Onychomycosis
Encyclopedia
Onychomycosis means fungal
Fungus
A fungus is a member of a large group of eukaryotic organisms that includes microorganisms such as yeasts and molds , as well as the more familiar mushrooms. These organisms are classified as a kingdom, Fungi, which is separate from plants, animals, and bacteria...

 infection
Dermatophytosis
Dermatophytosis or ringworm is a clinical condition caused by fungal infection of the skin in humans, pets such as cats, and domesticated animals such as sheep and cattle. The term "ringworm" is a misnomer, since the condition is caused by fungi of several different species and not by parasitic worms...

 of the nail
Nail (anatomy)
A nail is a horn-like envelope covering the dorsal aspect of the terminal phalanges of fingers and toes in humans, most non-human primates, and a few other mammals. Nails are similar to claws, which are found on numerous other animals....

. 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.

Classification

There are four classic types of onychomycosis:
  • Distal subungual onychomycosis
    Distal subungual onychomycosis
    Distal subungual onychomycosis is an infection of the nail plate by fungus, primarily involving the distal nail plate....

     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
    Nail plate
    The nail plate is the hard and translucent portion of the nail, composed of keratin.- See also :* Runner's toe, repetitive injury seen in runners...

    .
  • White superficial onychomycosis
    White superficial onychomycosis
    White superficial onychomycosis is an infection of the nail plate by fungus, primarily affecting the surface of the nail....

     (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
    Proximal subungual onychomycosis
    Proximal subungual onychomycosis is an infection of the nail plate by fungus, primarily affecting the proximal nailfold....

     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
    Candidal onychomycosis
    Candidal onychomycosis is an infection of the nail plate by fungus caused by Candida albicans....

     is Candida
    Candida (genus)
    Candida is a genus of yeasts. Many species are harmless commensals or endosymbionts of animal hosts including humans, but other species, or harmless species in the wrong location, can cause disease. Candida albicans can cause infections in humans and other animals, especially in immunocompromised...

    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
    Infection
    An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...

     or trauma
    Physical trauma
    Trauma refers to "a body wound or shock produced by sudden physical injury, as from violence or accident." It can also be described as "a physical wound or injury, such as a fracture or blow." Major trauma can result in secondary complications such as circulatory shock, respiratory failure and death...

    .

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
Dermatophytids
Dermatophytids are fungus-free disseminated skin lesions resulting from induced sensitization in patients with ringworm infections.The most common dermatophytid is an inflammation in the hands resulting from a fungus infection of the feet. Dermatophytids normally disappear when the primary ringworm...

 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
Rash
A rash is a change of the skin which affects its color, appearance or texture. A rash may be localized in one part of the body, or affect all the skin. Rashes may cause the skin to change color, itch, become warm, bumpy, chapped, dry, cracked or blistered, swell and may be painful. The causes, and...

 or itch
Itch
Itch is a sensation that causes the desire or reflex to scratch. Itch has resisted many attempts to classify it as any one type of sensory experience. Modern science has shown that itch has many similarities to pain, and while both are unpleasant sensory experiences, their behavioral response...

 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
Psychosocial
For a concept to be psychosocial means it relates to one's psychological development in, and interaction with, a social environment. The individual needs not be fully aware of this relationship with his or her environment. It was first commonly used by psychologist Erik Erikson in his stages of...

 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
Candida (genus)
Candida is a genus of yeasts. Many species are harmless commensals or endosymbionts of animal hosts including humans, but other species, or harmless species in the wrong location, can cause disease. Candida albicans can cause infections in humans and other animals, especially in immunocompromised...

, and nondermatophytic mold
Mold
Molds are fungi that grow in the form of multicellular filaments called hyphae. Molds are not considered to be microbes but microscopic fungi that grow as single cells called yeasts...

s. Dermatophytes are the fungi most commonly responsible for onychomycosis in the temperate western countries; while Candida
Candida (genus)
Candida is a genus of yeasts. Many species are harmless commensals or endosymbionts of animal hosts including humans, but other species, or harmless species in the wrong location, can cause disease. Candida albicans can cause infections in humans and other animals, especially in immunocompromised...

and nondermatophytic mold
Mold
Molds are fungi that grow in the form of multicellular filaments called hyphae. Molds are not considered to be microbes but microscopic fungi that grow as single cells called yeasts...

s are more frequently involved in the tropics and subtropics with a hot and humid climate.

Dermatophytes

Trichophyton rubrum
Trichophyton rubrum
Trichophyton rubrum is a fungus that is the most common cause of athlete's foot, jock itch and ringworm. This fungus was first described by Malmsten in 1845....

is the most common dermatophyte
Dermatophyte
Dermatophytes are a common label for a group of three types of fungus that commonly causes skin disease in animals and humans. These anamorphic genera are: Microsporum, Epidermophyton and Trichophyton. There are about 40 species in these three genera...

 involved in onychomycosis. Other dermatophytes that may be involved are T. interdigitale
Trichophyton interdigitale
Trichophyton interdigitale is a species of Trichophyton. It can produce penicillium.Some sources equate it with "Trichophyton mentagrophytes". As such is one of three common fungi which cause ringworm in companion animals. It has a major natural reservoir in rodents, but can also infect pet...

, Epidermophyton floccosum
Epidermophyton floccosum
Epidermophyton floccosum is an anthropophilic dermatophyte which can be found world-wide.-Taxonomy:The fungus was originally described by Carl Otto Harz in 1870, who named it Acrothecium floccosum...

, T. violaceum, Microsporum gypseum, T. tonsurans
Trichophyton tonsurans
Trichophyton tonsurans is a species of fungus in the Arthrodermataceae family. It is a common cause of tinea capitis in the United Kingdom....

, T. soudanense (considered by some to be an African variant of T. rubrum rather than a full-fledged separate species
Species
In biology, a species is one of the basic units of biological classification and a taxonomic rank. A species is often defined as a group of organisms capable of interbreeding and producing fertile offspring. While in many cases this definition is adequate, more precise or differing measures are...

) and the cattle
Cattle
Cattle are the most common type of large domesticated ungulates. They are a prominent modern member of the subfamily Bovinae, are the most widespread species of the genus Bos, and are most commonly classified collectively as Bos primigenius...

 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
Favus
Favus is a disease usually affecting the scalp, but occurring occasionally on any part of the skin, and even at times on mucous membranes.-Presentation:...

 skin infection of the mouse
Mouse
A mouse is a small mammal belonging to the order of rodents. The best known mouse species is the common house mouse . It is also a popular pet. In some places, certain kinds of field mice are also common. This rodent is eaten by large birds such as hawks and eagles...

; though this fungus may be transmitted from mice
MICE
-Fiction:*Mice , alien species in The Hitchhiker's Guide to the Galaxy*The Mice -Acronyms:* "Meetings, Incentives, Conferencing, Exhibitions", facilities terminology for events...

 and their dander
Dander
Dander is an informal term for a material shed from the body of various animals, similar to dandruff. It may contain scales of dried skin and hair, or feathers. It is a cause of allergies in humans....

s to humans, it generally infects skin and not nails.

Other

Other causative pathogens include Candida and nondermatophytic mold
Mold
Molds are fungi that grow in the form of multicellular filaments called hyphae. Molds are not considered to be microbes but microscopic fungi that grow as single cells called yeasts...

s, in particular members of the mold generation Scytalidium
Scytalidium
Scytalidium is a genus of fungi in the Helotiales order. The relationship of this taxon to other taxa within the order is unknown , and it has not yet been placed with certainty into any family. This genus of anamorphic fungi has a widespread distribution and contains 18 species. Scytalidium...

(name recently changed to Neoscytalidium
Neoscytalidium
Neoscytalidium is a genus of fungi in the Botryosphaeriaceae family....

), Scopulariopsis
Scopulariopsis
Scopulariopsis is a genus of anamorphic fungi that are saprobic and pathogenic to animals. The widespread genus contains 22 species....

, and Aspergillus
Aspergillus
Aspergillus is a genus consisting of several hundred mold species found in various climates worldwide. Aspergillus was first catalogued in 1729 by the Italian priest and biologist Pier Antonio Micheli...

.
Candida spp. mainly cause fingernail onychomycosis in people whose hands are often submerged in water. Scytalidium mainly affects people in the tropics
Tropics
The tropics is a region of the Earth surrounding the Equator. It is limited in latitude by the Tropic of Cancer in the northern hemisphere at approximately  N and the Tropic of Capricorn in the southern hemisphere at  S; these latitudes correspond to the axial tilt of the Earth...

, 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
Psoriatic nails
Psoriatic nails is a nail disease. It is common in those suffering from psoriasis, with reported incidences varying from 10% to 78%. Elderly patients and those with psoriatic arthritis are more likely to have psoriatic nails.-Symptoms:...

, lichen planus
Lichen planus
Lichen planus is a chronic mucocutaneous disease that affects the skin, tongue, and oral mucosa. The disease presents itself in the form of papules, lesions, or rashes. Lichen planus does not involve lichens, the fungus/algae symbionts that often grow on tree trunks; the name refers to the dry and...

, contact dermatitis
Contact dermatitis
Contact dermatitis is a term for a skin reaction resulting from exposure to allergens or irritants . Phototoxic dermatitis occurs when the allergen or irritant is activated by sunlight....

, trauma
Physical trauma
Trauma refers to "a body wound or shock produced by sudden physical injury, as from violence or accident." It can also be described as "a physical wound or injury, such as a fracture or blow." Major trauma can result in secondary complications such as circulatory shock, respiratory failure and death...

, nail bed tumor
Tumor
A tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer...

 or yellow nail syndrome
Yellow nail syndrome
Yellow nail syndrome is a very rare medical syndrome that includes pleural effusions, lymphoedema and yellow dystrophic nails. Approximately 40% will also have bronchiectasis. It is also associated with chronic sinusitis and persistent coughing...

, laboratory confirmation may be necessary. The three main approaches are potassium hydroxide
Potassium hydroxide
Potassium hydroxide is an inorganic compound with the formula KOH, commonly called caustic potash.Along with sodium hydroxide , this colorless solid is a prototypical strong base. It has many industrial and niche applications. Most applications exploit its reactivity toward acids and its corrosive...

 smear, culture
Tissue culture
Tissue culture is the growth of tissues or cells separate from the organism. This is typically facilitated via use of a liquid, semi-solid, or solid growth medium, such as broth or agar...

 and histology
Histology
Histology is the study of the microscopic anatomy of cells and tissues of plants and animals. It is performed by examining cells and tissues commonly by sectioning and staining; followed by examination under a light microscope or electron microscope...

. This involves microscopic
Microscopic
The microscopic scale is the scale of size or length used to describe objects smaller than those that can easily be seen by the naked eye and which require a lens or microscope to see them clearly.-History:...

 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
Biopsy
A biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically...

 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
Terbinafine
Terbinafine hydrochloride is a...

 and itraconazole
Itraconazole
Itraconazole , invented in 1984, is a triazole antifungal agent that is prescribed to patients with fungal infections. The drug may be given orally or intravenously.-Medical uses:...

, or topical, such as nail paints containing ciclopirox or amorolfine
Amorolfine
Amorolfine , is a morpholine antifungal drug that inhibits D14 reductase and D7-D8 isomerase, which depletes ergosterol and causes ignosterol to accumulate in the fungal cytoplasmic cell membranes....

. There is also evidence for combining systemic
Systemic
Systemic refers to something that is spread throughout, system-wide, affecting a group or system such as a body, economy, market or society as a whole. Systemic may also refer to:-In medicine:...

 and topical
Topical
In medicine, a topical medication is applied to body surfaces such as the skin or mucous membranes such as the vagina, anus, throat, eyes and ears.Many topical medications are epicutaneous, meaning that they are applied directly to the skin...

 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
Topical
In medicine, a topical medication is applied to body surfaces such as the skin or mucous membranes such as the vagina, anus, throat, eyes and ears.Many topical medications are epicutaneous, meaning that they are applied directly to the skin...

 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
    Butenafine
    Butenafine hydrochloride is a synthetic benzylamine antifungal, marketed under the trade names Mentax, Butop and is the active ingredient in Schering-Plough's Lotrimin Ultra. It is structurally related to synthetic allylamine antifungals such as terbinafine.-Pharmacology:Butenafine hydrochloride...

     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
    Amorolfine
    Amorolfine , is a morpholine antifungal drug that inhibits D14 reductase and D7-D8 isomerase, which depletes ergosterol and causes ignosterol to accumulate in the fungal cytoplasmic cell membranes....

     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
Terbinafine
Terbinafine hydrochloride is a...

 in comparison to placebo
Placebo
A placebo is a simulated or otherwise medically ineffectual treatment for a disease or other medical condition intended to deceive the recipient...

, itraconazole
Itraconazole
Itraconazole , invented in 1984, is a triazole antifungal agent that is prescribed to patients with fungal infections. The drug may be given orally or intravenously.-Medical uses:...

 and griseofulvin
Griseofulvin
Griseofulvin is an antifungal drug that is administered orally. It is used both in animals and in humans, to treat fungal infections of the skin and nails...

 in treating fungal infections of the nails. The main findings were for reduced fungus, terbinafine
Terbinafine
Terbinafine hydrochloride is a...

 was found to be significantly better than itraconazole
Itraconazole
Itraconazole , invented in 1984, is a triazole antifungal agent that is prescribed to patients with fungal infections. The drug may be given orally or intravenously.-Medical uses:...

 and griseofulvin
Griseofulvin
Griseofulvin is an antifungal drug that is administered orally. It is used both in animals and in humans, to treat fungal infections of the skin and nails...

, and terbinafine
Terbinafine
Terbinafine hydrochloride is a...

 was better tolerated than itraconazole
Itraconazole
Itraconazole , invented in 1984, is a triazole antifungal agent that is prescribed to patients with fungal infections. The drug may be given orally or intravenously.-Medical uses:...

.
  • 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
    Debridement
    Debridement is the medical removal of a patient's dead, damaged, or infected tissue to improve the healing potential of the remaining healthy tissue...

     of the nail, combined with oral terbinafine
    Terbinafine
    Terbinafine hydrochloride is a...

    , significantly reduced symptom frequency over terbinafine alone.
  • A 2007 randomised clinical trial with 249 patients showed a combination of amorolfine
    Amorolfine
    Amorolfine , is a morpholine antifungal drug that inhibits D14 reductase and D7-D8 isomerase, which depletes ergosterol and causes ignosterol to accumulate in the fungal cytoplasmic cell membranes....

     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
Cataract
A cataract is a clouding that develops in the crystalline lens of the eye or in its envelope, varying in degree from slight to complete opacity and obstructing the passage of light...

 surgery
Surgery
Surgery is an ancient medical specialty that uses operative manual and instrumental techniques on a patient to investigate and/or treat a pathological condition such as disease or injury, or to help improve bodily function or appearance.An act of performing surgery may be called a surgical...

, 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 2011, several lasers were seeking approval and two been cleared by the Food and Drug Administration
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...

.

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

Alternative medicine

As with many diseases, there are also some scientifically unverified folk or alternative medicine
Alternative medicine
Alternative medicine is any healing practice, "that does not fall within the realm of conventional medicine." It is based on historical or cultural traditions, rather than on scientific evidence....

 remedies.
  • Australian tea tree oil
    Tea tree oil
    Tea tree oil, or melaleuca oil, is a pale yellow colour to nearly clear essential oil with a fresh camphoraceous odor. It is taken from the leaves of the Melaleuca alternifolia, which is native to the northeast coast of New South Wales, Australia...

     has been tested, but there is insufficient information to make recommendations for its use for onychomycosis.
  • Grapefruit seed extract
    Grapefruit seed extract
    Grapefruit seed extract , also known as citrus seed extract, is a liquid derived from the seeds, pulp, and white membranes of grapefruit. Self-made natural GSE processed in the laboratory without solvents or synthetic agents is prepared by grinding the grapefruit seed and juiceless pulp, then...

     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
    Snakeroot
    Ageratina is a genus of about 250–290 perennials and rounded shrubs in the sunflower family .These plants grow mainly in the warmer regions of the Americas. Over 150 species are native to Mexico. Some flourish in the cooler areas of the eastern United States. Two Mexican species have become a pest...

     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
Diabetes mellitus
Diabetes mellitus, often simply referred to as diabetes, is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced...

 and is 56% more frequent in people suffering from psoriasis
Psoriasis
Psoriasis is an autoimmune disease that appears on the skin. It occurs when the immune system mistakes the skin cells as a pathogen, and sends out faulty signals that speed up the growth cycle of skin cells. Psoriasis is not contagious. However, psoriasis has been linked to an increased risk of...

.
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