JAMA: The Journal of the American Medical Association: Published on January, 2018

TAKE-HOME MESSAGE

CLINICAL QUESTION

Which oral antifungal medication is associated with the highest clinical (ie, normal appearance of the toenail) and mycological (negative culture, microscopy, or both) cure rates vs placebo or other antifungals when used to treat fungal infections?

The authors investigated different oral antifungal medications used to treat toenail fungal infections.

BOTTOM LINE

Both terbinafine and azole-based medications were associated with higher clinical and mycological cure rates compared with placebo (high-quality evidence).

Azoles were associated with lower cure rates than terbinafine when compared directly.

DISCUSSION:

In this JAMA Clinical Evidence Synopsis, the results of 48 randomized controlled trials for the treatment of fungal nail disease done between 1984 and 2014 are summarized.

Systemic therapy with oral terbinafine or azole drugs each works better than placebo. No surprise here!

• Terbinafine 250 mg orally once daily for 3 to 4 months is preferred over the azoles. It works up to 70% of the time in selected patients who still have growing nails and mild to moderate involvement. There are also fewer concerns for drug interactions and hepatotoxicity with terbinafine.
• Itraconazole or fluconazole including pulse therapy regimens are preferred when a yeast or mold is identified as the cause of the onychomycosis, but the treatment failure rate (24%–69%) makes this a second-line drug.
• Ketoconazole should avoid in view of cases of fatal hepatotoxicity since safer alternatives are available.  Griseofulvin is simply not as effective and would need to be used for a prolonged time until the nail completely grows out.

The synopsis also points out that, even when systemic agents clear fungal infections of the nail, recurrence rates are high. Maintaining remission may be possible with daily use of anti-fungal powers or application of topical medications, but these prove to be cumbersome over time, and lack of adherence is most probably the primary reason for recurrence.

Making the right diagnosis is critical. This requires appropriate confirmatory tests (KOH, fungal culture and PCR) and a willingness to expand your differential diagnosis of dystrophic nails to include conditions such as psoriasis, lichen planus, trauma, and chronic eczema.