TY - JOUR T1 - Reaching the Threshold: A Multilayer Pathogenesis of Macrophage Activation Syndrome JF - The Journal of Rheumatology JO - J Rheumatol DO - 10.3899/jrheum.121233 SP - jrheum.121233 AU - Raffaele Strippoli AU - Ivan Caiello AU - Fabrizio De Benedetti Y1 - 2013/04/15 UR - http://www.jrheum.org/content/early/2013/04/10/jrheum.121233.abstract N2 - Macrophage activation syndrome (MAS) is a potentially fatal complication of rheumatic diseases. The condition is considered part of secondary hemophagocytic lymphohistiocytoses (HLH). There are similarities in genetic background, pathogenesis, and clinical and laboratory features with primary HLH (p-HLH). We describe findings in mouse models of secondary HLH, comparing them with models of p-HLH and the cellular and molecular mechanisms involved, and relate them to recent findings in patients with secondary HLH. A multilayer model is presented in which background inflammation, infections, and genetics all contribute in different proportions and in several ways. Once the “threshold” has been reached, inflammatory cytokines are the final effectors, independent of the interplay between different upstream pathogenic factors. ER -