JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
VOL. 81, NO. 2, 2023
ª 2023 THE AUTHORS. PUBLISHED BY ELSEVIER ON BEHALF OF THE AMERICAN
COLLEGE OF CARDIOLOGY FOUNDATION. THIS IS AN OPEN ACCESS ARTICLE UNDER
THE CC BY-NC-ND LICENSE (http://creativecommons.org/licenses/by-nc-nd/4.0/).
JACC FOCUS SEMINAR: TROPICAL MEDICINE
JACC FOCUS SEMINAR
Takayasu Arteritis
JACC Focus Seminar 3/4
George Joseph, DM,a Ruchika Goel, DM,b Viji S. Thomson, DM,a Elizabeth Joseph, DNB,c Debashish Danda, DMb
ABSTRACT
Takayasu arteritis is a rare idiopathic large-vessel vasculitis that typically affects young women. An early "prepulseless"
stage is often missed, associated with nonspecific constitutional symptoms (fever, malaise, and weight loss) and
elevated inflammatory markers. Unchecked disease progression leads to the "pulseless" stage, manifest clinically by
missing pulses, vascular tenderness, and ischemic symptoms (limb claudication, dizziness, angina, and renovascular
hypertension), and is characterized pathologically by arterial wall thickening and stenotic/occlusive lesions or aneurysm
formation. Vascular complications (stroke, blindness, heart failure, and aneurysm rupture) could follow unless
disease progression is halted by immunosuppressive therapy and critical lesions are palliated by timely endovascular
therapy or open surgery. Early diagnosis, effective therapy, and lifelong surveillance for disease activity relapses
and vascular disease progression are critical to successful long-term outcomes. The outlook for patients has
improved significantly in recent years with the establishment of diagnostic and classification criteria, better
investigational modalities, and more effective medical and invasive therapy. (J Am Coll Cardiol 2023;81:172–186)
© 2023 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an
open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
T
akayasu arteritis (TAK) is a chronic idiopathic
been made in managing TAK, and the outlook for pa-
granulomatous large-vessel vasculitis that
tients with TAK has improved significantly. The aim
affects the aorta, its main branches, and pul-
of the present review was to provide a synopsis of
monary arteries. It typically affects young women and
the current status of TAK and its management.
is often not diagnosed until late in the disease
because of its rarity, often indolent course, nonspe-
HISTORICAL PERSPECTIVE
cific early symptoms, and lack of specific diagnostic
Listen to this manuscript’s
markers. Uncontrolled disease progression leads to
TAK is eponymous with Mikito Takayasu, professor of
the formation of obstructive and aneurysmal vascular
ophthalmology at Kanazawa University, Japan, who
lesions, which can result in crippling morbidities such
described wreath-like anastomoses in the retinal
as stroke, blindness, refractory hypertension, heart
vasculature of a 21-year-old woman at the Annual
failure, and death. Chronicity of the disease and
Meeting of the Japanese Ophthalmology Society in
frequent need for long-term immunosuppressive
1905. At the same meeting, 2 other ophthalmologists,
therapy create the challenges of lifelong surveillance,
Katsutomo Onishi and Tsurukichi Kagoshima, pre-
medication side effects, poor quality of life, and the
sented cases with similar eye findings and noted
burdens of loss of productivity and recurring medical
missing radial pulses as well. 1 In 1940, Kunio Ohta
expenses. Nevertheless, much recent progress has
confirmed that TAK is a panarteritis and that the
audio summary by
Editor-in-Chief
Dr Valentin Fuster on
www.jacc.org/journal/jacc.
From the aDepartment of Cardiology, Christian Medical College, Vellore, India; bDepartment of Clinical Rheumatology, Christian
Medical College, Vellore, India; and the cDepartment of Radiology, Christian Medical College, Vellore, India.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’
institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information,
visit the Author Center.
Manuscript received August 19, 2022; revised manuscript received September 6, 2022, accepted September 21, 2022.
ISSN 0735-1097
https://doi.org/10.1016/j.jacc.2022.09.051
JACC VOL. 81, NO. 2, 2023
Joseph et al
JANUARY 17, 2023:172–186
Takayasu Arteritis
EPIDEMIOLOGY
HIGHLIGHTS
ABBREVIATIONS
AND ACRONYMS
Early Takayasu arteritis often goes undiagnosed because clinical features are
nonspecific, but progression is associated
with obstructive or aneurysmal lesions.
Immunosuppressive medication is needed
to arrest progression of disease, and
invasive therapy may be needed to
palliate critical vascular lesions.
Early diagnosis, effective therapy, and
continued surveillance are essential to
successful long-term outcomes.
TAK has a worldwide, but heterogeneous,
distribution, generally more common among
Asian populations. 3,4 A recent systematic re-
CTA = computed tomography
angiography
cases per million and an annual incidence of
DMARD = disease-modifying
0.4
to
2.6
cases
per
million.4
Female
preponderance is characteristic of TAK, but
antirheumatic drug
ET = endovascular therapy
female-to-male ratios vary from 12:1 in Turkey
EULAR = European League
to 3:1 in China and India.3,5 Patients experi-
Against Rheumatism
ence onset of disease with TAK usually be-
HLA = human leukocyte
tween 20 and 30 years of age, but onset after
antigen
the age of 40 years is not uncommon, varying
IL = interleukin
3
MRA = magnetic resonance
angiography
characteristic optic fundal finding resulted from
ischemia due to obstructed cervical arteries. The
AECA = antiendothelial cell
antibody
view found a global prevalence of 3.2 to 40.0
from 9% to 32%.
TAK = Takayasu arteritis
PATHOLOGY
name “Takayasu arteritis” for this disease was
accepted at the 2012 revised International Chapel Hill
TAK is a panarteritis, but the initial site of inflam-
Consensus Conference on the nomenclature of
mation is around the vasa vasorum and at the medio-
vasculitides.2
adventitial junction. 6 In the early phase, the active
F I G U R E 1 Proposed Immunopathogenesis of Takayasu Arteritis
Putative antigen triggers
Exogenous:
Mycobacterium tuberculosis
Endogenous:
Heat-shock protein-60
Dendritic
cell
stimulation
Y
↑Toll-like
receptor
expression
↓ Programmed cell death
ligand-1 expression
Macrophage
Monocyte
JAK
PD1
Immune cell infiltration
Abnormal adventitial
dendritic cell
Vasa
vasorum
Macrophages
and other cells
Y
Interleukin-6,
-12, -18, -23, -1β
T cell activation
T cell
B cell
survival
factors
Interleukin-6, -18
PDGF, VEGF
B cell
CD8+
Anti-endothelial
cell antibody
Perforin, Granzymes
mTOR
pathway
173
Th1
Th17
Interleukin-6, -17, -22, -23
NK
cell
Interferon-γ
Matrix
metalloproteinase2, -3, -9
Tumor necrosis
factor-α
Granuloma
formation
Endothelin-1
Endothelial cell activation
Intimal proliferation
Neo-angiogenesis
Vascular smooth muscle cell
proliferation and fibrosis
Activation by unknown antigens of inherently abnormal adventitial dendritic cells causes cytokine release that drives T-cell differentiation into cytotoxic CD8þ T cells, T
helper 1 (Th1) cells, and T helper 17 (Th17) cells. Cytotoxic cells release the cytotoxic proteins perforin and granzymes. The Th cells are vasculitogenic, rich in
programmed cell death protein-1 (PD1), with increased Janus kinase (JAK)-signal transducer and activator of transcription proinflammatory signaling. The resultant
immune cell infiltration leads to endothelial cell activation, intimal and vascular smooth muscle cell proliferation, and fibrosis. Interferon-g released by natural killer
(NK) cells contributes to granuloma formation. Matrix metalloproteinases released by inflammatory macrophages also contribute to granuloma formation and cause
digestion and leakiness of the endothelial barrier. B cells promote endothelial cell activation by secreting antiendothelial cell antibodies. mTOR ¼ mammalian target of
rapamycin; PDGF ¼ platelet-derived growth factor; VEGF ¼ vascular endothelial growth factor.
174
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genome-wide level of significance (P < 5 10–8 ) were
T A B L E 1 American College of Rheumatology 1990 Classification Criteria for
found in the HLA region and elsewhere. 9 Two non-
Takayasu Arteritis
HLA genetic loci, IL12B encoding for the common
Definition
Age at disease onset <40 y
Development of symptoms or findings related to Takayasu
arteritis at age <40 y
Claudication of extremities
Development and worsening of fatigue and discomfort in
muscles of 1 or more extremities while in use,
especially the upper extremities
Decreased brachial artery
pulse
Decreased pulsation of 1 or both brachial arteries
Blood pressure difference
>10 mm Hg
Difference of >10 mm Hg in systolic blood pressure
between the arms
Bruit over subclavian
arteries or aorta
Bruit audible on auscultation over 1 or both subclavian
arteries or abdominal aorta
Arteriogram abnormality
Arteriographic narrowing or occlusion anywhere in the
aorta, its primary branches, or large arteries in the
proximal upper or lower extremities, not due to
arteriosclerosis, fibromuscular dysplasia, or similar
causes; changes usually focal or segmental
p40 subunit of interleukin (IL)-12 and IL-23, and MLX,
have synergistic effects with the allele HLA-B*52:01,
increasing
TAK
susceptibility.10
Similarly,
IL6,
encoding the pro-inflammatory cytokine IL-6, has
been identified as a genetic susceptibility locus for
TAK surpassing genome-wide level of significance.8
PATHOGENESIS
Large-sized and medium-sized arteries are largely
immune-privileged sites. Vascular dendritic cells in
the proximity of the vasa vasorum act as gatekeepers,
limiting the access of lymphoid cells and blunting
immune-inflammatory responses (Figure 1).11 Im-
A patient is said to have Takayasu arteritis if at least 3 of these 6 criteria are present. Adapted with permission
from Arend et al.17
mune tolerance is breached by activation of inherently abnormal dendritic cells, which have lower
expression of regulatory receptors such as pro-
inflammatory component and necrotizing character
are conspicuous. 7 Mononuclear cell infiltration (lymphocytes, histiocytes, and plasma cells) and edema
are seen.6,7 Fragmentation of elastic fibers is prominent, and giant cell granulomatous reaction and
laminar medial necrosis may occur. 6 Later, there is
reactive fibrosis and increased ground substance in
the intima, with overlying mural thrombus and a
band of neovascularization at the intimal medial
junction. Rapid or more severe inflammation leads to
loss of smooth muscle cells, medial weakening,
vascular dilatation, and aneurysm formation. In the
healed phase, the adventitial fibrosis and scarring
along with laminar medial necrosis are more impressive, although lymphoplasmacytic inflammation and
multinucleated giant cells also persist.7 The adventitial and periadventitial fibrosis observed in TAK exceeds that seen in any other inflammatory disorder of
the aorta.6
grammed cell death ligand-1 and overexpression of
surface Toll-like receptors. Exposure to yet unknown
stimuli results in the maturation of dendritic cells
leading to the release of cytokines, including IL-12,
IL-23, and IL-1 b, and an influx of activated vasculitogenic T cells into the adventitia and media.
The vascular topography of TAK may be linked to
differential expression of Toll-like receptors along the
arterial tree; binding of ligands to different Toll-like
receptors activates arterial wall–integrated dendritic
cells to initiate and promote T effector cell accumulation and distinct types of vasculitis.12 The cellular
infiltrate contains macrophages, T helper 1 and
T helper 17 cells, CD8 þ T cells, gd T cells, natural killer
cells, and neutrophils. 13 Release of growth factors
leads to wall edema, extracellular matrix deposition,
and the proliferation of myofibroblasts that invade
the intima, ultimately leading to arterial stenosis.
Arterial dilatation can also occur, caused by excessive
local release of toxic reactive oxygen species and
GENETICS
matrix metalloproteinases by macrophages, resulting
in degeneration and thinning of the tunica media,
The etiology of TAK involves a complex genetic
death of vascular smooth muscle cells, and disruption
contribution, which includes genes encoding human
of elastin.11
leukocyte antigen (HLA) class I and class II specificities,
immune
response
regulators,
and
Molecular mimicry between a host and a microbial
proin-
heat shock protein (hsp60 and hsp65, respectively)
flammatory cytokines, all of which relate to known
may drive immune responses in TAK; it is hypothe-
processes involved in TAK pathogenesis; the most
sized that an unknown stimulus triggers heat shock
robust genetic signal comes from HLA-B*52, which
protein and major histocompatibility complex class I
has been confirmed in several ethnicities.8 A recent
chain-related A expression in aortic tissue; the latter
meta-analysis of patients with TAK from 5 different
is recognized by specific gd T cells and natural killer
populations provides data suggesting additional ef-
cells, leading to their releasing perforins, granzymes,
fects beyond HLA-B*52 in TAK; multiple genetic loci
and pro-inflammatory cytokines, resulting in acute
with independent association with the disease and
vascular inflammation. 13
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Takayasu Arteritis
T A B L E 2 Modified Ishikawa Criteria for Diagnosis of Takayasu Arteritis
Brief Description
Major criteria
1. Left mid-subclavian artery lesion
Most severe obstruction between points 1 cm proximal and 3 cm distal to the left vertebral artery ostium
2. Right mid-subclavian artery lesion
Most severe obstruction between the right vertebral artery ostium and a point 3 cm distal to it
3. Characteristic signs and symptoms
of at least 1 mo duration
Limb claudication, pulselessness or pulse differences in limbs, unobtainable BP or systolic BP difference
>10 mm Hg in limb, fever, neck pain, transient amaurosis, blurred vision, syncope, dyspnea, or
palpitations
Minor criteria
1. High ESR
Unexplained ESR >20 mm/h at diagnosis or evidence in patient’s history
2. Carotid artery tenderness
Unilateral or bilateral common carotid artery tenderness
3. Hypertension
Persistent BP >140/90 mm Hg brachial/>160/90 popliteal
4. Aortic regurgitation or
annulo-aortic ectasia
By auscultation, Doppler/2-dimensional echocardiography, or angiography
5. Pulmonary artery lesion
Lobar or segmental arterial occlusion on angiography or perfusion scintigraphy, or presence of stenosis,
aneurysm, luminal irregularity on angiography
6. Left mid-common carotid lesion
Most severe obstruction in the 5-cm length from a point 2 cm distal to its ostium
7. Brachiocephalic trunk lesion
Most severe obstruction in the distal third
8. Descending thoracic aorta lesion
Narrowing, dilation or aneurysm, luminal irregularity; tortuosity alone is unacceptable
9. Abdominal aorta lesion
Narrowing, dilation or aneurysm, luminal irregularity
10. Coronary artery lesion
Documented before age 30 y, absence of risk factors such as hyperlipidemia or diabetes mellitus
The presence of 2 major or 1 major and 2 minor or 4 minor criteria suggests a high probability of Takayasu arteritis. Adapted from Sharma et al.18
BP ¼ blood pressure; ESR ¼ erythrocyte sedimentation rate.
F I G U R E 2 Computed Tomography Angiography in a 26-Year-Old Woman With Takayasu Arteritis
Sagittal (A) and coronal (B) images show markedly irregular descending aortic luminal outline, calcification (yellow arrows), and wall
thickening (blue arrows). Early (C) and delayed (D) acquisition of corresponding axial images shows a mural double ring in the latter,
consisting of an inner poorly enhancing (dark) rim representing hyperplastic intima, and an outer late-enhancing (bright) rim (red arrow)
representing vasa vasorum neoangiogenesis in the media and adventitia.
175
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F I G U R E 3 Numano Angiographic Classification System for Takayasu Arteritis
Shaded areas represent regions of arterial involvement by the disease process. Adapted from Hata et al.20
antibodies
(Table 1) to help create homogeneous groups for
(AECAs) have been documented in TAK, indicating a
Antiaorta
and
antiendothelial
cell
research studies, which limits its applicability to
role for B cell–mediated autoimmunity. 13 The target
clinical practice; age <40 years at onset was 1 of 6
autoantigens of AECAs have recently been identified
criteria proposed. Both sets of criteria have been
using a complementary DNA–based expression clon-
criticized for their age restriction and low sensitivity
ing system.14 Endothelial protein C receptor and
in TAK patients with predominant aortic involve-
scavenger receptor class B type 1 were identified as
ment.18 In 1995, modifications (Table 2) to the Ishi-
endothelial antigens targeted by AECAs; these anti-
kawa diagnostic criteria were proposed, including
gens act as negative regulators of endothelial activa-
removing the age criterion, which increased the
tion, but when AECAs block their function, a
sensitivity
proinflammatory phenotype results.
respectively.
and
specificity
to
92.5%
and
95%,
Accelerated atherosclerosis may occur in TAK due
to a combination of direct vascular and systemic
IMAGING AND ANGIOGRAPHIC CLASSIFICATION
inflammation, traditional risk factors, and treatment
effects and may contribute to cardiovascular adverse
events.
15
Initial vascular imaging in TAK is usually performed
by using computed tomography angiography (CTA),
which, in addition to being widely available and less
DIAGNOSIS
expensive, provides better image resolution than
magnetic resonance angiography (MRA). CTA reveals
Ishikawa16 proposed the first diagnostic criteria for
luminal narrowing and dilatation and changes in the
TAK in 1988, with age <40 years at diagnosis or onset
vessel wall such as wall thickening, calcification,
of characteristic symptoms/signs as an obligatory
and contrast enhancement 19 (Figure 2). The site
criterion. In 1990, the American College of Rheuma-
and extent of arterial involvement in TAK are highly
tology proposed classification criteria for TAK 17
variable,
making
angiographic
classification
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Takayasu Arteritis
desirable. The most widely used angiographic classification scheme for TAK is the Numano system
177
T A B L E 3 Clinical Manifestations of Takayasu Arteritis According to Vascular
Region Affected
(Figure 3), which defines 6 types of TAK based on the
Symptoms and Signs
topography of arterial lesions; coronary and pulmonary artery involvement are separately designated Cþ
and Pþ, respectively.20 The Numano classification
system has improved reporting standards of TAK and
has helped reveal ethnic differences in arterial lesion
distribution; however, its formulation was empirical
General
Constitutional symptoms
Fatigue, low-grade fever, night sweats, weight loss >2 kg
Other symptoms of active
disease
Myalgia, arthralgia, arthritis, abdominal pain
Vascular involvement
Weak or missing pulses, vascular bruit, vascular tenderness
Specific
and not evidence based.
Carotid arteries
Dizziness, amaurosis fugax, vision loss, transient ischemic
attacks, stroke
CLINICAL FEATURES
Subclavian arteries
Arm claudication, inter-arm blood pressure difference
>10 mm Hg. Proximal subclavian obstruction can cause
subclavian steal
Clinical manifestations of TAK vary depending on the
Vertebral arteries
Stenosis/occlusion can cause vertigo or contribute to cerebral
ischemic symptoms when multiple arch branches are
obstructed
Ascending and arch of
aorta
Aortic regurgitation due to aortic dilatation, aneurysm, rarely
aorta stenosis
Descending aorta
Systemic hypertension, dyspnea, and heart failure due to aorta
stenosis, aneurysm
stage of the disease and the vascular region involved
(Table 3). Clinical features progress through 2 stages,
although not all patients conform to this pattern:
Stage I is the “prepulseless” phase, characterized by
constitutional symptoms, which are seen in <50% of
Abdominal aorta
Systemic hypertension, lower limb claudication, aneurysm
patients.21 Stage II is the “pulseless” phase marked by
Renal arteries
Systemic hypertension, renal failure
symptoms and signs of vascular inflammation and
Mesenteric arteries
Postprandial abdominal pain, weight loss, sitophobia,
gastrointestinal hemorrhage
ischemia.
A
“fibrotic”
third
stage
has
been
described,11,22 which is burnt-out disease void of
inflammation
and
presents
with
complications
Iliac and femoral arteries
Lower limb claudication or fatigue
Coronary arteries
Angina, heart failure, myocardial infarction
Pulmonary arteries
Dyspnea, cough, chest pain, pulmonary hypertension
resulting from vascular damage. Very few patients
present in the third stage, and progression through all
3 stages (triphasic pattern) is observed in only 19% of
Adapted with permission from Kim ESH, Beckman J. Takayasu arteritis: challenges in diagnosis and management.
Heart. 2018;104:558-565.
patients.22 Clinical features seen in different ethnic
groups are presented in Table 4. White and East Asian
At our center, relapse within 5 years was 34%, whereas
patients tend to have more arch branch involvement
a persistent complete response to treatment (no re-
and higher age at presentation. South Asian patients
lapses at any time) was obtained in 46%; 6% of patients
tend to present earlier, with a lower female propor-
were refractory to therapy, with persistently active
tion and more abdominal aorta involvement. Mexican
and progressive disease.25 Disease activity states
patients also present early and have the most type V
defined by the European League Against Rheumatism
disease.
(EULAR) 26 are presented in Table 5.
NATURAL HISTORY
DISEASE ACTIVITY ASSESSMENT
The natural history of TAK is highly variable. In 1996,
Assessment of disease activity is essential in diag-
Ishikawa23 described 4 patterns of clinical symptoms
nosis, prognostication, tailoring of immunosuppres-
from their onset to the point where the diagnosis was
sive
first made: A, plateau; B, decrescendo; C, decrescendo-
assessment is therefore required repeatedly in the
plateau-crescendo; and D, plateau-crescendo. Subse-
management of patients with TAK. Disease activity
quent 12-year survival was 91% with patterns A and B,
determined by clinical assessment and acute-phase
and 70% with patterns C and D. With the widespread
reactant levels correlates poorly with activity seen
use of immunosuppressive therapy in the past few
in biopsy specimens; also, the appearance of new
decades, most available data on the natural history of
arterial lesions was observed in 61% of patients
the disease are in treated patients. Kerr et al 21 found
thought to be inactive. 21 Nowadays, imaging infor-
that 20% of patients had a monophasic self-limiting
mation is combined with clinical and laboratory data
disease and did not require immunosuppressive
to improve disease activity assessment. In 1994,
treatment; in the remainder who did, remission could
Kerr 21 defined active disease with a 4-category system
not be induced in one-quarter, and about one-half of
that has been widely used (Table 6). The advantages
those who achieved remission later relapsed. Comar-
of this system are its simplicity, composite nature,
mond et al24 found that 41% of patients in remission
and inclusion of angiographic information; however,
experience a relapse of disease activity within 5 years.
it has not been validated, and cut-off levels of
therapy,
and
timing
of
invasive
therapy;
178
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Takayasu Arteritis
JANUARY 17, 2023:172–186
MEDICAL THERAPY
T A B L E 4 Clinical Features of Takayasu Arteritis in Various Geographic Regions
Country
Advances in medical therapy for TAK have contrib-
United States
Japan
India
Mexico
uted significantly to the marked decline in mortality
Schmidt et al43
Watanabea
Danda et al5
Sotob
and improved quality of life in patients with TAK over
1984-2009
2001-2011
1998-2017
1976-2003
the last 2 decades. These advances include up-front
126
1,372
602
110
82.5% White
East Asian
South Asian
Mestizo
Age at onset, y, median
(IQR) or mean SD
29 (15)
35 (35)
26 (12)
26 9
Proportion with age at
onset >40 y
25
43
10
9
91
84
77
85
I
20
28
19
19
treat-to-target approach in TAK. Judicious use of
IIa
6
16
5c
3
invasive therapy after controlling disease activity has
IIb
7
17
-c
4
also improved outcomes.
III
5
7
5
4
IV
5
6
16
2
EMPHASIS ON LOWER DOSES OF CORTICOSTEROID.
V
57
26
49
69
Fatigue/malaise
54
14
32
30
Fever
29
35
19
20
remission rates as high as 60%.21 However, the asso-
Neck pain
15
10
6
21
ciated side effects and frequent progression of dis-
Headache
45
8
21
70
ease or relapse while on glucocorticoid monotherapy
Dizziness/light-headedness
49
9
6
55
have prompted efforts to reduce dependence on
Upper limb claudication
40
66
52d
NA
18
10
-d
glucocorticoids. An effective
Lower limb claudication
NA
Author
Period of study
N
Ethnicity of patients
Female proportion
Numano angiographic types
20
Chest pain
6
2
12
32
Systemic hypertension
38
39
53
53
use of synthetic disease-modifying antirheumatic
drugs (DMARD) during the initial induction regimen,
better DMARDs, and lower doses of steroids. In
addition, the formulation of disease activity scoring
systems such as the activity version of the Indian
Takayasu Clinical Activity Score has enabled a
Glucocorticoid monotherapy has been the cornerstone of medical therapy in TAK in the past, achieving
strategy has been
combining lower initial and cumulative glucocorticoid doses with DMARDs.
Renal impairment
NA
11
8
28
DMARDs
Aortic regurgitation
NA
33
7
41
DMARDs are currently available (Table 7). DMARDs
Cerebrovascular accidents
11
5
8
9
are classified as synthetic or biologic. Synthetic
a
Values are % unless otherwise specified. Watanabe Y, Miyata T, Tanemoto K. Current clinical features of new
patients with Takayasu arteritis observed from cross-country research in Japan: age and sex specificity. Circulation. 2015;132:1701-1709. bSoto ME, Espinola N, Flores-Suarez LF, Reyes PA. Takayasu arteritis: clinical features
in 110 Mexican Mestizo patients and cardiovascular impact on survival and prognosis. Clin Exp Rheumatol.
2008;26(3 suppl 49):S9-S15. cNumano angiographic types IIa and IIb combined is 5% (separate data is not
available). dUpper and lower limb claudication combined is 52% (separate data is not available).
NA ¼ data not available.
AND THEIR
EFFECTS. Several
effective
DMARDs can be conventional (eg, methotrexate,
azathioprine, mycophenolate, leflunomide, cyclophosphamide) or targeted (eg, the novel Janus kinase
inhibitor tofacitinib, which blocks proinflammatory
cytokine signaling). Biologic DMARDs target IL-driven
pathways (eg, tocilizumab, an anti–IL-6 receptor
individual items are not specified. The Indian
antibody) or inhibit tumor necrosis factor-alpha (eg,
Takayasu Clinical Activity Score and its activity
infliximab,
etanercept,
adalimumab).
Biologic
are also composite scores to assess disease
DMARDs are usually reserved for refractory cases or
activity that additionally allow grading of disease
when rapid control of disease activity is required. A
version
27
activity and incorporate cardiovascular weighting.
recent extensive meta-analysis29 summarized the ef-
However, it does not include imaging data; it is
fects of DMARDs (Table 8). Biologic DMARDs are more
widely used during follow-up of patients with TAK.
effective than conventional synthetic DMARDs in
F-fluorodeoxyglucose positron emission tomogra-
inducing remission, stabilizing vascular disease, and
phy co-registered with computed tomography imag-
reducing inflammation; however, they are associated
18
ing identifies enhanced metabolic activity in the
with more relapses, adverse events, and infections.
arterial wall and may improve diagnostic accuracy
CURRENT IMMUNOSUPPRESSIVE DRUG STRATEGIES
and influence therapeutic decisions. However, the
IN TAK. The 2018 EULAR guidelines26 for pharmaco-
role of this modality during follow-up is limited
logic treatment of TAK recommend a 2-phase strategy,
because cumulative radiation exposure is a concern,
with
and sensitivity and specificity in low-grade activity
DMARD combination in phase I, and a biologic DMARD
glucocorticoid
and
conventional
synthetic
are poor.19 Also, uptake that is confined to arterial
in phase II if relapse occurs (Figure 4). The 2021
graft sites in patients with TAK does not correlate
American College of Rheumatology guidelines 30 also
with clinically relevant disease activity and may
recommend combination therapy of glucocorticoids
reflect a foreign body reaction.
28
with DMARDs but differ in recommending tumor
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Takayasu Arteritis
necrosis factor inhibitors as an option in initial therapy; tocilizumab is recommended in refractory dis-
179
T A B L E 5 EULAR Consensus Definitions for Disease Activity States in
Large-Vessel Vasculitis
ease, an indication for which this drug has seen
EULAR Consensus Definition
widespread use.
OTHER MEDICATIONS. Recently, Kwon et al
31
showed
Active disease
1. Presence of typical signs and symptoms of active LVV
2. At least 1 of the following:
a. Current activity on imaging or biopsy
b. Ischemic complications attributed to LVV
c. Persistently elevated inflammatory markers (after other causes
have been excluded)
Major relapse
Recurrence of active disease with either of the following:
that patients with TAK receiving concomitant statin
and immunosuppressive therapy experienced significantly fewer disease relapses than those not receiving
statins; proportions of patients with hypercholester-
1. Clinical features of ischemia
2. Evidence of active aortic inflammation resulting in progressive
aortic or large-vessel dilatation, stenosis, or dissection
olemia and levels of total cholesterol did not differ
between the 2 groups, suggesting that pleiotropic effects of statins, rather than cholesterol-lowering ef-
Minor relapse
fects, may play a role. Antiplatelet therapy is
Refractory
Inability to induce remission despite the use of standard care therapy
Remission
Absence of all clinical signs and symptoms attributable to active LVV and
normalization of ESR and CRP
Sustained remission
1. Remission for at least 6 mo
2. Achievement of the individual target glucocorticoid dose
Glucocorticoid-free
remission
1. Sustained remission
2. Discontinued glucocorticoid therapy (but could still be receiving
other immunosuppressive therapy)
associated with a lower frequency of ischemic events
in patients with TAK. 32 Antiplatelet therapy is recom-
Recurrence of active disease, not fulfilling the criteria for a major relapse
mended in critical cerebrovascular disease in TAK 30
but not routinely.26
FOLLOW-UP OF PATIENTS
Clinical follow-up with inflammatory marker level
monitoring is prudent every 1 to 3 months for a year
Adapted with permission from Hellmich et al.26
CRP ¼ C-reactive protein; ESR ¼ erythrocyte sedimentation rate; EULAR ¼ European League Against
Rheumatism; LVV ¼ large-vessel vasculitis.
after initiation of immunosuppressive therapy and
every 3 to 6 months afterward.26 Response to therapy
is typically monitored every 6 to 12 months for the
first 2 years using CTA or MRA. 11 MRA has the
advantage of not involving radiation or iodinated
contrast; acquisition time can be reduced if the study
is limited to assessing the arterial lumen, which allows accurate assessment of disease extent.
11
Once
disease control has been achieved, annual clinical
and depends on the mix of cases and locally available
expertise.33 Invasive therapy is best conducted at
centers specializing in TAK management, with a
multidisciplinary
team
involving
surgeons,
in-
terventionists, and rheumatologists. 26 Invasive therapy is best avoided in active disease. It is prudent to
delay such procedures until disease activity is
controlled with immunosuppressive therapy; active
evaluation and imaging using MRA are required,
disease is associated with more frequent complica-
although duplex ultrasound evaluation may suffice in
tions such as anastomotic aneurysm formation and
some situations. Surveillance should be lifelong,
mortality after open surgery and restenosis after
given the possibility of relapse after a period of
ET. 26,34 If invasive therapy is unavoidable in active
remission.
disease, high-dose oral glucocorticoids are recom-
INVASIVE THERAPY
Vascular lesions in TAK are responsible for most of
the morbidity and mortality associated with the disease, and efforts to palliate them by invasive therapy
form an essential component of disease management.
Open surgery was the only modality available for
decades; today, endovascular therapy (ET) plays an
mended in the perioperative setting.30
STRATEGIES
IN
INVASIVE
THERAPY. In
most
studies, the primary treatment modality used in ET
has been balloon angioplasty, with stenting reserved
for suboptimal angioplasty results. Restenosis was
higher with adjunctive stenting than stand-alone
balloon angioplasty, 35 probably because this strategy
channels lesions prone to restenosis toward stenting.
increasingly important role. Current guidelines favor
restricting invasive therapy in TAK to life- or organ-
T A B L E 6 Criteria for Active Disease in Patients With Takayasu Arteritis
threatening situations, refractory hypertension, or
1. Systemic features, such as fever, musculoskeletal pain (no other cause identified)
when patient activities are significantly affected. 30
2. Elevated erythrocyte sedimentation rate (C-reactive protein added later)
The rationale for this guarded stance includes lack
of good quality data, improvement of ischemic
3. Features of vascular ischemia or inflammation, such as claudication, diminished or absent
pulse, bruit, vascular pain (carotidynia), asymmetric blood pressure in either upper or lower
limbs (or both)
symptoms with medical therapy and spontaneous
4. Typical angiographic features
collateral formation (Figure 5), and the risks associated with open surgery. The proportion of patients
requiring invasive therapy varies widely (17%-70%)
New onset or worsening of 2 or more features indicates "active disease." They are also referred to as the National
Institutes of Health criteria or NIH score. Adapted with permission from Kerr et al21.
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T A B L E 7 Prospective Studies of DMARDs in Takayasu Arteritis
Drug
(Type)
Author/Study/
Year
Study Type
Patients
Patient Selection/
Study Details
Follow-Up
Duration
Dose
(Standard or Mean)
Patients refractory to
GC alone
2.8 y
17.1 mg/wk
Remission in 13 (81%),
sustained in 8 (50%).
Disease progression despite
treatment in 3 (19%).
1y
2 mg/kg/d
Remission in all 15 with no
significant angiographic
changes compared with
baseline.
AZA well tolerated.
23.3 mo
2 g/d
Clinical remission, decrease
in ESR and CRP levels,
significant steroid dose
reduction attained in
9 (90%).
Outcome
Methotrexate (CS) Hoffman
et al,a
1994
Open-label
18
(2 exited)
Azathioprine
(CS)
Valsakumar
et al,b
2003
Open-label
15
Newly diagnosed
with active
disease
Mycophenolate
(CS)
Shinjo et al,c Open-label
2007
10
Active disease
despite GC
Leflunomide
(CS)
Cui et al,d
2020
56
Active disease.
LEF for induction, 41
CYC resistant, 15
12 mo
16.8 mg/d
Complete remission in
55.4%, partial response
in 14.3%; 85.7%
continued LEF
treatment at 14 mo
(mean) with good
tolerance.
Tofacitinib
(TS)
Kong et al,e Open-label
2022
comparative
Active disease
Rapid GC taper
during 0-6
mo and slow
taper during
6-12 mo
12 mo
TOF 5 mg twice daily
MTX 10-15 mg/wk
Comparing the TOF and
MTX groups,
respectively:
Complete remission at
12 mo was 88% and
56% (P ¼ 0.02);
Median relapse-free
duration was 11.6 and
10.5 mo (P ¼ 0.03);
Mean GC dose at 3, 6, and
12 mo was less in TOF
group (P < 0.05).
Tocilizumab
(B)
Nakaoka
et al,f
TAKT study
2018
162 mg/wk
In the intention-to-treat
analysis, the primary
efficacy endpoint (time
to relapse while oral GC
was tapered in both
groups) had a hazard
ratio of 0.41
(P ¼ 0.059).
Open-label
Phase 3 doubleblind RCT
27 TOF
26 MTX
18 drug
18 placebo
Patients with recent
19/12 wk
relapse, remission drug/placebog
induced with
oral GC
Continued on the next page
Restenosis is a significant problem after ET for
obstructive
lesions
in
TAK
and
occurs
PREGNANCY AND TAK
more
frequently than occlusion of surgical bypass grafts
Women with TAK are at increased risk of adverse
(43% vs 17% in a large meta-analysis). 36 Repeat ET
pregnancy outcomes. A French study 39 of 98 preg-
procedures (usually balloon angioplasty) can effec-
nancies in 52 patients with diagnosed TAK reported
tively treat restenotic lesions, yielding high assisted
obstetric complications in 40% and maternal com-
patency rates.37 In the coronary arteries, which are
plications in 39% (mainly new-onset or worsening
involved in 18% of patients with TAK 5 by both
hypertension); active disease was an independent
vasculitis and premature atherosclerosis, 33 coronary
risk factor for both. Conception should, therefore,
artery bypass grafting is the preferred treatment op-
only be planned after remission is achieved and if
tion in patients remaining symptomatic despite
contraindications to pregnancy do not exist.40 Medi-
medical therapy, as percutaneous coronary inter-
cations safe in pregnancy should be used to control
vention is associated with a significantly higher
hypertension (labetalol, hydralazine, and alpha-
restenosis rate. 38 Open surgery has been the standard
methyldopa) and for immunosuppression (steroids
of care for treating aortic aneurysms in TAK, but the
and azathioprine); disease flare-ups can be treated
less
repair
with tumor necrosis factor inhibitors. Most patients
(Figure 6), is steadily making inroads into this field.
can have a vaginal delivery, although the second
Invasive strategies in specific lesions and arteries are
stage of labor may have to be expedited to limit
detailed in Table 9.
surges in blood pressure; Cesarean section is usually
invasive
alternative,
endovascular
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Takayasu Arteritis
181
T A B L E 7 Continued
Drug
(Type)
Author/Study/
Year
Study Type
Patients
Patient Selection/
Study Details
Follow-Up
Duration
Dose
(Standard or Mean)
Outcome
Tocilizumab
(B)
Nakaoka
et al,h
TAKT study
2020
Open-label
36 (28 got TOC
for 96 wk)
Patients completing
the double-blind
period of TAKT
study
96 wk
162 mg/wk
GC dose reduced
to <0.1 mg/kg/d in
46% of patients.
Imaging evaluations:
improved in 18%,
stable in 68%.
Physical and mental wellbeing scores improved.
Tumor necrosis
factor inhibitorj
(B)
Park et al,i
2018
Open-label
12 (1 excluded)
Active disease. FDGPET performed at
baseline and 30 wk
54 wk
5 mg/kg at wk 0, 2, 6, then
q8wk until wk 46
Primary efficacy endpoint
(at 30 wk): complete
remission in 3 (27%) and
partial remission in
6 (55%). Significant
improvements were
seen in ITAS-2010 and
ITAS-A scores, ESR,
CRP, and FDG-PET
parameters.
a
Hoffman GS, Leavitt RY, Kerr GS, Rottem M, Sneller MC, Fauci AS. Treatment of glucocorticoid-resistant or relapsing Takayasu arteritis with methotrexate. Arthritis Rheum. 1994;37:578-582. bValsakumar
AK, Valappil UC, Jorapur V, Garg N, Nityanand S, Sinha N. Role of immunosuppressive therapy on clinical, immunological, and angiographic outcome in active Takayasu’s arteritis. J Rheumatol. 2003;30:17931798. cShinjo SK, Pereira RM, Tizziani VA, Radu AS, Levy-Neto M. Mycophenolate mofetil reduces disease activity and steroid dosage in Takayasu arteritis. Clin Rheumatol. 2007;26:1871-1875. dCui X, Dai X,
Ma L, et al. Efficacy and safety of leflunomide treatment in Takayasu arteritis: case series from the East China cohort. Semin Arthritis Rheum. 2020;50:59-65. eKong X, Sun Y, Dai X, et al. Treatment efficacy
and safety of tofacitinib versus methotrexate in Takayasu arteritis: a prospective observational study. Ann Rheum Dis. 2022;81:117-123. fNakaoka Y, Isobe M, Takei S, et al. Efficacy and safety of tocilizumab in
patients with refractory Takayasu arteritis: results from a randomised, double-blind, placebo-controlled, phase 3 trial in Japan (the TAKT study). Ann Rheum Dis. 2018;77:348-354. gMedian treatment
duration. hNakaoka Y, Isobe M, Tanaka Y, et al. Long-term efficacy and safety of tocilizumab in refractory Takayasu arteritis: final results of the randomized controlled phase 3 TAKT study. Rheumatology
(Oxford). 2020;59:2427-2434. iPark EH, Lee EY, Lee YJ, et al. Infliximab biosimilar CT-P13 therapy in patients with Takayasu arteritis with low dose of glucocorticoids: a prospective single-arm study.
Rheumatol Int. 2018;38:2233-2242. jInfliximab biosimilar CT-P13.
AZA ¼ azathioprine; B ¼ biologic disease-modifying antirheumatic drug; CS ¼ conventional synthetic disease-modifying antirheumatic drug; CYC ¼ cyclophosphamide; DMARD ¼ disease-modifying
antirheumatic drug; FDG-PET ¼ 18F-fluorodeoxyglucose positron emission tomography co-registered with computed tomography; GC ¼ glucocorticoid; ITAS-2010 ¼ Indian Takayasu Clinical Activity
Score; ITAS-A ¼ activity version of the Indian Takayasu Clinical Activity Score; LEF ¼ leflunomide; MTX ¼ methotrexate; q8wk ¼ every 8 weeks; RCT ¼ randomized controlled trial; TAKT ¼ Takayasu arteritis
treated with tocilizumab; TOC ¼ tocilizumab; TOF ¼ tofacitinib; TS ¼ targeted synthetic disease-modifying antirheumatic drug; other abbreviations as in Table 5.
reserved for severe hypertension, severe aortic
with that of the general population (standardized
regurgitation, and obstetric indications.
mortality ratio 3.0). Ishikawa and Maetani 44 reported
OCULAR INVOLVEMENT
enced by vascular complications, progressive clinical
in 1994 that survival in TAK was negatively influcourse of disease (crescendo pattern), and elevated
The common forms of ocular involvement in TAK are
erythrocyte
Takayasu retinopathy (15%), ocular ischemic syn-
Comarmond
drome (7%), hypertensive retinopathy (16%), and
complication-free survival in TAK as 70% and 54%,
steroid-induced
cataract
(23%);
retinopathy
and
ocular ischemic syndrome are only seen in patients
sedimentation
et
al24
rate.
reported
More
5-
recently,
and
10-year
respectively; progressive clinical course (<1 year from
symptom
onset
to
diagnosis),
thoracic
aorta
with aortic arch involvement and were associated
with low or nonrecordable upper limb blood pres-
T A B L E 8 Effects of DMARDs in Takayasu Arteritis
sure. 41 A recent systematic review of the treatment of
Type of DMARD
ocular ischemia in 66 patients with TAK found that
carotid revascularization by open surgery or ET
All
Biologic
Conventional
Synthetic
64
effectively improved both acute and chronic vision
At least partial clinical remission attained
78
84
loss; the visual prognosis was better in patients with
Angiographic stabilization
85
86
81
less severe retinopathy and better visual acuity at
Improvement of PET-CT parameters
69
69
ND
baseline.42
Normalization of inflammatory markers
90
92
80
Relapses
22
26
15
Adverse events
18
21
13
Infections
6
8
2
Median reduction in prednisolone dose
81
81
ND
Mean reduction in prednisolone dose
65
70
63
PROGNOSIS
The prognosis of patients with TAK has improved in
this millennium, which is attributable to several factors (Central Illustration). The overall survival was
Values are %. Extracted with permission from Misra et al.29
97% at 10 years and 86% at 15 years in a North
DMARD ¼ disease-modifying antirheumatic drug; PET-CT ¼ positron emission tomography co-registered with
computed tomography; ND ¼ no data.
43
American study ; mortality was increased compared
182
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F I G U R E 4 The 2018 EULAR Algorithm for Pharmacologic Treatment of Takayasu Arteritis
Phase I
Diagnosis of Takayasu arteritisa
Start glucocorticoid
(GC) 40-60 mg/day
+
Start csDMARDb
Taper GC to 15-20 mg/day
within 2-3 months and then to
≤10 mg/day after 1 year
Continue taper
Yes
Targetc achieved?
No
Phase II
Consider
tocilizumab or
TNF-inhibitor
Major
relapse
Minor
relapse
Increase
GC to 40-60
mg/day
Increase
GC to last
effective
dose
Taper GC
Taper tocilizumab
or TNF-inhibitor
Yes
Targetc
achieved?
No
Consult expert
center
Proposed 2-phase treatment protocol involving glucocorticoids (GC) and conventional synthetic disease-modifying antirheumatic drugs
(csDMARDs) in phase I, and biologic DMARD if relapse occurs (phase II). aThe clinical diagnosis of Takayasu arteritis should be confirmed by
imaging. bCyclophosphamide should be used only if all other csDMARDs are ineffective. cThe treatment target is sustained remission plus the
ability to taper GCs to the specified target without relapse. TNF ¼ tumor necrosis factor. Adapted with permission from Hellmich et al.26
involvement, and retinopathy were identified as risk
robust, gold standard criteria for diagnosing TAK and
factors for vascular complications. The prognosis in
determining disease activity are 2 critical lacunae.
patients with pulmonary artery involvement is worse
Reliable biomarkers are required to distinguish sub-
in those with pulmonary hypertension than those
sets of large-vessel vasculitis, assess disease activity,
without it.45
and predict response to specific therapies.11 Safe imaging techniques with high sensitivity and specificity
DIRECTIONS FOR FUTURE RESEARCH
in detecting areas of vascular inflammation are
another area of need. A deeper understanding of the
Several lacunae exist in the management of TAK that
pathogenesis of TAK may unravel new targets for
could be the focus of future research. The lack of
effective drug development. More clarity is required
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Takayasu Arteritis
F I G U R E 5 Middle Aortic Syndrome in a 38-Year-Old Woman With Takayasu Arteritis
(A) Reconstructed computed tomography angiography image showing severe stenosis of the descending thoracic and abdominal aorta with multiple bridging collaterals, including bilateral Winslow pathway collaterals (yellow arrows). Baseline descending thoracic (B) and abdominal aortic (C) conventional angiograms and
corresponding 1-year follow-up angiograms (D, E) after successful endovascular therapy using an endograft (blue arrow in D) and a braided self-expanding bare stent
(red arrow in E).
in managing advanced vascular disease, and ran-
CONCLUSIONS
domized trials may be required to settle issues that
have eluded resolution. A global registry to capture
The outlook for patients with TAK has improved
the heterogeneity in TAK worldwide would be ideal.
significantly in recent years with the establishment of
183
184
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F I G U R E 6 Aneurysms in a 27-Year-Old Woman With Takayasu Arteritis
Reconstructed computed tomography angiography images are shown. (A) Descending thoracic aorta and left subclavian artery (yellow arrow)
aneurysms. (B) Six-year follow-up after successful endovascular therapy of both aneurysms. The celiac artery received a covered stent
(white arrow) to treat ostial stenosis.
T A B L E 9 Invasive Strategies for Specific Lesions and Arteries
Strategy
Comment
Aortic/mitral regurgitation
Valve replacement surgery
Hospital mortality 4.8% with aortic valve replacement, late
dilatation of ascending aorta 11.1%a
Coronary artery occlusion/stenosis
Coronary artery bypass surgery if refractory to medical
treatment
PCI is associated with 39% restenosis compared with 9% with
bypass surgeryb
Carotid artery
occlusion/stenosis
Balloon angioplasty adjunctive stenting, or bypass surgery
High incidence of brain hyperperfusion after carotid artery
bypass surgeryc
Subclavian artery
occlusion/stenosis
Balloon angioplasty adjunctive stenting in short lesions
(<8 cm); conservative Rx in long lesions
High restenosis rates in long lesions Distal anastomosis to
small arteries may impact bypass surgery resultsd
Descending thoracic stenosis
Endovascular therapy/bypass surgery
Long endografts enable safe high-pressure lesion dilatation
(Figure 5)
Visceral aorta occlusion or stenosis
Endovascular therapy/bypass surgery
Access to aortic side branches is possible via braided selfexpanding stent strutse
Infra-renal aorta and iliac occlusion/
stenosis
Endovascular therapy/aorto-bi-iliac or -femoral bypass
surgery
Covered stents are preferred in occlusions to avoid rupture and
bare stents for stenosis
Mesenteric/renal aorto-ostial
occlusion/stenosis
Balloon angioplasty adjunctive stenting or elective
covered stentd
Bypass surgery/renal autotransplant if endovascular therapy is
not feasible
Pulmonary artery occlusion/stenosis
Balloon angioplasty adjunctive stenting; staged
revascularization
Angioplasty improves survival in patients with pulmonary
hypertensionf
Aortic aneurysms
Open surgery/Bentall procedure/endovascular therapy
(Figure 6)
Hospital mortality 7.4% with Bentall procedurea
93% 5 y survival in a recent hybrid series of thoracic aortic
aneurysmsg
a
Matsuura K, Ogino H, Kobayashi J, et al. Surgical treatment of aortic regurgitation due to Takayasu arteritis: long-term morbidity and mortality. Circulation. 2005;112:3707-3712. bHuang et al.38 cLuo XY,
Wu QH, Zhang FX. Open and endovascular management of severe cerebral ischemia in Takayasu’s arteritis. Ann Vasc Surg. 2017;42:101-110. dPorter and Mason.33 eJoseph G, George PV, Pati PK, Chandy ST.
Feasibility of angioplasty and stenting for abdominal aortic lesions adjacent to previously stented visceral artery lesions in patients with Takayasu arteritis. Cardiovasc Intervent Radiol. 2007;30:293-296.
f
Zhou YP, Wei YP, Yang YJ, et al. Percutaneous pulmonary angioplasty for patients with Takayasu arteritis and pulmonary hypertension. J Am Coll Cardiol. 2022;79:1477-1488. gOishi K, Mizuno T, Fujiwara T,
et al. Surgical strategy for inflammatory thoracic aortic aneurysms in the endovascular surgery era. J Vasc Surg. 2022;75:74-80.e2.
PCI ¼ percutaneous coronary intervention; Rx ¼ treatment.
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Takayasu Arteritis
C ENTR AL I LL U STRA T I O N Components of Patient Care in Takayasu Arteritis
Early diagnosis
• An initial "prepulseless" phase often
goes undiagnosed, characterized by:
• nonspecific constitutional symptoms
(fever, malaise, weight loss)
• raised acute phase reactants (ESR, CRP)
• 18FDG uptake in inflamed arterial walls
revealed by PET-CT
• Immunosuppressive therapy relieves
symptoms and prevents vascular damage
Vascular damage assessment
• CT and MR angiography are the
commonly used imaging modalities
• Involved arteries typically show
wall thickening, obstructive lesions,
ectasia, or aneurysm formation
Optimal
long-term
patient
outcome
Life-long surveillance
• Disease activity and vascular damage
need life-long periodic assessment given
the persistent potential for relapse
• Modalities include clinical assessment,
acute phase reactant levels, MR or CT
angiography, and duplex-ultrasonography
Immunosuppressive therapy
• Halts progressive vascular damage
• Corticosteroids and DMARDs
(synthetic or biologic) are often
used in combination
• Dose and duration are tailored to
suppress disease activity that is
assessed periodically using clinical
and imaging parameters
Invasive therapy
• Performed to palliate critical
obstructive or aneurysmal vascular
lesions
• Open surgery and endovascular
therapy play complementary roles
Joseph G, et al. J Am Coll Cardiol. 2023;81(2):172–186.
Five vital contributing arms of management that together lead to optimal long-term patient outcomes are depicted.
18
FDG ¼
18
fluoro-deoxy-glucose;
CRP ¼ C-reactive protein; CT ¼ computed tomography; DMARD ¼ disease-modifying antirheumatic drug; ESR ¼ erythrocyte sedimentation rate;
MR ¼ magnetic resonance; PET-CT ¼ positron emission tomography co-registered with computed tomography.
diagnostic and classification criteria, better investi-
FUNDING SUPPORT AND AUTHOR DISCLOSURES
gational modalities, and more effective medical and
invasive therapy. However, the understanding of
disease pathogenesis remains poor, diagnosis of TAK
The authors have reported that they have no relationships relevant to
the contents of this paper to disclose.
tends to be delayed, and advanced vascular injury at
presentation is common. Dependence on corticosteroid therapy, although reduced, is still too high.
ADDRESS
Monitoring of disease activity and vascular disease
Joseph, Department of Cardiology, Christian Medical
FOR
CORRESPONDENCE:
progression remains suboptimal. Much work remains
College, Vellore-632004, India. E-mail: joseph59@
to be done more than a century after the initial
gmail.com OR josephg@cmcvellore.ac.in. Twitter:
description of this disease.
@GeorgeJoseph59.
Dr
George
185
186
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JANUARY 17, 2023:172–186
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KEY WORDS antirheumatic agents,
endovascular procedures,
immunosuppression, invasive procedures,
vasculitis