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Hairy Leukoplakia

Leukoplakia Hairy Oral

Hairy leukoplakia is a patch of white observed laterally on the tongue with a typical ridged appearance. It is associated with conditions leading to immunodeficiency and primarily AIDS syndrome and is mainly caused by the Epstein-Barr virus.


Leukoplakia involves white, flat, smooth, hairy-like patches forming at the sides of the tongue [9] and not necessarily in a symmetric fashion: both or only one side may be involved. These patches often produce no symptoms [5] and may go away and reappear automatically, also changing their appearance while they are present. They may either appear continuously or separately along the lateral sides of the tongue and can also expand to the ventral or dorsal side. Typically, scraping the lesions will produce no results, as it will only separate the superficial layers from the underlying ones; this feature differentiates hairy leukoplakia lesions from a candida infection. Regions where the paths have become thicker or stiffer may appear and, seldom, they can be observed on the pharynx or esophagus. Should symptoms be produced, these involve moderate pain [9] and unnatural sensation in the tongue and an impaired sense of taste. Other than the lesions themselves, the tongue exhibits no signs of inflammation and patients are many times concerned about aesthetic reasons [9] [10].

In cases where the patches appeared inflamed, red and raised, suspicion for an underlying malignancy should be raised, although this is a rare phenomenon.

  • Keywords: Exfoliative cytology, immunosuppressed, oral hairy leukoplakia Introduction The oral cavity presents with a plethora of manifestations of systemic pathologies.[ncbi.nlm.nih.gov]
  • Chest X-ray was suggestive of pulmonary tuberculosis but the sputum was repeatedly negative for AFB.[ijdvl.com]
Lesion of the Tongue
  • The patient was a 47-year-old woman with bilateral lesions on the tongue. The clinic and histologic appearances were typical of hairy leukoplakia, and Epstein-Barr virus was demonstrated in the epithelial cells by DNA in situ hybridization.[ncbi.nlm.nih.gov]
  • Hairy Leukoplakia, also known as Oral Hairy Leukoplakia, refers to a characteristic lesion of the tongue which manifests grossly as white patches with a corrugated ('hairy') appearance.[pathwaymedicine.org]
  • See also: leukoplakia hair·y leu·ko·pla·ki·a ( hār'ē lū'kō-plā'kē-ă ) White raised lesion seen on tongue, occasionally on buccal mucosa, in an immunocompromised host.[medical-dictionary.thefreedictionary.com]
  • A 29-year-old man presented with non-painful white lesions on his tongue that he had recently noticed while brushing his teeth. Testing for oral candidal infection by his general practitioner was negative.[cmaj.ca]
Hairy Tongue
  • Even though its name is similar to the one of hairy tongue, these two should not be confused. Oral hairy leukoplakia and hairy tongue are two separate medical conditions, with different symptoms and treatments.[mddk.com]
  • Hairy leukoplakia occurs on the tongue and has a similar name to hairy tongue, but these are separate conditions with different causes.[en.wikipedia.org]
  • Hairy tongue (keratin accumulation on the tips of the filiform papillae) – This generally involves the dorsum of the tongue only, where filiform papillae are located.[visualdx.com]
  • It is distinct from other condition of the oral mucosa such as the oral thrush or hairy tongue as the white patches in hairy leukoplakia cannot be wiped off from the tongue.[healthh.com]
Decreased Renal Function
  • Intravenous acyclovir may precipitate in the kidney and decrease renal function, so renal function tests should be followed. HIV-positive individuals also may develop true precancerous or cancerous leukoplakia like oral lesions.[derm101.com]


Hairy leukoplakia can be diagnosed either by a histologic examination of a biopsy specimen retrieved from the tongue, or by a cytologic examination of superficial cells [11]. As far as histopathological features are concerned, the most typical findings in patients with hairy leukoplakia include the following 5 characteristics [12]:

  • Hyperkeratosis of the superficial layer, which is responsible for the hairy-like appearance of the lesions. The epithelial layer which has been subject to hyperkeratosis may additionally sustain infections with Candida or other bacteria; these conditions remain superficial.
  • Parakeratosis in the superficial layer, with retention of the cellular nuclei in the layer. 
  • Acanthosis of the stratum spinosum, regarding the epithelial mid-layer. Cells expand and appear with a typical ground-glass presentation and Cowdry type A intranuclear bodies.  
  • No signs of inflammation or insignificant inflammation.
  • Normal histologic findings regarding the basal cells of the epithelium.

A definitive diagnosis of hairy leukoplakia cannot be established with the aforementioned observations alone, as none is pathognomonic to the condition. Matching histologic and cytologic findings, alongside the confirmation of an EBV infection are necessary for such a diagnosis. However, these procedures are likely not to be performed, as they are reserved only for patients with a suspected underlying malignancy.

Normal Chest X-Ray
  • Radiological and scan examination of head and abdomen were normal. Chest X-ray was suggestive of pulmonary tuberculosis but the sputum was repeatedly negative for AFB.[ijdvl.com]
Intranuclear Inclusion Bodies
  • Third, the ground glass intranuclear inclusion bodies consisted of central, medium electron-dense, finely granular material containing frequent herpesvirus nucleocapsids and partially surrounded or capped by prominent, clumped chromatin.[ncbi.nlm.nih.gov]


Since hairy leukoplakia arises as a result of a persistent EBV infection on the grounds of immunosuppression and none of the two conditions can be eradicated, it is not expected to respond long-term well to therapeutic measures. Antiviral agents are administered, which resolve the condition within 1 or 2 weeks [13], including acyclovir (800 mg, 5 times per day [14]), valacyclovir (3 times per day, 1g) and famcyclovir (500 mg, 3 times a day). These agents hinder the reproduction of EBV, reducing the infection to a state of latency.

Podophyllin resin solution can also be applied locally, even though it may cause pain and taste impairment and patients relapse after several weeks [15]. Patients with smaller lesions can be candidates for ablation therapy and cryotherapy has also produced positive results, remaining, however, limited in use [16].

The administration of HAART (highly active antiretroviral therapy) against the HIV virus has succeeded in decreasing the number of patients who develop hairy leukoplakia.


The prognosis of patients exhibiting hairy leukoplakia is directly related to their CD4 T count. Even though almost all patients exhibit a considerable degree of immunodeficiency when the condition is diagnosed, patients' CD4 T count usually ranges from 235 to 468 per cubic milliliter. In individuals with a count greater or equal to 300, the average survival time is expected to be 25 months. On the contrary, patients with normal counts are expected to have a median survival of 52 months. In general, hairy leukoplakia is first detected after HIV antibodies have started to be produced and the average survival time of all patients is estimated to be around 20 months upon diagnosis.


Hairy leukoplakia is believed to be a result of the Epstein-Barr virus, one of the viruses belonging to the group of Herpesviridae (or herpes viruses) [3]. It is transferred from one person to another and it is an extremely common virus which affects a staggering percentage of worldwide population. During the period of adolescence or early adulthood, the EB virus causes mononucleosis.

EBV typically remains dormant in a person's organism after the very first infection. If the immune system is weakened, such as in HIV-positive individuals who are moderately or severely immunodeficient, the Epstein-Barr virus is reactivated, causing the oral infection known as hairy leukoplakia [4].


Hairy leukoplakia is one of the most frequent complications of a HIV infection, with the point prevalence amounting to 25% amongst HIV-positive individuals [5]. As far as the risk factors for developing hairy leukoplakia on the grounds of HIV are concerned, it is believed that male sex and a smoking habit increase the possibility of exhibiting it [6]. 

A definitive connection between the CD4 T count and the onset of hairy leukoplakia has yet to be established; it is generally known that it can also arise in patients with a CD4 T count greater than 500 cells/cubic millimeter. New radical antiretroviral therapies alongside medications against the herpesviridae have contributed to the decline of hairy leukoplakia prevalence amongst HIV patients.

Sex distribution
Age distribution


All herpesviruses infect the host for the latter's entire life and EBV is no exception. The pharyngeal basal epithelial cells are the first to be infected by the virus; as it reproduces within the cells, it also infiltrates type B white cells, where it is harbored. Cytotoxic T lymphocytes are unable to exterminate the virus, but do, however, contribute greatly to the preservation of the latency state of the virus. This is why defects of the immune system leading to a decrease in the cytotoxic lymphocytes' number cause a reactivation of EBV.

The Epstein-Barr virus can be found throughout the world and is one of the most common viral agents, infecting approximately 90% of the population. Hairy leukoplakia is itself caused by a reactivation of EBV in immunosuppressed patients, following a complex pathogenetic path. It is believed that this reactivation is facilitated when a person is infected anew by EBV. Other researchers have suggested that the viral genome evolves to escape eradication and that specific genes contribute to its latency period. Findings that reveal a diminished number of Langerhans cells in biopsy specimens from hairy leukoplakia patients further illustrate how the virus escapes eradication mechanisms, given the antigen-presentation ability of these cells [7] [8]. At any case, both systemic and local host immunosuppression are vital factors, contributing to the viral regeneration pattern [3].


Maintaining an immune system that is as potent as possible is the key to avoiding hairy leukoplakia. Patients need to follow their drug regimen responsibly, eat healthy, quit smoking, exercise regularly and use protection when engaging in sexual intercourse. A doctor or healthcare provider is the person responsible for deciding on a therapeutic plan and for making any adaptation needed.


Hairy leukoplakia is a medical condition which causes white lesions with hairy-like features, appearing at the sides of the tongue. It is caused by the Epstein-Barr virus (EBV). After the initial EBV infection, the virus displays a latency feature, namely it remains in the organism without causing any type of symptomatology, only to be reactivated under certain circumstances: a potential compromise of the immune system. This is why hairy leukoplakia is mainly associated with the HIV infection and more specifically, the AIDS syndrome or AIDS-related complex (ARC). 

Other circumstances, under which a reactivation of EBV and subsequently hairy leukoplakia could occur, include organ transplants and the administration of chemotherapy [1] [2]. A patient is rendered immunodeficient and the ground is fertile for the EB virus to be regenerated.

Hairy leukoplakia is a non-malignant condition and it is sometimes an indication of unsuccessful HIV treatment. It can also be the first sign of immunocompromise due to an undiagnosed HIV infection or a sign of a secondary infection. At any case, it is a marker whose appearance shows that the immune system is impaired.

Patient Information

Hairy leukoplakia is a condition which causes white patches to appear at the sides of the tongue, which exhibit a characteristic hairy-like appearance. They arise when a person's immune system is weak and are mainly associated with an HIV infection or other causes of immunodeficiency.


The Epstein-Barr (EBV) virus is believed to be responsible for the onset of hairy leukoplakia. EBV infects a person and then remains in their organism indefinitely. The virus can be reactivated when the carrier has a weak immune system and hairy leukoplakia emerges. Conditions that cause immunosuppression involve HIV (primarily) and people with autoimmune diseases (eg. ulcerative colitis) or those who have received transplants.

Men with a weakened immune system and particularly those who smoke run a higher risk of developing hairy leukoplakia than women.


Hairy leukoplakia could be the first indication that a person has been infected with the HIV virus and that their immune system is declining. Typical manifestations include white patches that appear either on both sides of the tongue or on one only. The patches are usually not painful and appear as though covered by short hair. In some locations, those lesions may appear thicker or harder and they can rarely be observed on the pharynx too. If the lesions start to be painful, a doctor should be promptly consulted, as an underlying cancer may be present.

The white hairy patches may be easily mistaken for a Candida infection, which is a fungal infection and very distinct to hairy leukoplakia.


Hairy leukoplakia can be diagnosed by a biopsy, a cell sample brushed off the tongue and further examinations. Not every patient needs to undergo all these procedures and most are diagnosed with clinical criteria. If a person is a known HIV-positive patient or has any other type of diagnosed immunodeficiency, the doctor will proceed to treating hairy leukoplakia. If an otherwise healthy individual exhibits the white lesions, they need to be examined in order to determine what lead to such a disease.


Hairy leukoplakia is, in the majority of the cases, a direct result of an underlying immunodeficiency. Therefore, treating it alone is like treating the symptom and not the disease. In order to potentially eliminate the lesions and provide a patient with better standards of living, the cause of immunodeficiency must be treated. In cases of HIV or AIDS, strong antiviral agents are administered, which hinder the reproduction of the HIV virus and help to exterminate hairy lesions. Other antiviral drugs like acyclovir, ganciclovir or valacyclovir can be administered to treat the symptom, if the patients are not treated for HIV and the lesions cause problems with taste or pain. Antifungal drugs also help treat co-infection with Candida.



  1. Arley SJ, Nikolaos GN; Valli M, et al. Oral hairy leukoplakia as a sign of HIV infection. Brazilian Journal of Oral Sciences. 2004; pp. 628-632.
  2. Schmidt-Westhausen A, Gelderblom HR, et al. Oral hairy leukoplakia in an HIV-seronegative heart transplant patient. J Oral Pathol Med. 1990 Apr; 19(4):192-4.
  3. Sachithanandham J, Kannangai R, Pulimood SA, et al. Significance of Epstein-Barr virus (HHV-4) and CMV (HHV-5) infection among subtype-C human immunodeficiency virus-infected individuals. Indian J Med Microbiol. 2014 Jul-Sep; 32(3):261-9.
  4. Miziara ID, Weber R. Oral candidosis and oral hairy leukoplakia as predictors of HAART failure in Brazilian HIV-infected patients. Oral Dis. 2006 Jul; 12(4):402-7.
  5. Reichart PA, Langford A, Gelderblom HR, et al. Oral hairy leukoplakia: observations in 95 cases and review of the literature. J Oral Pathol Med. 1989; 18:410-415.
  6. Boulter AW, Soltanpoor N, Swan AV, et al. Risk factors associated with Epstein-Barr virus replication in oral epithelial cells of HIV-infected individuals. AIDS. 1996; 10:935-940.
  7. Daniels TE, Greenspan D, Greenspan JS, et al. Absence of Langerhans cells in oral hairy leukoplakia, an AIDS-associated lesion. J Invest Dermatol. 1987 Aug; 89(2):178-82.
  8. Gondak RO, Alves DB, Silva LF, et al. Depletion of Langerhans cells in the tongue from patients with advanced-stage acquired immune deficiency syndrome: relation to opportunistic infections. Histopathology. 2011 Dec 14.
  9. Greenspan D, Greenspan JS, Conant M, et al. Oral "hairy" leukoplakia in male homosexuals: Evidence of association with both papillomavirus and a herpes-group virus. Lancet. 1984; 2:831-834.
  10. Greenspan JS, Greenspan D. Oral hairy leukoplakia: diagnosis and management. Oral Surg Oral Med Oral Pathol. 1989;6 7:396-403.
  11. De Souza YG, Freese UK, Greenspan D, et al. Diagnosis of Epstein-Barr virus infection in hairy leukoplakia by using nucleic acid hybridization and noninvasive techniques. J Clin Microbiol. 1990; 28:2775-2778.
  12. Eversole LR, Jacobsen P, Stone CE, et al. Oral condyloma planus (hairy leukoplakia) among homosexual men: a clinicopathologic study of thirty-six cases. Oral Surg Oral Med Oral Pathol. 1986; 61:249-255.
  13. Schofer H, Ochsendorf FR, Helm EB, et al. Treatment of oral 'hairy' leukoplakia in AIDS patients with vitamin A acid (topically) or acyclovir (systemically). Dermatologica. 1987; 174(3):150-1.
  14. Resnick L, Herbst JS, Ablashi DV, eet al. Regression of oral hairy leukoplakia after orally administered acyclovir therapy. JAMA. 1988 Jan 15; 259(3):384-8.
  15. Brasileiro CB, Abreu MH, Mesquita RA. Critical review of topical management of oral hairy leukoplakia. World J Clin Cases. 2014 Jul 16; 2(7):253-6.
  16. Goh BT, Lau RK. Treatment of AIDS-associated oral hairy leukoplakia with cryotherapy. Int J STD AIDS. 1994 Jan-Feb; 5(1):60-2.

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Last updated: 2019-07-11 21:31