Treatment of fungal nail infection

Conformation of the diagnosis should be done before initiating antifungal therapy (1).

When to treat (1):

• a positive microscopy (fungal elements seen) is sufficient to start antifungals
• a positive dermatophyte culture with negative microscopy is still significant
• a negative microscopy or culture does not rule out fungal infection, particularly with kerion and nail infections; if clinical appearance very suggestive of fungal infection, repeat sample and start treatment
  
  

Treatment of onychomycosis should vary according to the nature of the infecting organism and the extent of the infection.

• Dermatophyte infection
• Candida infection
• Non-dermatophyte, mould infection e.g. scopulariopsis brevicaulis, Fusarium species, Aspergillus species

"..There has been debate as to whether treatment of toenail onychomycosis is justified or whether it is more a cosmetic concern. However, as toenail infections present a risk as a portal of entry for significant bacterial sepsis (cellulitis), particularly in diabetics and those with peripheral vascular disease, the cost-benefit ratio of treatment today seems irrefutable.." (2)

Topical therapy: (4)

The newer topical antifungal therapies have improved cure rates for mild to moderate cases in patients who prefer to avoid systemic antifungals. Meta-analyses have shown the mycological cure rate for terbinafine is 76%, itraconazole pulse dosing is 63%, and fluconazole is 48% effective.

Conversely, topical therapy mycological cure rates are 55% for efinaconazole and 36% for tavaborole or ciclopirox.

5% amorolfine nail lacquer used once or twice a week 6 months for fingernails and 12 months for toe nails is recommended

Topical therapy together with vigorous debridement may improve the rate of success

Systemic therapy (1)

The most effective treatments for onychomycosis are systemic antifungals. Due to an increased risk of subungual ulceration, one also should consider oral antifungal therapy in moderate to severe disease, especially in patients with diabetes mellitus.

• Terbinafine 250 mg daily for 6-12 weeks in finger nail and 3-6 months in toe nail infections
• Itraconazole - 200 mg twice a day 2 courses of 7 days/month for finger nail and 3 courses of 7 days/month for toe nail infections

Note - terbinafine carries a contraindication for concurrent use with phenothiazines and pimozide for increased risk of QT prolongation (5)

Devices

Devices have diverse mechanisms of action

• laser device systems are thought to act through selective photothermolysis, which is the conversion of light energy into heat energy that is confined to a specific target
  • specific target in this case is fungi, which selectively absorb heat that leads to cell death
• Photodynamic therapy uses a narrow-spectrum light source to activate topically-applied photosensitisers

There is currently not enough evidence to recommend or discourage the use of 1064-nm Nd:YAG laser, or photodynamic therapy (6)

Key points:

• take nail clippings; start therapy only if infection is confirmed
• oral terbinafine is more effective than oral azole
• liver reactions 0.1 to 1% with oral antifungals
• if candida or non-dermatophyte infection is confirmed, use oral itraconazole
• topical nail lacquer is not as effective
• to prevent recurrence: apply weekly 1% topical antifungal cream to entire toe area
• children: seek specialist advice

Notes:

• for non-dermatophyte moulds other than Candida spp. seek the advice of a microbiologist or dermatologist (1)
• for infections with candida or non-dermatophyte moulds use oral itraconazole (1)
• idiosyncratic liver and other severe reactions occur very rarely with terbinafine and itraconazole (1)
• for children, seek specialist advice (1)
• other topical therapies (3):
  • once-daily application of topical 10% efinaconazole, a new triazole antifungal agent has been found to be an effective treatment, with mycological cure rates approaching 50% and complete cure (defined as mycological and clinical cure) in 15% of patients after 48 weeks
  • new topical formulations of terbinafine are being investigated, with early data showing promising clinical and mycological results
  • butenafine, bifonazole, salicylic acid, over-the-counter mentholated ointment, ozonized sunflower oil and undecenoates have been used, but there are limited data to support their use as monotherapy for onychomycosis
  • a 40% urea ointment is now available for the treatment of onychomycosis
    • urea ingredient provides non-surgical nail ablation of onychomycosis
• in a small clinical case series, Vicks VapoRub seemed to have a positive clinical effect in the treatment onychomycosis (7)

Reference:

1. Asz-Sigall D, Tosti A, Arenas R. Tinea Unguium: Diagnosis and Treatment in Practice. Mycopathologia. 2017 Feb;182(1-2):95-100
2. Dermatology in Practice 2007;15(4):16-18.
3. Ameen M et al. Guidelines for treatment of onychomycosis. British Journal of Dermatology 2014;171:937-958
4. Wollina U, Nenoff P, Haroske G, Haenssle HA. The Diagnosis and Treatment of Nail Disorders. Dtsch Arztebl Int. 2016 Jul 25;113(29-30):509-18.
5. Ricardo JW, Lipner SR. Safety of current therapies for onychomycosis. Expert Opin Drug Saf. 2020 Nov;19(11):1395-1408.
6. Foley K et al.Topical and device-based treatments for fungal infections of the toenails. Cochrane Systematic Review 16th January 2020.
7. Derby R et al. Novel Treatment of Onychomycosis using Over-the-Counter Mentholated Ointment: A Clinical Case SeriesThe Journal of the American Board of Family Medicine Jan 2011, 24 (1) 69-74; DOI: 10.3122/jabfm.2011.01.100124