ONYCHOMYCOSIS

By Gary M. White, MD

Onychomycosis Note the powdery, crumbly, yellow subungual debris.


Onychomycosis is infection of the nail by a fungal organism--most commonly a dermatophyte. One study of patients over 60 [AD 1997;133;1172] found that 66% of patients had dystrophic nails suggestive of onychomycosis but culture showed that only 40% actually were infected.

See also superficial white onychomycosis, proximal subungual onychomycosis, endonyx onychomycosis and onychomycosis by Candida and molds.

Clinical

Distal subungual onychomycosis (DSO) is the most common pattern of fungal infection of the nail. In DSO, the fungal organism invades the nail via the hyponychium. In the second most common type--lateral subungual--the fungus invades the nail along the lateral nail sulcus. Clinically, one sees separation of the nail plate from the bed distally and laterally with build up of subungual debris. When viewed from above, the nail appears thickened, yellowish and often raised. At times, a dark color is observed.

Superficial white onychomycosis is a pattern of infection on the surface of the nail. The clinical appearance is that of a powdery, rough nail surface.

Proximal subungual onychomycosis is a rare type of infection in which the fungus invades the area under the nail via the proximal nail fold. This type of infection is most common in the HIV-positive population. Clinically one sees a proximal whitish discoloration under the nail.

In endonyx onychomycosis, there is only color change of the nail plate (usually milky white) without onycholysis nor buildup of subungual debris.

Secondary onychomycosis is fungal invasion of an already damaged nail (e.g., by age, psoriasis).

Diagnosis and Differential Diagnosis

In the older patient, the nail may be dystrophic for a variety of reasons including poor circulation, trauma and old age. KOH staining and examination of subungual debris obtained using a 2 mm curette is both sensitive and rapid. PAS staining of nail clippings may also be done but the cost is higher and the results delayed [JAAD 2015;72;909]. Culturing a combination of nail clippings and curettings of subungual debris (with a 1-2 mm curette) is one good approach [JAAD 1998;39;1015] to both verify the diagnosis and identify the pathogen.

Treatment

Diagnose Definitively or Treat Empirically?

A recent study found that empiric treatment with oral terbinafine for patients suspected of having onychomycosis is more cost-effective than confirmatory testing across all prevalence of disease, with minimal effect on patient safety [JAMA Derm 2016;152;276].

Other Comments

Observation

Treatment is not necessary. Keeping the nails trimmed and filed may be adequate. However, this approach does not prevent progression of the disease with the potential for total destruction of the nail and infection of other uninvolved nails. In addition, the infected nails may constantly seed the skin. If therapy is desired, oral agents are most effective. However, any therapy that clears the nails is not a permanent cure. Relapses with any successful therapy are common.

Factors that reduce the likelihood of success of treatment include extensive involvement (e.g., multiple nails, > 75% of a nail, matrix involvement), long duration of disease (e.g., > 1 year), slow-growing nails, and old age.

Terbinafine

Oral terbinafine 250 mg/day for 6 weeks (fingernails) and 12 weeks (toenails) is the standard first-line treatment.  Cure rates are on the order of 75%. Terbinafine can rarely cause liver and blood abnormalities so CBC and LFTs are often checked baseline and at 3-4 weeks. With regard to retreating, there is no consensus. One expert recommends seeing the patient 1 month after a 3 month course and if the toenails look no better, he gives another 3 month course.

Off-label dosing regimens are commonly used. One study looked at skipping the middle month of terbinafine. Results (mycological cure rates--negative KOH and culture) at 72 weeks of that and several other regimens were as follows:

  1. 83.7% Terbinafine 250 mg/day for 4 weeks; 4 weeks no treatment; 4 weeks of terbinafine 250 mg/day
  2. 78.1% Terbinafine 250 mg/day for 12 weeks
  3. 56.7% Itraconazole pulse of 200 mg twice daily for 7 days on, 21 days off. Three pulses given.

"Pulse-dosing," i.e., giving terbinafine 250 mg/day for 1 week per month for 2-4 months, has also been recommended.

Terbinafine in Children

In studies of terbinafine treatment of onychomycosis in children, for those > 40 kg, the standard adult dose of 250 mg/day was used. For children 20-40 kg, 125 mg/day and for children 10-20 kg, 62.5 mg/day was given. Some investigators have suggested a weight-based dose of 4 to 5 mg/kg/day as an alternative.

Itraconazole

Approved dosing regimens for itraconazole are as follows:

Fluconazole

Fluconazole is not FDA-approved to treat onychomycosis. Fluconazole has been given 150-450 mg/week for 24 weeks or until the nail is cleared. One usually checks LFTs baseline. Complete cure rates at 6 months post treatment, in one study of distal subungual onychomycosis that spared the proximal toenail fold by at least 2 mm using 450 mg/week, was 48% (vs. 3% placebo)[JAAD 1998 Jun;38:S77]. Mean treatment duration was 6-7 months.

One DBPCT of 349 patients treated with fluconazole once weekly ("Fungal Friday" or "Toenail Tuesday") found it to be safe and effective in eradicating distal subungual onychomycosis of the fingernail caused by dermatophytes [JAAD 1998;38:S87-94]. Clinical cure rates at end of therapy were 76%, 85%, and 90% for fluconazole 150, 300, and 450 mg, respectively, compared with 3% for placebo.

Topical Agents for Onychomycosis

Topical agents may be reasonable for mild disease and early onset (< 1 year).

Efinaconazole

Efinaconazole 10% nail solution (Jublia®) is a topical treatment of distal and lateral subungual onychomycosis of the toenails. From the two pivotal studies, complete cure at 1 year was 17.8% and 15.2% with Jublia® compared to only 3.3% and 5.5% with vehicle. However, in patients with onychomycosis for less than 1 year, 42% had a complete cure after 52 weeks of treatment.

Ciclopirox

Penlac nail lacquer contains 8% ciclopirox and is intended for topical use on fingernails and toenails and the immediately adjacent skin for the treatment of mild to moderate onychomycosis without involvement of the lunula. In a 32 week DBPCT of children with nonmatrix onychomycosis [Pediatr Dermatol 2013;30:316-22], 77% of treated patients achieved mycologic cure compared with 22% of the control group. Ciclopirox lacquer or vehicle was applied daily for 32 weeks, with weekly removal of the lacquer and mechanical trimming.

Tavaborole

Topical tavaborole is FDA-approved as well and cleared onychomycosis in about 8% of patients after a year of treatment.

Lasers for Onychomycosis

DBPCTs have yet to prove the efficacy of lasers. For example, a randomized, controlled trial of 1064-nm Nd:YAG laser for the treatment of onychomycosis did not show any benefit [JAAD 2014 May]. However, an uncontrolled study of 356 onychomycotic nails treated with 3 sessions of fractional CO2 laser therapy at 4 week intervals combined with once-daily application of terbinafine cream for 3 months resulted in approximately 80% KOH and culture negative nails at 6 months [JAAD 2016;74;916].

Onychomycosis and Clothing

Clothing may be a source of reinfection. To kill fungus, it is recommended to wash socks in hot water for at least 45 minutes (note: using Eco Mode on washing machine is not as good).

Preventing Reinfection

A patient handout is available.

Additional Photos

Onychomycosis Onychomycosis Onychomycosis Onychomycosis

Onychomycosis Onychomycosis

Onychomycosis presenting as onycholysis.
Onychomycosis presenting as onycholysis

The subungual debris is best for culture.
Onychomycosis: curettage to obtain culture

Superficial white onychomycosis.
Superficial White Onychomycosis

Onychomycosis mimicking longitudinal melanonychia.
Onychomycosis mimicking longitudinal melanonychia

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