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
5. EPIDEMIOLOGY
• Predominantly a disease of young females in their 2 nd
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-Middle Aortic
syndrome
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.
7. 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
8. 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
9. 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
10. 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
11. • 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
12. 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)
13. 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
15. 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
16. 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.
17. 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
18. Obligatory criteria
+
2 Major criteria
or
1 Major and ≥ 2 Minor criteria
or
≥4 Minor criteria
High probability of Takayasu’s disease
( sensitivity:84%)
19. 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
20. 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.
21. 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
22. • 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.
23. 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%)
24.
25. 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.
26. 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.
27. Criteria for Active Disease in Patients with
Takayasu Arteritis*
Kerr, G. S. et. al. Ann Intern Med 1994;120:919-929
29. 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.
30. 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.
32. Frequency of clinical features of Takayasu arteritis at presentation and during
the course of disease
Kerr, G. S. et. al. Ann Intern Med 1994;120:919-929
33. 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
34. 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.
35. 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.
36. Evaluation Of Takayasu’s Arteritis
• Hematology:
Mild Anaemia
Leucocytosis
• Markers of disease activity :
E S R >40mm
50% cases progress with N ESR
CRP
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.
37. Matrix Metalloproteinases as Novel Disease Markers in
Takayasu Arteritis
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.
38. 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 .
39. Ultrasound scan of the internal carotid artery
demonstrating marked thickening of the arterial walls
40. Fluorescein Angiogram
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.
42. A B
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).
43. 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. Rt CCA Long
Stenosis
Lt SCA Not Seen
Rt SCA Narrowing
49. 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).
50. 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
51. 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
54. • Decongestive therapy
• Anti hypertensive therapy
• Treatment of renal failure
• Antiplatelet therapy
• Anti tuberculous therapy
caution: ????? Steroids in aneurismal
dilation of vessels
55. 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.
56. 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.
57. 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
58. Therapeutic Strategies (Cont)
• 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
59. 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.
60. Fig.5. The onset segments of the celiac trunk, superior mesenteric artery and
inferior mesenteric artery are occlusive completely but the vessel wall of the distal
extremity has no hyperplasia lesion and the true lumen still exists.
Fig.6. The infra-diaphragm aortic artery has no stenosis.
Fig.7. The Aorto-SMA grafting by-pass.
Fig.8. End to side anastomosis, 6-mm e-PTFE graft without outer rings, Gore.
61. 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
62.
63. Sirolimus-Eluting Stent for In-Stent Restenosis of Left
Main Coronary Artery in Takayasu Arteritis
Circ J 2005; 69: 752 –755
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.
64. 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%.
65. 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.
66. Fig. 3 - Herculink stent implantation in renal artery lesion; pre and
postintervention.
68. Fig. 5 - Successful previous interventions remained
unchanged. Lesion in the right common carotid artery.
69. Fig. 6 - Herculink stent implantation in carotid artery lesion;
pre and postintervention.
70.
71. Balloon aortoplasty of aorta in TA
Author No: Balloon Results : aorta at Major Follow up
of diamet stenosis complications
pts. er Befor After Dilated % Durat reste
e ion(m nosis
onths
)
Gu et al 16 10-20 4.6m 10.2m 14(87.5%) Dissection-1 19.1 Nil
– 1991 m m
Rao et 16 All(100%) Cerebral 21.4 19%
al – infarct-1
1993 Axillary artery
stenosis-1
Dissection-2
Sharma 10 5-12 80.5 14% 8(80) Dissection-2 17.8 Nil
- 1994 %
Tyagi – 146 7-20 4.2m 9.9mm 120(82.2) Long 54.4 8.2%
1992 & m 141(96.5) dissection-4
1999 with Retro
stent peritoneal
72. Percutaneous transluminal renal angioplasty in TA
Author No: Initial results Complicat Follow up
of ions Duration results
lesion
s
Dong et al- 32 D↑from 1.8 to 16.7 % 25.5 Htn ↓ 87%
1987 4.8mm
Gu et al- 6 No stenosis-1 - - Htn ↓
1988 Partial stenosis-5
Park et al- 9 All dilated Nil 4 Restenosis 22%
1989
Kumar et 9 6/9 dilated 33.3% -
al 1989
Fava et al- 12 83% success - - 5 yr patency
1993
Sharma et 66 Success 91/96(95%) 6(9.1%) 22±17 Restenosis 16%
al-1998 (96)
Tyagi et al 148 Ptra success – 85.6% 7(3.4%) 47±38.5 Restenosis -17%
73. 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.
