The primary genital herpes infection tends to have both local and generalized systemic symptomatology. The infection typically presents with multiple, painful, vesicular or ulcerated lesions. Patients may experience parasthesias prior to the appearance of vesicles. Within a few days of sexual contact, vesicles erupt on labia majora, introitus, urethra, and perineum; thighs and buttocks may also be involved. The vesicles are typically superficial, small (1–2 mm in diameter), and have an erythematous border. After approximately 1 week new lesions begin to form. Concomitantly, earlier lesions become more ulcerated and may coalesce. After approximately 2 weeks a dry crust forms and lesions begin to heal without developing a scar. Vulvar herpes is often accompanied by vaginal lesions and, less commonly, cervical lesions. Tender, firm and, often, bilateral inguinal lympadenopathy may also be present. During the primary infection, 70% of women may experience a “prodrome” of symptoms including fever, malaise, or myalgias. Moreover, symptoms of vaginal or urethral discharge may also be present with herpetic cervicitis or urethritis. The incubation period is 2–12 days and the patient may shed viruses for up to 3 weeks after the appearance of vesicles. The entire primary infection usually resolves within 2–6 weeks but viral shedding may persist for longer.

The diagnosis of genital herpes may be made by clinical history and physical examination with the assistance of laboratory evaluation. One must suspect genital herpes when a sexually active woman presents with the above prodromal symptoms and described genital lesions. Most HSV-2 seropositive individuals do not present with the classic signs and symptoms described above; therefore, history and clinical presentation are insufficient for diagnosis. It is prudent in the work-up of such a patient to rule out other sexually transmitted infections such as syphilis and chancroid, among others. Therefore, cultures for these and other infections should be sent as indicated, in order that the appropriate therapy can be initiated expediently. In addition to sexually transmitted infections, the differential diagnosis should include erosive lichen planus, atopic dermatitis and urethritis.

The laboratory tests that may be useful to confirm the clinical diagnosis of herpes simplex infection include cytology (Tzank smear), direct antibody staining, viral culture, polymerase chain reaction (PCR) and serology. Cytologic specimens that exhibit multinucleated giant cells and intranuclear inclusions may aid in the diagnosis but these tests are neither sensitive nor specific for HSV infection. Direct fluorescent antibody staining or immunohistochemistry may be used to detect type-specific HVS antigen using monoclonal antibodies on viral culture or lesional smear samples; these tests are specific and sensitive, but not widely available. Viral cultures are the “gold standard” diagnostic test. Samples obtained from fresh vesicles with a cotton tip applicator have a high rate of virus isolation but with a higher false-negative rate than PCR analysis, which can detect extremely low concentrations of viral DNA and is thus the most sensitive test. Although this is the laboratory evaluation of choice, it is still not widely available for genital sampling.