2. 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 as well as the
pulmonary artery and its branches.
4. History
• 1761- Morgagni- Reported first Case
• 1856- Savory - reported a case
• 1908- Takayasu, professor of ophthalmology -
21 yrs woman with characteristic fundal
arterio- venous anastomoses and absent
radial pulse
• 1921- SHIKARE- first case report in india
• 1951- Shimizu and Sano- Pulseless Disease
• 1962 & 1971 –Sen – Middle Aortic Syndrome
and association with TB in 101cases.
• 1993- Chappel Hill - Takayasu Arteritis as
granulomatous inflammations of Aorta
and its major branches.
5. EPIDEMIOLOGY
• Predominantly a disease of young females in their 2nd
or 3rd decades.
Less than 40 yrs – obligatory crtiteria
Childhood onset is not rare.
Mean age European study- 41yrs, Japan-29yrs
India –age of onset mean -24yrs, Age at Δ -28
yrs
• Sex: F>M
• Geographical variation : Japan - 8:1, Israel - 1.2:1,
Mexico - 5:1, India - 4 : 1 (recently,panja et al - 6.4:1)
• Geographical variation :Japan-proximal Aorta
(Aortic Site) SE Asia-
MiddleAorticsyndrome
North Europeans: patchy
.,assoc. RArthritis,SLE
• Incidence & prevalence : most commonly seen in
Japan, South East Asia, India, and Mexico.
Hospital based studies- 0.8 -2.6per million.
6. ETIOPATHOGENESIS
Genetic:
India HLA B5, B21 (kumar et al)
USA HLADR4, MB3
Japan HLADR2, MB1, Bw52, DW2, DQW1
HLA Bw52-IHD,AR,Pul involvement
HLA B39-Renal artery stenosis
Autoimmunity:
immune reaction against elastin
circulating gammaglobulins (alpha1& globulins,IgG,
IgA, IgM, CMI, ANA, Anti - Aorta Ab (AA), Anti -
endothelial cell Ab) , raised ESR, leucocytosis,
arthralgia and high titers of anti-aorta antibodies
Cell mediated immunity
7. Rheumatic :
(Upmark 1954) some pts had raised ASO titre
Female predilection :
Urinary estrogens elevated. Estradiol and
progesterone, but not testosterones, enhance
leucocyte adhesion to endothelial cells in the
presence of TNF.
?Infection:
hypersensitivity to Mycobacterium tuberculosis
8. Tuberculosis and TA
• Lupi-Herrera et al.
previous tuberculosis in 48% of Japanese patients
• Sen et al.
tuberculosis in 71% patients in India
• Pantell and Goodman 1961 to 1981
tuberculin test positive in 73.3% – 100% of cases
active tuberculosis in 0.26% – 4.2% of the cases.
• Heightened response to tubercular antigens especially
the 65 kDa HSP
• Tubercular aortitis lesions- discrete, aneurysm
formation, nonobstructive.
• Granulomas -caseating in nature in TB. In TA -
proliferative without caseation.
• No evidence for causation
• ?Viral etiology
9. 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
10. • Variable amount of adventitial or periadventitial
fibrous thickening over involved part of aorta.
• 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
11. 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.
Relative involvement of branch arteries: (%)(Panja et al)
Coronaries 16.75 Lt.CCA 7.5
Innominate 7.5 Coeliac A 3.75
Rt.SCA 13.75 Sup.Mesentric A 16.75
Lt.SCA 40 Renal A 63.75
Rt.CCA 11.25
Commenest lesion in branches is ostial stenosis.
BL Renal A Stenosis > UL(2.5 times)
12. VESSELS INVOLVED
Subclavian 93%
Common carotid 58%
Abdominal aorta 47%
Renal 38%
Aorticarch&root 35%
Vertebral 35%
Coeliac axis 18%
Superior mesentric 18%
Iliac 17%
Pulmonary 10%
Coronary <10% KERR ET AL
14. 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
15. 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.
16. Left mid comon 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
17. Obligatory criteria
+
2 Major criteria
or
1 Major and ≥ 2 Minor criteria
or
≥4 Minor criteria
High probability of Takayasu’s disease
( sensitivity:84%)
18. 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%)
19. 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.
20. 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
21. • 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.
22. Classification Proposed by Ueno et al,
modified by Lupi Herrera
• Type I - involvement of aortic arch and
its branches (16%)
• Type II -Thoraco abdominal aorta,but
spares arch (8%)
• Type III-Features of I &II (76%)
• Type IV-Pulmonary artery involvement
(Lupi herrera et al) (36%)
• Type V-Coronary artery involvement
(Panja et al) (10%)
23.
24. 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.
Clinical Features
25. Early phase
Non specific systemic symptoms :
fever, loss of weight, head ache, fatigue, gen
weakness, night sweats, anoreia, arthralgia, skin
rash, splenomegaly, cervical lymphadenopathy,
pleurisy, myocarditis, pericarditis, CVA.
Lab abnormalities :
↑ESR, mild leukocytosis, anemia, CRP, IGs, RA factor,
ANF, ANCA, mild proteinuria, albuminuria.
26. Kerr, G. S. et. al. Ann Intern Med 1994;120:919-929
Criteria for Active Disease in Patients with
Takayasu Arteritis*
28. Hypertension
– 33–83% of patients, more among Indians
– renal artery stenosis in 28–75%
Aortic regurgitation -20-24%
– dilatation of the ascending aorta
– separation of the valve leaflets
– Valve thickening (Chhetri et al)
Congestive cardiac failure
– hypertension
– aortic regurgitation
– myocarditis.
29. Pulmonary involvement
– 70% angiographic studies (36% - Panja et al)
– segmental and subsegmental branches, more in the
upper lobes
– haemoptysis, chest pain, disproportionate PAH abnormal
ventilation-perfusion scan
Coronary involvement
– in 10%
– usually ostial and proximal
– diffuse lesions or arteritis and aneurysm rarely occur.
Neurological
– Secondary to hypertension or ischaemia.
31. 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
32. Takayasu’s Disease in Children
• Not as frequent as in adults
• Clinical profile same
• Manifestations may be more severe
• Most common cause for renovascular HTN
• Presenting features: HTN, CCF
• An association with TB has been hypothesized ,
never proven
33. PREGNANCY
• Pregnancy per se does not exacerbate the disease
• Management of hypertension is essential.
• Maternal complications: superimposed pre-
eclampsia, congestive cardiac failure, progressive
renal impairment.
• Abdominal aortic involvement and a delay in seeking
medical attention predicted a poor perinatal
outcome.
34. Natural history
• Subramanyam et al- cumulative survival at 5
years-91%,10 yrs-84%. Event free survival-75%
• Ishikawa-Survival rate: 83.1 at 5 years after
diagnosis.
• Cardiac failure - most common cause of death.
• Spontaneous improvement can occur in young
patients.
• Childhood-onset particularly when associated
with a DCM like picture carries ominous
prognosis.
• Failed angioplasty implicates high mortality.
35. 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.
36. 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
37. Non –invasive imaging modalities
• USG: Duplex Scanning
• 2DECHO: Assessment of LV Dysfunction,
Valvular involvement.
• CT Angiography: Aorta & Pulmonary Artery
• MRI : Mural involvement ;dilatation of
vasavasorum
• Flouroscein Angiogram of retinal vessels
Ophthalmodynamometry .
• PET SCAN
38. Ultrasound scan of the internal carotid artery
demonstrating marked thickening of the arterial walls
39. Filling defect: A
filling defect may
be present in
either the retinal
or choroidal
circulation which
may be produced
by emboli seen in
Takayasu's
disease.
Fluorescein Angiogram
40. Magnetic resonance imaging of the aorta and its major
proximal branches. There is thickening of the aortic
arch that extends into both common carotid arteries
(A), with almost complete obliteration of the right
carotid artery and both subclavian arteries (B).
A B
42. Catheterization and Angiography
• Pan-aortography,
preferably with intrarterial digital
subtraction angiography
most important diagnostic investigation
helps in planning management
Visualisation of entire Aorta& its major branches
special attention to innominate, subclavian&
extracranial portions of carotid arteries.
• Coronary Angiography
• Pulmonary Angiography
48. Diagnosis of systemic arterial diseases with whole body 3D contrast-
enhanced magnetic resonance angiography
Chin Med J 2006;
Fig. 1. A 45-year-old patient with
polyarteritis nodosa. Whole-body
MRA reveals multiple aneurysms of
different size in bilateral lower
extremity arteries (arrows).
Fig. 2. A 70-year-old man with
clinically
documented abdominal aorta
aneurysm. A:
Whole-body MRA demonstrates
multiple aortic aneurysms and
concomitant PAOD (arrows).
B:Oblique sub-volume maximum-
intensity-projection shows the
aneurysm at the aortic arch
(arrow). C:Sub-volume maximum-
intensity-projection shows multiple
aneurysms in the thoraco-
abdominal,
abdominal aorta and iliac arteries
(arrows).
49. Management of TA
• Depend on : Clinical presentation
Disease activity
• One of the challenges in the management of TA is
determining disease activity.
Kerr et al define active disease as any two or more
of the following
1. New or worsening:Signs or symptoms of vascular
ischemia or inflammation
2. Increase in sedimentation rate
3. Angiographic features
4. Systemic symptoms not attributable to another
disease
50. Therapeutic Strategies
• Medical Therapy:
– Active or Early Lesions,
– Not In Need of Interventions.
– Co-Morbid Conditions.
– Refuse Interventions.
Steroids
Antihypertensives
Decongestants
Cytotoxic Drugs
Oral Anticoagulants
53. • Decongestive therapy
• Anti hypertensive therapy
• Treatment of renal failure
• Antiplatelet therapy
• Anti tuberculous therapy
caution: ????? Steroids in aneurismal
dilation of vessels
54. Minocycline for the Treatment of Takayasu Arteritis
Annals of Internal Medicine
Actions of minocycline in these diseases are thought
to be independent of antimicrobial activity and are
related to pleiotropic effects, including inhibition of
MMP activities
Minocycline may be a valuable additive to steroids or
an alternative to immunosuppressive agents for
patients with Takayasu arteritis and should be tested in
randomized, controlled trials.
55. Mycophenolate Mofetil for the
Treatment of Takayasu Arteritis
mycophenolate mofetil could represent a valid
alternative to conventional therapy in patients
with Takayasu arteritis. Although the rareness
of the disease is an obstacle to designing
prospective, controlled clinical trials, this first
description of mycophenolate mofetil therapy
in patients with Takayasu arteritis is
encouraging.
56. Infliximab is Effective for Takayasu Arteritis Refractory
to
Glucocorticoid and Methotrexate
The pathogenesis of TA includes vessel injury due to products from activated T
cells, natural killer cells, γ/δ T cells and macrophages. One of the important
humoral factors is TNF-α, the molecular target for human autoimmune diseases
Glucocorticoid therapy is usually introduced for TA, but glucocorticoid alone is
sometimes not efficient; Kerr et al reported that about half of active TA patients
did not respond well to glucocorticoid alone (6). In addition to glucocorticoid, an
immunosuppressive regime such as cyclophosphomide, methotrexate and
azathioprine has been used to treat TA (6-8); however, some patients are
refractory to both glucocorticoid and immunosuppressants. Hoffman et al have
recently reported the efficacy of TNF blockers toward TA refractory to
conventional glucocorticoid therapy and immunosuppressants Patient selection
criteria described by Hoffman et al include:1] required toxic doses of
glucocorticoids to maintain remission, and 2] either experienced multiple
relapses while receiving conventional and experimental therapy or refused re-
treatment with glucocorticoids following relapses
57. • Surgical Therapy: (Definitive Treatment for
occlusive disease & Aneurysm)
– Stenosis
• Hypertension
• End organ Damage
– Bypass Grafting, Endarterectomy, Patch
Aortoplasty, Resection of Narrow Segment,
Excision of Saccular Aneurysms and AVR
Therapeutic Strategies(Cont)
58. Surgical treatment Indications
• Hypertension with critical renal artery stenosis
• Extremity claudication limiting activities of daily living,
• Cerebrovascular ischaemia or critical stenoses of three or
more cerebral vessels
• Moderate or severe aortic regurgitation
• Cardiac ischaemia with confirmed coronary artery
involvement.
• Thoracic aneurysms> 6 cm;abd aortic aneurysms> 5 cm.
• Surgery is recommended at a time of quiescent disease to
avoid complications like restenosis, anastamotic failure,
thrombosis, haemorrhage, and infection.
59. Angioplasty
Balloon Angioplasty ± Stenting of the
involved segment.
– For discrete aortic lesions
– low rates of restenosis (0%–19%)
– Renal angioplasty successful in 95%
– Stent-supported angioplasty for subclavian and
carotid artery obstructions with good success
rates (86%) and moderate rates of restenosis
60.
61. Sirolimus-Eluting Stent for In-Stent Restenosis of Left Main
Coronary Artery in Takayasu Arteritis
In conclusion, Takayasu arteritis with LMCA in-stent
restenosis was successfully treated by a SES.
Because of its immunosuppressive effects in the
inflamed arterial walls, the SES shows promise for
the treatment of stenotic lesions in patients with
Takayasu arteritis.
Circ J 2005; 69: 752 –755
62. Coronary and pulmonary angiographic findings during the first hospitalization for angina. (A) Left
coronary selective injection revealed 90% stenosis in the ostium of the left main coronary artery (LMCA).
(B) Intact right coronary artery. (C) Totally occluded left pulmonary artery. (D) Left coronary angiography
after percutaneous coronary stenting. The 90% stenosis of the LMCA was successfully dilated to 0%.
63. Multiple stenting in a patient
Fig. 2 - Preinterventional angiography: A and B: left and right coronary arteries, respectively, with no obstructive lesions;
C: left common carotid artery with severe obstruction; D: right common carotid artery with mild obstruction; E: left
subclavian artery with occlusion in the proximal third; F and G: right and left renal arteries with moderate and severe
lesions, respectively; H: left iliac artery with occlusion in the proximal third; I: left ventricle with diffuse hypokinesia; J:
aortic valve regurgitation and ectasia of the ascending aorta.
64. Fig. 3 - Herculink stent implantation in renal artery lesion; pre and postintervention.
66. Fig. 5 - Successful previous interventions remained unchanged. Lesion in
the right common carotid artery.
67. Fig. 6 - Herculink stent implantation in carotid artery lesion; pre and
postintervention.
68. Author No:
of
pts.
Balloon
diamet
er
Results : aorta at
stenosis
Major
complications
Follow up
Befor
e
After Dilated % Durat
ion(m
onths
)
reste
nosis
Gu et al
– 1991
16 10-20 4.6m
m
10.2m
m
14(87.5%) Dissection-1 19.1 Nil
Rao et
al –
1993
16 All(100%) Cerebral
infarct-1
Axillary artery
stenosis-1
Dissection-2
21.4 19%
Sharma
- 1994
10 5-12 80.5
%
14% 8(80) Dissection-2 17.8 Nil
Tyagi –
1992 &
1999
146 7-20 4.2m
m
9.9mm 120(82.2)
141(96.5)
with
stent
Long
dissection-4
Retro
peritoneal
leak-1
54.4 8.2%
Balloon aortoplasty of aorta in TA
69. Author No:
of
lesion
s
Initial results Complicat
ions
Follow up
Duration results
Dong et al-
1987
32 D↑from 1.8 to 4.8mm 16.7 % 25.5 Htn ↓ 87%
Gu et al-
1988
6 No stenosis-1
Partial stenosis-5
- - Htn ↓
Park et al-
1989
9 All dilated Nil 4 Restenosis 22%
Kumar et
al 1989
9 6/9 dilated 33.3% -
Fava et al-
1993
12 83% success - - 5 yr patency
Sharma et
al-1998
66
(96)
Success 91/96(95%) 6(9.1%) 22±17 Restenosis 16%
Tyagi et al
- 1999
148
(205)
Ptra success – 85.6%
Ptra + stenting –95%
7(3.4%)
Major-
2(1%)
47±38.5 Restenosis -17%
Percutaneous transluminal renal angioplasty in TA
70. A follow-up study of balloon angioplasty and de-novo stenting in Takayasu
arteritis.
Sharma BK, Jain S, Bali HK, Jain A, Kumari S (PGIMER) Int J
Cardiol. 2000 Aug 31;75 Suppl 1:S147-52
• Percutaneous balloon angioplasty(PTBA) was done in 20 pts with TA.
• All pts received steroids, aspirin and ticlodipine (for stenting) prior to
procedure.
• Angioplasty was carried in pts with symptomatic stenotic vessel of more
than 70% of N. D or a peak systolic gradient of more than 50 mm across
stenotic aortic lesion.
• Stenting was performed for ostial lesion, long segment lesion or
incomplete relief of stenosis and dissection following angioplasty.
• Carotid angioplasty and stenting was performed in 5 patients,
• aortic angioplasty in 9 pts, aortic angioplasty and stenting in 4 pts,
• renal angioplasty in 3 pts, renal angioplasty and stenting in 2 pts and
• subclavian angioplasty in 2pts,subclavian angioplasty & stenting in 3pts &
• coronary angioplasty and stent placement in 1 patient.
• The procedure was successful in all but 1 patient.
• On following up, 2 patients with carotid stent placement had restenosis.
A saccular aneurysm developed at the lower end of stent in 1 patient
with aortic stenting.
• The PTBA with or without stent placement is a safe and effective
method for relief of stenotic lesion in patients with TA.
