- Takayasu Arteritis is an idiopathic inflammatory disease that causes inflammation and narrowing of the large arteries, mainly the aorta and its branches. - Early diagnosis is difficult due to nonspecific initial symptoms. Management is challenging due to the lack of reliable disease activity markers and low levels of evidence regarding treatment. - High-dose corticosteroids are effective for inducing remission but relapses often occur upon tapering. Additional immunosuppressants are usually needed to sustain remission and prevent disease progression and damage.

1. Takayasu Arteritis
A COMPREHENSIVE REVIEW

2. Definition
idiopathic inflammatory disease of the
large elastic arteries
young
occlusive or ectatic changes mainly in the
aorta and its immediate branches
(aortic arch syndrome) as well as the
pulmonary artery and its branches.

3. Why management of TA is not easy???
• early diagnosis is difficult
• lack of standard and reliable parameters reflecting
disease activity
• Low level of evidence.

4. Synonyms
• Takayasu’s Arteritis
• Aortoarteritis
• Pulseless Disease
• Young female Arteritis
• Occlusive thromboaortopathy
• Aortic arch syndrome

5. Pathology and pathogenesis
• medium- and large-sized arteries
• strong predilection for the aortic arch and its branches; the
pulmonary artery
• more marked at their origin than distally.
• panarteritis with inflammatory mononuclear cell infiltrates
and occasionally giant cells.
• marked intimal proliferation and fibrosis, scarring and
vascularization of the media, and disruption and
degeneration of the elastic lamina.
• Narrowing of the lumen occurs with or without thrombosis.
• vasa vasorum are frequently involved.
• compromise of blood flow through the involved vessels.

6. Pathology - Lesions in the AORTA
• Localised involvement of a segment of Aorta varying in size 2-7 cms.
• Multiple short segments with normal “skipped areas” in between.
• Diffuse involvement of large portion of aorta with a stretch of normal
aorta in between.
• Proximally,lesion may start at aortic valve
Distribution of lesion in the Aorta
Localized: 37.5% - Adults:- Abdominal Aorta
Children:-Thoracic+Abdominal
Diffuse: 62.5% -thoraco-abdominal
Descending thoracic Aorta is maximally affected area
Aortic Arch: Distal involvement more than proximal.
Dilatation of Ascending Aorta seen in portion proximal to obstructive
lesion.
Aneurysm may occur without any obstructive lesion.

7. FOUR Types of luminal changes:
1.Irregular lumen
2.Ectasia
3.Obstructive lesion-”stenosis” (hallmark
of disease)
4.Aneurysms-saccular & fusiform

8. Relative involvement of branch arteries: (%)(Panja et al)
ARTERY %
RENAL 63.75
LEFT SUBCLAVIAN 40
SUPERIOR MESENTRIC 16.75
CORONARY 16.75
RIGHT SUBCLAVIAN 13.75
RT.CCA 11.25
LT.CCA 7.5
INNOMINATE 7.5
COELIAC 3.75
Commenest lesion in branches is ostial stenosis.
BL Renal A Stenosis > UL (2.5 times)

9. Frequency of Arteriographic Abnormalities and
Potential Clinical Manifestations of Arterial
Involvement in Takayasu's Arteritis
Kerr, G. S. et. al. Ann Intern Med 1994;120:919-929

10. DIAGNOSTIC CRITERIA
• ISHIKAWA CRITERIA (1988)
• ACR CRITERIA (1990)
• SURI & SHARMA et. al CRITERIA (1995)

11. Diagnostic Criteria ISHIKAWA’S
• Obligatory:
Age< 40yrs ; at the time of diagnosis, at onset of characteristic
symptoms & signs of 1 month duration
• Major :
– Left Mid Subclavian Artery Lesion
– Right Mid Subclavian Artery Lesion
*Most severe obstruction occurs in mid portion 1cm
proximal to lt vertebral to 3cm distal

12. MINOR CRITERIA
 High ESR :
unexplained high ESR > 20mm at diagnosis or presence of evidence
in history.
 CAROTID ARETRY TENDERNESS :
unilateral or bilateral tenderness on carotid palpation.
 HYPERTENSION :
persistent BP brachial > 140/90 or popliteal >160/90 at age < 40 yrs
or history at age <40 yrs
 AR or annuloaortic ectasia :
by auscultation or doppler echo or angiography
 Pulmonary artery lesion :
lobar or segmental artery occlusion or equivalent (by angio or
perfusion scintigraphy )or stenosis, aneurysm, luminal irregularity or
any combination in pulmonary trunk or in unilateral or bilateral
pulmonary arteries.

13.  Left mid common carotid lesion :
presence of most severe occlusion in mid portion of 5cm in
length from the point 2cm distal to its orifice determined by
angiography
 Distal brachiocephalic lesion :
presence of severe stenosis or occlusion in distal third in
angiography
 Descending thoracic aorta lesion :
narrowing dilatation , aneurysm or luminal irruegularity or any
combination determined by angiography . Tortuosity alone is
unacceptable
 Abdominal aorta lesion :
narrowing dilatation , aneurysm or luminal irruegularity or any
combination and absence of lesion in aortoiliac region consisting
of 2cm of terminal aorta and bilateral common iliac arteries
determined by angiography . Tortuosity alone is unacceptable

14. Obligatory criteria
+
2 Major criteria
or
1 Major and ≥ 2 Minor criteria
or
≥4 Minor criteria
High probability of Takayasu’s disease
( sensitivity:84%)

15. American College Of Rheumatology (ACR)criteria
• Age at disease onset ≤ 40 yrs
• Claudication of extremities.
•  Brachial Artery pulse
• Systolic BP difference of > 10 mm Hg between arms
• Bruit over Subclavian Artery or Aorta.
• Aortogram abnormality.
≥ 3 criteria — TA
( sensitivity 90.5%, specificity 97.8%)

16. Suri & Sharma et. al Criteria (PGI)
 Removal of the obligatory criteria of age less than 40
years.
Inclusion of characteristic signs and symptoms as a
major criteria.
 Removal of age in defining hypertension.
Deletion of the absence of aorto-iliac lesion, in defining
abdominal aortic lesion and.
 An addition of coronary artery lesion in absence of risk
factors.

17. three major criteria:
• left and right mid subclavian artery lesions
• characteristic signs and symptoms of at least one month
duration and
• Ten minor criteria:
– High ESR
– HTN
– Carotid artery tenderness
– AR or Annuloaortic ectasia
– Left mid CCA lesion
– Distal brachiocephalic trunk lesion
– Descending thoracic aorta lesion
– Abdominal aorta lesion
– Coronary artery lesion.
– PA lesion
two major or one major and two minor criteria or four
minor criteria

18. • Sensitivity of 92.5% and specificity of 95% that was
higher
• Adoption of these criteria is expected to prevent the
possibility of an under diagnosis of TA.

19. Clinical Features
Disease Basically evolves through 
1. Early Pre-pulseless (50%): Active phase
Nonspecific symptoms & signs: Fever, Wt
loss, Fatigue, Headache, Arthralgias,
Splenomegaly, LNpathy etc.
- challenge in the early diagnosis
2. Pulseless Phase (Ischemic): (sequel of
occlusion of arch of aorta)
HTN,  / No Pulse, Bruit,, HF, Abnormal Fundi.

20. Frequency of Arteriographic Abnormalities and
Potential Clinical Manifestations of Arterial
Involvement in Takayasu's Arteritis
Kerr, G. S. et. al. Ann Intern Med 1994;120:919-929

21. Kerr, G. S. et. al. Ann Intern Med 1994;120:919-929
Frequency of clinical features of Takayasu arteritis at presentation and during
the course of disease

22. Evaluation Of Takayasu’s Arteritis
• Hematology:
Mild Anaemia
Leucocytosis
• Markers of disease activity :
E S R >40mm
50% cases progress with N ESR
C R P
ASO titre – increased in 50% cases but not correlated with activity
RA factor, ANA, fibrinogen , p-ANCA
• CXR: Aortic knob widening
Thoracic Aorta irregularity
 Pulm. Vascularity
Aortic calcification
Cardiomegaly.
Notching of upper ribs  prox. Subclavian block
lower ribs Abd. Aortic stenosis
• X-ray Abdomen: Abd. Aorta calcification.
• Echocardiogram
• fundus

23. OCULAR :
• Amaurosis fugax
• Hypertensive retinopathy [keith-wagner]
arteriolar narrowing, av crossing changes
silver wiring, exudates, papilloedema.
• Ischemic retinopathy [ Uyama and Asayama]
Stage 1 : dilatation of small vessels
stage 2 : micro aneurysm formation
stage 3 : wreath like AV anastamosis
formation surrounding optic
papillae
stage 4 : cataract ,secondary glacoma ,rubeosis,
neo vascularisation, proliferative
retinopathy, vitreous hemorrhage.

24. Histologic Findings
• early stage
• continuous or patchy granulomatous inflammatory reaction involving macrophages,
lymphocytes, and multinucleated giant cells.
• Inflammation initially occurs in the vasa vasorum  artery wall becomes irregularly
thickened and the lumen becoming narrowed.
• sclerotic stage=intimal and adventitial fibrosis and scarring of the media.
• initially inflammatory and later become occlusive.
• Inflammatory cells—pCD4 and CD8 lymphocytes, macrophages, plasma cells,
histiocytes, and giant cells—invade the adventitia and media but not the intima.

25. HOW TO ASSESS DISEASE ACTIVITY??

26. Kerr, G. S. et. al. Ann Intern Med 1994;120:919-929
Criteria for Active Disease in Patients with
Takayasu Arteritis*

27. • Systemic inflammatory response does not always show a
positive correlation with inflammatory activity in the vessel
wall.
• may be active despite a normal ESR and serum CRP level,
and vice versa
• apparent clinical and laboratory remission, arterial
specimens may show histological signs of vasculitis
• absence of systemic clinical features does not exclude
ongoing vascular inflammation nor does the presence of
ischemic symptoms always suggest active inflammation.
• 44% of clinically inactive patients were found to have
active vasculitis when tissue samples were taken from
vessels at surgery performed for obstructive lesions.
Hoffman GS. Takayasu arteritis: lessons from the American National
Institutes of Health experience. Int J Cardiol 1996; 54

28. Imaging – Conventional angiography
– Gold standards =anatomy
– Serial evaluation =progression
• Limitations
– Inability to evaluate arterial wall changes, so may
not detect activity early
33

29. • NON-INVASIVE MODALITIES
– MRA
– colour Doppler ultrasound (CDU),
– CTA
– PET SCAN
• characteristic, homogeneously thickened vessel walls
and luminal changes
• early inflammatory signs (vessel wall thickening and
mural inflammation)
• late complications (stenosis and aneurysms).
•

30. NON INVASIVE MODALITIES
• monitoring disease activity and response to
treatment in TA.
• Increased vessel wall thickness, vessel wall oedema
and mural contrast enhancement =active disease
• Vessel wall oedema, mural contrast enhancement or
18F-FDG uptake = decrease with successful
immunosuppression.
• decrease in wall thickness =controlled
• presence or progression of aortic regurgitation or left
ventricular hypertrophy

31. Imaging – MR angiogram
– Mural thickening
– Luminal changes
– Aneurysmal dilation
• Delayed contrast enhanced
MRI -arterial wall
inflammation
36

32. CMC Vellore study
• Aortic wall thickness > 4mm was sensivite
– Over sensitive
– no clear correlation of vessel edema with disease
activity or progression*
*Tso E. Arthritis Rheum 2002;46:1634–42
37

33. High-resolution Doppler ultrasound
38
Activity common carotid arterial
wall thickness
vessel diameter
Active lesions 2.5–5.0mm 10mm
Inactive lesions 1.1–2.0mm <7mm
Good for common carotids and vertebral arteries
Cantu C. Stroke 2000;31:2197–202

34. circulating levels of MMP-2 =diagnosing TA
MMP-3 and MMP-9 =disease activity markers
.
Matrix Metalloproteinases as Novel Disease Markers in Takayasu
Arteritis

35. Potential Biomarkers
• Pentraxin-3
• MMP-9
• IL-18
41

36. ITAS2010 –
IndianTaka
yasu’s
Arteritis
Activity
Score
Tick Box only if abnormality
is present and new or worse
within the past 3/12.
Tick box only if abnormality
is ascribed to current, active
vasculitis

37. MANAGEMENT

38. Supportive measures
• Diet, low salt intake, calcium, vitamin D corection
and regular exercise
• Monitoring and control of blood pressure
– BP measurements should be made in the
unaffected extremities
– In treatment-resistant HTN, the possibility of
reno-vascular HTN should be considered

39. • Atherosclerosis risk is increased
• Antiplatelet agents have a protective effect against
ischemic events

40. Atherosclerosis risk is increased
• intima of affected blood vessels becomes activated,
leading to endothelial cell activation and damage, and an
ensuing immune response—factors that can all promote
atherosclerosis.
• endothelial cells can expose adhesion molecules and
secrete cytokines
• increase in secretion of mediators of inflammation
promotes enhanced adhesion between the endothelial
cells and monocytes,
• proatherogenic substrate by promoting plaque formation.

41. Atherosclerosis risk is increased in TA
• vasculitis might also promote increased expression of
autoantigens (such as heat shock proteins) on
activated endothelial cells
• accumulation of oxLDL can promote activation of
endothelial cells, monocytes, and macrophages, as
well as formation of foam cells.
• generalized endothelial dysfunction characterized by
impaired endothelium-dependent vasodilatation.

42. IMMUNOSUPPRESSION

43. Outline
– Efficacy of steroids
– Efficacy of additional Immunosuppressant
– Biological agents
49

44. Treat to target
• Inducing stable disease state
• Sustaining stable disease
• Prevent progression of damage
• Attain regression of disease
50

45. • active disease=high-dose (1 mg/kg/day) prednisolone
or its equivalents.
• Favourable
• relapses may occur while gradually tapering
• adverse effects of long-term treatment
STEROIDS

46. 100% improvement in aorto-arteritis associated
myocarditis with immunosuppression
on prednisolone & CYC
At 12, 24, 52 weeks
52
Clinical Improvement 100%
ESR drop 48 +/- 12 mm/1st h to 31 +/- 12 mm/1st h,
p < 0.05
Resolution of EM biopsy changes 100%
Arterial lesions static, no new lesions
Talwar KK etal. Int J Cardiol. 1993 Apr;39(1):79-84

47. Treatment with glucocorticoids- an independent
predictor for remission
• Independent predictors for Remission
– Low ESR at diagnosis &
– Treatment with glucocorticoids
Park MC etal. Scand J Rheumatol. 2005 Jul-Aug;34(4):284-92
53

48. Data from recent studies
54
Remission with additional IS 93% (28/30)
Remission with steroid monotherapy 20 % (6/30)
Sustained remission (≥6 months on
<10mg/kg)
28% (8/28)
Sustained remission till last follow up 18% (5/28)
Persistent active disease 2
No. of relapses correlated with likelihood of disability (p< 0.0001)
Maksimowicz-Mc Kinnon etal. A& R 2007; 56 (3); 1000-1009 (Cleveland Clinics)

49. Steroids in pediatric TA(CMC Vellore)
• Relapse in 15 children at a median duration of 16.5 (9.5- 47 months)
55
Steroids with 2nd line agents 34 (85%)
Remission 30/ 34
Sustained remission till last follow up 15/ 34
Persistent active disease 4
Goel R, Kumar TS, Danda D, Joseph G, Bacon P, Jayaseelan V [unpublished data]
Higher disease progression was observed in patients with persistent active/ relapsing disease

50. 56
Treatment of Glucocorticoid-resistant or relapsing Takayasu Arteritis with Methotrexate
Gary S. Hoffman etal. Arthritis & Rheumatism 1994;37(4) : 578-582
Methotrexate
: sustained remission for 18 months in 50%
patients

51. Steroids with Azathioprine : arrested disease progression in 100%
• N= 65 new patients (1996 -2001)
• 15 had active disease, treated with azathioprine + prednisolone
• At 3 months :
– Clinical improvement : 100%
• At 1 year:
– Clinical Improvement sustained
– Angiogram showed no progression / new lesions in any patient
57
Valsakumar AK, Valappil UC, Jorapur V, Garg N, Nityanand S, Sinha N . J Rheumatol. 2003;30(8):1793-8

52. Mycophenolate & Azathioprine probably better than
Methotrexate (Indirect evidence)
58
0
5
10
15
20
25
30
35
40
45
MTX sustained
remission
improvement
43
28
CCF cohort (MTX based)
No.ofpatients(%)
Maksimowicz-Mc Kinnon etal. A& R 2007; 56 (3); 1000-1009

53. Mycophenolate & Azathioprine probably better than
Methotrexate (Indirect evidence)
59
0
10
20
30
40
50
60
70
80
90
100
NO OF PTS sustained
remission
improvement
43
28
23
100 100
Methotrexate based
Azathioprine based
No.ofpatients(%)
Maksimowicz-Mc Kinnon etal. A& R 2007; 56 (3); 1000-1009
Valsakumar AK etal. J Rheumatol. 2003;30(8):1793-8

54. Mycophenolate & Azathioprine probably better than
Methotrexate (Indirect evidence)
60
0
10
20
30
40
50
60
70
80
90
100
Mtx/Aza/ MMf
used
sustained
remission
improvement
43
28
23
100 100
19
50
15
96
methotrexate based*
azathioprine based ** (n= 15/65) at 1yr
follow up
mycophenolate based$ (n=19/40)
Adult TA (MMf)% (n=21/21)
No.ofpatients(%)
Maksimowicz-Mc Kinnon etal. A& R 2007; 56 (3); 1000-1009
Valsakumar AK etal. J Rheumatol. 2003;30(8):1793-8
Goel R, Kumar TS, Danda D, Joseph G, Jayaseelan V. [unpublished]
Goel R, Danda D, Mathew J, Edwin N. Clin Rheumatol (2010) 29:329–332

55. TURKISH TA STUDY GROUP DEFINITION OF
REFRACTORY DISEASE IN TA
• A
Saruhan-Direskeneli G, Hughes T, Aksu K, et al. Identification of multiple genetic
susceptibility loci in Takayasu arteritis. Am J Hum Genet. 2013;93:298-305.
Biologic agents IS THE SOLUTION

56. TNF alpha blocker : works in refractory cases
• 10 pts had a durable response
• Median duration in remission was 26 months
(range : 3 months to 6 yrs)
• 6 pts had achieved sustained remission without requiring
glucocorticoids
Hoffman GS et al. Arthritis & Rheumatism 2004;50: 2296-304
63

57. TNF alpha blocker : works in refractory cases
– complete remission in 37%
– partial remission in 53.5%
– Non responders 9.5%
C Comarmond. Autoimmunity Reviews, vol. 11, no. 9, pp. 678–684, 2012
64

58. Tocilizumab (anti IL-6)
65
Response No. of patients (n= 10)
Sustained remission (during 6 doses) 6
Reduction in steroids to <10mg/day 7
Sustained remission post TCZ withdrawal 2
Major adverse events 0
Mean steroid dose reduction : 24 ± 15 to 5.4 ± 4.9 mg/day
Goel R, Danda D, Kumar S, Joseph G. Int J Rheum Dis. 2013 Dec;16(6):754–61

61. ENDOVASCULAR AND SURGICAL
INTERVENTIONS

62. NO INTERVENTION IN ACTIVE DISEASE
Surgery Endovascular interventions
Balloon angioplasty
Stent
Stent graft replacement
Should be tried only after inflammation in the vessel wall has been controlled
Post-interventional Immunosuppression is also recommended
Park MC, Lee SW, Park YB et al. Postinterventional immunosuppressivetreatment and vascular
restenosis in Takayasu’sarteritis. Rheumatology 2006;45: 6005.

63. Critical Arterial Stenosis
Short-segment
Balloon angioplasty
or
Stent graft replacement
Long-segment stenosis
with extensive peri-arterial
fibrosis or occlusion
Surgical bypass of the affected
segment

64. Advantages and Disadavantages of Endovascular
Procedures
Percutaneous Transluminal Angioplasty Stent GRAFTS
Less invasive and safe More invasive
Cheaper Costlier
Restenosis rate ̴ 77.3% Restenosis rate ̴17%
Less Cost Effective More Cost effective

65. Anti-platelet Agents
Decreases restenosis
Visona` A, Tonello D, Zalunardo B et al. Antithrombotic treatment before and after
peripheral artery percutaneous angioplasty. Blood Transfus 2009;7:1823.

66. Indications for surgery in TA
• Critical cerebrovascular ischemia
• Coronary artery ischemia
• Extremity claudication
• Severe renal artery stenosis
• Progressive aneurysm enlargement with a tendency
for dissection or rupture
• Severe AR and aortic coarctation
Giordano JM. Surgical treatment of Takayasu’s arteritis.
Int J Cardiol 2000;75(Suppl 1):S1238.

67.  Complications
• Stroke
• Intracranial haemorrhage
• Seizures
• Graft stenosis and/or occlusion
• Ischemia
• Organ failure
• Complications of hypertension
• Foetal injury
• Valvular heart disease
• Retinopathy
• Renovascular hypertension
• Long-term use of corticosteroids: infection, adrenal suppression, cataracts,
hyperglycemia, hypertension (which complicates blood pressure control), osteoporosis,
and aseptic necrosis.

68.  Morbidity and mortality
• 10-year survival rate =90%.
• Rate is reduced in =major complications.
• 5- and 10-year survival rates =69% and 36%, respectively, in patients with 2 or
more complications.
• 5- and 10-year survival rates associated with 1 or fewer complications = 100% and
96%, respectively.
• Most common causes of death= CCF/CVA/MI/ANEURYSMAL RUPTURE/RENAL
FAILURE
Disease remission is the only factor that positively influences physical and mental
quality of life.