Abstract Introduction Hemophagocytic lymphohistiocytosis (HLH) and Macrophage activation syndrome (MAS) are two overlapping, life-threatening hyperinflammatory syndromes characterized by excessive immune activation. HLH is typically associated with infections and malignancy, while MAS is classically associated with rheumatologic conditions. HLH and MAS remain diagnostically challenging due to overlapping features with other conditions such as infections, acute pancreatitis and flares of autoimmune disease that can cause fevers, cytopenias, elevated inflammatory markers, and organ dysfunction. Case Presentation A 24-year-old female with Systemic Lupus Erythematosus (SLE), bilateral orbital pseudotumor and dacryocystitis was admitted for fatigue, fever, gastrointestinal symptoms, and periorbital edema. She was noted to be febrile and tachycardic and was empirically initiated on broad-spectrum antibiotics. Initial workup demonstrated elevated inflammatory markers, anemia, thrombocytopenia, elevated transaminases, and acute renal failure requiring hemodialysis. She had normal IgG4, C3 and C4 levels. The patient was noted to have elevated lipase of 238 U/L, elevated ferritin 27,000 ng/mL, elevated triglycerides of 345 mg/ dl, low fibrinogen of 181 mg/dl, and elevated soluble IL-2 receptor of 2461.5 pg/mL. Urinalysis and blood cultures did not show signs of infection. Computed tomography (CT) of the head and neck showed swollen bilateral lacrimal glands with bilateral cervical and parotid lymphadenopathy, CT angiography of chest showed a right lower lobe pulmonary embolism, and CT Abdomen and pelvis demonstrated acute pancreatitis, prominent ileocolic and mesenteric lymph nodes as well as splenomegaly. Fine needle aspiration of the left cervical lymph node showed a reactive node with negative flow cytometry. Left renal biopsy showed acute tubular injury and segmental sclerosis with no immune complex deposition. Bone marrow biopsy showed hyperplasia without morphological evidence of HLH. Due to elevated H score (257 points, 99% probability), there was high clinical concern for HLH related to acute pancreatitis vs MAS in the setting of SLE. Patient was initiated on intravenous methylprednisolone and Anakinra with initial clinical improvement. However, she subsequently developed septic shock secondary to Citrobacter bacteremia that was complicated by multi-organ dysfunction and ultimately death. Discussion HLH and MAS are typically diagnosed by clinical criteria including fever, splenomegaly, cytopenias, hyperferritinemia, hypertriglyceridemia, hypofibrinogenemia, and hemophagocytosis on biopsy. However, in some cases, diagnosis can remain elusive due to incomplete criteria or lack of histopathological evidence. It is key to note that the absence of hemophagocytosis on bone marrow does not exclude these diseases. Early recognition and targeted therapy are crucial but require careful integration of clinical, laboratory, imaging, and histopathologic data. This abstract is funded by: none
Scott et al. (Fri,) studied this question.