Haemophagocytic Lymphohistiocytosis: An Uncommon Presentation in Systemic Lupus Erythematosus and Acute Leukaemia

Abstract

Introduction: Haemophagocytic lymphohistiocytosis (HLH) is a rare and potentially life-threatening hyperinflammatory syndrome, characterised by uncontrolled activation of cytotoxic T lymphocytes, natural killer cells and macrophages, leading to a cytokine storm and subsequent multiorgan damage. While HLH predominantly affects paediatric populations, it is increasingly recognised in adult patients, often occurring in association with malignancies, infections or autoimmune diseases.

Case description: We present two distinct adult cases of HLH. Case 1 involves a 21-year-old woman with newly diagnosed systemic lupus erythematosus (SLE), who developed macrophage activation syndrome (MAS)-associated HLH. She presented with prolonged fever, polyarthralgia, malar rash, hepatosplenomegaly, bicytopenia, hypofibrinogenaemia, hypertriglyceridaemia and elevated serum ferritin levels. Case 2 describes a 44-year-old woman with acute monoblastic leukaemia (AML-M5) and malignancy-associated HLH, who presented with fever, malaise, hepatosplenomegaly, hypofibrinogenaemia, hypertriglyceridaemia and hyperferritinaemia. An initial haematological response was achieved; however, disease progression ultimately led to fatal multiorgan failure secondary to neutropenic pancolitis caused by Clostridioides difficile infection.

Discussion: Both cases illustrate key clinical and pathophysiological differences in the evolution, management and outcomes of HLH, depending on the underlying cause. While both fulfilled the HLH-2024 diagnostic criteria, they exhibited markedly different responses to therapy and outcomes.

Conclusion: These cases highlight the need to suspect HLH in patients with prolonged fever, cytopaenia, organomegaly and high ferritin. Early treatment improves prognosis, especially in autoimmune HLH, where steroids are effective, while malignancy-related HLH often has poorer outcomes.

Learning points: Haemophagocytic lymphohistiocytosis (HLH) should be suspected in patients with persistent fever, cytopaenia, organomegaly and markedly elevated ferritin, particularly in the context of autoimmune diseases or haematologic malignancies.Early therapeutic intervention significantly improves prognosis in autoimmune-associated HLH, where corticosteroid therapy is often effective, while malignancy-driven HLH typically carries poorer outcomes despite aggressive treatment.A multidisciplinary approach is essential for HLH management, with treatment strategies tailored to the underlying cause rather than following a uniform protocol.

Keywords: Haemophagocytic lymphohistiocytosis; acute monoblastic leukaemia; hyperferritinaemia; macrophage activation syndrome; systemic lupus erythematosus.