Fungal infection of the nail

By Professor Rodney Sinclair and Dr Eshini Perera

Even after successful treatment, onychomycosis can be a peskily persistent condition.

Case
John is a 59-year-old male who presents with bilateral dystrophy of his great toenails. He is embarrassed by the appearance of his nails and avoids wearing open footwear.

He eventually attends his GP after several years upon noting that the whole nail has become affected (top figure) and is now causing him increasing discomfort when walking.

Culture confirms Trichophyton rubrum onychomycosis and John is treated by a dermatologist with Canesten Fungal Nail Treatment Set, together with 250mg of oral terbinafine once daily for three months.

Incidence
Onychomycosis is the term used for fungal infection of the nail. It is responsible for up to 80% of diseases of the toenails.1

The condition is commonly caused by dermatophyte moulds. Of the three dermatophyte moulds that cause skin disease in animals and humans (microsporum, epidermophyton and trichophyton), only Trichophyton sp. affect the nail.

Onychomycosis can occasionally be caused by non-dermatophyte moulds or yeasts such as Candida albicans.


Figure 2: Distal subungal onychomycosis.

Clinical hallmarks
Onychomycosis may involve a single nail or multiple nails, and, rarely, all nails. Toenails are seven times more likely to be affected than fingernails.2

The clinical hallmarks of onychomycosis are thickened, discoloured, friable nails with a build-up of subungual hyperkeratosis. The fungus most commonly invades the undersurface of the nail from the distal free edge.

Linear yellow hyperkeratotic bands that grow proximally towards the lunula (half-moon) are pathognomonic for onychomycosis. Figures 2-4 illustrate alternate presentations of onychomychosis.

Predisposing factors
Onychomycosis is multifactorial. Patients with diabetes are twice as likely to experience onychomycosis, and it can predispose cellulitis and diabetic ulcers as diseased nails can puncture surrounding skin.

This may go unnoticed if there is an associated sensory neuropathy.3 Smoking, peripheral vascular disease and increasing age lead to slow-growing nails and also increase the risk of onychomycosis.

Other predisposing factors include AIDS and psoriasis. External risk factors that injure the nail or alter the integrity of the nail unit also predispose patients to onychomycosis.

These include jogging or skiing with ill-fitting shoes/boots, exposure to wet work, commercial swimming pools, walking barefoot and nailbiting.

 
Figure 3: White superficial onychomychosis.

Management
Indications for topical therapy include distal onychomycosis that involves less than 50% of the nail plate, fewer than three or four nails being involved and superficial white onychomycosis.

Involvement of the matrix is a contraindication to topical therapy.

Amorolfine 5% lacquer has broad-spectrum fungicidal and fungistatic activity, and has been recommended for cases of onychomycosis without matrix involvement.

Ciclopirox, which has broad spectrum antifungal activity, is available as an 8% lacquer and is applied once daily for 24 weeks on fingernails and 48 weeks for toenails.

Canesten fungal nail treatment set is a dual-phased topical treatment containing 40% urea and 1% bifonazole. Phase 1 involves softening of the nail with urea ointment and scraping this with a plastic nail scraper for 2-3 weeks.

Phase 2 involves the application of bifonazole cream to the nail bed over four weeks. Side effects from lacquers and topical treatments include nail fold erythema, burning and pruritus.

This is usually temporary and transient. Avulsion and debridement with 40% urea can help reduce fungal mass and increase the penetration of antifungal treatment.

Oral therapies are generally more effective than topical treatments. However, they have more adverse effects and interactions. The three main systemic drugs indicated for the treatment of onychomycosis are terbinafine, fluconazole and itraconazole.

Terbinafine is both fungistatic and fungicidal with lower activity against Candida sp. It is given as a daily 250mg dose for six weeks in fingernail and 12-16 weeks in toenail infections.

Baseline liver function testing is recommended and periodic monitoring (4-6 weeks) is suggested. Terbinafine should be discontinued immediately in the case of abnormal liver function tests.

In people with diabetes, it is the treatment of choice and is preferred over itraconazole. Itraconazole can also induce hypoglycaemia in diabetic patients due to drug interactions.

Itraconazole is fungistatic and active against yeast, dermatophyte and non-dermatophyte moulds.4 It is less active against dermatophytes than terbinafine.

Itraconazole is contraindicated in patients with heart failure or liver abnormalities. Griseofulvin has lower efficacy and higher relapse rates then either terbinafine or itraconazole but is the only agent licensed for children.

It is also contraindicated when a person has liver impairment.


Figure 4: Distal and lateral subungual onychomycosis with Trichophyton rubrum.

Outcomes
Cure rates with oral terbinifine range from 50-70%. Combination therapy increases the cure rate to 70-90%.

Combination therapy is recommended when there is matrix involvement, significant sub-ungual hyperkeratosis or subungual dermatophytoma. Surgical nail avulsion is only required in very rare circumstances.

The main indication is extensive non-dermatophyte nail infection that is refractory to topical and systemic therapy.

Toenails take about nine months to regrow. After three months of antifungal treatment, most toenails will still look abnormal.

Onychomycosis cure should be defined as the absence of clinical signs and the presence of negative culture, with or without negative microscopy, after an adequate wash-out period of 3-6 months.

Even with optimal management, 20% of cases will recur within two years and 50% will recur within five years.5

Professor Rodney Sinclair is director of dermatology at Epworth Hospital, Melbourne.
Dr Eshini Perera is a research fellow, department of dermatology at Epwirth Hospital, Melbourne. 

References available on request.

This first article appeared in Australian Doctor on the 22nd of July, 2014

Even after successful treatment, onychomycosis can be a peskily persistent condition. Case John is a...

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