An Immunocompetent Host With Severe Disseminated Herpes Simplex Virus Type 2 Infection With Hepatorenal Involvement

Herpes simplex virus type 2 (HSV-2) most commonly causes localized mucocutaneous infections, whereas disseminated disease with visceral involvement is rare, particularly in immunocompetent individuals. HSV hepatitis is a potentially life-threatening manifestation that often presents with nonspecific symptoms and markedly elevated liver enzymes, making early recognition difficult. We report a 58-year-old immunocompetent man with good performance status (Eastern Cooperative Oncology Group (ECOG) 0) who presented with fever, malaise, and a progressive vesicular rash involving the face, hands, and trunk. Laboratory investigations revealed elevated transaminases, hyperbilirubinemia, acute kidney injury, and electrolyte abnormalities. Imaging demonstrated mild hepatosplenomegaly without obstruction, and polymerase chain reaction testing confirmed HSV-2 in both serum and skin lesions. Other infectious and autoimmune evaluations were negative. The patient was treated with intravenous acyclovir followed by oral valacyclovir, resulting in complete resolution of symptoms and normalization of liver and renal function. Given ongoing high-risk sexual behavior, he was also counseled on long-acting injectable HIV pre-exposure prophylaxis with lenacapavir. The current case highlights that disseminated HSV-2 infection with hepatic and renal injury can occur in an immunocompetent host. Early recognition and prompt antiviral therapy are critical to improving clinical outcomes. Physicians should consider a high index of suspicion for HSV hepatitis in candidates presenting with unexplained transaminitis and systemic symptoms, even in the absence of classic mucocutaneous findings or immunosuppression.