Takayasu's arteritis is an inflammatory disease affecting the aorta, its branches, and pulmonary arteries. It occurs predominantly in young women. Etiology is unknown. Vascular inflammation may cause arterial stenosis, occlusion, dilation, or aneurysms. It causes asymmetric pulses and symptoms and signs of arterial obstruction. Diagnosis is by aortic arteriography or magnetic resonance angiography. Treatment is with corticosteroids and, for organ-threatening ischemia, vascular interventions such as bypass surgery.

Takayasu's arteritis is rare. It is more common among Asians but occurs worldwide. Female:male ratio is 8:1, and age at onset is typically 15 to 30. In North America, annual incidence is estimated to be 2.6 cases/million.

Etiology

The cause is unknown. Cell-mediated immune mechanisms may be involved and may be similar to those in giant cell arteritis.

Pathophysiology

Takayasu's arteritis affects primarily large elastic arteries. The most commonly affected are the innominate and subclavian arteries, aorta (mainly the ascending aorta and the arch), common carotid arteries, and renal arteries. Most patients have stenoses or occlusions. Aneurysms occur in about one third of patients. Usually, the wall of the aorta or its branches thickens irregularly, with intimal wrinkling. When the aortic arch is affected, orifices of the major arteries emerging from the aorta may be markedly narrowed or even obliterated by intimal thickening. In one half of patients, pulmonary arteries are also affected.

Histologically, early changes consist of adventitial mononuclear infiltrate with perivascular cuffing of the vasa vasorum. Later, intense mononuclear inflammation of the media may occur, sometimes accompanied by granulomatous changes, giant cells, and patchy necrosis of the media. Morphologic changes may be indistinguishable from those of giant cell arteritis. Panarteritic inflammatory infiltrates cause marked thickening of the affected artery and subsequent luminal narrowing and occlusion.

Symptoms and Signs

Most patients present with only focal symptoms that reflect hypoperfusion of the affected organ or limb. Takayasu's arteritis may have 3 stages:

• Systemic disease, usually with systemic, nonspecific symptoms (eg, fever, malaise, night sweats, weight loss, arthralgias, fatigue)
• Vascular inflammatory phase, with ischemic manifestations that may wax and wane
• Inactive (burned-out) disease, sometimes with acute or progressive occlusion (including thrombosis)

Only 1/3 of patients have systemic symptoms at presentation or recall having had such symptoms.

Repetitive arm movements and sustained arm elevation may cause pain and fatigue. Arterial pulses in arms and legs may be diminished and asymmetric. Bruits are often audible over the subclavian arteries, brachial arteries, carotid arteries, abdominal aorta, or femoral arteries. Reduced BP in one or both arms is common.

When the carotid and vertebral arteries are affected, cerebral blood flow decreases, leading to dizziness, syncope, orthostatic hypotension, headaches, transient visual disturbances, transient ischemic attacks, or strokes. Stenotic lesions in a subclavian artery near the origin of a patent vertebral artery can cause posterior circulation neurologic symptoms or syncope when the arm is used (called subclavian steal syndrome). Retrograde flow through the vertebral artery supplies the subclavian artery distal to the stenosis, and vasodilation of the arterial bed in the upper limb during exercise compromises posterior cerebral blood flow.

Angina pectoris or MI may result from narrowing of the coronary artery orifice due to aortitis or coronary arteritis. Aortic regurgitation may occur if the ascending aorta is markedly dilated. Heart failure can develop.

Obstruction of the descending thoracic aorta sometimes causes signs of aortic coarctation (eg, hypertension, headache, leg claudication). Renovascular hypertension may develop if the abdominal aorta or renal arteries are narrowed.

Pulmonary arteries are often affected, sometimes causing pulmonary hypertension. Because Takayasu's arteritis is chronic, collateral circulation can develop. Thus, ischemic ulcerations or gangrene due to obstruction of the arteries to the extremities is rare.

Diagnosis

• Aortic arteriography or magnetic resonance angiography
• Monitoring of disease activity

The diagnosis is suspected when symptoms suggest ischemia of organs supplied by the aorta or its branches or when peripheral pulses are decreased or absent in patients at low risk of atherosclerosis and other aortic disorders, especially in young women. In these patients, arterial bruits and right-left or upper extremity–lower extremity discrepancies in pulses or in BP also suggest the diagnosis. Confirmation of the diagnosis requires aortic arteriography or magnetic resonance angiography to evaluate all branches of the aorta. Characteristic findings include stenosis, occlusion, irregularities in arterial lumens, poststenotic dilation, collateral arteries around obstructed vessels, and aneurysms.

BP is measured in both arms. However, measurement can be difficult. If both subclavian arteries are severely affected, systemic BP can be accurately measured only in the legs. If the disorder affects both subclavian arteries in patients with coarctation of the descending aorta or involvement of both iliac or femoral arteries, BP cannot be accurately measured. Then, central arterial pressure must be measured via angiography to detect occult hypertension, which can cause complications.

Laboratory tests are nonspecific and not helpful in diagnosis. Common findings include anemia of chronic disease, elevated platelet levels, occasionally elevated WBC counts, and elevated ESR and C-reactive protein.

Once Takayasu's arteritis is diagnosed, disease activity must be monitored to look for the following:

• New systemic symptoms, which may reflect active arthritis or infection (secondary to immunosuppression therapy)
• Evidence of inflammation detected by blood tests (although markers of inflammation may miss active arteritis)
• Development of stenosis, aneurysms, or ischemic symptoms in previously unaffected arteries, as assessed with periodic imaging (usually magnetic resonance angiography)

Periodic imaging of the aorta and large arteries is important because the disorder may progress silently, without clinical symptoms or evidence of inflammation in blood. Once the disorder is diagnosed, BP should be measured periodically in an unaffected limb because hypertension must be controlled.

Table 3
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Imaging Tests Used in Takayasu's Arteritis Test Uses Comments Conventional angiography Preferred when a surgical intervention is being considered and when proximal aortic BP cannot be measured any other way May be preferred to MRI in elderly patients because resolution is better and ionizing radiation is less of a concern Provides descriptive anatomic information about the vascular lumen Magnetic resonance angiography of the aorta and large arteries Avoids the risk of arterial puncture and of exposure to iodinated contrast or radiation Usually the test of choice in young women, who are less likely to have extensive atherosclerosis and are more susceptible to radiation-induced cancer Provides some information about arterial wall anatomy Does not provide sufficient information about distal aortic branches because the resolution is too low Provides no information about the content of arterial plaque, making discrimination between vasculitic and atherosclerotic disease difficult CT angiography Used to generally survey the aorta and its proximal branches when magnetic resonance angiography is contraindicated or is not available Can characterize aortic calcification May provide information about arterial wall thickness Unclear whether it is useful in monitoring disease activity Positron emission tomography with fluorine-18 (18F) deoxyglucose Used to assess regional differences in glucose metabolism and may help locate regions of inflammation (because inflammatory cells take up more glucose) Does not provide information about changes in lumen size

Disorders that mimic Takayasu's arteritis must be excluded. They include inherited connective tissue disorders (eg, Ehlers-Danlos or Marfan syndrome), vascular infections (tuberculous, fungal, or syphilitic), fibromuscular dysplasias, disorders causing arterial thrombosis (eg, hypercoagulable states), and idiopathic inflammatory conditions (eg, ankylosing spondylitis with aortitis, Cogan's or Behçet's syndrome, Kawasaki disease, sarcoidosis); all can affect large vessels.

Prognosis

For 20% of patients, the course is monophasic. For the rest, the course is relapsing and remitting or chronic and progressive. Even when symptoms and laboratory abnormalities suggest quiescence, new lesions occur and are evident on imaging studies. A progressive course and the presence of complications (eg, hypertension, aortic regurgitation, heart failure, aneurysms) predict a less favorable prognosis.

Treatment

• Corticosteroids
• Sometimes immunosuppressants
• Antihypertensives
• Vascular interventions

Drugs: Corticosteroids are the cornerstone of treatment. The optimal dose, tapering schedule, and length of treatment have not been determined. Treatment with corticosteroids alone induces remission in most patients. PrednisoneSome Trade Names
DELTASONE
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is usually used. The starting dose is 1 mg/kg po once/day for 1 to 3 mo; the dose is then tapered slowly over several months. Lower starting doses may also induce remission. About ½ of patients relapse when the drug is tapered or stopped, despite initial response.

MethotrexateSome Trade Names
RHEUMATREX
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, cyclophosphamideSome Trade Names
CYTOXAN
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, azathioprineSome Trade Names
IMURAN
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, mycophenolate mofetilSome Trade Names
CELLCEPT
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, and tumor necrosis factor inhibitors (eg, etanerceptSome Trade Names
ENBREL
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, infliximabSome Trade Names
REMICADE
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) have been used in some patients. They can be tried if corticosteroids are insufficiently effective or cannot be tapered. MethotrexateSome Trade Names
RHEUMATREX
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is given with a corticosteroid. Often, the starting dose is 0.3 mg/kg once/wk, which is increased up to 25 mg/wk. Mycophenolate mofetilSome Trade Names
CELLCEPT
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can also be tried. CyclophosphamideSome Trade Names
CYTOXAN
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should be considered in patients with coronary vasculitis or other serious complications thought to be due to active arteritis.

An antiplatelet drug (eg, aspirinSome Trade Names
BUFFERIN
ECOTRIN
GENACOTE
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325 mg po once/day) is frequently used because platelet-mediated occlusion cannot be excluded. Hypertension should be treated aggressively; ACE inhibitors may be effective.

Procedures: Vascular intervention, usually a bypass procedure, may be needed to reestablish blood flow to ischemic tissues if drug therapy is ineffective. Indications include the following:

• Severe hypertension that is refractory to medical management because renal artery stenosis is present (although reocclusion and thrombosis of grafts is common)
• Ischemia in the extremities that interferes with daily activities
• Ischemia of cerebral arteries
• New York Heart Association (NYHA) class II heart failure secondary to a discrete coronary artery stenosis or occlusion
• Cardiac ischemia caused by stenosis of the coronary arteries
• Coarctation of the aorta
• Dissection or enlargement of an aortic aneurysm

Bypass grafting preferably with an autologous graft has the best patency rates. The anastomosis should be made at disease-free sites of the affected arteries to help prevent aneurysm formation and occlusion.

Percutaneous transluminal coronary angioplasty (PTCA) has few risks and may be effective for short lesions. But long-term restenosis rates seem much higher than those with bypass grafting. Vascular stenting is usually not recommended because the restenosis rate is high.

For aortic regurgitation, valvular surgery with aortic root replacement may be necessary.

Last full review/revision May 2008 by Carmen E. Gota, MD

Content last modified February 2012