Beyond the heart: hidden lymphoma-induced HLH driving cardiogenic shock

Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening hyperinflammatory condition triggered by factors like genetic abnormalities, malignancies, and infections. It leads to uncontrolled macrophage activity and cytokine release, causing tissue damage and multi-organ failure. Prompt recognition and diagnosis are essential due to its nonspecific presentation and high mortality. A 76-year-old male with known atrial fibrillation, presented with progressive fatigue. The patient was being treated with steroids and methotrexate (MTX) for a recent episode of sudden onset blurry vision while further evaluation of suspected temporal arteritis was being pursued. Upon admission, the patient developed cardiogenic shock, respiratory failure, and mental status changes, requiring intensive care. Lab findings showed thrombocytopenia, elevated ferritin, high triglycerides, and pancytopenia, fulfilling 5 of the 8 HLH diagnostic criteria. A bone marrow biopsy confirmed B-cell non-Hodgkin’s lymphoma, leading to a diagnosis of lymphoma-induced HLH. The patient was treated with etoposide and later transitioned to R-CHOP chemotherapy, leading to significant clinical improvement and stabilization of HLH markers. This case illustrates the diagnostic complexity of HLH. Early suspicion, diagnosis, and treatment are crucial to improving outcomes in patients with multi-organ dysfunction and nonspecific systemic symptoms. • Rare Case of Lymphoma-Induced HLH: The case describes a 76-year-old male who developed hemophagocytic lymphohistiocytosis (HLH) secondary to previously undiagnosed B-cell non-Hodgkin’s lymphoma, leading to cardiogenic shock and multi-organ dysfunction. • Diagnostic Complexity: The patient initially presented with non-specific symptoms of progressive fatigue and palpitations. Despite initial management for suspected temporal arteritis, he deteriorated rapidly with pancytopenia, thrombocytopenia, and worsening hemodynamic instability, making early diagnosis challenging. • Fulfillment of HLH Criteria: The patient met five of the eight HLH diagnostic criteria, including thrombocytopenia, hyperferritinemia, hypertriglyceridemia, pancytopenia, and hemophagocytosis confirmed via bone marrow biopsy. • Progression to Cardiogenic Shock: HLH led to severe cardiac involvement, including elevated troponins and worsening hemodynamic instability, culminating in cardiogenic shock that required intensive care management. • Effective Multi-Disciplinary Management: The patient received timely treatment with etoposide and was subsequently transitioned to R-CHOP chemotherapy after confirmation of lymphoma, leading to clinical improvement and stabilization of HLH markers. • Importance of Early Recognition: This case underscores the need for early suspicion and diagnosis of HLH in critically ill patients with multi-organ dysfunction, particularly when the underlying malignancy is not yet identified. • Key Learning Points for Clinicians: HLH should be considered in cases with unexplained fever, cytopenias, and organ failure. Elevated ferritin and progressive pancytopenia should prompt further hematologic evaluation. • Clinical Implications: Prompt initiation of HLH-directed therapy, even before definitive diagnosis, can improve survival outcomes. A high index of suspicion is necessary, especially in patients with concurrent malignancy or unexplained systemic inflammation.