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| {{SI}} | | __NOTOC__ |
| | {{Onychomycosis}} |
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| '''For patient information, click [[Onychomycosis (patient information)|Onychomycosis]]''' | | '''For patient information, click [[Onychomycosis (patient information)|here]]''' |
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| {{CMG}}; {{AE}} {{KS}} | | {{CMG}}; {{AE}} {{KS}} |
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| '''''Synonyms and keywords:''''' Tinea unguium; fungal nail infection
| | {{SK}}Fungal infection of claw; Fungal infection of nail; Ringworm of nail |
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| ==Overview== | | ==[[Onychomycosis overview|Overview]]== |
| '''Onychomycosis''' means [[fungus|fungal]] infection of the [[Nail (anatomy)|nails]]. It represents up to 20% of all [[nail disorder]]s.
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| This condition may affect toe- or [[fingernail]]s, but [[toenail]] infections are particularly common. The most common type of onychomycosis (80-90%), caused by [[dermatophyte]]s, is technically known as [[tinea unguium]] ([[tinea]] of the nails).<ref>{{cite journal |author=Perea S, Ramos MJ, Garau M, Gonzalez A, Noriega AR, del Palacio A |title=Prevalence and risk factors of tinea unguium and tinea pedis in the general population in Spain |journal=J. Clin. Microbiol. |volume=38 |issue=9 |pages=3226-30 |year=2000 |pmid=10970362 |doi= |url=http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=87362}}</ref> It can result in discoloration, thickening, chalkiness, or crumbling of the nails and is often treated by powerful oral medications which, rarely, can cause severe side effects including [[liver failure]].
| | ==[[Onychomycosis historical perspective|Historical Perspective]]== |
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| == Classification == | | ==[[Onychomycosis classification|Classification]]== |
| ; Distal Subungual Onychomycosis: The most common form of tinea unguium usually caused by Trichophyton rubrum, which invades the nail bed and the underside of the nail plate.
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| ; White Superficial Onychomycosis: Caused by fungal invasion of the superficial layers of the nail plate to form "white islands" on the plate. Accounts for only 10 percent of onychomycosis cases.
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| ; Proximal Subungual Onychomycosis: 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 found more commonly when the patient is immunocompromised.
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| ; Candidal Onychomycosis: Candida species invade 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.
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| ; Total Dystrophic Onychomycosis: Total destruction of the nail plate. It is the end result of any of the above four types.
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| == Causes == | | ==[[Onychomycosis pathophysiology|Pathophysiology]]== |
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| Dermatophytes are the [[fungi]] most commonly responsible for onychomycosis.
| | ==[[Onychomycosis causes|Causes]]== |
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| Two dermatophyte [[species]], ''Trichophyton rubrum'' and ''Trichophyton interdigitale'', cause the vast majority of onychomycosis cases worldwide.
| | ==[[Onychomycosis differential diagnosis|Differentiating Onychomycosis from other Diseases]]== |
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| Other related dermatophyte fungi that may be involved are ''Epidermophyton floccosum'', ''Trichophyton violaceum'', ''Microsporum gypseum'', ''Trichophyton tonsurans'', ''Trichophyton soudanense'' (considered by some to be an African variant of ''T. rubrum'' rather than a full-fledged separate species) and the cattle [[ringworm]] fungus ''Trichophyton verrucosum''. A common outdated name that may still be reported by medical laboratories is ''Trichophyton mentagrophytes'' for ''T. interdigitale''.
| | ==[[Onychomycosis epidemiology and demographics|Epidemiology and Demographics]]== |
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| 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 [[dander]]s to humans, it generally infects skin and not nails.
| | ==[[Onychomycosis natural history, complications and prognosis|Natural History, Complications and Prognosis]]== |
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| Other causal fungi include [[yeast]]s (5-17%), ''e.g.'', ''[[Candida (genus)|Candida]]'', and non-dermatophytic [[mould]]s, in particular members of the mould genera ''Scytalidium'' (name recently changed to ''Neoscytalidium''), ''Scopulariopsis'', and ''[[Aspergillus]]''.
| | ==Diagnosis== |
| | [[Onychomycosis history and symptoms| History and Symptoms]] | [[Onychomycosis physical examination | Physical Examination]] | [[Onychomycosis laboratory findings|Laboratory Findings]] | [[Onychomycosis other imaging findings|Other Imaging Findings]] | [[Onychomycosis other diagnostic studies|Other Diagnostic Studies]] |
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| [[Yeast]]s 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. | | ==Treatment== |
| | [[Onychomycosis medical therapy|Medical Therapy]] | [[Onychomycosis surgery|Surgery]] | [[Onychomycosis primary prevention|Primary Prevention]] | [[Onychomycosis secondary prevention|Secondary Prevention]] | [[Onychomycosis future or investigational therapies|Future or Investigational Therapies]] |
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| Other moulds mainly affect people over the age of 60, and their presence in the nail reflects a slight weakening in the nail's ability to defend itself against fungal invasion.
| | ==Case Studies== |
| | [[Onychomycosis case study one|Case#1]] |
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| ==Epidemiology and Demographics==
| | [[Category:Disease]] |
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| The prevalence of onychomycosis is about 6-8% in the adult population.<ref>{{cite web |title=Impact 07 - Dermatology |url=http://www.baybio.org/pdf/IMPACT07_Derm.pdf |format=PDF |year=2007 |publisher=Bay Bio |accessdate=2007-06-13}}</ref>
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| == Diagnosis ==
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| If all nails are affected then fungal infection is improbable. To avoid misdiagnosis as [[psoriasis]], [[lichen planus]], [[contact dermatitis]], [[Physical trauma|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 that the most sensitive diagnostic approaches are direct smear combined with histological examination<ref>PMID 17222296</ref> and nail plate biopsy using periodic acid-Schiff stain<ref>PMID 12894064</ref>.
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| ===Symptoms===
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| 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. <ref>http://www.emedicine.com/derm/topic300.htm</ref>
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| [[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.
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| ===Physical Examination===
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| The following images show examples of how an onychomycosis patient's nails may look like. The nails may have a brown appearance.
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| (Images courtesy of Charlie Goldberg, M.D., UCSD School of Medicine and VA Medical Center, San Diego, CA)
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| <div align="left">
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| <gallery heights="175" widths="175">
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| Image:Onychomycosis due to Trychophyton rubrum, right and left great toe PHIL 579 lores.jpg|Onychomycosis due to ''Trychophyton rubrum'', right and left great toe.
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| Image:extremities_onychomycosis.jpg|Onychomycosis: Chronic fungal infection causing discoloration and deformity of nails.
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| Image:extremities_onychomycosis2.jpg|Onychomycosis: Chronic fungal toenail infection causing deformity and discoloration.
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| </gallery>
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| </div>
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| [http://www.peir.net Image shown below is courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology]
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| <div align="left">
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| <gallery heights="175" widths="175">
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| Image:Onykomycosis.Nail.jpg
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| </gallery>
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| </div>
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| =====Nails=====
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| <gallery>
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| Image:Onychomycosis01.jpg|Onychomycosis. <SMALL><SMALL>''[http://www.atlasdermatologico.com.br/ With permission from Dermatology Atlas.]''<ref name="Dermatology Atlas">{{Cite web | title = Dermatology Atlas | url = http://www.atlasdermatologico.com.br/}}</ref></SMALL></SMALL>
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| Image:Onychomycosis02.jpg|Onychomycosis. <SMALL><SMALL>''[http://www.atlasdermatologico.com.br/ With permission from Dermatology Atlas.]''<ref name="Dermatology Atlas">{{Cite web | title = Dermatology Atlas | url = http://www.atlasdermatologico.com.br/}}</ref></SMALL></SMALL>
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| Image:Onychomycosis03.jpg|Onychomycosis. <SMALL><SMALL>''[http://www.atlasdermatologico.com.br/ With permission from Dermatology Atlas.]''<ref name="Dermatology Atlas">{{Cite web | title = Dermatology Atlas | url = http://www.atlasdermatologico.com.br/}}</ref></SMALL></SMALL>
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| Image:Onychomycosis04.jpg|Onychomycosis. <SMALL><SMALL>''[http://www.atlasdermatologico.com.br/ With permission from Dermatology Atlas.]''<ref name="Dermatology Atlas">{{Cite web | title = Dermatology Atlas | url = http://www.atlasdermatologico.com.br/}}</ref></SMALL></SMALL>
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| </gallery>
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| == Treatment ==
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| 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. Mild onychomycosis sometimes responds to a combination of topical antifungal medication, sometimes applied as special medicinal nail lacquer, and periodic filing of the nail surface. For advanced onychomycosis, especially if more than one nail is infected, systemic medication (pills) is preferred.
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| === Pharmacotherapy ===
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| Most treatments are either systemic [[antifungals|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.<ref name="pmid11237081">{{cite journal |author=Rodgers P, Bassler M |title=Treating onychomycosis |journal=Am Fam Physician |volume=63 |issue=4 |pages=663–72, 677–8 |year=2001 |pmid=11237081 |doi= |url= http://www.aafp.org/afp/20010215/663.html}}</ref>
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| For superficial white onychomycosis systemic rather than topical antifungal therapy is advised.<ref name="pmid17610995">{{cite journal |author=Baran R, Faergemann J, Hay RJ |title=Superficial white onychomycosis--a syndrome with different fungal causes and paths of infection |journal=J. Am. Acad. Dermatol. |volume=57 |issue=5 |pages=879–82 |year=2007 |pmid=17610995 |doi=10.1016/j.jaad.2007.05.026}}</ref>
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| ====Chronic Pharmacotherapies====
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| '''Relative effectiveness of treatments'''
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| In July 2007 a meta-study reported on clinical trials for [[topical]] treatments of fungal nail infections. The study included 6 randomised controlled trials dating up to March 2005.<ref name="pmid17636672">{{cite journal |author=Crawford F, Hollis S |title=Topical treatments for fungal infections of the skin and nails of the foot |journal=Cochrane Database Syst Rev |volume= |issue=3 |pages=CD001434 |year=2007 |pmid=17636672 |doi=10.1002/14651858.CD001434.pub2}}</ref> The main findings are:
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| * There is some evidence that ciclopiroxolamine and [[butenafine]] are both effective but both need to be applied daily for prolonged periods (at least 1 year).
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| * There is evidence that topical ciclopiroxolamine has poor cure rates and that amorolfine might be substantially more effective.
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| * Further research into the effectiveness of antifungal agents for nail infections is required.
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| A 2002 study compared the efficacy and safety of [[terbinafine]] in comparison with placebo, [[itraconazole]] and [[griseofulvin]] in treating fungal infections of the nails.<ref>{{cite journal |author=Haugh M, Helou S, Boissel JP, Cribier BJ |title=Terbinafine in fungal infections of the nails: a meta-analysis of randomized clinical trials |journal=Br. J. Dermatol. |volume=147 |issue=1 |pages=118–21 |year=2002 |pmid=12100193 |doi=}}</ref> The main findings were that for reduced fungus terbinafine was found to be significantly better than itraconazole and griseofulvin, and terbinafine was better tolerated than itraconazole.
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| * A small study in 2004 showed that ciclopirox nail paint was more effective when combined with topical urea cream.<ref>{{cite news
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| |author=Mitchel L. Zoler
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| |pages=69
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| |title=Boosts drug entry into nails: urea, ciclopirox combo tested for onychomycosis.(Focus on Skin Disorders)
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| |date=April 1, 2004
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| |publisher=Internal Medical News
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| }}</ref>
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| * A study of 504 patients in 2007 found that aggressive [[debridement]] of the nail combined with oral terbinafine significantly reduced symptom frequency over terbinafine alone.<ref>{{cite journal |author=Potter LP, Mathias SD, Raut M, Kianifard F, Landsman A, Tavakkol A |title=The impact of aggressive debridement used as an adjunct therapy with terbinafine on perceptions of patients undergoing treatment for toenail onychomycosis |journal=The Journal of dermatological treatment |volume=18 |issue=1 |pages=46–52 |year=2007 |pmid=17373090 |doi=}}</ref>
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| * A 2007 randomised clinical trial with 249 patients show that a combination of [[amorolfine]] nail lacquer and oral terbinafine enhances clinical efficacy and is more cost-effective than terbinafine alone.<ref>{{cite journal |author=Baran R, Sigurgeirsson B, Berker DD, ''et al'' |title=A multicentre, randomized, controlled study of the efficacy, safety and cost-effectiveness of a combination therapy with amorolfine nail lacquer and oral terbinafine compared with oral terbinafine alone for the treatment of onychomycosis with matrix involvement |journal= British Journal of Dermatology|volume= 157|issue= |pages= 149|year=2007 |pmid=17553051 |doi=10.1111/j.1365-2133.2007.07974.x}}</ref>
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| '''Most drug development activities are focused on:'''
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| * the discovery of new antifungals
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| * novel delivery methods to promote access of existing antifungal drugs into the infected nail plate
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| Active clinical trials investigating Onychomycosis:<ref>[http://clinicaltrials.gov/ct/search?term=Onychomycosis&submit=Search clinicaltrials.gov]</ref>
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| '''Some phase III clinical trials revolving around onychomycosis are shown below.'''
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| * A medicinal nail lacquer, NM100060 from NexMed,<ref>{{ClinicalTrialsGov|NCT00459537}}</ref> contains terbinafine as the active ingredient and a permeation enhancer which facilitates the delivery of the drug into the nail bed where the fungus resides. Commercial sale of the product is expected to begin no earlier than in 2010.<ref>[http://www.nexmed.com/products/Nail.php NEXMED Medicines of the Future<!-- Bot generated title -->]</ref>
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| * A comparison of delivery methods for Itraconzole.<ref>{{ClinicalTrialsGov|NCT00356915}}</ref>
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| * Safety and tolerability of topical Terbinafine.<ref>{{ClinicalTrialsGov|NCT00443820}} and {{ClinicalTrialsGov|NCT00443898}}</ref>
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| '''Some phase II clinical trials revolving around onychomycosis are show below.'''
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| * A topical treatment, AN-2690, is being developed by Schering-Plough Corp and Anacor Pharmaceuticals. It is active against [[Trichophyton]] species.<ref name="pmid17668368">{{cite journal |author=Barak O, Loo DS |title=AN-2690, a novel antifungal for the topical treatment of onychomycosis |journal=Curr Opin Investig Drugs |volume=8 |issue=8 |pages=662–8 |year=2007 |pmid=17668368 |doi=}}</ref>
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| * [[Posaconazole]], taken orally.<ref>{{ClinicalTrialsGov|NCT00491764}}</ref>
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| * A topical treatment, NB-002, is being developed by NanoBio Corporation.<ref>{{ClinicalTrialsGov|NCT00356915}}</ref> It has completed Phase II trails.<ref>[http://www.nanobio.com/Dermatology/Onychomycosis.html NanoBio - Onychomycosis]</ref>
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| A non-pharmalogical approach with encouraging preliminary results is [[ultraviolet germicidal irradiation]] which has been shown to deactivate dermatophytes both ''in vitro'' and ''ex vivo''.<ref>{{PMID|18410410}}</ref>
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| '''Natural remedies'''
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| As with many diseases, there are also some scientifically unverified folk or [[alternative medicine]] remedies.
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| * Australian [[tea tree oil]].<ref name="pmid8195735">{{cite journal |author=Buck DS, Nidorf DM, Addino JG |title=Comparison of two topical preparations for the treatment of onychomycosis: Melaleuca alternifolia (tea tree) oil and clotrimazole |journal=J Fam Pract |volume=38 |issue=6 |pages=601–5 |year=1994 |pmid=8195735 |doi=}}</ref><ref name="pmid9055360">{{cite journal |author=Nenoff P, Haustein UF, Brandt W |title=Antifungal activity of the essential oil of Melaleuca alternifolia (tea tree oil) against pathogenic fungi in vitro |journal=Skin Pharmacol. |volume=9 |issue=6 |pages=388–94 |year=1996 |pmid=9055360 |doi=}}</ref> In a study at the University of Rochester [[tea tree oil]] applied twice daily in conjunction with [[debridement]] was found to be an appropriate initial treatment strategy, equally effective to topical use of [[clotrimazole]]<ref name="scratch">[http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=8195735&dopt=AbstractPlus].</ref>.
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| *[[Grapefruit seed extract]] as a natural antimicrobial is not demonstrated. Its effectiveness is scientifically unverified. Multiple studies indicate that the universal antimicrobial activity is due to contamination with synthetic preservatives that were unlikely to be made from the seeds of the grapefruit.<ref>{{cite journal |author=von Woedtke T, Schlüter B, Pflegel P, Lindequist U, Jülich WD |title=Aspects of the antimicrobial efficacy of grapefruit seed extract and its relation to preservative substances contained |journal=Pharmazie |volume=54 |issue=6 |pages=452–6 |year=1999 |pmid=10399191 |doi=}}</ref><ref>{{cite journal |author=Sakamoto S, Sato K, Maitani T, Yamada T |title=[Analysis of components in natural food additive "grapefruit seed extract" by HPLC and LC/MS]|language=Japanese |journal=Eisei Shikenjo hōkoku. Bulletin of National Institute of Hygienic Sciences |volume= |issue=114 |pages=38–42 |year=1996 |pmid=9037863 |doi=}}</ref><ref>{{cite journal |author=Takeoka G, Dao L, Wong RY, Lundin R, Mahoney N |title=Identification of benzethonium chloride in commercial grapefruit seed extracts |journal=J. Agric. Food Chem. |volume=49 |issue=7 |pages=3316–20 |year=2001 |pmid=11453769 |doi=}}</ref><ref>{{cite journal |author=Takeoka GR, Dao LT, Wong RY, Harden LA |title=Identification of benzalkonium chloride in commercial grapefruit seed extracts |journal=J. Agric. Food Chem. |volume=53 |issue=19 |pages=7630–6 |year=2005 |pmid=16159196 |doi=10.1021/jf0514064}}</ref><ref>{{cite journal |author=Ganzera M, Aberham A, Stuppner H |title=Development and validation of an HPLC/UV/MS method for simultaneous determination of 18 preservatives in grapefruit seed extract |journal=J. Agric. Food Chem. |volume=54 |issue=11 |pages=3768–72 |year=2006 |pmid=16719494 |doi=10.1021/jf060543d}}</ref>
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| *Another procedure is to apply two drops of distilled white vinegar to the nail base, or, additionally, nail plate and under the nail, two or three times daily for approximately six months or until the fungus is gone. This treatment is very effective, due to the vinegar's acidity, if followed consistently.
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| '''New developments'''
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| * A medicinal nail lacquer, NM100060 from NexMed is in [[clinical trial|Phase III clinical trials]]<ref>{{ClinicalTrialsGov|NCT00459537}}</ref>. It contains terbinafine as the active ingredient and a permeation enhancer which facilitates the delivery of the drug into the nail bed where the fungus resides. Commercial sale of the product is expected to begin no earlier than in 2008. <ref>[http://www.nexmed.com/products/Nail.php]</ref>
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| * A topical treatment, AN-2690, is being developed by Schering-Plough Corp. It is active against [[Trichophyton]] species. Phase II and IIb trials are underway. <ref name="pmid17668368">{{cite journal |author=Barak O, Loo DS |title=AN-2690, a novel antifungal for the topical treatment of onychomycosis |journal=Current opinion in investigational drugs (London, England : 2000) |volume=8 |issue=8 |pages=662–8 |year=2007 |pmid=17668368 |doi=}}</ref>
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| Active clinical trials investigating Onychomycosis: [http://clinicaltrials.gov/ct/search?term=Onychomycosis&submit=Search].
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| ===Primary Prevention===
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| * Avoid walking barefoot in public areas such as showers, communal changing rooms.
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| * Keeping feet clean and dry.
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| * Avoid sharing shoes and socks
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| ===Antimicrobial Regimen===
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| *Onychomycosis
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| :*Fingernail Treatment Options
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| ::*Preferred regimen: [[Terbinafine]] 250 mg PO q24h (children <20 kg: 67.5 mg/day, 20–40 kg: 125 mg/day, >40 kg: 250 mg/day) for 6 weeks {{or}} [[Itraconazole]] 200 mg PO q24h for 3 months {{or}} [[Itraconazole]] 200 mg PO bid for 1 week/month for 2 months {{or}} [[Fluconazole]] 150–300 mg PO q week for 3–6 months
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| :*Toenail Treatment Options
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| ::*Preferred regimen: [[Terbinafine]] 250 mg PO q24h (children <20 kg: 67.5 mg/day, 20–40 kg:125 mg/day, >40 kg: 250 mg/day) for 12 weeks {{or}} [[Itraconazole]] 200 mg PO q24h for 3 months {{or}} [[Itraconazole]] 200 mg bid for 1 week/month for 3–4 months {{or}} [[Fluconazole]] 150–300 mg PO q week for 6–12 months
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| ==References==
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| {{Reflist|2}}
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| == See also == | | == See also == |
| *[[Nail disease]] | | * [[Nail disease]] |
| *[[List of tinea infections]] | | * [[List of tinea infections]] |
| | | * [[Dermatophytosis]] |
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| {{Mycoses}} | | {{Mycoses}} |
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| [[Category:Nail diseases]] | | [[Category:Nail diseases]] |
| [[Category:Fungal diseases]] | | [[Category:Fungal diseases]] |
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