Takayasu Arteritis

Abstract

Takayasu arteritis is an idiopathic granulomatous vasculitis of the aorta and its main branches and it constitutes one of the more common vasculitides in children. Inflammation and intimal proliferation lead to wall thickening, stenotic or occlusive lesions, and thrombosis, while destruction of the elastica and muscularis layers originates aneurysms and dissection. Carotid artery tenderness, claudication, ocular disturbances, central nervous system abnormalities, and weakening of pulses are the most frequent clinical features. The diagnosis is usually confirmed by the observation of large vessel wall abnormalities: stenosis, aneurysms, occlusion, and evidence of increased collateral circulation in angiography, MRA or CTA imaging. The purpose of this revision is to address the current knowledge on pathogenesis, investigations, classification, outcome measures and management, and to emphasize the need for timely diagnosis, effective therapeutic intervention, and close monitoring of this severe condition.

Keywords: Takayasu; aorta; arteritis; children; large vessel; vasculitis.

Figure 1

Immunopathogenesis of Takayasu arteritis. Schematic figure showing possible mechanisms in the aortic wall. Dendritic cells in the adventitia expressing specific HLA molecules are activated by a stimulus so far unrecognized. Expression of the 65 kDa HSP in the aortic tissue might play a role in dendritic cell activation. These cells synthesize and release proinflammatory cytokines (such as IL-18) and homing chemokines that recruit T cells to the vessel wall and initiate an aberrant T cell response. After interaction with dendritic cells, CD4-positive T cells with a Th1 phenotype release cytokines such as interferon (IFN)-γ and tumor necrosis factor (TNF)-α, which induce differentiation and increased function of macrophages, and also induce the coalescence of multinucleated giant cells, thus promoting the formation of granuloma. T cells with an induced Th17 phenotype release IL-17, which attracts and activates neutrophils in the vessel wall. Macrophages release IL-1 and IL-6, MMP, and ROS (which induce oxidative injury and degradation of media and intima layers, and disruption of the elastic laminae), VEGF (leading to neoangiogenesis), FGF, and PDGF, which results in exuberant intimal proliferation. These phenomena contribute to the structural damage in the aortic wall. IFN-γ, TNF-α, IL-6, IL-8, IL-17A, and IL-18 likely play a role in vessel wall damage (through the recruitment of mononuclear cells in the vessel wall) and systemic features of TA. CD8-positive T cells, γδ T-cells, and natural killer (NK) cells release of perforin and granzyme-B, which contribute to apoptosis and necrosis of smooth muscle cells and damage in the intimate layer. AAECA may also have a role in pathogenesis through the activation of endothelial cells and induction of complement- and cell-mediated cytotoxicity. Degenerative changes in the media and adventitia, as well as intimal fibrocellular hyperplasia, eventually lead to muscular layer weakening, aneurismal formation, vascular stenosis and thrombus formation. HSP, heat shock protein; HLA, human leukocyte antigen; PMN, polymorphonuclear neutrophil; NK, natural killer cell; MMP, matrix metalloproteinase; ROS, reactive oxygen species; PDGF, platelet-derived growth factor; VEGF, vascular endothelial growth factor; FGF, fibroblast growth factor; AAECA, anti-aortic endothelial cell antibodies.

Figure 2

Angiography showing stenosis in the brachiocephalic trunk at the subclavian emergence (*). Occlusion of left carotid artery close to the aortic arch (arrow). Left dilated vertebral artery emerging from the aortic arch (LV). Female, 7 year-old patient with Takayasu arteritis.

Figure 3

Same patient as in Figure 1. (A) right internal carotid artery (RICA) supplying the left hemisphere through the anterior communicating artery (ACA). (B) contrast into the left, hypertrophic vertebral artery (LVA) provides supply to the right vertebral artery (RVA) and the territory of the (occluded) left carotid artery.

Figure 4

(A) Magnetic resonance angiography demonstrating large, secular aneurysm in the aortic arch (*), stenosis in the thoracic aorta (arrow), and irregularity of the thoracic and abdominal aorta, including stenotic areas and a long aneurysm (arrowhead) proximal to the renal arteries in a 13 year-old girl with recent-onset Takayasu arteritis. (B) CT scan and three-dimensional reconstruction of the same patient, demonstrating same findings, but providing better quality-anatomical details.

Figure 5

(A) 3D reconstruction CT images of the whole aorta in a 12 year-old female Takayasu arteritis patient with thoraco-abdominal aortic aneurysm (bracket) proximal to a stenotic lesion (arrow) at the renal artery emergence site. (B) Detail of the aneurysmal dilatation and stenosis of the abdominal aorta (arrow), and stenosis of left renal artery (arrowhead).