The Hyperferritinemic Syndrome: Macrophage Activation Syndrome, Still's Disease, Septic Shock and Catastrophic Antiphospholipid Syndrome

BMC Med. 2013 Aug 22;11:185. doi: 10.1186/1741-7015-11-185.

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".

Publication types

  • Review

MeSH terms

  • Animals
  • Antiphospholipid Syndrome / blood*
  • Antiphospholipid Syndrome / diagnosis
  • Antiphospholipid Syndrome / epidemiology
  • Cataract / blood
  • Cataract / congenital
  • Cataract / diagnosis
  • Cataract / epidemiology
  • Catastrophic Illness / epidemiology
  • Ferritins / blood*
  • Humans
  • Inflammation Mediators / blood
  • Iron Metabolism Disorders / blood
  • Iron Metabolism Disorders / congenital
  • Iron Metabolism Disorders / diagnosis
  • Iron Metabolism Disorders / epidemiology
  • Macrophage Activation Syndrome / blood*
  • Macrophage Activation Syndrome / diagnosis
  • Macrophage Activation Syndrome / epidemiology
  • Shock, Septic / blood*
  • Shock, Septic / diagnosis
  • Shock, Septic / epidemiology
  • Still's Disease, Adult-Onset / blood*
  • Still's Disease, Adult-Onset / diagnosis
  • Still's Disease, Adult-Onset / epidemiology

Substances

  • Inflammation Mediators
  • Ferritins

Supplementary concepts

  • Hyperferritinemia, hereditary, with congenital cataracts