C50-18 HSV-Triggered Hemophagocytic Lymphohistiocytosis (HLH) With Persistent Encephalopathy in an Immunocompetent Elderly ICU Patient

Abstract Case Presentation An 81-year-old immunocompetent man with hyperlipidemia and hypothyroidism presented after a fall, reporting several days of progressive fatigue and low-grade fever. Laboratory evaluation revealed pancytopenia, marked transaminitis, and elevated inflammatory markers. He rapidly decompensated, necessitating ICU transfer for worsening hepatic injury, hypotension, and early multiorgan involvement. Workup demonstrated ferritin 9000 ng/mL, triglycerides 473 mg/dL, low fibrinogen, and soluble IL-2 receptor 8836 U/mL, fulfilling five diagnostic criteria for hemophagocytic lymphohistiocytosis (HLH). Bone marrow biopsy was limited but showed no evidence of malignancy. Viral studies revealed HSV-1 viremia and hepatitis, suggesting a trigger for secondary HLH.During the ICU course, the patient developed acute kidney injury requiring dialysis, disseminated intravascular coagulation (DIC) with multiple retroperitoneal and mesenteric hematomas, and pulmonary edema. Given his age, coagulopathy, and hepatic dysfunction, cytotoxic therapy with etoposide and calcineurin inhibitors such as cyclosporine were deemed prohibitively high risk. Management was initiated with high-dose dexamethasone according to the HLH-94 protocol and adjunctive anakinra for cytokine suppression. He also completed a 14-day course of intravenous acyclovir targeting HSV. Laboratory parameters improved, including down-trending ferritin (9000 ng/mL), stabilized blood counts, and normalization of inflammatory markers; however, his encephalopathy persisted despite correction of metabolic derangements and absence of active infection. MRI brain was unrevealing. Following multidisciplinary discussions and alignment with family goals of care, he was transitioned to comfort-focused management and discharged home with hospice support. Discussion HLH is a life-threatening hyperinflammatory syndrome caused by uncontrolled immune activation. While typically described in children or immunocompromised adults, it can rarely occur in immunocompetent elderly patients, often mimicking sepsis or multiorgan failure. HSV-1 hepatitis likely served as the inciting trigger in this case. Standard cytotoxic therapy was limited by age, hepatic dysfunction, and coagulopathy, prompting use of anakinra as a targeted anti-cytokine therapy. Persistent encephalopathy despite systemic improvement highlights potential central nervous system involvement, possibly mediated by cytokine-induced neurotoxicity. This case underscores the importance of early recognition, individualized treatment planning, and multidisciplinary collaboration. Conclusion HLH should be considered in adults with unexplained fever, cytopenias, and multiorgan dysfunction, even in immunocompetent individuals. Treatment must be tailored to comorbidities and organ function. Persistent encephalopathy may signal CNS involvement and poor neurologic prognosis. Early diagnosis, targeted therapy, and careful balancing of immunosuppressive strategies are essential to optimize outcomes. This abstract is funded by: None