Dermatology · PANCE / PANRE

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)

Clinical patterns of onychomycosis and their organism associations.

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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