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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Question 1DermatologyMedium
A 64-year-old man presents with a thickened, yellow-brown, crumbly right great toenail that has worsened over 8 months. He has type 2 diabetes and coexisting moccasin-pattern scaling on both soles. Examination shows subungual hyperkeratosis and distal onycholysis. He has no skin plaques, nail pitting, or joint complaints. His clinician plans 12 weeks of oral terbinafine but wants laboratory confirmation of fungal infection first. Which of the following is the most appropriate next diagnostic test?
AWood lamp examination of the nail
BPAS stain of a nail-clipping specimen
CSerum beta-D-glucan fungal assay
DPunch biopsy of the nail matrix tissue
EGram stain of the subungual debris
Reveal answer & full explanation
Correct answer: B — PAS stain of a nail-clipping specimen
AWood lamp examination of the nail
BPAS stain of a nail-clipping specimen✓
CSerum beta-D-glucan fungal assay
DPunch biopsy of the nail matrix tissue
EGram stain of the subungual debris
Why PAS stain of a nail-clipping specimen is correct
PAS staining of a nail clipping (histopathology) is the most sensitive single test for confirming onychomycosis, outperforming KOH preparation and fungal culture, and is a preferred way to document fungal infection before starting systemic therapy.
Because oral terbinafine commits this diabetic patient to ~12 weeks of therapy with LFT monitoring, fungal elements should be confirmed first; clinical appearance overlaps substantially with psoriasis and trauma.
The specimen is a simple distal clipping, results return in days rather than the weeks culture requires, and the stain reliably detects hyphae within the keratinized nail plate.
Why the others are wrong
Gram stain of the subungual debris - designed to detect bacteria, such as Pseudomonas in green nail syndrome or the staphylococci and streptococci of acute paronychia; it is not a validated method for demonstrating dermatophyte hyphae in nail keratin.
Serum beta-D-glucan fungal assay - a serum marker that supports invasive fungal infection (invasive candidiasis, aspergillosis, Pneumocystis pneumonia); dermatophyte infection confined to the keratinized nail plate is not expected to raise serum levels, so the test can neither confirm nor exclude onychomycosis.
Punch biopsy of the nail matrix tissue - invasive and reserved for suspected nail tumors or a longitudinal pigmented band concerning for subungual melanoma, not routine confirmation of fungus.
Wood lamp examination of the nail - highlights fluorescent infections such as Microsporum tinea capitis or the coral-red glow of erythrasma, but Trichophyton rubrum, the usual cause of onychomycosis, does not fluoresce, and the exam cannot demonstrate fungal elements in the nail plate.
Additional high-yield points
KOH preparation and fungal culture are acceptable alternatives: KOH is quick and inexpensive, and culture identifies the organism (including nondermatophyte molds and Candida) but takes weeks; pairing PAS or KOH with culture maximizes yield. Dermoscopy and Wood lamp examination are bedside aids that cannot confirm fungal elements.
Question 2DermatologyMedium
A 58-year-old man presents with a thickened, yellow-brown right great toenail that has slowly worsened over the past year and now catches on his socks. He also has scaling and maceration between his toes. His medical history includes hypertension treated with amlodipine, and he reports no liver disease or alcohol use. A periodic acid-Schiff stain of a nail clipping shows septate hyphae consistent with a dermatophyte. Baseline AST and ALT are normal. Which of the following is the most appropriate initial management?
AOral itraconazole for 12 weeks
BOral griseofulvin for 12 months
CTopical ciclopirox for 48 weeks
DOral terbinafine for 12 weeks
EOral fluconazole for 6 months
Reveal answer & full explanation
Correct answer: D — Oral terbinafine for 12 weeks
AOral itraconazole for 12 weeks
BOral griseofulvin for 12 months
CTopical ciclopirox for 48 weeks
DOral terbinafine for 12 weeks✓
EOral fluconazole for 6 months
Why Oral terbinafine for 12 weeks is correct
Oral terbinafine 250 mg/day for 12 weeks (toenails) is the guideline-defined first-line therapy for dermatophyte onychomycosis, with the highest cure rates (~70%) of the oral agents.
This patient has a PAS-confirmed dermatophyte infection, normal baseline LFTs, and no contraindication, so systemic terbinafine is appropriate.
Coexisting tinea pedis should also be treated (topical allylamine) to reduce reinfection, but the nail itself requires a systemic allylamine.
Why the others are wrong
Oral itraconazole for 12 weeks — an effective azole reserved for when terbinafine is contraindicated or for Candida/non-dermatophyte molds; as a CYP3A4 inhibitor it interacts with the patient's amlodipine (a CYP3A4-cleared calcium channel blocker), making terbinafine the better fit here.
Topical ciclopirox for 48 weeks — a topical lacquer with notably lower cure rates, appropriate for mild disease or when oral therapy is contraindicated, not for confirmed thick subungual disease in a candidate for systemic treatment.
Oral fluconazole for 6 months — an off-label alternative most useful for Candida; it is less effective than terbinafine against dermatophytes and is not first-line.
Oral griseofulvin for 12 months — a first-line oral agent for tinea capitis in children and the original systemic treatment for nail infection, but toenail courses run 12-18 months with low cure rates and frequent relapse, so terbinafine has replaced it for dermatophyte onychomycosis.
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Tinea pedis (the most common source of dermatophyte nail infection; frequently coexists and drives reinfection)
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
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.
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); terbinafine is not recommended in chronic or active liver disease
Drug interactions: itraconazole (CYP3A4 inhibitor) with statins, benzodiazepines, warfarin, calcium channel blockers — review medications carefully; contraindicated with several CYP3A4-cleared drugs; boxed warning: do not use itraconazole for onychomycosis in patients with CHF or ventricular dysfunction (negative inotrope)
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 single 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.
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