Blau syndrome, the prototypic auto-inflammatory granulomatous disease

Pediatr Rheumatol Online J. 2014 Aug 6;12:33. doi: 10.1186/1546-0096-12-33. eCollection 2014.


Blau syndrome is a monogenic disease resulting from mutations in the pattern recognition receptor NOD2, and is phenotypically characterized by the triad of granulomatous polyarthritis, dermatitis and uveitis. This paper reviews briefly the classical clinical features of the disease, as well as more recently described extra-triad symptoms. From an ongoing prospective multicenter study, we provide new data on the natural history of Blau syndrome, focusing on functional status and visual outcome. We also present an update of the range of different NOD2 mutations found in Blau syndrome as well as recent data on morphologic and immunohistochemical characteristics of the Blau granuloma. Finally, emerging insights into pathogenic mechanisms including activation of NOD2 signal transduction, and potential biomarkers of disease activity are discussed.

Keywords: Blau syndrome; Granulomatous diseases; NOD2; RIP2 kinase; Sarcoidosis; Uveitis.

Publication types

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

MeSH terms

  • Arthritis / genetics
  • Arthritis / pathology
  • Cranial Nerve Diseases / genetics*
  • Cranial Nerve Diseases / pathology*
  • Cranial Nerve Diseases / physiopathology
  • Dermatitis / genetics
  • Dermatitis / pathology
  • Granuloma / genetics*
  • Granuloma / pathology*
  • Granuloma / physiopathology
  • Hereditary Autoinflammatory Diseases / genetics*
  • Hereditary Autoinflammatory Diseases / pathology*
  • Hereditary Autoinflammatory Diseases / physiopathology
  • Humans
  • Mutation / genetics
  • Nod2 Signaling Adaptor Protein / genetics
  • Prospective Studies
  • Sarcoidosis
  • Signal Transduction / physiology
  • Synovitis / genetics*
  • Synovitis / pathology*
  • Synovitis / physiopathology
  • Uveitis / genetics*
  • Uveitis / pathology*
  • Uveitis / physiopathology


  • NOD2 protein, human
  • Nod2 Signaling Adaptor Protein

Supplementary concepts

  • Blau syndrome