Systemic juvenile idiopathic arthritis (sJIA) is a heterogeneic disease of unknown pathogenesis. Some 20% of cases have a monophasic and very mild disease course, in contrast to the other extreme subtype with chronic relapsing systemic features and progressive polyarthritis. The majority of cases have systemic features mainly in the early phase of the disease but often develop a severe destructive polyarthritis later. Since its original description in 1890 by Mayer Diamantberger in Hôpital Rothschild in Paris, France1, and in 1897 by George Frederick Still in England, sJIA is still defined by the classic triad of spiking fever of at least 2 weeks’ duration, arthritis, and one of the following symptoms: typical exanthema, lymphadenopathy, hepato splenomegaly, or ascites2. Recent laboratory studies identified key cytokines such as interleukin 1 (IL-1), IL-6, and IL-18, as well as natural killer (NK) cell dysfunction that cannot be found in any other subtype of JIA3,4,5,6. The heterogeneity is further illustrated by description of cases with spiking fever, exanthema associated with this typical cytokine pattern, and NK cell dysfunction but without arthritis. In fact, sJIA can be viewed as an autoinflammatory disease rather than an autoimmune disease. Macrophage activation syndrome (MAS) is … Address correspondence to Dr Wulffraat; E-mail: n.wulffraat{at}umcutrecht.nl