(511) Death in One Week: Fatal Hemophagocytic Lymphohistiocytosis Post-Elective Hysterectomy

Introduction: Hemophagocytic lymphohistiocytosis (HLH) is a rare syndrome characterized by an abnormal immune response that can rapidly progress to death. Primary HLH is universally fatal and secondary HLH—usually triggered by infection, malignancy, or surgery—carries a 40% mortality rate. It may present by mimicking sepsis or a post-operative complication, leading to delay in diagnosis and treatment. We present a case of HLH identified one week after surgery with coincident HSV meningitis.

Description: A 50-year-old female was discharged home following an elective total laparoscopic hysterectomy. She was admitted to the hospital two days later with fever and started on sepsis protocol fluids and antibiotics. Urinalysis was negative and blood cultures were collected. Pulmonary embolism, DVT and intra-abdominal infection were ruled out. On hospital day 4, the patient developed hypoxia, hypotension and critical leukopenia. Repeat imaging identified interval development of ascites, gonadal vein thrombosis, and splenomegaly. She developed worsening mental status changes requiring intubation and vasopressors. HSV meningitis was confirmed by lumbar puncture. She met 5/8 criteria for HLH including fever, hyperferritinemia, hypertriglyceridemia, hypofibrinogenemia, and pancytopenia. Hemophagocytosis was confirmed by bone marrow biopsy. Unfortunately, she succumbed to her illness on hospital day five before having the chance at HLH treatment.

Discussion: HLH can present like sepsis and often a full sepsis workup is appropriately initiated. The pathophysiology is hyperactivation of macrophages which become hemophagocytic due to failure of cytotoxic cells to terminate an immune response. The excessive proliferation of cytokines results in tissue destruction and multi-organ failure. The HLH-2004 protocol requires five or more of the eight diagnostic criteria to initiate treatment. It is essential to support the body while identifying and eliminating any HLH triggers. Simultaneously, the exaggerated inflammatory response must be treated with glucocorticoids and chemotherapy, consisting of etoposide, cyclosporine and methotrexate.
This case teaches us to carry a high index of suspicion for HLH in any critically ill patient who presents with prolonged fever and unexplained cytopenias with multi-organ involvement.