|Classification and external resources|
Left anterior oblique angiographic image of Takayasu's arteritis showing areas of stenosis in multiple great vessels
|eMedicine||med/2232 ped/1956 neuro/361 radio/51|
Takayasu's disease (also known as "aortic arch syndrome", "nonspecific aortoarteritis" and the "pulseless disease":841) is a form of large vessel granulomatous vasculitis with massive intimal fibrosis and vascular narrowing, affecting often young or middle-aged women of Asian descent. It mainly affects the aorta (the main blood vessel leaving the heart) and its branches, as well as the pulmonary arteries. Females are about 8–9 times more likely to be affected than males. Patients often notice the disease symptoms between 15 and 30 years of age. In the Western world, atherosclerosis is a more frequent cause of obstruction of the aortic arch vessels than Takayasu's arteritis. Takayasu's arteritis is similar to other forms of vasculitis, including giant cell arteritis. Due to obstruction of the main branches of the aorta, including the left common carotid artery, the brachiocephalic artery, and the left subclavian artery, Takayasu's arteritis can present as pulseless upper extremities (arms, hands, and wrists with weak or absent pulses on the physical examination) which may be why it is also commonly referred to as the "pulseless disease".
Some patients develop an initial "inflammatory phase" characterized by systemic illness with symptoms of malaise, fever, night sweats, weight loss, arthralgia, fatigue and syncope. Syncope may result from subclavian steal syndrome or carotid sinus hypersensitivity. There is also often anemia and marked elevation of the ESR or C-reactive protein (nonspecific markers of inflammation). The initial "inflammatory phase" is often followed by a secondary "pulseless phase". The "pulseless phase" is characterized by vascular insufficiency from intimal narrowing of the vessels manifesting as arm or leg claudication, renal artery stenosis causing hypertension, and neurological manifestations due to decreased blood flow to the brain. Of note is the function of renal artery stenosis in causation of high blood pressure: Normally perfused kidneys produce proportionate amount of a substance called renin. Stenosis of the renal arteries causes hypo-perfusion (decreased blood flow) of the juxtaglomerular apparatus, resulting in exaggerated secretion of renin, and high blood levels of aldosterone, eventually leading to water and salt retention and high blood pressure. The neurological symptoms of the disease vary depending on the degree, and the nature of the blood vessel obstruction and can range from lightheadedness, to seizures in severe cases. One rare but important feature of the Takayasu's arteritis is ocular involvement in form of visual field defects, vision loss, or retinal hemorrhage. Some patients with Takayasu's arteritis may 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. As with all aneurysms, possibility of rupture and vascular bleeding is existent and requires monitoring. Raynaud's phenomenon is commonly found in this disease, mainly due to decreased circulation of the blood to the arms.
Although its etiology 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).
The biggest challenge is assessing the disease to optimise treatment. Indian Takayasu activity score 2010 (ITAS2010) is the recently introduced tool validated by applying it on more than 300 patients and has been published on Oxford Rheumatology August 16, 2013 issue. Although it is derived from BVAS, ITAS is heavily weighted on cardiovascular features and sensitive to change in disease status. Takayasu`s is a very rare and hard to treat condition.
The great majority of patients with Takayasu’s arteritis respond to steroids such as 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. Promising results are achieved with Mycophenolate and Toccilizumab. If treatment is not kept to a high standard then long term damage and or death can occur. Stress is a major factor that should be avoided at all costs; if this is not taken into account the surge of adrenaline can have a damaging effect on the heart.
Surgical options may need to be explored for patients who do not respond to steroids. Re-perfusion of tissue can be achieved by large vessel reconstructive surgery such as bypass grafting. Grafting autologous tissue has the highest rates of success. Stenting often obviates the need for surgery. Percutaneous transluminal coronary angioplasty (PTCA) is not as effective in the long term but has fewer risks.
The first case of Takayasu’s arteritis was described in 1908 by Japanese ophthalmologist Mikito Takayasu at the Annual Meeting of the Japan Ophthalmology Society. Takayasu described a peculiar "wreathlike" appearance of the blood vessels in the back of the eye (retina). Two Japanese physicians at the same meeting (Drs. Onishi and Kagoshima) also 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 an angiogenic response to the arterial narrowings in the neck, and that the absence of pulses noted in some patients occurs because of narrowings of the blood vessels to the arms. The eye findings described by Takayasu are rarely seen in patients from North America and British Columbia.
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