Abstract Introduction Adult-Onset Still’s Disease (AOSD) is a rare systemic autoinflammatory disorder characterized by fever, rash, arthralgia, lymphadenopathy, and hyperferritinemia. Macrophage activation syndrome (MAS) can occur in 10-15% of cases with a mortality rate between 20-53%. Corticosteroids are first-line therapy, with Interleukin (IL)-1 and IL-6 inhibitors considered in refractory disease. Emapalumab, an anti-Interferon gamma (IFNγ) monoclonal antibody, was recently FDA approved for management of refractory MAS-AOSD, though clinical experience is still limited. Case Presentation A 41-year-old woman with a known diagnosis of Adult-Onset Still’s Disease (AOSD) on chronic systemic corticosteroids, presented with several weeks of fevers and arthralgia. She was initially treated with anakinra and was subsequently upgraded to the medical ICU (MICU) for hypotension and altered mental status. Her physical examination revealed diffuse arthralgia, lower extremity edema and altered mental status. Laboratory studies on ICU admission showed WBC 13.2 × 10³/µL, Hgb 11.2 g/dL, platelets 197 × 10³/µL, Na 133 mmol/L, K 3.8 mmol/L, Cr 0.70 mg/dL, Ca 8.3 mg/dL, and Mg 1.3 mg/dL. Liver tests revealed AST 90 U/L, ALT 21 U/L, albumin 2.9 g/dL, and total bilirubin 0.2 mg/dL. Coagulation was normal (PT 12 sec, INR 1.0). Lactate was 2.1 mmol/L. Inflammatory markers were markedly elevated with ferritin 25,630 ng/mL, triglycerides 634 mg/dL, LDH 1,184 U/L, and CRP 79.25 mg/L, all rapidly rising on serial testing. A comprehensive infectious evaluation was negative, and the patient was started on one gram of methylprednisolone intravenously. Her hospital course was complicated by generalized tonic-clonic seizures secondary to aseptic meningoencephalitis confirmed by MRI and CSF analysis, as well as distributive shock, requiring intubation and vasopressor support. Repeat ferritin peaked at 97,000 ng/mL on hospital day 16. Following multidisciplinary discussion with rheumatology and infectious disease, emapalumab was initiated. Within 48 hours, the fever resolved, inflammatory markers declined, and vasopressors were weaned. She was extubated five days after emapalumab initiation with full neurologic recovery (figure 1). Discussion IFNγ blockade with emapalumab resulted in complete clinical and biochemical resolution of severe refractory MAS secondary to AOSD. Our case highlights the importance of rapid recognition of severe MAS and expedited initiation of appropriate therapy in refractory cases. CNS involvement in MAS is uncommon but underscores the importance of early recognition and escalation beyond corticosteroids and IL-1 blockade. Conclusion Emapalumab can achieve rapid remission of life-threatening MAS secondary to AOSD with CNS and hemodynamic compromise. Early consideration of IFNγ blockade may be lifesaving when standard therapies fail. This abstract is funded by: None
Mukhopadhyay et al. (Fri,) studied this question.