Epidemiology

This is one of the most commonly occurring dermatological conditions. International prevalence reports a range from 3-26% worldwide,^[2] whilst UK prevalence studies report a range of 3-8% in the UK.^[3]The incidence of new cases of onychomycosis (OM) appears to be rising due to the increasing prevalence of diabetes in the population, more frequent incidence of immunosuppression and an ageing population.^[3]

Risk factors

• Age - adults are ~30 times more likely than children to suffer the condition (affects 2.6% of children younger than 18 years, but as many as 90% of people older than 70 years).^[3]
• Immunosuppression - illness or medications that suppress immune responses greatly increase the likelihood of suffering OM.
• Diabetes mellitus - one study found that clinical onychomycosis was found in 162 of 321 patients with type 2 diabetes mellitus.^[4]
• Cutaneous fungal infection co-exists with OM in about 30% cases.^[3]
• Living in a warm, humid climate.
• Participation in athletic/sporting activities, regular communal bathing and occlusive footwear.
• Prior trauma to the nail.

Infecting organisms^[2][3]

Dermatophytes

• Trichophyton rubrum or Trichophyton mentagrophytes causes over 90% of cases,^[5]   with T. rubrum being responsible for about 70% of the total.
• Other organisms in this group include Epidermophyton spp. and Microsporum spp.

Yeasts

These cause ~8% of total infections, particularly Candida albicans in the UK and Malassezia furfur  (called Pityrosporum orbiculare in its yeast-like form) in tropical climes.

Non-dermatophyte moulds

These cause about 1-10% of total infections, eg Scopulariopsis brevicaulis.^[6]

Presentation^[2][3]  

The toenails are affected in about 80% of cases of OM.

Distal and lateral subungual onychomycosis

Distal and lateral subungual onychomycosis (DLSO) form the vast majority of cases of OM:

• Nearly always caused by dermatophytes.
• Can either affect a healthy nail or one already diseased, eg by psoriasis.
• Affect the hyponychium (epithelium of nail bed), often at the lateral edges initially.
• Spread proximally along the nail bed, causing creamy/buff discolouration, subungual hyperkeratosis and onycholysis.
• The nail plate is not affected initially but may become so in time.
• May be confined to one side of the nail or spread sideways to involve the whole nail bed.
• Relentless progression until it reaches the posterior nail fold. Progression can occur within weeks or more slowly over months or years with the nail becoming opaque, thickened and cracked, friable and raised from the nail bed.
• The nail plate becomes friable and may disintegrate, particularly after trauma.
• Surrounding skin is nearly always affected by tinea pedis.
• Approximately 80% of cases occur on the feet, especially on big toes, often affecting both toenails and fingernails. Fingernail DLSO has a similar appearance although nail thickening is less common; toenail infection usually precedes it.

Superficial white onychomycosis

Superficial white OM (SWO) is less common than DLSO:

• It is usually due to dermatophyte infection with T. mentagrophytes.
• It presents as white chalky plaque on the proximal nail plate, almost exclusively on the toenails.
• The surface of the nail plate is affected rather than the nail bed. The nail plate may become eroded and even lost.
• There is white rather than creamy discolouration.
• There is a notably flaky surface on the nail plate.
• Onycholysis is not usually a feature.
• Concurrent tinea pedis is less common than in DLSO.

Proximal subungual onychomycosis

This is uncommon:

• Candidal OM occurs in three different types:
  • Candida paronychia: initially appears as oedema, erythema and pain of the nail fold, from which pus can be expressed at times. Also, the nail plate becomes dystrophic with patches of opacification or discolouration (white, yellow, green or black) with transverse furrows. Usually, pressure on the nail causes pain. Most cases are on fingernails - usually the middle finger.
  • Subungual abscess with DLSO occurring in the setting of onycholysis.
  • Total nail dystrophy: affects all or a large proportion of nails, associated with chronic mucocutaneous candidiasis (CMC). The entire fingernail may become thickened and dystrophic.
• Causes chronic paronychia with secondary nail dystrophy.
• May affect the distal nail alone without paronychial involvement (usually in cases of Raynaud's phenomenon or peripheral vascular disease).
• Usually affects fingernails without toenail involvement in those whose occupations cause them constantly to have wet or allergen-irritated hands.
• Cuticular detachment and signs of infection and inflammation in the nail matrix may be observed.
• May complicate CMC or as a secondary infection due to other causes of nail disease, eg psoriasis.

Total dystrophic onychomycosis

• Represents a long-standing, severe, end-stage disease progressing from all the above clinical patterns.
• Complete destruction of the nail plate is observed.

Differential diagnosis^[2][3]

Only about 50% of discoloured or dystrophic-appearing nails have a fungal infection confirmed with dermatophyte on culture. Other causes include:

• Onychogryphosis (thickening and distortion of the nail, typically of the big toe, thought to be due to previous nail bed trauma).
• Trauma (tight shoes, nail biting).
• Poor foot care.
• Eczema (irritant or allergic contact dermatitis).
• Lichen planus.
• Subungual melanoma.
• Psoriatic nail disease.
• Bacterial paronychia, eg pseudomonas infection.
• Systemic disease, eg thyroid disease, diabetes, peripheral vascular disease.
• Rare systemic disorders, eg keratosis follicularis (Darier's disease), yellow nail syndrome, nail-patella syndrome, pachyonychia congenita.
• Idiosyncratic drug reaction (especially tetracyclines, quinolones and psoralens).

Investigations^[3][7]

Testing for infection is not needed if treatment would not be given.

• Nail material should be sent for microscopy. There is a high false negative rate (30-40%) and even positive results should be interpreted with caution, as fungal organisms may exist as saprophytes, rather than as an invasive infection.
• Culture of nail material should also be undertaken, as this increases sensitivity and will determine species but may take several weeks.
• Nail histology is not usually necessary unless there is reason to suspect another cause of nail pathology, such as psoriasis.^[2]

Interpretation of results

Microscopy results take a few days, but culture results may take 4-6 weeks. The results are regarded as positive:^[8] 

• For dermatophytes, if either microscopy or culture is positive.
• For Candida spp; if both microscopy and culture are positive.
• For non-dermatophytes if both microscopy and culture are positive on at least two samples taken at different times.Non-dermatophyte moulds are rare causes of nail infection (usually secondary infection following trauma or an underlying dermatophyte infection).

Associated diseases^[2][3]

• DM
• Any cause of immunocompromise
• Raynaud's phenomenon
• Peripheral vascular disease
• Tinea pedis
• Occupational dermatitis of hands
• CMC
• Psoriasis
• Nail trauma

Management^[3][7][8]

To treat or not to treat?

Traditionally there has been a reluctance to treat fungal nail infection as it has been seen as a trivial cosmetic problem. However, without treatment, the condition often spreads to multiple toenails and can form a portal for recurrent bacterial infections. It is common in diabetics and can contribute to foot problems.

• There is no medical necessity to treat and patients should be given the information to make an informed decision based on:
  • Even after successful treatment of the fungal infection, the nail may not look completely normal.
  • Treatment is only successful in up to 50% of people.
  • Even in those in whom it is successful, nails may appear abnormal for over 12 months due to their slow growth.
  • Relapse occurs in about 20-25% of people.^[9]
  • Oral medication is taken for six weeks for fingernail infections and for three months for toenail infections.
  • Topical treatments may need to be applied for up to 12 months.
  • All medication has potential side-effects.
• However, anyone who presents should probably be offered treatment, as the condition is likely to be causing significant distress if it has brought them to consult.
• If the condition progresses it can cause significant morbidity and functional disturbance, particularly in the elderly.
• There is also a public health argument for treating it, to lessen the reservoir of fungal spores in communal bathing areas, through reduction in the number of sufferers.

Cosmetic treatment

Referral to a chiropodist may be helpful.

• Nail filing and nail polish can lessen cosmetic effects.
• It is helpful to trim dystrophic nails.
• In DLSO, remove nail and hyperkeratotic nail bed with clippers.
• In SWO debride abnormal nail with a curette.

Medical treatment

Topical therapy: in general, topical treatments are slightly better than placebo but often fail due to poor penetration of the nail plate.

• They should be reserved for mild distal disease in up to two nails, or for superficial white onychomycosis, or where there are contra-indications to systemic therapy.^[10]
• Treatment should be given daily for six months to one year.
• Can be used in cases of SWO or early DLSO where infection is confined to the distal edge of the nail.
• 5% amorolfine is effective and appears to be the best topical agent in terms of its ability to penetrate the nail matrix. 28% tioconasole is also available but the evidence base for its effectiveness is weak. 
• Newer topical therapies such as tavaborole, efinaconazole and luliconazole are currently being explored.^[9]
• Evidence for combination treatment with oral and topical antifungals is weak and not currently recommended.^[8]  
• Various methods using chemical and physical enhancement techniques to improve the transmisison of topical drugs across the nail bed are being researched.^[11]

Systemic therapy:^[3][7][8]systemic treatment is recommended for most people, as it is more effective. The slow growth of nails means that they do not appear normal even after effective treatment.

• Terbinafine:
  • Currently first-line with evidence of greater efficacy compared to itraconazole.
  • High cure rates and is usually effective after three months of therapy.
  • It is not licensed for use in children.
  • There have been cases of severe idiosyncratic skin and hepatotoxic reactions.
  • It interacts with rifampicin and cimetidine.
• Itraconazole:
  • Highly active against Candida spp. but much less so against dermatophytes.
  • It can be given in a pulsed rather than continuous regimen (one week on, three weeks off). Cure rates are similar for both regimes.
  • It can cause hepatotoxicity and LFTs should be checked for treatment lasting longer than a month.
  • It is contra-indicated in pregnancy and not licensed for use in children.
  • It interacts with a wide variety of commonly used pharmaceutical agents, including warfarin, antihistamines, antipsychotics, digoxin, H2-antagonists, some statins and phenytoin.
• Griseofulvin:
  • May be used in adults and children.
  • It is not expensive and there is a long experience of its use.
  • It requires long duration of treatment (at least six months) and has low cure and high relapse rates.
  • It interacts with warfarin, ciclosporin and the combined oral contraceptive pill (it is an hepatic enzyme inducer).
  • It is rarely used now, although it is still used for trichophyton infections in children.
• Fluconazole may be a useful systemic agent but is not currently licensed for this indication.

Side-effects:

• Side-effects of systemic antifungals include headache, itching, loss of sensation of taste, gastrointestinal symptoms, rash, fatigue and abnormal liver function.^[12]
• One meta-analysis looking at safety of antifungals used to treat superficial fungal infections found a low incidence of adverse events in an immunocompetent population.^[13] The risk of having asymptomatic serum transaminase elevation which did not require treatment discontinuation was less than 2.0% for all treatment regimens. The risk of an adverse liver reaction requiring treatment to be stopped ranged from 0.1% (continuous itraconazole) to 1.2% (continuous fluconazole).

Surgery

Nail avulsion, removal of nail plate, chemical treatments (eg, 40–50% urea solution for very thickened nails) and matrixectomy may enhance the effectiveness of oral treatment.

Current UK guidelines^[14] advise against combining oral and topical treatments, as there is insufficient evidence of benefit; however, others argue that using topical, systemic and/or surgical treatments in combination reduces costs and length of treatment.^[3]

Studies are reporting the successful use of laser treatment, but further randomised controlled trials are needed to evaluate long-term success of treatment.^[9] [15]

Refer where:^[8]

• Diagnostic uncertainty remains.
• There is no response to medical treatment.
• The patient's choice is to have surgical intervention.
• Children are concerned - it is a rarer condition in children compared to adults and there are more limited treatment options.
• There is suspected immune deficiency - eg, mucocutaneous candidiasis.
• There is extensive disease.
• There are recurring candidal nail infections.

Complications^[16]

• Poor cosmetic appearance of hands/feet.
• Disfigurement and total destruction of the nail plate.
• Paronychia.
• Damage to diabetic feet.
• Cellulitis, osteomyelitis, sepsis and necrosis in elderly patients and diabetics.
• Psychosocial problems due to embarrassment at cosmetic appearance.
• Pain and limitation of function, particularly in older patients.

Prognosis

• Studies report mycobiological cure rates of 48-76% for patients on oral therapy.^[16]
  There is often a discrepancy in clinical and microbiological cure rates in clinical trials.^[14][17] Cure, as defined by successful eradication of fungus on microscopy and culture, will not always result in a normal appearance of the affected nail due to:
  
  

  • Delay of 6–12 months as the damaged nail grows out.
  • The nail may have been dystrophic to begin with, predisposing it to fungal infection.
• Fingernail infections usually have much higher cure rates, in the region of 70%.
• Untreated, fungal nail disease is usually progressive, leading to gradual destruction of the nail plate. However, there may be cases that spontaneously remit that do not present to their doctor.

Prevention

Primary prevention is not practised, except where there is a cause of immunocompromise, such as AIDS, where prophylactic therapy may be considered.

Secondary prevention with topical terbinafine cream after cure with systemic terbinafine appears to be effective in reducing relapse rates.^[16]

Suggested hygiene measures to limit spread and prevent relapse include:^[8]

• Treating other fungal infections, such as athlete's foot.
• Wearing footwear in public environments such as communal bathing places, locker rooms, and gymnasiums.
• Replacing old footwear, as this could be contaminated with fungal spores.
• Keeping the area clean, drying well after bathing, changing socks regularly.
• Avoiding trauma to the nails.
• Avoidance of towel sharing.
• Avoidance of repeated hand washing/immersion of the hands in water if the fingernails are affected.
• Wearing sandals or slippers in communal bathing places, locker rooms, gyms, etc.