Because HIV-infected individuals are immunocompromised, viral infections, which are opportunistic infections, occur more frequently and with greater severity. Some of these infections have long been known to occur in the oral cavity, but some others have been reported only since the outbreak of the AIDS epidemic. The increased prevalence produces more diverse clinical findings, often complicating diagnosis and management.
HIV protein rarely is found in the lesion, confirming the indirect effect of immunodeficiency as being the underlying cause of HIV-related pathology. These viral infections pose an increased threat to partners who may suffer also from immunodysregulation and susceptibility.
Herpes simplex virus-1 and sometimes HSV-2 are seen more frequently in HIV-infected individuals as compared to immunocompetent persons. The attacks are usually more severe, with recurrent lesions involving the lips (herpes labial is, "cold sores") and the oral mucosa. In both sites, lesions can persist for extended periods, they can be large, and they can occur as multiple ulcerations. Thus recognition can at times be difficult. leading to the use of wrong and ineffective therapeutic approaches.
When adults experience herpetic lip lesions for the first time or if attacks become more frequent and/or severe, immunosuppression should be suspected and included in the differential diagnosis. If a mucocutaneous herpetic flare is progressive and continues for more than 1 month in an HIV-positive patient, this condition meets the CDC criteria for an AIDS-defining disease. Intraoral recurrent herpes can occur on any mucosal surface, keratinized or unkeratinized, and can have quite diverse appearances of the ulcerative manifestations. Thus the differential diagnosis can be complex. There is almost always associated pain of varying degrees for both lip and mucosal sites.
The clinical diagnosis can be confused with toxic. allergic. and bacterial etiologies. When the clinical diagnosis is uncertain, the diagnosis can be confirmed by cultures to identify HSV, smears reacted with HSV-specific monoclonal antibodies, or cytologic scrapings to identify pseudogiant cells, which result from DNA proliferation without cell division. If a biopsy is obtained, HSV can be identified by morphologic cellular changes and immunoreactive stains.
Treatment depends on patient status and the severity (signs and symptoms) of the lesion(s). When there is evidence that a patient can still mount an immune response, management approaches can be by empirical supportive measures. Specific antiviral treatment involves the use of acyclovir (Zovirax). Because acyclovir is poorly absorbed and significant blood levels are required, daily dosages are high, ranging from 1 to 4 g.
Acyclovir itself is an inactive drug. It must be phosphorylated to the triphosphate form to be effective. This occurs in response to an enzyme, thymidine kinase, which is produced by the herpes virus. Acyclovir does not kill the virus; its effect is based on interference with DNA polymerase. temporarily stopping viral proliferation. Resistance to acyclovir takes place when HSV no longer produces thymidine kinase. Foscarnet (Foscavir) is an effective alternative antiviral drug, but it must be given intravenously. Topical antiviral oil1lments and creams have not been shown to be reproducibly helpful.
Recurrences are unpredictable, but expected. A prophylactic regimen can be useful, but effective dosages usually are determined on a trial-and-error basis. as are durations of treatment. Supportive measures should be instituted, including analgesic agents and adequate nutrition and hydration.
Herpes virus-6 has been of recent interest because of its occurrence in humans and some indications that it facilitates HIV infection of cells in vitro.
EBV might well be a co-factor in several HIV-associated oral lesions. The most common is the association between EBV and OHL. OHL is almost always found unilaterally or bilaterally on the lateral border of the tongue. It usually presents as a corrugated or hair-like white lesion that can appear at times as flat white patches. Occasionally, OHL can occur on another oral mucosal surface. The extent of OHL is not necessarily correlated with the stage of HIV infection. In fact, OHL can be the first sign of HIV infection in some patients.
A clinician must be careful in establishing the diagnosis, since similar appearing changes can occur in HIV-negative persons. Some examples include lichen planus, leukoplakia, candidiasis, immunosuppression secondary to chemotherapy, and irritational keratoses. OHL is not related to precancerous leukoplakia or dysplasias.
When uncertainties exist or more information is needed for management, the diagnosis is established by biopsy to identify tissue patterns and EBV. Characteristic features include epithelial hyperplasia, immature surface keratin (no keratohyaline granules), vacuolated squamous cells (koilocytes), and variable to no connective tissue inflammation. When required to further confirm the diagnosis, EBV can be detected using in situ hybridization and special DNA probes. Cytologic smears from OHL will frequently reveal pathognomonic margination and clumping of nuclear protein.
OHL primarily occurs in homosexual and bisexual men, although it has been reported in other HIV-afflicted groups. This suggests some other unidentified co-factor(s) that may well be transmitted most efficiently by anal sex. While EBV is associated with OHL, its exact role in the etiology and transmission is not clear. Absence of Langerhans cells and altered mucosal immunity seem to play roles also.
If a patient does not know his/her HIV status, OHL mandates HIV testing. OHL is rarely symptomatic. Since there is no clear cut relationship between removing OHL and either quality of life or survival, treatment is elective and usually on the basis of a patient complaint that the lesion is "bothersome."
Many different approaches will temporarily control OHL, but once a treatment is discontinued, OHL will sooner or later recur. Successful temporary control has been obtained using antivirals in high dosages (acyclovir), starting AZT antiretroviral therapy, in patients who are being simultaneously treated with trimethoprim-sulfamethoxazole (Bactrim or Septra) for pneumocystic pneumonia, topical application of 0.05% Retin A solution, and topical application of keratinolytic podophyllin (25% solution in tincture of benzoin).
In the immunocompromised patient, the risk exists for reactivation of latent chickenpox virus. When this happens, the disease takes the form of varicella zoster, more commonly referred to as herpes zoster or shingles. The vesicles formed by the virus eventually break and scab or are covered by pseudomembranes. Zoster lesions present a classical unilateral pattern and are associated with both pruritus and pain. They can become secondarily infected.
While the lesions are usually self-limiting, the most important symptoms are the postzoster neuropathy and pain which can be excruciating. Therefore high-dose acyclovir treatment is instituted (e.g., 800 mg every 5 to 6 hours). Simultaneous high-dose prednisone may be helpful. Control of fever and pain as well as adequate nutrition and hydration are important in the treatment. Famciclovir is a more recent antiviral drug that has been useful for acute zoster (500 mg three times daily). Recurrences are uncommon. However, the occurrence of zoster in the HIV patient often indicates advanced staging, development of other opportunistic infections, and a poor prognosis for lengthy survival.
CMV antibodies are found in over 50% of the normal population, indicating the frequency of human exposure to this virus. Antibodies to CMV can almost always be found in patients made immunodeficient with HIV, and frequently the virus itself can be cultivated. In the HIV-positive patient, CMV can cause many debilitating conditions. The most common is CMV retinitis, which may even lead to blindness.
While oral lesions due to CMV are rarely reported, this might be due to difficulties in establishing the diagnosis. They usually present as nonspecific ulcers that can be mistaken for other infections, granulomatous lesions, inflammatory/immunologic diseases, or malignancies. Pain is the common complaint. Diagnosis is established by biopsy, recognition of suggestive microscopic morphologic changes (e.g., "owl-eye cells"), and the use of immunoreactive stains.
CMV may also serve as a co-factor in salivary gland enlargement and hypofunction leading to xerostomia. Therefore the role of CMV in many HIV associated conditions has yet to be completely clarified. CMV may even be a co-factor in HIV progression. In any event, the antiviral drug ganciclovir (Cytovene) has been selectively effective in controlling CMV infections.
The presence of HPV is so common in oral mucosa that the significance of being causal, co-factor, or passenger is difficult to document. However, certain strains are known to be related to condylomata acuminata (venereal warts) and their increased occurrence in HIV patients. This is due to an increase in unprotected sex as well as immunosuppression. Often these individuals also manifest genital and anal condylomata. When the strain is HPV-16, the infection risks are associated with the development of squamous carcinomas (anus, uterine cervix). In HIV-positive women, carcinoma of the cervix is an AIDS-defining disease.
The diagnosis of oral condyloma can usually be made by appearance and history. While they primarily appear as verruca, the lesions can be somewhat flat and smooth; resembling fibromas. Biopsy and appropriate probes or PCR techniques can establish HPV presence and strain.
Treatment of oral lesions involves tissue removal of significant depth to remove all localized virus. Electrosurgical and laser techniques are well suited for these procedures. Since reinfection is common, control of warts at other sites and counseling regarding infected partners are essential. While condylomata are not necessarily consistent with HIV infection, because of similar high-risk behavior a possible association must be presumed until ruled out.
Molluscum contagiosum (MC) is a DNA virus of the poxvirus family. While intraoral lesions are extremely rare, facial skin lesions are not too uncommon in HIV-immunocompromised patients. The lesions occur as papules that can burst and become secondarily infected. Me is of concern because of appearance, discomfort, and the possibility of spread by direct contact. There is no reproducibly effective treatment.
No specific oral lesions are associated with hepatitis viruses. However, because of the virulence and transmission risks of hepatitis viruses B (HB V) and C (HCV, previously non-A, non-B) and similar modes of transmission with HIV, these viruses are of significance to clinicians.
Because of improved acceptance and use of barrier techniques and sterilization methods, there have been no reported cases of transmission from HBV positive dentists to dental patients since 1987. Conversely, following the large acceptance of the effective HBV vaccine, HBV infection has nor been a significant threat to practitioners. However, with the now known diversity of transmission of HCV (similar to HBV) and the lack of a vaccine, a possible risk remains. HCV infection is associated with increased sickness and greater risk for chronic hepatitis. Two other hepatitis strains are now recognized: the more often fatal D, which requires HBV antigen for infection, and E.