Sarcoidosis Pathophysiology and Clinical Characteristics

Core Immunologic Mechanism

The American College of Physicians suggests that sarcoidosis is fundamentally a T-cell mediated inflammatory disorder characterized by the formation of compact, non-caseating granulomas that result from an exaggerated immune response to unidentified antigens in genetically susceptible individuals 1
Abnormal cellular immune activation with accumulation of CD4+ T helper cells at sites of disease activity, which release pro-inflammatory cytokines, particularly IL-2 and TNF-alpha, driving the inflammatory cascade 1

The American Thoracic Society notes that the hallmark pathologic feature is the formation of well-organized, non-caseating granulomas with distinctive architecture, consisting of a central core of tightly packed epithelioid histiocytes and multinucleated giant cells, and a peripheral zone containing loosely organized lymphocytes 2, 3
Granulomas remain discrete and non-necrotic, though focal minimal ischemic necrosis may occur, and fibrosis begins at the granuloma periphery and extends centrally, with or without calcification, representing the healing phase 2, 3

The American Journal of Respiratory and Critical Care Medicine reports that granulomas follow a characteristic perilymphatic distribution, located around bronchovascular bundles and fibrous septa containing pulmonary veins, and concentrated near visceral pleura 2, 3, 4

The American Journal of Respiratory and Critical Care Medicine states that abnormal vitamin D metabolism occurs within granulomatous lesions, with granulomas producing elevated 1,25-dihydroxyvitamin D levels, leading to hypercalcemia and hypercalciuria in affected patients 4, 5
Parathyroid hormone levels remain normal to low despite calcium abnormalities 4, 5