Onychomycosis

Onychomycosis
Classification and external resources
A toenail affected by onychomycosis
ICD-10	B35.1
ICD-9	110.1
DiseasesDB	13125
MedlinePlus	001330
eMedicine	derm/300
MeSH	D014009

Onychomycosis (also known as "dermatophytic onychomycosis,"^[1] "ringworm of the nail,"^[1] and "tinea unguium"^[1]) means fungal infection of the nail.^[2] It is the most common disease of the nails and constitutes about a half of all nail abnormalities.^[3]

This condition may affect toenails or fingernails, but toenail infections are particularly common. The prevalence of onychomycosis is about 6-8% in the adult population.^[4]

Classification

There are four classic types of onychomycosis:^[5]

• Distal subungual onychomycosis is the most common form of tinea unguium, and is usually caused by Trichophyton rubrum, which invades the nail bed and the underside of the nail plate.
• White superficial onychomycosis (WSO) is caused by fungal invasion of the superficial layers of the nail plate to form "white islands" on the plate. It accounts for only 10 percent of onychomycosis cases. In some cases, WSO is a misdiagnosis of "keratin granulations" which are not a fungus, but a reaction to nail polish that can cause the nails to have a chalky white appearance. A laboratory test should be performed to confirm.^[6]
• Proximal subungual onychomycosis is fungal penetration of the newly formed nail plate through the proximal nail fold. It is the least common form of tinea unguium in healthy people, but is found more commonly when the patient is immunocompromised.
• Candidal onychomycosis is Candida species invasion of the fingernails, usually occurring in persons who frequently immerse their hands in water. This normally requires the prior damage of the nail by infection or trauma.

Signs and symptoms

Onychomycosis

The nail plate can have a thickened, yellow, or cloudy appearance. The nails can become rough and crumbly, or can separate from the nail bed. There is usually no pain or other bodily symptoms, unless the disease is severe.^[7]

Dermatophytids are fungus-free skin lesions that sometimes form as a result of a fungus infection in another part of the body. This could take the form of a rash or itch in an area of the body that is not infected with the fungus. Dermatophytids can be thought of as an allergic reaction to the fungus. People with onychomycosis may experience significant psychosocial problems due to the appearance of the nail. This is particularly increased when fingernails are affected.^[8]

Causes

The causative pathogens of onychomycosis include dermatophytes, Candida, and nondermatophytic molds. Dermatophytes are the fungi most commonly responsible for onychomycosis in the temperate western countries; while Candida and nondermatophytic molds are more frequently involved in the tropics and subtropics with a hot and humid climate.^[9]

Dermatophytes

Trichophyton rubrum is the most common dermatophyte involved in onychomycosis. Other dermatophytes that may be involved are T. interdigitale, Epidermophyton floccosum, T. violaceum, Microsporum gypseum, T. tonsurans, T. soudanense (considered by some to be an African variant of T. rubrum rather than a full-fledged separate species) and the cattle ringworm fungus T. verrucosum. A common outdated name that may still be reported by medical laboratories is Trichophyton mentagrophytes for T. interdigitale. The name T. mentagrophytes is now restricted to the agent of favus skin infection of the mouse; though this fungus may be transmitted from mice and their danders to humans, it generally infects skin and not nails.

Other

Other causative pathogens include Candida and nondermatophytic molds, in particular members of the mold generation Scytalidium (name recently changed to Neoscytalidium), Scopulariopsis, and Aspergillus. Candida spp. mainly cause fingernail onychomycosis in people whose hands are often submerged in water. Scytalidium mainly affects people in the tropics, though it persists if they later move to areas of temperate climate.

Other molds more commonly affect people older than 60 years, and their presence in the nail reflects a slight weakening in the nail's ability to defend itself against fungal invasion.

Risk factors

Risk factors for onychomycosis include family history, increasing age, poor health, prior trauma, warm climate, participation in fitness activities, immunosuppression (e.g., HIV, drug induced), communal bathing, and occlusive footwear.

Diagnosis

To avoid misdiagnosis as nail psoriasis, lichen planus, contact dermatitis, trauma, nail bed tumor or yellow nail syndrome, laboratory confirmation may be necessary. The three main approaches are potassium hydroxide smear, culture and histology. This involves microscopic examination and culture of nail scrapings or clippings. Recent results indicate the most sensitive diagnostic approaches are direct smear combined with histological examination,^[10] and nail plate biopsy using periodic acid-Schiff stain.^[11] To reliably identify nondermatophyte molds, several samples may be necessary.^[12]

Treatment

Treatment of onychomycosis is challenging because the infection is embedded within the nail and is difficult to reach. As a result, full removal of symptoms is very slow and may take a year or more.

Pharmacological

Most treatments are either systemic antifungal medications, such as terbinafine and itraconazole, or topical, such as nail paints containing ciclopirox or amorolfine. There is also evidence for combining systemic and topical treatments.^[13]

For superficial white onychomycosis, systemic rather than topical antifungal therapy is advised.^[14]

In July 2007, a meta-study reported on clinical trials for topical treatments of fungal nail infections. The study included six randomised, controlled trials dating up to March 2005.^[15] The main findings are:

• There is some evidence ciclopiroxolamine and butenafine are both effective, but both need to be applied daily for prolonged periods (at least 1 year).
• There is evidence topical ciclopiroxolamine has poor cure rates, and that amorolfine might be substantially more effective.
• Further research into the effectiveness of antifungal agents for nail infections is required.

A 2002 study compared the efficacy and safety of terbinafine in comparison to placebo, itraconazole and griseofulvin in treating fungal infections of the nails.^[16] The main findings were for reduced fungus, terbinafine was found to be significantly better than itraconazole and griseofulvin, and terbinafine was better tolerated than itraconazole.

• A small study in 2004 showed ciclopirox nail paint was more effective when combined with topical urea cream.^[17]
• A study of 504 patients in 2007 found aggressive debridement of the nail, combined with oral terbinafine, significantly reduced symptom frequency over terbinafine alone.^[18]
• A 2007 randomised clinical trial with 249 patients showed a combination of amorolfine nail lacquer and oral terbinafine enhanced clinical efficacy and is more cost-effective than terbinafine alone.^[19]

Lasers

A Noveon-type laser, already in use by physicians for some types of cataract surgery, is used by some podiatrists, although the only scientific study on its efficacy, while showing positive results, included far too few test subjects for the laser to be proven generally effective.^[20]

In 2011, several lasers were seeking approval and two been cleared by the Food and Drug Administration.^[21]

Light Age, Inc. has approval to market a Nd:YAG laser for onychomycosis treatment.^[22]

Alternative medicine

As with many diseases, there are also some scientifically unverified folk or alternative medicine remedies.

• Australian tea tree oil^[23][24] has been tested, but there is insufficient information to make recommendations for its use for onychomycosis.^[25]
• Grapefruit seed extract as a natural antimicrobial is not demonstrated. Its effectiveness is scientifically unverified. Multiple studies indicate the universal antimicrobial activity is due to contamination with synthetic preservatives that were unlikely to be made from the seeds of the grapefruit.^{[26][27][28][29][30]}
• Snakeroot leaf extract has, in studies, shown ability to treat superficial onychomycosis, although the results show it is less effective, and equal to conventional drugs ciclopirox and ketaconazole, respectively.^[31][32]

Epidemiology

A 2003 survey of diseases of the foot in 16 European countries found onychomycosis to be the most frequent fungal foot infection and estimates its prevalence at 27%.^[33][34] Prevalence was observed to increase with age. In Canada, the prevalence was estimated to be 6.48%.^[35] Onychomycosis affects approximately one-third of diabetics^[36] and is 56% more frequent in people suffering from psoriasis.^[37]

Research

Most drug development activities are focused on the discovery of new antifungals and novel delivery methods to promote access of existing antifungal drugs into the infected nail plate. Active clinical trials investigating onychomycosis:^[38]

Phase III

• A topical treatment, AN2690, is being developed by Anacor Pharmaceuticals.^[39] It is active against Trichophyton species.^[40]
• A medicinal nail lacquer, MycoVa from Apricus Biosciences,^[41] contains terbinafine as the active ingredient and a permeation enhancer DDAIP which facilitates the delivery of the drug into the nail bed where the fungus resides.^[42][43]
• A comparison of delivery methods for itraconzole^[44]
• Safety and tolerability of topical terbinafine^[45]
• Laser-based treatments^[46]
• Topical IDP-108^[47]
• Bifonazole cream application after nail ablation with urea paste^[48]

Phase II

• Posaconazole, taken orally.^[49]
• A topical treatment, NB-002, is being developed by NanoBio Corporation.^[44] It has completed Phase II trials.^[50]

References

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38. ^ clinicaltrials.gov
39. ^ ClinicalTrials.gov NCT01270971 >
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42. ^ "Apricus Biosciences Announces Expanded European Patent Coverage For MycoVa(TM) For Nail Fungus". The Street. http://www.thestreet.com/story/11027033/1/apricus-biosciences-announces-expanded-european-patent-coverage-for-mycovatm-for-nail-fungus.html. Retrieved 2011-03-14. 
43. ^ NEXMED Medicines of the Future
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50. ^ NanoBio - Onychomycosis