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Onychomycosis

(Tinea Unguium)

By Chris G. Adigun, MD, Board-Certified Dermatologist, Dermatology & Laser Center of Chapel Hill

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Onychomycosis is fungal infection of the nail plate, nail bed, or both. The nails typically are deformed and discolored white or yellow. Diagnosis is by appearance, wet mount, culture, PCR, or a combination. Treatment, when indicated, is with oral terbinafine or itraconazole.

About 10% (range 2 to 14%) of the population has onychomycosis. Risk factors include

Toenails are 10 times more commonly infected than fingernails. About 60 to 80% of cases are caused by dermatophytes (eg, Trichophyton rubrum); dermatophyte infection of the nails is called tinea unguium. Many of the remaining cases are caused by nondermatophyte molds (eg, Aspergillus, Scopulariopsis, Fusarium). Immunocompromised patients and those with chronic mucocutaneous candidiasis may have candidal onychomycosis (which is more common on the fingers). Subclinical onychomycosis can also occur in patients with recurrent tinea pedis. Onychomycosis may predispose patients to lower extremity cellulitis.

Symptoms and Signs

Nails have asymptomatic patches of white or yellow discoloration and deformity. There are 3 common characteristic patterns:

  • Distal subungual, in which the nails thicken and yellow, keratin and debris accumulate distally and underneath, and the nail separates from the nail bed (onycholysis)

  • Proximal subungual, a form that starts proximally and is a marker of immunosuppression

  • White superficial, in which a chalky white scale slowly spreads beneath the nail surface

Diagnosis

  • Clinical evaluation

  • Potassium hydroxide wet mount examination

  • Histopathologic examination of periodic acid-Schiff–stained nail clippings and subungual debris

  • Culture

Onychomycosis is suspected by appearance; predictive clinical features include involvement of the 3rd or 5th toenail, involvement of the 1st and 5th toenails on the same foot, unilateral nail deformity, but only if the patient has tinea pedis. Subclinical onychomycosis should be considered in patients with recurrent tinea pedis.

Differentiation from psoriasis or lichen planus is important because the therapies differ, so diagnosis is typically confirmed by microscopic examination and, unless microscopic findings are conclusive, culture of scrapings or rarely PCR of clippings. Scrapings are taken from the most proximal position that can be accessed on the affected nail and are examined for hyphae on potassium hydroxide wet mount and cultured. Histopathologic examination of periodic acid-Schiff (PAS)–stained nail clippings and subungual debris may also be helpful.

Obtaining an adequate sample of nail for culture can be difficult because the distal subungual debris, which is easy to sample, often does not contain living fungus. Therefore, removing the distal portion of the nail with clippers before sampling or using a small curette to reach more proximally beneath the nail increases the yield. PCR can be done if cultures are negative and the cost of finding a definitive diagnosis is warranted.

Treatment

  • Selective use of oral terbinafine or itraconazole

  • Occasional use of topical treatments (eg, efinaconazole, tavaborole, ciclopirox 8%, amorolfine)

Onychomycosis is not always treated because many cases are asymptomatic or mild and unlikely to cause complications, and the oral drugs that are the most effective treatments can potentially cause hepatotoxicity and serious drug interactions. Some proposed indications for treatment include the following:

  • Previous ipsilateral cellulitis

  • Diabetes or other risk factors for cellulitis

  • Presence of bothersome symptoms

  • Psychosocial impact

  • Desire for cosmetic improvement (controversial)

Treatment is typically oral terbinafine or itraconazole. Terbinafine 250 mg once/day for 12 wk (6 wk for fingernail) achieves a cure rate of 75 to 80% and itraconazole 200 mg bid 1 wk/mo for 3 mo achieves a cure rate of 40 to 50%, but the recurrence rate is estimated to be as high as 10 to 50%. It is not necessary to treat until all abnormal nail is gone because these drugs remain bound to the nail plate and continue to be effective after oral administration has ceased. The affected nail will not revert to normal; however, newly growing nail will appear normal.

The newer topical agents efinaconazole and tavaborole can penetrate the nail plate and are more effective than older topical agents (1–4).

Investigative treatments that have less frequent and/or less severe adverse effects include laser therapy, new formulations of topical agents (including efinaconazole), and new delivery systems for terbinafine (5,6). Topical antifungal nail lacquer containing ciclopirox 8% or amorolfine 5% (not available in the US) is occasionally effective as primary treatment (cure rate of about 30%) and can improve cure rate when used as an adjunct with oral drugs, particularly in resistant infections.

To limit relapse, the patient should trim nails short, dry feet after bathing, wear absorbent socks, and use antifungal foot powder. Old shoes may harbor a high density of spores and, if possible, should not be worn.

Treatment references

  • Elewski BE, Tosti A: Tavaborole for the treatment of onychomycosis. Expert Opin Pharmacother 15(10):1439-1448, 2014. doi: 10.1517/14656566.2014.921158

  • Gupta AK, Daigle D: Tavaborole (AN-2690) for the treatment of onychomycosis of the toenail in adults. Expert Rev Anti Infect Ther 12(7):735-742, 2014. doi: 10.1586/14787210.2014.915738.

  • Elewski BE, Rich P, Pollak R, et al: Efinaconazole 10% solution in the treatment of toenail onychomycosis: Two phase III multicenter, randomized, double-blind studies. J Am Acad Dermatol 68(4):600-608, 2013. doi: 10.1016/j.jaad.2012.10.013.

  • Jo Siu WJ, Tatsumi Y, Senda H, et al: Comparison of in vitro antifungal activities of efinaconazole and currently available antifungal agents against a variety of pathogenic fungi associated with onychomycosis. Antimicrob Agents Chemother 57(4):1610-1616, 2013. doi: 10.1128/AAC.02056-12.

  • Adigun CG, Vlahovic TC, McClellan MB, et al: Efinaconazole 10% and tavaborole 5% penetrate across poly-ureaurethane 16%: Results of in vitro release testing and clinical implications of onychodystrophy in onychomycosis. J Drugs Dermatol 1;15(9):1116-1120, 2016.

  • Baker SJ, Zhang YK, Akama T, et al: Discovery of a new boron-containing antifungal agent, 5-fluoro-1,3-dihydro-1-hydroxy-2,1- benzoxaborole (AN2690), for the potential treatment of onychomycosis. J Med Chem 27;49(15):4447-4450, 2006.

Key Points

  • Onychomycosis is highly prevalent, particularly among older men and patients with compromised distal circulation, nail dystrophies, and/or tinea pedis.

  • Suspect the diagnosis based on appearance and the pattern of nail involvement and confirm it by microscopy and sometimes culture or PCR.

  • Treatment is warranted only if onychomycosis causes complications or troublesome symptoms.

  • If treatment is warranted, consider terbinafine (the most effective treatment) and measures to prevent recurrence (eg, limiting moisture,discarding old shoes, trimming nails short).

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