Takayasu Arteritis

Chapter: Takayasu Arteritis
McMaster Section Editor(s): Jonathan D. Adachi
Section Editor(s) in Interna Szczeklika: Andrzej Budaj, Wiktoria Leśniak
McMaster Author(s): Dylan Kelly, Stephanie Garner, Nader Khalidi
Author(s) in Interna Szczeklika: Marzena Frołow
Additional Information

Definition, Etiology, PathogenesisTop

Takayasu arteritis (TA) is a granulomatous vasculitis of large and medium vessels of unknown etiology that affects mostly the aorta and its branches. Less frequently, it may involve other arteries, such as the pulmonary arteries.

Typically, TA causes numerous segmental stenoses of the aortic branches. Thrombi may form in the stenotic segments and sometimes cause peripheral thromboembolism. Aneurysms usually occur distally to the stenosis. TA rarely leads to aortic dissection or rupture.

In general terms, large-vessel vasculitis occurring in patients aged >50 years is usually diagnosed as or has a clinical form of giant cell arteritis/temporal arteritis. In younger people (<50 years and more so <40 years) the clinical presentation and diagnosis is usually that of Takayasu arteritis.

Clinical FeaturesTop

Eighty to 90% of patients with TA are women. The age of onset is typically 10 to 40 years of age. The prevalence is highest in people of Asian descent.

1. Systemic manifestations: Early manifestations usually include influenza-like or rheumatic-like symptoms, such as low-grade fever, fatigue, myalgia, and arthralgia. Acute symptoms usually resolve spontaneously but may occur throughout the disease course.

2. Vascular manifestations: Patients with chronic disease develop symptoms of stenosis and arterial occlusion. Typical findings include weak or asymmetric pulses in the upper extremities (“pulseless disease”) and bruits in the aorta and its main branches. With inflammation of the vasculature, pain and tenderness over the affected vessels may occur.

1) Aortic disease: The presenting manifestation may be an incidentally detected large thoracic aortic aneurysm. Patients may have audible bruits over stenoses within the aorta and a diastolic murmur of aortic regurgitation (an adverse prognostic factor). Heart failure from aortic insufficiency may occur.

2) Subclavian arteries: Stenosis or occlusion of a subclavian artery may lead to subclavian artery bruits, upper extremity claudication, and subclavian steal syndrome (reversal of ipsilateral vertebral artery flow leading to symptoms of vertebrobasilar ischemia). In patients with stenotic or occluded subclavian arteries, traditional blood pressure measurements are unreliable. A systolic blood pressure differential between the arms >10 mm Hg is abnormal. Systolic blood pressure should be measured on lower extremities with a Doppler device used for ankle-brachial index measurements.

3) Carotid and vertebral arteries: Manifestations depend on the location of stenosis and include dizziness, syncope, headache, visual disturbances, transient ischemic attacks, stroke, seizures, and claudication of the jaw.

4) Renal arteries: Patients commonly develop renal artery stenosis and resultant hypertension.

5) Gastrointestinal arteries: Abdominal pain, diarrhea, and gastrointestinal bleeding can occur from celiac and mesenteric artery involvement.

6) Pulmonary arteries: Dyspnea, hemoptysis, and chest pain can be evidence of pulmonary artery involvement.

7) Coronary arteries: Manifestations of myocardial ischemia may occur from coronary artery involvement or ostial narrowing.

DiagnosisTop

Diagnostic Tests

1. Blood tests: Laboratory findings in patients with TA are not specific and reflect the underlying inflammation. A normochromic, normocytic anemia is common. Erythrocyte sedimentation rate and C-reactive protein can reflect disease activity, but values within reference ranges alone are not sensitive enough to exclude active disease. Other laboratory abnormalities may include an elevated fibrinogen concentration, hypoalbuminemia, polyclonal hypergammaglobulinemia, and an elevated interleukin-6 (IL-6) concentration (a newly proposed laboratory test that is not currently widely available).Evidence 1Low Quality of Evidence (low confidence that we know the true sensitivity and specificity of erythrocyte sedimentation rate and C-reactive protein to screen for active disease in patients with Takayasu arteritis). Quality of Evidence lowered due to small sample sizes with the lack of access to a gold standard to assess disease activity and different outcomes between studies. Kerr GS, Hallahan CW, Giordano J, et al. Takayasu arteritis. Ann Intern Med. 1994 Jun 1;120(11):919-29. doi:10.7326/0003-4819-120-11-199406010-00004. PubMed PMID: 7909656. Dagna L, Salvo F, Tiraboschi M, et al. Pentraxin-3 as a marker of disease activity in Takayasu arteritis. Ann Intern Med. 2011 Oct 4;155(7):425-33. doi: 10.7326/0003-4819-155-7-201110040-00005. PubMed PMID: 21969341. Matsuyama A, Sakai N, Ishigami M, et al. Matrix metalloproteinases as novel disease markers in Takayasu arteritis. Circulation. 2003 Sep 23;108(12):1469-73. Epub 2003 Sep 2. doi:10.1161/01.CIR.0000090689.69973.B1. PubMed PMID: 12952836.

2. Imaging studies: Magnetic resonance angiography (MRA), computed tomography angiography (CTA), and angiography of the affected vessels demonstrate smooth luminal narrowing and possibly occlusion. CTA and MRA also have the added benefit of demonstrating wall thickening of the affected vessels. Positron emission tomography is being investigated as an imaging technique to monitor disease activity. Transthoracic echocardiogram is useful to assess for proximal aortic abnormalities and concomitant aortic insufficiency. Ultrasound of other affected vessels can also be useful if available.

Diagnostic Criteria

The American College of Rheumatology classification criteria for TA were designed to differentiate TA from other forms of vasculitis but are useful to help guide diagnosis. The classification requires that at least 3 of the following 6 criteria are met:

1) Disease onset at an age ≤40 years (note that many experts now use an age <50 years).

2) Claudication of any extremity (abnormal fatigue or discomfort with use, especially in the case of the upper extremities).

3) Weak or absent pulse in a brachial artery.

4) A systolic blood pressure differential between the arms ≥10 mm Hg.

5) Bruit over the subclavian artery or abdominal aorta.

6) Angiographic abnormalities not attributable to other causes, including stenosis or occlusion of the aorta, its branches, or proximal segments of the limb arteries.

Differential Diagnosis

Giant cell arteritis, aortic arch atherosclerosis, upper thoracic outlet syndrome, fibromuscular dysplasia of arteries, Behçet disease, Ehlers-Danlos syndrome, and ergotism.

Treatment Top

Pharmacotherapy

1. Glucocorticoids: Initial treatment for active disease with high-dose glucocorticoids (oral prednisone 1 mg/kg daily) for 3 months is suggested.Evidence 2Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Low Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to collected data coming from observational and retrospective studies with small numbers of patients. Because glucocorticoids are consistently used as initial treatment in these studies, comparisons with other potential first-line therapies are not available. Kerr GS, Hallahan CW, Giordano J, et al. Takayasu arteritis. Ann Intern Med. 1994 Jun 1;120(11):919-29. doi:10.7326/0003-4819-120-11-199406010-00004. PubMed PMID: 7909656. Maksimowicz-McKinnon K, Clark TM, Hoffman GS. Limitations of therapy and a guarded prognosis in an American cohort of Takayasu arteritis patients. Arthritis Rheum. 2007 Mar;56(3):1000-9. PubMed PMID: 17328078. Park MC, Lee SW, Park YB, Chung NS, Lee SK. Clinical characteristics and outcomes of Takayasu's arteritis: analysis of 108 patients using standardized criteria for diagnosis, activity assessment, and angiographic classification. Scand J Rheumatol. 2005 Jul-Aug;34(4):284-92. PubMed PMID: 16195161. If inflammatory markers normalize, constitutional symptoms improve, and clinical findings do not progress, the dose can be tapered down at a maximum rate of 10% of the dose per week. Most patients will remain on low-dose glucocorticoids to prevent relapse.

2. Glucocorticoid-sparing agents: In the case of glucocorticoid failure or an inability to taper down the dose, the use of methotrexate, mycophenolate mofetil, azathioprine leflunomide, or cyclophosphamide is suggested.Evidence 3Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Low Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to collected data coming from observational and retrospective studies with small numbers of patients. Because glucocorticoids are consistently used as initial treatment in these studies, comparisons with other potential first-line therapies are not available. Kerr GS, Hallahan CW, Giordano J, et al. Takayasu arteritis. Ann Intern Med. 1994 Jun 1;120(11):919-29. doi:10.7326/0003-4819-120-11-199406010-00004. PubMed PMID: 7909656. Maksimowicz-McKinnon K, Clark TM, Hoffman GS. Limitations of therapy and a guarded prognosis in an American cohort of Takayasu arteritis patients. Arthritis Rheum. 2007 Mar;56(3):1000-9. PubMed PMID: 17328078. Park MC, Lee SW, Park YB, Chung NS, Lee SK. Clinical characteristics and outcomes of Takayasu's arteritis: analysis of 108 patients using standardized criteria for diagnosis, activity assessment, and angiographic classification. Scand J Rheumatol. 2005 Jul-Aug;34(4):284-92. PubMed PMID: 16195161.

3. Biologic agents: In patients with disease refractory to glucocorticoid-sparing agents or in those who relapse with attempts to discontinue glucocorticoids, the anti–tumor necrosis factor alpha agent infliximab is suggested. In patients with disease refractory to infliximab, a trial of tocilizumab, an interleukin-6 receptor antibody, can be considered.Evidence 4Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Low Quality of Evidence (low confidence that we are certain patients refractory to disease-modifying antirheumatic drug therapy benefit from biologic agents). Quality of Evidence lowered because studies are limited to open-label observational studies. Clifford A, Hoffman GS. Recent advances in the medical management of Takayasu arteritis: an update on use of biologic therapies. Curr Opin Rheumatol. 2014 Jan;26(1):7-15. doi: 10.1097/BOR.0000000000000004. Review. PubMed PMID: 24225487.

Surgical Treatment

Invasive treatment (surgical or endovascular) depends on the clinical features of organ ischemia. Restenosis following vascular interventions is common and can occur in as many as 50% of patients after 2 years.Evidence 5Low Quality of Evidence (low confidence that we know the true rate of restenosis following surgical intervention for stenosis in Takayasu arteritis). Quality of Evidence lowered because studies are limited to chart reviews with large heterogeneity between the revascularization procedures performed. Park MC, Lee SW, Park YB, Lee SK, Choi D, Shim WH. Post-interventional immunosuppressive treatment and vascular restenosis in Takayasu's arteritis. Rheumatology (Oxford). 2006 May;45(5):600-5. Epub 2005 Dec 13. doi:10.1093/rheumatology/kei245. PubMed PMID: 16352637. Liang P, Tan-Ong M, Hoffman GS. Takayasu's arteritis: vascular interventions and outcomes. J Rheumatol. 2004 Jan;31(1):102-6. PubMed PMID: 14705227. Surgery may be required in patients with aortic regurgitation.

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