Oral manifestations of viral infections more pronounced in immunosuppressed

July 1997

SAN FRANCISCO — Careful examination of the oral mucosal and salivary glands is an essential aspect of infectious disease evaluation, as well as the general physical workup of all patients.

"The mouth is the mirror of the body. But often it is overlooked," said John S. Greenspan, DDS, PhD, professor and chair of the department of stomatology and director of the Oral AIDS Center at the School of Dentistry, University and California San Francisco.

"Diseases due to viruses in the mouth are quite common in the general, otherwise healthy, population," said Greenspan at the annual meeting of the American Academy of Dermatology here. The occurrence is greater among immunosuppressed people, though. "In the context of HIV infection and other forms of immunosuppression, such as kidney transplant patients, there is an increase in the frequency of these oral viral lesions."

Moreover, these diseases often manifest differently in the immunosuppressed population. "Even new lesions have been seen," noted Greenspan.

Oral hairy leukoplakia

---Oral hairy leukoplakia is a marker for immunosuppresion.

Oral hairy leukoplakia is a white lesion of the tongue that Greenspan and his colleagues first discovered in 1981. They published the initial report of its existence among homosexual men in San Francisco in 1984. It is just as prevalent among kidney transplant recipients as among HIV-infected individuals. The disorder is also observed among bone-marrow recipients and those on long-term steroid therapy.

"It is a disease whereby the Epstein-Barr virus reactivates because of a weakened immune system," explained Greenspan. The disorder is also a significant marker for immunosuppression. "Hairy leukoplakia, as well as the other oral lesions, is an important barometer of the state of the immune system."

The white patch lesion — often corrugated or even "hairy" in appearance — usually appears on the lateral margin of the tongue. "Hairy leukoplakia can also occur on the buccal mucosa, floor of the mouth, and other parts of the oral mucosa, but does not affect the vaginal or anal mucosa," said Greenspan.

The presence of Epstein-Barr virus is required for definitive diagnosis of the disorder, "although presumptive diagnosis can be made on clinical appearance alone," he said. Hairy leukoplakia is usually symptomless, but complaints about its discomfort and appearance can justify treatment. "The lesion shows a striking but temporary response to high doses of acyclovir [Zovirax, Glaxo Wellcome] or ganciclovir [Cytovene-IV, Roche], and also to podophyllin and retinoin," said Greenspan.

Herpes simplex

---Acyclovir-resistant intraoral herpes simplex may cause serious progressive disease.

Herpes simplex virus causes both primary and recurrent oral disease. These painful oral lesions start as vesicles and then rupture to form ulcers that can occur on any mucosal surface.

"There's an underlying level of viral disease in the healthy population," said Greenspan. "But we don't know why, for example, people who have herpes simplex virus living in the sensory ganglia in the head break out with herpes lesions in the mouth, as well as on the lips." Herpes lesions on the lips can be precipitated by sunlight, steroids, trauma or even an association with phases of the menstrual cycle. "But within the mouth, we get a similar outbreak of herpes simplex, such as little ulcers on the palate and on the gingivae," he noted.

"In general, we tend not to treat herpes simplex in the mouth in the immunocompetent population," said Greenspan. "But when we see herpes simplex in the HIV population and others who are immunosuppressed, it is more widespread, it is more severe and can be in places where we otherwise never see it. So, we often treat it."

Topical or systemic acyclovir is often effective therapy. However, Greenspan and his colleagues have occasionally detected acyclovir-resistant herpes. "We haven't seen as much of it as we thought we would. We first saw it about six years ago. But it has not become a major problem."

Acyclovir-resistant herpes simplex may cause serious progressive disease "involving the oral cavity, lips and face," he said. Such lesions usually respond to foscarnet (Foscavir, Astra).

Other herpes viruses

---Oral warts may be removed surgically, but the recurrence rate is high.

Oral ulcers caused by cytomegalovirus "can be quite troublesome," noted Greenspan. "But we've only seen them in association with more widespread cytomegalovirus disease. So treatment is part of the treatment of cytomegalovirus for the whole body." Diagnosis is made on histological examination with immunohistochemistry.

Another herpesvirus, varicella zoster, may present with a "prodrome of dental pain, preceding oral and skin vesicles and ulcers following one or more branches of the trigeminal nerve," said Greenspan. Again, acyclovir can be effective.

Oral warts are common in HIV infection. "In the immunocompromised patient, warts can be a significant treatment challenge. We don't really have an overall, effective treatment," Greenspan said. Oral warts can be removed surgically, but the recurrence rate is high.

One unusual form of flat wart — focal epithelial hyperplasia — is due to human papillomavirus (HPV) types 13 and 32. The more common cauliflower and spiky warts are also HPV-triggered, including types 2, 11, 16 and 18. However, HPV 7, which is not detected in the mouth before HIV infection, can also be responsible. "Some warts show epithelial atypia and these contain new HPV types," said Greenspan.

Kaposi's sarcoma

---Radiation therapy may be required for large oral Kaposi's sarcoma lesions.

Kaposi's sarcoma should be considered a viral disease. "It's pretty clear that it is due to a new member of the herpes-virus group, which we're calling HHV8 or Kaposi's sarcoma herpesvirus," said Greenspan, director of the university's AIDS clinical research center.

Kaposi's sarcoma may be the first presentation of HIV with lesions occurring most commonly on the palate. However, "the role of oral transmission of HHV8 has yet to be determined," said Greenspan. The lesions first appear as small red or purple patches, eventually becoming nodular and ulcerating if traumatized.

Small oral lesions may be treated with "surgical debulking, intralesional vinblastine or sclerosing solutions," said Greenspan. Large lesions may be cosmetically unacceptable and hinder speaking and eating; therefore, radiation therapy may be required.

"Drugs such as ketoconazole [Nizoral, Janssen] and zidovudine [Retrovir, Glaxo Wellcome] can cause oral pigmentation which, although usually brown, should not be confused with the reddish or purple color of Kaposi's sarcoma lesions," cautioned Greenspan.

The lymphomas seen in the mouth of HIV-infected individuals and occasionally from renal and other transplant recipients are mostly due to viruses, either Epstein-Barr or HHV8.

For your information:

• Greenspan J. Oral manifestations of viral infections. Presented at the American Academy of Dermatology. March 21-26. San Francisco.