Onychomycosis and nail sampling

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Onychomycosis is infection of nail keratin by dermatophytes, yeasts or non-dermatophyte moulds. Distal lateral subungual disease is the commonest pattern: colour and debris begin beneath the free edge and progress proximally. Superficial white disease affects the plate surface, while proximal disease is unusual and should prompt consideration of immune compromise. Toenails are affected more often because occlusion, slow growth, tinea pedis, trauma, diabetes and poor circulation create a favourable reservoir.

Appearance alone is unreliable. Psoriasis can cause onycholysis, subungual hyperkeratosis and discolouration; repetitive footwear trauma thickens great toenails; lichen planus may scar the matrix. Fungal infection can also coexist with these conditions. Laboratory confirmation matters most before months of oral treatment. The best specimen is abundant active diseased keratin close to the advancing border, not a small clean distal tip. Explain what will be clipped and obtain consent, particularly when nail is painful or vascular supply is poor.

Treatment depends on organism, site, number of nails, matrix involvement, symptoms, host risk and patient preference. Topical lacquer avoids systemic toxicity but requires prolonged meticulous use and penetrates poorly through extensive thick nail. Oral terbinafine is effective for many dermatophytes but has liver and interaction risks. A normal-looking nail is not immediate proof of cure, and residual dystrophy after eradication should not trigger repeated tablets without renewed sampling.

Key points

Onychomycosis commonly produces distal or lateral yellow-white discolouration, subungual debris, thickening, brittleness and onycholysis, but psoriasis and trauma can look identical.
Examine every nail plus toe webs, soles, palms and scalp; untreated tinea pedis can repeatedly reseed a treated toenail.
Before oral therapy, clean away surface contaminants, clip back to the most proximal diseased nail possible and include subungual debris for microscopy and culture or the local validated molecular pathway.
A negative result after a small distal clipping or recent antifungal use does not exclude infection; repeat a technically better sample when suspicion remains and treatment would be consequential.
Limited distal disease without matrix involvement can be treated with amorolfine 5% lacquer once weekly, usually for six months on fingernails and nine to twelve months on toenails.
For confirmed dermatophyte disease needing systemic treatment, terbinafine 250 mg orally once daily is commonly used for six weeks for fingernails and twelve weeks for toenails.
Check liver disease, baseline liver function, pregnancy, interactions and the exact product information before oral terbinafine; repeat liver tests after four to six weeks under the SmPC.
Clinical cure lags microbiological cure because clear nail must grow from the matrix. Toenails may take twelve to eighteen months to look normal even after fungus is eradicated.
Treat shoes, moisture and coexisting foot fungus pragmatically, but do not expose every cosmetically dystrophic nail to systemic medicine when benefit is small or diagnosis unconfirmed.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Dermatophyte infection

Trichophyton species invade nail keratin from adjacent tinea pedis and account for most established toenail fungal disease in the UK.

Yeast and mould infection

Candida more often affects damaged fingernails and folds, while non-dermatophyte mould causation requires careful exclusion of environmental contamination.

Host and mechanical susceptibility

Age, diabetes, immune compromise, poor circulation, occlusive footwear, slow growth and repeated trauma permit fungal persistence and recurrence.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Fungus invades keratin
Organisms digest nail plate and subungual keratin, producing opacity, fragility and debris while advancing toward the growth matrix.
2
Plate separates from bed
Accumulating subungual material lifts the nail, creating onycholysis, further trauma and a protected space for ongoing fungal growth.
3
Slow growth delays recovery
Even after organisms die, damaged plate persists until matrix produces enough normal keratin to replace it, especially in toenails.
4
Skin reservoirs reseed nail
Untreated toe-web or plantar dermatophyte repeatedly inoculates adjacent nail and footwear, contributing to recurrence after an apparently effective course.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Distal lateral disease

Yellow-white colour, onycholysis and crumbly subungual hyperkeratosis advance proximally from one side or the free edge.

Superficial white plate

Powdery white islands can be scraped from the dorsal plate, although trauma and keratin granulation from polish are mimics.

Proximal subungual pattern

White or discoloured change begins near the proximal fold and is unusual enough to prompt immune and alternative-diagnosis review.

Coexisting tinea pedis

Toe-web maceration, plantar scale or an active border supports a dermatophyte reservoir and requires concurrent skin treatment.

Dermatophytoma

A dense longitudinal white-yellow spike or compact fungal mass may respond poorly to ordinary lacquer and needs specialist sampling and treatment.

Pigmented-lesion warningRed flag

A new irregular longitudinal band, Hutchinson pigment, nail destruction, bleeding or a mass is not assumed fungal and needs urgent lesion assessment.

Red flags requiring action

A new irregular pigmented nail band, periungual pigment, ulceration, bleeding or a nail-bed mass requires urgent melanoma assessment; painful spreading erythema, diabetic foot ulceration, ischaemia or systemic infection needs prompt acute foot or infection care.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
Representative nail clipping and subungual debrisFirst step
Why
Obtain active infected keratin for laboratory confirmation before systemic treatment.
Interpretation and limitations
Clean surface, clip proximally into diseased plate and scrape debris from the advancing edge; a distal cosmetic clipping has a high false-negative risk.
02
Direct microscopy
Why
Detect fungal elements quickly in prepared nail keratin.
Interpretation and limitations
Visible hyphae support fungal infection but do not always identify species or viability; a negative result can reflect sampling error or previous therapy.
03
Fungal culture or validated PCR
Why
Identify organism and distinguish dermatophyte from yeast or mould where treatment differs.
Interpretation and limitations
Culture is slow and contamination occurs; non-dermatophyte mould often requires repeat concordant isolation and compatible microscopy before attribution.
04
Histological nail clipping
Why
Demonstrate organisms within nail when routine mycology is repeatedly negative but suspicion remains.
Interpretation and limitations
Special stains can increase sensitivity but do not provide susceptibility and require the laboratory to know the specimen is nail keratin.
05
Baseline liver function and medicine reconciliation
Why
Reduce avoidable harm before oral terbinafine or another systemic antifungal.
Interpretation and limitations
Do not use oral terbinafine in chronic or active hepatic disease; check CYP2D6 interactions and relevant renal, pregnancy and haematological context.
06
Nail dermoscopy and biopsy referral
Why
Assess a pigmented band, mass or destructive single-nail process for melanoma or tumour.
Interpretation and limitations
Dermoscopy informs urgency but nail-matrix biopsy is a specialist procedure with permanent dystrophy risk and must not be replaced by fungal treatment trials.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Nail psoriasis

Pits, oil-drop colour, onycholysis with an erythematous margin and psoriasis elsewhere support inflammatory dystrophy, though fungal infection can coexist.

Traumatic onychodystrophy

Repeated footwear pressure commonly thickens or separates great toenails and often produces repeatedly negative good-quality mycology.

Nail lichen planus

Longitudinal ridging, thinning, fissuring or pterygium suggests matrix inflammation that can scar permanently and warrants dermatology assessment.

Subungual melanoma

A new irregular longitudinal pigment band, periungual extension, bleeding, mass or progressive nail destruction requires urgent tumour evaluation.

Bacterial pigmentation

Green colour beneath onycholysis suggests Pseudomonas colonisation and needs moisture and host assessment rather than automatic systemic antifungal therapy.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01ConfirmSample before systemic exposureFirst stepNail dystrophy is uncertain or oral antifungal treatment is being considered.

1Stop cosmetic polish, clean the plate and examine all nails, skin and feet for psoriasis, trauma, tinea and a suspicious pigmented or destructive lesion.
2Clip the most proximal accessible diseased plate and collect generous subungual material, sending the exact site and treatment history for microscopy and culture or local PCR.
3If a weak sample is negative but clinical probability remains high, repeat from a better active site before declaring resistance or prescribing months of systemic therapy.

02Limited diseaseUse lacquer for an achievable targetConfirmed disease is distal, affects a small number of nails and has not reached the matrix.

1Thin or file affected plate as the product directs, protect surrounding skin and apply amorolfine 5% lacquer once weekly to the entire affected nail and accessible edge.
2Continue approximately six months for fingernails or nine to twelve months for toenails, cleaning equipment and treating coexisting foot fungus to reduce reseeding.
3Review for clear proximal growth and adherence rather than expecting the old damaged nail to change colour immediately; switch strategy if disease reaches the matrix or progresses.

03Systemic treatmentTreat confirmed dermatophyte disease safelySeveral nails, matrix involvement, marked thickening or functional symptoms make topical penetration inadequate and benefit outweighs risk.

1Confirm organism, check liver history and baseline liver tests, reconcile prescription and non-prescription medicines and review pregnancy and breastfeeding.
2Use oral terbinafine 250 mg once daily for the licensed site duration, usually six weeks for fingernails and twelve weeks for toenails, adjusting only through product or specialist advice.
3Repeat liver tests after four to six weeks, stop promptly for hepatic symptoms or serious reaction and assess response through new clear growth after the course finishes.

04Failure or recurrenceReconfirm organism and diagnosisNail fails to clear, worsens during treatment or becomes dystrophic again after apparent response.

1Check whether enough normal nail growth time has elapsed and whether adherence, footwear trauma, tinea pedis or untreated household reservoirs explain apparent failure.
2Repeat mycology from active proximal disease and reconsider psoriasis, lichen planus, tumour or non-dermatophyte mould rather than automatically extending terbinafine.
3Refer severe host risk, dermatophytoma, resistant confirmed infection or a suspicious single nail to dermatology, podiatry or microbiology as appropriate.

Key medicines and prescribing safety2 treatments · regimens, roles and cautions

Systemic fungicidal treatment for confirmed dermatophyte onychomycosis when extent, matrix involvement or symptoms make topical treatment inadequate.

Terbinafine 250 mg tablets

Take 250 mg by mouth once daily for six weeks for fingernail infection and twelve weeks for toenail infection unless specialist advice changes duration.

Contraindicated in chronic or active hepatic disease. Check baseline liver function and repeat after four to six weeks; stop for anorexia, nausea, fatigue, right-upper-quadrant pain, jaundice, dark urine or pale stool, and review CYP2D6 interactions, rash, taste, smell and blood dyscrasia symptoms.

Topical treatment for mild distal fungal nail infection affecting a limited number of nails without matrix involvement.

Amorolfine 5% medicated nail lacquer

Apply to affected nails once weekly after filing and cleaning, continuing about six months for fingernails and nine to twelve months for toenails until healthy nail has regrown.

Avoid skin, eyes and mucosa, use dedicated files and do not use cosmetic artificial nails over treatment. Extensive, matrix or painful disease and diabetes or poor circulation require clinician review rather than self-treatment.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Pain and impaired mobility

Thick distorted toenails press against shoes, making walking and self-care difficult, particularly with arthritis, neuropathy or visual impairment.

Recurrent cellulitis portal

Fissured tinea pedis and traumatised nail folds permit bacterial entry, especially in diabetes, chronic oedema and poor circulation.

Permanent nail dystrophy

Longstanding matrix injury, severe infection or an incorrect inflammatory diagnosis can leave persistent deformation after microbiological cure.

Systemic treatment toxicity

Oral terbinafine can cause hepatic, skin, blood, taste, smell and interaction-related harm, making confirmation and monitoring central.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

For oral terbinafine, document baseline liver assessment and repeat liver tests after four to six weeks with a named clinician responsible for action.
Ask urgently about hepatic symptoms, severe rash, infection, mouth ulcers, bruising, altered taste or smell and relevant interacting medicines during systemic therapy.
Measure a clear proximal nail-growth zone and photograph consistently; toenail appearance can lag effective treatment for twelve to eighteen months.
Treat and review tinea pedis, footwear moisture and nail trauma so reinfection is not mislabelled primary drug resistance.
Re-sample recurrent or non-responsive disease before another systemic course and re-examine any single pigmented or destructively changing nail.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

The active edge is proximal

Fungus advances toward the matrix beneath nail, so the most proximal accessible diseased plate and debris contain more diagnostic material than the free tip.

Dystrophy is not fungus

Psoriasis, lichen planus and footwear trauma can reproduce colour, thickening and onycholysis and may coexist with genuine infection.

Mould needs stronger proof

Environmental mould easily contaminates culture, so compatible microscopy and repeated isolation help distinguish pathogen from an incidental laboratory guest.

Cure grows out

Antifungal eradication cannot repair old keratin; improvement appears as a new clear nail segment extending distally over months.

Feet form one reservoir

Persistent toe-web or plantar dermatophyte can reseed an apparently cured nail, making concurrent skin examination and treatment part of recurrence prevention.

11Common pitfallsFrequent interpretation and management errors.

01
Diagnosing fungus from yellow colour alone and missing psoriasis, trauma or melanoma.
02
Sending a tiny distal clipping without subungual debris and trusting a negative result absolutely.
03
Starting oral terbinafine without mycological confirmation, liver assessment and interaction review.
04
Repeating tablets because damaged nail remains visible before enough normal growth time has elapsed.
05
Calling one non-dermatophyte mould culture causative without compatible microscopy or repeat evidence.
06
Ignoring coexisting tinea pedis and interpreting preventable reseeding as drug resistance.