Herpes simplex

Herpes simplex virus (HSV) is a double-stranded DNA virus that has 2 subtypes: HSV-1 and HSV-2. Stress, fever, and sunlight may precipitate reactivation of HSV, which usually lies dormant in nearby ganglia. After this stimulus, or decreased immune surveillance, the virus travels down peripheral nerves to produce lesions. The frequency and the severity of these recurrences vary, but the lesions most commonly occur on the vermilion of the lips and are sometimes preceded by a burning or tingling sensation. Numerous small (<1 mm) vesicles appear, which sometimes coalesce into larger vesicles. These then rupture and leave behind painful, weeping ulcerations. These ulcerations are highly infectious until they eventually crust over, which usually takes approximately 3-5 days. The normal duration of lesions is 7-10 days in immunocompetent individuals.

Immunodeficiency, as seen with HIV disease, permits reactivation of latent herpes infections. Until disproved, all perineal and orolabial ulcerations should be evaluated for HSV in patients who are infected with HIV. Compared with individuals who are immunocompetent, HSV infection in a patient who is HIV positive is more aggressive, prolonged, and diffuse.

Intraoral lesions occur most commonly on the keratinized mucosa, such as the dorsal aspect of the tongue, gingiva, and hard palate. Here, they form single or multiple coalescing vesicles with irregular margins that rupture into ulcerations. Although the keratinized mucosa is usually infected, HSV lesions can manifest on nonkeratinized surfaces in immunocompromised hosts. These include the labial mucosa, ventral tongue, floor of the mouth, buccal mucosa, and the soft palate. Herpetic lesions may extend to other areas, including the tonsillar pillars and the esophagus.

Diagnosis is made by physical examination and a history of prodrome at the site of the vesicles. A Tzanck smear demonstrating multinucleate giant cells is suggestive, but culture and antibody stain results are diagnostic. Tissue biopsy can also be used to obtain a definitive diagnosis. Thymidine kinase inhibitors are the most commonly used antivirals to treat HSV infections. These include acyclovir, valacyclovir, and famciclovir. However, acyclovir-resistant strains are more common among HIV-infected individuals. In these instances, the infections are treated aggressively with intravenous foscarnet.

Hairy leukoplakia

Hairy leukoplakia (HL) most commonly manifests as corrugated white plaques most commonly on the lateral portions of the tongue. These plaques can range in appearance from very thin and homogenous to a thickened, rough area that mimics hyperplastic candidiasis. The infectious agent responsible for these lesions is Epstein-Barr virus (EBV), located within the epithelial cells. In the early 1980s, HL was first identified and characterized in patients who were HIV positive, but it has also been described in persons with other states of immunocompromise (eg, renal transplant recipients). HL remains the most specific manifestation of HIV disease to occur in the mouth, and its presence has prognostic implications for the progression to AIDS because patients rarely manifest the condition with CD4 counts greater than 200 cells/L. The white verrucous plaques vary greatly in size, are not premalignant, and are usually asymptomatic. These lesions can be clinically mistaken for candidiasis, and a biopsy should be performed for definitive diagnosis.

Histologically, hairlike folds can be seen, which demonstrate hyperparakeratosis, acanthosis, and groups of ballooning cells, with little inflammatory infiltrate present. Definitive diagnosis may be made with in situ hybridization of the DNA from EBV in surface epithelial cells.

Although the severity of HL is not directly correlated with HIV stage, HL has been shown to precede the diagnosis of AIDS in patients with HIV infection, and it appears to be a prognostic indicator of advanced disease and death within several years. An analysis of 198 patients with HL in the pre–highly active antiretroviral therapy (HAART) era demonstrated that the median time to onset of AIDS was 24 months and to death was 41 months. Oral HL may be the presenting sign in as many as 5% of patients who are HIV positive. Because HL is usually asymptomatic, treatment is elective. HL responds to antiviral medication, such as oral acyclovir, but lesions generally recur after cessation of therapy. If a patient reports symptoms associated with HL, the lesions are most likely superinfected with Candida species. Antifungal treatment usually ameliorates the symptoms.