Abstract Introduction Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening syndrome of excessive immune activation. Although often associated with malignancies, HLH may also occur in autoimmune diseases such as systemic lupus erythematosus (SLE). In severe cases, HLH may lead to Macrophage activation syndrome (MAS) marked by persistent fever, cytopenias, coagulopathy, hyperferritinemia, liver dysfunction, and central nervous system involvement. Early diagnosis remains challenging due to nonspecific presentations that mimic infectious, malignant, or other inflammatory processes. Description Of Case A 21-year-old male presented with 1-month history of syncopal episodes, fatigue, night sweats, and a 30 pound weight loss. He was noted to be febrile, tachycardic, and pancytopenic (Hgb 12.4, WBC 1.6, Plt 103) on presentation. Initial imaging revealed retroperitoneal/upper abdominal lymphadenopathy. He was started on broad-spectrum antibiotics and later antifungals due to concern for systemic infection and neutropenia. He remained febrile with an oral temperature of 105.6 °F. An extensive infectious workup was negative. Given persistent fevers, progressive cytopenias, transaminitis, and hyperferritinemia (12,205ng/mL), HLH and hematological malignancy were suspected. A bone marrow biopsy showed hypocellularity without hemophagocytosis. Autoimmune workup was suggestive of SLE. He subsequently developed 2 episodes of hematemesis as well as worsening kidney injury, transaminitis, encephalopathy and was transferred to the ICU. An EGD was performed, revealing multiple bleeding angiodysplastic gastric lesions, managed with endoscopic cautery and octreotide. Repeat imaging revealed hepatosplenomegaly (Figure 1). Due to rapid neurologic decline, high-dose IV methylprednisolone (1g/d x 3 days) and anakinra (200 mg q12h) were initiated for cytokine storm. The H-score was recalculated at 218, consistent with a 90% probability of HLH, raising concern for SLE-associated HLH. He remained encephalopathic with persistent cytopenias and fevers, and met criteria for Macrophage activation syndrome (MAS). Serum sIL2R returned elevated, further favoring HLH. He was started on dexamethasone and etoposide. Over the next 48 hours, the patient’s mental status improved significantly, ferritin levels downtrended, and fevers subsided. He made a quick recovery on continued immunosuppressive therapy and was eventually discharged. Discussion This case highlights the diagnostic complexity and rapid deterioration in secondary HLH-MAS due to an autoimmune disease. Though hemophagocytosis was absent on bone marrow biopsy, the patient met clinical and laboratory criteria for HLH. This case underscores the importance of suspecting HLH in persistently febrile patients with cytopenias and multiorgan dysfunction, even in the absence of expected findings, early in the disease course. Prompt treatment is crucial in improving outcomes in this life-threatening condition. Figure 1. Coronal CT Abdomen showing hepatosplenomegaly. This abstract is funded by: None
Patel et al. (Fri,) studied this question.