Large and medium-vessel vasculitides

Vasculitis of large elastic arteries, such as the aorta and its proximal branches, is a typical manifestation of giant-cell arteritis (GCA) and Takayasu’s arteritis (TA) and rarely occurs with other autoimmune diseases. Within the wall of affected arteries, T lymphocytes and macrophages form granulomatous arrangements and elicit a maladaptive tissue-repair-response, causing aneurysmal dilation and dissection or luminal occlusion and tissue ischemia. Lesional T cells produce a broad spectrum of proinflammatory effector molecules [interferon-γ, interleukin (IL)-17, IL-21, IL-2, IL-9, etc.] and regulate tissue-damaging macrophages that secrete cytokines, chemokines, metalloproteinases, growth and angiogenesis factors, and reactive oxygen species. Immuno-stromal interactions implicate endothelial cells, fibroblasts, and smooth-muscle cells in the disease process. Vascular inflammation is often combined with extravascular disease, which is characterized by an intense hepatic acute phase response and manifests with constitutional symptoms. Causative events have not been identified, but host age is the strongest risk factor and abnormalities in the local tissue microenvironment may render select arteries susceptible to vasculitis. Corticosteroids remain the cornerstone of therapy. Therapeutic blockade of IL-6 may be helpful in controlling the hepatic acute phase response and extravascular disease. Frontiers in long-term management include the identification and targeting of tissue-resident T cells that give rise to chronic smoldering vasculitis. Noninvasive imaging techniques are critical in diagnosing TA and in following patients with large-vessel vasculitis on chronic immunosuppression. In the case of GCA histologic evaluation of the temporal artery is highly valuable in guiding diagnostic and therapeutic decisions.