TAKAYASU’S AORTOARTERITIS

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Dr. B.K. Barik

            Takayasu arteritis is a chronic, non-specific, idiopathic inflammatory disease that primarily affects large vessels. The clinical features reflect limb or organ ischamia due to gradual stenosis of involved arteries. It often occurs in females in their reproductive years.

            Takayasu’s arteries (TA) is synonymous with non-specific aortoarteritis, aortic arch syndrome, pulseless disease, Martorell Syndrome.

            Early reports suggested that the disease was confined to females from Eastern Asia, but it has been recognized world wide in both sexes but among populations, manifestations vary. There are several cohort studies in different parts of both Eastern and Western hemispheres. The results of different studies are dealt with the etiological factors, various markers, clinical features diagnostic criteria and management plans.

            The study in India resulted in modification of diagnostic criteria for Indian patients and these criteria are more sensitive and specific than diagnostic criteria used earlier. 

INTRODUCTION

            Non specific aortorarteritis was introduced to the medical fraternity in 1827 by R. Adams who was the first physician to note the absence of pulses in all four extremities. In 1856, Savroy reported a case of a young female with absence of pulses. In 1908 , Mikito Takayasu a Japanese opthamologist described peculiar peculiar wreath like appearance of retinal blood vessels with absence of radial pulse.  

PATHOGENESIS

            Takayasu’s arteritis is synonymous with non-specific aortoarteritis aortic arch syndrome, pulseless disease, Martorell Syndrome.

            It is an inflammatory vascular disease involving large size arteries resulting in occlusive and ecstatic changes mainly in the aorta and its branches. It is a panarteritis. In the first phase, there is acute florid inflammation of all three coats of a large artery (advantitia, medic, intima). In healed fibrotic phase, there is cuffing of vasa vasorum, destruction of elastic tissue and media, followed by fibrosis. There is hyalinization, thickening plaque and patch formation. All these give rise to ‘tree bark’’ appearance of inner wall of large arteries. Adventitia shows most prominent inflammatory reaction. Skipped areas of aortic involvement are quite characteristic of aortorarteritis.

ETIOLOGY

            Till date, no definite etiological factor has been established. Infection has been considered to play an important role in the pathogenesis of Takayasu arteritis. Tuberculosis has been particularly implicated in view of the high prevalence of infection in affected patients in endemic zones. Seko et al have reported that CD4, CD8 and natural respond) is expressed strongly in arterial wall. Takayasu arteritis has been associated with different HLA alleles in different populations. Sequence analysis has shown that some of the alleles have specific epitopes which strengthen the argument in favour of an auto-immune pathogenesis. The associated HLA are HLA-DR₂, MB₁, BW₅₂, DR₁₂, DQW₁, HLA-DR₄, HLAB₅, B₂₁ and others.

CLINICAL FEATURES

            It is predominatly a disease of young females in their second or third decade. It occurs worldwide, but commonly seen is Japan, East Asia, India and Mexico. Age of onset may range from infancy to middle age. The disease has predilection for fermales with wide geographical variations. The natural history of this disease has to phases. In the first Pre-pulseless phase, there are non-specific sysmptoms like night sweats, malaise, weight loss, arthralgia, mild anemia etc. It may remit spontaneously in 3 months or progress to pulseless chronic phas.e The symptoms are due to stenotic  lesions and are dyspnoea, headahe, diminished urination, intermittent claudication (upper link>lower limb), visual disturbances, Raynaud’s phenomenon, light headedness, leg ulcer etc.

CHARACTERISTIC FEATURES

1.                  Diminished or absent pulses associated with CURRENT MEDICAL JOURNAL OF INDIA: VOL.X, NO. 8 NOVEMBER’ 2004 limb claudication and BP discrepancy (84-96% of patients).

2.                  Vascular bruit, often at multiple sites such as carotids, subclavians, abdominal vessels etc. (80-94% of patients.)

3.                  Hypertension generally due to RA stenosis (33-83%), atypical coarctation, diminished aortic capacity and diminished baroreceptor activity.

4.                  Takayasu’s retinopathy (37%).

5.                  Aortic regurgitition resulting from ring dilatation of aorta, separation of valve cusps, valve thickening (20-24)% etc.

6.                  Congestive heart failure associated with hypertension AR, DCM etc.

7.                  Neurological features secondary to hypertension and /or ischaemia including postural dizziness seizures, amaurosis (complete loss of vision).

8.                  Pulmonary artery involvement (14-100%) evidenced by oligemic lung fields in chest X-ray. Usually involves right upper lobe artery.

9.                  Coronary artery involvement is usually limited to ostium and proximal part may cause angina AMI, CCF and sudden death.

10.             Erythema nodosum of skin.

DIFFERENTIAL DIAGNOSIS

            Inflammatory aortoarteritis : which may be seen in syphilis, tuberculosis, SLE rheumatoid arthritis, spondyloarthropathy, Beheet’s disease. Kawasaki disease, Gaint cell arteritis coarctation of aorta, Marfan’s syndrome. Elher Danlos Syndrome etc.

INVESTIGATIONS

A. SERUM AND SEROLOGICAL MARKERS

i)                    High ESR:

·        Ishikawah found patients with equal distribution in all categories and higher value in younger.

·        In a study by Hall et al, 3/4^th of patients reported high ESR.

·        In a study by Keer et al, 72% of patients with active disease had high ESR, 36% on remission had high ESR.

ii)                  Other markers:

CRP, vWF, thrombomodulin, tissue factor tPA, various adhesion molecules, IL-IB, IL-6 RANTES etc.

Etiological studies in India and surrogate markers:

• Strong association with HLAB5 (B51, B52).
• No association with any one of five alleles of MICA gene.
• ICMA-I VCAM-I, E- selection, PECAM-I.
• Total T cell in TA patients were significantly higher i.e., high CD4: ratio.
• Increased basal activity of protein kinase C and increase basal level of intracellular Ca+ in T cell.
• Anti-aorta antibody.
• Anti-endothelial Ab.
• Anti-cardio-lipin Ab (IgG)

B. Doppler USG is a very useful tool for early diagnosis and treatment . it is not –invasive and can assess vascular wall inflammation narrowing and blood flow.

C. Angiography as an investigation is the gold standard.

MANAGEMENT

            It includes management of active disease, regular follow-up and management of different complications.

CRITERIA OF ACTIVE DISEASE

1. Systemic features
2. High ESR.
3. Clinical features of vascular ischamia or inflammation
4. Typical angiographic features.

MEDICAL MANAGEMENT

            Drugs used presently are the glucocorticoids (Prednisolone), Cytotoxic agents (Cylophosphamide, azathioprine, methotrexate) and mycophenolate mofetil. Plan suggested by Kerr et al is shown in Flow chart on the next page.

Failure of Cytotoxic Agents.

            After starting cytotoxic agent, if it is not possible to taper glucocorticoid to alternate day regimen in 6 months or to discontinue completely within 12 months, then it is failure of cytotoxic agents.

            Patients with cytotoxic failure should be treated with minimum does of glucocorticoids.

            Anti-hypertensive agents to be started in patients with hypertension but hypertension is worsened by steroids. ACE inhibitors requires careful monitoring in renovascular hypertension.

B. PERCUTANEOUS TRANSLUMINAL CORONARY ANGIOPLASTY (PTCA)

            Major advancement in the treatment of this otherwise morbid condition has been brought by PTCA. Lesions in aortoarteritis are purely stenitic in 85% of patients, purely dilative in 2% and mixed in 13%. Stenotic lesions in aorta, renal artery, subclavian, carotid, iliac/ saphernofemoral arteries have been dilated by ballon angioplasty with or without stenting in several patients in India with excellent immediate and long –term follow-up results. After successful PTCA, hypertension is controlled in 87% of patient and claudication improved in 86% patients. Five year mortality rate decreased to 9% in successful angioplasty from 42% in failed angioplasty.

C. SURGICAL MANAGEMENT.

THE INDICATIONS ARE:

• Hypertension associated with critical stenosis of RA.
• Extremity ischaemia limiting activities of daily living.
• Clinical features of cerebro –vascular ischaemia or critical stenosis (70% narrowing) or both of at least three cerebral vessels.
• Cardiac ischaemia in the setting of proven coronary artery disease.

PROCEDURES

• Bypass grafting using synthetic (Dacron graft or autologus vessel (saphenous) graft.
• Rescretion and replacement of inter-position graft.
• Patch aortoplasty, endarterectomy and repair of aneurysm.
• Aortic valve replacement in AR.

RECENT TRENDS IN INDIA

            Several studies have been reported from India an Japan on takayasu’s artertis. Some of the finding are as follows:

            The age of onset in Indian patient  is either second or third decade whereas in Japan, the median age of onset is 29 yrs and in Europe, it is 41 yrs. There is a gross geographical variation of predilection for females. In japan, females:male ration is 8:1 Mexico 5:1, Israel 1:2:1 , In India 6:4:1 (by Panja et al), 1:5:1 (by Jain et al), 1:2:1 (by Sharma et al). In Japan, the disease mainly involves proximal aorta with features of reversed coarctation where as in India decending thoracic aorta and abdominal aorta are mainly involved and is known as Middle Aortic syndrome. Association with other disease like SLE, rheumatoid arthritis, polymyalgia rheumatica have been reported in India and other countries.

In India, Jain reported anemia in 63.3% cases high ESR in 56 patients out of 93 patients, high creatinine (>2mg%) in 12.3% cases, LVH (by ECG) in 59.4% cases, cardiomegaly in 32% cases and abnormal urogram in 52 out of 77 cases (table-1)

The angiographic finding reported by Jain differ from the findings by Kerr et al in North America (Studyof 60 patients)

ISHIKAWA’S CLINICAL CLASSIFICATIONS OF TA

            This classification is based on natural history complications and prognosis of the disease in an individual. The four most important complications are the retinopathy secondary hypertension, aortic regurgiation and aneurusm formation. Each complication is graded as mild, moderate and severe.

Table No-I

CLINICAL FEATURES

IN 106 PATIENTS WITH TA (JAIN ET AL)

The classification is as follows:

• Group-I Uncomplicated with or without pulmonary artery involvement.
• Group-II A- Mild/ Moderate single complication with uncomplicated disease.
• Group-II B Severe single complication with uncomplicated disease.
• Group-III Two or more than two complications or any patients with arteries.

ANGIOGRAPHIC CLASSIFICATION

            There are various angiographic classification for TA. The first one is proposed by Ueno et al (1967) . In 1975 Lupi Herrera et al proposed another classification. In Japan, few physicians are still following Nasu’s classification. But previously used angiographic classification are susperseded by new angiographic classification proposed in Takayasu conference in 1994 and are as follows:

Type –I Involvement  of branches from aortic arch

Type –II a Involvement of ascending aortaarch and its braches.

Type-II b Involvement of ascending aorta and its branches and thoracic aorta

Type –III Involvement of descending and abdominal aorta and / or renal artery.

Type-IV Involvement of abdominal aorta and/ or renal artery.

Type-V Combined II b +IV

Note:- Involvement of coronary artery is designated as c (+) and involvement of pulmonary artery is designated as p(+).

This classification is helpful in comparing the patients groups according to vessels involved planning surgery . But is of little value in prognosis.

Based on the analysis of 96 patients Ishikawa proposed a criteria for clinical diagnosis in 1988 and is shown in Table-3.

CRITERIA:

A. OBLIGATORY CRITERIA

Age <40 years at diagnosis or onset of characteristic signs / symptoms of 1 month duration.

Table No-3

ANGIOGRAPHIC STUDIES

A comparative study of vascular lesions of the patients from Japan (total No of patients 396) and India (total no of patients 510) by angiography:

B. TWO MAJOR CRITERIA.

1. Left mid-subclavian artery lesion by angiography.
2. Right mid-subclavian artery lesion by angiography.

C. NINE MINOR CRITERIA

1. High ESR> 20mm first hour (Westergren)
2. Carotid artery tenderness.
3. Hypertension 140/90mm Hg in brachial or > 160/90mmHg in popliteal at age <40 years.
4. Aortic regurgitation or annuloarotic ectasia.
5. Pulmonary artery lesion
6. Left mild –common carotid artery lesion.
7. Distal brachio-cephalic aorta lesion.
8. Decending thoracic aorta lesion.
9. Abdominal aorta lesion, with absence of lesion in aorta-iliac region consisting of 2 cm of terminal aorta and bilateral common iliac arteries determined by angiography.