Published June 4, 2004Kathleen
Maksimowicz-
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| DEFINITION |
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DefinitionPrevalencePathophysiologyClinical
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Takayasu's arteritis (TA) is a large-vessel vasculitis of unknown etiology that has a predilection for the aorta and its primary branches. Sustained inflammation of involved vessels leads most often to stenotic lesions, but may also result in aneurysm formation. |
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| PREVALENCE | |||
TA is a rare disorder, occurring most frequently in the Far East. In Japan, about 100 new cases of TA are identified yearly, and autopsy studies detect evidence of TA in 1 of every 3000 postmortems.1 In Olmstead County, Minnesota, the incidence is only 2.6 cases/million population/year.2 Females are affected up to 10 times more often than males, with the peak incidence occurring in the 3rd decade of life. |
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| PATHOPHYSIOLOGY | |||
Vascular injury is mediated by the actions of macrophages, cytotoxic T cells, gamma delta T cells, and natural killer cells.3 The vessel wall is breached by leukocytes via the adventitial vasa vasorum, followed by their migration towards the luminal intima. Cytokines such as perforin, IL-6, RANTES, and TNF-alpha induce and propagate further inflammation and tissue injury.4 These processes lead to myointimal proliferation, with subsequent vessel wall thickening and luminal stenosis. If smooth muscle cell and elastic fiber destruction dominates, the result may be aneurysm formation. The latter most commonly occurs in the aortic root and arch. Infectious agents, especially mycobacterial pathogens, have long been suspected to play a role in TA, but there is no conclusive evidence to support their role in causality. |
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| CLINICAL MANIFESTATIONS | |||
One of the difficulties
in making a diagnosis of TA lies in the heterogeneity of presentations.
TA presents with the acute onset of clinically apparent signs and symptoms
of systemic inflammation in fewer than 50% of patients. The most common
symptom of TA is upper extremity claudication, which occurs in over 60%
of cases.5 This is a consequence of the
frequent involvement of aortic arch vessels. The most common clinical
signs of TA include blood pressure asymmetry of extremities (40-96%),
and vascular bruits (up to 80%).6 Bruits
may be detected over any large vessel and are most often found over the
carotid, subclavian, and aortic vessels. Visual manifestations
of TA may be due to vitreous hemorrhage and retinopathy. TA retinopathy
is seen in up to 25% of Japanese patients8,
but is rare elsewhere. Secondary causes of visual impairment can be due
to the effects of corticosteroid therapy (e.g. glaucoma, cataracts). Although pulmonary abnormalities are detected in up to 70% of TA patients on imaging studies9, clinical symptoms such as cough, chest pain, dyspnea, or hemoptysis only occur in about 25%. Pulmonary manifestations include interstitial changes, pleural effusion, pulmonary hemorrhage, and pulmonary artery stenoses.10-12 Visceral artery involvement is not uncommon, but clinical symptoms are infrequent. Lesions of the celiac trunk or mesenteric arteries may result in ischemia of the abdominal viscera. Surgical intervention should occur when patients exhibit symptoms of chronic abdominal angina or acute visceral infarction. Dermatologic manifestations occur in up to 28% of patients with TA. These features are nonspecific and include erythema nodosum, pyoderma gangrenosum, and erythema induratum.13 Rare cases of cutaneous necrotizing and granulomatous vasculitis have been described. |
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| DIAGNOSIS | |||
The diagnosis of TA is based on clinical findings in the setting of compatible vascular imaging abnormalities. There are no serologic tests with sufficient sensitivity and specificity to be considered a gold standard for a diagnosis of TA. For diagnostic imaging, catheter-directed angiography is the gold standard in TA. It provides opportunities for luminal imaging, intravascular pressure measurements, and methods for intervention (e.g. angioplasty). The important limitation of catheter-directed angiography is its inability to provide information about the vessel wall per se. The use of MR, or more recently experimental protocols that combine PET imaging with MR or CAT, will hopefully aid in better identifying the presence or absence of inflammation within large vessels. Acute phase reactants may be helpful in assessing disease activity in an individual in whom they have been found to parallel disease activity as determined by vascular imaging and clinical symptoms. However, they are unreliable guides in many patients. Normal acute phase reactants do not assure disease remission. Sequential imaging evaluations have revealed disease progression (as determined by the presence of new vascular lesions) in over 60% of patients with clinically stable profiles and normal ESRs.14 Clinical evaluation alone may also face the same inaccuracies: 44% of patients with TA with apparent clinically quiescent disease undergoing bypass have been noted to have histopathologic evidence of vascular inflammation.5 |
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| DIFFERENTIAL DIAGNOSIS | |||
TA has many mimics. Diseases such as Marfan's syndrome, Ehlers-Danlos syndrome, and other congenital disorders of connective tissue may manifest with aneurysmal disease and aortic valve insufficiency. However, it would be uncommon for these diseases to be associated with large vessel stenoses, the hallmark of TA. In general, signs and symptoms of systemic inflammation are absent in these disorders as well. Infectious etiologies of large vessel aneurysms should be considered in all patients. Agents known to cause aortic aneurysms include bacterial, syphilitic, mycobacterial, and mycotic pathogens. Again, stenotic disease in the setting of infection would be uncommon. Atherosclerotic vascular disease may present similarly to TA, but the setting in which these disorders occur helps to distinguish each of them. TA is more prevalent in young females, and preferentially affects the large vessels of the upper extremities and the aortic root. Atherosclerosis more often occurs in older individuals, and is more frequent in the vessels of the lower extremities and abdominal aorta. Other vasculitides,
such as Cogan's syndrome, Behcet's syndrome, SLE and the spondyloarthropathies
may be associated with large vessel vasculitis. Fortunately, in most cases
their other disease manifestations help to distinguish them from TA. Sarcoidosis
shares many features of TA. Biopsy of involved organs may be necessary
to distinguish between these diseases. The presence of hilar lymphadenopathy,
parenchymal lung disease and proliferative synovitis favors a diagnosis
of sarcoidosis. |
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| THERAPY | |||
One of the challenges in the management of TA is determining disease activity. Kerr et al define active disease as any two or more of the following:5 New or worsening:
These features may
be helpful when present, but their absence does not insure disease remission.
These criteria, used in conjunction with serial imaging, are currently
the most effective means available for monitoring of TA activity. The detection and treatment of HTN in TA is essential. The diagnosis of HTN is often delayed because of the high frequency of subclavian and innominate artery involvement, which may result in a falsely low (compared to the aortic root) peripheral blood pressure reading. When stenoses involve all extremities, there may not be any peripheral source available to reflect central aortic pressures accurately. Thus, it is crucial for the clinician to have a "road map" of the entire large vessel anatomy to identify potential territories at risk and to provide proper care for patients with TA. The importance of complete vascular imaging at the time of diagnosis cannot be overemphasized. When stenoses are present, especially if affecting upper extremity large vessels, invasive angiography with central aortic pressure measurements and gradient determinations is critical to assess the reliability of peripheral blood pressure cuff measurements. Treatment of HTN in TA can be complex. Even when the accuracy of peripheral measurements has been established, identifying a target pressure range that minimizes end organ damage while allowing for vital organ perfusion in the setting of arterial stenoses can be challenging. Close monitoring with avoidance of abrupt decreases in mean pressures is desirable. Kerr et al found that 50% (30/60) patients followed over a mean period of 5 years (range: 6 months-20 years) required intervention for either vessel stenosis or aortic regurgitation.5 Interventions included bypass procedures, percutaneous transluminal angioplasty, aortic root replacement, and aortic root repair. Revascularization procedures in TA ideally should be performed during disease remission. Overall, bypass grafting maintained better sustained patency than did angioplasty or stenting.16 In our experience, stenting has almost always led to occlusion and need for bypass. At the time of bypass procedures, tissue should be obtained from the origin and/or insertion of grafts whenever possible to help determine disease activity. This is particularly important because clinical symptoms and acute phase reactants may not accurately reflect disease activity. Surgical risk is increased in patients with TA. One series, following 106 patients over a mean period of 19.8 years, stratified post-operative mortality into early and late deaths. Early deaths, defined as death occurring during hospitalization, occurred in 11.3% of patients.17 Death occurred in most as a result of cardiovascular complications including congestive heart failure, aneurysm rupture, stroke, or hemorrhage. However, another series of 33 patients reported only one perioperative death (resulting from infection) over a mean followup period of 3 years.18 Perioperative mortality is influenced by a number of factors, with the experience of the surgical team and medical center in caring for TA patients a crucial element in surgical success and outcomes. Morbidity and mortality in patients with TA are directly correlated with the vascular territories involved and the extent of disease. In addition, the morbidity associated with immunosuppressive therapies (eg cataracts, osteoporosis, or infections related to corticosteroid use) should not be discounted. Patients with aortic aneurysms, hypertension, cardiac involvement or severe functional disability have a greater risk of premature death.7 Sudden death may result from myocardial infarction, stroke, or rupture or dissection of an aortic aneurysm.7 Despite these potential life-threatening complications, 5-10 year survival rates have been reported as high as 74-90%. 7 19 Patients with TA require a multidisciplinary approach for optimal care. The team should include a rheumatologist, cardiologist, imaging specialist, and when appropriate, vascular and cardiothoracic surgeons. |
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| SPECIAL CONSIDERATIONS | |||
It is important to be mindful of the heterogeneity of presentations of TA. The diagnosis of TA should be entertained in the setting of vascular bruits or claudicatory symptoms, the absence of pulses, or asymmetry of blood pressures, especially when detected in a younger patient. |
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| REFERENCES | |||
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