INTRODUCTION
Onychomycosis is an infection of the nail bed or nail plate by fungal organisms. These organisms are predominantly dermatophytes and less commonly yeasts, but recent research revealed an increasing prevalence of non-dermatophyte molds and mixed infection.1 It is highly prevalent in North America, affecting at least 13% of the population.2 In addition, underrepresented groups (eg, Blacks, Hispanics) exhibit a disproportionately high burden of onychomycosis after adjusting for variables such as concomitant tinea pedis, diabetes mellitus, immune compromise, nail psoriasis, and insurance status.3
There are well defined clinical patterns of onychomycosis, which include the following: distal lateral subungual (DLSO), superficial white, proximal subungual, endonyx, and total dystrophic.4 Distal lateral subungual is the most common pattern in the US and worldwide.4 Superficial white onychomycosis is characterized by invasive fungal localization to the dorsal surface of the nail plate and is frequently associated with human immunodeficiency virus (HIV).5 Proximal subungual onychomycosis is the rarest form in immunocompetent individuals where fungal invasion occurs at the proximal nailfold into the nail matrix and then spreads distally as the nail plate forms.6 Endonyx is onychomycosis described by diffuse milky-white discoloration of the nail plate with normal thickness and absence of onycholysis and nail bed hyperkeratosis.7 Total dystrophic onychomycosis is involvement of the entire nail unit and is either considered as a distinct subtype or the end result of any of the aforementioned patterns.8 The causative organisms vary across the different clinical patterns and are determined by specific patient characteristics.
While onychomycosis is generally self-limited, this condition has a large effect on quality of life (QoL).9 There is also a significant economic burden on the healthcare system given the availability of treatment options and utilization rates.10,11 This paper will focus on the more commonly encountered DLSO in toenails and review the currently available efficacy data for topical treatment options for both adult and pediatric patients, as well as complementary and alternative medicine.
Current Evidence for Topical Anti-Fungal Therapies
Currently, there are only 3 topical agents approved to treat onychomycosis of the toenails by the US Food and Drug Administration (FDA). These include ciclopirox 8% lacquer, tavaborole 5% solution, and efinaconazole 10% solution. According to the phase 3 and phase 4 trials, daily application for at least 48 weeks is recommended. It is important to note that, since toenail growth can take 12 months or more, complete cure rates may increase with longer duration of treatment and that an almost clear nail may represent a more clinically meaningful and realistic outcome for patients.12 The clinical efficacy and adverse events associated with each of these treatments are reviewed next.
Ciclopirox
Ciclopirox differs mechanistically and chemically from other antifungal therapies such as allylamines and azoles in that it does not affect sterol biosynthesis. It chelates polyvalent ions (ie, Fe3+), thereby leading to inhibition of metal-dependent enzymes that fungi rely on for the degradation of toxic peroxides. As such, it exhibits broad spectrum antifungal activity. While ciclopirox has been marketed since April 1975 as a 1% cream, 1% lotion, and 0.77% gel, the 8% lacquer formulation was approved in the US in 1999 for mild-to-moderate onychomycosis.
Gupta et al performed 2 parallel randomized, controlled trials assessing the efficacy of ciclopirox 8% lacquer vs placebo applied daily in adult patients aged 18 to 70 with onychomycosis of the great toenail.13 Subjects demonstrated target nail involvement
