Onychomycosis: Strategies to Minimize Recurrence

March 2016 | Volume 15 | Issue 3 | Original Article | 279 | Copyright © March 2016

Aditya K. Gupta MD PhD FRCPC,a Boni E. Elewski MD,b Ted Rosen MD,c Bryan Caldwell DPM,dd David M Pariser MD,e Leon H. Kircik MD,f Neal Bhatia MD,g and Antonella Tosti MDh

aUniversity of Toronto, Toronto, Canada
bDepartment of Dermatology, University of Alabama at Birmingham School of Medicine, Birmingham, AL
cDepartment of Dermatology at Baylor College of Medicine, Houston, TX
dCollege of Podiatric Medicine at Kent State University, Independence, OH
eVirginia Clinical Research, Norfolk, VA
fIcahn School of Medicine at Mount Sinai, New York, NY; Indiana University School of Medicine, Indianapolis, IN; Physicians Skin Care, PLLC, Louisville, KY
gTherapeutics Clinical Research, San Diego, CA
hDepartment of Dermatology & Cutaneous Surgery Leonard Miller School of Medicine University of Miami, FL

Abstract
Recurrence (relapse or re-infection) in onychomycosis is common, occurring in 10% to 53% of patients. However, data on prevalence is limited as few clinical studies follow patients beyond 12 months. It has been suggested that recurrence after continuous terbinafine treatment may be less common than with intermittent or continuous itraconazole therapy, probably due to the fungicidal activity of terbinafine, although these differences tended not to be significant. Relapse rates also increase with time, peaking at month 36. Although a number of factors have been suggested to play a role in recurrence, only the co-existence of diabetes has been shown to have a significant impact. Data with topical therapy is sparse; a small study showed amorolfine prophylaxis may delay recurrence. High concentrations of efinaconazole have been reported in the nail two weeks’ post-treatment suggesting twice monthly prophylaxis with topical treatments may be a realistic option, and may be an important consideration in diabetic patients with onychomycosis. Data suggest that prophylaxis may need to be continued for up to three years for optimal effect. Treating tinea pedis and any immediate family members is also critical. Other preventative strategies include avoiding communal areas where infection can spread (such as swimming pools), and decontaminating footwear.

J Drugs Dermatol. 2016;15(3):279-282.

INTRODUCTION

Despite the number of available treatments, not all patients with onychomycosis are cured and recurrence (relapse or re-infection) is not uncommon, with percentages reported in various clinical studies ranging from 10% to 53%.1 Definition of recurrence is less clear, since differentiating relapse from re-infection remains imprecise. Relapse implies some improvement in the disease, but then a reappearance of the same or similar clinical symptoms following treatment due to incomplete eradication of the initial infection. Re-infection usually occurs some length of time after the initial nail infection is ostensibly cured, either with the same or a different fungal organism. When the same organism is involved, relapse or re-infection has sometimes been differentiated by an arbitrary 1 or 2-year cut-off. It has been suggested that the inability to obtain long-term cure may be a result of genetic susceptibility, strain type switching, emergence of drug-resistant fungal strains, or continual contact with fungal material shed from the patient at the time of active infection.1-4

Recurrence With Systemic Therapy

Data on recurrence rates are limited, primarily because most clinical studies have concentrated on 9 to 12 months’ outcome. Few studies have followed the clinical course of patients beyond 12 months.5,6 A meta-analysis of five trials found that relapses were more common after treatment with itraconazole (intermittent or continuous) compared to terbinafine (continuous) after long-term follow-up (more than two years after the end of therapy).7 The long-term benefits of terbinafine are probably related to its fungicidal action, compared with the fungistatic action of itraconazole.6 However, only 251 patients were included in the meta-analysis,8-12 and the studies were not comparable in terms of outcome with only one assessing complete cure.12 In one study, nail lacquer was applied to some patients as a prophylactic measure with no significant impact on relapse.12
A prospective, long-term study (1.25 to 7 years’ post-enrolment) in 166 mycologically and 43 completely cured onychomycosis patients compared recurrence rates following treatment with intermittent itraconazole, pulsed itraconazole, continuous terbinafine, and combination terbinafine/itraconazole. Although itraconazole was associated with higher recurrence rates, no statistically significant differences were detected.13