Case Presentation: This is a 69-year-old male with a past medical history significant for prostate cancer on active radiation therapy and androgen deprivation therapy who presented to the emergency room for evaluation of hypotension. He reported four days of nausea, myalgias, and night sweats.On physical examination, he was noted to be tachycardic and hypotensive, with a maculopapular rash on the abdomen. Initial laboratory evaluation revealed elevated lactic acid, transaminitis, and pancytopenia. There was concern for severe sepsis based on tachycardia, hypotension, and elevated lactate. Infectious workup was unrevealing. Ferritin level obtained the day after admission was markedly elevated. The patient subsequently developed fevers.Given the combination of fever, pancytopenia, and hyperferritinemia, there was clinical suspicion for hemophagocytic lymphohistiocytosis (HLH). Three days after hospitalization, he developed new wrist pain and worsening rash accompanied by recurrent fevers, raising concern for adult-onset Still’s disease (AOSD). Although AOSD typically causes neutrophilic leukocytosis, it can present with pancytopenia, most often in the setting of secondary HLH or macrophage activation syndrome (MAS).The patient was ultimately diagnosed with adult-onset Still’s disease complicated by macrophage activation syndrome (MAS). He was started on prednisone with a month-long taper, with good clinical response and improvement of symptoms prior to discharge.
Discussion: Adult-onset Still’s disease (AOSD) complicated by macrophage activation syndrome (MAS) typically presents with acute, severe systemic inflammation characterized by persistent high fevers, hepatosplenomegaly, lymphadenopathy, cytopenias (particularly thrombocytopenia), liver dysfunction, coagulopathy, and extreme hyperferritinemia.MAS results from a dysregulated immune response marked by excessive activation of monocytes and macrophages and a cytokine storm driven by both innate and adaptive immune pathways. Hallmark features include expansion of intermediate and classical monocyte subsets, reduced natural killer (NK) cell activity, and a pronounced interferon signature—particularly IFN-γ and type I interferons. These abnormalities promote uncontrolled macrophage activation and hemophagocytic activity, leading to multi-organ involvement.Recent evidence also implicates mTORC1 signaling in monocytes as a mechanistic link between AOSD and MAS, contributing to inflammatory gene expression and hemophagocytosis.
Conclusions: Early recognition of macrophage activation syndrome (MAS) in patients with adult-onset Still’s disease (AOSD) is critically important, as MAS is a life-threatening complication associated with high morbidity and mortality. A key finding is the presence of cytopenias instead of leukocytosis in a patient who otherwise presents with features suggestive of AOSD. Prompt diagnosis and urgent, targeted therapy are essential to improving outcomes.