Takayasu's arteritis

Synonyms: Martorell's syndrome, Martorell-Fabré syndrome, Rµder-Harbitz syndrome, Takayasu-Martorell-Fabré syndrome, Takayasu-Onishi syndrome, Danaraj's disease, aortic arch syndrome, brachiocephalic ischaemia, idiopathic arteritis of Takayasu, occlusive thrombo-aortopathy, pulseless disease, reverse coarctation, young female arteritis - amongst many others

What is Takayasu's arteritis?

Takayasu arteritis (TAK) is a rare, idiopathic systemic inflammatory disease affecting large arteries, including the aorta, its major branches and the pulmonary arteries.¹

The inflammatory process results in stenosis, occlusion, dilation or aneurysm formation in the arterial wall.²

It is of unknown aetiology, although there is some evidence to support a genetic predisposition.

Takayasu's arteritis was first described by Mikito Takayasu in 1908.³

Takayasu's arteritis epidemiology³

• Takayasu's arteritis is rare. It occurs worldwide but is much more common in Asia, especially Japan, than it is in Western countries.

• Takayasu's arteritis affects women more frequently than men. It is closely associated with the HLA-B52 haplotype.

• Takayasu's arteritis is predominantly a disease of young adults, typically presenting in the second and third decades of life, and may also affect children.¹

Takayasu's arteritis symptoms (Presentation)⁴

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. Slightly more patients present with systemic stage than occlusive stage.

Systemic stage
The symptoms are due to inflammation of the artery prior to any occlusion and include:

• Fever, fatigue, weight loss.

• Arthralgia and nonspecific pains.

• Tenderness overlying the affected arteries.

Occlusive stage
Ischaemic phenomena are responsible for symptoms, dependent on the site. They include:

• Vascular - claudication of the jaw or extremities, back pain (due to involvement of the aorta), syncope (rare), hypertension (the most common presentation in children).^{5 6}

• Neurological - dizziness, headaches, transient ischaemic attacks (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 blood pressure (SBP) difference >10 mm Hg between arms.

• Peripheral pulses may not be palpable.

• Arterial bruits over any large artery and bruit of aortic regurgitation.

• High BP in 50%, due to renal artery involvement.

• Characteristic changes in blood vessels visible with an ophthalmoscope.

• Anaemia.

• Muscle wasting.

• Skin vasculitis.

Diagnostic criteria

The mandatory criterion is angiography (conventional, CT or MRI) of the aorta or its main branches and pulmonary arteries showing aneurysm/dilatation, narrowing, occlusion or thickened arterial wall not due to fibromuscular dysplasia, or similar causes. The diagnostic criteria are:⁷

Major criteria

• Signs and symptoms characteristic for more than one month.

• Claudication of limbs.

• Absence of pulses or differential pulse between arms >10 mm Hg.

• Palpitations.

• Syncope.

• Dyspnoea.

• Cervical pain.

• Fever.

• Amaurosis fugax (transient loss of vision in one or both eyes due to a lack of blood flow to the eye).

• Blurred vision.

• Pathological radiological findings in the middle region of the right or left subclavian artery.

Minor criteria

• Elevation of ESR >20 mm/hour.

• Carotodynia (unilateral tenderness of the carotid artery, near the bifurcation).

• High BP.

• Aortic regurgitation or anulo-aortic ectasia.

Differential diagnosis⁸

• Acute lymphoblastic leukaemia.

• Behçet's disease.

• Pyrexia of unknown origin.

• Hodgkin's disease.

• Polyarteritis nodosa.

• Rheumatic fever.

• Giant cell arteritis.

• Buerger's disease.

• Systemic lupus erythematosus.

• Fibromuscular dysplasia.

• Systemic-onset juvenile idiopathic arthritis.

• Migraine.

• Infection.

• Malignancy.

• Cogan's syndrome (interstitial keratitis associated with vestibulo-auditory symptoms, cause unknown).

Investigations⁸

Laboratory investigations

• There are no diagnostic blood tests.

• FBC may show a normocytic anaemia in 50% of patients. ESR may be high (50 mm/hour or more) in the early stages but normal in the later stages. The leukocyte count may be normal or slightly raised.

• Circulating anti-endothelial antibodies may be present in high titres but these can be found in many connective tissue diseases.

• Hypoalbuminaemia and increased levels of fibrinogen, alpha-2 globulin and gamma globulin are frequently found.

• Clinical and laboratory assessment of disease activity is difficult and no circulating markers for staging or prognosis have been identified.⁹

Radio-imaging⁷

• 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 contrast, can show soft tissue as well as arterial walls and this may be useful in identifying active from inactive disease.

• Positron emission tomography using radioisotope (¹⁸ F) fluorodeoxyglucose (FDG-PET) as a marker for tissue with high glucose uptake has been 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 be used in combination with other tests in the chronic stage.

Takayasu's arteritis treatment and management^{12 13}

• The most commonly used drugs include corticosteroids and conventional immunosuppressive agents - eg, azathioprine, methotrexate and cyclophosphamide. Most patients respond to steroids.¹⁴

• In patients who remain resistant and/or intolerant to these agents, biological drugs including TNF inhibitors, rituximab and tocilizumab appear to be effective.

• Antiplatelet treatment may also lower the frequency of ischaemic events.

• Hypertension should be aggressively managed.

• In the presence of short-segment, critical arterial stenosis, balloon angioplasty or stent graft replacement may be useful.

• Long-segment stenosis with extensive periarterial fibrosis or occlusion requires surgical bypass of the affected segment.

• Both endovascular intervention and surgical procedures should generally be avoided during the active phase of the disease.

Complications of Takayasu's arteritis

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

• Loss of vision.

• Hypertension.

• Stroke.

• Aortic regurgitation.

• Myocardial infarction.¹⁵

Prognosis

• 20% have self-limiting monophasic disease. A picture, however, is emerging of long-term disability and reliance on steroids to reduce the remission rate.¹⁶

• The mortality rate is 2-35% over five years overall. This wide variation may reflect differing diagnostic criteria or differences in the level of care.

• In the absence of major complications, five-year survival is excellent.

• In the presence of major complications (eg, stroke, myocardial infarction, severe hypertension, heart failure, aneurysm), five-year survival is not as favourable, depending on the extent of complications.

• In one longitudinal study of 16 patients, 81% had one or more relapses but 94% achieved long-term remission.¹⁷

• Death may occur if the disease is 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.¹⁸