Takayasu Arteritis

Updated: Apr 13, 2016
  • Author: Jefferson R Roberts, MD; Chief Editor: Herbert S Diamond, MD  more...
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Overview

Background

Takayasu arteritis is a rare, systemic, inflammatory large-vessel vasculitis of unknown etiology that most commonly affects women of childbearing age. It is defined as "granulomatous inflammation of the aorta and its major branches" by the Chapel Hill Consensus Conference on the Nomenclature of Systemic Vasculitis. [1] See the image below. (See Etiology and Epidemiology.)

Complete occlusion of the left common carotid arte Complete occlusion of the left common carotid artery in a 48-year-old woman with Takayasu disease. Also note narrowing of the origin of the right subclavian artery and a narrowed small vessel with subsequent aneurysmal dilatation on the right side. Image courtesy of Robert Cirillo, MD.

Takayasu arteritis commonly occurs in woman younger than age 50 years; however, it has been reported in patients as young as age 6 months (see Pediatric Takayasu Arteritis). Takayasu arteritis can manifest as isolated, atypical, and/or catastrophic disease. It can involve any or all of the major organ systems. The disease has been reported in all parts of the world, although it appears to be more prevalent in Asians. (See Epidemiology.)

Angiography-based categories

Takayasu arteritis can be divided into the following six types based on angiographic involvement (see Workup) [2] :

  • Type I - Branches of the aortic arch
  • Type IIa - Ascending aorta, aortic arch, and its branches
  • Type IIb - Type IIa region plus thoracic descending aorta
  • Type III - Thoracic descending aorta, abdominal aorta, renal arteries, or a combination
  • Type IV - Abdominal aorta, renal arteries, or both
  • Type V - Entire aorta and its branches

Patient education

Patients need to understand the nature of the disease and the need to take medications to prevent complications. When in remission or when experiencing mild forms of Takayasu arteritis, patients are tempted to stop antihypertensive drugs, thus increasing their risk of serious neurologic and other systemic complications. (See Treatment and Medication.)

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Pathophysiology

Takayasu arteritis is an inflammatory disease of large- and medium-sized arteries, with a predilection for the aorta and its branches. Advanced lesions demonstrate a panarteritis with intimal proliferation.

Lesions produced by the inflammatory process can be stenotic, occlusive, or aneurysmal. All aneurysmal lesions may have areas of arterial narrowing. Vascular changes lead to the main complications, including hypertension, most often due to renal artery stenosis or, more rarely, stenosis of the suprarenal aorta; aortic insufficiency due to aortic valve involvement; pulmonary hypertension; and aortic or arterial aneurysm.

Congestive heart failure is a common finding, much more so than dilated cardiomyopathy, myocarditis, and pericarditis, which also have been reported. In patients in whom the pulmonary artery is involved, the right artery appears to be affected more than the left, with patients developing pneumonia, interstitial pulmonary fibrosis, and alveolar damage.

Other pathophysiologic consequences include hypotensive ischemic retinopathy, vertebrobasilar ischemia, microaneurysms, carotid stenosis, hypertensive encephalopathy, and inflammatory bowel disease. Rarely, Takayasu arteritis has also been associated with glomerulonephritis, systemic lupus, polymyositis, polymyalgia rheumatica, rheumatoid arthritis, Still disease, and ankylosing spondylitis.

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Etiology

The etiology of Takayasu arteritis is unknown. The underlying pathologic process is inflammatory, with several etiologic factors having been proposed, including infection with spirochetes, Mycobacterium tuberculosis, and streptococcal organisms, and circulating antibodies due to an autoimmune process. Genetic factors may play a role in the pathogenesis.

An antigen may stimulate aortic tissue, leading to the expression of heat shock protein–65, which, in turn, induces major histocompatibility (MHC) class I–related chain A (MICA). Natural killer cells and gamma-delta T cells expressing NKG2D receptors may infiltrate and recognize MICA on vascular smooth muscle cells, leading to acute inflammation. Proinflammatory cytokines are also released from the natural killer and T-cells, inducing the production of matrix metalloproteinases (MMPs) and amplifying the inflammatory response. This, in turn, would induce more MHC antigen and stimulate molecule expression on vascular cells, recruiting more mononuclear cells.

Histocompatibility complexes are activated through Toll-like receptors. Th1 lymphocytes, through interferon-gamma, activate macrophages, which, in turn, release vascular endothelial growth factor (VEGF). This ultimately results in smooth muscle migration and intimal proliferation. Th17 cells induced by the interleukin (IL)–23 microenvironment also contribute to vascular lesions through activation of infiltrating neutrophils.

Previous studies have shown that the cellular infiltrate in Takayasu arteritis contains about 15% each of CD4+ and CD8+ T cells. IL-6 is a proinflammatory cytokine mainly synthesized by activated monocytes, macrophages, and T cells. IL-6 activates B cells and enhances T-cell cytotoxicity, natural killer cell activity, fibroblast proliferation, and acute-phase protein synthesis. Amplification of proinflammatory cytokine genes from aortic tissue reveals strong expression of IL-6 transcripts. [3]

In a case report, M tuberculosis and its 65-kd heat shock protein was implicated in the etiology. Patients with Takayasu arteritis were found to have higher immunoglobulin G (IgG), immunoglobulin M (IgM), and immunoglobulin A (IgA) titers against the M tuberculosis extract than did patients without the condition. [4]

One article reported the presence of CD3+ T cells and IgG antibodies reactive to circulating antimycobacterial heat shock protein 65 (mHSP65) antibodies and to its human homologue, hHSP60. [5] This suggests a possible cross-reactivity of immune response between mHSP65 and hHSP60. Case reports suggesting the role of antiendothelial cell, anticardiolipin, and antiaorta antibodies also exist.

In Japanese patients, human leukocyte antigen Bw52 (HLA-Bw52), which is in linkage disequilibrium with human leukocyte antigen DR4 (HLA-DR4), has been observed with increased frequency. Patients with the Bw52 genotype had a higher rate of aortic regurgitation. However, studies of HLA antigens in North American populations have not confirmed this.

A study comparing HLA-B alleles in Mexican patients with Takayasu arteritis and tuberculosis showed distinct, specific alleles. Takayasu arteritis was characterized by HLA-B39, -B44 and -B52; pulmonary tuberculosis, by HLA-B35; and extrapulmonary tuberculosis, by HLS-B39 and -B40. [6] Takayasu arteritis is associated with HLA-B22 in the United States.

One study demonstrated an association between several cases of Takayasu arteritis and CD36 deficiency (CD36d). [7] The human CD36 antigen is a multifunctional membrane glycoprotein that belongs to the class B scavenger receptor family. It is expressed on monocytes, platelets, and endothelial cells, and contributes to myocardial fatty acid transport. In patients with CD36d, myocardial I-15-(p-iodophenyl)-3-(R,S)-methyl pentadecanoic acid (BMIPP) uptake was absent.

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Epidemiology

Occurrence in the United States

Takayasu arteritis is estimated to affect 2.6 persons per million annually. The prevalence is 2.6-6.4 persons per million population. Any discrepancy in terms of pinpointing the prevalence is attributed to genetic factors and difficulty in diagnosis.

Between 1971 and 1983 in Olmsted County, Minnesota, three cases were recorded, thus establishing an annual incidence of 2.6 cases per million population. [8]

International occurrence

Worldwide incidence of Takayasu arteritis is estimated at 2.6 cases per million per year. Although the disease has a worldwide distribution, it is observed more frequently in Asian countries such as Japan, Korea, China, India, Thailand, and Singapore, as well as in Turkey, Israel, and Central and South America. About 100-200 new cases of Takayasu arteritis are registered each year in Japan. [9]

The prevalence of the disease in Sweden is similar to that in the United States (ie, 2.6-6.4 persons per million population). In the United Kingdom, the annual incidence is 0.15 case per million.

Race-, sex-, and age-related demographics

Takayasu arteritis is observed more frequently in patients of Asian or Indian descent. Japanese patients with Takayasu arteritis have a higher incidence of aortic arch involvement. In contrast, series from India report higher incidences of abdominal involvement. [9, 10]

Approximately 80% of patients with Takayasu arteritis are women; however, the high female-to-male ratio seems to decrease west of Japan. In India, the female-to-male ratio is as low as 1.6:1. [9]

Most patients with Takayasu arteritis are aged 4-63 years, with the mean age of onset being approximately 30 years. Fewer than 15% of cases present in individuals older than 40 years.

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Prognosis

Takayasu arteritis is associated with substantial morbidity and may be life-threatening. Its course usually extends for many years, with varying degrees of activity. Approximately 20% of patients have a monophasic and self-limited disease. In others, Takayasu arteritis is progressive or relapsing/remitting and requires immunosuppressive treatment. [11, 12, 13]

A National Institutes of Health study of 60 patients with Takayasu arteritis showed that 20% of patients had a monophasic illness, self-limiting illness and therefore did not require immunosuppressive treatment. In the remaining 80% of patients, who did not have a monophasic illness and who experienced a single exacerbation, immunosuppressive therapy resulted in remission in 60%. Of these, one half experienced relapse after immunosuppressive therapy was stopped.

Complications

The overall morbidity in Takayasu arteritis depends on the severity of the lesions and their consequences. Complications of the disease include the following:

  • Stroke
  • Intracranial hemorrhage
  • Seizures
  • Graft stenosis and/or occlusion
  • Ischemia
  • Organ failure
  • Complications of hypertension
  • Fetal injury
  • Valvular heart disease
  • Retinopathy
  • Renovascular hypertension

Long-term use of corticosteroids can lead to infection, adrenal suppression, cataracts, hyperglycemia, hypertension (which complicates blood pressure control), osteoporosis, and aseptic necrosis.

Morbidity and mortality

Takayasu arteritis is a chronic relapsing and remitting disorder. The overall 10-year survival rate is approximately 90%; however, this rate is reduced in the presence of major complications. [11]

The 5- and 10-year survival rates are approximately 69% and 36%, respectively, in patients with 2 or more complications. The 5- and 10-year survival rates associated with 1 or fewer complications are 100% and 96%, respectively. [14]

Strict management of traditional cardiovascular risk factors such as dyslipidemia, hypertension, and lifestyle factors that increase the risk of cardiovascular disease is mandatory to minimize secondary cardiovascular complications. These complications are the major cause of death in Takayasu arteritis.

A 2008 study assessing quality of life with Takayasu arteritis showed worse scores for physical and mental health compared with many other chronic diseases associated with peripheral vascular disease. Disease remission is the only factor that positively influences physical and mental quality of life. [15] Patients with rheumatoid arthritis or ankylosing spondylitis rated their quality of life as similar to those with Takayasu arteritis. [16]

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