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Hairy Leukoplakia

Definition

Hairy Leukoplakia (HL) or Oral hairy Leukoplakia is a distinctive white coloured lesion of the oral mucosa.

Picture of Hairy Leukoplakia

Image source- Harrison’s principles of Internal Medicine

When the disease was first described in the 1980s, it was initially thought to be restricted and hence pathognomonic of HIV related immune suppression. The view held strong till 1990s when HL cases started to be reported in HIV seronegative patients as well. Now it is known that about 20% of lesions are seen in patients who are immunocompromised due to other reasons. But of late its occurrence has significantly decreased in relation to HIV because patients are now treated with aggressive antiretroviral chemotherapy.

Etiology and Pathophysiology

Hairy Leukoplakia has no established racial or age related predilection and is most commonly observed in homosexual HIV positive men.

Recent studies have frequently detected the presence of Ebstein-Barr virus (EBV) in immunofluorescence stained biopsy specimens from HL patients suggesting a causal association between the two. However the mere presence of EBV infection without significant immune compromise is not enough to cause hairy leukoplakia. Infection with Epstein Barr virus is quite widespread globally and the infection begins in the basal epithelial cells of the pharynx where the virus undergoes active replication and is then discharged into the saliva. As is typical of herpes viruses, it persists lifelong in the infected host. The virus initially remains dormant because though Cytotoxic T lymphocytes cannot eliminate the virus from the body; these prevent full blown disease. But when the immune system gets compromised, the number of EBV-specific Cytotoxic T lymphocytes declines allowing replication and resultant increase in number of circulating EBV-infected B cells. This finally leads to the development of HL.

In addition, HL biopsy tissues show a significant decrease or even absence of Langerhans cells (LC) which are the antigen-presenting immune cells required for an immune response to the viral infection their deficiency permits continued viral replication and hence EBV infection persists unchecked.

Diagram showing the EBV Replication cycle

In HIV positive patients, HL can be suspected when the CD4+ count is less than 500 cells/mm³ and the risk of developing this condition doubles with each 300 unit decrease in CD4+ count. High viral load is in itself has been linked to HL disease severity. Cigarette smoking (> 1pack/day) imparts a higher risk of HL in HIV positive homosexual men. Decrease in systemic immunity responsible for development of HL in non sero-positive patients can be due to cancer (including leukaemia) chemotherapy, post organ transplant immune-suppression and steroid therapy (e.g. in autoimmune conditions like Rheumatoid arthritis, SLE etc). Other less important risk factors for Hairy Leukoplakia include Behcet syndrome and Ulcerative Colitis.

Clinical features and Diagnosis of Hairy Leukoplakia

Hairy Leukoplakia is characterised by the presence of non-tender clusters of fluffy (hence the name “hairy”) hyperkeratotic thickening. These lesions may vary from smooth, flat, small lesions in mild cases to irregular ones of severe form which have vertical raised edges and prominent folds or projections (“corrugated /folded appearance”). The plaques are firmly adherent to the mucosa and not completely removable upon scraping (in contrast to Candidal Leukoplakia). Another distinguishing feature is the absence of underlying erythematic inflammation. Lesions may be either continuous or discontinuous, clustered along one or both sides of the tongue and they often are bilaterally asymmetrical unlike frictional keratosis. Less commonly other parts of the oral cavity may be involved. Extraoral manifestations are not seen.

Disease onset is usually missed by the patient due to lack of symptoms. The appearance may change daily and the lesions may appear or disappear spontaneously. Patients often consult doctor because of cosmetic disfiguration but few may experience symptoms like dysgeusia (alteration of taste sensation), dysesthesia (unpleasant sense of touch) and mild pain especially in the presence of concurrent Candida infection.

Before and while seeking medical attention, a patient should:

Write down the most pressing questions that have to asked.
Arrange the aid of another person to help ask questions and remember what the health-care provider advises including all important instructions regarding medicines and their dosage, tests and details of any follow-up appointment scheduled.
The Contact details of the health-care provider may be obtained.

When a doctor encounters white lesion of oral mucosa, certain pertinent issues must be taken into consideration.

The name Hairy “Leukoplakia” is a misnomer. HL is not a type of Leukoplakia. According to WHO Guidelines, Leukoplakia is diagnosed on the basis of exclusion i.e. all possible etiology for a white lesion of the mouth including HL have to be excluded. Furthermore, Leukoplakia is a pre-malignant condition while HL is benign with no documented risk for cancer and treatment for both is different.
HL closely resembles few other conditions which need to be excluded before confirming the diagnosis.

In most circumstances, the diagnosis of HL is made on the basis of clinical findings as shown below.

If the clinical diagnosis still remains in question, the investigator may order a Gram’s stain or potassium hydroxide (KOH) stain to identify Candidal Leukoplakia and histopathological assessment along with demonstration of EBV infection to rule out other disease etiology and definitively establish the diagnosis of HL. Immune-histochemical and in situ hybridization kits are commonly used for this purpose and tissue biopsy is reserved for lesions that have atypical feature and/or indicative of cancer.

Commonly seen histologic features of Hairy Lekuloplakia are:

Hyperparakeratosis of upper epithelial layer
Acanthosis in stratum spinosum with ballooning koilocyte-like cells. The nuclei have a homogenous ground-glass appearance and may contain Cowdry type A intranuclear inclusions.
Minimal or no inflammation in the epithelial and subepithelial tissues
Histologically normal basal epithelial layer

Presence of the afore-mentioned histologic findings suggest HL but in themselves are not sufficient for diagnosis which also requires the demonstration of EBV DNA, RNA or protein within epithelial cells of the lesion.