Herpes simplex virus
Oral herpetic lesions can range from routine herpes labialis to severe stomatitis causing large, painful ulcerations throughout the mouth. The severity of lesions dramatically increases with increasing degrees of immunosuppression. The incidence of recurrent oral HSV lesions in myelosuppressed cancer patients has been considerably reduced with the use of prophylactic acyclovir and valacyclovir regimens.[32,33,34] Additionally, the severity and duration of actual HSV lesions have been reduced by antiviral therapies.
Breakthrough infections are uncommon but can occur. While true resistance to antivirals occurs, clinical infection in the face of antiviral therapy is more likely caused by insufficient dosing or compromised gastrointestinal absorption of oral acyclovir. The introduction of valacyclovir appears to have reduced the incidence of breakthrough oral HSV infections. Topical therapy alone is generally not efficacious in the immunocompromised patient.
In patients who are not receiving antiviral prophylaxis, oral lesions typically emerge concurrent with chemotherapy or chemoradiation therapy during the period of most significant immunosuppression (white blood cell nadir). Typically, in HSCT patients, this represents the period a few days pretransplant through day 35 posttransplant. The risk of HSV reactivation remains higher than normal until immune reconstitution occurs. Similar patterns of risk are noted in patients who are receiving high-dose (immunosuppressive) chemotherapy.
Recurrent oral HSV infections occurring simultaneously with cancer therapy–induced oral mucositis can result in the development of extensive, confluent mucosal ulcerations clinically similar to primary herpetic stomatitis. As such, HSV stomatitis can be confused with cancer therapy–induced ulcerative mucositis. Viral cultures from lesions in HSV seropositive patients are essential for accurate diagnoses. Assays that produce more rapid results, including direct immunofluorescence, shell vial testing, and specific immunoassay for HSV antigen and/or biopsy, may also be useful.
Unlike in myelosuppressed cancer patients, incidence of HSV reactivation in patients undergoing head and neck radiation is very low. Therefore, HSV prophylaxis in patients scheduled to receive head and neck radiation is not recommended.
VZV infection classically distributes via dermatomes, although the clinical manifestations can be altered in immunocompromised patients, and multiple dermatomes or more widespread distribution of lesions can be seen. In patients who are receiving high-dose chemotherapy, orofacial VZV lesions are typically observed several weeks after cessation of chemotherapy—unlike HSV, which often occurs within 2 to 3 weeks after chemotherapy is discontinued. For reasons that are not entirely clear, the period of increased risk of VZV reactivation essentially extends from approximately 3 to 12 months posttransplant, with allogeneic transplant recipients being at highest risk. Acyclovir, valacyclovir, and famciclovir are the primary drugs used for treatment.