Case Presentation: A 75-year-old woman developed fever on day X-4 and visited a clinic on day X-3. Rapid antigen tests for COVID-19 and influenza were negative, and symptomatic therapy was provided. Because the fever persisted, she re-presented; laboratory testing showed mild inflammatory elevation and increased hepatobiliary enzymes, prompting referral. After intravenous ceftriaxone at the clinic, a rash appeared. On arrival at our hospital, she was febrile but hemodynamically stable. Examination revealed a poorly demarcated erythematous rash over the right upper limb and from the abdomen to the lower legs; Murphy’s sign was negative, and no other focal findings were noted. Blood tests confirmed systemic inflammation and cholestatic enzyme elevation. Contrast-enhanced CT demonstrated biliary sludge and gallbladder wall thickening, unchanged from prior imaging and suggestive of chronic cholecystitis. Endoscopic ultrasonography revealed no biliary obstruction. Because fever persisted without a source, bone marrow examination was performed and showed hemophagocytosis. PCR assays for severe fever with thrombocytopenia syndrome virus and Rickettsia were negative; EBV/CMV serology indicated past infection. Random skin biopsy showed no malignancy. Given hyperinflammation with hemophagocytosis, idiopathic hemophagocytic syndrome was provisionally considered, and methylprednisolone pulse therapy was initiated on day X+5. Defervescence was transient; fever and rash recurred during tapering. Owing to steroid-refractory activity, cyclosporine A was started on day X+8. She subsequently developed sore throat and cough and was transferred to a collagen-vascular disease service. Based on quotidian fever, evanescent rash, pharyngitis, exclusion of infection and obstructive hepatobiliary disease, and steroid responsiveness with relapse, AOSD complicated by macrophage activation was diagnosed.
Discussion: Rash is a major Yamaguchi criterion for AOSD; however, in hyperinflammatory states (e.g., macrophage activation/HLH), drug eruptions or paraneoplastic rashes can mimic AOSD, complicating diagnosis in the elderly. In this patient, initial evaluations suggested biliary disease or infection, yet repeated negative infectious studies, non-obstructive EUS, relapsing quotidian fever, and steroid responsiveness—followed by recurrence—favored AOSD complicated by macrophage activation. AOSD in older adults often requires early immunosuppression beyond glucocorticoids; cyclosporine is a reasonable option when hemophagocytosis is present or steroid taper precipitates relapse.
Conclusions: When older patients exhibit sustained fever, sore throat, and an evanescent rash despite unrevealing infectious workup and non-obstructive biliary imaging, clinicians should maintain a high index of suspicion for AOSD, evaluate for macrophage activation, and initiate timely immunomodulatory therapy.