Emapalumab's role in a severe and treatment-resistant paediatric macrophage activation syndrome.

Abstract

Introduction
Macrophage activation syndrome (MAS) is a life-threatening hyperinflammatory condition. Emapalumab, an IFNγ-directed antibody, is approved for use in the USA but not in Europe. Case
A 15-year-old girl presented with fever, odynophagia and a transient rash. After 9 days of hospitalization under empirical antibiotics, she developed pancytopenia, hypofibrinogenaemia, elevated ALT, AST, LDH, triglycerides, soluble CD25, serum calprotectin and ferritin (peak 357,976 ng/ml), and hepatosplenomegaly. Infectious and immune workups were negative, and bone biopsy confirmed haemophagocytosis. MAS was diagnosed, which was complicated by acute respiratory distress and supraventricular tachycardia. High-dose corticosteroids, anakinra and ciclosporin were initiated, with transient improvement. Subsequent drug-induced hepatotoxicity and microangiopathy, and infections worsened her condition. Given refractoriness to standard therapy, emapalumab was started under compassionate use, leading to sustained clinical and laboratory remission. She was discharged and remains stable at six-month follow-up, off corticosteroids and on canakinumab maintenance. Discussion
This case illustrates the challenges of treating severe, refractory MAS. Emapalumab, used for the first time in Portugal, was well tolerated and associated with complete and sustained remission after failure of multiple therapeutic lines.