Reaching the threshold: A multilayer pathogenesis of macrophage activation syndrome

Raffaele Strippoli, Ivan Caiello, Fabrizio De Benedetti

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)761-767
Number of pages7
JournalJournal of Rheumatology
Issue number6
Publication statusPublished - Jun 2013


  • Etiology
  • Hemophagocytic Lymphohistiocytoses
  • Juvenile Idiopathic Arthritis
  • Macrophage Activation Syndrome

ASJC Scopus subject areas

  • Rheumatology
  • Immunology
  • Immunology and Allergy


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