Oral Hairy Leukoplakia

Oral hairy leukoplakia (OHL) is a benign, white, corrugated lesion of the lateral tongue caused by Epstein-Barr virus (EBV) replication in the superficial epithelium (productive replication in the spinous layer, without malignant transformation).

It was first described in HIV-infected men and is a marker of immunosuppression. It occurs in 20 to 25 percent of untreated HIV patients, most commonly with CD4 counts below 300 cells per microlitre.

It predicts progression to AIDS (about 48 percent progress within 16 months, and 83 percent within 31 months in untreated persons).

Prevalence has fallen since antiretroviral therapy (ART), but OHL still occurs in patients with late diagnosis in Kenya. It also occurs in other immunosuppressed groups: transplant recipients, those on prolonged corticosteroids or inhaled steroids, and rarely in immunocompetent persons. It is not premalignant, and unlike other forms of leukoplakia, it is caused by virus rather than epithelial dysplasia. Lesions usually regress with immune recovery on ART.

• White, corrugated or "hairy" plaques on the lateral borders of the tongue, bilateral in many patients, with vertical folds; can extend to the dorsum, ventral surface, buccal mucosa, and palate.
• Cannot be scraped off (differentiating from candidiasis).
• Usually asymptomatic; may cause cosmetic concern, altered taste, and mild discomfort; not painful.
• Often with coexisting oral candidiasis.
• Red flags: ulceration, induration, red areas (exclude carcinoma), systemic symptoms of advanced HIV (weight loss, fever, chronic diarrhoea, opportunistic infection), CD4 below 200.

• Clinical diagnosis in a patient with HIV or other immunosuppression, based on a non-scrapable bilateral white corrugated lesion of the lateral tongue.
• HIV test with CD4 count and viral load if status is unknown or the diagnosis is new; consider screening for tuberculosis, syphilis, and hepatitis B and C.
• Biopsy for confirmation when atypical or in immunocompetent people: acanthosis, parakeratosis with a corrugated surface, ballooning cells in the upper spinous layer with a "halo" appearance, minimal inflammation; EBV detected by in situ hybridisation (EBER), immunohistochemistry (EBV-LMP), or PCR.
• Smear for Candida (KOH).
• Exclude oral candidiasis, leukoplakia, lichen planus, frictional keratosis (cheek biting), geographic tongue, white sponge nevus, and squamous cell carcinoma.

• Treat the HIV infection: antiretroviral therapy, starting on the day of diagnosis or within 7 days, with tenofovir disoproxil fumarate 300 mg, lamivudine 300 mg and dolutegravir 50 mg orally once daily (as a fixed dose combination, one tablet daily for life); OHL regresses in most patients within 3 to 6 months of immune recovery.
• Asymptomatic lesion: no specific treatment is needed.
• Cosmetic or symptomatic lesion: aciclovir 800 mg orally five times daily for 2 weeks, or valaciclovir 1 g orally twice daily for 7 to 14 days, or famciclovir 500 mg orally three times daily for 7 to 14 days; lesions usually recur within weeks to months after stopping if the immunosuppression persists.
• Topical therapy: podophyllin resin 25 percent solution applied by a clinician once to the lesion weekly for 2 to 4 weeks (avoid in pregnancy); tretinoin 0.025 percent, or retinoid gel applied twice daily for 2 to 4 weeks; maintenance with aciclovir 400 mg orally twice daily in recurrent symptomatic disease.
• Treat associated candidiasis: fluconazole 100 to 200 mg orally once daily for 7 to 14 days, or miconazole oral gel 20 mg/g, 2.5 mL four times daily for 14 days.
• Opportunistic infection prophylaxis: co-trimoxazole 960 mg orally once daily when CD4 is below 200 per microlitre, stopped once CD4 exceeds 200 for 6 months.
• Follow up: review at 3 and 6 months after starting ART; CD4 count at 6 months; viral load at 6 and 12 months; refer lesions that do not regress for biopsy.
• Counselling: OHL is not contagious in daily contact and is not cancer, but it signals immune suppression; adherence to ART is the best treatment.