January 17, 2007

Hairy Leukoplakia

Synonyms and related keywords: oral hairy leukoplakia, OHL, AIDS, HIV, Epstein-Barr virus, EBV, immunosuppression, immunocompromise, homosexual men, IV drug users


Background: Oral hairy leukoplakia (OHL) is an oral mucosal disease that first was described in 1984. It is associated with Epstein-Barr virus (EBV) and occurs almost exclusively in patients who are immunocompromised, particularly those infected with HIV.

Pathophysiology: Affected mucosa has diminished numbers of Langerhans cells and T-helper cells. Keratinocytes do not contain HIV, but EBV receptors have been detected in surrounding normal mucosa. Whether OHL develops after superinfection with EBV or activation of latent infection due to reduced immune surveillance is not known. Latent membrane protein-2 (LMP-2) may regulate reactivation from latency by interfering with normal B-cell signal transduction processes, which may be important for viral persistence. Multiple strains of EBV have been demonstrated in OHL lesions.



Race: No racial predilection has been established.

Sex: OHL is observed more commonly in homosexual men who are HIV positive. In one study, OHL was observed in 6.1% of women who were HIV positive.

Age: No age predilection has been established.


History: Patients may complain of nonpainful white plaque along the lateral tongue borders. The appearance may change daily.




Condyloma Acuminatum

Other Problems to be Considered:

Frictional keratosis
Squamous cell carcinoma
Geographic tongue
Lichen planus
Tobacco-associated leukoplakia
Human papillomavirus (HPV)–induced neoplasia
Condyloma acuminatum
Syphilitic mucous patch

White oral lesions resembling OHL have been observed in patients negative for both HIV and EBV. Yeast and bacteria may be present but do not contribute to the process. Candida (thrush) is common in immunodeficient persons, is not adherent, is more generalized, and may be painful. Frictional keratosis (from rubbing upon poorly fitting dental work or jagged teeth) may appear similar but is usually unilateral.


Lab Studies:


Histologic Findings: The mucosal epithelium is acanthotic and hyperkeratotic, with occasional parakeratosis. Vacuolated keratinocytes are evident in the spinous layer only, a key to histopathologic diagnosis. Cowdry type A nuclear inclusions may be observed in vacuolated cells.

Electron microscopy demonstrated 100-nm intranuclear virions and 240-nm encapsulated virus particles.


Medical Care:

Consultations: Consultations with dermatologists or infectious disease specialists may be in order depending upon the underlying disease process resulting in OHL.

Diet: Diet may be as tolerated.


OHL is rarely treated. Painful superinfection with Candida can be addressed with nystatin and other antifungals. Recurrence is frequent and requires periodic retreatment. Symptomatic patients have been treated with podophyllum resin. Acyclovir, valacyclovir, famciclovir, ganciclovir, or foscarnet are often effective therapies for EBV and, therefore, OHL. Institution of HAART, now standard care in the United States, is also useful. See Early Symptomatic HIV Infection and Acquired Immunodeficiency Syndrome (AIDS).

Drug Category: Antifungals -- These agents reduce Candida superinfection.
Drug Name
Nystatin (Nilstat, Mycostatin, Nystex) -- Fungicidal and fungistatic antibiotic obtained from Streptomyces noursei; effective against various yeasts and yeastlike fungi. Changes permeability of fungal cell membrane after binding to cell membrane sterols, causing cellular contents to leak.
Treatment should continue until 48 h after disappearance of symptoms. Drug is not absorbed significantly from GI tract.
Adult Dose200,000 U lozenges; 1-2 lozenges, 4-5 times daily
Pediatric DoseAdminister as in adults
ContraindicationsDocumented hypersensitivity
InteractionsNone reported
Pregnancy C - Safety for use during pregnancy has not been established.
PrecautionsDo not use to treat systemic mycoses
Drug Category: Antiviral agents -- Nucleoside analogs initially are phosphorylated by viral thymidine kinase to eventually form a nucleoside triphosphate.
Drug Name
Podophyllum resin (Pod-Ben-25, Podofin, Podocon-25) -- Arrests mitosis in metaphase; active agent is podophyllotoxin; type of podophyllum resin used determines strength. American podophyllum contains one fourth the amount of Indian source. Used in symptomatic OHL.
Adult DoseApply 25% liquid for 20 min
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity; diabetes; impaired peripheral circulation; avoid use on mucous membranes, eyes, bleeding warts, moles, birthmarks, or unusual warts with hair
InteractionsNone reported
Pregnancy X - Contraindicated in pregnancy
PrecautionsPowerful caustic and severe irritant; do not use if surrounding tissue swollen or irritated; 25% solution should not be applied near mucous membranes; do not use large amounts; avoid contact with cornea; avoid use on mucous membranes, eyes, bleeding warts, moles, birthmarks, or unusual warts with hair
Drug Name
Acyclovir (Zovirax) -- Has affinity for viral thymidine kinase and, once phosphorylated, causes DNA chain termination when acted on by DNA polymerase. Patients experience less pain and faster resolution of lesions when used within 48 h from onset of outbreak. May prevent recurrent outbreaks. Early initiation of therapy is imperative.
Adult Dose400 mg PO bid/qid
Pediatric Dose20-40 mg/kg bid
ContraindicationsDocumented hypersensitivity
InteractionsProbenecid or zidovudine prolongs half-life and increases CNS toxicity
Pregnancy B - Usually safe but benefits must outweigh the risks.
PrecautionsCaution in renal failure or when using nephrotoxic drugs
Drug Name
Valacyclovir (Valtrex) -- Prodrug rapidly converted to active drug acyclovir. More expensive but has more convenient dosing regimen than acyclovir.
Adult Dose1 g/d PO tid
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity
InteractionsProbenecid, zidovudine, or cimetidine prolongs half-life and increases CNS toxicity
Pregnancy B - Usually safe but benefits must outweigh the risks.
PrecautionsCaution in renal failure and coadministration of nephrotoxic drugs; associated with onset of hemolytic uremic syndrome
Drug Name
Famciclovir (Famvir) -- Pro-drug that when biotransformed into active metabolite, penciclovir, may inhibit viral DNA synthesis/replication.
Adult Dose500 mg/d PO bid
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity
InteractionsProbenecid or cimetidine may increase toxicity; increases bioavailability of digoxin
Pregnancy B - Usually safe but benefits must outweigh the risks.
PrecautionsCaution in renal failure or coadministration of nephrotoxic drugs
Drug Name
Ganciclovir (Cytovene, Vitrasert) -- Indication is for CMV retinitis and prevention of CMV infection in individuals who are HIV positive.
Adult Dose1000 mg PO tid
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity
InteractionsCytotoxic drugs such as dapsone, vinblastine, doxorubicin, pentamidine, flucytosine, vincristine, amphotericin B, trimethoprim/sulfamethoxazole combinations, or other nucleoside analogs may result in additive toxicity in bone marrow, spermatogonia, and germinal layers of skin and GI mucosa (coadminister only if potential benefits outweigh risks); imipenem-cilastatin may cause generalized seizures (use only if potential benefits outweigh risks); cyclosporine or amphotericin B may increase serum creatinine; probenecid reduces renal clearance; administration of didanosine either 2 h prior to or simultaneously may increase bioavailability; zidovudine may decrease bioavailability, while ganciclovir increases bioavailability of zidovudine
Pregnancy C - Safety for use during pregnancy has not been established.
PrecautionsClinical toxicity includes granulocytopenia, anemia, and thrombocytopenia; since oral ganciclovir associated with higher rate of CMV retinitis progression than IV formulation, use only when benefits outweigh risks (advanced HIV disease); half-life and plasma/serum concentrations may be increased as result of reduced renal clearance; dosages >6 mg/kg IV may result in increased toxicity; rapid infusions may result in increased toxicity; initially, reconstituted solutions of IV ganciclovir have a high pH (11); phlebitis or pain may occur at site of IV infusion despite further dilution in IV fluids; administration should be accompanied by adequate hydration; photosensitization (photoallergy or phototoxicity) may occur
Drug Name
Foscarnet (Foscavir) -- Indicated only for acyclovir-resistant mucocutaneous herpes simplex virus, which occurs almost exclusively in individuals who are HIV positive.
Adult Dose40 mg/kg IV tid
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity
InteractionsPotentially nephrotoxic drugs (eg, aminoglycosides, amphotericin B, IV pentamidine) may increase nephrotoxicity (do not administer unless potential benefits outweigh risks); IV pentamidine may cause hypocalcemia
Pregnancy C - Safety for use during pregnancy has not been established.
PrecautionsMay cause decline in renal function; for correct dosing, obtain 24-h serum creatinine at baseline and continue to monitor (discontinue if serum creatinine less than 0.4 mL/min/kg); hydration may reduce nephrotoxicity
Carefully monitor electrolytes (eg, calcium, magnesium); assess for electrolyte and mineral level abnormalities if mild perioral numbness, paresthesia symptoms, or seizures; granulocytopenia and anemia may occur (regularly monitor CBC)
Infuse foscarnet solutions into veins with adequate blood flow to avoid local irritation; to avoid toxicity do not administer by rapid or bolus IV injection





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