Description

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

Epidemiology

• 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

Etiology

• 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)

Pathophysiology

• 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