Therapeutic Update: Onychomycosis

A question we hear very often, yet do not often have a great answer for. A painfully common and seemingly mundane condition, the management of onychomycosis can actually be quite difficult with frequent treatment failures and post treatment relapses. Onychomycosis affects 10% of all American adults and 48% of people aged 70 years.¹ Americans will spend approximately $1.26 billion annually on oral and topical prescriptions for onychomycosis, which speaks to the fact that patients are motivated to seek out remedies to improve the appearance of their nails.² Although often considered a cosmetic ailment, a recent survey of 1017 residents of Hong Kong dubbed the “Fungal Nail Perception Survey” found that those who suffer from onychomycosis are perceived as less likely to form good social relationships, more likely to be excluded from social activities, and less able to perform well in their chosen career than those not affected.³ As physicians we are limited in our ability to treat onychomycosis by variable efficacy and poor penetration of topical agents, long courses of treatment, and of course the ever-looming threat of rare but life-threatening side effects of systemic agents.

Onychomycosis is most commonly caused by Trichophyton rubrum but can also result from infection with other dermatophytes as well as yeast. There are four subtypes: distal subungual onychomycosis typically caused by T. rubrum; white superficial onychomycosis usually due to T. mentagrophytes (unless that patient is HIV positive in which case T. rubrum is more common); proximal subungual onychomycosis, which is usually due to T. rubrum and can be a sign of HIV infection; and candidal onychomycosis with results in severe destruction of the nail plate in patients who often also have mucocutaneous disease. There are two primary endpoints to consider when treating onychomycosis: mycologic cure and a clinically normal appearing nail. Patients should be followed for 6 months after discontinuation of treatment to adequately assess for clinical cure. Prior to initiating treatment, appropriate cultures or diagnostic studies should be obtained to distinguish true fungal infection from other causes of nail dystrophy such as trauma.

For patients with mild disease and for those who are not candidates for systemic therapies, topical treatment still plays a role in the management of onychomycosis. Treatment success with topical agents, however, is generally considered to be less than 10%.⁴ One of the most commonly utilized topical treatments is ciclopirox (Loprox, Penlac), which is manufactured as a cream, gel, suspension, solution, or nail lacquer and is indicated for Trichophyton rubrum onychomycosis without lunula involvement. Ciclopirox has a high affinity for trivalent metal cations and thus exerts its antimicrobial activity by inhibiting metal-dependent enzymes that are responsible for the degradation of peroxides within the fungal cell.⁵ When applied daily for 6 to 12 months with concomitant nail debridement, the complete cure rate at 48 weeks is only 6-9%.⁶ Chemical avulsion of the nail plate with urea under occlusion may improve efficacy slightly.

Efinaconazole 10% solution (Jublia, Valeant, Montreal, Canada) is a new triazole antifungal that recently completed Phase III clinical trials. A pooled analysis of two Phase III clinical trials that included 1436 subjects showed eficonazole to be superior to the placebo in attaining both mycologic cure (negative KOH and fungal culture) and complete cure (0% clinical involvement and mycologic cure).⁷ Specifically, the complete cure rate in the eficonazole group was 18.5% compared to 4.7% in the placebo at 48 weeks (P<0.001).⁷ Notably, approximately 20% of subjects began to achieve <10% nail involvement by week 24.⁷ In contrast to the studies of ciclopirox, efficacy was not contingent upon daily nail debridement. Authors concluded that eficonazole may become the preferred first line agent for topical therapy. It may also be a useful adjunct to existing therapies either as dual therapy or to prevent recurrence after treatment with systemic therapy.