C50-09 Destination Central Nervous System: Unmasking A Diagnostic Rarity in Hemophagocytic Lymphohistiocytosis

Abstract Introduction Hemophagocytic lymphohistiocytosis (HLH) is a severe, difficult-to-diagnose syndrome of excessive immune activation. Primary HLH is the result of a genetic mutation, while secondary HLH is acquired, triggered by malignancy, infection, or autoimmune disease. Sustained immune activation leads to a proinflammatory cytokine cascade, causing multiorgan dysfunction. We present a notable finding of foamy histiocytes in the cerebrospinal fluid (CSF), coupled with the absence of hemophagocytes on bone marrow biopsy, highlighting a rare diagnostic discordance. Case Report A 31-year-old female with recurrent nephrolithiasis, autoimmune hepatitis, and primary biliary cholangitis presented with flank pain. She was diagnosed with obstructive nephrolithiasis and underwent nephrostomy tube placement. Subsequently developing encephalopathy, fever, and tachycardia prompting ICU admission. She developed pancytopenia which prompted bone marrow biopsy. Her clinical deterioration raised concern for HLH, prompting transfer to a tertiary center for chemotherapy.Upon arrival, she was intubated for encephalopathy and respiratory distress. She was started on dexamethasone 10mg, vancomycin, and piperacillin-tazobactam. Hematology initiated etoposide; she met five HLH-2004 diagnostic criteria: fever, splenomegaly, bi-cytopenia, hypertriglyceridemia, and hyperferritinemia. Bone marrow biopsy was normal. A lumbar puncture performed to evaluate her encephalopathy revealed foamy histiocytes, suggestive of HLH.Her multiorgan failure progressed despite appropriate management. She developed bilateral mydriasis, imaging revealed cerebral edema with herniation, suspected secondary to hyperammonemia. Given her poor prognosis, the family elected for hospice care. Discussion This case highlights secondary HLH presenting with the rare finding of foamy histiocytes in CSF despite the absent hemophagocytes on bone marrow biopsy. HLH is a rare and underrecognized, often mimicking sepsis in critically ill patients. Secondary HLH is triggered by infection, malignancy, or autoimmune disease; in this patient, bacterial infection related to nephrolithiasis was most likely.Pathogenesis involves dysregulated cytotoxic T-cell and natural killer cell activity, resulting in uncontrolled cytokine release and multiorgan dysfunction. Neurologic involvement is less common in adults when compared to primary HLH. In our patient, CSF cytology revealed foamy histiocytes, consistent with macrophage activation, even when bone marrow findings were unrevealing. Treatment remains challenging and requires prompt initiation of immunosuppressive therapy tailored to the underlying trigger. Despite evolving treatment algorithms, mortality remains high. This case underscores the importance of further research that is necessary to target inflammatory biomarkers to manage HLH. Maintaining a high index of suspicion for HLH and that CSF cytology can provide diagnostic clues, even when bone marrow biopsy is negative. This abstract is funded by: None