Takayasu arteritis is a large-vessel vasculitis that primarily affects the aorta and its main branches. Chronic inflammation of involved vessels commonly leads to stenosis, occlusion, dilation, and aneurysms in the arterial wall.¹

Pulseless disease

Aortitis syndrome

Aortic arch arteritis

Nonspecific aortoarteritis

Aortic arch syndrome

In the U.S., the incidence is estimated around 0.4 to 2.6 per million people and about 4.7 to 8.0 cases per million outside of the U.S.² The highest prevalence of Takayasu arteritis has been described in Japan, where all cases of Takayasu arteritis are registered by the government, and it has been estimated that 200 to 400 new cases occur every 3 yr.³ It has a female predominance, with female:male ratio around 8:1.² Age of onset is between 10 and 40 yr with median age of onset of 20 yr.⁴

Takayasu arteritis manifests with clinically nonspecific signs and symptoms of systemic inflammation, including general fatigue, weight loss, generalized arthralgias, myalgias, and low-/high-grade fever.^5,6 These symptoms are usually subacute, which leads to delay in the diagnosis from months to years.² Vascular symptoms are rare at presentation, and localized symptoms and signs vary depending on the location of the affected arteries.^2,3

• Table E1 summarizes common symptoms and signs in Takayasu arteritis. “Red flags” for Takayasu arteritis are summarized in Table E2
• The occlusive stage of Takayasu arteritis may progress to stenosis or aneurysm of the aorta and its primary branches and may manifest as a variety of clinical signs and symptoms, such as^2,3,5:
  1. Arm or leg claudication, weakness, and numbness
  2. Amaurosis fugax, diplopia, headache, orthostasis, vertigo, memory loss, or syncope
  3. Angina or myocardial infarction
  4. Vascular bruits of the carotid artery, subclavian artery, and aorta
  5. Discrepancy of blood pressures between the upper extremities, typically of ≥10 mm Hg
  6. Diminished or absent pulses, ischemic ulcerations, or gangrene in advanced disease
  7. Hypertension
  8. Retinopathy
  9. Aortic insufficiency as a result of aortic root dilation and aneurysm formation
  10. Weakness of the arterial walls may give rise to localized aneurysms/dissection
  11. Dyspnea or hemoptysis
  12. Skin lesions similar to erythema nodosum
  13. GI symptoms (abdominal pain, diarrhea, and GI bleed) secondary to mesenteric artery ischemia

As with most types of vasculitis, the cause of Takayasu arteritis is not known. Cell-mediated mechanisms (cytotoxic T cell, macrophage, natural killer cells, and others) and cytokine release (such as tumor necrosis factor-alpha [TNF-α], interleukin-6 [IL-6], and interferon-gamma [IFN-γ]) are thought to be important to the pathogenesis.⁶ Both pathways contribute to the induction and amplification of inflammation and tissue injury.⁶

• Infiltration by inflammatory cells (lymphocytes, macrophages, and multinucleated giant cells) into the vasa vasorum and media of the large elastic arteries (Fig. E1) leads to production of matrix metalloproteinases (MMP), which cause destruction of elastic fibers in the arterial wall, neovascularization, and other inflammatory changes.^7,8 An intermediate stage, driven in part by TNF-α, leads to mucopolysaccharide deposition and proliferation of fibroblasts and smooth muscle cells, causing intimal hypertrophy.⁸
• With chronic disease, inflammatory lesions progress to either thick fibrotic calcified narrowings or aneurysms if fibrosis is insufficient and the arterial wall is instead thinned and dilated.¹
• Infection, in particular, tuberculosis, has been implicated in the pathogenesis, with several studies reporting an increased incidence of caseating granulomas in patients with Takayasu arteritis.⁹ Additional immunologic studies lend support to a pathogenic role of CD4 and CD8 T cells in this patient population.⁶

Table E3 describes pathologic characteristics of selected forms of vasculitis. Other causes of inflammatory arteritis must be excluded:

• Temporal arteritis (giant cell arteritis)
• Atherosclerosis
• Infectious aortitis
• Syphilis
• Tuberculosis
• Systemic lupus erythematosus
• Rheumatoid arthritis
• Buerger disease
• Behçet disease
• Marfan syndrome
• Ehlers-Danlos syndrome
• Cogan syndrome
• Kawasaki disease
• Spondyloarthropathies
• Fibromuscular dysplasia
• Relapsing polychondritis

Any young patient with findings of absent pulses and loud bruits merits a workup for Takayasu arteritis. There are no diagnostic laboratory tests to diagnose Takayasu arteritis.² Nonspecific inflammatory biomarkers, including C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), are useful markers for diagnosis, but normal values shouldn’t be used to rule out the disease.² In most patients, the diagnosis is made by clinical findings and imaging of the arterial branches.^2,7 Advanced imaging modalities, including contrast-enhanced magnetic resonance angiography (MRA) and computed tomography angiography (CTA), allow for not only early diagnosis but also detailed assessment of vascular lesions.^2,7 Three-dimensional reconstructions of the whole aorta and neck arteries using CTA are especially useful for surveying lesions.^2,7 Ultrasound and fluorodeoxyglucose-PET are commonly used for diagnosis as well as in serial monitoring of disease activity.⁷ Catheter-based angiography is used to rule out ischemia and to measure core blood pressure when all four limbs arterial stenosis prevent accurate blood pressure measurement.⁷

• ESR and serum CRP levels are usually but not always elevated.^2,10
• A CBC may reveal a normal or elevated white blood cell count as well as anemia.¹⁰
• Immunologic studies may include elevated immunoglobulins (IgG and IgA) and complement components (C3 and C4).¹⁰
• Hypercoagulation and increase in platelet aggregation.¹⁰

• Imaging of the entire aorta and major branch vessels using angiography, CTA, or MRA.⁷
• CTA can detect changes in the vessel wall and provide an accurate representation of luminal diameters.⁷
• MRA provides information on vessel lumen and wall thickening, cardiac morphology and function, and myocardial tissue characterization.⁷
• Angiography can show the narrowing of the aorta and its branches, aneurysm formation, poststenotic dilation, and the development of any collateral circulation.^3,7 Angiographic findings are classified into five major types (Fig. E3):
  1. Type I: Lesions that involve only branches of the aortic arch
  2. Type IIa: Lesions that involve the ascending aorta, the aortic arch, and its branches
     1. Type IIb: Lesions from IIa plus the thoracic descending aorta
  3. Type III: Lesions that involve the thoracic descending aorta, abdominal aorta, and/or renal arteries
  4. Type IV: Lesions that involve the abdominal aorta and/or renal arteries
  5. Type V: Lesions that involve the entire aorta and its branches
• Ultrasound: Carotid, thoracic, and abdominal ultrasound are useful adjunctive imaging studies to diagnose the occlusive disease that results from Takayasu arteritis. The addition of Doppler is helpful to assess blood flow and absent pulses.⁷
• PET using radioisotope fluorodeoxyglucose (FDG-PET) as a marker for tissue with high glucose uptake has shown promising results in terms of specificity and sensitivity, especially in combination with CT (PET-CT) and MRI (PET-MR). The yield of using PET scans to measure disease activity is still under study.⁷

High-dose glucocorticoids are first-line therapy for suppressing systemic symptoms and stopping disease progression.¹ Prednisone (1 mg/kg/day, up to a maximum daily dose of 60 to 80 mg) can be used for 3 mo or intravenous steroids can be administered initially.^1,5,7

Attempts to taper prednisone can be made with resolution of constitutional symptoms, significant decline in the ESR and C-reactive protein levels, and in accordance with imaging studies.^3,5

Because of steroids’ side effects and the high rate of relapse while tapering, it is recommended to use a glucocorticoid sparing agent at the time prednisone is prescribed. Commonly used second agents include^3,5:

• Leflunomide
• Methotrexate
• Mycophenolate mofetil
• Azathioprine
• Tocilizumab
• Anti-TNF agents
• Cyclophosphamide

• Patients with Takayasu arteritis are monitored closely for signs of relapse and disease complications with clinical assessment, inflammatory biomarkers (e.g., ESR and CRP), and imaging.^1,5 Multiple indexes exist for the assessment of disease activity, including the NIH criteria for active disease, the Disease Extent Index-Takayasu (DEI.Tak), and the Indian Takayasu Arteritis Score (ITAS).¹
• Percutaneous angioplasty or bypass grafts should be considered for irreversible arterial stenoses with severe ischemia (cardiac or cerebral), severe hypertension in renal artery stenosis, or aneurysmal enlargement with risk of rupture.⁵ 5-yr arterial complication rate after surgical or endovascular revascularization is around 40%.¹¹ The likelihood of complications increases sevenfold when inflammation is present at the time of revascularization.¹¹
• Aortic regurgitation may require valve replacement or repair by surgery, although the need to manipulate inflamed, friable tissue can lead to complications such as valvular detachment after replacement.¹²
• Treatment of hypertension in patients with Takayasu arteritis can be difficult, especially because there is usually concurrent glucocorticoid therapy and there is the potential for renovascular hypertension. Special monitoring should be employed when using ACE inhibitors due to the high frequency of renal artery stenosis in this population.^1,5

• Immunosuppressant therapy may achieve clinical remission.⁵
• Approximately 50% of patients will relapse during corticosteroid taper.¹ Corticosteroid-sparing agents should be added to reduce the risk of relapse and minimize corticosteroid-associated adverse effects.^1,5
• In the absence of major complications (MI, stroke, severe hypertension, heart failure, and aneurysm), 5-yr survival rates reach 80% to 90%. In the presence of major complications, 5-yr survival is 50% to 70%.⁷
• Death can occur suddenly from a ruptured aneurysm, a myocardial infarction, or a cerebrovascular accident.

Referral to specialist in high risk pregnancy. Pregnancy in Takayasu arteritis is considered a high risk pregnancy.¹ The disease may cause uncontrolled hypertension, myocardial infarction, congestive heart failure, renal failure, and preeclampsia, which may lead to maternal and fetal comorbidity and mortality.¹ Also, medical management with antihypertensive agents or immunosuppressants during pregnancy is challenging.

Whenever the diagnosis of vasculitis is suspected, a rheumatology consultation is appropriate.⁵ Vascular surgery and cardiology consultations are recommended for any evidence of carotid, peripheral, or coronary artery disease or if a large abdominal aneurysm is found.⁵

• No studies have proved that treatment results in regression of stenosis, although there are limited case reports describing the return of pulses with treatment.⁷
• Only one fifth of patients have a self-limited course. The majority show a progressive or relapsing remitting course that requires long-term immunosuppressive therapies.¹⁴
• Although short-term prognosis of the disease is favorable, long-term prognosis depends on the incidence of complications and the presence of progressive course. The presence of both major complications along with progressive course is associated with the worst prognosis. The prognosis and vascular complications of Takayasu arteritis are improving. Fatal or serious complications have diminished in the past decade.^1,3

Vasculitis, Systemic (Related Key Topic)