Periodic fever syndromes

Best Pract Res Clin Rheumatol. 2017 Aug;31(4):596-609. doi: 10.1016/j.berh.2017.12.001. Epub 2018 Jan 11.


Periodic fever syndromes are autoinflammatory diseases. The majority present in infancy or childhood and are characterised by recurrent episodes of fever and systemic inflammation that occur in the absence of autoantibody production or identifiable infection. The best recognised disorders include CAPS, FMF, TRAPS and MKD. Understanding the molecular pathogenesis of these disorders provides unique insights into the regulation of innate immunity. Diagnosis relies on clinical acumen and is supported by genetic testing. With the exception of FMF, which is prevalent in populations originating from the Mediterranean, these syndromes are rare and easily overlooked in the investigation of recurrent fevers. Disease severity varies from mild to life threatening, and one of the most feared complications is AA amyloidosis. Effective therapies are available for many of the syndromes, including colchicine, IL-1 blockade and anti-TNF therapies, and there is an increasing interest in blocking interferon pathways.

Keywords: Aphthous stomatitis; Blau syndrome; Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature syndrome (CANDLE); Cryopyrin-associated periodic syndromes (CAPS); Deficiency of IL-1 receptor antagonist (DIRA); Deficiency of IL-36 receptor antagonist (DITRA); Deficiency of adenosine deaminase 2 (DADA2); Familial Mediterranean fever (FMF); Mevalonate kinase deficiency (MKD); Pharyngitis and cervical adenitis (PFAPA); Tumour necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS).

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Child
  • Child, Preschool
  • Colchicine / therapeutic use
  • Cryopyrin-Associated Periodic Syndromes / diagnosis
  • Cryopyrin-Associated Periodic Syndromes / drug therapy
  • Familial Mediterranean Fever / diagnosis
  • Familial Mediterranean Fever / drug therapy
  • Fever / diagnosis
  • Fever / drug therapy
  • Hereditary Autoinflammatory Diseases* / diagnosis
  • Hereditary Autoinflammatory Diseases* / drug therapy
  • Humans
  • Immunity, Innate
  • Infant
  • Syndrome
  • Tumor Necrosis Factor-alpha / therapeutic use


  • Tumor Necrosis Factor-alpha
  • Colchicine

Supplementary concepts

  • Periodic fever, familial, autosomal dominant