Breaking the Storm: Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome as the First Manifestation of Systemic Lupus Erythematosus/Mixed Connective Tissue Disease in an Adolescent Successfully Treated With Anakinra

Macrophage activation syndrome (MAS), a form of secondary hemophagocytic lymphohistiocytosis (HLH), is an uncommon but life-threatening complication of autoimmune disease and may occasionally represent the first clinical manifestation of systemic lupus erythematosus (SLE).We describe the case of a previously healthy 15-year-old girl who initially presented with persistent fever, mucocutaneous ulcerations, fatigue, and pancytopenia.Her evaluation revealed low complement levels, elevated lactate dehydrogenase, and splenomegaly, and subsequent serologic testing confirmed new-onset SLE with features of mixed connective tissue disease and Class II lupus nephritis.Although she showed early improvement after receiving corticosteroids and hydroxychloroquine, her condition unexpectedly deteriorated with rising ferritin, hypertriglyceridemia, worsening cytopenias, and progressive liver enzyme elevation, raising concern for an evolving hyperinflammatory syndrome.She ultimately fulfilled five HLH-2004 criteria and had an HScore of 261, indicating a very high probability of HLH/MAS, despite the absence of hemophagocytosis on bone marrow biopsy.Targeted immunomodulatory therapy with anakinra was initiated promptly and resulted in rapid clinical and biochemical improvement.This case highlights the diagnostic challenges of MAS when it emerges in parallel with newly diagnosed SLE, emphasizes the importance of distinguishing MAS from SLE flare or infection, and introduces interleukin-1 blockade as a potential therapeutic option.Early recognition and timely introduction of targeted anti-inflammatory therapy may contribute to rapid stabilization and to be lifesaving when corticosteroids alone are insufficient to halt the cytokine-driven inflammatory cascade.