It is well known by clinicians and patients that topical treatment of toenail onychomycosis, specifically with griseofulvin, is generally ineffective. When antifungal agents such as fluconazole, itraconazole and terbinafine were first introduced, reports of cure rates in the range of 35 to 80 percent began to appear. Epstein analyzed studies through Medline that purported to define the efficacy of oral treatment of toenail onychomycosis and also sought to determine how long the nail actually remained disease free.
Twenty-six articles that described clinical results, used both culture and microscopy for diagnosis and included clinical evaluation data were included in the study. However, only seven studies provided results in terms of a “disease-free nail.” These studies covered 11 trials, three with itraconazole and eight with terbinafine. There has been concern as to how often and when a successful dermatologic result turns into a failed treatment. Depending on the study, such failures have been labeled “relapse,” “recurrence” or “reinfection.” The important aspect is the reappearance of nail dystrophy, irrespective of its mechanism. “Disease reappearance” describes a disease-free nail without implying the mechanism responsible.
Three months of treatment with itraconazole produced a disease-free nail in about 35 percent of patients, whether or not the treatment was given continuously at 200 mg per day or as a one-week pulse each month of 400 mg per day. Mycologically negative patients whose nails had cleared or had markedly improved were referred to as an “overall success” in one study. In that study, fewer than 35 percent of the patients would have achieved a disease-free nail according to the definition.
Treatment with terbinafine achieved a disease-free nail in about 40 to 50 percent of patients, except in one study (of 17 subjects), which reported a 76 percent cure rate. Although the regimen that is usually recommended for terbinafine treatment of toenails is 250 mg daily for 12 weeks, in five of the eight trials it was prescribed for 16 weeks or longer. Only one study adequately assessed the frequency of disease reappearance. Of 31 patients who achieved a disease-free nail at one year of follow-up, five patients showed recurrent nail dystrophy at the two-year evaluation, resulting in a reappearance rate of 17 percent. However, this result applied only to the appearance of the nail. The mycologic failure rate was much higher. At the two-year evaluation, only 55 percent of the fungal cultures were negative. Forty-two percent of patients demonstrated mycologic failure during a one-year period. Although itraconazole and terbinafine have been in clinical trials for more than eight years, only one study provided data at both one and two years after treatment.
Results of this analysis demonstrate the importance of determining the negativity of results of microscopy and fungal culture. The assumption behind this goal is that failure to clear the fungal infection will sooner or later result in a dystrophic nail. Many of the studies used the term “clinical remission” as their end points but failed to further define the term. Of the 26 studies reviewed, only 14 used a normal-appearing nail as the end point.
The author concludes that in order to successfully treat patients with toenail onychomycosis, physicians must have the data to know not only how often the infection can be cleared but how long the nails will remain free of disease. Disease reappearance is an important issue faced by clinicians attempting to treat toenail onychomycosis.
editor's note: In an accompanying essay, Bigby stresses the importance of basing dermatologic therapy on the best evidence available, rather than on anecedotal or expert opinion. With the advent of free-standing clinics offering such destructive modalities as chemical peels, dermabrasion and cryotherapy, it is up to the referring physician to discuss new therapies honestly with the patient—are new therapies more effective than the existing ones that may not be as heavily or as shrewdly marketed? The editors of this dermatology journal should be commended for addressing the importance of an evidence-based approach to therapy.—b.a.