Takayasu's arteritis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor-In-Chief: Cafer Zorkun, M.D., Ph.D. [2]

Synonyms and keywords: Aortic arch syndrome, nonspecific aortoarteritis, pulseless disease

Overview

Takayasu's arteritis is an inflammatory disease of unknown etiology that affects mainly the aorta and its branches.

Historical Perspective

The first case of Takayasu’s arteritis was described in 1908 by Dr. Mikito Takayasu at the Annual Meeting of the Japan Ophthalmology Society. Dr. Takayasu described a peculiar "wreathlike" appearance of blood vessels in the back of the eye (retina). Two Japanese colleagues at the same meeting (Dr. Onishi and Dr. Kagoshima) reported similar eye findings in patients whose wrist pulses were absent. It is now known that the blood vessel malformations that occur in the retina are a response (new blood vessel growth) to arterial narrowings in the neck, and that the absence of pulses noted in some patients occur because of narrowings of blood vessels to the arms. The eye findings described by Takayasu are rarely seen in patients from North America.

Epidemiology and Demographics

Race

Although Takayasu's arteritis has been reported worldwide, there is a predilection for young Asian women. In the Western world, atherosclerosis is a more frequent cause of obstruction of the aortic arch vessels than is Takayasu's arteritis.

Age

The age of onset is typically between 15 and 30 years.

Gender

Females are about 8–9 times more likely to be affected by Takayasu's arteritis than males.

Natural History, Complications and Prognosis

Those with the disease often notice symptoms between 15 and 30 years of age. Early on, there is often an anemia and marked elevation of the ESR. This phase gradually subsides and is followed by a more chronic stage characterized by inflammatory and obliterative changes in the aorta (aortitis) and its branches. The other half of patients with Takayasu's arteritis present with only late vascular changes, without an antecedent systemic illness. In the late stage, weakness of the arterial walls may give rise to localized aneurysms.

Classification

Four types of late-phase Takayasu arteritis are described on the basis of the sites of involvement as follows:

• Type I - Classic pulseless type that involves the brachiocephalic trunk, carotid arteries, and subclavian arteries
• Type II - Combination of type I and III
• Type III - Atypical coarctation type that involves the thoracic and abdominal aortas distal to the arch and its major branches
• Type IV - Dilated type that involves extensive dilatation of the length of the aorta and its major branches

Pathophysiology

Although its cause is unknown, the condition is characterized by segmental and patchy granulomatous inflammation of the aorta and its major derivative branches. This inflammation leads to arterial stenosis, thrombosis, and aneurysms. There is also irregular fibrosis of the blood vessels due to chronic vasculitis, leading to sometimes massive intimal fibrosis (fibrosis of the inner section of the blood vessels). Prominent narrowing due to inflammation, granuloma, and fibrosis is often seen in arterial studies such as magnetic resonance angiography (MRA), computed tomography angiography (CTA), or arterial angiography (DSA).

The genetic contribution to the pathogenesis of Takayasu's arteritis is supported by the genetic association with HLA-B∗52. A recent large collaborative study uncovered multiple additional susceptibility loci for this disease, increasing the number of genetic loci for this disease to five risk loci across the genome. About 200,000 genetic variants were genotyped in two ethnically divergent Takayasu's arteritis cohorts from Turkey and North America by using a custom-designed genotyping platform (Immunochip). Additional genetic variants and the classical HLA alleles were imputed and analyzed. The study identified and confirmed two independent susceptibility loci within the HLA region (r2 < 0.2): HLA-B/MICA (rs12524487, OR = 3.29, p = 5.57 × 10-16) and HLA-DQB1/HLA-DRB1 (rs113452171, OR = 2.34, p = 3.74 × 10-9; and rs189754752, OR = 2.47, p = 4.22 × 10-9). In addition, a genetic association was identified and confirmed between Takayasu's arteritis and the FCGR2A/FCGR3A locus on chromosome 1 (rs10919543, OR = 1.81, p = 5.89 × 10-12). The risk allele in this locus results in increased mRNA expression of FCGR2A. In addition, a genetic association between IL12B and Takayasu arteritis was established (rs56167332, OR = 1.54, p = 2.18 × 10-8). A fifth genetic locus for the disease on chromosome 21q22 downstream of PSMG1 was also revealed (P=4.39X10-7).

Diagnosis

To assist in diagnosis, American College of Rheumatology (ACR) has established a diagnostic criterion for Takayasu arteritis.

The patient needs to meet 3 out of 6 criteria for the diagnosis of takayasu arteritis.

• Age at the onset of disease <40 years
• Claudication of the extremities
• Decreased or absent brachial artery pulse in one or both arms
• Difference of at least 10 mmHg in systolic blood pressure in between the arms
• Bruit over either one or both subclavian arteries or abdominal artery
• Arteriography demonstration of narrowing of aorta or its primary branches, not due to atherosclerosis, fibromuscular dyaplasia or other causes.

Symptoms

The disease can be divided into two phases; the Initial phase is pre-pulseless phase, in which patients presents which non-specific constitutional symptoms of vasculitis, which may include any of the following:

• Fatigue
• Fever of unknown origin
• Weight loss
• Myalgia
• Arthralgia

With progression of the disease and involvement of the branches of aorta, the specific signs appear secondary to narrowing/occlusion of the branches of aorta.

• Involvement of subclavian artery is common and leads to claudication of upper extremities (pain with activity). The stenosis of subclavian artery sometimes leads to subclavian steel syndrome. In this phenomenon, the stenosis of subclavian artery, proximal to the origin of Vertebral Artery leads to retrograde flow of blood from the vertebral artery back to subclavian artery during exercise, secondary to vasodilation of blood vessels. The retrograde flow of blood from the vertebral artery back towards subclavian compromises blood flow in posterior cerebral bed, leading to various neurological symptoms including presyncope/syncope.

• Involvement of carotid and vertebral arteries: headache, vertigo, syncope, convulsions and dementia

• Involvement of coronary arteries: chest pain, angina which may progress to myocardial infarction

• Involvement of ascending aorta may: aortic regurgiatation

• Skin lesions resemble erythema nodosum, erythema multiforme, pyoderma gangrenosum

In rare instances, the disease may involve abdominal, pulmonary vessels. In advance stages of the disease, the occlusion of the vessels to the extremities may can ischemic ulcerations. Due to chronic nature of the disease, collateral circulation develops in the affected area.

Treatment

The great majority of patients with Takayasu’s arteritis respond to prednisone. The usual starting dose is approximately 1 milligram per kilogram of body weight per day (for most people, this is approximately 60 milligrams a day). Because of the significant side effects of long-term high–dose prednisone use, the starting dose is tapered over several weeks to a dose that the physician feels is tolerable for the patient.

External links

• Johns Hopkins Vasculitis Center Discusses Takayasu's Arteritis
• Takayasu's Arteritis Research Association
• Vasculitis Association
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