A chronic granulomatous disease (CGD) with noncaseating epithelioid giant cell granulomas in multiple organs that has two distinct variants often differentiated by age of onset


  • Early-onset sarcoidosis (EOS)/Blau syndrome
    • Incidence 0.29/100,000/year
    • No gender or geographic predominance
    • Triad of arthritis, uveitis, and dermatitis presenting prior to age 5 years
  • Adult-type disease (ATD)
    • Incidence 1.02/100,000/year
    • Likely more common in the southwestern part of the United States
    • More often with systemic symptoms
    • Pulmonary involvement may also occur in older adolescents.
    • CNS involvement (rare): seizures, cranial neuropathy, hypothalamic dysfunction

Risk Factors


  • EOS/Blau
    • Mutation in the CARD15/NOD2 gene on chromosome 16 (different location than Crohn disease) either spontaneous (EOS) or familial AD (Blau)
  • ATD
    • African Americans are more commonly affected than whites.
    • Specific genetic tendencies not identified


  • Unknown (possibly an inflammatory response to an unknown antigen—infection)
  • EOS/Blau—NOD2 is a bacterial sensor in dendritic cells; mutation is a gain-of-function leading to exuberant inflammation; possibly changes in autophagy
  • Possible association with substantial dust inhalation (e.g., collapse of World Trade Center towers in New York City in 2001)


  • EOS/Blau—large polycyclic granulomas with dense lymphocytic coronas, CD68+ macrophages, and CD4+ T lymphocytes; abundant inflammatory cytokine expression
  • ATD—noncaseating epithelioid granulomas with monocytes/macrophages/epithelioid and multi-nucleated giant cells in the center surrounded by CD4+ T lymphocytes, plasma cells

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