Approach Considerations
Laboratory test results in individuals with Takayasu arteritis tend to be nonspecific. The erythrocyte sedimentation rate may be high, generally greater than 50 mm/h, in early disease but normal later. Leukocyte count may be normal or slightly elevated. A moderate, normochromic anemia may be present in individuals with active disease. [17, 23]
Autoantibodies observed in other connective tissue diseases, including rheumatoid factor, antinuclear antibodies, anticardiolipin antibodies, and antineutrophil cytoplasmic antibodies (ANCA), are as common as in the general population. Circulating antiendothelial antibodies may be present in high titers. This finding is considered nonspecific, because it is reported sporadically and may be present in other connective tissue diseases and in angiitis obliterans. Antiaorta antibodies may be present, but testing for them seldom is performed, if ever.
Some researchers found that the levels of soluble vascular cell adhesion molecule–1 (VCAM-1) were significantly higher in patients with Takayasu arteritis compared with normal, healthy controls and that they were also significantly higher in older patients than in younger ones, suggesting that VCAM-1 may serve as a marker of disease activity and progression with age. Tripathy et al reported that cell adhesion molecule levels remain elevated in patients with inactive Takayasu arteritis. [33]
Hypoalbuminemia and increased levels of fibrinogen, alpha2-globulin, and gamma globulin are common. Urinalysis may be consistent with nephrotic syndrome.
HLA typing is not a standard diagnostic procedure for North American patients. Presumably, a finding of HLA-B*52 in such patients reinforces the diagnosis; it is not a definite diagnostic tool.
Imaging studies
Although conventional angiography has historically been the standard for diagnosis and evaluation of the extent of disease, computed tomography and magnetic resonance techniques have gained favor for initial evaluation, as they are less invasive than standard angiography and allow diagnosis of Takayasu arteritis earlier in the disease course. [34, 35] Ultrasonography is useful for carotid assessment, while 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) is useful for patients with no vascular signs or symptoms, fever of unknown origin, or an unexplained acute-phase response. (See the images below.) [36, 35, 34]
Takayasu arteritis. MRI of thorax of 15-year-old girl with Takayasu arteritis. Note aneurysms of descending aorta. Image courtesy of Christine Hom, MD.
Takayasu arteritis. Coronal MRI of abdomen of 15-year-old girl with Takayasu arteritis. Note thickening and tortuosity of abdominal aorta proximal to kidneys. Image courtesy of Christine Hom, MD.
For complete discussion, see Takayasu Arteritis Imaging
Diagnostic Criteria
Ishikawa criteria
The Ishikawa criteria (1986) have been useful in defining Takayasu arteritis. One criterion is age younger than 40 years at diagnosis or at onset of characteristic signs and symptoms of 1-month duration.
Two major criteria involve lesions in the left and right midsubclavian artery, with the most severe stenosis or occlusion present in the mid portion of the artery from a 1 cm point proximal to the left and right, respectively, of the vertebral artery orifices to a 3-cm distal point to the orifice, as determined by angiography.
The minor criteria consist of annuloaortic ectasia or aortic regurgitation on angiography or echocardiography, and lesions of any of the following vessels:
-
Pulmonary artery
-
Left mid ̶ common carotid artery
-
Distal brachiocephalic trunk
-
Descending aorta
-
Abdominal aorta
American College of Rheumatology criteria
The American College of Rheumatology (ACR; 1990) put forward the following diagnostic criteria:
-
Angiographic criteria must show narrowing or occlusion of the entire aorta, its primary branches, or large arteries in the proximal upper or lower extremities
-
These changes are not due to arteriosclerosis, fibromuscular dysplasia, or similar causes
-
Changes are usually focal or segmental
These criteria probably allow greater flexibility to account for variability in actual clinical practice. In comparison to the Ishikawa criteria, which were established based on Japanese patients only, the ACR criteria may better reflect the North American population. The lesions can include stenosis, occlusion, or aneurysms.
The sensitivity and specificity of the American College of Rheumatology criteria are 90.5% and 97.9%, respectively.
Assessing Disease Activity
Assessing disease activity in patients with Takayasu arteritis is frequently challenging, since clinical, biologic, and radiologic information do not always correlate. Prospective study criteria established by Kerr et al (National Institutes of Health) are used to assess disease activity in patients with Takayasu arteritis. New onset or worsening of 2 or more of the following features indicates active disease [17] :
-
Systemic features, such as fever and arthralgias (no identified cause)
-
Elevated erythrocyte sedimentation rate
-
Features of vascular ischemia or inflammation, such as claudication, diminished or absent pulse, bruit, carotodynia, or asymmetrical blood pressure in either the upper or lower limbs (or both)
-
Typical angiographic features
Pentraxin-3 (PTX3), a member of the superfamily of acute- phase proteins such as C-reactive protein (CRP) and serum amyloid P, has been suggested as a possible biomarker for identifying disease activity in patients with an established diagnosis of Takayasu arteritis. In a cross-sectional, noninterventional study, PTX3 plasma levels were shown to be more accurate than the erythrocyte sedimentation rate (ESR) and CRP level for differentiating active from inactive disease in 57 patients with previously diagnosed Takayasu arteritis. PTX3 levels greater than 1 ng/mL were more accurate than normal thresholds of CRP and ESR for defining disease activity. Patients with unknown or equivocal disease status were excluded from the study. [37]
Certainly, PTX3 plasma levels may play a future role as a possible disease marker. However as pointed out by the authors of the study, PTX3 needs to be assessed in a broader spectrum of patients whose disease activity is unknown or equivocal before recommending using it clinically. [37]
Other measures of disease activity in Takayasu arteritis include the Birmingham Vasculitis Activity Score (BVAS), Disease Extent Index for Takayasu's Arteritis (DEI.Tak), and Indian Takayasu's Arteritis Score (ITAS). The ITAS seems to have good correlation; however, none of those scores has been validated. [38, 39]
Imaging modalities for assessment of disease activity are limited by various factors, and no consensus has been reached on their sensitivity and specificity. Computed tomography angiography is limited by the amount of exposure to contrast. Magnetic resonance angiography is useful for providing information on vessel wall thickness, edema, and contrast enhancement; however, its ability to discriminate between acute versus inactive disease has been questioned.
18-Fluorodeoxyglucose positron emission tomography (FDG-PET) is a promising imaging modality, given its noninvasiveness and ability to visualize regional distribution in the vascular tree. No consensus has been reached on its sensitivity and specificity in determining acute versus inactive disease. Increased vascular uptake may be visible on an18F-FDG scan performed years after the acute phase. [40]
Novel ligands such as radioactive PK11195 that bind to peripheral benzodiazepine receptors on activated monocyte/macrophages are under investigation to improve specificity of PET for active disease. [38]
Angiography
Angiography, the criterion standard for the diagnosis and evaluation of Takayasu arteritis, is used to evaluate only the appearance of the lumen and cannot be used to differentiate between active and inactive lesions. (See the images below.) Takayasu arteritis can be divided into the following 6 types based on angiographic involvement: [4]
-
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
Takayasu arteritis. 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. Characteristic long, tapered narrowing of the distal aorta and iliac vessels. Image courtesy of Robert Cirillo, MD.
Takayasu arteritis. Image obtained in the same patient as in Image 2 reveals narrowing of the proximal descending aorta and right brachiocephalic artery. Image courtesy of Robert Cirillo, MD.
Takayasu arteritis. Aortogram of a 15-year-old girl with Takayasu arteritis. Note large aneurysms of descending aorta and dilatation of innominate artery. Image courtesy of Christine Hom, MD.
Imaging Studies
Ultrasonography
Color Doppler ultrasonography provides details of the vascular wall, lumen, and flow and is a useful tool for screening and follow-up, particularly for carotid and subclavian arteries.
CT scanning
CT helical scanning angiography is a sensitive and specific diagnostic tool. CT scanning or ultrasonography may be used to assess the thickness of the aorta. One study found that multi-slice CT scanning was useful in detecting lesions. [41]
MRA
The sensitivity of magnetic resonance angiography (MRA) is the same as or greater than that of angiography for revealing lesions in the aorta and its brachycephalic branches but is less sensitive for helping to detect smaller branch involvement. MRA that uses fast spin-echo sequences designed to enhance the detection of vessel wall edema shows promise in assessing disease activity before irreversible lesions develop.
Advances in technology have substantially improved the sensitivity and specificity of MRA, and the entire arterial vasculature can be displayed in less than 90 seconds. The risks are practically nonexistent. [42]
PET scanning
The modality 18-F-FDG-PET has been shown to be useful in monitoring disease activity and response to treatment in preliminary studies. The presence or absence of FDG uptake correlates well with a patient’s clinical state and MRI findings. Its use in patients with Takayasu arteritis requires further investigation.
Several studies have shown that whole-body PET scanning demonstrates anatomic changes consistent with the diagnosis of Takayasu arteritis. [36, 35, 34]
Other imaging modalities
Single-photon emission computed tomography (SPECT) scanning has been used to assess cerebral blood flow and may be useful in patients who undergo bypass surgery.
Gallium scanning has been used to assess inflammatory involvement of the vessels.
Tissue Biopsy
In contrast to other vasculitides, tissue biopsy plays little to no role in the diagnosis of Takayasu arteritis, as histologic examination of the great vessels is usually possible only at the time of vascular procedures or postmortem. Biopsy of medium- to large-sized vessels may be diagnostic in early stages of the disease; however, in the chronic phase, diagnosis based on biopsy alone is inadequate. Whenever possible, the feasibility of submitting arterial tissue should be discussed with the attending surgeon prior to any surgical revascularization procedure.
Histologic Findings
Takayasu arteritis is characterized by a special pattern of histopathologic changes. The early stage consists of a continuous or patchy granulomatous inflammatory reaction involving macrophages, lymphocytes, and multinucleated giant cells. Inflammation initially occurs in the vasa vasorum, with the artery wall becoming irregularly thickened and the lumen becoming narrowed. Takayasu arteritis progresses to a sclerotic stage, with intimal and adventitial fibrosis and scarring of the media. Lesions are initially inflammatory and later become occlusive.
In the early phase of Takayasu arteritis, histologic features include granulomatous changes in the media and adventitia of the aorta and its branches, followed by intimal hyperplasia, medial degeneration, and adventitial fibrosis of the sclerotic type. The duration is variable. Inflammatory cells—predominantly CD4 and CD8 lymphocytes, macrophages, plasma cells, histiocytes, and giant cells—invade the adventitia and media but not the intima.
In the vasoocclusive stage, the lesions are characterized by occlusion and signs of ischemia. The adventitia and media are replaced by fibrous scarring, the vasa vasorum are obliterated, and the intima undergoes irregular thickening. Medial degeneration, disruption of the elastic lamellae, and thrombosis can occur. Aneurysms can form, but no aneurysms attributed to Takayasu arteritis have been identified in the intracranial circulation. The literature reports a few cases of intracranial aneurysms that are considered to be incidental.
The ground substance in the intima is increased markedly, histochemically showing a basophilic acid mucopolysaccharide in a state of gelatinous swelling.
An increase in CD4 and decrease in CD8 lymphocytes, along with reduced B lymphocytes, have suggested a defect in T-cell regulation (cell-mediated immunity). Biopsy samples exhibit infiltrates of lymphocytes and monocytes in both the vessel walls and a peripheral nerve vasculitis. Lymphocytes and monocytes are attracted to the vessel wall either by an infectious agent or an autoimmune response, modulated by intercellular adhesion molecules (ICAMs).
-
Takayasu arteritis. 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. Characteristic long, tapered narrowing of the distal aorta and iliac vessels. Image courtesy of Robert Cirillo, MD.
-
Takayasu arteritis. Image obtained in the same patient as in Image 2 reveals narrowing of the proximal descending aorta and right brachiocephalic artery. Image courtesy of Robert Cirillo, MD.
-
Takayasu arteritis. Aortogram of a 15-year-old girl with Takayasu arteritis. Note large aneurysms of descending aorta and dilatation of innominate artery. Image courtesy of Christine Hom, MD.
-
Takayasu arteritis. MRI of thorax of 15-year-old girl with Takayasu arteritis. Note aneurysms of descending aorta. Image courtesy of Christine Hom, MD.
-
Takayasu arteritis. Coronal MRI of abdomen of 15-year-old girl with Takayasu arteritis. Note thickening and tortuosity of abdominal aorta proximal to kidneys. Image courtesy of Christine Hom, MD.
