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Oral Hairy Leukoplakia

Key Points

  • OHL is caused by infection with Epstein-Barr virus (EBV), and usually presents as corrugated white plaques of the lateral tongue.
  • OHL is a clinical manifestation of immunosuppression and classically presents in the setting of HIV infection.
  • OHL is a chronic condition that is managed over time rather than cured. Therapy is only indicated if it is symptomatic.

Introduction

Oral hairy leukoplakia (OHL) has to date been pathognomonic of immunosuppression usually due to HIV infection. In one series, it was present in 11.5% of HIV-infected individuals, designating it as the fourth most common oral manifestation in this population after oral candidiasis (39.3%), melanotic hyperpigmentation (19.5%), and oral ulcers (11.8%). Other studies investigating oral manifestations in this population have determined a lower prevalence in the range of 0.33-2.7%. OHL is caused by reactivation of Epstein-Barr virus (EBV), a virus that infects up to 90% of all adults, though commonly asymptomatic in immunocompetent hosts. It is classically an opportunistic infection of HIV-infected individuals; risk of reactivation increases with elevated viral load and reduced CD4 lymphocyte count. OHL has also been described in other immunocompromised individuals, including patients with hematologic malignancy, persons undergoing chemotherapy, and organ transplant recipients. Increased numbers of EBV-infected B cells and reduced numbers of EBV-specific cytotoxic T cells noted in biopsies of OHL, in addition to the absence or reduced number of Langerhans cells, suggest key immunologic factors associated with viral reactivation in affected lesions.

Clinically, OHL typically presents as vertically corrugated white lesions of the lateral tongue. It may be unilateral or bilateral, and may also affect the dorsal or ventral tongue, gingiva, or oral mucosa. Lesions of OHL may appear as smooth white papules or plaques with a broad range of morphologic variation, including corrugation or papillated surfaces. A key feature distinguishing OHL from common oral mucosal diseases such as candidiasis is that OHL is firmly adherent to the mucosal or tongue surface, whereas lesions stemming from candida are relatively easily removed by a scalpel blade. A second distinguishing feature of OHL is that there is typically an absence of erythema or inflammation underlying the white papules or plaques. It is characteristically asymptomatic, though patients may complain of dysgeusia, dysesthesia, mild pain, or concerns regarding cosmetic appearance. Biopsy reveals characteristic histopathologic features including epithelial hyperkeratosis with papillomatosis, acanthosis, and ballooning degeneration within the epidermis. Viral changes can also be noted and also detected by immunohistochemistry or by in situ hybridization. Since the EBV infection is chronic and lifelong, therapy will clear but will not cure lesions, and OHL will usually reappear once treatment is stopped. Therapy is usually not indicated, as OHL is asymptomatic and may remit spontaneously in 10% of cases. OHL will also resolve in association with immune reconstitution due to anti-retroviral medications. Pseudo-OHL is clinically similar but does not contain EBV, allowing differentiation by histological examination.

Initial Evaluation

Oral hairy leukoplakia

Differential diagnosis

Oral candidiasis

Geographic tongue

Syphilitic mucous patches

Oral Graft-versus-host-disease

Lichen planus of the tongue

Treatment

First-line therapy: All patients suspected of having OHL should first be evaluated by KOH preparation to exclude a diagnosis of oral candidiasis as well as consideration of a cause for immunocompromise or immunosuppression in the affected patient. OHL and oral candidiasis may also occur concurrently in any given patient.

  • Patients with OHL must be evaluated for the presence of HIV infection and other forms of immunosuppression if HIV tests are negative. Successful HIV treatment with anti-retroviral medications will likely result in resolution of OHL.
  • In addition, treat the frequently associated thrush, if present, with clotrimazole troches (first-line) or oral nystatin suspension.
  • Topical tretinoin 0.1% cream (such as Atralin, Avita, Refissa, Renova, Retin-A, Retin-A Micro), adapalene cream (such as Differin), or tazarotene (such as Tazorac) may be applied twice daily. Topical acyclovir ointment applied to the lesion 4 times daily may also result in resolution of lesions.

Alternative therapy

  • Oral acyclovir 2.0 to 3.2 g per day (400 mg 5 times daily, or 800 mg 4 times daily) for 10-14 days. OHL will resolve with intravenous acyclovir, but this is rarely indicated.
  • Chronic suppression with retinoic acid or topical acyclovir may be used. However, as OHL is totally asymptomatic and hidden, suppressive therapy has no proven benefit.

Pitfalls

  • Failure to evaluate for HIV infection or other cause of immunocompromise.
  • Side effects from oral acyclovir are rare. They include rashes and mild GI upset. 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. The diagnosis of OHL should be considered only when in its characteristic location (lateral tongue bilaterally). A biopsy is required to establish the diagnosis of OHL when seen at other locations in the oral cavity.
  • Epstein-Barr virus serologies play no role in the management or diagnosis of OHL.

Clinical Case

Case 1

  • 37-year-old male with recent diagnosis of HIV infection
  • Not yet started on anti-retroviral medications
  • Elevated viral load and reduced CD4 lymphocyte count (240)
  • Presents for evaluation and management of long-standing “tongue ulcers” with concern for herpes simplex virus or candidal infection

Initial evaluation

  • Thin appearing adult male
  • Bilateral tongue with thick, adherent white hyperkeratotic corrugated plaques without underlying erythema or edema
  • No evidence of oral candidiasis on exam – KOH preparation is negative
  • Topical tretinoin cream b.i.d. to affected areas
  • Referral to HIV primary care for evaluation and consideration of restart of anti-retroviral regimen
  • Follow-up in four weeks (moderately improved)

Bodhade AS, Ganvir SM, Hazarey VK (2011) Oral manifestations of HIV infection and their correlation with CD4 count, J Oral Science, 53:203-211.

Di Lernia V, Mansouri Y (2013) Epstein-Barr virus and skin manifestations in childhood, Int J Dermatol, 52:1177-1184.

Patton LL (2013) Oral manifestations associated with HIV disease, Dent Clin N Am, 57:673-698.