PT  - JOURNAL ARTICLE
AU  - Raffaele Strippoli
AU  - Ivan Caiello
AU  - Fabrizio De Benedetti
TI  - Reaching the Threshold: A Multilayer Pathogenesis of Macrophage Activation Syndrome
AID  - 10.3899/jrheum.121233
DP  - 2013 Apr 15
TA  - The Journal of Rheumatology
PG  - jrheum.121233
4099  - http://www.jrheum.org/content/early/2013/04/10/jrheum.121233.short
4100  - http://www.jrheum.org/content/early/2013/04/10/jrheum.121233.full
AB  - 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.