Sarcoidosis

Basics

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

Genetics

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

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

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