Takayasu arteritis also known as pulseless disease, occlusive thromboaortopathy, and Martorell syndrome is a rare disorder characterized by the progressive inflammation and damage of one or more of the larger arteries and medium arteries and their branches leading to the heart and nonspecific constitutional symptoms such as fever, malaise, weight loss, anorexia, hypertension, neurologic manifestations, and upper limb claudication occurs secondary to arterial insufficiency. The main artery of the heart (aorta) and the pulmonary (lung) artery, among others, may be affected. It usually involves the aorta and its major branches, particularly the renal arteries, carotid arteries, and subclavian arteries, and leads to stenosis, occlusions, or aneurysmal degeneration of these large arteries. When this disorder causes progressive inflammation of many arteries, it is known as polyarteritis. One of the consequences of polyarteritis is the reduction of blood flow to any of several organs and/or arms and legs. Arteries in the head and arms may be affected, and this can result in the loss of the major pulse points in the body. Some people with Takayasu arteritis have irregular narrowing of portions of the large arteries (segmental stenosis) and abnormal backward flow of blood from the aorta into the left ventricle of the heart (aortic regurgitation). Other patients may have symptoms of ballooning and weakening (aneurysm) of the wall of a major vessel.
Symptoms
About half of the patients with Takayasu arteritis display a general feeling of weakness (malaise). In addition, patients may complain of muscle aches (myalgias), and joint pain (arthralgias). Progressive obstructive arterial disease and narrowing of the arteries (stenosis) may follow the initial phase of the disease. When the aorta and the major arteries in the neck (carotid arteries) are affected by Takayasu arteritis, the patient usually experiences lightheadedness, dizziness, and brief moments of unconsciousness (syncope). These symptoms are the result of a decrease in blood supply to the brain (cerebral ischemia). The pulses that are normally found in the neck and on the temples (carotid and superficial temporal pulses) may be absent. Most often, the progression of the arteritis is slow so that there is sufficient time to develop adequate alternate circulation (collateral or secondary circulation).
People with Takayasu arteritis may develop impairment of heart and brain function due to the insufficient flow of blood to these organs. In some cases an artery may rupture due to weakness of the vessels’ wall (aneurysm), and/or difficulty speaking (aphasia) may occur. Other symptoms may include episodes of blindness, dim vision, and abnormal sensitivity to light (photophobia). Involvement of the arteries in the neck (brachial involvement) may cause weakness in the arms and weakness and cramps in the legs (claudication), cool skin, and the absence of pulses in the wrists (radial). Blood pressure may be very difficult to measure.
CHARACTERISTIC FEATURES
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Diminished or absent pulses in 84–96% of patients associated with limb claudication and blood pressure discrepancies.
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Vascular bruits in 80–94% of patients, often multiple, and particularly affecting the carotids, subclavian, and abdominal vessels.
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Takayasu retinopathy in up to 37% of patients.
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Aortic regurgitation results from dilatation of the ascending aorta, separation of the valve leaflets, and valve thickening in 20–24%.
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Congestive cardiac failure is associated with hypertension, aortic regurgitation, and dilated cardiomyopathy.
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Neurological features secondary to hypertension and/or ischemia, including postural dizziness, seizures, and amaurosis.
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Pulmonary artery involvement in 14–100% of patients, depending on the method used to assess pulmonary vasculature. Oligaemic lung fields on plain chest x-ray correlate with pulmonary vasculopathy in approximately a third of cases. Pulmonary artery disease shows little correlation with the systemic pattern of arterial involvement, but can be useful in the differential diagnosis by helping to confirm Takayasu arteritis.
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Other symptoms include dyspnoea, headaches, acrodynia, myocardial ischemia, chest wall pain, and erythema nodosum.
Intermittent attacks of decreased blood flow to the hands and feet (Raynaud’s phenomenon) typically occur in people with Takayasu arteritis. Additional symptoms may include heart murmurs (systolic) and inflammation of the blood vessels that result in nodules under the skin that are red and tender (erythema nodosum). Sometimes people with Takayasu arteritis experience cloudiness of the lens of the eyes (cataracts) at an early age, and there may be a progressive weakness in the muscles and soft tissues of the face.
Causes
The exact cause of Takayasu arteritis is not known. Certain laboratory findings, such as elevated levels of globulins and the presence in serum of unusual antibodies, suggest a defect in the immune system and a possible autoimmune association. Autoimmune disorders are caused when the body’s natural defenses (e.g., antibodies) against “foreign” or invading organisms begin to attack healthy tissue for unknown reasons.
It is thought that Takayasu arteritis may also run in families and occurs with greater frequency in certain races. Studies have shown an increased frequency of Takayasu arteritis in Asians who have a particular antigen on chromosome 6 (HLA-Bw52). There appears to be an increase in this disorder in North Americans who carry a particular HLA (HLA-DR4). Infectious agents such as bacteria and viruses do not appear to play a role in the cause of this disorder. It may be that some people are genetically predisposed to this disease. A genetic predisposition means that a person may carry a gene for a disease but it may not be expressed unless something in the environment triggers the disease.
Other studies have suggested that at least some cases of Takayasu arteritis may be inherited as an autosomal recessive genetic trait. Human traits, including the classic genetic diseases, are the product of the interaction of two genes, one received from the father and one from the mother. In recessive disorders, the condition does not appear unless a person inherits the same defective gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier of the disease, but usually will not show symptoms. The risk of transmitting the disease to the children of a couple, both of whom are carriers of a recessive disorder, is twenty-five percent. Fifty percent of their children risk being carriers of the disease but generally will not show symptoms of the disorder. Twenty-five percent of their children may receive both normal genes, one from each parent, and will be genetically normal (for that particular trait). The risk is the same for each pregnancy.
Diagnosis
In addition to a complete medical history and careful physical examination, several imaging techniques are used to evaluate the condition of the blood vessels. These include:
Clinical suspicion is needed to diagnose Takayasu arteritis, and thus a good, complete history and physical exam is a necessity. Imaging is vital, and CTA has recently become the standard for initial staging of disease distribution (previously it was conventional angiography) in Takayasu arteritis. This standard is based on the 1994 Tokyo International Conference Classification of Takayasu arteritis. CTA will allow for visualization of vessel wall thickening and luminal narrowing. MRI and MRA may also be used for identification and provide excellent multiplanar imaging without ionizing radiation use. However, like with all MRA, it tends to overestimate the degree of stenotic disease, and access to MRI or MRA is much more difficult.
X-ray examination to see the location and seriousness of any damage to the arteries; magnetic resonance imaging (MRI) to isolate and indicate vessel narrowing or aneurysms; computer axial tomography (CAT) scans to determine what damage, if any, has affected an organ of the body; and angiography, which permits the physician to see the interior of the artery to help determine the type of treatment.
Treatment
When the diagnosis of Takayasu arteritis is suspected, treatment should begin quickly to avoid serious complications such as the blockage of arteries and/or blindness. Corticosteroid drugs usually control initial local and systemic symptoms. Prednisone and prednisolone, the preferred corticosteroids, work rapidly to reduce symptoms. However, some patients are resistant to prednisone and its derivatives. The dosage of the corticosteroids is reduced over time but treatment may last for 2 years or longer to prevent a recurrence. Takayasu arteritis must be carefully monitored through blood tests (sedimentation rate). Immunosuppressive medications have also been used in place, or combination with corticosteroids. However, studies have not conferred an overall advantage on these medications.
Reconstructive vascular surgery, including cardiac bypass surgery, may be helpful in selected patients with Takayasu arteritis. The surgery may provide new pathways for the arterial circulation, bypassing those vessels that have narrowed. The blood-thinning drug, heparin, may be given to those patients who experience episodes of decreased blood supply to various parts of the body (ischemia).
Surgical revascularization is now rapidly evolving into a primary treatment choice. Transluminal angioplasty has been studied in the past. However, its overall role is limited in the treatment of patients with Takayasu arteritis. The fibrous nature of the arterial obliteration mitigates any durable long-term benefit[rx]. A study at the Cleveland Clinic revealed that 78% of their patient cohort treated with angioplasty in various anatomic locations experienced restenosis during a median 3-year follow-up, and 93% required reintervention at some point. Thus, PTA should be viewed as a short-term strategy for symptomatic relief if other medical needs must be attended to first in a given patient.
Arterial reconstruction is the other surgical option in patients with Takayasu arteritis. The type of reconstruction depends on where known lesions lie, as well as the patient’s surgical anatomy. In general, Dacron or polytetrafluoroethylene (PTFE) would be used for major aortic reconstructions, while autogenous saphenous vein would be used for extremity or isolated renal or mesenteric revascularization. Caution should be used when using autogenous saphenous veins secondary to their known propensity for aneurysmal degeneration. Both proximal and distal anastomotic sites must be free of any inflammatory involvement. Anastomosis onto involved arterial segments is a setup for early graft failure. In a study of 40 patients with TA at the University of Southern California, renovascular procedures were most common[rx]. Other procedures included various aortic reconstructions, aorta-carotid bypasses for cerebrovascular insufficiency, and bypasses to distal subclavian, axillary, or brachial arteries for upper extremity ischemia.
Surgical therapy is usually well tolerated due to the young age of most patients with Takayasu arteritis. Most have dramatic improvements in their symptoms following surgery, whether it be decreases, or even curing, of hypertension following renovascular reconstruction, or resolving of upper limb ischemia following upper extremity bypass for example. These findings suggest that surgical correction of symptomatic Takayasu arteritis will continue to rise.[rx][rx][rx][rx]
Take-home messages
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Takayasu arteritis is rare, affects mainly women, and is most commonly seen in Japan, South East Asia, India, and Mexico, where it usually presents in the 2nd or 3rd decade of life
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Manifestations range from asymptomatic disease, found as a result of impalpable pulses or bruits, to catastrophic neurological impairment
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Disease presentation varies between different populations
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Angiography remains the gold standard for diagnosis
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The four most important complications for classification are Takayasu retinopathy, secondary hypertension, aortic regurgitation, and aneurysm formation, each being graded as mild/moderate or severe at the time of diagnosis
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Four grades of disease are described, which can be used for prognostic and treatment assessment: cohort studies suggest a good prognosis for those with uncomplicated or monocomplicated disease
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Approximately half of those patients treated with steroids will respond, and half of the remaining patients respond to methotrexate; mycophenolate mofetil may be useful
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Treatment should aim to control disease activity and preserve vascular competence, with minimal long-term side effects; those with a disease that carries a good prognosis should not be put at risk by the treatment that is more harmful than the disease itself
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Fertility is not adversely affected and pregnancy does not appear to exacerbate the disease, although management of hypertension is essential
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