Over-the-counter and Natural Remedies for Onychomycosis: Do They Really Work? Pierre Halteh; Richard K. Scher, MD; Shari R. Lipner, MD, PhD PRACTICE POINTS • Natural remedies, including tea tree oil, natural topical cough suppressants, natural coniferous resin lacquer, Ageratina pichinchensis extract, and ozonized sunflower oil, have shown antifungal activities in in vitro studies. • Some of these products have efficacy and appear to be safe in clinical studies. • Larger randomized clinical trials demonstrating efficacy are required beforecopy we can recommend these products to our patients. not Onychomycosis is a fungal infection of the nail unit effective, and cost-effective options for onychomy- that may lead to dystrophy and disfigurement over cosis therapy, there has been a renewed interest time. It accounts for up to 50% of all nail condi-Doin natural and over-the-counter (OTC) alternatives. tions, with toenails affected more commonly than This review will synthesize the laboratory data, fingernails. Onychomycosis may affect quality of known antifungal mechanisms, and clinical studies life and increase the prevalence and severity of assessing the efficacy of OTC and natural prod- foot ulcers in patients with diabetes. Available ucts for onychomycosis treatment. oral agents approved by the US Food and Drug Cutis. 2016;98:E16-E25. Administration (FDA) for the treatment of ony- chomycosis include terbinafine and itraconazole, which have demonstratedCUTIS good efficacy but are nychomycosis is a fungal infection of the associated with the risk of systemic side effects nail unit by dermatophytes, yeasts, and non- and drug-drug interactions. Topical medications Odermatophyte molds. It is characterized by that are FDA approved for onychomycosis include a white or yellow discoloration of the nail plate; ciclopirox, efinaconazole, and tavaborole. These hyperkeratosis of the nail bed; distal detachment therapies generally have incomplete efficacy com- of the nail plate from its bed (onycholysis); and pared to systemic agents as well as long treatment nail plate dystrophy, including thickening, crum- courses and possible local side effects such as bling, and ridging. Onychomycosis is an important erythema and/or blisters. Given the need for safe, problem, representing 30% of all superficial fungal infections and an estimated 50% of all nail diseases.1 Mr. Halteh is from Weill Cornell Medical College, Qatar, Ar-Rayyan. Reported prevalence rates of onychomycosis in the Drs. Scher and Lipner are from the Department of Dermatology, United States and worldwide are varied, but the mean Weill Cornell Medical College, New York, New York. prevalence based on population-based studies in Mr. Halteh reports no conflict of interest. Dr. Scher is a consultant for Europe and North America is estimated to be 4.3%.2 Valeant Pharmaceuticals International, Inc. Dr. Lipner has served on It is more common in older individuals, with an inci- the advisory board for Sandoz, a Novartis company. Correspondence: Shari R. Lipner, MD, PhD, Department of dence rate of 20% in those older than 60 years and 3 Dermatology, Weill Cornell Medical College, 1305 York Ave, 50% in those older than 70 years. Onychomycosis New York, NY 10021 ([email protected]) is more common in patients with diabetes and E16 CUTIS® WWW.CUTIS.COM Copyright Cutis 2016. No part of this publication may be reproduced, stored, or transmitted without the prior written permission of the Publisher. Onychomycosis Treatments 1.9 to 2.8 times higher than the general population.4 preparation and negative fungal culture with a com- Dermatophytes are responsible for the majority of pletely normal appearance of the nail. Mycological cases of onychomycosis, particularly Trichophyton cure is defined as potassium hydroxide microscopy rubrum and Trichophyton mentagrophytes.5 and fungal culture negative. Clinical cure is stated as Onychomycosis is divided into different sub- 0% nail plate involvement but at times is reported as types based on clinical presentation, which in turn less than 5% and less than 10% involvement. are characterized by varying infecting organisms Terbinafine and itraconazole are the only US and prognoses. The subtypes of onychomycosis are Food and Drug Administration (FDA)–approved distal and lateral subungual (DLSO), proximal sub- systemic therapies, and ciclopirox, efinaconazole, ungual, superficial, endonyx, mixed pattern, total and tavaborole are the only FDA-approved topicals. dystrophic, and secondary. Distal and lateral sub- Advantages of systemic agents generally are higher ungual onychomycosis are by far the most com- cure rates and shorter treatment courses, thus better mon presentation and begins when the infecting compliance. Disadvantages include greater inci- organism invades the hyponychium and distal or dence of systemic side effects and drug-drug interac- lateral nail bed. Trichophyton rubrum is the most com- tions as well as the need for laboratory monitoring. mon organism and T mentagrophytes is second, but Pros of topical therapies are low potential for adverse Candida parapsilosis and Candida albicans also are effects, no drug-drug interactions, and no monitor- possibilities. Proximal subungual onychomycosis is ing of blood work. Cons include lower efficacy, long far less frequent than DLSO and is usually caused treatment courses, and poor patient compliance. by T rubrum. The fungus invades the proximal nail Terbinafine, an allylamine, taken orally once folds and penetrates the newly growing nail plate.6 daily (250 mg) for 12 weeks for toenails and 6 weeks This pattern is more common in immunosuppressed for fingernails copycurrently is the preferred systemic patients and should prompt testing for human immu- treatment of onychomycosis, with complete cure nodeficiency virus.7 Total dystrophic onychomycosis rates of 38% and 59% and mycological cure rates of is the end stage of fungal nail plate invasion, may 70% and 79% for toenails and fingernails, respec- follow DLSO or proximal subungual onychomycosis, tively.not12 Itraconazole, an azole, is dosed orally at and is difficult to treat.6 200 mg daily for 3 months for toenails, with a Onychomycosis causes pain, paresthesia, and dif- complete cure rate of 14% and mycological cure ficulty with ambulation.8 In patients with peripheral rate of 54%.13 For fingernail onychomycosis only, neuropathy and vascular problems, including Dodia- itraconazole is dosed at 200 mg twice daily for betes, onychomycosis can increase the risk for foot 1 week, followed by a treatment-free period of ulcers, with amputation in severe cases.9 Patients 3 weeks, and then another 1-week course at the also may present with aesthetic concerns that may same dose. The complete cure rate is 47% and the impact their quality of life.10 mycological cure is 61% for this pulse regimen.13 Given the effect on quality of life along with Ciclopirox is a hydroxypyridone and the 8% nail medical risks associated with onychomycosis, a safe lacquer formulation was approved in 1999, making and successful treatment modality with a low risk it the first topical medication to gain FDA approval of recurrence is desirable. CUTISUnfortunately, treatment for the treatment of toenail onychomycosis. Based of nail fungus is quite challenging for a number of on 2 clinical trials, complete cure rates for toenails reasons. First, the thickness of the nail and/or the are 5.5% and 8.5% and mycological cure rates are fungal mass may be a barrier to the delivery of topi- 29% and 36% at 48 weeks with removal of residual cal and systemic drugs at the source of the infection. lacquer and debridement.14 Efinaconazole is an azole In addition, the nail plate does not have intrinsic and the 10% solution was FDA approved for the immunity. Also, recurrence after treatment is com- treatment of toenail onychomycosis in 2014.15 In mon due to residual hyphae or spores that were not 2 clinical trials, complete cure rates were 17.8% previously eliminated.11 Finally, many topical medi- and 15.2% and mycological cure rates were 55.2% cations require long treatment courses, which may and 53.4% with once daily toenail application for limit patient compliance, especially in patients who 48 weeks.16 Tavaborole is a benzoxaborole and the want to use nail polish for cosmesis or camouflage. 5% solution also was approved for the treatment of toenail onychomycosis in 2014.17 Two clinical trials Currently Approved Therapies reported complete cure rates of 6.5% and 9.1% and for Onychomycosis mycological cure rates of 31.1% and 35.9% with Several definitions are needed to better interpret the once daily toenail application for 48 weeks.18 results of onychomycosis clinical trials. Complete Given the poor efficacy, systemic side effects, cure is defined as a negative potassium hydroxide potential for drug-drug interactions, long-term WWW.CUTIS.COM VOLUME 98, NOVEMBER 2016 E17 Copyright Cutis 2016. No part of this publication may be reproduced, stored, or transmitted without the prior written permission of the Publisher. Onychomycosis Treatments treatment courses, and cost associated with cur- efficacy (P<.001). This study showed that TTO, rent systemic and/or topical treatments, there has particularly TTO-NC, was effective in inhibiting been a renewed interest in natural remedies and the growth of T rubrum in vitro and that using nano- over-the-counter (OTC) therapies for onychomyco- capsule technology may increase nail penetration sis. This review summarizes the in vitro and in vivo and bioavailability.31 data, mechanisms of action, and clinical efficacy of Much of what we know about TTO’s antifun- various natural and OTC agents for the treatment gal mechanism of action comes from experiments of onychomycosis. Specifically, we summarize the involving C albicans. To date, it has not been studied data on tea tree oil (TTO), a popular topical cough in T rubrum or T mentagrophytes, the 2 most com- suppressant (TCS), natural coniferous resin (NCR) mon etiologies of onychomycosis.5 In C albicans, lacquer, Ageratina pichinchensis (AP) extract, and TTO causes altered permeability of plasma mem- ozonized sunflower oil.