**1. Introduction**

Giant cell arteritis (GCA), also known as temporal arteritis or Horton disease, is a systemic inflammatory large-vessel vasculitis that usually affects the aorta and its major branches [1].

The pathophysiology of GCA is complex and not fully understood. Histopathology studies reveal inflammation of the artery wall with predominance of CD4+ T lymphocytes and macrophages, which frequently undergo granulomatous organization with formation of giant cells. Immunopathology and molecular studies performed with temporal artery biopsies have led to the current pathogenic model [2].

GCA is primarily an immune-mediated disease due to a maladaptive response to endothelial injury, occurring in susceptible individuals and triggered by factors that have not been identified with certainty. Several microbe and viral sequences, including varicella-zoster virus, have been detected in temporal artery lesions, but no convincing causal relationship has been demonstrated [3].

The initial inflammatory response involves the activation of dendritic cells, present in the adventitia of normal arteries, through pathogen- or damage-sensing receptors, such as toll-like receptors, producing chemokines able to attract and retain dendritic cells as well as lymphocytes and macrophages. Once activated, dendritic cells are enabled to process and present antigens and strongly express major histocompatability complex (MHC) class II and costimulatory molecules (CD83 and CD86) required for T-cell recruitment [4].

Once activated, both T helper (Th)1 and Th17 differentiation pathways contribute to the development of vascular inflammation. Interleukin (IL)-12 and IL-18 produced by dendritic cells stimulate Th1 differentiation and production of interferon (IFN)-gamma which is noticeably expressed in GCA-involved arteries. IFN-gamma causes endothelial cells and vascular smooth muscle to recruit more Th1 cells, CD8+ T cells, and monocytes which differentiate into macrophages and the characteristic giant cells that produce growth factors, interleukins and proteolytic enzymes playing a distinctive role granuloma formation that progressively narrow and obstruct the vessel wall [5].

Moreover, IL-1-beta, IL-6, and IL-21 promote Th17 differentiation, which is maintained by IL-23 and results in IL-17A expression. IL-17A, profusely expressed in GCA lesions, is a proinflammatory cytokine having pleiotropic effects on a variety of cells, namely macrophages, fibroblasts, endothelial cells and vascular smooth muscle cells [6].

Systemic manifestations are related the inflammatory process and cytokine amplification. Inflammation-induced vascular remodeling leads to concentric intimal hyperplasia occurring as a repair mechanism in response to injury of the blood vessel wall. End-organ involvement results from mural hyperplasia which can narrow the arterial lumen, resulting in distal ischemia and ischemic complications of the disease [7].
