Fungal nail infections

Synonyms: onychomycosis, tinea unguium

What are fungal nail infections?

Different fungal organisms may infect the nails, with different patterns of presentation, affecting any part of the nail from the nail bed to the nail matrix and plate. The most common result is a poor cosmetic appearance of the affected nail(s); however, the condition may also cause pain, disfigurement and functional impairment.

Whilst not life-threatening, quality of life may be impaired through psychological distress caused by the appearance of the nails and localised pain. ¹

This is one of the most frequently diagnosed dermatological conditions. Global prevalence is around 5.5%. ² UK prevalence studies report a range of 3-8% in the UK which is similar to that in the United States. 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.⁴

Risk factors for fungal nail infections³²¹

• Age - adults are ~30 times more likely than children to suffer the condition and it increases in incidence with age.²

• Immunosuppression - illness or medications that suppress immune responses greatly increase the likelihood of developing fungal nail infections.

• Diabetes mellitus - one study found that clinical onychomycosis was found in 162 of 321 patients with type 2 diabetes mellitus.⁵

• Cutaneous fungal infection (tinea pedis).

• Living in a warm, humid climate.

• Obesity.

• Prior trauma to the nail.

• Psoriasis.

• Family history of fungal nail infections.

Dermatophytes

• Trichophyton rubrum or Trichophyton mentagrophytes causes between 50 and 70% of fungal nail infections.³⁸

• Other organisms in this group include Epidermophyton spp. and Microsporum spp.

Yeasts

Yeasts are increasingly found in nail samples where onychomycosis is suspected. This could be due to Candida onychomycosis but it is also thought possible that the yeasts are secondary colonisers and do not cause disease. Candida cultured from toenails is often found in asymptomatic nails whereas onychomycosis is more likely if yeasts are found on fingernail material.⁸

Non-dermatophyte moulds

These cause about 10% of total infections globally and are increasing in incidence. They are much more common in tropical and subtropical regions, with over 50% of fungal nail infections in Iran being found to be due to non-dermatophyte moulds.⁸

The toenails are affected much more frequently than fingernails.³⁹

Toe onychomycosis

© James Heilman, MD, CC BY-SA 3.0, via Wikimedia Commons

Distal lateral subungual onychomycosis (DLSO) ³

DLSO form the vast majority of cases of fungal nail infections.

• Nearly always caused by dermatophytes.

• Can either affect a healthy nail or one already diseased - eg, by psoriasis.

• Affects the hyponychium (epithelium of nail bed), often at the lateral edges initially.

• Spreads 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 (SWO)³

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 (PSO)³

PSO is uncommon but is more common in patients with AIDS.

• 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 arterial 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 (TDO)³

• Represents a long-standing, severe, end-stage disease progressing from any fungal nail infection.

• It can take 10-15 years to develop.

• Complete destruction of the nail plate is observed.

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 spp. infection.

• Systemic disease - eg, thyroid disease, diabetes, peripheral arterial 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).

• Yellow nail syndrome.

Testing for fungal infection is not needed if treatment would not be given. However tests should always be done if treatment is requested. Treating without confirmed fungal nail infection is not advised.

• 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 a few weeks.

• Nail histology is not usually necessary unless there is reason to suspect another cause of nail pathology, such as psoriasis.⁶

• Polymerase chain reaction is an effective method of detecting dermatophytes but is not used in routine practice.

Interpretation of results¹¹

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

• 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 less common causes of nail infection (usually secondary infection following trauma or an underlying dermatophyte infection).

• Diabetes mellitus.

• Any cause of immunocompromise.

• Raynaud's phenomenon.

• Peripheral arterial disease.

• Tinea pedis that has often been present for years.

• Occupational dermatitis of hands.

• Psoriasis.

• Nail trauma.

• Hereditary predisposition.

To treat or not to treat?

There is no need to treat if the person is not worried about the appearance, or there are no symptoms and no comorbidities which could increase the risk of complications.

• 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.³

  • Cure is not achieved in 20-40% of patients.

  • 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.⁸

  • 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.

• If the condition progresses, it can cause significant morbidity and functional disturbance, particularly in the elderly.

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.

Medical treatment

Self-care management¹¹¹³

• Nails should be trimmed short.

• Looser footwear should be worn, without high heels or narrow toes. Old footwear, which could be contaminated, should be considered for replacement.

• Shoes should not be shared and it is best to avoid sandals or going barefoot in public places.

• Cotton, absorbent socks should be worn.

• Good foot hygiene is important.

• Protective footwear should be worn in communal areas - eg, changing rooms, and gyms - to avoid re-exposure.

• Prolonged or frequent exposure to warm, damp conditions should be avoided if possible.

• Trauma to the nails should be avoided if possible.

Topical therapy¹¹

Topical therapy can be bought over the counter.

More recent topical therapies have significantly better efficacy than in the past. Topical terbinafine has a 76% cure rate whilst itraconazole pulse dosing has a 63% cure rate, and fluconazole 48%.³However, guidelines advise that topical treatment should only be used where there is very minor disease or where oral treatments are contra-indicated.

Treatment should be given daily for 6 months for fingernails and 9-12 months for toenails .

Systemic therapy¹⁰¹¹

Systemic treatment is recommended if topical treatment fails or is contra-indicated. The slow growth of nails means that they do not appear normal even after effective treatment so it remains important to confirm ongoing fungal nail infection.

If dermatophyte nail infection is confirmed

• Terbinafine:

  • Currently first-line with evidence of greater efficacy compared to itraconazole.

  • Prescribe 250 mg once a day for between six weeks for fingernails, and for three to six months for toenails.

  • Advise the person that visible improvement may be seen after the end of two months of fingernail treatment and three months of toenail treatment.

  • It is not licensed for use in children.

  • There have been cases of severe idiosyncratic skin and hepatotoxic reactions.

  • Terbinafine should not be prescribed to anyone with hepatic impairment. LFTs should be checked before treating and some guidelines advise repeating LFTs after 4-6 weeks.

  • Terbinafine should not be prescribed to anyone with severe renal impairment. Caution should be used with more moderate renal impairment, as well as with psoriasis or auto-immune disease.

  • It interacts with rifampicin and cimetidine.

• Itraconazole:

  • Should be offered if an alternative to terbinafine is indicated.

  • Highly active against Candida spp. but much less so against dermatophytes.

  • It can be given in a pulsed rather than continuous regimen. 200 mg twice a day for one week, with subsequent courses repeated after a further 21 days.

  • Prescribe two pulses for fingernails and three pulses for toenails.

  • 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-receptor antagonists, some statins, and phenytoin.

Griseofulvin is no longer recommended as a treatment for fungal nail infections.

Side-effects

• Side-effects of systemic antifungals include headache, itching, loss of sensation of taste, gastrointestinal symptoms, rash, fatigue, abnormal liver function, urticaria, and Stevens-Johnson syndrome along with others. ¹⁴¹⁵

• There are very few recent studies looking at the safety of antifungal treatments. A meta-analysis in 2007 suggested that 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). ¹⁶

• Recent studies also confirm that the risks are low but not zero. ¹⁷

If candidal or non-dermatophyte nail infection is confirmed

Use itraconazole first-line and terbinafine second-line.

Treatment failure

• Manage any comorbidities which may be hampering the effectiveness of treatment.

• Consider re-investigating the cause.

• Consider referral to a podiatrist if available in your area or to a dermatologist.

• Refer to a paediatric dermatologist in a child as fungal nail infections are significantly less common in children.

Surgery

Keratolysis with 40% urea preparations under occlusion has become the accepted method of atraumatic nail removal. However, even surgical treatment is ineffective without anti-fungal treatment. It is unlikely that surgical management will be available on the NHS.

Refer where:

• Diagnostic uncertainty remains.

• There is no response to medical treatment.

• 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.

• 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 people with diabetes.

• Psychosocial problems due to embarrassment at cosmetic appearance.

• Pain and limitation of function, particularly in older patients.

• The prognosis is variable and depends on the type of infection as well as host factors such as comorbidities and age. Meta-analyses report mycotic cure rates of 76% for terbinafine, 63% for itraconazole with pulse dosing, 59% for itraconazole with continuous dosing and 48% for fluconazole.¹⁸
  

• 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.

Secondary prevention with topical terbinafine cream after cure with systemic terbinafine appears to be effective in reducing relapse rates,²⁰ but it is not recommended as standard management.