View source for Hairy leukoplakia

{{Distinguish|Hairy tongue}}
<!-- another tongue condition with "hairy" in the name, but completely different etiology -->
{{Infobox medical condition (new)
| name            = Hairy leukoplakia
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| synonyms        =  '''Oral hairy leukoplakia''',<ref name="Andrews">{{cite book |author1=James, William D. |author2=Berger, Timothy G. |title=Andrews' Diseases of the Skin: clinical Dermatology |publisher=Saunders Elsevier |year=2006 |isbn=978-0-7216-2921-6 |display-authors=etal}}</ref>{{rp|385}} OHL, or '''HIV-associated hairy leukoplakia'''<ref name="Cawson 2002">{{cite book|vauthors=Cawson RA, Odell EW, Porter S |title=Cawsonś essentials of oral pathology and oral medicine.|year=2002|publisher=Churchill Livingstone|location=Edinburgh|isbn=978-0443071065|pages=223, 224|edition=7th}}</ref>
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'''Hairy leukoplakia'''  is a white patch on the side of the tongue with a corrugated or hairy appearance. It is caused by [[Epstein-Barr virus]] (EBV) and occurs usually in persons who are [[immunocompromise]]d, especially those with [[human immunodeficiency virus]] infection/[[acquired immunodeficiency syndrome]] (HIV/AIDS). The white [[lesion]], which cannot be scraped off, is benign and does not require any treatment, although its appearance may have diagnostic and prognostic implications for the underlying condition.

Depending upon what definition of [[leukoplakia]] is used, hairy leukoplakia is sometimes considered a subtype of leukoplakia, or a distinct diagnosis.

==Signs and symptoms==
There are no symptoms associated with the lesion itself,<ref name="Cherry-Peppers 2003" /> although many and varied symptoms and signs may be associated with the underlying cause of immunosuppression. The lesion is a white patch, which almost exclusively occurs on the [[lateral (anatomy)|lateral]] surfaces of the tongue, although rarely it may occur on the [[buccal mucosa]], [[soft palate]], [[pharynx]] or [[esophagus]].<ref name="Neville 2002" /> The lesion may grow to involve the [[dorsum (anatomy)|dorsal]] surface of the tongue. The texture is vertically corrugated ("hairy") or thickly furrowed and shaggy in appearance.<ref name="Neville 2002" />

==Causes==
The white appearance is created by [[hyperkeratosis]] (overproduction of [[keratin]]) and [[epithelium|epithelial]] [[hyperplasia]].<ref name="Neville 2002">{{cite book|vauthors=Neville BW, Damm DD, Allen CM, Bouquot JE|title=Oral & maxillofacial pathology|url=https://archive.org/details/oralmaxillofacia00nevi|url-access=registration|year=2002|publisher=W.B. Saunders|location=Philadelphia|isbn=978-0721690032|pages=[https://archive.org/details/oralmaxillofacia00nevi/page/n253 241]–242|edition=2nd}}</ref> The causative agent implicated is Epstein-Barr virus, the same virus that causes [[infectious mononucleosis]] (glandular fever). After the primary EBV infection has been overcome, the virus will persist for the rest of the host's life and "hides" from the immune system by latent infection of [[B lymphocytes]].<ref name="Gulley 2001">{{cite journal|last=Gulley|first=ML|title=Molecular diagnosis of Epstein-Barr virus-related diseases.|journal=The Journal of Molecular Diagnostics|date=February 2001|volume=3|issue=1|pages=1–10|pmid=11227065|pmc=1907346|doi=10.1016/s1525-1578(10)60642-3}}</ref> The virus also causes [[lytic cycle|lytic infection]] in the [[oropharynx]], but is kept in check by a normal, functioning [[immune system]]. Uncontrolled lytic infection is manifested as oral hairy leukoplakia in immunocompromised hosts. OHL usually arises where the immunocompromise is secondary to HIV/AIDS.<ref name="Neville 2002" /> Rarely are other causes of immunocompromise associated with OHL, but it has been reported in people who have received transplants<!-- <ref name="Neville 2002" /> --> and are taking immunosuppressive medication. OHL may also accompany chronic [[graft versus host disease]].<ref name="Scully 2008" /> Even more rare are reports of OHL in persons with competent immune systems.<ref name="Neville 2002" />

==Diagnosis==
The white lesion cannot be wiped away,<ref name="Scully 2008" /> unlike some other common oral white lesions, e.g. [[oral candidiasis|pseudomembranous candidiasis]], and this may aid in the diagnosis. Diagnosis of OHL is mainly clinical, but can be supported by proof of EBV in the lesion (achieved by [[in situ hybridization]], [[polymerase chain reaction]], [[immunohistochemistry]], [[Southern blotting]], or [[electron microscopy]]) and HIV serotesting.<ref name="Scully 2008" /> When clinical appearance alone is used to diagnose OHL, there is a [[false positive]] rate of 17% compared to more objective methods.<ref name="Chapple 2000" /> The appearance of OHL in a person who is known to be infected with HIV does not usually require further diagnostic tests as the association is well known. OHL in persons with no known cause of immunocompromise usually triggers investigations to look for an underlying cause. If tissue [[biopsy]] is carried out, the [[histopathology|histopathologic]] appearance is of hyperplastic and parakeratinized epithelium, with "balloon cells" (lightly staining cells) in the upper [[stratum spinosum]] and "nuclear beading" in the superficial layers (scattered cells with peripheral margination of [[chromatin]] and clear nuclei, created by displacement of chromatin to the peripheral nucleus by EBV replication). [[Candida (fungus)|Candida]] usually is seen growing in the parakeratin layer, but there are no normal inflammatory reactions to this in the tissues.<ref name="Neville 2002" /> There is no [[dysplasia]] (OHL is not a [[premalignant]] lesion).<ref name="Neville 2002" />

===Classification===
In a classification of the oral lesions in HIV disease,<ref>EC Clearinghouse. Oral Problems Related to HIV Infection, revised classification.</ref> OHL is grouped as "lesions strongly associated with HIV infection" (group I).<ref name="Chapple 2000">{{cite journal|last=Chapple|first=IL|author2=Hamburger, J|title=The significance of oral health in HIV disease.|journal=Sexually Transmitted Infections|date=August 2000|volume=76|issue=4|pages=236–43|pmid=11026876|pmc=1744197|doi=10.1136/sti.76.4.236}}</ref> It could also be classed as an [[opportunistic infection|opportunistic]], [[virus|viral]] disease. Hairy leukoplakia occurs on the tongue and has a similar name to [[hairy tongue]], but these are separate conditions with different causes.{{cn|date=January 2021}}

==Treatment==
Treatment is not necessary since the lesion is benign, however the person may have aesthetic concerns about the appearance. The condition often resolves rapidly with high dose [[acyclovir]] or [[desiclovir]] but recurs once this therapy is stopped, or as the underlying immunocompromise worsens.<ref name="Chapple 2000" /><ref name="Neville 2002" /> [[Topical medication|Topical]] use of [[podophyllum]] resin or [[retinoid]]s has also been reported to produce temporary remission. [[Antiretroviral drug]]s such as [[zidovudine]] may be effective in producing a significant regression of OHL.<ref name="Neville 2002" /> Recurrence of the lesion may also signify that [[highly active antiretroviral therapy]] (HAART) is becoming ineffective.<ref name="Cherry-Peppers 2003" />

==Prognosis==
The oral lesion itself is benign and self-limiting,<ref name="Scully 2008">{{cite book|author=Scully C|title=Oral and maxillofacial medicine : the basis of diagnosis and treatment|year=2008|publisher=Churchill Livingstone|location=Edinburgh|isbn=9780443068188|pages=216, 308, 310–312|edition=2nd}}</ref> however this may not necessarily be the case for the underlying cause of immunocompromise. For instance, OHL with HIV/AIDS is a predictor of bad prognosis,<ref name="Scully 2008" /> (i.e. severe immunosuppression and advanced disease).<ref name="Neville 2002" />

==Epidemiology==
Hairy leukoplakia is one of the most common oral manifestations of HIV/AIDS, along with [[oral candidiasis]].<ref name="Scully 2008" /> It is the most common HIV/AIDS related condition caused by EBV, although EBV associated lymphomas may also occur.<ref name="Neville 2002" /> OHL mainly occurs in adult males, less commonly in adult females and rarely in children.<ref name="Chapple 2000" /> The incidence rises as the [[CD4]] count falls,<ref name="Chapple 2000" /> and the appearance of OHL may signify progression of HIV to AIDS.<ref name="Jung 1998">{{cite journal|last=Jung|first=AC|author2=Paauw, DS|title=Diagnosing HIV-related disease: using the CD4 count as a guide.|journal=Journal of General Internal Medicine|date=February 1998|volume=13|issue=2|pages=131–6|doi=10.1046/j.1525-1497.1998.00031.x|pmid=9502375|pmc=1496917}}</ref>  A study from 2001 reported a significant decrease in the incidence of some oral manifestations of AIDS (including OHL and [[Necrotizing periodontal diseases#Necrotizing ulcerative periodontitis|necrotizing ulcerative periodontitis]]), which was attributed to the use of HAART, whilst the incidence of other HIV-associated oral lesions did not alter significantly.<ref name="Cherry-Peppers 2003">{{cite journal|last=Cherry-Peppers|first=G|author2=Daniels, CO |author3=Meeks, V |author4=Sanders, CF |author5= Reznik, D |title=Oral manifestations in the era of HAART.|journal=Journal of the National Medical Association|date=February 2003|volume=95|issue=2 Suppl 2|pages=21S–32S|pmid=12656429|pmc=2568277}}</ref>

==History==
Oral hairy leukoplakia was first described by Greenspan ''et al.'' in 1984,<ref>{{cite journal|last=Greenspan|first=D|author2=Greenspan, JS|author3=Conant, M|author4=Petersen, V|author5=Silverman S Jr|author6=de Souza, Y|title=Oral "hairy" leucoplakia in male homosexuals: evidence of association with both papillomavirus and a herpes-group virus.|journal=Lancet|date=Oct 13, 1984|volume=2|issue=8407|pages=831–4|pmid=6148571|doi=10.1016/s0140-6736(84)90872-9|s2cid=7928436}}</ref><!-- landmark primary source included for use in history section only --> a few years after the start of the [[AIDS epidemic]]. A link with OHL was not initially reported as scientific understanding of HIV/AIDS was just beginning to develop at that time. It was subsequently thought to occur only in HIV-infected, homosexual males, however this is now known to not always be the case.<ref name="Chapple 2000" />

==Research directions==
It has been suggested that OHL be renamed according to its causative factor as “EBV leucoplakia”.<ref name="Chapple 2000" />

== References ==
{{Reflist}}

== External links ==
{{Medical resources
|   ICD10          = {{ICD10|K|13|3|k|00}}
|   ICD9           = {{ICD9|528.6}}
|   ICDO           =
|   OMIM           =
|   DiseasesDB     = 5594
|   MedlinePlus    =
|   eMedicineSubj  = med
|   eMedicineTopic = 938
|   MeshID         = D017733
}}
{{Oral pathology}}

{{DEFAULTSORT:Hairy Leukoplakia}}
[[Category:Conditions of the mucous membranes]]
[[Category:HIV/AIDS]]
[[Category:Epstein–Barr virus-associated diseases]]
[[Category:Oral mucosal pathology]]
[[Category:Tongue disorders]]