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 thrombo-aortopathy, pulseless disease, reverse coarctation, young female arteritis, amongst many others

Takayasu's arteritis is a rare autoimmune vasculitic disorder which predominantly affects young women.
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.

Mikito Takayasu who described the syndrome in 1908 was professor of ophthalmology at the University of Kanazawa.¹ The syndrome was also described by Japanese physician Rokushu Yamamoto in 1830 and may have been described as early as 1761 by the Italian pathologist Giovanni Battista Morgagni.²

Epidemiology

• 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.³
• It has been reported all over the world, but is most common in Asia, particularly Japan.

Presentation

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% of 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 nonspecific pains.
  • Tenderness overlying the affected arteries.

Occlusive stage

• 50-60% of patients present at this 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).^3,4
  • 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 changes are usually focal or segmental.⁵

• Age at onset ≤40 years.
• Claudication of the extremities.
• Reduced pulsation of one or both brachial arteries.
• >10 mm Hg BP difference between arms.
• Hypertension defined as systolic/diastolic BP greater than 95th centile for height.
• Bruit over one or both subclavians or the abdominal aorta.
• Acute phase reactant - ESR ≥20 mm per first hour or CRP any value above normal (according to the local laboratory).

Differential diagnosis⁶

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

Investigations⁶

Laboratory Investigations

• There are no diagnostic blood tests.
• FBC 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 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.

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 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 (¹⁸F) fluorodeoxyglucose (FDG-PET) as a marker for tissue with high glucose uptake has recently been assessed and shows promising results in terms of specificity and sensitivity.^7,8

Procedures

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

Management

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

Pharmacological

• Most patients respond to prednisolone, usually at a starting dose of 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 a cerebrovascular event.
• Anti-tumour necrosis factor (anti-TNF) has recently been used with encouraging results.⁹

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 artery.¹⁰

Complications

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

• Loss of vision
• Hypertension
• Stroke
• Aortic regurgitation
• Myocardial infarction (MI)¹¹

Prognosis¹²

• 20% have self-limiting monophasic disease. A picture, however, is emerging of long-term disability and reliance on steroids to reduce the remission rate.¹³
• 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, 5-year survival is >95%.
• In the presence of major complications (e.g. stroke, MI, severe hypertension, heart failure, aneurysm), 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.¹⁴
• 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.¹⁵

Document references

1. Takayasu, M; A case with peculiar changes of the central retinal vessels. Acta Soc Ophthalmol Jap, Tokyo 1908, 12: 554
2. Di Giacomo V; A case of Takayasu's disease occurred over two hundred years ago. Angiology. 1984 Nov;35(11):750-4. [abstract]
3. Cakar N, Yalcinkaya F, Duzova A, et al; Takayasu arteritis in children. J Rheumatol. 2008 May;35(5):913-9. Epub 2008 Mar 15. [abstract]
4. Peera MA, Locurto M, Elfond M; A Case of Takayasu Arteritis Causing Subclavian Steal and Presenting as Syncope. J Emerg Med. 2008 May 10. [abstract]
5. Ozen S, Pistorio A, Iusan SM, et al; EULAR/PRINTO/PRES criteria for Henoch-Schonlein purpura, childhood polyarteritis Ann Rheum Dis. 2010 May;69(5):798-806. [abstract]
6. Gulati A, Bagga A; Large vessel vasculitis. Pediatr Nephrol. 2010 Jun;25(6):1037-48. Epub 2009 Oct 17. [abstract]
7. Walter MA, Melzer RA, Schindler C, et al; The value of <18F>FDG-PET in the diagnosis of large-vessel vasculitis and the assessment of activity and extent of disease. Eur J Nucl Med Mol Imaging. 2005 Jun;32(6):674-81. Epub 2005 Mar 4. [abstract]
8. Haensch CA, Rohlen DA, Isenmann S; F-18-fluorodeoxyglucose positron emission tomography-computed tomography for the diagnosis of Takayasu's arteritis in stroke: a case report. J Med Case Reports. 2008 Jul 24;2:239. [abstract]
9. Arnaud L, Kahn JE, Girszyn N, et al; Takayasu's arteritis: An update on physiopathology. Eur J Intern Med. 2006 Jul;17(4):241-6. [abstract]
10. Purkayastha S, Jayadevan ER, Kapilamoorthy TR, et al; Suction thrombectomy of thrombotic occlusion of the subclavian artery in a case of Takayasu's arteritis. Cardiovasc Intervent Radiol. 2006 Mar-Apr;29(2):289-93. [abstract]
11. Peake ST, Mason JC, Mittal T, et al; Growing pains--and a heart attack. Lancet. 2008 Aug 16;372(9638):600.
12. Numano F, Okawara M, Inomata H, et al; Takayasu's arteritis. Lancet. 2000 Sep 16;356(9234):1023-5.
13. Maksimowicz-McKinnon K, Hoffman GS; Takayasu arteritis: what is the long-term prognosis? Rheum Dis Clin North Am. 2007 Nov;33(4):777-86, vi. [abstract]
14. Petrovic-Rackov L, Pejnovic N, Jevtic M, et al; Longitudinal study of 16 patients with Takayasu's arteritis: clinical features and therapeutic management. Clin Rheumatol. 2008 Sep 17. [abstract]
15. Park MC, Lee SW, Park YB, et al; Clinical characteristics and outcomes of Takayasu's arteritis: analysis of 108 patients using standardized criteria for diagnosis, activity assessment, and angiographic classification. Scand J Rheumatol. 2005 Jul-Aug;34(4):284-92. [abstract]

Internet and further reading

• Bucurescu G, Neurological Manifestations of Takayasu Arteritis, Medscape, Sep 2009
• Hom C, Pediatric Takayasu Arteritis , Medscape, Aug 2010
• Cirillo R, Arteritis, Takayasu, Medscape, Sep 2008

Acknowledgements