Therapeutic Recommendations for the Treatment of Toenail Onychomycosis in the US

October 2021 | Volume 20 | Issue 10 | Original Article | 6291 | Copyright © October 2021


Published online September 9, 2021

Shari R. Lipner MD PhDa, Warren S. Joseph DPMb, Tracey C. Vlahovic DPMc, Richard K. Scher MDa, Phoebe Rich MDd, Mahmoud Ghannoum PhDe, C. Ralph Daniel MDf, Boni Elewski MDg

aWeill Cornell Medicine, New York, NY
bArizona College of Podiatric Medicine, Midwestern University, Glendale, AZ
cTemple University School of Podiatric Medicine, Philadelphia, PA
dOregon Health and Science University, Portland, OR
eCase Western Reserve University, and University Hospitals Cleveland Medical Center, Cleveland, OH
fUniversity of Mississippi Medical Center, Jackson, MS
gUniversity of Alabama at Birmingham School of Medicine, Birmingham, AL

Abstract
Background: Onychomycosis affects around 14% of individuals in North America and Europe and is undertreated. Treatment is challenging as toenail growth can take 12–18 months, the nail plate may prevent drug penetration, and disease recurrence is common. National guidelines/consensus documents on onychomycosis diagnosis and treatment were last published more than 5 years ago and updated medical guidance is needed.
Methods: This document aims to provide recommendations for the diagnosis and pharmaceutical treatment of toenail onychomycosis following a roundtable discussion with a panel of dermatologists, podiatrists, and a microbiologist specializing in nail disease.
Results: There was a general consensus on several topics regarding onychomycosis diagnosis, confirmatory laboratory testing, and medications. Onychomycosis should be assessed clinically and confirmed with microscopy, histology, and/or culture. Terbinafine is the primary choice for oral treatment and efinaconazole 10% for topical treatment. Efinaconazole can also be considered for off-label use for maintenance to prevent recurrences. For optimal outcomes, patients should be counseled regarding treatment expectations as well as follow-up care and maintenance post-treatment.
Conclusions: This article provides important updates to previous guidelines/consensus documents to assist dermatologists and podiatrists in the diagnosis and treatment of toenail onychomycosis.

J Drugs Dermatol. 2021;20(10): doi:10.36849/JDD.6291

INTRODUCTION AND PRIOR TREATMENT

Onychomycosis—a fungal infection of the nail bed or plate caused by dermatophytes, non-dermatophyte molds, or yeasts—affects up to 14% of individuals in North America.1,2 It is undertreated3 and treatment is challenging as toenail growth can take up to 12 months or more,4,5 the infection is frequently located under the keratinized nail plate,6 and disease recurrence is common.5 Oral medications are generally efficacious, but there are safety concerns such as drug-drug interactions, smell/taste disturbances, allergic reactions, or possible liver toxicity.7,8 In addition, there may be evidence of recent emergence of antifungal resistance to terbinafine.9,10

For diagnosis and testing, prior guidelines and consensus publications on onychomycosis treatment have noted that in addition to clinical examination, confirmatory laboratory testing should be performed using one or more of the following: microscopic examination (eg, potassium hydroxide [KOH], periodic acid-Schiff test [PAS]), or fungal culture.11-16 While polymerase chain reaction (PCR) techniques were considered useful for confirming diagnosis, they were deemed not cost effective enough for general use.12-14,16

For pharmaceutical treatments administered orally, terbinafine was considered first-line and was preferred over itraconazole.1,12 While fluconazole is not approved for onychomycosis treatment in the US, it was considered an alternative to terbinafine or itraconazole.12 Griseofulvin was generally not recommended due to low efficacy and high recurrence rates compared with other oral antifungal agents.12 Oral medications were recommended for severe cases,14,15 though some oral drugs were to be avoided or required caution when used in patients with certain comorbidities or concomitant medications.1,12

Topical medications (ciclopirox, tavaborole, efinaconazole) were recommended for pediatric patients13,14 and adults with mild-to-moderate disease (20%–60%, <50%, or <65% involvement),1,11,13-15 especially those taking concomitant medications or with other