Familial Mediterranean fever and related periodic fever syndromes/autoinflammatory diseases

Curr Opin Rheumatol. 2012 Jan;24(1):103-12. doi: 10.1097/BOR.0b013e32834dd2d5.


Purpose of review: The spectrum of periodic fever syndromes (PFS)/autoinflammation diseases is continuously expanding. This review provides an overview of the primary research and an update on the main clinical developments in these disorders published in the past 12-18 months.

Recent findings: IL-1β is pivotal to the pathogenesis of most of the PFS. In familial Mediterranean fever (FMF) MEFV mutations lead to gain of pyrin function, resulting in inappropriate IL-1β release that is dependent on ASC but not the NLRP3 inflammasome. Anti-IL-1 therapy is effective in tumour necrosis factor receptor-associated periodic syndrome (TRAPS), whilst both spontaneous and pathogen-associated molecular patterns (PAMPs) induced IL-1β release have been demonstrated in NLRP12-associated periodic syndrome (NAPS12). Somatic NLRP3/CIAS1 mosaicism is a significant cause of cryopyrin-associated periodic syndromes (CAPS). Close connections have also been established between metabolic and inflammatory pathways. In TRAPS increased reactive oxygen species (ROS) of mitochondrial origin leads to production of pro-inflammatory cytokines, whilst NLRP3 inflammasome activation in type 2 diabetes (T2D) is induced by oligomers of islet amyloid polypeptides (IAPP).

Summary: Caspase 1 activation and IL-1β release is central to the pathogenesis of many autoinflammatory syndromes. This is supported by the effectiveness of anti-IL-1 biologics in treatment of these disorders.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Caspase 1 / metabolism
  • Familial Mediterranean Fever / drug therapy
  • Familial Mediterranean Fever / etiology*
  • Familial Mediterranean Fever / metabolism
  • Humans
  • Interleukin-1beta / metabolism
  • Mevalonate Kinase Deficiency / drug therapy
  • Mevalonate Kinase Deficiency / etiology*
  • Mevalonate Kinase Deficiency / metabolism


  • Interleukin-1beta
  • Caspase 1