Takayasu’s arteritis (TA) is a chronic vasculitis that predominantly affects the aorta, its main branches, and the pulmonary arteries. Although it is the third most common vasculitis worldwide, the cause is largely unknown[1, 2]. The classic patient phenotype is an Asian woman who is between 20 to 30 years old. It is relatively uncommon in North America and Europe, with a female to male predominance of 8.5:1. In pediatrics the disease typically presents between the ages of 10 and 20 years old, but it has presented as early as 24 months of age. The delay in diagnosis from initial disease manifestation can be 2–11 years in adults and sometimes longer in children.
In general, TA is viewed as having two phases, an acute inflammatory phase and a chronic fibrotic phase. The acute phase is characterized by a lymphocytic infiltrate with occasional giant cells of the media and fibroblast proliferation causing thickening of the intima of large vessels. Inflammation transitions to fibrosis during the chronic phase. Elastic tissue in vessel walls is replaced by collagen resulting in thickening of all three layers of the vessel. The intima may become rigid, and aneurysmal formation can occur secondary to mural stress on the vessel wall.
Although, the exact pathogenesis of TA is not well understood, several lines of evidence support the important role of cellular autoimmunity. The vaso vasorum is thought to act as a gateway allowing the accumulation of cellular infiltrate into the vessel walls via upregulation of cellular adhesion molecules and adventitial neovascularisation. The cellular infiltrate is characterized by a mixture of lymphocytes, predominately CD4+ T cells, dendritic cells, macrophages, giant cells and B cells. Pro-inflammatory T-cell cytokines, such as TNF-α, IL-6 and IFN-γ, have been identified in the peripheral circulation in TA patients, both expressed in sera and by peripheral blood mononuclear cells. TNF-α is an important contributor to granuloma formation and has also been identified in aortic tissue of patients with TA, therefore implicating TNF-α as a possible therapeutic target.
Clinically, the early symptoms of the disease are nonspecific, including night sweats, anorexia, weight loss, fatigue, myalgia, and arthritis. These symptoms can be followed by unexplained hypertension. The most frequent presentation in childhood is hypertension, followed by headaches, fever, dyspnea, weight loss, and vomiting. Organ manifestations arise from reduced blood supply due to vascular stenosis and subsequent ischemia. Claudication and poor or absent arterial pulses occur in areas of vessel involvement. The combination of nonspecific symptoms with decreased/absent pulses should raise suspicion for Takayasu’s arteritis, coined the ‘pulseless disease’.
The first report of coronary involvement with TA was described in 1951[9, 10]. It has since been estimated that 10-20% of all Takayasu’s patients have coronary artery involvement[3, 9], based on autopsy and case series. One large cohort study of 129 patients in Korea, with a mean age of 29.5 years, found the prevalence of coronary artery involvement to be 23% (30 patients) between 1987 and 1991, when coronary arteriography was used to screen patients without symptoms of angina. This series did not address the prognosis of patients with asymptomatic coronary involvement, however coronary ischemia is a recognized cause of death in these patients that warrants aggressive treatment once found[10, 12]. Even if immediate ischemia does not occur due to coronary artery occlusion, vessels which have been inflamed in systemic vasculitides, such as TA, show premature atherosclerosis, placing patients at risk for myocardial infarction.
Three types of coronary artery lesions have been described pathologically. Type 1 is stenosis or occlusion of the coronary ostia and the proximal segment of the coronary arteries. Ostial stenosis occurs from extension of the inflammation-induced intimal proliferation and fibrous contraction from the ascending aorta and the coronary ostia[10, 13]. Type 2 is diffuse or focal coronary arteritis, which can extend to all epicardial branches or may involve focal segments (skip lesions). Type 3 is the presence of coronary artery aneurysms. Type 1 is believed to be the most common lesion, while types 2 and 3 are considered uncommon.
Once the diagnosis of TA is made, evaluation of the extent of disease becomes important for management of its complications. To our knowledge, there is little data on the evaluation of pediatric TA patients for coronary artery involvement and even less data on the management of such patients. Because of the life threatening complications of coronary artery involvement, a thorough baseline evaluation should be performed, as the medical and surgical options for repair depend on symptoms of ischemia and grade of lesions present[10, 14].