Takayasu's Arteritis

Synonyms: Martorell's syndrome, Martorell-Fabré syndrome, Ræder-Harbitz syndrome, Takayasu-Martorell-Fabré syndrome, Takayasu-Onishi syndrome, Danaraj's disease, Aortic arch syndrome, Brachiocephalic ischaemia, Idiopathic arteritis of Takayasu, Occlusive thromboaortopathy, Pulseless disease, Reverse coarctation, Young female arteritis, amongst many others.

Takayasu's arteritis is a rare autoimmune vasculitic disorder which predominantly affects young women.¹
Mikito Takayasu who described the syndrome in 1908 was professor of ophthalmology at the University of Kanazawa.^2,3 The syndrome was also described by Japanese physician Rokushu Yamamoto in 1830 and may have been described as early as 1761 the Italian pathologist Giovan Battista Morgagni.⁴

The classic description is of a chronic, progressive, inflammatory, occlusive disease of the aorta and its branches. The inflammation of the arteries involved causes partial or complete occlusion or aneurysm of the artery and many of the signs and symptoms of the disease happen as a direct consequence of this. It is of unknown aetiology, although there is some evidence to support a genetic predisposition. Atherosclerosis is the more common cause of occlusive disease in these vessels in the Western world.

• Takayasu's arteritis is rare, with an approximate incidence worldwide of 2-3 cases per year per million head of population.
• The annual incidence in the UK is 0.15 per million.
• Takayasu's arteritis affects women more frequently than men with a 9:1 female:male ratio.
• It affects young adults up to the age of 40, but is most common in the age range 15-20. As diagnostic techniques progress, patients in younger age groups are being diagnosed.⁵
• It has been reported all over the world, but is most common in Asia, particularly Japan.

Symptoms

The symptoms of the disease mainly arise as a direct consequence of arterial insufficiency due to the inflammation.

The disease is commonly divided into two stages:

Systemic stage

• 40-50% patients present at this stage. The symptoms are due to inflammation of the artery prior to any occlusion.
• They include:
  • Fever, fatigue, weight loss.
  • Arthralgia and non-specific pains.
  • Tenderness overlying the affected arteries.

Occlusive stage

• 50-60% patients present at this stage.
• Ischaemic phenomena are responsible for symptoms, dependent on site. They include:
  • Vascular - claudication of jaw or extremities, back pain (due to involvement of the aorta), syncope (rare), hypertension (the commonest presentation in children)^6,5
  • Neurological - dizziness, headaches, TIAs, visual disturbance, seizures, stroke
  • Cardiac - angina, dyspnoea (from congestive cardiac failure - the primary cause of death)
  • Pulmonary - haemoptysis, pleuritis
  • Gastrointestinal - abdominal pain from ischaemia/infarction of bowel
  • Also renal (haematuria) and dermatological (rashes including erythema multiforme and induratum)

Signs

• Key finding is a systolic BP difference >10 mmHg between arms
• Peripheral pulses may not be palpable
• Arterial bruits over any large artery and bruit of aortic regurgitation
• High blood pressure in 50% due to renal artery involvement
• Characteristic changes in blood vessels visible with an ophthalmoscope
• Anaemia
• Muscle wasting
• Skin vasculitis

Diagnostic criteria From the American College of Rheumatology⁷

3 of 6 of the following should be present:

• Age at onset ≤40 years.
• Claudication of the extremities.
• Reduced pulsation of one or both brachial arteries
• >10 mmHg BP difference between arms
• Bruit over one or both subclavians or the abdominal aorta.
• Arteriographic narrowing/occlusion of the entire aorta, its primary branches or large arteries in upper/lower limbs, not due to atherosclerosis, fibromuscular dysplasia or other causes.

• Acute lymphoblastic leukemia
• Behcet syndrome
• Fever without a focus
• Hodgkin disease
• Polyarteritis nodosa
• Rheumatic fever
• Giant cell arteritis
• Buerger disease
• Systemic lupus erythematosus
• Fibromuscular dysplasia
• Systemic-onset juvenile rheumatoid arthritis
• Migraine
• Infection
• Malignancy
• Cogan syndrome (interstitial keratitis associated with vestibuloauditory symptoms, cause unknown)

Laboratory Investigations

• There are no diagnostic blood tests.
• Full blood count may show a normocytic anaemia in 50% of patients. ESR may be high (50 mm/h or more) in the early stages, but normal in the later stages. The leucocyte count may be normal or slightly raised.
• Circulating antiendothelial antibodies may be present in high titres, but these can be found in many connective tissue diseases.
• Hypoalbuminemia and increased levels of fibrinogen, alpha2-globulin and gamma globulin are frequently found.

Radio-Imaging

• Angiography - this has been used for many years as the main diagnostic test, However, it evaluates the arterial lumen only and cannot distinguish between active and inactive lesions. It is however still used to characterise the condition into types dependent on arterial involvement:
  • I - branches of aortic arch
  • IIa - ascending aorta, aortic arch and its branches
  • IIb - IIa plus thoracic descending aorta
  • III - thoracic descending aorta, abdominal aorta and/or renal arteries
  • IV - abdominal aorta and/or renal arteries
  • V - entire aorta and its branches
• Ultrasound - this is popular as it is non-invasive and can be used easily in children. It is a useful screening test for easily accessible areas of the body, but false negative findings are common. The method can be made more sensitive by colour doppler enhancement.
• CT scanning, using contrast enhancement is a sensitive tool for detecting arterial wall thickening. Multi-detector row CT can cover large areas and increase the speed and accuracy of the technique.
• MRI scanning, enhanced by gadolinium contract, can show soft tissue as well as arterial walls and this may be useful in identifying active from inactive disease.
• Positron emission tomography using (18)F-fluorodeoxyglucose as a marker for tissue with high glucose uptake is recently being assessed and shows promising results in terms of specificity and sensitivity.^10,11

Procedures

Arterial biopsy may be diagnostic in the early stages, but must used in combination with other tests in chronic stage.

• Patients with mild disease can be managed the outpatient setting.
• The goals of treatment are to reduce inflammation, return clinical and laboratory values to normal and prevent further vascular damage.

Drugs

• Most patients respond to prednisolone, usually at a starting dose 1 mg/kg/day
• Steroid sparing agents are also frequently used, including:
  • Methotrexate
  • Azathioprine
  • Cyclophosphamide
• Hypertension should be aggressively managed
• Anticoagulant drugs are occasionally used to prevent stroke
• Anti-tumour necrosis factor (anti -TNF) has recently been used with encouraging results¹²

Surgery

Surgical procedures are sometimes required to increase the flow of blood through an artery and procedures undertaken include:

• Angioplasty with stenting
• Vascular bypass procedures
• Aortic valve replacement
• Suction thrombectomy of the subclavian artery¹³

Complications occur as a result of narrowing or occlusion of the arteries and may include:

• Loss of vision
• Hypertension
• Stroke
• Aortic regurgitation
• Myocardial infarction

• 20% have self-limiting monophasic disease. A picture however is emerging of long-term disability and reliance on steroids to reduce the remission rate.¹⁴
• The mortality rate is 2-35% over 5 years overall. This wide variation may reflect differing diagnostic criteria or differences in the level of care.
• In the absence of major complications the 5 year survival is >95%.
• In the presence of major complications (eg stroke, MI, severe hypertension, heart failure, aneurysm), the 5 year survival is 50-70%.
• In one longitudinal study of 16 patients, 81% had one or more relapses but 94% achieved long-term remission.¹⁵
• Death may occur if not adequately treated, most commonly as a result of renovascular hypertension (heart failure or stroke).
• One study suggested that a low ESR, early treatment with steroids and a stable condition at presentation were factors which predicted a good prognosis.¹⁶