Nonspecific aortoarteritis (Takayasu's disease)

Non-specific aortoarteritis (aortic arch syndrome, Takayasu disease, pulseless disease) is a destructive-productive segmental aortitis and subaortic panarteritis of arteries rich in elastic fibers with possible damage to their coronary and pulmonary branches.

ICD 10 code

M31.4 Aortic arch syndrome (Takayasu).

Epidemiology of Takayasu's disease

Non-specific aortoarteritis begins most often at the age of 10 to 20 years, and predominantly affects females. In the overwhelming majority of observations, the first symptoms of the disease appear at the age of 8-12 years, but the onset of the disease is also possible in preschool age.

The disease is most common in Southeast Asia and South America, but cases of Takayasu's disease are recorded in various regions. The annual incidence varies from 0.12 to 0.63 cases per 100,000 population. Teenage girls and young women (under 40) are more often affected. Cases of HAA have been reported in children and the elderly.

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Causes of Takayasu's disease

The etiologic agent of this disease is unknown. A link between the disease and streptococcal infection has been identified, and the role of Mycobacterium tuberculosis is discussed.

Currently, it is believed that the imbalance of cellular immunity is of particular importance in the development of autoimmune disorders. In the blood of patients, a violation of the lymphocyte ratio is noted; the content of CD4 + T-lymphocytes increases and the number of CD8 + T-lymphocytes decreases. An increase in the number of circulating immune complexes, the content of elastin peptides and an increase in the activity of elastase, cathepsin G, an increase in the expression of MHC I and II antigens are noted.

Pathomorphological changes are most pronounced at the sites where the arteries branch off from the aorta. In the middle layer, foci of necrosis are observed, surrounded by cellular infiltrates consisting of lymphoid cells, plasma cells, macrophages and giant multinucleated cells.

What causes Takayasu's disease?

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Symptoms of Takayasu's disease

The early stages of the disease are characterized by fever, chills, night sweats, weakness, myalgia, arthralgia, and loss of appetite. Against this background, signs of widespread vascular disease (coronary, cerebral, peripheral) should be alarming, especially with involvement of the upper extremities (no pulse).

The advanced stage of Takayasu's disease is manifested by damage to the arteries that branch off from the aortic arch: subclavian, carotid and vertebral. On the affected side, there is increased fatigue of the arm under load, its coldness, a feeling of numbness and paresthesia, gradual development of atrophy of the muscles of the shoulder girdle and neck, weakening or disappearance of the arterial pulse, a decrease in blood pressure, systolic murmur in the common carotid arteries. Also characteristic are pain in the neck, along the vessels and their soreness upon palpation due to progressive inflammation of the vascular wall, transient ischemic attacks, transient visual impairment.

Much less frequently, symptoms occur that are caused by damage to the arteries extending from the abdominal aorta: the development of malignant vasorenal hypertension, attacks of “abdominal toad” caused by damage to the mesenteric arteries, the occurrence of intestinal dyspepsia and malabsorption syndromes.

In NAA, coronary vessel damage (coronariitis) occurs in 3/4 of patients; its peculiarity is damage to the coronary vessel orifice in 90% of cases, while the distal sections are affected less often. The onset of the disease is described as isolated stenosis of the coronary artery with the clinical picture of acute coronary syndrome or myocardial infarction (MI), often without characteristic ECG changes. Coronariitis can also manifest itself as the development of ischemic DCM with a diffuse decrease in cardiac contractility due to myocardial hibernation. Damage to the ascending aorta is often described - compaction in combination with dilation and the formation of aneurysms. In patients with NAA, aortic regurgitation often develops due to dilation of the aortic root and/or aortitis. AG occurs in 35-50% of cases and may be due to involvement of the renal arteries or development of glomerulonephritis, less often - formation of coarctation of the aorta or ischemia of the vasomotor center against the background of vasculitis of the carotid arteries. CHF in Takayasu's arteritis occurs due to AG, coronary arteritis and aortic regurgitation. Cases of thrombosis of the heart cavities, as well as myocardial damage with the development of myocarditis, confirmed by endomyocardial biopsy by detection of cardiomyocyte necrosis, mononuclear infiltration and associated with the active phase of the disease have been described.

Symptoms of Takayasu's disease

Classification of Takayasu's disease

Depending on the nature of the deformation, stenotic, deforming or combined (combination of aneurysms and stenosis) variants of nonspecific aortoarteritis are distinguished. According to the localization of the lesion, 4 types of nonspecific aortoarteritis are distinguished.

Types of non-specific aortoarteritis by localization of the lesion

Types	Localization
I	The aortic arch and the arteries branching off from it
I	Descending, abdominal aorta, celiac, renal, femoral and other arteries
III	Mixed variant (widespread vascular lesion in the arch area and other parts of the aorta)
IV	Pulmonary artery disease associated with any of the three types

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Diagnosis of Takayasu's disease

Laboratory changes: normochromic normocytic anemia, slight increase in platelet count, hyper-γ-globulinemia, increased ESR, fibrinogen concentration, a2-globulins, circulating immune complexes, rheumatoid factor. Increased CRP concentration is more closely associated with disease activity than ESR. In 20-35% of patients, aPL (IgG, IgM) associated with vascular occlusion, arterial hypertension, and valve damage are detected. Urine analysis reveals moderate proteinuria and microhematuria.

Of the instrumental methods, ophthalmoscopy is used, angiopathy of the vessels of the fundus is noted, and visual acuity is assessed (as a rule, it decreases).

The main method of instrumental diagnostics for Takayasu's disease is arteriography. It confirms the diagnosis and evaluates the state of the vessels in dynamics. It is necessary to examine the entire aorta: changes are manifested by narrowing of long sections or occlusion of arteries, the aortic region and the mouths of its visceral branches. Doppler ultrasound angioscanning and MRI are also used. Their advantage is the ability to diagnose the disease at an early stage. Histologically, Takayasu's disease is manifested by pan arteritis with localization of the infiltrate mainly in the adventitia and outer layers of copper, however, if the results of angiography and clinical symptoms are typical, then a biopsy of the vessel is not required.

Classification criteria for Takayasu's disease (Arend W. et al., 1990)

• Age of patients (disease onset <40 years).
• Intermittent claudication syndrome is weakness and discomfort, pain in the lower limbs when walking.
• Weakened brachial pulse - weakening or absence of pulsation in one or both brachial arteries.
• The difference in blood pressure in the brachial arteries is more than 10 mm Hg.
• On auscultation, there is noise over the subclavian artery on one or both sides or over the abdominal aorta.
• Angiographic signs - narrowing of the lumen of the aorta and its large branches up to occlusion or dilation, not associated with atherosclerotic lesions or developmental pathology.

The presence of three or more of any criteria serves as the basis for a reliable diagnosis of Takayasu's disease.

Differential diagnostics are carried out with other systemic inflammatory diseases, including APS, infections (infective endocarditis, syphilis, etc.), malignant neoplasms (including lymphoproliferative diseases), and atherosclerosis of large vessels.

Diagnosis of Takayasu's disease

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Treatment of Takayasu's disease

Treatment is aimed at suppressing inflammation in the vascular wall, immunopathological reactions, preventing complications, and compensating for the symptoms of vascular insufficiency.

Patients with Takayasu's arteritis are sensitive to glucocorticoids. The recommended treatment regimen is prednisolone at a dose of 40-60 mg/day for 1 month with subsequent gradual reduction, maintenance dose of 5-10 mg/day for at least 2-3 years. If monotherapy is insufficiently effective, improvement may occur with a combination of low doses of glucocorticoids and cytostatics. Preference is given to methotrexate (7.5-15 mg/week). Cyclophosphamide (cyclophosphamide) is used in severe cases with high activity of the inflammatory process. In cases resistant to treatment, pulse therapy with cyclophosphamide is carried out once a month for a period of 7 to 12 months.

Some patients require either percutaneous transluminal intervention for revascularization, or surgical replacement of severely stenotic areas of the vessels, or installation of an aortic valve prosthesis. Indication for surgical treatment is arterial stenosis of more than 70% with signs of ischemia. In case of stenosis of the coronary arteries, aortocoronary replacement surgery is performed.

Antihypertensive drugs (for arterial hypertension), anticoagulants (for thrombosis prevention), and, if indicated, statins, antiosteoporotic agents, and antiplatelet agents are required.

In cases of vasorenal hypertension that cannot be treated surgically, beta-blockers and AG1F inhibitors may be used, but they are contraindicated in bilateral renal artery stenosis.

How is Takayasu's disease treated?

Prevention of Takayasu's disease

Primary prevention has not been developed. Secondary prevention consists of preventing exacerbations and sanitizing infection foci.

Prognosis of Takayasu's disease

Adequate treatment helps to achieve a 5-10-15-year survival rate in 80-90% of patients.

Of the complications, the most common causes of death are strokes - 50%, myocardial infarction - 25%, ruptured aortic aneurysm - 5%. K. Ishikawa identifies 4 main groups of complications: retinopathy, arterial hypertension, aortic insufficiency and aneurysms (mainly aortic aneurysm). The prognosis for patients with these complications is significantly worse. Thus, the 5-year survival rate for patients with at least two of these syndromes is 58%,

History of the issue

In 1908, Japanese ophthalmologist M. Takayasu reported unusual changes in the retinal vessels during an examination of a young woman. That same year, K. Ohnishi and K. Kagoshimu noted similar changes in the fundus of their patients, which were combined with the absence of pulsation of the radial artery. The term "Takayasu's disease" was introduced only in 1952.

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