Onychomycosis (also known as "dermatophytic onychomycosis," "ringworm of the nail," and "tinea unguium") means fungal infection of the

nail. It is the most common disease of the nails and constitutes about a half of all nail abnormalities. 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.

A toenail affected by onychomycosis

Classification There are four classic types of onychomycosis:

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.

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 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. 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. 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. 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, and nail plate biopsy using periodic acid-Schiff stain. To reliably identify nondermatophyte molds, several samples may be necessary.

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. For superficial white onychomycosis, systemic rather than topical antifungal therapy is advised. 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. 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. 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. A study of 504 patients in 2007 found aggressive debridement of the nail, combined with oral terbinafine, significantly reduced symptom frequency over terbinafine alone.

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.

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. In 2009, several lasers were seeking approval and one has been cleared by the Food and Drug Administration.

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

Australian tea tree oil has been tested, but there is insufficient information to make recommendations for its use for onychomycosis. 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. 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.

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%. Prevalence was observed to increase with age. In Canada, the prevalence was estimated to be 6.48%. Onychomycosis affects approximately one-third of diabetics and is 56% more frequent in people suffering from psoriasis.

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:

Phase III

A topical treatment, AN2690, is being developed by Anacor Pharmaceuticals. It is active against Trichophyton species. A medicinal nail lacquer, MycoVa from Apricus Biosciences, 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. A comparison of delivery methods for itraconzole Safety and tolerability of topical terbinafine Laser-based treatments Topical IDP-108 Bifonazole cream application after nail ablation with urea paste

Phase II

Posaconazole, taken orally. A topical treatment, NB-002, is being developed by NanoBio Corporation. It has completed Phase II trials.

Overview Onychomycosis, commonly known as a fungal nail infection, is infection of the fingernails or toenails by forms of fungi and yeast. Fungal nail infections account for nearly one-half of all nail disorders. In the most common form of fungal nail infections, fungus grows under the growing portion of the nail and spreads up the finger (proximally) along the nail bed and the grooves on the sides of the nails. A less common type of fungal nail infection may occur in those with HIV/AIDS.

Who's At Risk Fungal nail infection may occur at any age but is more common in adults, particularly in older individuals. Diabetics may be more likely than other people to develop a fungal nail infection. Signs and Symptoms

In general, toenails are most commonly affected with fungal nail infection. If the fingernails are affected, the toenails are usually affected as well. Nails often become thicker and lift from the nail bed (onycholysis) starting at the growing portion of the nail. You might then see debris under the nails and discoloration of the affected area. In some forms of fungal nail infection, you might see black or white, powdery discoloration on the surface of the nail plate. In some forms of fungal nail infection, you might see these abnormal changes farther up the finger (proximally), where the nail originates. Fungal nail infection may occur in people with athlete's foot (tinea pedis) and/or oozing infection (paronychia), caused by inflammation and infection with yeast and/or bacteria in the region where the skin of the finger meets the origin of the nail. In fungal nail infection, one, a few, or all nails may be affected.

Self-Care Guidelines

None necessary except good hygiene and regular washing of the hands and feet. Home remedies that may be helpful include soaking the feet daily in Listerine, vinegar, vitamin E oil, Vicks VapoRub, or tea tree oil.

When to Seek Medical Care Fungal nail infection does not always require treatment, but see your doctor for any nail disorder. Diabetics with foot problems should be evaluated because of the possible risk for developing foot ulcers. Your doctor may perform testing, such as scraping a nail to examine for fungi or clipping a nail to look for bacterial or

fungal growth (culture) or to obtain a special stain to look for fungi under a microscope. Treatments Your Provider May Prescribe

Topical therapy with ciclopirox nail lacquer, which requires daily application for 912 months. Oral antifungal treatments offer the best chance for curing fungal nail infection. The most commonly used agents are terbinafine, itraconazole, and fluconazole. The medications may cause liver problems or may affect blood cell counts. Blood tests are usually performed before starting therapy and during therapy to look for possible side effects. In stubborn (refractory) fungal nail infection, surgical removal of part of the nail or the entire nail, removing the nail by applying a chemical, or thinning the nail by applying 40% urea ointment may be used, in addition topical or oral antifungal agents.

Nail Lifting Nail lifting (onycholysis) is the spontaneous separation (detachment) of the fingernail or toenail from the nail bed at the end of the nail (distal) and/or on the sides of the nail (lateral). The appearance of nail lifting may resemble a halfmoon, or the free edge of the nail may rise up like a hood. Nail lifting creates space under the nail that gathers dirt and debris made of protein in the nails (keratin). As water accumulates under the nail, bacteria and yeast can also cause the area to become infected. Nail lifting may occur with other skin conditions, such as various forms of eczema (including hand dermatitis), psoriasis, and lichen planus. Nail lifting may also occur with underlying medical problems, including thyroid disease, pregnancy, some forms of infection, and rarely some forms of cancer. Other possible causes are injury to the nails, use of nail cosmetics, and aggressive manicures. Nail lifting may be caused by some medications, such as chemotherapy and drugs made from vitamin A. Some medications (commonly tetracycline) may interact with sunlight to cause nail lifting.

Who's At Risk Nail lifting may affect people of all ages. Women are affected more frequently than men. Signs and Symptoms Nail lifting occurs on the fingernails and the toenails. The nail separates from the end (distal) and/or the sides (lateral) of the nail bed and may even separate completely from the finger.

Self-Care Guidelines

Thoroughly clip away as much of the detached nail as possible, repeating this at weekly intervals. Gently brush the nail and surrounding tissue with plain soap and water once daily, rinsing carefully, and then drying the area with a hair dryer. Protect the nails by wearing plastic gloves worn over light cotton gloves to avoid frequent contact with water. Use any mild cleanser as an alternative to water and soap.

When to Seek Medical Care See your doctor if the nail lifting becomes bothersome. Your doctor may perform tests for conditions or infection that may be causing the nail lifting. Treatments Your Provider May Prescribe In addition to the self-care measures noted above, your doctor may prescribe:

Treatment for any skin conditions, medical problems, or exposures that may be causing your nail lifting. If bacterial or fungal infection is present, you may require antibacterial or antifungal treatment.