eMedicine Specialties > Rheumatology > Vasculitis

Takayasu Arteritis

Author: Mohammed Mubashir Ahmed, MD, Associate Professor, Department of Medicine, Division of Rheumatology, University of Toledo College of Medicine
Coauthor(s): Robert E Wolf, MD, PhD, Professor Emeritus, Department of Medicine, Louisiana State University Health Sciences Center at Shreveport; Chief, Rheumatology Section, Medical Service, Overton Brooks Veterans Administration Medical Center of Shreveport
Contributor Information and Disclosures

Updated: Feb 14, 2008

Introduction

Background

Takayasu arteritis (TA) is classically defined as a chronic, progressive, inflammatory, occlusive disease of the aorta and its branches. The pulmonary arteries can also be involved. Takayasu arteritis is a systemic disease that may have isolated, atypical, and catastrophic manifestations. Takayasu described the retinal changes of the disease in 1908, the same year that the association between the retinal changes and pulse deficit was reported. However, the disorder was not termed Takayasu's disease until 1954.

Pathophysiology

Cell-mediated autoimmunity appears to play an important role in the mechanism of vascular injury. Takayasu arteritis is characterized by a specific pattern of histopathological changes. The early stage consists of a continuous or patchy granulomatous inflammatory reaction involving macrophages, lymphocytes, and multinucleated giant cells. The infiltrating T lymphocytes may be of restricted phenotype and have a restricted repertoire, suggesting an antigenic target in aortic tissue. Antiendothelial antibodies may be found in high titers in some patients, but this may be an epiphenomenon rather than one of pathogenetic importance.

Frequency

United States

The estimated annual prevalence is 2.6-6.4 persons per 1,000,000 population. The discrepancy is attributed to genetic factors and difficulty in diagnosis. Between 1971 and 1983 in Olmstead County, Minnesota, 3 cases were recorded, thus giving an annual incidence of 2.6 cases per million population.

International

Although Takayasu arteritis has a worldwide distribution, it is observed more frequently in Asia and India than in Western Europe and North America. Worldwide incidence is estimated at 2.6 cases per million persons per year. 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 cases per million persons.

Mortality/Morbidity

Takayasu arteritis is a chronic relapsing and remitting disorder. The 15-year survival rate has been reported to be 90-95%. In other studies, the mortality rate has been reported to range from 2-35% over 5 years. Such disparity may reflect differences in access to care, definitions of disease activity, and indications for treatment.

The overall morbidity depends on the severity of the lesions and their consequences and is usually the result of vascular complications such as aortic regurgitation, congestive heart failure, cerebrovascular events, myocardial infarction, aneurysm rupture, or renal failure.

Race

Takayasu arteritis is observed more frequently in patients of Asian or Indian descent. Japanese patients with Takayasu arteritis have a higher incidence of aortic arch involvement. In contrast, series from India report higher incidences of thoracic and abdominal involvement. In US patients with Takayasu arteritis, the most commonly involved vessels are the left subclavian, superior mesenteric, and abdominal aorta.

Sex

Approximately 80% of patients are women.

Age

Most patients are aged 4-63 years, with the mean age of onset being approximately 30 years. Fewer than 15% of cases present in individuals older than 40 years.

Clinical

History

The presentation of Takayasu arteritis is heterogeneous. Most patients present with systemic and vascular symptoms; however, approximately 20% of patients with Takayasu arteritis are clinically asymptomatic, with the disease being detected based on abnormal vascular findings upon examination. Constitutional symptoms usually precede clinical vascular involvement.

• The American College of Rheumatology has established classification criteria for Takayasu arteritis (3 of 6 criteria are necessary), as follows:
  • Age of 40 years or younger at disease onset
  • Claudication of the extremities
  • Decreased pulsation of one or both brachial arteries
  • Difference of at least 10 mm Hg in systolic blood pressure between arms
  • Bruit over one or both subclavian arteries or the abdominal aorta
  • 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
• Constitutional symptoms are typical in 40% of North American patients. They include the following:
  • Fever (40%; some patients initially present with fever of unknown origin in the prepulseless phase)
  • Weight loss (40-60%)
  • Malaise (40-60%)
  • Fatigue (40%)
  • Myalgias (40%)
  • Arthralgias (40-60%)
  • Arthritis (40%)
• Vascular features (60-70%) include the following:
  • Jaw claudication
  • Extremity claudication
• Neurological features (60%) include the following:
  • Transient ischemic attacks
  • Hemorrhagic or ischemic stroke
  • Transient or permanent blindness
  • Headaches
  • Seizures
  • Subclavian steal syndrome
• Cardiac features (50%) include the following:
  • Aortic regurgitation
  • Angina
  • Myocardial infarction
  • Myocarditis and cardiomyopathy
  • Congestive heart failure (primary cause of death)
  • Arrhythmias
  • Sudden death
• Pulmonary features (40%) include the following:
  • Pulmonary hypertension (often asymptomatic)
  • Hemoptysis
  • Pleuritis
  • Compromised pulmonary function tests
  • Abnormal findings on ventilation/perfusion scans (may be mistakenly diagnosed as thromboembolic disease)
• Renal manifestations include the following:
  • Renovascular hypertension (most frequent)
  • Mesangial proliferative glomerulonephritis with mesangial deposits of immunoglobulins M, G, and A and C3
  • Membranoproliferative and crescentic glomerulonephritis
  • Renal amyloidosis (rarely reported)
• Dermatological manifestations include the following:
  • Ulcerated subacute nodular lesions
  • Erythema nodosum
  • Erythema induratum
  • Papulonecrotic eruptions
  • Papular erythematous lesions of hands
  • Pyoderma gangrenosum
  • Erythema multiforme
• Gastrointestinal manifestations are rare and include the following:
  • Nausea
  • Vomiting
  • Diarrhea
  • Abdominal pain
  • Bleeding (due to mesenteric artery ischemia)

Physical

A thorough physical examination is essential, with particular attention to peripheral pulses, blood pressure in all 4 extremities, and an ophthalmologic examination.

• The most discriminatory finding is a systolic blood pressure difference (>10 mm Hg) between arms. Hypertension due to renal artery involvement is found in approximately 50% of patients.
• 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.
• Vessel tenderness (carotidynia) may be present.
• Bruits often are noted.
• Aortic regurgitation may be noted upon cardiac examination.
• Of note upon ophthalmologic examination may be 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).
• Skin vasculitis resembling erythema nodosum or ulcerating nodular lesions may be seen.

Causes

Takayasu arteritis is believed to be an autoimmune disease with no known cause. Genetic factors may play a role in the pathogenesis of Takayasu arteritis, with a possible major histocompatibility complex linkage. In Japan and Korea, Takayasu arteritis is associated with human leukocyte antigens HLA-A10, B5, Bw52, DR2, and DR4. These associations have not been confirmed in Western studies. Takayasu arteritis is associated with HLA-B22 in the United States.

A recent study demonstrated an association between 4 unrelated cases of Takayasu arteritis and CD36 deficiency (CD36d).¹ 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. CD36 thrombospondin signal is important in the apoptotic regulation of vascular endothelial cells. The defects in apoptotic machinery in patients with CD36d are hypothesized to predispose them to autoimmune disorders such as Takayasu arteritis.

• Search for CME/CE on This Topic »

• Takayasu Arteritis (Pediatrics: General Medicine)
• Takayasu Arteritis (Neurology)
• Arteritis, Takayasu (Radiology)
• Conduits for Vascular Reconstruction in the Pediatric Patient (Pediatrics: Surgery)

• Advances in Childhood Vasculitis