Large and Medium Vessel Vasculitides

Vasculitis of large elastic arteries, such as the aorta and its major proximal branches, is a typical manifestation of giant cell arteritis (GCA) and Takayasu's arteritis and rarely occurs as a complication other autoimmune syndromes. T lymphocytes and macrophages assemble in granulomatous arrangements within the walls of affected arteries and elicit a maladaptive response-to-injury, causing dissection, stenosis, or aneurysmal dilatation of the blood vessel. Causative events have not been identified but abnormalities in innate and adaptive immune function drive the vasculitis. Key pathogenic elements are vascular dendritic cells positioned in the adventitia which recognize danger signals and attract and prime CD4 T cells. CD4 T cells differentiate into IFN-γ-producing Th1 cells and IFN-γ holds a central function in orchestrating macrophage activation, giant cell formation, smooth muscle cell de-differentiation, and wall remodeling. In early vasculitis, Th1 cells are accompanied by IL-17-producing Th17 cells which contribute to activation of vascular cells. An array of proinflammatory cytokines, including IL-1β, IL-6, IL-12, IL-21, IL-23, IL-32, and IL-33 is present in the vasculitic lesions. Vessel-wall residing cells, such as endothelial cells and vascular smooth muscle cells, mount a hyperplastic response, leading to lumen-occlusive intimal hyperplasia. Diagnostic approaches rely on non-invasive imaging techniques to evaluate life-sustaining arteries, such as the aorta. In the case of GCA, the temporal artery is accessible for histological evaluation. Corticosteroids remain the cornerstone of therapy. They promptly control the systemic component of disease, but may not be able to induce remission of vessel wall inflammation.