Clinical meaning
Giant cell arteritis (GCA) is a granulomatous vasculitis of large and medium-sized arteries with a predilection for the extracranial branches of the carotid artery, particularly the temporal, ophthalmic, and vertebral arteries. The pathological process begins when dendritic cells in the vascular adventitia become activated (likely by an unknown antigenic trigger) and recruit CD4+ T-helper cells, which infiltrate the arterial wall through the vasa vasorum. These T cells differentiate into Th1 and Th17 subsets, producing interferon-gamma and interleukin-17 respectively, which activate macrophages in the media. Macrophages fuse into multinucleated giant cells at the intima-media junction and produce matrix metalloproteinases (MMPs) that fragment the internal elastic lamina — the histological hallmark on temporal artery biopsy. Concurrent intimal hyperplasia caused by platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF) narrows the arterial lumen, producing ischemic complications. The ophthalmic artery and its branches (posterior ciliary arteries) are particularly vulnerable because they are end-arteries without collateral circulation; occlusion causes anterior ischemic optic neuropathy (AION) with sudden, irreversible monocular vision loss. Interleukin-6 (IL-6) is the key cytokine driving the systemic inflammatory response, stimulating hepatic acute-phase protein production (markedly elevated ESR and CRP) and constitutional symptoms. This IL-6 predominance explains why tocilizumab (IL-6 receptor antagonist) is effective as a steroid-sparing agent but also why CRP cannot be used for disease monitoring during tocilizumab therapy.