Macrophage activation syndrome (MAS) is a life-threatening hyper-inflammatory syndrome characterised by excessive activation and proliferation of T lymphocytes and macrophages and a consequent massive production of cytokines, or ‘cytokine storm’. MAS is considered a secondary or acquired form of haemophagocytic lymphohistiocytosis (HLH) and is usually associated with infection (systemic Epstein-Barr virus or cytomegalovirus infections or tuberculosis), malignancy, or rheumatic diseases like systemic lupus erythematosus (SLE). SLE-MAS can occur both in adult and childhood-onset,1 2 at the time of diagnosis of SLE and frequently relapses in adults. There are no validated diagnostic or classification criteria for HLH/MAS in adults. HLH-2004 criteria developed for children are often used but are not sensitive enough to allow early diagnosis. These criteria include fever, splenomegaly, cytopenia affecting at least two lineages (hemoglobin 3, neutrophils 265 mg/dL) and/or hypofibrinogenemia (3 4 Other therapies have included ciclosporin, methotrexate, tacrolimus, intravenous immunoglobulin and biologics (rituximab, tocilizumab and anti-interferon gamma) in a very limited number of patients. Learning objectives Diagnose MAS in SLE Make differential diagnosis between SLE flare and MAS Treat SLE–associated MAS References Borgia RE, Gerstein M, Levy DM, et al. Features, Treatment, and Outcomes of Macrophage Activation Syndrome in Childhood-Onset Systemic Lupus Erythematosus. Arthritis & Rheumatology 2018;70(4):616–24. Gavand P-E, Serio I, Arnaud L, et al. Clinical spectrum and therapeutic management of systemic lupus erythematosus-associated macrophage activation syndrome: A study of 103 episodes in 89 adult patients. Autoimmunity Reviews 2017;16(7):743–49. Grom AA, Horne A, De Benedetti F. Macrophage activation syndrome in the era of biologic therapy. Nature Reviews Rheumatology 2016;12(5):259–68. La Rosée P, Horne A, Hines M, et al. Recommendations for the management of hemophagocytic lymphohistiocytosis in adults. Blood 2019;133(23):2465–77.