Background: Macrophage activation syndrome (MAS) is a rare but potentially life-threatening condition associated with systemic lupus erythematosus (SLE), as well as several other autoimmune conditions. Case Presentation: We present a case of MAS in a 30-year-old patient with a background of SLE presenting with persistent fever and hemodynamic instability. Broad-spectrum antibiotics were initially started for possible sepsis of unknown origin, but a lack of response or evidence of an infection source led to further laboratory investigations and additional diagnostic imaging. Hyperferritinemia, a low fibrinogen, hypertriglyceridemia, and pancytopenia raised the suspicion of MAS. Echocardiography revealed a pericardial effusion requiring pericardiocentesis. With rapid disease progression, multiorgan failure ensued, and shortly after a high dose, methylprednisolone was commenced; the patient’s condition worsened and she died after a cardiac arrest. Conclusion: This case highlights the challenges involved in diagnosing MAS and in differentiating it from more common presentations such as sepsis or autoimmune disease flares, and demonstrates the possible rapid disease progression. Therefore, early recognition of certain clinical features and laboratory markers are essential to enable early diagnosis, commencement of immunosuppressive treatment, and to ultimately improve outcomes in such critically unwell patients.

Keywords: Macrophage Activation Syndrome, Systemic Lupus Erythematosus, Rare Rheumatology Diseases, Diagnosis, Ferritin, Mortality, Abstract