A polymerase chain reaction (PCR) test of a lesion specimen should be performed for genital herpes simplex virus (HSV) infection. The patient has genital lesions characteristic of HSV infection (shallow ulcers on an erythematous base), and primary infection is likely because of the presence of multiple lesions, regional lymphadenopathy, and systemic symptoms. It is important that all first presentations of genital HSV infection be microbiologically confirmed. PCR is the most sensitive of the available testing modalities and can also distinguish between HSV-1 and HSV-2, which can help inform discussions with the patient regarding risk of recurrent genital ulcer disease. HSV-1 is the most common and is less likely to cause recurrent infection or asymptomatic shedding. If the diagnosis is confirmed, the patient should be offered screening for other sexually transmitted infections and counseled regarding the need to inform prospective sexual partners and her obstetrician should she become pregnant.

Direct florescent antibody testing of a genital lesion is a specific study for HSV infection and is also able to identify the type of virus present. However, it is less sensitive than PCR testing and is no longer recommended for the diagnosis of genital HSV.

Type-specific serum antibodies to HSV develop within weeks of primary infection and persist indefinitely. However, their presence does not confirm that the genital ulcers are caused by HSV; therefore, this study would not be appropriate for this patient.

Tzanck smear is an older test that assesses the presence of multinucleate giant cells in a lesion specimen that demonstrates the cytopathic effects of the virus. However, the sensitivity and specificity of this test are low, and the test does not differentiate among serotypes of HSV; it is therefore no longer used frequently.