Navigating the Diagnosis of Atypical Still’s Disease in the Absence of the Characteristic Rash

Although adult-onset Still’s disease (AOSD) typically presents with a triad of fever, rash, and arthritis, atypical manifestations can significantly hinder the diagnostic process of fever of unknown origin (FUO). We describe the case of a 57-year-old woman who presented with prolonged fever, serositis, and extreme hyperferritinemia (ferritin levels 117,904 ng/mL), further complicated by aseptic encephalitis. Following a comprehensive diagnostic workup to exclude infectious, neoplastic, and other autoimmune etiologies, the patient was evaluated using the Yamaguchi criteria. Despite the absence of the characteristic salmon-pink rash, the diagnosis of atypical AOSD was confirmed as the patient fulfilled three major (fever, arthralgia, and neutrophilic leukocytosis) and two minor (lymphadenopathy and/or splenomegaly and the absence of rheumatoid factor and antinuclear antibodies) criteria. Clinical remission and resolution of neurological symptoms were achieved through treatment with systemic corticosteroids and tocilizumab (8 mg/kg). This case emphasizes that AOSD remains a critical differential diagnosis in FUO even without an evanescent rash and highlights the potential for severe neurological involvement. Our findings support the utility of the Yamaguchi criteria in atypical presentations and illustrate the rapid therapeutic response to interleukin-6 inhibition in this clinical context.