VIRAL DISEASES

Oral Manifestations of HIV infection
By Drs. Deborah Greenspan and John S. Greenspan

Herpes Simplex

Herpes simplex virus causes both primary and recurrent oral disease, The primary event, herpetic gingivostomatitis, is most common among children and young adults in the general population and it is also seen in young people with HIV infection. Herpetic gingivostomatitis presents as ulcers and vesicles on the gingiva as well as elsewhere on the oral mucosa. The lesions are accompanied by fever and complaints of pain and loss of appetite. Recurrent herpes simplex may involve the lips or the intraoral mucosa. Lip lesions appear as small vesicles that rupture, ulcerate, and then form a crust. Recurrent intraoral herpes simplex starts as small crops of vesicles on the hard palate or gingiva that rupture to produce small, painful, coalescing ulcers. The oral lesions are usually confined to the keratinized mucosa, although lesions may appear on the dorsal surface of the tongue. The buccal mucosa and lateral margin of the tongue are very rarely involved. The lesions may be trivial and self limiting or, occasionally, troublesome, extensive, and persistent. Lesions that are slow to resolve can be treated with acyclovir, 1000 to 1600 mg daily for seven to ten days. Topical acyclovir is not effective in treating intraoral lesions and may not be effective in treating herpes labialis, Occasionally, herpes labialis is resistant to treatment with acyclovir; these lesions may respond to phosphonoformate.

Herpes Zoster

Orofacial herpes zoster, a reactivation of the varicella zoster virus, produces crops of vesicles along the distribution of one or more branches of the trigeminal nerve. Usually unilateral, the lesions may appear on the skin or intraorally on any mucosal surface. The skin lesions begin as vesicles, then rupture and crust over. The oral lesions are vesicles that rupture to form ulcers. Prodromal complaints may include pain referred to otherwise healthy teeth. Treatment is oral famciclovir (500 mg, every 8 hours for 7 days) or oral acyclovir (800 mg, five times a day for 7 to 10 days) and should be started as soon as possible.

Hairy Leukoplakia

Hairy leukoplakia (HL) is one of the most common HIV-associated oral lesions.' It is a nonremovable, white, corrugated or "hairy" lesion seen on the lateral margin of the tongue (Fig. 3) and occasionally elsewhere on the oral mucosa. AIthough HL occurs in all the risk groups for HIV infection, it is not common in children. Cases of HL have been reported in HIV-negative people in association with immunosuppressive therapy. HL is usually asymptomatic, although patients occasionally complain of its appearance or texture. Differential diagnosis includes lichen planus and epithelial dysplasia, so biopsy of the lesion may be necessary. The lesion is often secondarily infected by candida, but elimination of that organism with antifungal therapy does not cause the lesion to disappear. HL is caused by the Epstein-Barr virus (EBV), which can be seen on electron microscopy and with in-situ hybridization. As far as can be determined, HL is not a premaiignant lesion. HL can be eliminated with acyclovir at doses from 2.5 to 3.0 mg per day for two to three weeks, but the lesion usually recurs when treatment ends. Case reports have described responses to other agents, including ganciclovir, phosphonoformate, Retin A, and podophyllin resin, although, again, the lesion tends to recur within a few months. Although there were initial reports indicating that HL regressed in individuals during AZT therapy, in a larger series we have not found this to be the case.

Cytomegalovirus (CMV) Ulcers

We and others, using histochemistry, have found cytomegalovirus in oral mucosal ulcers, predominantly in patients with known CMV disease. These ulcers occur on both keratinized and nonkeratinized mucosa, appearing on the gingiva, buccal mucosa, and palate. Oral CMV ulcers may be confused with necrotizing ulcerative periodontitis, lymphoma, and atypical aphthous ulcers. When ganciclovir is used to treat CMV disease, the oral ulcers resolve.

Human Papillomavirus Lesions

As is true in other groups of immuno- suppressed individuals, lesions caused by human papillomavirus (HPV) are common on the skin and mucous membranes of those with HIV infection. In the mouth these lesions take the form of typical warts, caused by a variety of types of HPV, and focal epithelial hyperplasia (Heck's disease), caused by HPV types 13 and 32, These warts may appear cauliflower-like, spiky, or slightly raised with a flat surface. Application of 5% acetic acid may make them more visible. Although malignant transformation in these HPV lesions has not been reported, we and our colleagues at the German Cancer Research Center in Heidelberg have recently identified four new HPU types in these warts, and believe their long-term behavior merits study, Surgical or laser excision is the most effective way to remove HPV warts, but recurrence is common, so removal should probably be reserved for lesions that interfere with function or esthetics.