eMedicine Specialties > Pediatrics: General Medicine > Rheumatology

Takayasu Arteritis

Author: Christine Hom, MD, Assistant Professor, Department of Pediatrics, Division of Pediatric Rheumatology, New York Medical College
Contributor Information and Disclosures

Updated: Oct 31, 2008

Introduction

Background

In 1908, Mikito Takayasu, a Japanese ophthalmologist, reported the association of retinal arteriovenous anastomoses and absent upper extremity pulses. Takayasu arteritis (TA) is a chronic inflammatory disease of the aorta and its major branches. TA is a large vessel vasculitis of unknown origin that most often affects young women in the second and third decades of life. TA has been reported in children as young as 6 months and in adults of every age.

The initial complaints may be nonspecific constitutional signs and symptoms (eg, fever, weight loss, lethargy). Because these complaints lack specificity, the correct diagnosis may be delayed for months or years. Upon histologic examination, the aorta demonstrates evidence of inflammation. Mixed areas of stenosis or aneurysm formation are found on angiography or magnetic resonance angiography (MRA). Vascular insufficiency related to stenosis and thrombosis of affected vessels may cause renovascular hypertension, neurologic symptoms, or lower extremity claudications.

Cardiac involvement may include aortic regurgitation and congestive heart failure resulting from myocarditis or increased afterload. Often the diagnosis of TA is made when a widened mediastinum is appreciated on chest roentgenography and a tumor is suspected. CT scanning instead reveals a widened aortic arch.

Despite the term pulseless disease, which is a synonym for TA, the predominant finding in individuals with TA is asymmetric pulse. Absent peripheral pulses occur late in the course of the disease. Although 5-year survival rates exceed 90%, the disease has a high incidence of residual morbidity.

Pathophysiology

TA is characterized by granulomatous inflammation of the aorta and its major branches, leading to stenosis, thrombosis, and aneurysm formation. The lesions of TA are segmental with a patchy distribution.

Mononuclear infiltration of the adventitia occurs early in the course of the disease, with cuffing of the vasa vasorum. Granulomatous changes may be observed in the tunica media with Langerhans cells and central necrosis of elastic fibers and smooth muscle cells. A panarteritis with infiltrates of lymphocytes, plasma cells, histiocytes, and giant cells is present. Later, fibrosis of the media and acellular thickening of the intima compromise the vessel lumen. Wrinkling of the intima is visible upon gross examination.

Stenoses are found in 90% of patients with TA disease. Patients often have poststenotic dilatations and other aneurysmal areas. Stenotic arterial segments result in varied ischemic symptoms. These symptoms may range from abdominal pain after eating secondary to narrowing of the mesenteric arteries to renovascular hypertension to claudication of extremities. Endothelial activation leads to a hypercoagulable state predisposing the patient to thrombosis. Congestive heart failure in individuals with TA may occur as a result of hypertension, aortic root dilation, or myocarditis. Transient ischemic attacks, cerebrovascular accidents, mesenteric ischemia, carotidynia, and claudication may occur. Symptoms of vascular compromise may be minimized by the development of collateral circulation with the slow onset of stenosis. Vessel wall dissection or aneurysm may occur in areas weakened by inflammation.

One hypothesis for granulomatous vasculitis development is that antigens deposited in vascular walls activate CD4+ T cells, followed by release of cytokines chemotactic for monocytes. These monocytes are transformed into macrophages that mediate endothelial damage and granuloma formation in the vessel wall. A mouse model supports this hypothesis. When syngeneic T cells sensitized to vascular smooth muscle cells were injected into mice, a granulomatous vasculitis of the pulmonary arterioles occurred in 20% of the mice. Human studies suggesting endothelial cell activation have demonstrated increased expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in patients with TA. Humoral immunity is also believed to be involved in this disease; antiaorta antibodies and antiendothelial cell antibodies have been found in patients with TA. Immunoglobulin G, immunoglobulin M, and properdin are found in lesions from pathologic specimens.

Frequency

United States

In Minnesota's Olmstead County, incidence of TA was estimated at 2.6 per million. However, the applicability of this number to the diverse population of the United States as a whole is uncertain.

International

TA is common in underdeveloped countries, where the disease is closely associated with tuberculosis. The nature of this association is unclear because most patients with TA in the United States do not have tuberculosis. In contrast, many physicians in underdeveloped countries assume tuberculosis is present in every patient with TA.

Mortality/Morbidity

Because the disease is rare in the United States, accurate survival data are uncertain. One study reported a survival rate of 85-95% at 15 years. In a 1994 study, only 2% of deaths were attributed directly to TA. Japanese studies also support 90-95% survival rates.

In contrast, in a 1991 series involving 26 Mexican children aged 3-15 years, the 5-year survival rate was only 35%.¹ Deaths resulted from rupture of aorta or aneurysms (2), stroke (2), cardiac failure (2), and peritonitis and ventricular fibrillation.

Morbidities in persons with TA are related to ischemia and hypertension and include congestive heart failure, transient ischemic attacks, stroke, and visual disturbances. Chronic low-grade dissection of the aorta may cause recurrent chest pain for years. Upon autopsy, children with TA who have died from acute rupture of the aorta are often found to have evidence of multiple prior small dissections that did not progress.

Race

TA is more common in Asian populations but has been described in patients of all races. Japanese patients with TA 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 TA, the most commonly involved vessels are the left subclavian, superior mesenteric, and abdominal aorta. In US children with TA, lesions of the thoracic and abdominal aorta, rather than lesions of the aortic arch, are most common. However, all patterns of vascular involvement have been observed in every country.

Sex

In adults, females comprise 80-90% of patients with TA. Pediatric studies are more varied. Sex distribution usually mirrors the 80-90% female preponderance observed in adults. Series of studies of TA in childhood from India and South Africa report a 2:1 female-to-male ratio. However, these are countries in which TA is associated strongly with tuberculosis, and additional etiologic and pathophysiologic factors may be present.

Age

TA is the most common large vessel vasculitis of adolescence. TA is an uncommon vasculitis in children. The most common are postinfectious vasculitides, Henoch-Schönlein purpura, polyarteritis nodosa, and Kawasaki disease. Most cases of TA present in persons aged 10-30 years. In a series of patients with TA, 20-35% were younger than 20 years at diagnosis. The youngest patient reported was aged 6 months.

Clinical

History

• Systemic symptoms in Takayasu arteritis (TA) include the following:
  • Fever, night sweats
  • Fatigue
  • Weight loss
  • Myalgia and/or arthralgia and/or arthritis
  • Skin rash (eg, erythema nodosum, pyoderma gangrenosum)
  • Headaches and/or dizziness and/or syncope
  • Congestive heart failure, palpitations, angina
  • Hypertension (may be paroxysmal)
• Symptoms related to ischemia include the following:
  • Ischemic stroke and/or transient ischemic attack
  • Visual disturbances (eg, blurred vision, diplopia, amaurosis)
  • Carotidynia
  • Abdominal pain
  • Claudications (vary due to the development of collateral circulations; symptom is rare in children)

Physical

• Blood pressure difference greater than 30 mm Hg between arms
• Asymmetric pulses
• Diminished or absent pulses (midaortic lesions found in children may not affect pulses)
• Asymmetric pulses (common) and absent pulses (rare), even in the later stages of the disease (awareness of this is critical)
• Poststenotic dilatations producing what appear to be bounding pulses (often present)
• Hypertension (may be paroxysmal): Because this typically results from renovascular compromise, this is a high-renin hypertension.
• Bruits, especially over subclavian arteries or aorta
• Funduscopic examination
  • Retinal hemorrhages
  • Cotton-wool exudates
  • Venous dilatation and beading
  • Microaneurysms of peripheral retina
  • Optic atrophy
  • Vitreous hemorrhage
  • Classic wreathlike peripapillary arteriovenous anastomoses (extremely rare)
• Reported skin lesions including erythema nodosum–like lesions, pyoderma gangrenosum, leukocytoclastic vasculitis, and panniculitis

Causes

• TA has been reported in identical twins, leading to hypotheses of a hereditary basis for disease. In Japan and Korea, TA is associated with human leukocyte antigens (HLAs)-A10, B5, Bw52, DR2, and DR4. These associations have not been confirmed in Western studies. TA is associated with HLA-B22 in the United States.
• Although early reports associated tuberculosis with TA, these involved populations endemic for tuberculosis, and population studies have not borne out this association. Others report increased incidence of positive purified protein derivative relative to control patients. The true nature of the association with tuberculosis (if any) is unclear. Patients with TA do not improve with antituberculous treatment.

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