Onychomycosis
Fungal infection of the nail unit producing thickened, discolored, dystrophic nails.
Also known as: tinea unguium, fungal nail infection, nail fungus
Overview
Fungal infection of the nail plate, nail bed, or matrix, most commonly by dermatophytes (Trichophyton rubrum, T. interdigitale), and less commonly by non-dermatophyte molds (Scopulariopsis, Aspergillus, Fusarium) and yeasts (Candida). Toenails are far more frequently affected than fingernails.
Epidemiology
Most common nail disorder in adults; prevalence rises with age (up to 20-50% of those >60). More common in men, in patients with peripheral vascular disease, diabetes, immunosuppression, tinea pedis, and those who use occlusive footwear or communal showers.
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Risk factors
- Tinea pedis (a near-universal precursor in distal subungual onychomycosis)
- Older age
- Diabetes mellitus
- Peripheral arterial disease
- Immunosuppression (HIV, transplant, biologics)
- Hyperhidrosis, occlusive footwear
- Repetitive nail trauma (runners, dancers)
- Communal moisture exposure (locker rooms, pools)
Pathophysiology
Dermatophytes invade the keratinized nail unit, most commonly entering through the hyponychium and spreading proximally beneath the nail plate (distal lateral subungual onychomycosis). White superficial, proximal subungual, and total dystrophic patterns reflect different routes of invasion and host factors (e.g., proximal subungual disease in HIV).
Clinical presentation
Symptoms
- Most patients asymptomatic or report cosmetic concerns
- Pain, pressure, or difficulty with footwear in advanced disease
- Secondary cellulitis or ulceration in diabetic or immunocompromised patients
Signs / physical exam
- Distal subungual onychomycosis: yellow-brown discoloration starting distally, subungual hyperkeratosis, onycholysis, thickening
- White superficial onychomycosis: chalky white patches on the dorsal nail plate (T. interdigitale)
- Proximal subungual onychomycosis: white patch under the proximal nail fold; classically suggests immunosuppression (HIV)
- Total dystrophic onychomycosis: end-stage involvement of the entire nail unit
- Coexisting tinea pedis (moccasin scaling, interdigital maceration)
Classic findings
Thickened, yellow, crumbly toenail with subungual hyperkeratosis and concurrent tinea pedis.
Differential diagnosis
- Nail psoriasis — Pitting, oil-drop sign, salmon patches; concurrent psoriatic skin or joint disease; KOH negative
- Lichen planus of the nail — Longitudinal ridging, thinning, pterygium formation; oral or skin lichen planus
- Traumatic onychodystrophy — Single affected nail with history of trauma; KOH negative
- Yellow nail syndrome — All 20 nails yellow, slow growing, with lymphedema and respiratory disease
- Onycholysis from contact/irritant exposure — Distal nail separation from the bed without onychocryptosis or fungal hyphae; remove insult
- Subungual melanoma — Single longitudinal pigmented band with Hutchinson sign (pigment on proximal nail fold) — biopsy mandatory; do not assume fungal
Diagnostic workup
Diagnostic criteria
Confirmation of fungal elements (positive KOH, PAS, culture, or PCR) is recommended before systemic therapy, because clinical appearance overlaps substantially with psoriasis, trauma, and other dystrophies. Treat empirically only in limited circumstances when access to testing is poor and a confident clinical diagnosis is supported.
Labs
- KOH preparation of subungual debris — quick, low cost, requires experience
- Periodic acid-Schiff (PAS) staining of nail clipping — most sensitive office test; preferred per AAD
- Fungal culture of subungual debris — identifies organism; slow (4-6 weeks)
- PCR for dermatophytes when available — fast, sensitive, increasingly used
- Baseline ALT/AST before oral antifungal therapy
Imaging
- Generally not required
- Imaging of foot/ankle reserved for evaluation of associated osteomyelitis or diabetic complications, not the nail disease itself
Diagnostic algorithm
| Pattern | Typical Organism | Clinical Clue | Immunosuppression Association |
|---|---|---|---|
| Distal lateral subungual | T. rubrum | Distal yellow discoloration + hyperkeratosis | No |
| White superficial | T. interdigitale | Chalky white patches on nail surface | No |
| Proximal subungual | T. rubrum | White patch under proximal nail fold | Yes (HIV, organ transplant) |
| Total dystrophic | Various | Entire nail involved | Common in chronic disease |
| Candida onychomycosis | Candida albicans | Fingernails > toenails; chronic paronychia common | Yes (immunosuppression, wet work) |
Treatment
First-line
- Oral terbinafine 250 mg/day for 6 weeks (fingernails) or 12 weeks (toenails) — most effective oral agent for dermatophyte onychomycosis; cure rates ~70%
- Oral itraconazole 200 mg/day continuous × 12 weeks, or pulse dosing 200 mg BID × 1 week per month × 2 (fingernails) or 3 (toenails) cycles — useful when terbinafine contraindicated or for Candida/non-dermatophyte molds
- Oral fluconazole 150-300 mg weekly × 6-12 months — off-label but useful for Candida and as alternative
- Treat coexisting tinea pedis with topical terbinafine or other allylamine to reduce recurrence
- Patient education: rotate footwear, dry feet thoroughly, treat shoes, separate towels
Second-line / adjunct
- Topical efinaconazole 10% solution daily × 48 weeks — useful for mild-moderate disease or when systemic therapy contraindicated
- Topical tavaborole 5% solution daily × 48 weeks
- Topical ciclopirox 8% nail lacquer daily × 48 weeks — lower cure rates than newer topicals
- Nail debridement and chemical or surgical avulsion as adjuncts
- Laser and photodynamic therapy — modest evidence; not first-line
Complications
- Recurrence in 20-50% within several years even after cure
- Secondary bacterial cellulitis, particularly in diabetics and patients with vascular disease
- Diabetic foot ulceration originating at dystrophic nail
- Hepatotoxicity from terbinafine (monitor LFTs at baseline and consider at 6 weeks)
- Drug interactions: itraconazole (CYP3A4 inhibitor) with statins, benzodiazepines, warfarin, calcium channel blockers — review medications carefully; contraindicated with several CYP3A4-cleared drugs
PANCE pearls
- Confirm fungal infection before committing a patient to 3 months of oral antifungal therapy — many 'fungal' toenails are psoriasis or trauma.
- PAS-stained nail clipping is the highest-sensitivity office test and outperforms KOH and culture.
- Always look for tinea pedis — eradicate it or the nails will reinfect.
- Proximal subungual onychomycosis is uncommon and should prompt evaluation for HIV or other immunosuppression.
- Single nail with a longitudinal pigmented band is melanoma until proven otherwise — biopsy, do not treat as fungus.
- Terbinafine is first-line for dermatophytes; itraconazole is preferred for non-dermatophyte molds and Candida.
References
- AAD 2019 — Lipner SR, Scher RK. Onychomycosis: clinical overview and diagnosis (JAAD 2019)
- BAD 2014 — Ameen M et al. British Association of Dermatologists' guidelines for the management of onychomycosis (BJD 2014)
- Gupta meta-analysis — Gupta AK et al. Treatments for onychomycosis: a systematic review and network meta-analysis (BJD 2020)
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