TAKAYASU’S ARTERITIS

Dr. Aishwarya

DEFINITION

TAKAYASU’S ARTERITIS is an inflammatory and stenotic disease of medium and large sized arteries characterised by a strong prediliction for the aorta and its branches .

AORTIC ARCH SYNDROMEPULSELESS DISEASE.

HISTORY

Dr. Takayasu described the retinal changes of the disease in 1905 at the Annual Ophthalmology Society meeting in Japan, and his abstract was subsequently published in 1908. The condition is now called Takayasu arteritis in his honor.

INCIDENCE AND PREVALENCE

Uncommon disease.

Annual incidence rate 1.2-2.6 cases/million

Prevalent in adolescent and young women

M.C. in Asia

No racial/geographical distribution.

Race

Takayasu arteritis is observed more frequently in patients of Asian or Indian descent. Japanese have a higher incidence of aortic arch involvement. india report higher incidences of abdominal involvement.

Sex

80% of patients - women; however, the high female-to-male ratio seems to decrease west of Japan. In India, the female-to-male ratio is as low as 1.6:1.

AgeMost patients are aged 4-63 years, mean age of onset - 30

years. <15% of cases present in individuals older than 40 years.

PATHOLOGY

Panarteritis,inflammmatory mononuclear infiltrates,occasionally giant cells

Marked intimal proliferation ,fibrosis ,scarring and vascularisation of media

disruption,degeneration of elastic laminaNarrowing of lumen +/- thrombus

Pathology in the chronic phase of Takayasu’s Arteritis showing fibrosis in all the layers of the vessel wall and markedly thickened intima

Contd.

Immunopathologcial mechanism are suspected ,uncertain

Circulating immune complexes-demonstrated but their pathological signficance is unclear.

                                                                                             

Constitutional symptoms :Headache (50%-70%)Malaise (35%-65%)Arthralgias (28%-75%)Fever (9%-35%)Weight loss (10%-18%)

Cardiac and vascular features

Bruit, with the most common location being the carotid artery (80%)

Blood pressure difference of extremities (45%-69%)

Claudication (38%-81%)

Carotodynia or vessel tenderness (13%-32%)

Hypertension (28%-53%; 58% with renal artery stenosis in one series)

Aortic regurgitation (20%-24%)

Raynaud’s syndrome (15%) .Pericarditis (< 8%) ,Congestive heart failure (< 7%) , Myocardial infarction (< 3%).

NEUROLOGICAL FEATURES

Headache (50%-70%)Visual disturbance (16%-35%) - Strong

association with common carotid and vertebral artery disease

Stroke (5%-9%)Transient ischemic attacks (3%-7%) Seizures (0%-20%)

DERMATOLOGICAL MANIFESTATIONS

Erythema nodosum (6%-19%)Ulcerated subacute nodular lesions (< 2.5%)Pyoderma gangrenosum (< 1%)

Particular attention to peripheral pulses, blood pressure in all 4 extremities, and an ophthalmologic examination.

The most discriminatory finding is a systolic blood pressure difference (>10 mm Hg) between arms.

Hypertension due to renal artery involvement is found in approximately 50% of patients.

Absent or diminished pulses are the clinical hallmark of Takayasu arteritis, but pulses are normal in many patients and upper limbs are affected more often Than lower limbs.

PHYSICAL EXAMINATION

Physical examination contd…Carotidynia may be present.

Bruits are often noted.

Aortic regurgitation is a common finding.

Ophthalmologic examination may show retinal hemorrhages, cotton-wool exudates, venous dilatation and beading, microaneurysms of peripheral retina, optic atrophy, vitreous hemorrhage, and classic wreathlike peripapillary arteriovenous anastomoses (extremely rare).

Skin changes resembling erythema nodosum or ulcerating nodular lesions may be seen.

Artery percent Clinical manifestations

1.Subclavian 93 ARM CLAUIDACTION ,RAYNAUD’S PHENOMENON

2.Common carotid

58 VISUAL CHANGES,TIA,STROKE,SYNCOPE

3.Abdominal aorta

47 ABDOMINAL PAIN,NAUSEA ,VOMITING

4.Renal 38 HTN,RENAL FAILURE

5.Aortic arch/root

35 AORTIC INCOMPETENCE,CCF

ARTERY % CLINICAL MANIFESTATIONS

1. VERTEBRAL 35 Visual changesDizziness

2. COELIAC AXIS 18 Abd painNausea,vomiting

3. SUPERIOR MESENTRIC 18 Abd pain,nausea,vomiting

4. ILIAC 17 Leg claudication

5. PULMONARY 10-40 Atyp chestpain,dyspnea

6. CORONARY <10 Chest pain,MI

DIFFERENTIAL DIAGNOSIS

AORTIC COARCTATION

ATHEROSCLEROSIS

BEHCET’S DISEASE

BUERGER’S DISEASE (THROMBANGITIS OBLITERANS)

GIANT CELL ARTERITIS

KAWASAKI DISEASE

RHEUMATOID ARTHRITIS

SARCOIDOSIS

AMERICAN COLLEGE OF RHEUMATOLOGY – CLASSIFICATION CRITERIA

3 OF 6 NECESSARY

1.Age < 40 yr onset

2.Claudication of extremities

3.Decreased pulsation in one/both brachial arteries

4.Diff of at least 10mm of hg SBP between arms

5.Bruit over one/both sub cl art /abd aorta

6.Arteriografic narrowing/occlusion of entire abd aorta,its primary br. Or large arteries of both UL and LL

LABORATORY STUDIES

The acute-phase reactants and clinical parameters generally used to define active inflammatory disease do not universally reflect active blood vessel inflammation in Takayasu arteritis.

The ESR is elevated in most but not all patients during active inflammatory disease. Therefore, it is not a consistently reliable marker of disease activity, with both false-positive and false-negative associations reported.]

Tests:

Arteriogram

Angiogram

Complete blood count (CBC)

C-reactive protein (CRP)

Electrocardiogram (ECG)

Erythrocyte sedimentation rate (ESR)

Magnetic resonance angiography (MRA)

Magnetic resonance imaging (MRI)

Ultrasound

X-ray of the chest

Imaging StudiesWhile imaging studies (CT scanning, MRI) show typical

patterns of stenosis or aneurysms of the arteries, angiography remains the standard for diagnosis and evaluation of the extent of disease. recent studies suggest that noninvasive imaging modalities such as MRI, ultrasonography,and 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) allow diagnosis of Takayasu arteritis earlier in the disease course than standard angiography and provide a means for monitoring disease activity.

Angiography is used to evaluate only the appearance of the lumen and cannot be used to differentiate between active and inactive lesions.

Takayasu arteritis can be divided into 6 types based on angiographic involvement, as follows:

Type I - Branches of the aortic archType IIa - Ascending aorta, aortic arch, and its branchesType IIb - Type IIa region plus thoracic descending aortaType III - Thoracic descending aorta, abdominal aorta,

renal arteries, or a combinationType IV - Abdominal aorta, renal arteries, or bothType V - Entire aorta and its branches

Other tests

MRA is equally or more sensitive than angiography for revealing lesions in the aorta .

CT helical scanning angiography is a sensitive and specific diagnostic tool.

Color Doppler ultrasonography provides details of the vascular wall, lumen, and flow and is a useful tool for screening and follow-up, particularly forcarotid and subclavian arteries.

PET scanning with radioactive-labeled 18-fluorodeoxyglucose (FDG) has been shown to be useful in monitoring disease activity and response to treatment in preliminary studies. Presence or absence of FDG uptake correlates well with clinical state and MRI findings. Its use in patients with Takayasu arteritis requires further investigation.

MRA or CT angiography and FDG-PET may be useful to monitor vascular response to treatment.

a. MRA b. Conventional angiogram

MEDICAL CAREAssessing disease activity in patients with Takayasu arteritis is

frequently challenging, since clinical, biologic, and radiologic information do not always correlate.

Prospective study criteria established by Kerr et al (NIH) are used to assess disease activity in patients with Takayasu arteritis. New onset or worsening of two or more of the following features indicates active disease:

1.systemic features, such as fever and arthralgias (no identified cause)

2. erythrocyte sedimentation rate3.Features of vascular ischemia or inflammation, such as

claudication, diminished or absent pulse, bruit, carotodynia, or asymmetric blood pressure in either upper or lower limbs (or both)

4.Typical angiographic features

Treatment

Treatment of Takayasu arteritis is difficult, but patients who do have the right treatment can see positive results. Early detection is important.

Most patients are treated with steroids and immunosuppressive drugs. Surgery is reserved for complications caused by narrowed arteries.

Surgery to bypass narrowed arteries -- angioplasty or stent placement -- may be needed to supply blood or open up the constriction.

Therapeutic intervention includes corticosteroid therapy with or without cytotoxic agents.

Corticosteroids are the mainstay of therapy for active Takayasu arteritis, and some patients may require additional cytotoxic agents to achieve remission and taper of chronic corticosteroid treatment.

Oral corticosteroids are started at 1 mg/kg daily or divided twice daily and tapered over weeks to months as symptoms subside.

Long-term low-dose corticosteroid therapy may be required.

Osteoporosis prevention when patients are started on corticosteroids should be seriously considered

Cytotoxic agents are used for patients whose disease is steroid-resistant or relapsing. These agents are usually continued for at least one year after remission and are then tapered to discontinuation. The following agents with their respective doses are as follows:

Methotrexate - 7.5-25 mg/wk oralAzathioprine - 1-2 mg/kg/d oralCyclophosphamide - 2 mg/kg/d oral (should be

reserved for patients with the most severe and refractory disease states)

Strict management of traditional cardiovascular risk factors such as dyslipidemia, hypertension, and lifestyle factors is mandatory to minimize secondary cardiovascular complications, which are the major cause of death in this disease. Additionally, low-dose aspirin may have a therapeutic effect in large vessel vasculitis.

•Strict management of traditional cardiovascular risk factors such as dyslipidemia, hypertension, and lifestyle factors is mandatory to minimize secondary cardiovascular complications, which are the major cause of death in this disease. Additionally, low-dose aspirin may have a therapeutic effect in large vessel vasculitis.

ANTI –TNF AGENTS

In an uncontrolled series of 15 patients, adjunctive treatment with anti–tumor necrosis factor (TNF) agents was effective in patients with active, relapsing Takayasu arteritis despite treatment with steroids and multiple other immunosuppressive agents.

The initial dose of etanercept was 25 mg twice weekly (7 patients), and infliximab (11 patients [3 were switched from etanercept to infliximab]) was given at 3 mg/kg initially and at 2 weeks, 6 weeks, and every 8 weeks thereafter. I

In 9 of the 14 responders, an increase in the anti-TNF dosage was required to sustain remission.

The preliminary results suggest that anti-TNF therapy may be a require further studies. A larger randomized controlled study of anti-TNF therapy for Takayasu arteritis is puseful adjunct to corticosteroids in the treatment of patients with Takayasu arteritis and Planned

SURGICAL CARE Critical stenotic lesions should be treated by angioplasty or surgical revascularization during periods of remission.

Indications for surgical repair or angioplasty are as follows:

1.Renovascular stenosis causing hypertension

2.Coronary artery stenosis leading to myocardial ischemia

3.Extremity claudication induced by routine activity

4.Cerebral ischemia and/or critical stenosis of 3 or more cerebral vessels

5.Aortic regurgitation

6.Thoracic or abdominal aneurysms larger than 5 cm in diameter

7.Severe coarctation of the aorta

8.Percutaneous transluminal coronary angioplasty is followed by restenosis at the angioplasty site within 1-2 years in a substantial number of patients.

9.Bypass graft procedures have the best long-term patency rates

Response Of Aortitis To Treatment

MORTALITY/MORBIDITY Takayasu arteritis is a chronic relapsing and remitting disorder. 10-year survival rate is approximately 90%; however, this rate is

reduced in the presence of major complications.[6]

Complications of Takayasu arteritis include valvular heart disease, stroke, heart failure, retinopathy, and renovascular hypertension. The 5- and 10-year survival rates are approximately 69% and 36%, respectively, in patients with two or more complications. The 5- and 10-year survival rates associated with one or fewer complications are 100% and 96%, respectively.

A 2008 study assessing quality of life with Takayasu arteritis shows worse scores for physical and mental health compared with many other chronic diseases associated with peripheral vascular disease. Disease remission is the only factor that positively influences both physical and mental quality of life.Patients with RHEUMATOID ARTHRITIS or rate their quality of life as similar to those with Takayasu arteritis.

 In cortisone-resistant patients, stronger medications which suppress the immune system (immunosuppressive drugs), thereby further decreasing active inflammation of the arteries, have been used. Examples include prednisone, prednisolone,methotrexate (Rheumatrex, Trexall),cyclosporine, cyclophosphamide (Cytoxan), and azathioprine (Imuran). Strict control ofelevated blood pressure (hypertension) is important.

Pictured below is a close–up view of an angiogram of the left vertebral and subclavian arteries in a patient with Takayasu’s arteritis. Note the narrowing and irregularities that occur at several sites, and the “corkscrew” configuration of one vessel segment near the junction of the two arteries. These changes, caused by inflammation in the blood vessel wall, sometimes cause complete blockage of the artery.

Pictured below is a normal aortic arch on the left, with narrow, smooth blood vessels. On the right is an example of an abnormal aortic arch in a patient with Takayasu’s, with obvious dilation of the ascending aorta on the left side of the picture

Although the lung involvement in Takayasu’s is frequently overshadowed by involvement of systemic large blood vessels, the pulmonary arteries may also be affected in this disorder. Pictured below is a pulmonary angiogram demonstrating beading and cut–off lesions of the right pulmonary arteries, and a large aneurysm of the left pulmonary artery.

Indian journal of ophthalmology,vol 50,2002.

Bilateral anterior ischaemic optic neuropathy in Takayasu arteritis Abstract This report describes a case of a young male with bilateral, asymmetrical AION. He was subsequently diagnosed with Takayasu's disease

Publication of neurology society of India,vol 49,2001.

Single stage bilateral common carotid artery stenting in a patient of Takayasu arteritis.

» AbstractCarotid angioplasty and stenting is increasingly becoming a safe and efficacious modality of treatment in the management of carotid artery stenosis. Although atherosclerosis is the predominant cause of this morbid disease, Takayasu arteritis assumes special importance in south east Asia. The diffuse nature of this disease with associated inflammation and scarring of the vessel make revascularisation difficult. We report a case of Takayasu arteritis tid stenting was done in a single sitting.

JAPI, feb 2006Coexistence of Takayasu’s Arteritis with Ulcerative

ColitisAbstractThe association of ulcerative colitis with Takayasu’s

arteritis is rarely reported. The occurrence of the two together is possibly related to a common pathophysiology involving alteration in immune mechanisms.

Takayasu's arteritis is more prevalent in Japan and South East Asia whereas Ulcerative Colitis is more inWestern countries. The coexistence of these two diseases is uncommon and hence this report.

Clinical journal of immunology,vol 2009

Research Article Lack of Antilipoprotein Lipase Antibodies in Takayasu's

Arteritis

Abstract Background. Antilipoprotein lipase (anti-LPL) antibodies were

described in rheumatic diseases. In systemic lupus erythematosus they were highly associated with inflammatory markers and dyslipidemia, and may ultimately contribute to vascular damage. The relevance of this association in Takayasu's arteritis, which is characterized by major inflammatory process affecting vessels, has not been determined.

Pub MED.gov ,jul 9,2001

[Takayasu's disease: interest in methotrexate treatment].

Abstract We report a case in which methotrexate proved to be effective. CASE

REPORT: A 6-year-old girl presented with Takayasu's disease with elevated blood pressure of renovascular origin. Corticosteroids controlled the inflammatory syndrome but not the renal involvement and stopped the growth. Methotrexate (10 mg/m2/week) resulted in the control of the disease, the reduction of steroids and normal growth. CONCLUSION: In Takayasu's disease, steroids should be given as first-line therapy. In case of failure, side effects or steroid dependency, small doses of methotrexate may facilitate the disease's control and weaning from the steroids

Oxford journal of Rheumatology,nov 8,2005.

Post-interventional immunosuppressive treatment and vascular restenosis in Takayasu's arteritis

Abstract Objective. To investigate the outcome of vascular interventions and the

effect of post-interventional immunosuppressive treatment on the occurrence of vascular restenosis in patients with Takayasu's arteritis (TA).

Conclusion. Restenosis occurred in 31.7% of TA patients after intervention. A lower restenosis rate was observed when the vascular interventions were performed at the stable stage and when post-interventional immunosuppressive treatment was implemented.

American journal of Rheumatology,April 2008

Successful treatment of a patient with takayasu arteritis using a humanized anti–interleukin-6 receptor antibody

AbstractTakayasu arteritis (TA) is a chronic inflammatory disease

that involves the aorta and its major branches. Since overproduction of interleukin-6 (IL-6) seems to play a pathogenic role in TA, we used the anti–IL-6 receptor (IL-6R) antibody tocilizumab to treat a 20-year-old woman with refractory active TA complicated by ulcerative colitis (UC). Treatment with tocilizumab improved the clinical manifestations of TA and the abnormal laboratory findings in this patient and ameliorated the activity of UC. These results indicate that IL-6R inhibition with tocilizumab might be a future treatment option for .

JOURNAL OF PAEDIATRICS,Sept 2008

Treatment of Takayasu's Arteritis with Tumor Necrosis Factor Antagonists

Four children with Takayasu's arteritis were treated with tumor necrosis factor antagonists because of disease relapse during conventional therapy or as a first-line agent. Two patients went into remission; in the other 2, the response was partial. Anti-tumor necrosis factor agents can have a role in the treatment of Takayasu's arteritis; further controlled studies are required.

Curr Opin Rheumatology.2005;17(1) 2005

Advances in the medical and surgical treatment of Takayasu arteritis.

SUMMARY: In the future, greater therapeutic success may be achieved by addressing both the inflammatory and the myointimal proliferative components of Takayasu arteritis. New drugs that target intimal hyperplasia, as well as drug-eluting stents, deserve to be studied for possible utility as adjuncts to present treatments.

Journal of invasive cardiology,Nov 2009

Covered Stent for the Treatment of Coronary Aneurysm after Sirolimus-Eluting Stent Implantation a Patient with Takayasu’s Arteritis

ABSTRACT: Drug-eluting stents (DES) have been used

successfully to treat both de-novo and restenotic lesions in these patients.

Curr Opin Rheumatology,2009

Advances in the use of biologic agents for the treatment of systemic vasculitis.

RECENT FINDINGS: The greatest amount of experience with these agents for the treatment of systemic vasculitis is with antitumor necrosis factor agents, pooled intravenous immunoglobulin, and anti-B-cell therapies such as rituximab. SUMMARY: Biologic agents represent the next evolution in treatment for the primary systemic vasculitides.

Clinical Rheumatology journal.,2008

Mycophenolate mofetil in Takayasu’s arteritis

AbstractMycophenolate mofetil (MMf) has recently been

reported as a useful alternative immunosuppressive drug in autoimmune diseases.This study is the largest series till date establishing the use of mycophenolate as a safe and effective steroid-sparing immunosuppressant in Takayasu's arteritis

Indian jrnl of Paediatrics,july 2002.

Recent advances in the management of non-specific aorto-arteritis.

Today, percutaneous transluminar balloon angioplasty (PTBA) has emerged as a non-surgical, safe, effective alternative therapeutic option and endovascular stents have revolutionised the management. The disease must be suspected and diagnosed precisely with echocardiography and angiography before it is too late to manage.