Recurrent herpes simplex virus 2 (HSV-2) infection is the most likely cause of this patient's rash. HSV-2 is the leading cause of genital ulcerative disease in the world. Although herpes simplex virus 1 (HSV-1) is rapidly gaining prevalence as a cause of this form of herpetic infection in younger white populations, it tends to be milder, with significantly fewer recurrences; however, it is clinically indistinguishable from HSV-2. Therefore, the diagnosis of suspected HSV infection should be confirmed with viral culture, polymerase chain reaction assay, or type-specific serologic tests.

Primary infection follows introduction of the virus onto a mucosal surface or through damaged skin. The findings with primary infection are highly variable, ranging from no symptoms to severe, painful genital ulcers; fever; tender inguinal lymphadenopathy; and headache. However, this patient has had several episodes of a similar rash over the past year, suggesting recurrent disease from a primary infection that may have occurred in the distant past. Although HSV-2 lesions characteristically appear in the genital region, they may also present at locations not classically thought of as the genitalia, such as the gluteal and presacral surfaces. Sacral HSV infection may be accompanied by episodes of aseptic meningitis. The pattern of recurrence may be influenced by diverse factors, including systemic infection, hormonal fluctuations associated with menstrual cycles, stress, and immune dysfunction. Long-term valacyclovir treatment taken on a daily basis decreases the frequency of recurrences and significantly diminishes asymptomatic viral shedding (which may occur without active skin lesions), which helps decrease transmission.

Dermatitis herpetiformis is an autoimmune disease associated with a gluten-sensitive enteropathy leading to skin deposition of IgA antibodies to gluten-tissue transglutaminase found in the gut. The lesions take the form of erythematous papules or plaques with clustered herpetiform vesicles and are usually located on the extensor surfaces of knees and elbows, but they may also be present on the shoulders and buttocks. Once present, the disease is chronic with periods of exacerbation and remission.

Fixed drug eruptions are cutaneous disorders associated with systemic exposure to various medications. The mechanism of disease is postulated to be a cell-mediated response to the offending drug acting as a hapten when it binds to specific cells in the skin. Outbreaks may occur on any cutaneous surface but seem to be more common on the lip and genitalia, where they appear as erythematous patches (often with blisters), postinflammatory necrosis, and hyperpigmentation. NSAIDs are included among the dozens of medications associated with this condition.

Sacral dermatomal distribution of HSV lesions is often confused with herpes zoster. However, multiple recurrences of zoster in a relatively young, immunocompetent woman would be very unusual.