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Open Access Opinion

The Hyperferritinemic Syndrome: macrophage activation syndrome, Still’s disease, septic shock and catastrophic antiphospholipid syndrome

Cristina Rosário1, Gisele Zandman-Goddard23, Esther G Meyron-Holtz4, David P D’Cruz5 and Yehuda Shoenfeld12*

Author Affiliations

1 Center for Autoimmune Diseases, Sheba Medical Center (affiliated with the Tel-Aviv University), Tel-Hashomer 52621, Israel

2 Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel

3 Department of Medicine C, Wolfson Medical Center, Holon, Israel

4 Department of Biotechnology and Food Engineering, Technion - Israel Institute of Technology, Haifa, Israel

5 Louise Coote Lupus Unit, Guy’s and St Thomas’ Hospital, London, England, UK

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BMC Medicine 2013, 11:185  doi:10.1186/1741-7015-11-185

Published: 22 August 2013

Abstract

Background

Over the last few years, accumulating data have implicated a role for ferritin as a signaling molecule and direct mediator of the immune system. Hyperferritinemia is associated with a multitude of clinical conditions and with worse prognosis in critically ill patients.

Discussion

There are four uncommon medical conditions characterized by high levels of ferritin, namely the macrophage activation syndrome (MAS), adult onset Still’s disease (AOSD), catastrophic antiphospholipid syndrome (cAPS) and septic shock, that share a similar clinical and laboratory features, and also respond to similar treatments, suggesting a common pathogenic mechanism. Ferritin is known to be a pro-inflammatory mediator inducing expression of pro-inflammatory molecules, yet it has opposing actions as a pro-inflammatory and as an immunosuppressant. We propose that the exceptionally high ferritin levels observed in these uncommon clinical conditions are not just the product of the inflammation but rather may contribute to the development of a cytokine storm.

Summary

Here we review and compare four clinical conditions and the role of ferritin as an immunomodulator. We would like to propose including these four conditions under a common syndrome entity termed “Hyperferritinemic Syndrome”.

Keywords:
Hyperferritinemia; Macrophage activation syndrome (MAS); Adult onset Still’s disease (AOSD); Catastrophic antiphospholipid syndrome (cAPS); Septic shock