A Diagnosis of Exclusion: Unraveling Adult-Onset Still's Disease

Adult-onset Still's disease (AOSD) is a rare systemic autoinflammatory disorder characterized by quotidian fevers, arthralgia, transient rash, and elevated inflammatory markers, often leading to diagnostic delay due to overlap with infectious, autoimmune, and malignant conditions. We present the case of a 60-year-old Latina woman who developed daily fevers, polyarthralgia, rash, and hypoxemic respiratory failure. Despite broad-spectrum antibiotics, her symptoms persisted, and extensive infectious and hematologic evaluations were unrevealing. A diagnosis of AOSD was established based on the Yamaguchi criteria and markedly elevated ferritin. The patient responded to corticosteroids but later developed macrophage activation syndrome (MAS), requiring anakinra in addition to high-dose steroids. This case highlights the diagnostic challenges of AOSD in older adults, the potential for atypical systemic manifestations such as pulmonary nodules and anasarca, and the importance of early cytokine-directed therapy to prevent life-threatening complications.