Review

Macrophage activation syndrome in the era of biologic therapy

  • Nature Reviews Rheumatology 12, 259268 (2016)
  • doi:10.1038/nrrheum.2015.179
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Abstract

Macrophage activation syndrome (MAS) refers to acute overwhelming inflammation caused by a 'cytokine storm'. Although increasingly recognized as a life-threatening complication of various rheumatic diseases, clinically, MAS is strikingly similar to primary and secondary forms of haemophagocytic lymphohistiocytosis (HLH). Not surprisingly, many rheumatologists prefer the term secondary HLH rather than MAS to describe this condition, and efforts to change the nomenclature are in progress. The pathophysiology of MAS remains elusive, but observations in animal models, as well as data on the effects of new anticytokine therapies on rates and clinical presentations of MAS in patients with systemic juvenile idiopathic arthritis (sJIA), provide clues to the understanding of this perplexing clinical phenomenon. In this Review, we explore the latest available evidence and discuss potential diagnostic challenges in the era of increasing use of biologic therapies.

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Acknowledgements

A.A.G. is supported by NIH grants NIAMS R01-AR059049 and NIH P01-AR048929.

Author information

Affiliations

  1. Division of Rheumatology, ML 4010, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, Ohio 45229, USA.

    • Alexei A. Grom
  2. Department of Women's and Children's Health, Karolinska University Hospital, Karolinska vägen, 171 76 Solna, Stockholm, Sweden.

    • AnnaCarin Horne
  3. Division of Rheumatology, Ospedale Pediatrico Bambino Gesù, Piazza Sant'Onofrio, 4, Rome, Italy.

    • Fabrizio De Benedetti

Authors

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Contributions

A.A.G. contributed to researching data, discussions of content and writing of the article. A.C.H. contributed to discussions of content, review and editing of the manuscript before submission. F.D.B. contributed to discussions of content, review and editing of the manuscript before submission.

Competing interests

A.A.G declares that he has served as a consultant and speaker for Novartis and Roche and worked in collaboration with NovImmune. F.D.B declares that he has received unrestricted research grants from Pfizer, AbbVie, Novartis, NovImmune, Roche, and SOBI, and travel support from Roche. A.C.H. declares no competing interests.

Corresponding author

Correspondence to Alexei A. Grom.

Supplementary information

PDF files

  1. 1.

    Supplementary information S1 (table)

    Adjudication criteria for MAS cases