Abstract
Macrophage activation syndrome (MAS) is a subtype of secondary hemophagocytic lymphohistiocytosis (HLH) associated with rheumatic diseases. It is a life-threatening condition characterized by hypercytokinemia due to uncontrolled T-cell and macrophage activation. MAS is an uncommon complication in patients with mixed connective tissue disease (MCTD), particularly in those without a prior diagnosis or treatment. We report the case of a previously healthy 14-year-old Japanese girl admitted to our hospital with severe headache and persistent fever. Despite an initially unremarkable examination, she subsequently developed altered mental status, arthralgia, and a small erythema. Laboratory findings revealed cytopenia and coagulation abnormalities, along with elevated levels of C-reactive protein, liver enzymes, triglycerides, and ferritin. Although she did not meet the HLH-2004 diagnostic criteria established by the Histiocyte Society, MAS was suspected based on early diagnostic criteria for MAS associated with other rheumatic diseases. Prompt initiation of steroid pulse therapy led to rapid clinical improvement. Further serological testing revealed strongly positive anti-U1-ribonucleoprotein (RNP) antibodies, confirming a diagnosis of MCTD. Over one year of follow-up, the patient remained well-controlled on a tapered dose of prednisolone, with no serological relapse. This case highlights the importance of early diagnosis and treatment of MAS, even when the underlying disease is unknown. Additionally, cytokine profiling may provide valuable insights into understanding the pathogenesis of diseases that cause hypercytokinemia.