History
The presentation of Takayasu arteritis is heterogeneous. Approximately 10% of patients with Takayasu arteritis are asymptomatic, and the diagnosis is suggested only by abnormal vascular findings on physical exam. [17, 23] Constitutional symptoms may precede clinical vascular involvement.
Constitutional symptoms include the following: [20, 17, 23, 24]
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Headache (50-70%)
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Malaise (35-65%)
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Arthralgias (28-75%)
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Fever (9-35%)
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Weight loss (10-18%)
Cardiac and vascular features include the following: [20, 17, 23, 24, 25]
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Bruit, with the most common location being the carotid artery (80%)
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Blood pressure difference of extremities (45%-69%)
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Claudication (38-81%)
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Carotodynia or vessel tenderness (13-32%)
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Hypertension (28-53%; 58% with renal artery stenosis in one series)
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Aortic regurgitation (20-24%)
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Raynaud phenomenon (15%)
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Pericarditis (< 8%)
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Congestive heart failure (< 7%)
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Myocardial infarction (< 3%)
Neurologic features include the following: [20, 17, 23, 24, 25]
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Headache (50-70%)
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Visual disturbance (16-35%) - Strong association with common carotid and vertebral artery disease
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Stroke (5-9%)
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Transient ischemic attacks (3-7%)
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Seizures (0-20%)
Dermatologic manifestations include the following: [17, 24, 25]
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Erythema nodosum (6-19%)
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Ulcerated subacute nodular lesions (< 2.5%)
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Pyoderma gangrenosum (< 1%)
Classification criteria
The American College of Rheumatology has established classification criteria for Takayasu arteritis (3 of 6 criteria are necessary). The presence of any 3 or more criteria yields a sensitivity of 90.5% and a specificity of 97.8%. [26] The criteria are as follows:
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Age of 40 years or younger at disease onset
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Claudication of the extremities
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Decreased pulsation of one or both brachial arteries
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Difference of at least 10 mm Hg in systolic blood pressure between arms
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Bruit over one or both subclavian arteries or the abdominal aorta
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Arteriographic narrowing or occlusion of the entire aorta, its primary branches, or large arteries in the upper or lower extremities that is not due to arteriosclerosis, fibromuscular dysplasia, or other causes
Stages
Takayasu arteritis progresses through 3 stages. Thus, symptoms that clinicians encounter depend on how soon the patient presents; most patients present late, delaying the diagnosis. In actual practice, however, most patients do not fall readily into such groupings, and this 3-stage scheme is an oversimplification of the complex clinical presentation. Symptoms encountered can occur early or late in the course of the disease. In the aforementioned NIH series, which included 60 patients observed over 20 years, only 33% of patients had constitutional symptoms (corresponding to stage 1); 18% of patients never progressed to the third stage.
The first stage is an early systemic stage during which the patient may complain of constitutional symptoms (eg, fatigue, malaise, giddiness, fever). This stage is considered to be prevasculitic.
The second stage is the vascular inflammatory stage when stenosis, aneurysms, and vascular pain (carotidynia) tend to occur.
Signs and symptoms characterizing the vascular inflammatory stage include fatigue, fevers, malaise, pain in extremities and joints, dyspnea, palpitations, headaches, rash (erythema nodosum or a lupuslike butterfly rash, which can be photosensitive), hemoptysis, ulceration, and weight loss. A single case of thoracic and lumbar spine pain has been reported. Symptoms of vascular insufficiency include arm numbness, claudication in the legs (rare), blurry vision, double vision (which can be posture dependent), amaurosis fugax, stroke, transient ischemic attacks, hemiplegia, seizures, and paraplegia.
The constitutional systemic symptoms and vascular symptoms may occur at the same time, rendering the classification into stages practically impossible.
The third stage is the burned-out stage, when fibrosis sets in, and generally is associated with remission. This stage does not occur in all patients, and even in patients who are in remission, relapses can occur. Presumably, the burned-out stage manifests with minimal symptoms, but little supportive evidence is found in the literature.
Takayasu arteritis in pregnancy
Special mention should be made regarding pregnant women. The inflammatory activity is not enhanced by the pregnancy, but the perinatal period may be complicated by the associated symptoms. Blood pressure may not be measurable due to pulselessness, thus making patient monitoring difficult, if not impossible. Often, calf pressures need to be obtained.
In pregnant women with Takayasu arteritis, uncontrolled blood pressure may lead to subarachnoid/intracranial hemorrhage and subsequent seizures, eye changes, preeclampsia, aortic regurgitation, syncope, fetal complications, and nephrotic syndrome.
Physical Examination
A thorough physical examination is essential, with particular attention paid to peripheral pulses, blood pressure in all 4 extremities, and ophthalmologic examination. The most discriminatory finding is a systolic blood pressure difference (>10 mm Hg) between arms.
Hypertension due to renal artery involvement (and sometimes leading to hypertensive encephalopathy) is found in approximately 50% of patients. Carotidynia may be present. Aortic regurgitation is a common finding.
Absent or diminished pulses are the clinical hallmark of Takayasu arteritis, but pulses are normal in many patients and upper limbs are affected more often than lower limbs. When pulselessness occurs, patient monitoring can be difficult or impossible, and often, calf blood pressures must be obtained.
Ophthalmologic examination may show retinal ischemia, retinal hemorrhages, cotton-wool exudates, venous dilatation and beading, microaneurysms of peripheral retina, optic atrophy, vitreous hemorrhage, and classic, wreathlike peripapillary arteriovenous anastomoses (extremely rare).Fundus fluorescein angiography may show segmented retinal blood flow, also known as “boxcarring". [27]
Skin changes resembling erythema nodosum or ulcerating nodular lesions may be seen.
Other significant findings include the following:
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Amaurosis fugax
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Focal neurologic deficits consistent with cerebral infarction or transient ischemic attack
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Vascular bruits, most commonly in the carotid and abdominal arteries but also in the subclavian and femoral arteries
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Myocardial infarction
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Dilated cardiomyopathy
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Eclampsia
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Subarachnoid hemorrhage, probably secondary to hypertension
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Leg edema due to renal failure secondary to renal artery stenosis and glomerulonephritis
Less common associations have been seen with the following:
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Ulcerative colitis
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Sensorineural hearing loss
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Pulmonary hemorrhage
A case report described sensorineural hearing loss associated with Takayasu arteritis. [28] Whether a firm connection between the 2 syndromes exists, other than the inflammatory manifestations, has not been demonstrated. The pathologic etiology of the hearing loss was attributed to an immune-mediated process in the membranous labyrinth.
Another case report described the presence of Cogan syndrome with Takayasu arteritis. [29] Cogan syndrome involves interstitial keratitis and a vestibuloauditory syndrome. Variations of this with other types of inflammatory eye disease and vestibuloauditory arteritis have also been reported.
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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.
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Takayasu arteritis. Characteristic long, tapered narrowing of the distal aorta and iliac vessels. Image courtesy of Robert Cirillo, MD.
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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.
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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.
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Takayasu arteritis. MRI of thorax of 15-year-old girl with Takayasu arteritis. Note aneurysms of descending aorta. Image courtesy of Christine Hom, MD.
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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.
