Fungal infections of the toenails are difficult to cure. But one of the most vexing
questions is what constitutes a cure. Nails may look normal, but still harbour the
fungus that caused the problem, with the result that some time after the end of
treatment the infection recurs, and the cycle of treatment has to start again.
Study
A new review of terbinafine, itraconazole and fluconazole [1] sought the answer by
looking for evidence of disease-free nails one year or longer after the start of
treatment. A disease-free nail was defined as one that both looked normal and had
negative results from potassium hydroxide microscopy and culture. The search strategy
was reasonably comprehensive, and found seven studies, only some of which appeared to
be randomised. Studies had to describe results in toenails (distinct from
fingernails), use both culture and microscopy and include a clinical evaluation. Case
reports, series of fewer than 15 patients, those combining finger and toenails, and
those reporting on nails rather than patients were excluded.
Results
There were no data for fluconazole. The results for terbinafine and itraconazole are
shown in the Figure. For terbinafine, 217 of 491 patients (44%) had a disease-free
nail at one year. Most studies used terbinafine 250 mg daily for longer than the
recommended 12 weeks. For itraconazole, 99 of 291 patients (34%) had a disease-free
nail at one year. These results were obtained whether 200 mg daily was given, or as
400 mg daily for one week each month.
Figure 1: Disease free nails at one year with terbinafine (open circles and half
tone fill) and itraconazole (filled circles)
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Comment
Fungal nail infection is one of those seemingly innocuous subjects that seems to
get people vexed whenever it is raised. This interesting little paper poses an
important question for patient and practitioner - when is a cure not a cure?
Epstein points out the deficiencies in the definition - or lack of definition -
of a cure.
Bandolier 26 examined this subject, and found two randomised trials comparing
terbinafine with griseofulvin in toenails. One is in this review, but the other
had 48-week outcomes that might have been included by Epstein, but perhaps were
omitted because 48 weeks is less than one year (though one also had longer
outcomes). Disease-free nails at 48 weeks occurred in 67% of patients receiving
terbinafine. Including these trials (half-tone fill in the Figure) would increase
the one-year result for disease-free nails with terbinafine to 48%
These are expensive treatments for a condition which is not rare, and more
attention would seem to be needed. The concentration on suitable end-point is
pertinent, but the execution may be flawed. Is it time to have a good systematic
review, as we have for topical treatments from the Cochrane Library [2], and
especially as more randomised studies are being published?
Reference:
- E Epstein. How often does oral treatment of toenail onychomycosis produce a
disease-free nail? Archives of Dermatology 1998 134: 1551-4.
- F Crawford et al. Topical treatments for fungal infections of the skin and
nails of the foot. Cochrane Library 1999, 3.
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