Takayasu's arteritis (TA), also known as aortic arch syndrome, nonspecific aortoarteritis, and pulseless disease, is a form of large vessel

granulomatous A granuloma is an aggregation of macrophages that forms in response to chronic inflammation. This occurs when the immune system attempts to isolate foreign substances that it is otherwise unable to eliminate. Such substances include infectiou ...

vasculitis Vasculitis is a group of disorders that destroy blood vessels by inflammation. Both arteries and veins are affected. Lymphangitis (inflammation of lymphatic vessels) is sometimes considered a type of vasculitis. Vasculitis is primarily caused ...

American College of Physicians (ACP). Medical Knowledge Self-Assessment Program (MKSAP-15): Rheumatology. "Systemic Vasculitis." Pg. 65–67. 2009, ACP. with massive

intima The tunica intima (New Latin "inner coat"), or intima for short, is the innermost tunica (layer) of an artery or vein. It is made up of one layer of endothelial cells and is supported by an internal elastic lamina. The endothelial cells are in ...

fibrosis Fibrosis, also known as fibrotic scarring, is a pathological wound healing in which connective tissue replaces normal parenchymal tissue to the extent that it goes unchecked, leading to considerable tissue remodelling and the formation of perma ...

and vascular narrowing, most commonly affecting young or middle-aged women of

Asia Asia (, ) is one of the world's most notable geographical regions, which is either considered a continent in its own right or a subcontinent of Eurasia, which shares the continental landmass of Afro-Eurasia with Africa. Asia covers an are ...

n descent, though anyone can be affected. It mainly affects the

aorta The aorta ( ) is the main and largest artery in the human body, originating from the left ventricle of the heart and extending down to the abdomen, where it splits into two smaller arteries (the common iliac arteries). The aorta distributes o ...

(the main blood vessel leaving the heart) and its branches, as well as the

pulmonary arteries A pulmonary artery is an artery in the pulmonary circulation that carries deoxygenated blood from the right side of the heart to the lungs. The largest pulmonary artery is the ''main pulmonary artery'' or ''pulmonary trunk'' from the heart, and ...

. Females are about 8–9 times more likely to be affected than males. Those with the disease often notice symptoms between 15 and 30 years of age. In the

Western world The Western world, also known as the West, primarily refers to the various nations and states in the regions of Europe, North America, and Oceania.

atherosclerosis Atherosclerosis is a pattern of the disease arteriosclerosis in which the wall of the artery develops abnormalities, called lesions. These lesions may lead to narrowing due to the buildup of atheromatous plaque. At onset there are usually no s ...

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 Giant cell arteritis (GCA), also called temporal arteritis, is an inflammatory autoimmune disease of large blood vessels. Symptoms may include headache, pain over the temples, flu-like symptoms, double vision, and difficulty opening the mouth. ...

which typically affects older individuals. Due to obstruction of the main branches of the aorta, including the left

common carotid artery In anatomy, the left and right common carotid arteries (carotids) (Entry "carotid"
in
brachiocephalic artery The brachiocephalic artery (or brachiocephalic trunk or innominate artery) is an artery of the mediastinum that supplies blood to the right arm and the head and neck. It is the first branch of the aortic arch. Soon after it emerges, the brachioce ...

, and the left

subclavian artery In human anatomy, the subclavian arteries are paired major arteries of the upper thorax, below the clavicle. They receive blood from the aortic arch. The left subclavian artery supplies blood to the left arm and the right subclavian artery suppl ...

, 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." Involvement of renal arteries may lead to a presentation of renovascular hypertension.

Sign and symptoms

Some people develop an initial "inflammatory phase" characterized by systemic illness with signs and

symptom Signs and symptoms are the observed or detectable signs, and experienced symptoms of an illness, injury, or condition. A sign for example may be a higher or lower temperature than normal, raised or lowered blood pressure or an abnormality showi ...

s of

malaise As a medical term, malaise is a feeling of general discomfort, uneasiness or lack of wellbeing and often the first sign of an infection or other disease. The word has existed in French since at least the 12th century. The term is often used ...

fever Fever, also referred to as pyrexia, is defined as having a temperature above the normal range due to an increase in the body's temperature set point. There is not a single agreed-upon upper limit for normal temperature with sources using val ...

night sweats Night sweats, also referred to as nocturnal hyperhidrosis (Hyperhidrosis - a medical term for excessive sweating + nocturnal - night), is the repeated occurrence of excessive sweating during sleep Sleep is a sedentary state of mind and bo ...

weight loss Weight loss, in the context of medicine, health, or physical fitness, refers to a reduction of the total body mass, by a mean loss of fluid, body fat ( adipose tissue), or lean mass (namely bone mineral deposits, muscle, tendon, and other co ...

joint pain Arthralgia (from Greek ''arthro-'', joint + ''-algos'', pain) literally means ''joint pain''. Specifically, arthralgia is a symptom of injury, infection, illness (in particular arthritis), or an allergic reaction to medication. According to MeSH, ...

fatigue Fatigue describes a state of tiredness that does not resolve with rest or sleep. In general usage, fatigue is synonymous with extreme tiredness or exhaustion that normally follows prolonged physical or mental activity. When it does not resolve ...

, and fainting. Fainting may result from

subclavian steal syndrome In general, Subclavian means beneath the clavicle, and it may refer to: * Subclavian vein * Subclavian artery In human anatomy, the subclavian arteries are paired major arteries of the upper thorax, below the clavicle. They receive blood from t ...

carotid sinus In human anatomy, the carotid sinus is a dilated area at the base of the internal carotid artery just superior to the bifurcation of the internal carotid and external carotid at the level of the superior border of thyroid cartilage. The carot ...

hypersensitivity. There is also often

anemia Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, t ...

and marked elevation of the ESR or

C-reactive protein C-reactive protein (CRP) is an annular (ring-shaped) pentameric protein found in blood plasma, whose circulating concentrations rise in response to inflammation. It is an acute-phase protein of hepatic origin that increases following interleukin- ...

(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 Claudication is a medical term usually referring to impairment in walking, or pain, discomfort, numbness, or tiredness in the legs that occurs during walking or standing and is relieved by rest. The perceived level of pain from claudication can be ...

renal artery stenosis Renal artery stenosis (RAS) is the narrowing of one or both of the renal arteries, most often caused by atherosclerosis or fibromuscular dysplasia. This narrowing of the renal artery can impede blood flow to the target kidney, resulting in renov ...

causing hypertension, and neurological manifestations due to decreased blood flow to the brain. Of note is the function of renal artery stenosis in the causation of high blood pressure: Normally perfused kidneys produce a proportionate amount of a substance called

renin Renin (etymology and pronunciation), also known as an angiotensinogenase, is an aspartic protease protein and enzyme secreted by the kidneys that participates in the body's renin–angiotensin–aldosterone system (RAAS)—also known as the ...

. Stenosis of the renal arteries causes hypoperfusion (decreased blood flow) of the juxtaglomerular apparatus, resulting in exaggerated secretion of renin, and high blood levels of

aldosterone Aldosterone is the main mineralocorticoid steroid hormone produced by the zona glomerulosa of the adrenal cortex in the adrenal gland. It is essential for sodium conservation in the kidney, salivary glands, sweat glands, and colon. It plays a c ...

, eventually leading to water and salt retention and high blood pressure. The neurological symptoms of the disease vary depending on the degree; the nature of the blood vessel obstruction; and can range from lightheadedness to seizures (in severe cases). One rare, important feature of the Takayasu's arteritis is

ocular Eyes are organs of the visual system. They provide living organisms with vision, the ability to receive and process visual detail, as well as enabling several photo response functions that are independent of vision. Eyes detect light and conv ...

involvement in form of visual field defects, vision loss, or retinal hemorrhage. Some individuals with Takayasu's arteritis may present with only late vascular changes, without a preceding systemic illness. In the late stage, weakness of the arterial walls may give rise to localized

aneurysm An aneurysm is an outward bulging, likened to a bubble or balloon, caused by a localized, abnormal, weak spot on a blood vessel wall. Aneurysms may be a result of a hereditary condition or an acquired disease. Aneurysms can also be a nidus ( ...

s. As with all aneurysms, the possibility of rupture and vascular bleeding is existent and requires monitoring. In view of the chronic process and good collateral development,

Raynaud's phenomenon Raynaud syndrome, also known as Raynaud's phenomenon, eponymously named after the physician Auguste Gabriel Maurice Raynaud, who first described it in his doctoral thesis in 1862, is a medical condition in which the spasm of small arteries cau ...

or digital gangrene are very rare in Takayasu arteritis. A rare complication of this condition are coronary artery aneurysms. Takayasu LDH

Laser Doppler imaging Laser Doppler imaging (LDI) is an imaging method that uses a laser beam to scan live tissue. When the laser light reaches the tissue, the moving blood cells generate doppler components in the reflected ( backscattered) light. The light that comes ...

by near-infrared

digital holography Digital holography refers to the acquisition and processing of holograms with a digital sensor array, typically a CCD camera or a similar device. Image rendering, or reconstruction of object ''data'' is performed numerically from digitized interfero ...

can reveal characteristic blood flow waveforms in the central artery and vein of the retina in patients with vascular insufficiency who may exhibit a smooth systo-diastolic

pulse In medicine, a pulse represents the tactile arterial palpation of the cardiac cycle (heartbeat) by trained fingertips. The pulse may be palpated in any place that allows an artery to be compressed near the surface of the body, such as at the n ...

in the

central retinal artery The central retinal artery (retinal artery) branches off the ophthalmic artery, running inferior to the optic nerve within its dural sheath to the eyeball. Structure The central retinal artery pierces the eyeball close to the optic nerve, sendin ...

. This technique enables non invasive functional

microangiography Microangiography ( ) is a type of angiography that consists of the radiography of small blood or lymphatic vessels of an organ. While most other types of angiography cannot produce images of vessels smaller than 200 µm in diameter, microang ...

by high-contrast measurement of endoluminal blood flow profiles in vessels in the posterior segment of the eye with a spatial resolution comparable to state-of-the-art

indocyanine green Indocyanine green (ICG) is a cyanine dye used in medical diagnostics. It is used for determining cardiac output, hepatic function, liver and gastric blood flow, and for ophthalmic angiography.

angiography.

Pathophysiology

Although the cause of Takayasu arteritis is unknown, the condition is characterized by segmental and patchy

granuloma A granuloma is an aggregation of macrophages that forms in response to chronic inflammation. This occurs when the immune system attempts to isolate foreign substances that it is otherwise unable to eliminate. Such substances include infectious o ...

tous

inflammation Inflammation (from la, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, and is a protective response involving immune cells, blood vessels, and molec ...

of the aorta and its major derivative branches. This inflammation leads to arterial

stenosis A stenosis (from Ancient Greek στενός, "narrow") is an abnormal narrowing in a blood vessel or other tubular organ or structure such as foramina and canals. It is also sometimes called a stricture (as in urethral stricture). ''Stricture'' ...

thrombosis Thrombosis (from Ancient Greek "clotting") is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel (a vein or an artery) is injured, the body uses platelets (th ...

, and

s. There is 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).John Barone, M.D. USMLE Step 1 Lecture Notes. "Vascular Pathology." 2008, Kaplan Inc. pg 101. Prominent narrowing due to inflammation, granuloma, and fibrosis is often seen in arterial studies such as

magnetic resonance angiography Magnetic resonance angiography (MRA) is a group of techniques based on magnetic resonance imaging (MRI) to image blood vessels. Magnetic resonance angiography is used to generate images of arteries (and less commonly veins) in order to evaluate ...

(MRA),

computed tomography angiography Computed tomography angiography (also called CT angiography or CTA) is a computed tomography technique used for angiography—the visualization of arteries and veins—throughout the human body. Using contrast injected into the blood vessels, im ...

(CTA), or arterial

angiography Angiography or arteriography is a medical imaging technique used to visualize the inside, or lumen, of blood vessels and organs of the body, with particular interest in the arteries, veins, and the heart chambers. Modern angiography is perfor ...

(DSA).

Genetics

The genetic contribution to the pathogenesis of Takayasu's arteritis is supported by the genetic association with HLA-B∗52. A 2013 large collaborative study uncovered multiple additional susceptibility loci for this disease, increasing its number of genetic loci 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 at 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 in an intergenic region on chromosome 21q22 downstream of PSMG1 was revealed (P=4.39X10-7). A recent genome-wide association study (GWAS) identified genetic susceptibility loci for Takayasu arteritis with a genome-wide level of significance in IL6 (rs2069837) (odds ratio R2.07, P = 6.70 × 10(-9)), RPS9/LILRB3 (rs11666543) (OR 1.65, P = 2.34 × 10(-8)), and the intergenic locus on chromosome 21q22 (rs2836878) (OR 1.79, P = 3.62 × 10(-10)). The genetic susceptibility locus in RPS9/LILRB3 lies within the leukocyte receptor complex gene cluster on chromosome 19q13.4, and the disease risk variant in this locus correlates with reduced expression of multiple genes including the inhibitory leukocyte immunoglobulin-like receptor gene LILRB3 (P = 2.29 × 10(-8)). In addition, this study identified additional candidate susceptibility genes with suggestive levels of association (P < 1 × 10(-5)) including PCSK5, LILRA3, PPM1G/NRBP1, and PTK2B. Another gene associated with this condition is '' MLX'' (Max-like protein X) Tamura N, Maejima Y, Matsumura T, Vega RB, Amiya E, Ito Y, Shiheido-Watanabe Y, Ashikaga T, Komuro I, Kelly DP, Hirao K, Isobe M (2018) Single-nucleotide polymorphism of the MLX gene is associated With Takayasu arteritis. Circ Genom Precis Med 11(10):e002296. doi: 10.1161/CIRCGEN.118.002296.

Diagnosis

Diagnosis is based on the demonstration of vascular lesions in large and middle-sized vessels on angiography, CT scan,

or FDG PET.RA Watts et al., "Vasculitis in Clinical Medicine, 2010" Seeing abnormal diffuse arterial wall thickening, the 'macaroni sign', with

ultrasound Ultrasound is sound waves with frequencies higher than the upper audible limit of human hearing. Ultrasound is not different from "normal" (audible) sound in its physical properties, except that humans cannot hear it. This limit varies ...

is highly suggestive of the condition. FDG PET can help in diagnosis of active inflammation not just in patients with active Takayasu arteritis prior to treatment but also in addition in relapsing patients receiving immunosuppressive agents. Contrast angiography has been the gold standard. The earliest detectable lesion is a local narrowing or irregularity of the lumen. This may develop into stenosis and occlusion. The characteristic finding is the presence of "skip lesions," where stenosis or aneurysms alternate with normal vessels. Angiography provides information on vessel anatomy and patency but does not provide information on the degree of inflammation in the wall. The age at onset helps to differentiate Takayasu's arteritis from other types of large vessel vasculitis. For example, Takaysu's arteritis has an age of onset of <40 years, while

has an age of onset >60 years. Takayasu arteritis is not associated with ANCA,

rheumatoid factor Rheumatoid factor (RF) is the autoantibody that was first found in rheumatoid arthritis. It is defined as an antibody against the Fc portion of IgG and different RFs can recognize different parts of the IgG-Fc. RF and IgG join to form immune com ...

, ANA, and anticardiolipin antibodies.

Treatments

Most people with Takayasu’s arteritis respond to

steroids A steroid is a biologically active organic compound with four rings arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter membrane fluidity; and ...

such as

prednisone Prednisone is a glucocorticoid medication mostly used to suppress the immune system and decrease inflammation in conditions such as asthma, COPD, and rheumatologic diseases. It is also used to treat high blood calcium due to cancer and ad ...

. 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 In medicine, a side effect is an effect, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequenc ...

of long-term high-dose prednisone use, the starting dose is tapered over several weeks to a dose that controls symptoms while limiting the side effects of steroids. Promising results are achieved with

mycophenolate Mycophenolic acid (MPA) is an immunosuppressant medication used to prevent rejection following organ transplantation and to treat autoimmune conditions such as Crohn's disease and lupus. Specifically it is used following kidney, heart, and li ...

and

tocilizumab Tocilizumab, sold under the brand name Actemra among others, is an immunosuppressive drug, used for the treatment of rheumatoid arthritis, systemic juvenile idiopathic arthritis, a severe form of arthritis in children, and COVID19. It is a huma ...

. If treatment is not kept to a high standard, long-term damage or death can occur. Patients who do not respond to steroids may require revascularization, either via

vascular bypass A vascular bypass is a surgical procedure performed to redirect blood flow from one area to another by reconnecting blood vessels. Often, this is done to bypass around a diseased artery, from an area of normal blood flow to another relatively nor ...

or angioplasty and stenting. Outcomes following revascularization vary depending on the severity of the underlying disease.

History

The first case of Takayasu’s arteritis was described in 1908 by Japanese

ophthalmologist Ophthalmology ( ) is a surgical subspecialty within medicine that deals with the diagnosis and treatment of eye disorders. An ophthalmologist is a physician who undergoes subspecialty training in medical and surgical eye care. Following a med ...

Mikito Takayasu (1860–1938) was a Japanese ophthalmologist known for his discovery of Takayasu's arteritis. Graduated from Tokyo Imperial University in 1887 he worked at what was to become Kanazawa University School of Medicine in Kanazawa, Ishikawa Prefectur ...

at the Annual Meeting of the Japan Ophthalmology Society.M. Takayasu. A case with peculiar changes of the central retinal vessels. ''Acta Societatis ophthalmologicae Japonicae'', Tokyo 1908, 12: 554. Takayasu described a peculiar "wreathlike" appearance of the

blood vessel The blood vessels are the components of the circulatory system that transport blood throughout the human body. These vessels transport blood cells, nutrients, and oxygen to the tissues of the body. They also take waste and carbon dioxide awa ...

s in the back of the eye (

retina The retina (from la, rete "net") is the innermost, light-sensitive layer of tissue of the eye of most vertebrates and some molluscs. The optics of the eye create a focused two-dimensional image of the visual world on the retina, which the ...

). Two

Japan Japan ( ja, 日本, or , and formally , ''Nihonkoku'') is an island country in East Asia. It is situated in the northwest Pacific Ocean, and is bordered on the west by the Sea of Japan, while extending from the Sea of Okhotsk in the n ...

ese physicians at the same meeting (Drs. Onishi and Kagoshima) reported similar eye findings in individuals whose wrist pulses were absent. It is now known that the blood vessel malformations that occur in the retina are an

angiogenic Angiogenesis is the physiological process through which new blood vessels form from pre-existing vessels, formed in the earlier stage of vasculogenesis. Angiogenesis continues the growth of the vasculature by processes of sprouting and splittin ...

response to the arterial narrowings in the neck and that the absence of pulses noted in some people 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 North America is a continent in the Northern Hemisphere and almost entirely within the Western Hemisphere. It is bordered to the north by the Arctic Ocean, to the east by the Atlantic Ocean, to the southeast by South America and th ...

and British Columbia.

References

;Bibliography *

External links

{{DEFAULTSORT:Takayasu's Arteritis Vascular diseases Vascular-related cutaneous conditions Steroid-responsive inflammatory conditions Systemic connective tissue disorders