Onychomycosis: where do we stand?

Oral onychomycosis treatment is still the gold standard, but topical armamentarium use is rising, although use of many novel oral and topical agents is off-label.

An individualised therapy approach is crucial, even for this common disorder

“Onychomycosis is still a common disorder with the prevalence increasing and affecting about 50% of all nail disorders,” Prof. Asja Prohic (University of Sarajevo, Bosnia and Herzegovina) stated1. Risk factors include comorbidities (e.g. diabetes or disorders impairing the circulation in the legs), tinea pedis, exogenic factors like occlusive shoes, congenital deformities, and genetic disposition. In the majority of cases (60–90%), the causative pathogenic organisms are dermatophytes, but non-dermatophyte moulds (NDM) and yeasts also play a role1,2.

When treating onychomycosis, different forms of cure have been defined: the mycologic cure that has an outcome of negative microscopy and culture, the clinical cure that leads to a nail that appears to be clinically normal, and a complete cure that combines both other outcomes. Among the factors that might predict a poor treatment prognosis are older age, severe onycholysis, and dermatophytoma, as well as immunosuppressive comorbidities. But the treatment goal consists not only of achieving pathogen elimination and largely healthy nails with a nail growth of >0.5 mm per week, but also the prevention of a further spread of the infection.

Choosing the right therapy calls for an individualised approach that is influenced by the degree of involvement, the infecting organism, pre-existing diseases/medications, and of course also the patient’s preferences and costs of the treatment. Prof. Prohic underlined that to get reliable results from cultures, prior antifungal medication needs to wash out. Depending on the guideline, 4–8 weeks or 3–6 months are suggested, her personal recommendation is at least 2 months1,3,4.

Oral therapies are still the gold standard

“Oral therapies are still the gold standard for onychomycosis in both children and adults, because they have a shorter course of treatment and they have higher cure rates compared with the topical antifungal therapies,” Prof Prohic informed1. Oral therapy is especially indicated if more than 50% of 1 nail is affected, multiple nails are affected, the nail matrix is involved, and/or poor prognostic factors are present. Of course, contraindications also have to be excluded.

Terbinafine, itraconazole, and fluconazole are the currently available agents for oral onychomycosis treatment, all acting on dermatophytes and NDM, itraconazole and fluconazole also act on Candida species. None of these agents should be given during pregnancy and liver function monitoring is also recommended. Of note, fluconazole is not FDA-approved for onychomycosis but is nevertheless widely used off-label in the US.

“Terbinafine is still the gold standard for the oral treatment regarding mycologic and complete cure rates,” Prof. Prohic stated, presenting mycologic and complete cure rates of 79% and 59% for fingernails and 70% and 38% for toenails, respectively.

The list of novel oral therapies consists of posaconazole, fosravuconazole, oteseconazole, voriconazole, and albaconazole5. Prof. Prohic highlighted that only posaconazole is approved for onychomycosis, but solely in Japan. “All other drugs are already approved but for other indications, mostly for very invasive fungal infections. Moreover, albaconazole is not currently FDA-approved for any indication,” she pointed out. Prof. Prohic commented that the best efficacy was observed for voriconazole with a complete cure rate of 67.9%.

Topical therapy reserved for less extensive infestation

Topical therapies for onychomycosis are recommended in findings with less than 40–50% of nail involved, missing matrix involvement, less than 3 nails implicated, and for patients with contraindications to oral treatment. “Topicals need a longer treatment-time and can be less effective than orals. However, they don’t require laboratory controls and their side effects are mostly mild,” said Prof. Prohic. Topical therapy is more commonly used for the white superficial onychomycosis and in some cases for distal subungual onychomycosis.

It is important to advise patients to roughen/file the nail plate to enable penetration of the agents into the subungual space. Currently used agents directed against dermatophytes, NDM moulds, and yeast are amorolfine, efinaconazole, tavaborole, and ciclopirox, the latter also acting on bacteria. “According to the studies, amorolfine has superior mycological and complete cure rates,” Prof. Prohic expressed. Novel therapies like topical terbinafine, ciclopirox, and tazarotene show better penetration and higher cure rates, but further study results are still awaited.

To prevent the common problem of recurrence in onychomycosis, prophylaxis with a twice-weekly topical application of an antifungal solution is recommended. Last but not least, lifestyle changes like trimming nails, wearing non-occlusive shoes, and hot washing of socks can further help to prevent relapse.

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  1. Prohic A. Update on onychomycosis treatment. D2T07.3C, EADV Congress 2023, 11-14 October, Berlin, Germany.
  2. Sigurgeirsson B, Baran R. J Eur Acad Dermatol Venereol. 2014;28:1480-91.
  3. Nenoff P, et al. J Dtsch Dermatol Ges. 2023;21:678-92.
  4. Falotico JM, Lipner SR. Clin Cosmet Investig Dermatol. 2022:15:1933-57.
  5. Gupta AK, et al. Int J Dermatol. 2022 Dec;61(12):1431-1441.