Abstract Introduction Hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) are overlapping clinical syndromes characterized by dysregulation of the immune system that result in profound systemic inflammation and end-organ damage.1 A third autoinflammatory process, VEXAS syndrome, stems from a genetic mutation that results in recurrent fevers, cytopenias, and joint, skin, and lung inflammation.2 We present a case of critical illness due to severe immune dysregulation. Case A 59-year-old female with no significant past medical history presented to an outside hospital with less than twenty-four hours of high-grade fevers, nausea, vomiting, and altered mental status. On presentation she was febrile, hypotensive, and mildly hypoxic. Workup demonstrated leukopenia, thrombocytopenia, a bandemia of 30%, lactic acidosis, direct hyperbilirubinemia, and acute kidney and liver injuries. CT abdomen demonstrated severe diffuse circumferential gallbladder wall edema concerning for acute cholecystitis. She was started on broad spectrum antibiotics, pressors , and intubated for respiratory failure in the setting of severe metabolic acidosis. Cultures and viral panel were negative. Rheumatologic workup was negative except for positive ANA. Her labs were notable for a ferritinemia over 16,000, triglycerides in the 400s, and soluble IL-2R of nearly 14,000.Hematology recommended a bone marrow biopsy which revealed intracytoplasmic vacuoles in erythroid and myeloid precursors with negative flow cytometry. These findings taken together prompted consideration of HLH/MAS versus VEXAS syndrome. Next generation sequencing was negative for pathogenic mutations ruling out VEXAS syndrome. She met five of eight clinical criteria for secondary HLH and was treated with a prolonged steroid taper and an IL-1 antagonist with initial improvement. Her course has been complicated by ongoing intermittent encephalopathy in the setting of possible recurrent HLH flares. Discussion HLH and MAS can result from primary genetic mutations or can be secondary to rheumatologic conditions (MAS) or infection, malignancy, or medications (HLH).1 Both have similar clinical presentations with cyclic fevers, cytopenias, hepatosplenomegaly, significantly elevated serum ferritin, and coagulopathies.3 Criteria for diagnosing secondary HLH includes five of eight of the following: fever 38.5C, splenomegaly, bicytopenia, hypertriglyceridemia and/or hypofibrinogenemia, hemophagocytosis on tissue or bone marrow biopsy, low or absent natural killer cell activity, significantly elevated serum ferritin, and elevated soluble CD25 (soluble IL-2 receptor).4 Clinical suspicion can override strict criteria when not clearly met. Distinguishing between these syndromes guides therapy: treatment of the underlying rheumatologic disorder is the mainstay of treatment for MAS and VEXAS, whereas immunosuppression, anti-viral therapies, and/or chemotherapy agents are the mainstay for HLH.5,6 This abstract is funded by: N/A
Rowley et al. (Fri,) studied this question.