eMedicine Specialties > Neurology > Inflammatory and Demyelinating Diseases

Takayasu Arteritis

Author: Gabriel Bucurescu, MD, MS, Staff Neurologist, Neurology Service, Philadelphia Veterans Affairs Medical Center
Contributor Information and Disclosures

Updated: Dec 8, 2006

Introduction

Background

Takayasu arteritis (TA) is a chronic inflammatory disease of the large arteries, usually affecting the aorta and its large branches and the pulmonary arteries. It is one of the vasculitides and can manifest systemically, involving any or all of the major organ systems. The brain is a prime target.

Dr Mikito Takayasu first described TA in 1905, when he described a patient with a wreathlike coronary anastomosis of retinal vasculature surrounding the papilla. Since then, the disease has been reported in all parts of the world, although it appears to be more prevalent in Asians.

Pathophysiology

TA is an inflammatory disease of large- and medium-sized arteries, with a predilection for the aorta and its branches. Advanced lesions demonstrate a panarteritis with intimal proliferation.

Lesions produced by the inflammatory process can be stenotic, occlusive, or aneurysmal. All aneurysmal lesions may have areas of arterial narrowing. Vascular changes lead to the main complications, including hypertension, most often due to renal artery stenosis or, more rarely, stenosis of the suprarenal aorta; aortic insufficiency due to aortic valve involvement; pulmonary hypertension; and aortic or arterial aneurysm. Congestive heart failure is a common finding, much more so than dilated cardiomyopathy, myocarditis, and pericarditis, which also have been reported. In patients in whom the pulmonary artery is involved, the right artery appears to be affected more than the left, with patients developing pneumonia, interstitial pulmonary fibrosis, and alveolar damage.

Other pathophysiologic consequences include hypotensive ischemic retinopathy, vertebrobasilar ischemia, microaneurysms, carotid stenosis, hypertensive encephalopathy, and inflammatory bowel disease. Rarely, TA has also been associated with glomerulonephritis, systemic lupus, polymyositis, polymyalgia rheumatica, rheumatoid arthritis, Still disease, and ankylosing spondylitis.

Frequency

United States

• The prevalence is 2.6-6.4 persons per million population. The discrepancy is attributed to genetic factors and difficulty in diagnosis.
• Between 1971-1983 in Olmstead County, Minnesota, 3 cases were recorded, thus giving an annual incidence of 2.6 cases per million population.

International

• Worldwide incidence is estimated at 2.6 cases per million per year.
• Many cases of TA are reported from Southeast Asia, where the condition is believed to be most common. However, it has been reported in all parts of the world and in all racial groups.
• The prevalence in Sweden is similar to that in the United States (ie, 2.6-6.4 persons per million population).
• In the United Kingdom, the annual incidence is 0.15 case per million.

Mortality/Morbidity

• Because TA is rare, data on mortality and morbidity are limited. The site of the lesions and the degree of involvement determine the extent and the clinical severity. A National Institutes of Health (NIH) study of 60 patients with TA prospectively demonstrated a 3% mortality rate. This result was similar to data from Japan and China but markedly different from other reports (which reported mortality as high as 35%). Such disparity may reflect differences in access to care, definitions of disease activity, and indications for treatment.
• The same NIH study showed that 20% of patients had a monophasic illness, which was self-limiting; they did not require immunosuppressive treatment. In the remaining 80% of patients who did not have a monophasic illness and experienced one exacerbation, immunosuppressive therapy resulted in remission in 60%. Of these, one half experienced relapse after immunosuppressive therapy was stopped. The overall morbidity depends on the severity of the lesions and their consequences.

Race

Cases have been reported worldwide, but TA is most common in Southeast Asia and the Indian subcontinent.

Sex

TA is primarily a disease of young women. Men are rarely affected.

Age

TA primarily affects young women, especially those in the childbearing ages. Peak onset is in individuals in their 30s. Less than 15% of cases present in individuals older than 40 years.

Clinical

History

TA progresses through 3 stages. Thus, symptoms that clinicians encounter depend on how soon the patient presents; most patients present late, delaying the diagnosis. However, in actual practice, 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 NIH series including 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.
  • 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.
  • 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 (TIAs), 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.
• 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 TA, uncontrolled blood pressure may lead to subarachnoid/intracranial hemorrhage and subsequent seizures, eye changes, preeclampsia, aortic regurgitation, syncope, fetal complications, and nephrotic syndrome.

Physical

• The main finding is absent pulse(s) or a pulse discrepancy of greater than 30 mm Hg between the right and left arms.
• Other significant findings include the following:
  • Vascular bruits, most commonly in the carotid and abdominal arteries but also in the subclavian and femoral arteries
  • Focal neurologic deficits consistent with cerebral infarction or TIA
  • Hypertension, sometimes leading to hypertensive encephalopathy, usually due to renal artery stenosis
  • Amaurosis fugax
  • Retinal ischemia and microaneurysms
  • Myocardial infarction
  • Dilated cardiomyopathy
  • Eclampsia
  • Subarachnoid hemorrhage, probably secondary to hypertension
  • Leg edema due to renal failure secondary to renal artery stenosis and glomerulonephritis
• Less common associations have been seen with the following:
  • Ulcerative colitis
  • Sensorineural hearing loss
  • Pulmonary hemorrhage
• Blood pressure may not be measurable due to the pulselessness, making patient monitoring difficult or impossible. Often, calf blood pressures must be obtained.
• A case report of sensorineural hearing loss associated with TA also has been reported. Whether a firm connection between the two 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.
• A case report of Cogan syndrome with TA also has been reported. Cogan syndrome, first described in 1945, involves interstitial keratitis and a vestibuloauditory syndrome. Variations of this with other types of inflammatory eye disease and vestibuloauditory arteritis have been reported.

Causes

The etiology is unknown. The underlying pathologic process is inflammatory, with several etiologic factors having been proposed, including spirochetes, Mycobacterium tuberculosis, streptococcal organisms, and circulating antibodies due to an autoimmune process.

An antigen may stimulate aortic tissue, leading to the expression of heat shock protein-65, which, in turn, induces major histocompatibility (MHC) class I–related chain A (MICA). Natural killer cells and gamma-delta T cells expressing NKG2D receptors may infiltrate and recognize MICA on vascular smooth muscle cells, releasing porfrin and leading to acute inflammation. Proinflammatory cytokines are also released from the natural killer and T-cells, inducing the production of matrix metalloproteinases (MMPs) and amplifying the inflammatory response. This, in turn, would induce more MHC antigen and stimulate molecule expression on vascular cells, recruiting more mononuclear cells.

• In a case report, the role of M tuberculosis and its 65-kd heat shock protein has been implicated in the etiology. Patients with TA were found to have higher immunoglobulin G (IgG), immunoglobulin M (IgM), and immunoglobulin A (IgA) titers against the M tuberculosis extract than patients without the condition.
• A recent article reports the presence of CD3⁺ T cells and IgG antibodies reactive to circulating antimycobacterial heat shock protein 65 (mHSP65) antibodies and to its human homologue, hHSP60. This suggests a possible cross reactivity of immune response between mHSP65 and hHSP60.
• Other case reports involving the role of antiendothelial cell, anticardiolipin, and antiaorta antibodies also exist.
• In Japanese patients, human leukocyte antigen Bw52 (HLA-Bw52), which is in linkage disequilibrium with human leukocyte antigen DR4 (HLA-DR4), has been observed with increased frequency. Patients with the Bw52 genotype had a higher rate of aortic regurgitation. However, studies of HLA antigens in North American populations have not confirmed this.
• A recent study demonstrated an association between several cases of TA and CD36 deficiency (CD36d). The human CD36 antigen is a multifunctional membrane glycoprotein that belongs to the class B scavenger receptor family. It is expressed on monocytes, platelets, and endothelial cells, and contributes to myocardial fatty acid transport. In patients with CD36d, myocardial I-15-(p-iodophenyl)-3-(R,S)-methyl pentadecanoic acid (BMIPP) uptake was absent.

• Search for CME/CE on This Topic »

• Takayasu Arteritis (Pediatrics: General Medicine)
• Takayasu Arteritis (Rheumatology)
• Arteritis, Takayasu (Radiology)
• Renovascular Hypertension (Pediatrics: Surgery)