7/7/23, 11:13 AM Clinical features and diagnosis of Takayasu arteritis - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Clinical features and diagnosis of Takayasu arteritis : Peter A Merkel, MD, MPH : Kenneth J Warrington, MD : Philip Seo, MD, MHS All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Feb 10, 2023. INTRODUCTION Takayasu arteritis (TAK) is classified as a large-vessel vasculitis because it primarily affects the aorta and its primary branches. It also shares some histologic and clinical features with giant cell (temporal) arteritis (GCA), the other major large-vessel vasculitis. Patients may present initially with constitutional symptoms but later develop symptoms associated with vascular damage. The pathogenesis, pathology, clinical manifestations, and diagnosis of TAK will be reviewed here. The treatment of this disorder is discussed separately (see "Treatment of Takayasu arteritis"). Overviews of the vasculitides in children and in adults are also discussed elsewhere. (See "Vasculitis in children: Incidence and classification" and "Overview of and approach to the vasculitides in adults".) EPIDEMIOLOGY Women are affected in 80 to 90 percent of cases, with an age of onset that is usually between 10 and 40 years [1,2]. It has a worldwide distribution, with the greatest prevalence in Asia [3-5]. In Japan, it has been estimated that 150 new cases occur each year [6]. PATHOGENESIS The pathogenesis of Takayasu arteritis (TAK) is poorly understood. Cell-mediated mechanisms are thought to be of primary importance and may be similar to those in giant cell arteritis (GCA) https://www.uptodate.com/contents/clinical-features-and-diagnosis-of-takayasu-arteritis/print 1/28 7/7/23, 11:13 AM Clinical features and diagnosis of Takayasu arteritis - UpToDate [7] (see "Pathogenesis of giant cell arteritis"). Some studies have identified genetic links to disease susceptibility that may help explain differences in prevalence geographically and could lead to a deeper understanding of key underlying pathways of disease pathogenesis [8,9]. Immunohistopathologic examination has shown that the infiltrating cells in aortic tissue mainly consist of cytotoxic lymphocytes, especially gamma delta T lymphocytes [10]. These cells may cause vascular injury by releasing large amounts of the cytolytic protein perforin. Recognition of heat shock protein-65 might facilitate recognition and adhesion of the infiltrating cells. In another report, the T cell receptors on the infiltrating T cells had a restricted repertoire, suggesting that a specific but as yet unidentified antigen in aortic tissue might be targeted [11]. This change was not seen in atherosclerotic aortic aneurysms. Additional data suggest that mast cells may play a role in regulating vascular lesions in TAK. A small study including 30 patients with TAK found an increase in mast cell numbers in TAK arterial lesions compared with noninflammatory aortic biopsy lesions [12]. The inflammation may be localized to a portion of the thoracic or abdominal aorta and branches, or may involve the entire vessel. Although there is considerable variability in disease expression (possibly due to geographic differences [13]), the initial vascular lesions frequently occur in the left middle or proximal subclavian artery. As the disease progresses, the left common carotid, vertebral, brachiocephalic, right middle or proximal subclavian artery, right carotid, vertebral arteries, and aorta may also be affected. The abdominal aorta and pulmonary arteries are involved in approximately 50 percent of patients [14]. Patterns of arterial disease in TAK may be important clues for underlying disease pathogenesis [15]. The inflammatory process within the vessel can lead to narrowing, occlusion, or dilation of involved portions of the arteries, which causes a wide variety of symptoms. CLINICAL FEATURES Symptoms and signs The onset of symptoms in Takayasu arteritis (TAK) tends to be subacute, which often leads to a delay in diagnosis that can range from months to years [16], during which time vascular disease may start and progress to become symptomatic. It is not uncommon for the consequences of the arterial disease to be the first sign of TAK noticed at presentation. As progression of narrowing, occlusion, or dilation of arteries occurs, there is resulting pain in arms or legs (limb claudication) and/or cyanosis, lightheadedness or other symptoms of reduced blood flow, arterial pain and tenderness, or nonspecific constitutional symptoms. The following features can be seen [17-21]: https://www.uptodate.com/contents/clinical-features-and-diagnosis-of-takayasu-arteritis/print 2/28 7/7/23, 11:13 AM Clinical features and diagnosis of Takayasu arteritis - UpToDate Constitutional symptoms Constitutional symptoms are common in the early phase of TAK, including weight loss and low-grade fever. Fatigue is very common. Arthralgias Arthralgias or myalgias occur in about one-half of cases. Clinically evident synovitis is less common. Articular symptoms can be transient or continuous over several months or longer. Carotidynia Tenderness of a carotid artery (carotidynia) is observed in 10 to 30 percent of patients at presentation [17]. Absent or weak peripheral pulse(s) Absent or diminished peripheral pulses is most common at the level of the radial arteries and is often asymmetric [18]. In unusually severe cases, occlusion of the vessels to the extremities may result in ischemic ulcerations or gangrene; however, such complications are usually precluded by the development of collateral arterial circulation in the areas involved by vasculitis, protecting extremities from critical ischemia. Collateral vessels are evidence of the slow progression of the disease. Limb claudication Limb claudication may be observed. Subclavian artery involvement is common, and a stenotic lesion proximal to the origin of the vertebral artery can lead to neurologic symptoms or syncope related to the so-called subclavian steal syndrome [22]. In this phenomenon, retrograde flow through the vertebral artery supplies the subclavian distal to the stenosis and vasodilation of the arterial bed in the upper limb with exercise compromises posterior cerebral blood flow (see "Overview of upper extremity peripheral artery disease", section on 'Presentation' and "Subclavian steal syndrome", section on 'Clinical features'). Other claudicatory symptoms are common, including mild to severe upper- or lower-extremity pain with modest activity, often limiting patients' functional capacity for activities of daily living, ambulation, or employment. Arterial bruit In patients with stenoses, bruits are usually audible over the subclavian arteries, brachial arteries, carotid arteries, and abdominal vessels. Clinical signs of aortic regurgitation due to dilatation of the ascending aorta may be present in patients who have this abnormality, and moderate to severe stenosis can be present even in the absence of a bruit. (See "Examination of the arterial pulse" and "Clinical manifestations and diagnosis of chronic aortic regurgitation in adults".) Discrepant blood pressure between arms Reduced blood pressure in one or both arms is common; a differential of more than 10 mmHg between the arms is typically present and pressures may be unmeasurable, especially by automated devices. It is imperative for patients and clinicians to be aware of such unreliable blood pressure readings to ensure https://www.uptodate.com/contents/clinical-features-and-diagnosis-of-takayasu-arteritis/print 3/28 7/7/23, 11:13 AM Clinical features and diagnosis of Takayasu arteritis - UpToDate proper pressures are recorded in limbs not affected by arterial narrowing; this frequently requires measuring the blood pressure in legs. Hypertension Hypertension develops in more than one-half of cases due to narrowing of one or both renal arteries, or narrowing and decreased elasticity of the aorta and branches. Severe (malignant) hypertension may occur. However, narrowing or occlusion of the arteries in the arms may make it difficult to assess the blood pressure. In these cases, the blood pressure may be measured using a wide cuff on an uninvolved thigh, or by direct measurements of the proximal aorta via arterial catheterization. Because TAK often affects young people, modest elevations in blood pressure are often overlooked. (See "Blood pressure measurement in the diagnosis and management of hypertension in adults".) Angina Angina pectoris occurs due to coronary artery ostial narrowing from aortitis or coronary arteritis. Myocardial infarction and death may occur. Gastrointestinal symptoms Abdominal pain, particularly post-prandial pain, diarrhea, and gastrointestinal hemorrhage may result from mesenteric artery ischemia [21]. Skin lesions Skin lesions resembling erythema nodosum or pyoderma gangrenosum are found over the legs in a minority of cases. Respiratory symptoms The pulmonary arteries are involved pathologically in up to 50 percent of cases; however, symptoms related to pulmonary arteritis are less common [20]. Pulmonary manifestations include chest pain, dyspnea, hemoptysis, and pulmonary hypertension [21]. Dyspnea may also be due to angina or heart failure resulting from aortic dilation, aortic regurgitation, or malignant hypertension. Neurologic symptoms Involvement of the carotid and vertebral arteries causes decreased cerebral blood flow, leading to lightheadedness, vertigo, syncope, orthostasis, headaches, convulsions, and strokes. Visual impairment is a late manifestation of severe disease and is due to arterial insufficiency [19]. Physical examination Several aspects of the physical examination merit particular attention whenever a patient with TAK is seen in clinical practice. Measurement of blood pressure should be done in all four extremities to evaluate for arterial stenoses and accurately measure the true central arterial pressure. Many patients with TAK will have partial or complete occlusion of one or both subclavian, axillary, or brachial arteries, or the brachiocephalic artery, leading to falsely low pressure readings in the ipsilateral arm. Similarly, femoral or more distal arterial stenoses will falsely lower leg blood pressures and stenosis of the aorta may lead to bilateral low blood pressure readings. It is important that clinicians, nurses, and other clinical staff enter all four https://www.uptodate.com/contents/clinical-features-and-diagnosis-of-takayasu-arteritis/print 4/28 7/7/23, 11:13 AM Clinical features and diagnosis of Takayasu arteritis - UpToDate extremity blood pressure readings into a patient's medical records to best allow for determination of which readings are reliable and to gain insight into the patient's vascular anatomy. Bruits should be listened for over the bilateral carotid, subclavian, axillary, renal, and femoral arteries, as well as the abdominal aorta. Cardiac auscultation may reveal signs of aortic valvular disease, pulmonary hypertension, or heart failure. Pulses should be felt for and evaluated (full, reduced, absent) at bilateral temporal, carotid, brachial, femoral, and dorsal pedal arteries, and any arterial tenderness should also be noted. Signs of limb ischemia should be sought. Availability of a device using Doppler technology can enhance the vascular examination in patients with TAK. Physical examination may reveal findings suggestive of vascular disease. Many of the abnormal exam findings above have been shown to be fairly specific, although not highly sensitive, for identification of arterial lesions subsequently confirmed by imaging tests [23]. Laboratory findings Laboratory abnormalities in patients with TAK are nonspecific and generally reflect an inflammatory process [17]. Acute phase reactants such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) may be elevated; however, these tests do not reliably reflect disease activity and can be normal in the setting of active disease [21]. Other abnormalities that may be observed in the complete blood count include a normochromic normocytic anemia suggestive of the anemia of chronic disease as well as a leukocytosis and/or thrombocytosis. DIAGNOSIS Our approach In most cases, a clinical diagnosis of Takayasu arteritis (TAK) can be made in a patient with both suggestive clinical findings (eg, constitutional symptoms, hypertension, diminished or absent pulses, and/or arterial bruits) and imaging showing narrowing of the aorta and/or its primary branches (see 'Symptoms and signs' above and 'Imaging' below). It is appropriate to consider the conditions listed below (see 'Differential diagnosis' below) and selectively conduct additional testing as clinically indicated. Occasionally, the diagnosis of TAK is made incidentally either in patients with imaging consistent with vasculitis obtained for other clinical indications (eg, "aortitis" suspected on an abdominal computed tomography [CT] obtained to evaluate for possible malignancy or incidentally discovered aortic aneurysm) or when vasculitis is found on histologic examination of surgically removed segments of arteries. In such circumstances, we recommend examining other regions of the aorta and its primary branches with either magnetic resonance angiography (MRA) or CT https://www.uptodate.com/contents/clinical-features-and-diagnosis-of-takayasu-arteritis/print 5/28 7/7/23, 11:13 AM Clinical features and diagnosis of Takayasu arteritis - UpToDate angiography (CTA) and considering the possibility of a diagnosis of another form of large-vessel vasculitis. (See 'Differential diagnosis' below.) There are no diagnostic laboratory tests for TAK. Testing for acute phase reactants such as the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) may provide additional support for the presence of a systemic inflammatory process; however, normal values of ESR or CRP should not markedly deter making the diagnosis of TAK. Imaging Imaging studies are essential for establishing the diagnosis of TAK and for determining the extent of vascular involvement. Patients with suspected TAK should undergo imaging of the arterial tree by MRA or CTA to evaluate the arterial lumen. The diagnostic and physiologic importance of arterial wall enhancement on MR or CT imaging remain uncertain. In general, we favor using MRA to evaluate for TAK since it avoids the radiation exposure and risks of iodinated contrast of CTA; similarly, if periodic repeat studies are anticipated, MRA is again the preferred choice. Imaging of the arterial tree of the chest, abdomen, head and neck, or other areas by MRA or CTA demonstrates smoothly tapered luminal narrowing or occlusion ( image 1) that is sometimes accompanied by thickening of the wall of the vessel ( image 2A-B) [24-29]. Color Doppler ultrasound examination of the common carotid and proximal subclavian arteries may show vessel wall thickening and luminal narrowing, especially if bruits or diminished pulses are found on examination, and may provide complementary information to MRA/CTA about hemodynamics. With the increased availability of ultrasound within rheumatology practices, there is increased interest in using this imaging modality to follow the disease course in TAK. However, ultrasound examination cannot reach vessels in deeper areas, and multiple procedures and more time are necessary to cover the same regions seen by a single MR or CT study. While conventional arteriography generally provides clear outlines of the lumen of involved arteries ( image 3), it does not allow arterial wall thickening to be assessed (the importance of which is not fully clear) and is an invasive test associated with some risks. Therefore, if a therapeutic intervention (eg, stenting for revascularization) is not anticipated, a less invasive imaging technique is preferred. (See "Treatment of Takayasu arteritis", section on 'Revascularization'.) Catheter-based angiography allows for the measurement of core blood pressure, and this may be needed when four-limb arterial stenosis prevents accurate blood pressure assessments; documenting aortic pressures should always be part of this procedure. Furthermore, cardiac catheterization may be a critically important form of angiography to perform when cardiac https://www.uptodate.com/contents/clinical-features-and-diagnosis-of-takayasu-arteritis/print 6/28 7/7/23, 11:13 AM Clinical features and diagnosis of Takayasu arteritis - UpToDate ischemia is suspected, although in some situations CT-based coronary imaging may be performed. When selected site angiography is planned, it may be quite appropriate to extend the scope of the study to include more/all of the aorta and primary branches since the initial risk of arterial puncture was already planned; time, costs, and the risks of using additional contrast dye must be considered. Positron emission tomography (PET), often in combination with CT (PET-CT) or MR (PET-MR) is an increasingly utilized test to evaluate for possible large-vessel vasculitis. The finding of "hot" segments (ie, those with increased standardized uptake values [SUVs]) in the right clinical setting may be quite suggestive of large-vessel vasculitis. There is increasing use of PET to aid in the diagnosis of TAK. There is less consensus on this test's usefulness as a measure of disease activity, and the role of PET to measure disease activity in large-vessel vasculitis remains under study [30]. Histopathology The diagnosis of TAK is seldom made histologically since biopsy of the large arteries is obviously impractical. However, occasionally arterial tissue may become available after a revascularization procedure or aneurysm repair. Such tissue samples should be sought whenever reasonably feasible if it will help either establish a diagnosis or evaluate the state of the disease (eg, active inflammation versus inactive scar) and lead to change in therapy. Active inflammation is indicated by the presence of mononuclear cells, predominantly lymphocytes, histiocytes, macrophages, and plasma cells [31]. Giant cells and granulomatous inflammation are typically found in the media [32]. Destruction of the elastic lamina and the muscular media can lead to aneurysmal dilation of the affected vessel. Alternatively, progressive inflammation and dense scarring may proceed from the adventitia leading to a compromise of the vascular lumen. Intimal proliferation may also contribute to the development of stenotic arterial lesions. If active inflammation abates, dense scar tissue remains as an indication of prior vasculitis. Nomenclature and classification criteria The disease names and definitions of the vasculitides continue to evolve as our understanding of the pathogenesis advances. The international Chapel Hill Consensus Conference (CHCC) has developed one of the most widely used nomenclature systems, which specifies the names and definitions for most forms of vasculitis [33,34]. The CHCC nomenclature system has changed over the past few decades, and definitions that were put forth by the CHCC in 1994 have since been revised in the 2012 CHCC ( table 1 and table 2). Classification criteria have been developed for TAK as a means of categorizing patients for research studies. The 1990 American College of Rheumatology (ACR) classification criteria were https://www.uptodate.com/contents/clinical-features-and-diagnosis-of-takayasu-arteritis/print 7/28 7/7/23, 11:13 AM Clinical features and diagnosis of Takayasu arteritis - UpToDate developed to help distinguish one form of vasculitis from another, but they are limited in terms of their use in clinical practice [2,35,36]. Age at disease onset 40 years Claudication of the extremities Decreased pulsation of one or both brachial arteries Difference of at least 10 mmHg in systolic blood pressure between the arms Bruit over one or both subclavian arteries or the abdominal aorta Arteriographic narrowing or occlusion of the entire aorta, its primary branches, or large arteries in the proximal upper or lower extremities, not due to arteriosclerosis, fibromuscular dysplasia, or other causes Patients are said to have TAK if at least three of the six criteria are present. The 2022 ACR/European Alliance of Associations for Rheumatology (EULAR) classification criteria for TAK uses a weighted algorithm that includes clinical and imaging criteria ( table 3). These criteria were constructed in part to reflect the growing role of noninvasive imaging for the evaluation of patients with TAK [37]. It is anticipated that these new 2022 ACR/EULAR classification criteria will gradually gain acceptance for use in research studies. (See "Overview of and approach to the vasculitides in adults", section on 'Nomenclature'.) The main role for these criteria and nomenclatures systems is for clinical research purposes. None has been validated for establishing clinical diagnoses, and while these criteria may inform clinicians' approach to evaluating patients, these criteria should not be used as diagnostic criteria. DIFFERENTIAL DIAGNOSIS The differential diagnosis of Takayasu arteritis (TAK) includes atherosclerotic, inflammatory, infectious, and hereditary diseases that affect the large arteries. Giant cell arteritis Perhaps the most difficult distinction is between TAK and giant cell arteritis (GCA). Both conditions involve the aorta and its major branches and are indistinguishable histopathologically. Distinction between the two disorders can usually be made based upon the age of the patient and the distribution of lesions ( table 4) [38,39], although such a dichotomy is strongly driven the by the somewhat arbitrary age-based criteria. https://www.uptodate.com/contents/clinical-features-and-diagnosis-of-takayasu-arteritis/print 8/28 7/7/23, 11:13 AM Clinical features and diagnosis of Takayasu arteritis - UpToDate However, with the increasing recognition of overlapping clinical features of these two conditions, and especially that GCA may involve the aorta and its major branches in at least 30 percent of patients, the differentiation between TAK and GCA has become more difficult [40,41]. (See "Diagnosis of giant cell arteritis" and "Clinical manifestations of giant cell arteritis".) Other forms of large-vessel vasculitis/aortitis There are several other diseases associated with aortitis that can present with clinical and radiographic features identical to TAK, including Cogan syndrome, relapsing polychondritis, and spondyloarthritis. However, in most of these situations, the finding of other clinical features pathognomonic for the specific diagnosis can differentiate among these types of aortitis. (See "Cogan syndrome" and "Clinical manifestations of relapsing polychondritis" and "Overview of the clinical manifestations and classification of spondyloarthritis".) Beh et syndrome Arterial involvement in Beh et syndrome can lead to dilatations and aneurysms of the medium- and large-sized arteries. However, patients with Beh et are likely to have other clinical features such as oral and/or genital ulcerations, ocular disease, and arthritis. (See "Clinical manifestations and diagnosis of Beh et syndrome".) IgG4-related disease IgG4-related disease has been recognized as a rare cause of noninfectious aortitis. Histologic evidence of lymphoplasmocytes and storiform fibrosis as well as non-arterial manifestations of disease can differentiate IgG4-related disease from TAK. (See "Pathogenesis and clinical manifestations of IgG4-related disease", section on 'Aortitis and periaortitis'.) Infectious aortitis Similar to TAK, patients with infectious aortitis may present with nonspecific symptoms such as fever and elevated acute phase reactants. However, patients with TAK will have negative blood cultures. Infections of the aorta usually lead to aneurysm formation. Mycobacterial infection of the aorta can present with a more chronic process that bacterial infections. On CT angiography (CTA), patients with infectious aneurysms may have a perivascular fluid collection or intramural air, whereas inflammatory aneurysms often have findings suggestive of periaortic fibrosis and adhesions of adjacent structures (see "Overview of infected (mycotic) arterial aneurysm", section on 'Differential diagnosis'). All patients with aortitis should be tested for syphilis. (See "Syphilis: Screening and diagnostic testing", section on 'Approach to testing'.) Genetic causes of aortic aneurysms Genetic defects that lead to abnormalities in connective tissue metabolism can predispose patients to thoracic aortic aneurysm and dissection. Examples include Marfan syndrome, vascular Ehlers-Danlos syndrome, Loeys- https://www.uptodate.com/contents/clinical-features-and-diagnosis-of-takayasu-arteritis/print 9/28 7/7/23, 11:13 AM Clinical features and diagnosis of Takayasu arteritis - UpToDate Dietz syndrome, and Turner syndrome. Patients with these conditions generally do not have systemic symptoms as do patients with TAK. These conditions are associated with a specific genetic abnormality and other typical clinical features. (See "Epidemiology, risk factors, pathogenesis, and natural history of thoracic aortic aneurysm and dissection", section on 'Syndromic connective tissue disorders' and "Epidemiology, risk factors, pathogenesis, and natural history of thoracic aortic aneurysm and dissection", section on 'Turner syndrome'.) Fibromuscular dysplasia Fibromuscular dysplasia must be considered when large arterial stenosis are seen. However, this syndrome often has characteristic radiographic findings, is usually more focal in its involvement, and is not associated with the systemic symptoms of TAK. (See "Clinical manifestations and diagnosis of fibromuscular dysplasia".) Atherosclerosis It is likely that atherosclerosis is the cause of more lesions of the aorta and its major branches than all forms of inflammatory disease combined. Differentiating atherosclerosis from vasculitis may be easier in younger people but can be a challenge in many patients. Longer, smoother, non-calcified lesions are more characteristic of non- atherosclerotic disease. However, atherosclerosis can be associated with some degree of inflammation and increased signal on positron emission tomography (PET), and luminal characteristics are not fully reliable when evaluating lesions. Furthermore, patients with large-vessel vasculitis can also develop atherosclerosis. Evaluation of all patients with TAK for risk factors and evidence of atherosclerosis is appropriate. (See "Overview of established risk factors for cardiovascular disease".) SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Takayasu arteritis".) INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." th th The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more th th sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading https://www.uptodate.com/contents/clinical-features-and-diagnosis-of-takayasu-arteritis/print 10/28 7/7/23, 11:13 AM Clinical features and diagnosis of Takayasu arteritis - UpToDate level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.) Beyond the Basics topics (see "Patient education: Vasculitis (Beyond the Basics)") SUMMARY AND RECOMMENDATIONS Epidemiology Takayasu arteritis (TAK) is an uncommon chronic vasculitis of unknown etiology, which primarily affects the aorta and its primary branches. Women are affected in 80 to 90 percent of cases, with an age of onset that is usually between 10 and 40 years. It has a worldwide distribution, with the greatest prevalence in Asia. (See 'Introduction' above and 'Epidemiology' above.) Pathogenesis The pathogenesis of TAK is poorly understood. The inflammation may be localized to a portion of the thoracic or abdominal aorta and branches, or may involve the entire vessel. Although there is considerable variability in disease expression, the initial vascular lesions frequently occur in the left middle or proximal subclavian artery. As the disease progresses, the left common carotid, vertebral, brachiocephalic, right middle or proximal subclavian artery, right carotid, vertebral arteries, and aorta may also be affected. The abdominal aorta and pulmonary arteries are involved in approximately 50 percent of patients. The inflammatory process within the vessel can lead to narrowing, occlusion, or dilation of involved portions of the arteries in which causes a wide variety of symptoms. (See 'Pathogenesis' above.) Clinical manifestations The onset of symptoms in TAK tends to be subacute, which often leads to a delay in diagnosis that can range from months to years, during which time vascular disease may start and progress. It is not uncommon for the consequences of the arterial disease to be the first sign of TAK noticed at presentation. As progression of narrowing, occlusion, or dilation of arteries occurs, there is resulting pain in arms or legs (limb claudication) and/or cyanosis, lightheadedness or other symptoms of reduced blood flow, arterial pain and tenderness, or nonspecific constitutional symptoms. (See 'Symptoms and signs' above.) Physical examination The physical examination of a patients with TAK should particularly focus on accurate measurements of blood pressure, palpation of pulses, https://www.uptodate.com/contents/clinical-features-and-diagnosis-of-takayasu-arteritis/print 11/28 7/7/23, 11:13 AM Clinical features and diagnosis of Takayasu arteritis - UpToDate identification of bruits, and careful cardiac auscultation. (See 'Physical examination' above.) Diagnosis The diagnosis of TAK should be suspected in a patient who has constitutional symptoms, hypertension, diminished or absent pulses, and/or arterial bruits. In most cases, the diagnosis is based upon suggestive clinical features and specific imaging findings of the aorta and/or its branches. Additionally, TAK or other forms of large-vessel vasculitis must be considered either in patients incidentally found to have findings suspicious for vasculitis on imaging obtained for other clinical indications or when vasculitis is found on histologic examination of surgically removed segments of arteries. (See 'Our approach' above.) Laboratory findings There are no diagnostic laboratory tests for TAK. Testing for acute phase reactants such as the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) may provide additional support for the presence of a systemic inflammatory process; however, normal values of ESR or CRP should not markedly deter making the diagnosis of TAK. (See 'Our approach' above and 'Laboratory findings' above.) Imaging Imaging studies are essential for establishing the diagnosis of TAK and for determining the extent of vascular involvement. Patients with suspected TAK should undergo imaging of the arterial tree by magnetic resonance angiography (MRA) or CT angiography (CTA) to evaluate the arterial lumen. In general, we favor using MRA to evaluate for TAK, since it avoids the radiation exposure and risks of iodinated contrast of CTA; similarly, if periodic repeat studies are anticipated, MRA is again the preferred choice. Imaging of the arterial tree of the chest, abdomen, head and neck, or other areas by MRA or CTA demonstrates smoothly tapered luminal narrowing or occlusion ( image 1) that is sometimes accompanied by thickening of the wall of the vessel ( image 2A-B). There is an increasing use of positron emission tomography (PET), often in combination with CT (PET- CT) or MR (PET-MR) to aid in the diagnosis of TAK, but there is less consensus on this test's usefulness as a measure of disease activity, and its role remains under study. (See 'Imaging' above.) Differential diagnosis Conditions that should be considered in the differential diagnosis of TAK include giant cell (temporal) arteritis (GCA), IgG4-related disease, Beh et syndrome, infectious aortitis, fibromuscular dysplasia, atherosclerosis, genetic causes of aneurysms such as Ehlers-Danlos syndrome, and other diseases which can feature large-vessel vasculitis/aortitis such as Cogan syndrome, relapsing polychondritis, and spondyloarthropathies. (See 'Differential diagnosis' above.) https://www.uptodate.com/contents/clinical-features-and-diagnosis-of-takayasu-arteritis/print 12/28 7/7/23, 11:13 AM Clinical features and diagnosis of Takayasu arteritis - UpToDate ACKNOWLEDGMENT The editorial staff at UpToDate acknowledge Gene Hunder, MD, who contributed to an earlier version of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Lupi-Herrera E, S nchez-Torres G, Marcushamer J, et al. Takayasu's arteritis. Clinical study of 107 cases. 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