Treatment of Oral Hairy Leukoplakia
Oral hairy leukoplakia (OHL) in HIV-positive patients typically does not require treatment unless symptomatic, and when treatment is needed, high-dose acyclovir or other antivirals targeting Epstein-Barr virus (EBV) are the primary therapeutic options.
Diagnostic Confirmation
- OHL cannot be reliably diagnosed on clinical appearance alone, as white plaques on the lateral tongue are frequently mistaken for oral candidiasis 1, 2.
- The key distinguishing feature is that OHL lesions cannot be scraped off, unlike candidal plaques which are easily removed 1.
- Persistence after a trial of topical antifungal therapy is highly suggestive of OHL rather than candidiasis, as 52% of clinically suspected OHL cases are actually candidal infections 2.
- Definitive diagnosis requires biopsy with histopathologic examination demonstrating EBV DNA by in-situ hybridization or polymerase chain reaction 2, 3.
Treatment Indications
- Most cases of OHL do not require treatment, as the lesions are benign and asymptomatic 4, 3.
- Treatment should be reserved for patients with symptomatic lesions causing discomfort, pain, or significant cosmetic concerns 3.
- The primary goal of treatment is symptom relief, not eradication, as recurrence after therapy cessation is universal 3.
Therapeutic Options
First-Line: Antiviral Therapy
- High-dose acyclovir (800 mg five times daily) or valacyclovir can result in clinical improvement by inhibiting EBV replication 4.
- Treatment duration is typically continued until clinical resolution, but lesions recur after discontinuation 4, 3.
Alternative: Topical Gentian Violet
- Topical gentian violet solution applied directly to the tongue has demonstrated complete clinical resolution after three treatments in case reports 5.
- This represents an inexpensive, FDA-approved over-the-counter option that targets reactive oxygen species induced by EBV 5.
Antiretroviral Therapy
- Initiation or optimization of antiretroviral therapy (ART) is the most important long-term strategy, as immune reconstitution reduces the incidence and severity of OHL 1.
- Effective ART addresses the underlying immunosuppression that permits EBV replication in oral epithelium 4.
Critical Pitfalls to Avoid
- Do not treat clinically suspected OHL without first ruling out candidiasis with a trial of topical antifungals (clotrimazole troches or nystatin), as misdiagnosis is extremely common 1, 2.
- Do not confuse OHL with oral candidiasis—candidal plaques scrape off easily, while OHL plaques are fixed and have a corrugated or "hairy" surface 1, 4.
- Do not expect permanent cure with antiviral therapy alone—recurrence is inevitable without immune reconstitution via ART 3.
- Do not biopsy without clinical suspicion—if lesions resolve with antifungal therapy, they were candidiasis, not OHL 2.
Management Algorithm
- Identify white, non-removable plaques on lateral tongue borders in an HIV-positive patient 1, 4.
- Attempt to scrape lesions—if they remove easily, treat as candidiasis with fluconazole 100-200 mg daily for 7-14 days 1, 6.
- If lesions persist after 7-14 days of antifungal therapy, presume OHL and consider biopsy for confirmation if diagnosis impacts management 2.
- For asymptomatic OHL, observe without treatment and optimize ART 3.
- For symptomatic OHL, initiate high-dose acyclovir or valacyclovir until symptom resolution 4.
- Consider topical gentian violet as an alternative for patients unable to tolerate systemic antivirals 5.
- Ensure ART is optimized or initiated to achieve immune reconstitution and prevent recurrence 1.
Special Considerations
- OHL is a marker of progressive immune deficiency and predicts progression to AIDS in untreated HIV patients 4.
- The presence of OHL should prompt evaluation of CD4 count and HIV viral load, with consideration for ART initiation if not already on therapy 1.
- Langerhans cell counts are significantly decreased in OHL lesions, reflecting local immunosuppression 7.