eMedicine Specialties > Oncology > none

Hairy Leukoplakia

Author: Olga Kozyreva, MD, Staff Physician, Hematology Oncology Department, Tufts University School of Medicine
Coauthor(s): Sarah K May, MD, Consulting Staff, Department of Hematology-Oncology, Caritas Carney Hospital, Commonwealth Hematology-Oncology PC; Samer A Bleibel, MD, Staff Physician, Department of Internal Medicine, Wayne State University, St John's Hospital and Medical Centers; Hunter H Sams, MD, Consulting Staff, Denver Dermatology Consultants, PC; Alan Boyd, MD, Associate Professor, Department of Medicine, Division of Dermatology, Vanderbilt University
Contributor Information and Disclosures

Updated: Jul 18, 2007

Introduction

Background

Oral hairy leukoplakia (OHL) is a disease of the mucosa first described in 1984. This pathology is associated with Epstein-Barr virus (EBV) and occurs mostly in people with HIV, both immunocompromised and immunocompetent, albeit it can affect patients who are HIV negative. The first case in an HIV-negative patient was reported in 1999 in a 56-year-old patient with acute lymphocytic leukemia. Later, many cases have been reported in heart, kidney, and bone marrow transplant recipients and patients with hematological malignancies.

Pathophysiology

The Epstein-Barr virus (EBV), a ubiquitous herpesvirus estimated to infect 90% of the world's population, has been linked to a growing number of diseases, especially in immunocompromised hosts. Like all herpesviruses, EBV establishes a life-long, persistent infection of its host. The pathogenesis of hairy leukoplakia is clearly complex, potentially requiring a convergence of factors including EBV co-infection, productive EBV replication, EBV genetic evolution, expression of specific EBV "latent" genes, and immune escape. All of these factors are likely facilitated by local and systemic host immunodeficiency.

The virus initially infects basal epithelial cells in the pharynx, where it enters a replicative state leading to the release of infectious virus into the saliva throughout the life of the infected person. In the pharynx, the virus also enters B cells, where it persists indefinitely in a latent state. Cytotoxic T lymphocytes cannot eliminate EBV from the body, but they are essential in maintaining the latent state of the infection. In states of immune dysfunction in which the number of EBV-specific cytotoxic T lymphocytes is decreased, there is an increase in the number of circulating EBV-infected B cells.

In addition, there is a marked decrease or an absence of Langerhans cells in hairy leukoplakia biopsy tissues. Langerhans cells are the antigen-presenting immune cells that are required for an immune system response to the viral infection and their deficiency may permit EBV to persistently replicate and escape immune recognition.

Frequency

United States

Hairy leukoplakia is one of the most common virally-induced, oral diseases of HIV infected individuals with a point prevalence as high as 25%-53%.1 The 6-year incidence of OHL in this patient population was reported to be around 32%. A significant trend to a lower prevalence was observed in the group of patients who were already taking antiretroviral therapy, non-HAART and HAART (p < 0.001 and p = 0.004, respectively).2

Fewer cases of OHL have been reported in non-HIV patients. This is probably due to underdiagnosis and underreporting of this disease in patients with hematological malignancies or solid organ transplantation. Some studies have shown the prevalence of OHL in renal transplant recipients to be more than 11%.

International

The incidence of OHL is similar to that in the United States and thereby reflects the prevalence of HIV.
In populations where the prevalence of HIV is low, oral mucosal lesions alone are poor predictors of HIV infection.3

Mortality/Morbidity

In patients with HIV, the median CD4 count when OHL is first detected is 468/µL. If these patients do not have AIDS-defining disease at the time OHL is diagnosed, the probability of developing AIDS if not receiving highly active antiretroviral therapy (HAART) is 48% by 16 months and 83% at 31 months. In addition, studies have shown that patients with AIDS with OHL have a shorter lifespan than those that do not present this lesion. Furthermore, if these patients are concomitantly co-infected with hepatitis B virus, the risk of early progression to AIDS increases 4-fold.

Race

No racial predilection has been established.

Sex

OHL is most commonly observed in homosexual men who are HIV positive, especially in those who smoke.

Age

No age predilection has been established.

Clinical

History

Patients may report a nonpainful white plaque along the lateral tongue borders. The appearance may change daily. The natural history of hairy leukoplakia is variable. Lesions may frequently appear and disappear spontaneously. Hairy leukoplakia is often asymptomatic, and many patients are unaware of its presence. Some patients with hairy leukoplakia do experience symptoms including mild pain, dysesthesia, alteration of taste, and the psychological impact of its unsightly cosmetic appearance.

Physical

Unilateral or bilateral nonpainful white lesions can be seen on the margins, dorsal or ventral surfaces of the tongue, or on buccal mucosa. The lesions may vary in appearance from smooth, flat, small lesions to irregular "hairy" or "feathery" lesions with prominent folds or projections.

Lesions may be either continuous or discontinuous along both tongue borders, and they are often not bilaterally symmetric. Lesions are adherent, and only the most superficial layers can be removed by scraping. There is no associated erythema or edema of the surrounding tissue. Hairy leukoplakia may also involve dorsal and ventral tongue surfaces, the buccal mucosa, or the gingiva. On the ventral tongue, buccal mucosa, or gingiva, the lesion may be flat and smooth, lacking the characteristic "hairy" appearance.

Causes

OHL has been associated with HIV infection and/or immunosuppression.4 The risk of developing OHL doubles with each 300-unit decrease in CD4 count. A high viral load was strongly associated to the oral lesions occurrence independently of CD4+ cell count.1 More recently, it has been described in patients with other forms of severe immunodeficiency including those associated with chemotherapy, organ transplant, and leukemia. Rarely, it may occur in patients who are immunocompetent.

OHL also has been described in association with Behçet syndrome and ulcerative colitis.

Smoking more than a pack of cigarettes a day is positively correlated with the development of OHL in HIV positive men.

No increase in OHL was observed when controlled for number of oral sex partners.

More on Hairy Leukoplakia

Overview: Hairy Leukoplakia
Differential Diagnoses & Workup: Hairy Leukoplakia
Treatment & Medication: Hairy Leukoplakia
Follow-up: Hairy Leukoplakia
References
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References

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Further Reading

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Keywords

oral hairy leukoplakia, OHL, AIDS, HIV, Epstein-Barr virus, EBV, immunosuppression, immunocompromise, homosexual men, IV drug users, acute lymphocytic leukemia, ALL, heart transplant, bone marrow transplant, kidney transplant, hematological malignancy, tongue plaque, Behçet syndrome, ulcerative colitis, cigarette smoking

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Contributor Information and Disclosures

Author

Olga Kozyreva, MD, Staff Physician, Hematology Oncology Department, Tufts University School of Medicine
Disclosure: Nothing to disclose.

Coauthor(s)

Sarah K May, MD, Consulting Staff, Department of Hematology-Oncology, Caritas Carney Hospital, Commonwealth Hematology-Oncology PC
Sarah K May, MD is a member of the following medical societies: American Society of Clinical Oncology
Disclosure: Nothing to disclose.

Samer A Bleibel, MD, Staff Physician, Department of Internal Medicine, Wayne State University, St John's Hospital and Medical Centers
Samer A Bleibel, MD is a member of the following medical societies: American College of Physicians
Disclosure: Nothing to disclose.

Hunter H Sams, MD, Consulting Staff, Denver Dermatology Consultants, PC
Hunter H Sams, MD is a member of the following medical societies: American Academy of Dermatology and American Academy of Family Physicians
Disclosure: Nothing to disclose.

Alan Boyd, MD, Associate Professor, Department of Medicine, Division of Dermatology, Vanderbilt University
Alan Boyd, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, and American Society of Dermatopathology
Disclosure: Nothing to disclose.

Medical Editor

Sanjiv S Agarwala, MD, Associate Professor of Medicine, Division of Hematology and Oncology, University of Pittsburgh School of Medicine; Associate Chief, University of Pittsburgh Cancer Institute
Sanjiv S Agarwala, MD is a member of the following medical societies: American Association for Cancer Research, American Society for Head and Neck Surgery, American Society of Clinical Oncology, Eastern Cooperative Oncology Group, and European Society for Medical Oncology
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

CME Editor

Rajalaxmi McKenna, MD, FACP, Consulting Staff, Department of Medicine, Southwest Medical Consultants, SC, Good Samaritan Hospital, Advocate Health Systems
Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis
Disclosure: Nothing to disclose.

Chief Editor

Jules E Harris, MD, Visiting Professor of Medicine, Division of Hematology/Medical Oncology, Department of Internal Medicine, University of Arizona College of Medicine at Tucson; Consulting Staff, Arizona Cancer Center
Jules E Harris, MD is a member of the following medical societies: American Association for Cancer Research, American Association for the Advancement of Science, American Association of Immunologists, American Federation for Clinical Research, American Society of Clinical Oncology, American Society of Hematology, Central Society for Clinical Research, Society for Biological Therapy, and Society for Leukocyte Biology
Disclosure: GlobeImmune Salary Consulting; Amplimed Consulting fee Consulting

 
 
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