Takayasu Disease

1. Takayasu Disease

2. In 1908, there was an ophthalmologist named Dr. Mikoto Takayasu who reported ocular changes in a 21 year old Japanese woman. Subsequently, Dr. Onishi and Dr. Kagoshima mentioned similar manifestations with the addition of absent pulses in the arms. Data collected through the years framed the criteria for classifications and presentation of Takayasu's Arteritis. By 1975, the disease was formally labeled Takayasu's Arteritis.

3. Takayasu's Arteritis is a rare, chronic, inflammatory disease primarily of the aorta and its branches. TA is occasionally called "pulseless disease" because there is difficulty in detecting peripheral pulses that sometimes occurs as a result of the vascular narrowing. It is also common for a patient to exhibit vascular bruits, and symptoms of their arterial involvement.

4. Takayasu arteritis is a granulomatous vasculitis of unknown etiology that commonly affects the thoracic and abdominal aorta. It causes intimal fibroproliferation of the aorta, great vessels, pulmonary arteries, and renal arteries and results in segmental stenosis, occlusion, dilatation, and aneurysmal formation in these vessels. Takayasu arteritis is the only form of aortitis that causes stenosis and occlusion of the aorta.

5. 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 HLA-A10, B5, Bw52, DR2, and DR4. These associations have not been confirmed in Western studies. TA is associated with HLA-B22 in the US.

6. Synonyms include: - pulseless disease, - aorta arch syndrome, - reverse coarction, - young female arteritis

7. Pathophysiology: The mechanism of Takayasu disease has not been fully elucidated to date. It begins as a nonspecific, cell-mediated inflammatory process in the patient's first 2 decades of life and progresses to the formation of fibrotic stenoses of the aorta and its major branches.

8. Frequency:  * In the US: In Minnesota's Olmstead County, incidence of TA was estimated at 2.6 per million.   * Internationally: Most cases are reported in Asia, although the disease occurs worldwide. TA is a common affliction in third world countries, where the disease is associated closely with tuberculosis. The nature of this association is unclear because most patients with TA in the US do not have tuberculosis. In contrast, many third world physicians assume tuberculosis in every patient with TA.

9. Mortality related to Takayasu arteritis is usually the result of vascular complications such as hypertension, stroke, and aortic insufficiency. Because the disease is rare in the US, accurate survival data are uncertain. One study has quoted 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.

10. Race: Classic Takayasu arteritis is described in the Asian population; it is also reported in all ethnic groups. Sex: Takayasu arteritis most commonly occurs in female patients, with a female-to-male ratio of 8:1. Age: In approximately 90% of cases, Takayasu arteritis appears in patients younger than 30 years.

11. Takayasu disease is divided into early and late phases. The early phase is inflammatory and has been called the prepulseless phase, and the late phase is an occlusive one called the pulseless phase. Patients may present with nonspecific signs and symptoms such as fever, arthralgias, and weight loss.

12. * Systemic symptoms include the following: o Fever, night sweats o Fatigue o Weight loss o Myalgia and/or arthralgia and/or arthritis o Skin rash (eg, erythema nodosum, pyoderma gangrenosum) o Headaches and/or dizziness and/or syncope o Congestive heart failure, palpitations, angina o Hypertension (may be paroxysmal)

13. * Symptoms related to ischemia include the following: o Ischemic stroke and/or transient ischemic attack o Visual disturbances (eg, blurred vision, diplopia, amaurosis) o Carotidynia o Abdominal pain o Claudications (vary due to the development of collateral circulations)

14. Physical: * 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 * Poststenotic dilatations producing what appear to be bounding pulses (often present)

15. * Blood pressure difference greater than 30 mm Hg between arms * Hypertension (may be paroxysmal): Since this typically results from renovascular compromise, this is a high-renin hypertension. * Bruits, especially over subclavian arteries or aorta

16. Funduscopic examination o Retinal hemorrhages o Venous dilatation and beading o Microaneurysms of peripheral retina o Optic atrophy o Vitreous hemorrhage

17. * Reported skin lesions including: • erythema nodosum-like lesions, • pyoderma gangrenosum, • leukocytoclastic vasculitis, • panniculitis.

18. Neurologic symptoms are present in 80% of patients with Takayasu disease that involves the brachiocephalic arteries.

19. A 5- to 20-year interval may separate the acute inflammatory stage and symptomatic arterial occlusive stage.

20. 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 aortic arch and branches: brachiocephalic trunk, carotid arteries, and subclavian arteries * Type II - Localised to descending thoracic aorta (distal to the arch) and abdominal aorta and its major branches. * Type III - Combination of type I and II * Type IV - Localised to pulmonary artery.

21. The most common type is type III, which is found in as many as 65% of patients. The most commonly involved vessels include the left subclavian artery (50%), left common carotid artery (20%), brachiocephalic trunk, renal arteries, celiac trunk, superior mesenteric artery, and pulmonary arteries. Infrequently, the axillary, brachial, vertebral, coronary, and iliac arteries are involved.

22. Making the diagnosis of TA can be extremely difficult. Unfortunately, it is very common for the disease to "smolder" in the walls of large blood vessels for many years, causing only non- specific symptoms, until major complication results. This can eventually lead to occlusion, complete closing of the vessels. There can be major complications resulting, in the dilation of the aorta with stretching of the aortic valve in the heart, resulting in severe valve damage, and critically reduced blood flow to an arm or leg. In addition, a stroke caused by high blood pressure of the blood vessels going to the brain, renal failure, and many other serious afflictions are also possible. Delay in diagnosis is common even when working with physicians experienced in vascular disease.

23. Lab Studies: * TA has no specific markers. * Complete blood count reveals a normochromic normocytic anemia in 50% of patients with TA. Acute phase reactants are elevated, with leukocytosis and thrombocytosis. * Westergren erythrocyte sedimentation rate is elevated. * Comprehensive metabolic profile may indicate elevated transaminases and hypoalbuminemia

24. * The von Willebrand factor–related antigen (factor VIII–related antigen) may be elevated. * Antiendothelial antibodies are present. * Antinuclear antibody usually is negative. * Rheumatoid factor is elevated in 15% of individuals with TA. * Increased levels of immunoglobulins G, M, and A are present.

25. Imaging Studies: Arteriography is the criterion standard for assisting in making the diagnosis of TA. However, the use of MRA is increasing rapidly. Arteriography often demonstrates long, smooth, tapered narrowings or occlusions. Stenoses occur in 90-100% of patients with TA and aneurysm formation in only 27%. Some authors recommend arteriography of the entire aorta.

26. * Magnetic resonance imaging, magnetic resonance angiography, computed tomography o These examinations are useful for serial examinations and diagnosis in the early phase of TA. o CT scan and MRI may demonstrate mural thickening of the aorta and luminal narrowing. o Use of contrast may reveal inflammatory lesions prior to the development of stenoses; these lesions may be missed by angiography. o Aortic lesions including stenosis, dilatation, wall thickening, and mural thrombi are well visualized on MRI, which is less adequate in visualizing distal lesions of the subclavian vessels and common carotids.

27. * High-resolution ultrasonography o Duplex Doppler may be used to evaluate and monitor disease in the common carotids and subclavian arteries; however, this imaging study is not useful in evaluating the aorta. o Carotid evaluation reveals a homogenous circumferential thickening of the vessel wall that is distinguishable from atherosclerotic thickening.

28. * Chest radiography: Chest radiographs may reveal: • widening of the ascending aorta, • irregular descending aorta, • aortic calcifications, • rib notching (late findings).

29. * Echocardiography o Perform echocardiography at baseline to evaluate the aortic valve. o Perform follow-up echocardiography as indicated to monitor aortic insufficiency.

30. Histologic Findings: Mononuclear infiltration of the adventitia with perivascular cuffing of the vasa vasorum occurs early in the disease. Granulomatous changes may be observed in the tunica media with Langerhans cells and central necrosis of elastic fibers and smooth muscle cells. Later, fibrosis of the media and acellular thickening of the intima may compromise the vessel lumen. Grossly, wrinkling of the intima is found. Histologic specimens seldom are available due to the large vessels affected, with the exceptions of specimens obtained during autopsy and bypasssurgery.

31. Early corticosteroid therapy can improve the clinical findings and aid in subsidence of the active inflammatory process of Takayasu arteritis. Prednisone is usually effective in controlling the clinical symptoms of Takayasu arteritis and in controlling and decreasing the progression of active disease in patients. Other medications that can be used as alternative or adjuvant therapy include cyclophosphamide and methotrexate. Each has systemic adverse effects.

32. The long-term prognosis is not predictable. Some researchers have found that the prognosis is worse when the retina of the eyes are affected or if the aorta is damaged or when aneurysms develop. The effects of Takayasu arteritis vary greatly from patient to patient. These effects frequently depend on the impaired blood supply to body tissues (such as the brain leading to strokes or spinal cord leading to paralysis).

33. Angioplasty is an accepted and successful treatment of patients with Takayasu arteritis, especially after the acute inflammatory phase has abated. The best results have been obtained with short-segment stenoses, particularly in the iliac and renal arteries. Angioplasty is generally contraindicated during the acute phase of the disease. Stent use is reported in small numbers of cases as well.

34. Complications: * Congestive heart failure due to aortic insufficiency, myocarditis, and/or hypertension * Aortic aneurysms, thrombus formation, and rupture * Ischemic stroke * Clinically silent progressive disease and morbidity resulting from treatment medications (take into account with long-term treatment plans)

35. Prognosis: * TA is a chronic relapsing disease. Over half of patients with TA achieve control on corticosteroids alone; however, their relapse rate is high and they require long periods of steroid treatment. verll prgnosis in individuals with TA relates to the degree of vascular and end-organ damage, specifically retinal vasculopathy, aortic insufficiency, aortic aneurysms, and hypertension. * Survival rate at 15 years is as high as 95%. * Of patients with TA who are treated with glucocorticoids, 60% respond; however, as many as 40% relapse on tapering steroids.

36. Picture 1. Complete occlusion of the left common carotid artery in a 48-year-old woman with Takayasu disease. Also note narrowing of the origin of the right subclavian artery and a narrowed small vessel with subsequent aneurysmal dilatation on the right side.

37. Caption: Picture 2. Characteristic long, tapered, narrowing of the distal aorta and iliac vessels.

38. Picture 3. Image obtained in the same patient as in Image 2 reveals narrowing of the proximal descending aorta and right brachiocephalic artery.