Onychomycosis

Last updated
Onychomycosis
Other namesDermatophytic onychomycosis [1] tinea unguium [1]
Oncymycosis.JPG
A toenail affected by onychomycosis
Specialty Infectious disease
Symptoms White or yellow nail discoloration, thickening of the nail [2] [3]
Complications Lower leg cellulitis [3]
Usual onsetOlder males [2] [3]
CausesFungal infection [3]
Risk factors Athlete's foot, other nail diseases, exposure to someone with the condition, peripheral vascular disease, poor immune function [3]
Diagnostic method Based on appearance, confirmed by laboratory testing [2]
Differential diagnosis Psoriasis, chronic dermatitis, chronic paronychia, nail trauma [2]
TreatmentNone, anti-fungal medication, trimming the nails [2] [3]
Medication Terbinafine, ciclopirox [2]
Prognosis Often recurs [2]
Frequency~10% of adults [2]

Onychomycosis, also known as tinea unguium, [4] is a fungal infection of the nail. [2] Symptoms may include white or yellow nail discoloration, thickening of the nail, and separation of the nail from the nail bed. [2] Fingernails may be affected, but it is more common for toenails. [3] Complications may include cellulitis of the lower leg. [3] A number of different types of fungus can cause onychomycosis, including dermatophytes and Fusarium . [3] Risk factors include athlete's foot, other nail diseases, exposure to someone with the condition, peripheral vascular disease, and poor immune function. [3] The diagnosis is generally suspected based on the appearance and confirmed by laboratory testing. [2]

Contents

Onychomycosis does not necessarily require treatment. [3] The antifungal medication terbinafine taken by mouth appears to be the most effective but is associated with liver problems. [2] [5] Trimming the affected nails when on treatment also appears useful. [2]

There is a ciclopirox-containing nail polish, but there is no evidence that it works. [2] The condition returns in up to half of cases following treatment. [2] Not using old shoes after treatment may decrease the risk of recurrence. [3]

Onychomycosis occurs in about 10 percent of the adult population, [2] with older people more frequently affected. [2] Males are affected more often than females. [3] Onychomycosis represents about half of nail disease. [2] It was first determined to be the result of a fungal infection in 1853 by Georg Meissner. [6]

Signs and symptoms

A case of fungal infection of the big toe Toefungus.jpg
A case of fungal infection of the big toe
Advanced fungal infection of the big toe Advanced onychomycosis.png
Advanced fungal infection of the big toe

The most common symptom of a fungal nail infection is the nail becoming thickened and discoloured: white, black, yellow or green. As the infection progresses the nail can become brittle, with pieces breaking off or coming away from the toe or finger completely. If left untreated, the skin underneath and around the nail can become inflamed and painful. There may also be white or yellow patches on the nailbed or scaly skin next to the nail, [7] and a foul smell. [8] There is usually no pain or other bodily symptoms, unless the disease is severe. [9] People with onychomycosis may experience significant psychosocial problems due to the appearance of the nail, particularly when fingers – which are always visible – rather than toenails are affected. [10] 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.

Causes

The causative pathogens of onychomycosis are all in the fungus kingdom and include dermatophytes, Candida (yeasts), and nondermatophytic molds. [2] 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. [11]

Dermatophytes

When onychomycosis is due to a dermatophyte infection, it is termed tinea unguium. Trichophyton rubrum is the most common dermatophyte involved in onychomycosis. Other dermatophytes that may be involved are T. interdigitale , Epidermophyton floccosum , Tricholosporum violaceum , Microsporum gypseum , T. tonsurans , and T. soudanense . 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 genus Scytalidium (name recently changed to Neoscytalidium ), Scopulariopsis , and Aspergillus . Candida species 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.

Nail injury and nail psoriasis can cause damaged toenails to become thick, discolored & brittle. [12]

Risk factors

Advancing age (usually over the age of 60) is the most common risk factor for onychomycosis due to diminished blood circulation, longer exposure to fungi, nails which grow more slowly and thicken, and reduced immune function increasing susceptibility to infection. [13] Nail fungus tends to affect men more often than women and is associated with a family history of this infection.

Other risk factors include perspiring heavily, being in a humid or moist environment, psoriasis, wearing socks and shoes that hinder ventilation and do not absorb perspiration, going barefoot in damp public places such as swimming pools, gyms and shower rooms, having athlete's foot (tinea pedis), minor skin or nail injury, damaged nail, or other infection, and having diabetes, circulation problems, which may also lead to lower peripheral temperatures on hands and feet, or a weakened immune system. [14]

Diagnosis

The diagnosis is generally suspected based on the appearance and confirmed by laboratory testing. [2] The four main tests are a potassium hydroxide smear, culture, histology examination, and polymerase chain reaction. [2] [3] The sample examined is generally nail scrapings or clippings. [2] These being from as far up the nail as possible. [3]

Nail plate biopsy with periodic acid-Schiff stain appear more useful than culture or direct KOH examination. [15] To reliably identify nondermatophyte molds, several samples may be necessary. [16]

Classification

There are five classic types of onychomycosis: [17] [18]

Differential diagnosis

In many cases of suspected nail fungus there is actually no fungal infection, but only nail deformity. [20] [21]

To avoid misdiagnosis as nail psoriasis, lichen planus, contact dermatitis, nail bed tumors such as melanoma, trauma, or yellow nail syndrome, laboratory confirmation may be necessary. [2]

Other conditions that may appear similar to onychomycosis include: psoriasis, normal aging, green nail syndrome, yellow nail syndrome, and chronic paronychia. [22]

Treatment

A person's foot with a fungal nail infection ten weeks into a course of terbinafine oral medication. Note the band of healthy (pink) nail growth behind the remaining infected nails. A patient's left foot - after ten weeks of Terbinafine oral treatment.png
A person's foot with a fungal nail infection ten weeks into a course of terbinafine oral medication. Note the band of healthy (pink) nail growth behind the remaining infected nails.

Medications

Most treatments are with antifungal medications, either topically or by mouth. [2] Avoiding use of antifungal therapy by mouth (e.g., terbinafine) in persons without a confirmed infection is recommended, because of the possible side effects of that treatment. [20] First topical terbinafine medication (MOB-015) was launched in February 2024 in Sweden under the name Terclara. This medication recorded 76% mycological cure rate in two phase 3 studies. The topical property of this medication ensures that typical terbinafine side effects are not present (1000 times lower terbinafine levels in plasma). Roll-out in other countries will continue in the coming years. [23] [24]

Medications that may be taken by mouth include terbinafine (76% effective), itraconazole (60% effective), and fluconazole (48% effective). [2] They share characteristics that enhance their effectiveness: prompt penetration of the nail and nail bed, [25] and persistence in the nail for months after discontinuation of therapy. [26] Ketoconazole by mouth is not recommended due to side effects. [27] Oral terbinafine is better tolerated than itraconazole. [28] For superficial white onychomycosis, systemic rather than topical antifungal therapy is advised. [29]

Topical agents include ciclopirox nail paint, amorolfine, and efinaconazole. [30] [31] [32] Some topical treatments need to be applied daily for prolonged periods (at least one year). [31] Topical amorolfine is applied weekly. [33]

Efinaconazole, a topical azole antifungal, led to cure rates two or three times better than the next-best topical treatment, ciclopirox. [34] In trials, about 17% of people were cured using efinaconazole, as opposed to 4% of people using placebo. [35]

Topical ciclopirox results in a cure in 6% to 9% of cases. [2] [31] Ciclopirox when used with terbinafine appears to be better than either agent alone. [2] Although eficonazole, P-3051 (ciclopirox 8% hydrolacquer), and tavaborole are effective at treating fungal infection of toenails, complete cure rates are low. [36]

Other

Chemical (keratolytic) or surgical debridement of the affected nail appears to improve outcomes. [2]

As of 2014, evidence for laser treatment is unclear as the evidence is of low quality [37] and varies by type of laser. [38]

Tea tree oil is not recommended as a treatment on present data. It was found to irritate the surrounding skin in some trial participants. [39]

Cost

United States

According to a 2015 study, the cost in the United States of testing with the periodic acid–Schiff stain (PAS) was about $148. Even if the cheaper KOH test is used first and the PAS test is used only if the KOH test is negative, there is a good chance that the PAS will be done (because of either a true or a false negative with the KOH test). But the terbinafine treatment costs only $10 (plus an additional $43 for liver function tests). In conclusion the authors say that terbinafine has a relatively benign adverse effect profile, with liver damage very rare, so it makes more sense cost-wise for the dermatologist to prescribe the treatment without doing the PAS test. (Another option would be to prescribe the treatment only if the potassium hydroxide test is positive, but it gives a false negative in about 20% of cases of fungal infection.) On the other hand, as of 2015 the price of topical (non-oral) treatment with efinaconazole was $2307 per nail, so testing is recommended before prescribing it. [21]

The cost of efinaconazole treatment can be reduced to $65 per 1-month dose using drug coupons, bringing the treatment cost to $715 per nail. [40]

Canada

In 2019, a study by the Canadian Agency for Drugs and Technologies in Health found the cost for a 48-week efinaconazole course to be $178 for a big toe, and $89 for a different toe. [41]

Prognosis

Recurrence may occur following treatment, with a 20-25% relapse rate within 2 years of successful treatment. [13] Nail fungus can be painful and cause permanent damage to nails. It may lead to other serious infections if the immune system is suppressed due to medication, diabetes or other conditions. The risk is most serious for people with diabetes and with immune systems weakened by leukemia or AIDS, or medication after organ transplant. Diabetics have vascular and nerve impairment, and are at risk of cellulitis, a potentially serious bacterial infection; any relatively minor injury to feet, including a nail fungal infection, can lead to more serious complications. [42] Infection of the bone is another rare complication. [7]

Epidemiology

A 2003 survey of diseases of the foot in 16 European countries found onychomycosis to be the most frequent fungal foot infection and estimated its prevalence at 27%. [43] [44] Prevalence was observed to increase with age. In Canada, the prevalence was estimated to be 6.48%. [45] Onychomycosis affects approximately one-third of diabetics [46] and is 56% more frequent in people with psoriasis. [47]

Etymology

The term is from Ancient Greek ὄνυξonyx "nail", μύκηςmykēs "fungus", [48] and the suffix -ωσιςōsis "functional disease".

Research

Research suggests that fungi are sensitive to heat, typically 40–60 °C (104–140 °F). The basis of laser treatment is to try to heat the nail bed to these temperatures in order to disrupt fungal growth. [49] As of 2013 research into laser treatment seemed promising. [2] There is also ongoing development in photodynamic therapy, which uses laser or LED light to activate photosensitisers that eradicate fungi. [50]

Related Research Articles

<span class="mw-page-title-main">Tinea cruris</span> Fungal infection

Tinea cruris (TC), also known as jock itch, is a common type of contagious, superficial fungal infection of the groin and buttocks region, which occurs predominantly but not exclusively in men and in hot-humid climates.

<span class="mw-page-title-main">Nail disease</span> Medical condition

A nail disease or onychosis is a disease or deformity of the nail. Although the nail is a structure produced by the skin and is a skin appendage, nail diseases have a distinct classification as they have their own signs and symptoms which may relate to other medical conditions. Some nail conditions that show signs of infection or inflammation may require medical assistance.

<span class="mw-page-title-main">Athlete's foot</span> Skin infection caused by fungus

Athlete's foot, known medically as tinea pedis, is a common skin infection of the feet caused by a fungus. Signs and symptoms often include itching, scaling, cracking and redness. In rare cases the skin may blister. Athlete's foot fungus may infect any part of the foot, but most often grows between the toes. The next most common area is the bottom of the foot. The same fungus may also affect the nails or the hands. It is a member of the group of diseases known as tinea.

<span class="mw-page-title-main">Terbinafine</span> Antifungal medication

Terbinafine is an antifungal medication used to treat pityriasis versicolor, fungal nail infections, and ringworm including jock itch and athlete's foot. It is either taken by mouth or applied to the skin as a cream or ointment. The cream and ointment should not be used for fungal nail infections.

Dermatophyte is a common label for a group of fungus of Arthrodermataceae that commonly causes skin disease in animals and humans. Traditionally, these anamorphic mold genera are: Microsporum, Epidermophyton and Trichophyton. There are about 40 species in these three genera. Species capable of reproducing sexually belong in the teleomorphic genus Arthroderma, of the Ascomycota. As of 2019 a total of nine genera are identified and new phylogenetic taxonomy has been proposed.

<span class="mw-page-title-main">Tinea corporis</span> Medical condition

Tinea corporis is a fungal infection of the body, similar to other forms of tinea. Specifically, it is a type of dermatophytosis that appears on the arms and legs, especially on glabrous skin; however, it may occur on any superficial part of the body.

<span class="mw-page-title-main">Tinea capitis</span> Cutaneous fungal infection of the scalp

Tinea capitis is a cutaneous fungal infection (dermatophytosis) of the scalp. The disease is primarily caused by dermatophytes in the genera Trichophyton and Microsporum that invade the hair shaft. The clinical presentation is typically single or multiple patches of hair loss, sometimes with a 'black dot' pattern, that may be accompanied by inflammation, scaling, pustules, and itching. Uncommon in adults, tinea capitis is predominantly seen in pre-pubertal children, more often boys than girls.

<span class="mw-page-title-main">Ciclopirox</span> Antifungal medication

Ciclopirox is a synthetic antifungal agent for topical dermatologic treatment of superficial mycoses. It is most useful against tinea versicolor. It is often used clinically as ciclopirox olamine, the olamine salt of ciclopirox.

<span class="mw-page-title-main">Dermatophytosis</span> Fungal infection of the skin

Dermatophytosis, also known as tinea and ringworm, is a fungal infection of the skin, that may affect skin, hair, and nails. Typically it results in a red, itchy, scaly, circular rash. Hair loss may occur in the area affected. Symptoms begin four to fourteen days after exposure. The types of dermatophytosis are typically named for area of the body that they affect. Multiple areas can be affected at a given time.

<span class="mw-page-title-main">Tinea manuum</span> Medical condition

Tinea manuum is a fungal infection of the hand, mostly a type of dermatophytosis, often part of two feet-one hand syndrome. There is diffuse scaling on the palms or back of usually one hand and the palmer creases appear more prominent. When both hands are affected, the rash looks different on each hand, with palmer creases appearing whitish if the infection has been present for a long time. It can be itchy and look slightly raised. Nails may also be affected.

<i>Trichophyton rubrum</i> Species of fungus

Trichophyton rubrum is a dermatophytic fungus in the phylum Ascomycota. It is an exclusively clonal, anthropophilic saprotroph that colonizes the upper layers of dead skin, and is the most common cause of athlete's foot, fungal infection of nail, jock itch, and ringworm worldwide. Trichophyton rubrum was first described by Malmsten in 1845 and is currently considered to be a complex of species that comprises multiple, geographically patterned morphotypes, several of which have been formally described as distinct taxa, including T. raubitschekii, T. gourvilii, T. megninii and T. soudanense.

<span class="mw-page-title-main">Amorolfine</span> Chemical compound

Amorolfine, is a morpholine antifungal drug that inhibits Δ14-sterol reductase and cholestenol Δ-isomerase, which depletes ergosterol and causes ignosterol to accumulate in the fungal cytoplasmic cell membranes. Marketed as Curanail, Loceryl, Locetar, and Odenil, amorolfine is commonly available in the form of a nail lacquer, containing 5% amorolfine hydrochloride as the active ingredient. It is used to treat onychomycosis. Amorolfine 5% nail lacquer in once-weekly or twice-weekly applications was shown in two decades-old studies to be between 60% and 71% effective in treating toenail onychomycosis; complete cure rates three months after stopping treatment were 38% and 46%. However, full experimental details of these trials were not available, and since they were first reported in 1992 there have been no subsequent trials.

<span class="mw-page-title-main">Clotrimazole</span> Chemical compound

Clotrimazole, sold under the brand name Lotrimin, among others, is an antifungal medication. It is used to treat vaginal yeast infections, oral thrush, diaper rash, tinea versicolor, and types of ringworm including athlete's foot and jock itch. It can be taken by mouth or applied as a cream to the skin or in the vagina.

<span class="mw-page-title-main">Fungal folliculitis</span> Inflammation of hair follicles due to fungal infection

Majocchi's granuloma is a skin condition characterized by deep, pustular plaques, and is a form of tinea corporis. It is a localized form of fungal folliculitis. Lesions often have a pink and scaly central component with pustules or folliculocentric papules at the periphery. The name comes from Domenico Majocchi, who discovered the disorder in 1883. Majocchi was a professor of dermatology at the University of Parma and later the University of Bologna. This disease is most commonly caused by filamentous fungi in the genus Trichophyton.

<span class="mw-page-title-main">Efinaconazole</span> Chemical compound

Efinaconazole, sold under the brand name Jublia among others, is a triazole antifungal medication. It is approved for use in the United States, Canada, and Japan as a 10% topical solution for the treatment of onychomycosis. Efinaconazole acts as a 14α-demethylase inhibitor.

<span class="mw-page-title-main">Tavaborole</span> Chemical compound

Tavaborole, sold under the brand name Kerydin, is a topical antifungal medication for the treatment of onychomycosis, a fungal infection of the nail and nail bed with a complete clearance rate of 6-7% and partial clearance rate of 23-24% in individuals whose “infection border does not reach the cuticle at the base of the large toenail.” Tavaborole was approved by the US FDA in July 2014. The medication inhibits an essential fungal enzyme, leucyl-tRNA synthetase, that is required for protein synthesis. The inhibition of protein synthesis leads to termination of cell growth and then cell death, eliminating the fungal infection.

<i>Epidermophyton floccosum</i> Species of fungus

Epidermophyton floccosum is a filamentous fungus that causes skin and nail infections in humans. This anthropophilic dermatophyte can lead to diseases such as tinea pedis, tinea cruris, tinea corporis and onychomycosis. Diagnostic approaches of the fungal infection include physical examination, culture testing, and molecular detection. Topical antifungal treatment, such as the use of terbinafine, itraconazole, voriconazole, and ketoconazole, is often effective.

Two feet-one hand syndrome (TFOHS), is a long-term fungal condition where athlete's foot or fungal toe nail infections in both feet is associated with tinea manuum in one hand. Often the feet are affected for several years before symptoms of a diffuse scaling rash on the palm of one hand appear, which is when most affected people then seek medical help.

Topical antifungaldrugs are used to treat fungal infections on the skin, scalp, nails, vagina or inside the mouth. These medications come as creams, gels, lotions, ointments, powders, shampoos, tinctures and sprays. Most antifungal drugs induce fungal cell death by destroying the cell wall of the fungus. These drugs inhibit the production of ergosterol, which is a fundamental component of the fungal cell membrane and wall.

References

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  38. ↑ Liddell LT, Rosen T (April 2015). "Laser Therapy for Onychomycosis: Fact or Fiction?". Journal of Fungi. 1 (1): 44–54. doi: 10.3390/jof1010044 . PMC   5770012 . PMID   29376898.
  39. ↑ Halteh P, Scher RK, Lipner SR (November 2016). "Over-the-counter and natural remedies for onychomycosis: do they really work?". Cutis. 98 (5): E16–E25. PMID   28040821. there was no statistical difference between the clotrimazole and TTO treatment groups in mycologic cure, clinical assessment, or patient subjective assessment of the nails. Although there was an 80% complete cure in the butenafine and TTO group, it was 0% in the TTO group at week 36. Trial design, longer treatment periods, incorporation into nanocapsules, or combination treatment with other antifungal agents may influence our future use of TTO for onychomycosis, but based on the present data we cannot recommend this treatment in clinical practice.
  40. ↑ "Ortho Dermatologics Access Program". www.orthorxaccess.com. Retrieved 2021-08-10.
  41. ↑ "Table 5, CDR Cost Comparison Table for Onychomycosis". www.ncbi.nlm.nih.gov. 8 June 2019.
  42. ↑ Mayo clinic – Nail fungus: complications
  43. ↑ Burzykowski T, Molenberghs G, Abeck D, Haneke E, Hay R, Katsambas A, et al. (December 2003). "High prevalence of foot diseases in Europe: results of the Achilles Project". Mycoses. 46 (11–12): 496–505. doi:10.1046/j.0933-7407.2003.00933.x. hdl: 1942/429 . PMID   14641624. S2CID   20055970.
  44. ↑ Verma S, Heffernan MP (2008). Superficial fungal infection: Dermatophytosis, onychomycosis, tinea nigra, piedra. In K Wolff et al., eds., Fitzpatrick's Dermatology in General Medicine, 7th ed., vol 2, pp. 1807–1821. New York: McGraw Hill.
  45. ↑ Vender, Ronald B.; Lynde, Charles W.; Poulin, Yves (2006). "Prevalence and epidemiology of onychomycosis". Journal of Cutaneous Medicine and Surgery . 10 Suppl 2 (6_suppl): S28–S33. doi:10.2310/7750.2006.00056. PMID   17204229. S2CID   74819774.
  46. ↑ Gupta AK, Konnikov N, MacDonald P, Rich P, Rodger NW, Edmonds MW, et al. (October 1998). "Prevalence and epidemiology of toenail onychomycosis in diabetic subjects: a multicentre survey". The British Journal of Dermatology. 139 (4): 665–71. doi:10.1046/j.1365-2133.1998.02464.x. PMID   9892911. S2CID   22038748.
  47. ↑ Gupta AK, Lynde CW, Jain HC, Sibbald RG, Elewski BE, Daniel CR, et al. (May 1997). "A higher prevalence of onychomycosis in psoriatics compared with non-psoriatics: a multicentre study". The British Journal of Dermatology. 136 (5): 786–9. doi:10.1046/j.1365-2133.1997.6771624.x. PMID   9205520. S2CID   5969796.
  48. ↑ ὄνυξ, μύκης . Liddell, Henry George ; Scott, Robert ; A Greek–English Lexicon at the Perseus Project.
  49. ↑ "Device-based Therapies for Onychomycosis Treatment" . Retrieved 23 December 2012.
  50. ↑ Piraccini BM, Alessandrini A (March 2015). "Onychomycosis: A Review". Journal of Fungi. 1 (1): 30–43. doi: 10.3390/jof1010030 . PMC   5770011 . PMID   29376897.
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