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Case Note

Case Note: White Papules and Plaques on the Tongue

History

A 37-year-old male presents for evaluation and management of long-standing 'ulcers' on the tongue.

Initial evaluation

  • Thin-appearing adult male
  • Recent diagnosis of HIV infection
    • Not yet initiated anti-retroviral medications
  • Elevated viral load and reduced CD4 lymphocyte count (240)
  • Presents with thick, adherent, white hyperkeratotic corrugated plaques (without underlying erythema or edema) on the bilateral tongue
  • No evidence of oral candidiasis on exam - potassium hydroxide preparation is negative
  • Image 1
    Image 1

Enter your diagnosis

Diagnosis

  • A diagnosis of oral hairy leukoplakia (OHL) is rendered

Initial Treatment

  • Patient initiated on topical tretinoin cream twice daily to affected areas
  • Patient referred to HIV primary care for evaluation and consideration for start of anti-retroviral regimen
  • Follow up in 4 weeks

Follow-up evaluation strategy

4-week follow-up evaluation:

  • Moderate improvement

 Further recommendations:

  • Oral acyclovir 2.0-3.2 g per day (400 mg five times daily, or 800 mg four 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

 Subsequent treatment steps:

  • For individuals with HIV infection, successful treatment with anti-retroviral medications will likely result in resolution of OHL
  • If thrush, which is frequently associated with OHL, is present, treat with first-line clotrimazole troches or oral nystatin suspension

 Treatment pitfalls:

  • Failure to evaluate for HIV infection or other cause of immunocompromisation
  • Side effects from oral acyclovir
    • These are rare and include rashes and mild gastrointestinal 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 oral cavity
  • Epstein-Barr virus (EBV) serologies play no role in the management or diagnosis of OHL

General discussion

To date, OHL has 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 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 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 histologic examination.

Further reading

Bodhade AS, Ganvir SM, Hazarey VK. Oral manifestations of HIV infection and their correlation with CD4 count. J Oral Science 2011;53:203-11.

Di Lernia V, Mansouri Y. Epstein-Barr virus and skin manifestations in childhood. Int J Dermatol 2013;52:1177-84.

Patton LL. Oral manifestations associated with HIV disease. Dent Clin N Am 2013;57:673-98.

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