Predominately large vessel

Takayasu Arteritis

  • Takayasu arteritis (TA) is an inflammation of the large blood vessels leaving the heart and feeding the body and lungs with blood. Arteritis is a term used for arterial blood vessels; vasculitis means inflammation of either arterial and venous blood vessels and is oftentimes used to describe blood vessel inflammation. In TA the main artery leaving the heart, called the aorta, and the other major blood vessels branching from the aorta, become inflamed . Inflammation results in swelling and thickening of the artery wall. As the wall thickens, the space inside the vessel narrows and essential blood flow organs of the body decreases.
  • TA image
  • Vessels are inflamed for a long time, they can become damaged to the point of occlusion (blockage of blood flow through the vessel) or aneurysm formation (parts of the vessel weaken and form bulges). Collateral circulation can also occur in which the blood finds an alternate path around the blocked artery or vein via neighbouring smaller vessels.
  • TA is an invisible disease for a long time. It becomes apparent, when organ blood supply is critical. Typically this happens in the blood vessels feeding the kidneys, decreased blood supply results in high blood pressure in order to maintain blood flow to the kidney. Sometimes the inflammation can resolve without treatment, however it always leaves the blood vessels damaged. .More commonly, inflammation persists and requires immunosuppressive treatment to be stopped.

TA is an inflammatory disease. We currently don’t understand, why the immune system starts irritating the large blood vessels, no diet or other modifiable risk factor has been identified. There is an association between exposure to tuberculosis infections and TA, however many patients have never been in contact with TB. There appears to be a seasonal pattern with higher peaks of TA incidence in the winter months. Sometimes TA can develop in patients with inflammatory bowel disease or inflammation and arthritis of the sacroiliac joints

  • TA can affect children of all ages and ethnicities. It is more commonly occurring in girls and in children of Asian populations including Indian and Japanese populations.

Children are oftentimes diagnosed with TA when they present with systemic symptoms of fever or fatique paired with symptoms of decreased blood supply to vital organs such as high blood pressure, blood pressure differences between arms or legs, loss of pulses, strokes or transient ischemic attacks or pain which running (claudication). Blood markers of inflammation can further support the diagnosis. Imaging of the large blood vessel in so-called angiographies confirms the diagnosis of TA.

  • Click here for more detailed information on classifying TA using the EULAR/PRINTO/PRES framework,.
  • A combination of corticosteroids and other immunosupressants such as biologic agents and cyclophosphamide are used to control the severe inflammation of patients with Takayasu Arteritis. Surgery of the blood vessels may be used during the acute illness in in critical cases involving occlusion and stenosis leading to ischemia (inadequate blood supply provided to the dependent organ). Commonly surgery is considered once the inflammation has healed and blood vessels remain very narrow.
  • Click here for more detailed information on suggested treatment protocols.
  • According to the 2010 European League Against Rheumatism (EULAR)/ Pediatric Rheumatology International Trials Organization (PRINTO) and Pediatric Rheumatology European Society (PRES) criteria for classification of TA, a patient must present with angiographic abnormalities plus have a minimum of 1 of the following features:
    1. Decreased peripheral artery pulse(s) or claudication of extremities
    2. Blood pressure difference >10 mmHg in systolic blood pressure between arms.
    3. Bruits over the aorta or its major branches
    4. Hypertension
    5. Acute phase reactant (Erythrocyte sedimentation rate >20mm per first hour or CRP any value above normal)
  • In order to reach a diagnosis, it is important to consider a combination of clinical features, specific raised inflammatory markers, along with specific imaging patterns. For more details view the diagnostic algorithm for Takayasu arteritis.
  • A total of 10% of patients do not show symptoms at diagnosis. These patients do, however, show abnormal vascular patterns when examined.
  • The patients that do present with symptoms will likely experience some of the following:
Non-specific systemic symptoms Specific Symptoms Neurological Symptoms
Fatigue

 

Claudication (cramping in arms or legs) Headache
Fever Hypertension (high blood pressure), often renal hypertension Vision changes
Arthralgia (pain in joint) Lower blood pressure and weaker pulse in upper limbs Stroke
Weakness Coldness or numbness of fingers
Discrepancy in blood pressure between arms
Transient ischemic attack
Myalgia (muscle pain)
Night sweats
Weight loss
Malaise
Shortness of breath
Symptoms secondary to ischemia of organs
  • Inflammatory markers like erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) correlate well with disease activity. In adolescents, disease activity correlates with increased ESR levels. There is some evidence to suggest high levels of CRP are associated with higher risk of thrombotic complications.

Imaging tools used for diagnosis (sometimes in combination):

  • Magnetic resonance angiography (MRA) with contrast enhancement of vessel wall
  • CT angiography (CTA)
  • Conventional angiography
  • Doppler ultrasound
  • Fluoro-deoxy-glucose (FDG) positron emission tomography (PET)
  • Six distinct vascular pattern of TA have been described:
    • Type I – Branches of the aortic arch.
    • Type IIa – Ascending aorta, aortic arch, and its branches.
    • Type IIb – Type IIa region plus thoracic descending aorta.
    • Type III – Thoracic descending aorta, abdominal aorta, renal arteries, or a combination.
    • Type IV – Abdominal aorta, renal arteries, or both
    • Type V – Entire aorta and its branches.

Khanna NN, Rao S. Takayasu arteritis – Brief review. Journal of Indian College of Cardiology, 2016. 6(1): p. 147-52.

Of note: Angiography can reveal skip lesions, in which the blood vessel is inflamed in patches that ‘skip’ normal vessel areas. Pulmonary artery involvement can also be seen.


Ashish JM, Ruchika G, Sathish K, Debashish D. Childhood-onset Takayasu arteritis: an update. Int J Rheum Dis, 2016. 19(2): p. 116-26.

Figure 1: Angiogram of a patient with Takayasu arteritis (TA).  This image displays an angiogram of a paediatric TA patient with stenosis, poststenotic dilation and massive bilateral carotid dilation.  Retrieved from:  http://www.uptodate.com/contents/image?imageKey=PEDS/64547&topicKey=ALLRG%2F6401&source=outline_link&utdPopup=true

Figure 2: CT scan of a patient with Takayasu arteritis (TA)  Contrast-enhanced CT scan of a paediatric patient with TA with stenosis, poststenotic dilation and massive bilateral carotid dilation.  Retrieved from: http://www.uptodate.com/contents/image?imageKey=RHEUM/62264&topicKey=ALLRG%2F6401&source=outline_link&utdPopup=true


Brunner J, Feldman BM, Tyrrell RN, Kuemmerle-Deschner JB, Zimmerhackl LB, Gassner I, Benseler SM. Takayasu arteritis in children and adolescents. Rheumatology, 2010. 49(10): p. 1806-14.

Ashish JM, Ruchika G, Sathish K, Debashish D. Childhood-onset Takayasu arteritis: an update. Int J Rheum Dis, 2016. 19(2): p. 116-26.

In this image, you can see the diagnostic algorithm for TA by following the diagram from the “INDICATIONS FOR TESTING” box (at the top) to the bottom-left box for “Takayasu arteritis…”

Steroids

  • Corticosteroids
    • Glucocorticoids (such as prednisone) are usually used to suppress the systemic symptoms and arrest the progression of TA

Immunosuppressants

Immunosuppressants are often used in combination with steroids.

  • Methotrexate (MTX)
  • Azathioprine (AZA)
  • Mycophenolatemofetil (MMF)
  • Cyclophosphamide (CYC)
  • Monoclonal anti-TNF agents

Surgery

If the disease has persisted and caused vascular damage leading to cerebral, coronary, renal, visceral, and limb ischemia of an organ, surgery may be necessary.

  • Percutaneous transluminal angioplasty (PTA) with stenting along with therapy to alleviate the affected organ ischemia. This treatment is avoided in the active stage of the disease activity.
  • Bypass surgery
  • Balloon dilatation
  • Unilateral nephrectomy

Biological Therapy

  • TNF Agents
  • Infliximab
  • Etanercept
  • Adalimumab

Patients that do not respond to steroids or immunosupressants can be treated with biological therapies. Biological therapies have been used in adult patient populations, and in some cases, have shown a remission rate of 70-90% (Clifford & Hoffman, 2014). It should be noted that these methods of treatment are new and have not been extensively used in children to this date.

The systemic and vascular features of the disease should both be measured / monitored to understand the progression of the disease.

Outcome measures used include:

  • Disease-extent index (DEI.Tak)
    • Survey that is administered to monitor TA activity after diagnosis.It accounts for only clinical findings, (not imaging or biomarkers). It consists of 59 items assessing 11 domains including: systemic, cutaneous, mucous membranes, eyes, ENT (ear, nose, and throat), chest, abdomen, renal, nervous system, genitourinary, and cardiovascular domains.
  • Indian Takayasu Clinical Activity Score (ITAS2010)
    • Derived from DEI.Tak, ITAS2010 is used in monitoring disease activity. This test considers clinical manifestations as well as acute phase reactants such as ESR and CRP. The test contains 44 items, 33 of which focus on the cardiovascular system. Seven key items can be scored out of 2 while the rest can be scored out of 1. Higher scores are correlated with disease activity.
  • Takayasu Arteritis Damage Score (TADS)
    • Captures extent of damage caused by TA. There are 42 items for seven systems.

Physicians can also use our online Disease Activity Calculator to enter active items, determine the activity score, and print this form to add to the patient’s medical chart.

Source: Ozen S, Duzova A, Bakkaloglu A, Bilginer Y, Cil BE, Demircin M, Davin JC, Bakkalog M. Takayasu Arteritis in Children: Preliminary Experience with Cyclophosphamide Induction and Corticosteroids Followed by Methotrexate. J Pediatr, 2007. 150(1): p. 72-6.

There is currently no one superior agent used to treat childhood TA. However, individual centres have provided treatment protocols with a high success rate.

In one study[1], 6 patients between the ages of 12 to 17 years were treated using the following:

1.       If the disease was on only one side of the diaphragm with no pulmonary disease Oral steroids and oral MTX (12.5mg/m2/week)
2.       If the disease was more widespread Oral steroids and oral CYC (1.5-1.7 mg/kg/day) for a total of 12 weeks (max total dose of 150mg/kg) followed by oral MTX as above (12.5mg/m2/week) for 12 to 18 months
3.       Life threatening disease Pulse methylprednisolone given for 3 consecutive days
4.       In patients whose APRs were normal Oral prednisone started at 1 mg/kg/day for 4 weeks tapered to a maintenance dosage of 5 to 10 mg/day by 12 weeks.

In the last visit of this study, 5 patients were all found to be symptom-free. During the course of this study, one patient died and one patient had a relapse stenosis of the graft after one year (though found symptom-free later).  All patients were still on low-dose alternate-day corticosteroids as of June 1, 2006.

Figure 3: Flowchart outlining the treatment protocol of Takayasu arteritis


Hunter GG. Treatment of Takayasu arteritis. UpToDate: http://www.uptodate.com/contents/treatment-of-takayasu-arteritis?source=see_link. Accessed July 7, 2016.

Forsey J, Dhandayuthapani G, Hamilton MCK, Martin RP, Tizard EJ, Ramanan AV. Takayasu arteritis: key clinical factors for early diagnosis. Arch Dis Child, 2011. 96(5): p. 176-82.

Ozen S, Duzova A, Bakkaloglu A, Bilginer Y, Cil BE, Demircin M, Davin JC, Bakkalog M. Takayasu Arteritis in Children: Preliminary Experience with Cyclophosphamide Induction and Corticosteroids Followed by Methotrexate. J Pediatr, 2007. 150(1): p. 72-6.

Ashish JM, Ruchika G, Sathish K, Debashish D. Childhood-onset Takayasu arteritis: an update. Int J Rheum Dis, 2016. 19(2): p. 116-26.


Sources: Khanna NN, Rao S. Takayasu arteritis – Brief review. Journal of Indian College of Cardiology, 2016. 6(1): p. 147-52.
Maksimowicz-McKinnon K, Clark TM, Hoffman GS. Limitations of Therapy and a Guarded Prognosis in an American Cohort of Takayasu Arteritis Patients. Arthritis Rheum, 2007. 56(3): p. 1000-9.