Her past medical history was significant for a CD4 nadir of 14cells/mm³, recurrent skin infections and abscesses, chronic purulent otitis media requiring tympanostomy tubes, trichomonas, and Grade 1 cervical intraepithelial neoplasia. She was notably nonadherent to her HAART regimen of daily atazanavir, lamivudine, abacavir, and ritonavir. She was also on monthly aerosolized pentamidine for pneumocystis prophylaxis, but was not taking prophylaxis for mycobacterium avium intracellulare.

Three days later, the throat pain had worsened with extension to the right side. The patient remained febrile and was unable to take any solids or liquids orally due to pain. She also reported the development of a painful genital ulcer during the past week. She had vaginal intercourse with an asymptomatic male partner one week prior to the onset of symptoms and reported intermittent condom use. She denied any new sexual partners for the last 2 months and adamantly denied orogenital sexual contact.

The patient denied headaches, visual changes, vomiting, seizures, or other focal neurologic symptoms on review of systems.

Physical exam at this time revealed an ill-appearing young woman who was alert, and oriented with new enlargement of the right tonsil with erythema, new white plaques on the posterior pharynx without improvement of the left tonsil or the left side of the tongue. The patient demonstrated pain when opening her mouth for exam. On the genitourinary exam, there was labial swelling and a 1cm large open ulcer with cream-colored discharge centrally over the ulcer. There was also a creamy film covering the vaginal introitus. She was unable to tolerate a speculum and one-finger manual exam due to significant swelling and pain.

The patient was admitted to the hospital for worsening tonsillitis and pharyngitis not responding to dual oral antibiotic coverage, dehydration, and persistent fevers. She was started on intravenous ampicillin sulbactam, fluconazole, and acyclovir. Subsequent viral cultures from the throat, mouth, and genital ulcer became positive for HSV-2 at two days. Two years prior to the current presentation, qualitative determination of antibody status for specific IgG to both HSV-1 and HSV-2 using indirect chemiluminescence immunoassays was negative during the patient's pregnancy. Repeated evaluation using the same method for specific IgG to both HSV-1 and HSV-2 remained negative with the current illness at approximately two and a half weeks from onset of symptoms. Antibody status of HSV IgM was also negative. She was known to have had appropriate antibody responses to Hepatitis A and B vaccines. Other admission labs included a white blood cell count of 8600 per cubic millimeter with an absolute neutrophil count of 7040 per cubic millimeter, and normal complete metabolic panel with normal liver function markers.

Clinical presentations with a primary infection of genital herpes can range from asymptomatic to formation of painful lesions with or without other associated symptoms. Women, in particular, present with a higher frequency of systemic symptoms compared to men (68% versus 39%), which may be characterized by headache, fever, malaise, and myalgias [7]. While localized symptoms may involve pain or itching, dysuria, vaginal or urethral discharge, and tender inguinal adenopathy, complications can extend to include aseptic meningitis, paresthesias of the leg and perineum, other mucocutaneous lesions beyond the genital area, pharyngitis, esophagitis and visceral dissemination [4, 7].

HSV pharyngitis is not uncommon among patients presenting with primary genital herpes, although, interestingly, our patient developed pharyngitis symptoms prior to presenting with genital lesions [4, 7]. The several days of oral manifestations without genital lesions made the diagnosis of HSV more difficult. Individuals may complain of sore throat during the acute episode and clinical signs can range from mild erythema to a more severe diffuse ulcerative or exudative posterior pharyngitis, or tonsillitis. While a history of orogenital contact, which she adamantly denied, is a risk factor for development of pharyngeal infection, disseminated infection with the presence of pharyngitis in the absence of reported sexual contact has also been reported [8]. In one case series of patients with genital HSV infections, 11% of patients with a primary HSV-2 genital infection also had HSV-2 isolated from the pharynx. However, while almost half of all the patients with genital HSV infection in the case series reported performing recent oral sex (48% men, 51% women), the subset of patients with primary HSV-2 genital infections with concurrent pharyngeal infection who may have performed oral sex is not described [7]. Interestingly, in the same case series, several patients also had a prior recent diagnosis of streptococcal pharyngitis similar to our patient. Whether the mechanism is due to a bacterial superinfection of a herpetic ulcerative lesion or a synergistic relationship between HSV-2 and a bacterial infection causing a more severe clinical presentation it is not clear.

Many studies have demonstrated a synergistic relationship between HSV-2 and HIV acquisition and transmission [9]. There is also evidence demonstrating that the presence of coinfection with HSV-2 and HIV-1 is associated with atypical and more severe clinical presentations, as well as more frequent recurrences of secondary HSV reactivation and recurrence [10–12]. Additionally, there is also a relationship between greater degrees of immunosuppression and advanced HIV with more severe presentation of HSV disease [13].

Our patient did not demonstrate serologic evidence of prior HSV-2 infection or exposure. With the absence of IgG and IgM antibodies to both HSV-1 and HSV-2, and isolation of HSV-2 from viral cultures at both the pharyngeal and genital sites, this presentation is consistent with a primary HSV-2 infection simultaneously involving the genital area and pharynx. Given that our patient denied active lesions on her partner, we presume the patient acquired HSV-2 infection through asymptomatic shedding of the virus from her partner.