Takayasu arteritis

Takayasu Arteritis
A COMPREHENSIVE REVIEW

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

Scheme of presentation
• Brief review of epidemiology and pathophysiology
• Diagnosis of disease / activity status
• Medical treatment
• Surgical/interventional management

By the end of presentation we should be able to
decide?
• What investigations and when?
• What treatment and when?
• And most importantly WHAT NOT????

Ques1 ???? 1 month back we had a patient
• 19 years male presented with CCF
• RSOV aneurysm + erosion into the IVS+ severe LV
dysfunction
• We got him operated
• ESR CRP were high
• Hypertension + Carotidodynia +
• Left renal artery stenosis
• WAS IT TAKAYASU????
• DID WE MISS SOMETHING IN HIS DIAGNOSIS AND
TREATMENT?? CAUSE OF LV DYSFUNCTION??

Ques2 ???? 23 yrs female
• Fever +arthralgia +weight loss
• Angiography s/o aortoarteritis
• ESR CRP high
• Left renal stenosis-critical
• HOW TO TREAT????
• Steroids??? For how long???how to taper???alone or
in combination???
• What to do for RAS??

Ques3 ???? 23 yrs female
• Fever +arthralgia +weight loss NO
• Angiography s/o aortoarteritis
• ESR CRP high NO
• Left renal stenosis-critical
• HOW TO TREAT????
• Steroids??? For how long???how to taper???alone or
in combination???
• What to do for RAS??

QUES4?? ANGIOPLASTY IN A STENOTIC LESION
• DOES THE TYPE OF LESION AFFECT THE STRATEGY?
• WHICH IS BETTER POBA VS STENTING VS COVERED
STENT????
• SURGERY VERSUS PERCUTANEOUS INTERVENTION??

Why management of TA is not easy???
• First, early diagnosis is difficult and requires clinical
awareness and suspicion.
• lack of standard and reliable parameters reflecting
disease activity. (Second, and even more important)
• Low level of evidence.
• Current evidence reflects the results of open studies,
case series and expert opinion
• Rare disease/ lack of ideal outcome measures

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

Epidemiology
• Worldwide incidence: 2.6 cases per million per year.
• More frequent in Asian countries - Japan, Korea, China, India, Thailand, Singapore and Turkey.
• Japanese patients with Takayasu arteritis  higher incidence of aortic arch involvement.
• In contrast, series from India report higher incidences of abdominal/renal involvement.
Age:
• Predominantly a disease of young females: 2nd or 3rd decades.(less<40 :obligatory criteria)
• Mean age:
– European study - 41yrs
– Japan - 29yrs
– India – 24yrs
Sex:
• F>M (~80% women)
• India – F : M = 1.6 : 1 ( panja et al 6.4:1)

Pathology and pathogenesis
• The disease involves medium- and large-sized arteries, with
a strong predilection for the aortic arch and its branches;
the pulmonary artery may also be involved.
• The involvement of the major branches of the aorta is much
more marked at their origin than distally.
• The disease is a panarteritis with inflammatory
mononuclear cell infiltrates and occasionally giant cells.
There are 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. The vasa
vasorum are frequently involved. Pathologic changes in
various organs reflect the compromise of blood flow
through the involved vessels.

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.

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

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)

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

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

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

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.

 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

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

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%)

Suri & Sharma et. al Criteria (PGI)
The proposed modifications include:
 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.

The criteria proposed consists of three major criteria:
• left and right mid subclavian artery lesions and
• characteristic signs and symptoms of at least one month
duration and
• Ten minor criteria:
– High ESR
– Hypertension
– Carotid artery tenderness
– Aortic regurgitation or Annuloaortic ectasia
– Left mid common carotid lesion
– Distal brachiocephalic trunk lesion
– Descending thoracic aorta lesion
– Abdominal aorta lesion
– Coronary artery lesion.
– Pulmonary artery lesion
Presence of two major or one major and two minor
criteria or four minor criteria suggests a high
probability of TA

• Sensitivity of 92.5% and specificity of 95% that was
higher than that of Ishikawa's criteria (sensitivity
60.4%, specificity 95%) and American college of
Rheumatology criteria (sensitivity 77.4%, specificity
95%).
• Similarly, this criteria had a 96% sensitivity and
specificity when applied to 79 Japanese patients of
TA and 79 control subjects.
• Adoption of these criteria is expected to prevent the
possibility of an under diagnosis of TA.

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.

Frequency of clinical features of Takayasu arteritis at presentation and during
the course of disease

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

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.

Histologic Findings
• The 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.
• Takayasu arteritis progresses to a sclerotic stage, with intimal and adventitial fibrosis
and scarring of the media.
• Lesions are initially inflammatory and later become occlusive.
• Inflammatory cells—predominantly CD4 and CD8 lymphocytes, macrophages, plasma
cells, histiocytes, and giant cells—invade the adventitia and media but not the intima.

HOW TO ASSESS DISEASE ACTIVITY??

Criteria for Active Disease in Patients with
Takayasu Arteritis*

• Systemic inflammatory response does not always show a
positive correlation with inflammatory activity in the vessel
wall.
• Therefore TA may be active despite a normal ESR and
serum CRP level, and vice versa. In patients with apparent
clinical and laboratory remission, arterial specimens may
show histological signs of vasculitis
• The absence of systemic clinical features does not exclude
ongoing vascular inflammation nor does the presence of
ischemic symptoms always suggest active inflammation.
• As many as 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
Absence of constitutional symptoms and
normal ESR/CRP , does not rule out
active disease

Imaging – Conventional angiography
• Advantage:
– Gold standards for determining anatomy
– Serial evaluation good indicator of progression
• Limitations
– Invasive
– Contrast required
– Inability to evaluate arterial wall changes, so may not
detect activity early
41

• NON-INVASIVE MODALITIES
– magnetic resonance angiography (MRA),
– colour Doppler ultrasound (CDU),
– computerized tomography angiography (CTA)
– PET SCAN
• can visualize the characteristic, homogeneously
thickened vessel walls and luminal changes of large
arteries.
• can demonstrate early inflammatory signs (vessel wall
thickening and mural inflammation) as well as late
complications (stenosis and aneurysms).
•

NON INVASIVE MODALITIES
• Non-invasive imaging methods are essential for monitoring
disease activity and response to treatment in TA.
• Increased vessel wall thickness, vessel wall oedema and mural
contrast enhancement are usually considered evidence of active
disease . Vessel wall oedema, mural contrast enhancement or
18F-FDG uptake may decrease with successful
immunosuppression.
• A decrease in wall thickness provides information about
whether the disease has been well controlled over months or
years. However, these findings are not always reliable .
• Using echocardiography, the heart should also be monitored
for the presence or progression of aortic regurgitation or left
ventricular hypertrophy due to hypertension in TA
Absence of constitutional symptoms and
normal ESR/CRP , does not rule out
active disease
So in such a scenario- go for
NONINVASIVE MODALITIES

Imaging – MR angiogram
• Non invasive
• Useful for detecting
– Mural thickening
– Luminal changes
– Aneurysmal dilation
• Delayed contrast enhanced
MRI esp useful for arterial
wall inflammation
44

Three dimensional MRA
• N= 30 TA patients
• Direct comparison of angiography and MRA
• 90% agreement in identification of normal &
abnormal vessels
Yamada I et al. J Magn Reson Imaging 2000;11:481–7
Kumar S et al. Eur Radiol 1997;7:44–50
45

CMC Vellore study
• Aortic wall thickness > 4mm was sensivite (90%)
• Limitations:
– Over sensitive
– Post endovascular stent procedure
– no clear correlation of vessel edema with disease
activity or progression*
*Tso E. Arthritis Rheum 2002;46:1634–42
46

High-resolution Doppler ultrasound
47
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
Non Invasive
Operator dependent
Correlates closely with angiography and MRA (> 95% agreement)*
Cantu C. Stroke 2000;31:2197–202

conclusions
• monitoring disease activity in TA may be accomplished
by the integrated use of non-invasive imaging
methods, patient symptoms, clinical findings and acute
phase reactants.
• There is no single imaging modality that can provide all
the information required and each method has distinct
and complementary roles in monitoring.
• The use of non-invasive procedures providing a good
overview of the involved vessels without radiation
exposure, such as MRA, is recommended if available

In conclusion, the present results suggest that monitoring of
circulating levels of MMP-2 as a helpful marker in diagnosing TA
and those of MMP-3 and MMP-9 as disease activity markers
might help provide adequate evaluation of treatment and guide
therapeutic decision making for individual patients with TA.
These measurements can be part of routine hospital laboratory
examinations that are easy to perform at low cost. Furthermore,
the noninvasive nature of such measurements is attractive,
because patients can be spared from invasive angiographic
examination.
Matrix Metalloproteinases as Novel Disease Markers in Takayasu
Arteritis

Potential Biomarkers
• Pentraxin-3
• MMP-9
• IL-18
51

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

General principles of Management
• Patient education
– Nature of Disease
– Disease Course
– Medical Management Options- First and Second
lines
– Side effects and Compliance
– Surgical Management

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
– If unreliable measurements, presence of
hypertensive retinopathy may be a warning sign
– In treatment-resistant HTN, the possibility of
reno-vascular HTN should be considered

• Atherosclerosis risk is increased in TA
• Antiplatelet agents have a protective effect against
ischemic events in TA (hazard ratio =0.055, 95% confidence
interval: 0.06-0.514; P=0.011)
Seyahi E, Ugurlu S, Cumali R et al. Atherosclerosis in Takayasu arteritis. Ann Rheum
Dis 2006;65:12027.
de Souza AWS, Machado NP, Pereira VM et al. Antiplatelet therapy for the prevention of
arterial ischemic events in Takayasu arteritis. Circ J 2010;74: 123641.

Atherosclerosis risk is increased in TA
• Systemic vasculitides, such as giant cell arteritis, Takayasu
arteritis, polyarteritis nodosa, and anti-neutrophil cytoplasmic
antibody (ANCA)-associated vasculitis, are immune-mediated
rheumatological diseases characterized by inflammation of the
vasculature that results in accelerated atherosclerosis.
• In patients with vasculitis, the 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.
• After activation, endothelial cells can expose adhesion
molecules and secrete cytokines. This increase in secretion of
mediators of inflammation promotes enhanced adhesion
between the endothelial cells and monocytes, and serves as a
proatherogenic substrate by promoting plaque formation.

Atherosclerosis risk is increased in TA
• In addition to inflammatory reactions that can lead to
atherosclerosis, vasculitis might also promote
increased expression of autoantigens (such as heat
shock proteins) on activated endothelial cells.
Furthermore, accumulation of oxLDL can promote
activation of endothelial cells, monocytes, and
macrophages, as well as formation of foam cells.
• Importantly, patients with vasculitis have generalized
endothelial dysfunction characterized by impaired
endothelium-dependent vasodilatation.

Antiplatelets in takayasu arteritis
• Similar to other inflammatory diseases, atherosclerosis risk is
also increased in TA, and preventive measures should be
considered .
• There are some basic studies favouring the use of antiplatelet
agents in TA.
• In the limb affected by arterial stenosis, more platelet
aggregation and higher levels of thromboxane were reported,
and these findings were shown to improve after 80 mg/ day
aspirin treatment.
• A recent retrospective observational study suggested that
antiplatelet therapy was associated with a lower frequency of
ischaemic events in patients with TA .
• However, the relative efficacy of this treatment between
different angiographic stages of TA is not known .

Anti-platelet Agents
To decrease the occurrence of restenosis, antiplatelet
treatment should be used before and after
endovascular interventions in TA
Visona` A, Tonello D, Zalunardo B et al. Antithrombotic treatment before and after
peripheral artery percutaneous angioplasty. Blood Transfus 2009;7:1823.
STRICT CONTROL of dyslipidemia, hypertension, and lifestyle factors that
increase the risk of cardiovascular disease. These complications are the major
cause of death in Takayasu arteritis.

Outline
Evidence for
– Efficacy of steroids
– Efficacy of additional Immunosuppressant
– Biological agents
– Conclusion
62

Biological basis
Takayasu arteritis is a chronic relapsing autoimmune large vessel vasculitis
63
Schmidt J et al. Mayo Clin Proc. 2013;nn(n):1-9
No. of relapses correlates with likelihood of disability (p< 0.0001)
Maksimowicz-Mc Kinnon etal. A& R 2007; 56 (3); 1000-1009 (Cleveland Clinics)

Treat to target
• Inducing stable disease state
• Sustaining stable disease
• Prevent progression of damage
• Attain regression of disease
64

• In the presence of active disease, standard initial
treatment of TA is high-dose (1 mg/kg/day)
prednisolone or its equivalents.
• The response to high dose prednisolone is generally
favourable, but relapses may occur while gradually
tapering the dose and adverse effects of long-term
treatment can cause problems.
STEROIDS

Radial pulse became palpable in 5 patients with steroids
N= 84 Korean patients
Nakao et al. Circulation 1967; 35: 1141-1155
Steroids works in 62% of TA
66
The first data on efficacy of steroids in TA dates to 1967 when Nakao etal from Japan
showed fair to remarkable imrpovement in clinical status in 18/29 pts on steroids . In
fact they showed reversiblity of radial pulseloss in 5 of their pts with steriods

100% improvement in aorto-arteritis associated
myocarditis with immunosuppression
N= 13 non-specific aortoarteritis and myocarditis in EM biopsy
on prednisolone & CYC
At 12, 24, 52 weeks
70
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

No. 106
Steroids : 17
Remission: 5
Mortality : 17%
No. = 107
Steroids : 8
Remission : 1
Mortality : 15%
Lupi-Herrera E etal. Am Heart J 1977;93:94–103 Jain etal. Int J Cardiol 1996;54 Suppl:S111–6
Pre-steroid era
71

Success rate of steroids : 20% - 100%
No. 106
Steroids : 17
Remission: 5
Mortality : 17%
No. = 107
Steroids : 8
Remission : 1
Mortality : 15%
Kerr GS et al. Ann Surg 1987; 205: 157–166
Lupi-Herrera E etal. Am Heart J 1977;93:94–103
No. 60
Steroids : 28
Remission: 60%
Sustained Remission :40%
No response : 23%
Mortality : 3%
No. 118
Steroids : 78
Remission: 75%
Angio regression : 10%
Steroids stopped : 26%
Ishikawa K. Am J Cardiol 1991; 68: 410–413
Jain etal. Int J Cardiol 1996;54 Suppl:S111–6
72
POST STEROID ERA
THESE RESULTS MAKE STEROIDS THE FIRST LINE
IMMUNOSUPPRESSANTS IN TA

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
73

Outline
Evidence for
– Efficacy of additional Immunosuppressants
– Conclusion
74

Data from recent studies
• N= 75 ; 30 followed up 3 yrs (4 months-10 years)
• All patients who followed up were treated with steroids
• 73% required adjunctive immunosuppressive agents
75
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)

Steroids in pediatric TA(CMC Vellore)
• N= 40; follow up = 34 pts for 21.5 (IQR 8.7- 37.2)
• Relapse in 15 children at a median duration of 16.5 (9.5- 47 months)
• Median steroid dose at relapse – 5 (IQR -0-15)mg/day
76
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

78
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

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
79
Valsakumar AK, Valappil UC, Jorapur V, Garg N, Nityanand S, Sinha N . J Rheumatol. 2003;30(8):1793-8

Mycophenolate & Azathioprine probably better than
Methotrexate (Indirect evidence)
80
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

81
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(%)
Valsakumar AK etal. J Rheumatol. 2003;30(8):1793-8

82
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(%)
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

TURKISH TA STUDY GROUP DEFINITION OF
REFRACTORY DISEASE IN TA
• Angiographic or clinical progression despite treatment
• Presence of any of the following
– prednisolone dose >7.5 mg /day after 6 months of
treatment, despite administration of conventional
immunosuppresive agents
– need for new surgery due to persistent disease activity
– frequent flares (>3/year)
– death associated with disease activity
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

TNF alpha blocker : works in refractory cases
• N= 11 refractory pts with TA initiated on anti-TNF agents
• 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
85

TNF alpha blocker : works in refractory cases
• Recent review
• N= 84 treated with TNF-𝛼 antagonists
– 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
86

Tocilizumab (anti IL-6) as a stop gap measure
N= 10 active TA patients (disease duration 25.5 (1.5-60) months
87
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

Outline
Evidence for
– Efficacy of additional Immunosuppressants
– Conclusion
90

Summary-IMMUNOSUPPRESSANTS IN TA
•Inducing stable disease state √ (60%=93%)
•Sustaining stable disease √ (20-50%)
•Prevent progression of damage √ (upto 100%)
•Attain regression of disease +/- (few studies)
91

ENDOVASCULAR AND SURGICAL
INTERVENTIONS

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.

Biological inflammation at the time of vascular procedure independently associated with
procedure
Saadoun D et al. Circulation 2012;125:813-819
Copyright © American Heart Association
166 Vascular Procedures in 79 Patients With TA
100

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

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
Qureshi MA, Martin Z, Greenberg RK. Endovascular management of patients with
Takayasu arteritis: stents versus stent Grafts. Semin Vasc Surg 2011;24: 4452.

Anti-platelet Agents
To decrease the occurrence of restenosis, antiplatelet
treatment should be used before and after
endovascular interventions in TA
Visona` A, Tonello D, Zalunardo B et al. Antithrombotic treatment before and after
peripheral artery percutaneous angioplasty. Blood Transfus 2009;7:1823.

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 aortic regurgitation and aortic coarctation
Giordano JM. Surgical treatment of Takayasu’s arteritis.
Int J Cardiol 2000;75(Suppl 1):S1238.

Outcomes of 79 consecutive patients with TA who underwent 104 surgical and 62
endovascular procedures, the frequencies of complications were 37.5% and 50%,
respectively, after a follow-up of 6.5 years

Post interventional immunosuppressants

Prognosis
• Substantial morbidity and mortality.
• Approximately 20% of patients have a monophasic and self-limited disease.
• A National Institutes of Health (NIH) study of 60 patients with Takayasu arteritis:
– 20% of patients had a monophasic illness, self-limiting illness and therefore did not
require immunosuppressive treatment.
– Remaining 80% of patients, who did not have a monophasic illness and who
experienced 1 exacerbation, immunosuppressive therapy resulted in remission in 60%.
– Of these, one half experienced relapse after immunosuppressive therapy was stopped.

 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.

5 yr Survival And Event Free Survival rate

 Morbidity and mortality
• Overall 10-year survival rate is approximately 90%.
• Rate is reduced in the presence of major complications.
• 5- and 10-year survival rates are approximately 69% and 36%, respectively, in
patients with 2 or more complications.
• 5- and 10-year survival rates associated with 1 or fewer complications are 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.

Take home messages
 The diagnosis of TA should preferably be made before a
critical stenosis or occlusion occurs in the involved
arteries.=> HIGH INDEX OF SUSPICION WARRANTED FOR
THIS TO HAPPEN
 As acute phase responses are not always reliable, non-
invasive imaging methods are used to monitor disease
activity.=> MRA suitable for this
 As a rule, the information obtained from non-invasive
imaging methods should be integrated with patient
symptoms, clinical findings and acute phase reactants to
adjust the dose of IS agents and the duration of treatment.

Take home messages
 Biologics should be tried in treatment-resistant
Takayasu arteritis patients.
 Revascularization procedures may be performed
during the inactive phase of Takayasu arteritis.
 Low dose aspirin has been found to be protective
against ischemic events in TA patients
 Placebo-controlled,Large scale, randomized clinical
trials, are required to ascertain the treatment
strategies and outcome scores for this rare but
important disease entity

ROUTINE STENTS VS STENT GRAFTS

Takayasu arteritis

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