Macrophage Activation Syndrome in Rheumatic Diseases (MAS-HLH)

  • Alexei A. Grom
  • AnnaCarin Horne
  • Fabrizio De Benedetti
Chapter

Abstract

The term macrophage activation syndrome (MAS) refers to hemophagocytic syndromes presenting as a complication of a rheumatic disease. Although MAS has been reported in association with many inflammatory disorders, it is seen most frequently in systemic juvenile idiopathic arthritis and, in its adult equivalent, adult-onset Still’s disease. Like other hemophagocytic syndromes, MAS is caused by excessive activation and expansion of T lymphocytes and macrophagic histiocytes that exhibit hemophagocytic activity. In MAS, excessive activation and expansion of T lymphocytes and macrophagic histiocytes lead to a hyperinflammatory state associated with three cardinal features: cytopenias, liver dysfunction, and coagulopathy resembling disseminated intravascular coagulation. Extreme hyperferritinemia is another striking laboratory feature of MAS. It is a life-threatening condition and may progress to multiple organ failure. The reported mortality rates reach 20–30%. Currently, the mainstay of treatment of MAS presenting as a complication of rheumatic diseases remains high-dose corticosteroids, cyclosporine, anakinra, and, in more difficult instances, etoposide. IFN-γ is emerging as a potential therapeutic target as well.

Keywords

Macrophage activation syndrome Hemophagocytic lymphohistiocytosis Cytokine storm Systemic juvenile idiopathic arthritis Hyperferritinemia Adult-onset Still’s disease 

List of Abbreviations

MAS

macrophage activation syndrome

HLH

hemophagocytic lymphohistiocytosis

SJIA

systemic juvenile idiopathic arthritis

AOSD

adult-onset Still’s disease

SLE

systemic lupus erythematosus

DIC

disseminated intravascular coagulation

EBV

Epstein-Barr virus

CMV

cytomegalovirus

NK

natural killer

ESR

erythrocyte sedimentation rate

CRP

C-reactive protein

sIL2Ra

soluble IL-2 receptor alpha chain

LCMV

lymphocytic choriomeningitis virus

TLR

Toll-like receptor

LPS

lipopolysaccharides

ATG

antithymocyte globulin

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Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  • Alexei A. Grom
    • 1
  • AnnaCarin Horne
    • 2
  • Fabrizio De Benedetti
    • 3
  1. 1.Cincinnati Children’s Hospital Medical CenterDivision of Rheumatology, ML 4010CincinnatiUSA
  2. 2.Karolinska University Hospital SolnaStockholmSweden
  3. 3.Ospedale Pediatrico Bambino GesùRomeItaly

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