Refractory macrophage activation syndrome in adult-onset Still’s disease: response to interferon-γ blockade and JAK inhibition

A female patient in her mid-20s presented with fevers, rash and polyarthralgia and was ultimately diagnosed with macrophage activation syndrome (MAS), a widely recognised form of secondary haemophagocytic lymphohistiocytosis in the setting of autoinflammatory disease such as adult-onset Still’s disease. Extensive infectious and malignancy workup was negative. Her clinical course was complicated by persistently active disease despite initial immunomodulator therapies, including corticosteroids and anti-interleukin-1 therapy (anakinra). Further escalation of therapy with tocilizumab and etoposide yielded insufficient, partial improvement. Given the refractory nature of her condition, we initiated treatment with emapalumab, an anti-interferon-γ antibody, which led to significant symptom control. We subsequently added Janus kinase inhibitor (JAK), ruxolitinib, and continued anakinra until complete resolution of symptoms and normalisation of laboratory values. The patient was then discharged on a stable dose of ruxolitinib, anakinra and prednisone. This case illustrates the therapeutic challenges in managing refractory MAS and highlights the emerging role of targeted therapies such as emapalumab and JAK inhibitors in treatment-refractory cases.