For onychomycosis caused by Scopulariopsis or other nondermatophyte molds, itraconazole is more effective than terbinafine, achieving approximately 88% cure rates. 1

Dermatophytoma Presence

Dermatophytomas (dense white hyphal masses beneath the nail) require mechanical removal before antifungal therapy can be effective. 1

Diabetic Patients

Terbinafine is the preferred treatment in diabetic patients due to low risk of drug interactions and minimal hypoglycemia risk. 1

Factors Predicting Treatment Failure

• Nail thickness >2 mm 1
• Severe onycholysis 1
• Presence of dermatophytoma 1
• Immunosuppression 3
• Poor patient compliance 3

Follow-Up and Monitoring

Patients should be followed for at least 48 weeks from treatment initiation to detect relapse, as complete toenail regrowth requires up to 18 months. 1, 9

• End-of-therapy culture is recommended, especially in high-risk groups, to confirm mycological clearance 3
• Mycological cure rates are typically 30% higher than clinical cure rates because pre-existing nail dystrophy may persist despite fungal eradication 3

Recurrence Prevention

• Apply antifungal powders inside shoes and on feet regularly 1, 9
• Wear protective footwear in public bathing facilities, gyms, and hotel rooms 1
• Decontaminate shoes with naphthalene mothballs sealed in plastic bags for 3 days 9
• Treat all infected household members simultaneously 1
• Consider discarding old contaminated footwear 9

Common Pitfalls to Avoid

• Never initiate systemic antifungal therapy without mycological confirmation 3, 4, 5
• Do not use terbinafine for Candida onychomycosis—it has only 40% efficacy compared to 92% with itraconazole 1, 9
• Avoid itraconazole in patients with heart failure due to negative inotropic effects 3, 1
• Do not prescribe terbinafine in patients with creatinine clearance ≤50 mL/min 8
• Ensure adequate treatment duration—premature discontinuation leads to treatment failure 9