Summary

Takayasu's arteritis is a vasculitis of large vessels that particularly affects the aorta and its
primary branches.
Generally more common in women and typically presents before the age of 40 years.
Typical symptoms include limb claudication on exertion, chest pain, and systemic symptoms
of weight loss,
fatigue, low-grade fever, and myalgia.
On examination, vascular bruits may be audible over the carotids, abdominal aorta, or
subclavian vessels.
Unequal blood pressures may be recorded between sides, and a murmur of aortic
regurgitation may be
heard if there is aortic root dilation.
The diagnosis is usually made by vascular imaging.
Glucocorticoids form the mainstay of treatment, with the additional use of steroid-sparing
immunosuppressive agents for resistant disease. Surgery may be required for established
complications.
Long-term complications are due mainly to arterial occlusion and related damage, including
limb ischaemia
and cardiac and neurological manifestations.

Definition
Takayasu's arteritis is a chronic granulomatous vasculitis affecting large arteries: primarily
the aorta and its
main branches. Vascular inflammation can cause stenosis, occlusion, and aneurysm
formation. Symptoms
from vascular ischaemia include claudication and stroke. Diminished or absent pulses and
hypertension are
common. Constitutional symptoms, including fever and weight loss, are often accompanied
by elevation of
acute phase markers.[1] [2]

Epidemiology
Takayasu's arteritis is a rare disease. Its distribution is worldwide, although most cases are
reported in Asian
populations. The reported incidence in the US is 2.6 cases per million population per year in
Olmsted County,
Minnesota, and in Sweden the incidence has been estimated to be 1.2 cases per million
population per
year.[5] [9] These figures are likely to underestimate the true prevalence of the disease.
Autopsy studies in
Japan suggest a higher incidence, with evidence of Takayasu's arteritis in 1 in every 3000
autopsies.[10]
Although Takayasu's arteritis is often thought of as a disease of young women, the disease
has variable sex
predilection, with women in Japan affected about 8 times more frequently than men,
whereas in India men
and women are equally represented.[4] The peak incidence is usually in the third decade of
life, although
among Japanese people it typically presents between the ages of 15 and 25 years. In
European people the
mean age at diagnosis is 41 years.[2]
Disease expression varies in different populations. Compared with Japanese patients,
patients in the US are
more likely to have constitutional (43% in the US versus 27% in Japan) and musculoskeletal
symptoms (53%
in the US versus 6% in Japan), claudication (90% in the US versus 13% in Japan), and visual
changes (30%
in the US versus 6% in Japan).[2]

Aetiology
The aetiology of Takayasu's arteritis is unknown. Environmental and genetic factors are
thought to play
roles in the development of the disease. Cell-mediated immune mechanisms have been
implicated.[1]
Genetic screening has shown polymorphisms in IL-12, IL-6, and IL-2 genes in a population of
Turkish patients
with Takayasu's arteritis.[11] HLA-Bw5 and HLA-B39.2 are reportedly increased in frequency
in some
populations.[12] [13]

Pathophysiology
Takayasu's arteritis is an immune-mediated vasculitis characterised by granulomatous
inflammation of large
arteries. Cell-mediated immune mechanisms have been implicated.[1] Interleukin (IL)-6 is
thought to play an
important role in the pathogenesis of Takayasu's arteritis. A small number of patients have
been treated with
an IL-6 inhibitor with favourable responses.[14]
The immunological and inflammatory response seen in arteries is similar to that observed in
large arteries
in giant cell arteritis.[1] During the acute phase of vasculitis, inflammation begins in the
vasa vasora of the
adventitia of muscular arteries.[1] [7] T cells are prominent in the initial cellular response,
and anti-endothelial

c Classification
2012 International Chapel Hill Consensus Conference on
the
Nomenclature of Vasculitides[3]
Categorises vasculitis based upon the predominant type of vessels involved, and other
features including
aetiology, pathogenesis, type of inflammation, favoured organ distribution, clinical
manifestations, genetic
predispositions, and distinctive demographic characteristics.
• Large vessel vasculitis
• Takayasu's arteritis ell antibodies may also be involved.[1] [15] [16]

• Giant cell arteritis

• Medium vessel vasculitis
• Polyarteritis nodosa
• Kawasaki disease
• Small vessel vasculitis
• ANCA-associated vasculitis
• Microscopic polyangiitis
• Granulomatosis with polyangiitis (formerly known as Wegener's granulomatosis)
• Eosinophilic granulomatosis with polyangiitis (Churg-Strauss)
• Immune complex vasculitis
• Anti-glomerular basement membrane (anti-GBM) disease
• Cryoglobulinaemic vasculitis
• IgA vasculitis (Henoch-Schönlein)
• Hypocomplementaemic urticarial vasculitis
• Variable vessel vasculitis
• Behçet's disease
• Cogan's syndrome
• Single-organ vasculitis
• Vasculitis associated with systemic disease
• Vasculitis associated with probable aetiology
Angiographic classification of Takayasu's arteritis[4]
Classification is based on the vessels involved in the inflammatory process as seen on
angiography.
• Type I: Branches of the aortic arch
• Type IIa: Ascending aorta, aortic arch, and branches of the aortic arch
• Type IIb: Ascending aorta, aortic arch, and its branches and thoracic descending aorta
• Type III: Thoracic descending aorta, abdominal aorta, and/or renal arteries
• Type IV: Abdominal aorta and/or renal arteries
• Type V: Features of types IIb and IV

Case history
Case history #1
A 28-year-old woman presents with new left-arm pain. She was previously well but for 2
months has had
episodes of low-grade fever, night sweats, and arthralgia. She works as a shop assistant and
has noticed
left-arm pain when she stocks shelves. Her only medication is an oral contraceptive. She
does not smoke
cigarettes. On examination, her blood pressure is 126/72 in her right arm, but it cannot be
measured
in her left arm. The left radial pulse cannot be detected. There is a bruit over the left
subclavian artery.
Carotid pulses are normal but there is a bruit over the right carotid artery. Femoral and
pedal pulses are
Case history #2
A 39-year-old woman presents with headaches of insidious onset over 3 months. She has
lost 3 kilograms
during this time but feels otherwise well. On examination, bilateral blood pressures taken in
the arms are
190/110 on the right and 200/110 on the left. She is taking a multivitamin but no other
medications. For
the past 20 years she has smoked 10 cigarettes a day. Urinalysis reveals an estimated
protein of 360
mg/24 hour.
Other presentations
Non-specific constitutional symptoms, including fever, weight loss, and fatigue, are common.
[1] [5]
Patients may also present with an absent pulse or immeasurable blood pressure in 1
extremity.[6] Newonset hypertension or aortic regurgitation may be present. Coronary
artery involvement can lead to
angina pectoris, but pericarditis and congestive heart failure are uncommon presentations.
Pulmonary
artery involvement may result in chest pain, dyspnoea, or haemoptysis. Involvement of
cranial arteries
can present as a headache, transient ischaemic attack, or stroke. Visual symptoms may
include blurring,
scotoma, diplopia, and amaurosis fugax. The retinal arteriovenous anastomoses described
by Takayasu
are rare.[7] Mesenteric artery involvement can cause abdominal pain or gastrointestinal
haemorrhage.
Vascular bruits are often found on auscultation.[5] [6] Erythema nodosum is occasionally
noted.[8] normal and no abdominal bruits are heard. The left hand is cool but has no other
evidence of ischaemia.

Approach
Establishing the diagnosis of Takayasu's arteritis can be difficult, as it may present with non-
specific systemic
symptoms including fever, night sweats, and weight loss. Other presenting features may
include ischaemic
symptoms of extremity claudication, transient ischaemic attack, stroke, or chest pain.
Laboratory tests are
non-specific, reflecting inflammation. Biopsy of involved vessels is not usually feasible, and
the diagnosis
relies on vascular imaging.[1] [2] [7]
History
In the early stages, constitutional symptoms may include weight loss, low-grade fever, and
general
fatigue, and these are often ascribed to another cause. The diagnosis of Takayasu's arteritis
should
be considered in patients under age 40 years with symptoms of vascular ischaemia.
Although
relatively uncommon at presentation, claudication in the upper or lower limb may develop
over time.
Development of collateral circulation patterns can lead to a variety of other findings,
especially subclavian
steal syndrome caused by a stenotic lesion proximal to the origin of the vertebral artery
causing
lightheadedness on exercise of the upper limb.
Less common manifestations of Takayasu's arteritis include myalgia and arthralgia.
Pulmonary arteries
are often involved in Takayasu's arteritis but rarely cause symptoms. Chest pain, shortness
of breath, and
haemoptysis may be due to pulmonary artery stenosis, coronary artery involvement, or
heart failure from
aortic dilation. Pericarditis is possible but uncommon. Involvement of carotid and vertebral
arteries can
cause cerebral ischaemia, which may in turn cause visual symptoms (e.g., diplopia,
amaurosis fugax,
or scotoma), vertigo, lightheadedness, syncope, or headache. History of a previous transient
ischaemic
attack (TIA), or a TIA as a presenting symptom in a young patient, may indicate
inflammation of the
vertebral or carotid vessels. Less commonly, the mesenteric vessels may be involved,
causing abdominal
pain and diarrhoea.[1] [2] [7] [17] [18]
Examination
Careful examination of the vascular system is vital. Cool extremities and absent pulses
(most commonly
the radial pulse) may be noted, and a difference in blood pressure of >10 mmHg on each
arm may be
significant. If Takayasu's arteritis is suspected, it is advisable to measure the blood pressure
on both
arms and legs to look for a difference. Hypertension may be a feature, but the blood
pressure can also be
unusually low if there is a stenosis just proximal to the area of blood pressure measurement.
The carotid
pulses may feel weaker, and a bruit might be audible. Bruits may also be heard over the
supraclavicular
region or abdominal aorta. A cardiac murmur may be audible if there is aortic root
involvement and aortic
regurgitation. Evidence of a previous stroke may suggest central nervous system
involvement. The
arteriovenous anastomoses seen on examination of the retina and originally described by
Takayasu in
1908 are rarely seen today.[1] [2] [7] Less common manifestations include the appearance
of erythema
nodosum or pyoderma gangrenosum on the arms or legs.
Investigations
Acute phase markers, including erythrocyte sedimentation rate (ESR) and C-reactive protein
(CRP), are
usually elevated in patients with active disease. They can be followed as markers of disease
activity.[1] [2]
[7] Other non-specific markers of inflammation such as normocytic anaemia and
thrombocytosis may also
be noted. There are no specific laboratory tests for Takayasu's arteritis.

Imaging studies, including computed tomography, magnetic resonance vascular imaging,

and
conventional angiography, are the most important modalities for establishing a diagnosis of
Takayasu's

arteritis and can be helpful in monitoring disease activity. Positron emission tomography
with radiolabelled fluorodeoxyglucose (PET-FDG) can be used to identify
inflammation in the large arteries, and is therefore a useful technique to establish diagnosis.
However, the
performance of PET-FDG for assessing disease activity over time is still unclear.[19]
Non-invasive vascular ultrasonography is a useful tool for initial evaluation of a patient with
suspected
Takayasu's arteritis.[1] [2] [7] [18] [20] [21]
Histopathology
Biopsy cannot usually be obtained from one of the vessels typically involved, due to the
vessels' size
and function as large arteries, and is therefore not part of the usual approach to diagnosis.
Biopsy
specimens from patients who have undergone revascularisation procedures secondary to
complications
of Takayasu's arteritis may show histopathological findings identical to those of giant cell
arteritis.

Temporal artery biopsy is not helpful in making the diagnosis.[1] [2] [7] [18] History
and exam
Key diagnostic factors
presence of risk factors (common)

• Takayasu's arteritis is more common in people of Asian descent, is 8 times more common
in women
than in men, and typically presents below age 40 years.
upper or lower limb claudication (common)
• Progressive symptoms of claudication are more common than claudication as a presenting
feature.
A history of pain on exertion of the upper or lower limb may be given; upper limb
claudication is more
common.
absent pulse(s) (common)
• Often found to have unilateral absence of brachial, radial, or carotid pulse due to occlusive
disease.
unequal blood pressures (common)
• A discrepancy of >10 mmHg between the 2 arms may be noted.
vascular bruits (common)
• Bruits may be heard over subclavian, carotid, or abdominal vessels due to eccentric flow.
low-grade fever (common)
• A systemic sign, often present during the acute phase of inflammation.
Other diagnostic factors
transient ischaemic attack (TIA) (common)
• History of a previous TIA, or a TIA as a presenting complaint in a young patient, may
indicate
inflammation of the vertebral or carotid vessels.
myalgia (common)
• A systemic symptom, seen in the acute phase; may be accompanied by a rise in
inflammatory
markers.
arthralgia (common)
• A systemic symptom, seen in the acute phase; may be accompanied by a rise in
inflammatory
markers.
weight loss (common)
• A systemic symptom, seen in the acute phase; may be accompanied by a rise in
inflammatory
markers.
fatigue (common)
• A systemic symptom, seen in the acute phase; may be accompanied by a rise in
inflammatory
markers.
dizziness on upper-limb exertion (common)
• May result from subclavian steal syndrome due to a stenotic lesion developing proximal to
the origin of
the vertebral artery.

hypertension (common) May develop due to involvement and narrowing of the

renal arteries. Can be falsely low if there is a
narrowed segment proximally.
stroke (uncommon)
• Evidence of a previous stroke may be suggestive of central nervous system involvement
and arteritis
affecting the vertebral or carotid vessels.
chest pain (uncommon)
• This can be a feature of Takayasu's arteritis if the coronary vasculature is involved,
causing coronary
ischaemia, or if pulmonary arteries are affected.
abdominal pain (uncommon)
• May result from involvement of the mesenteric branches of the aorta.
diarrhoea (uncommon)
• May result from involvement of the mesenteric branches of the aorta.
shortness of breath (uncommon)
• Due to pulmonary artery stenosis, coronary artery involvement, or aortic regurgitation.
haemoptysis (uncommon)
• May result from pulmonary artery stenosis or heart failure due to aortic root dilation and
aortic
regurgitation.
night sweats (uncommon)
• Constitutional symptom that may be reported during the acute phase.
vertigo (uncommon)
• May result from cerebral ischaemia.
syncope (uncommon)
• May result from cerebral ischaemia.
headache (uncommon)
• May result from cerebral ischaemia or hypertension.
heart murmur (uncommon)
• Aortic regurgitation may result from aortic root dilation.
visual symptoms (uncommon)
• Due to cerebral ischaemia secondary to carotid and vertebral involvement. May include
amaurosis
fugax, scotoma, or diplopia. The retinopathy originally described by Mikoto Takayasu is
rarely seen and
is usually a late sign.
erythema nodosum (uncommon)
• Uncommonly found on the arms or legs.
pyoderma gangrenosum (uncommon)

• Uncommonly found on the legs.

Risk factors
Strong
genetic predisposition
• Takayasu's arteritis is most prevalent in Japan, Southeast Asia, India, and Mexico.[1] [2]
[9] [10]
Polymorphisms in interleukin genes have been demonstrated in a population of Turkish
patients with
Takayasu's arteritis, and certain HLA antigens have been found in greater-than-expected
frequency in
some patient populations.[11] [12]

female sex
• Takayasu's arteritis is generally more common in females.[1] [4]
age <40 years
• Patients are usually under age 40 years at presentation.[1] [5] [9]

Asian ethnicity
• There are more reported cases in Asian populations compared with non-Asian, although
the reasons
for this are unclear, and there may be a genetic basis confounding this association.

Investigations
1st test to order
Test Result
erythrocyte sedimentation rate (ESR)
• A marker of inflammation, but it lacks specificity and
sensitivity. Most
typically >50 mm/hour
patients with elevated ESR do not have Takayasu's arteritis,
with active disease
and
patients with active disease can have a normal ESR.[1] [2] [18]
[22]
C-reactive protein (CRP)
• A marker of inflammation. Lacks specificity, as it can be raised typically elevated with
by any active disease
inflammatory process. Sensitivity is moderate.[1] [2] [18] [22]
segmental narrowing
or
computed tomography angiography (CTA) occlusion, occasionally
• CTA may be performed with helical scanning and 3D dilation, of affected
reconstruction. vessels; aortic
It has high sensitivity and specificity (over 95%) for the aneurysms
diagnosis may be seen;
of Takayasu's arteritis. It is preferable to catheter angiogram thickening
due to of vessel walls may be
reduced contrast load.[21] [23] seen but is of
uncertain
significance
Computed tomography angiogram, with 3D reconstruction
of the aortic arch and major vessels, showing proximal
occlusion of the left subclavian artery and patent left vertebral
artery distal to the occlusion (left vertebral steal syndrome)
From the collection of Kenneth J. Warrington, MD
segmental narrowing,
magnetic resonance angiography (MRA)
occlusion, or dilation of
• MRA is used to identify arterial involvement, and it may be useful in
the assessment of disease activity, with vessel wall thickening and
involved arteries; vessel
oedema thought to reflect active disease.[24] wall inflammation may be
detectable
Magnetic resonance angiogram of the aortic arch and major vessels
showing occlusion of bilateral subclavian arteries; left common carotid
artery has small diameter; proximal vertebral arteries are not
identified
From the collection of Kenneth J. Warrington, MD

Other tests to consider

Test Result

segmental narrowing
or
catheter angiogram
occlusion, occasionally
• Conventional angiogram using contrast can reveal
dilation of affected
abnormalities in
vessels, aortic
the aorta and its branches.
aneurysms
may be seen
Catheter angiogram showing bilateral renal artery stenosis
From the collection of Kenneth J. Warrington, MD
Doppler ultrasound
• Particularly useful in the early vascular evaluation of patients with
segmental narrowing,
suspected Takayasu's arteritis, as it is a non-invasive procedure.
Abdominal ultrasound may reveal mesenteric or renal artery stenosis,
occlusion, and/or dilation
and transthoracic/trans-oesophageal studies can detect abnormalities of involved arteries
in the upper aorta and subclavian and carotid arteries.[25]
positron emission tomography with radiolabelled
fluorodeoxyglucose (PET-FDG)
• Can be used to identify inflammation in the large arteries and is
therefore a useful technique to establish diagnosis. However, the
performance of PET-FDG for assessing disease activity over time is may show increased
still unclear.[19] uptake in actively
• PET tracer uptake has been correlated with areas of active disease inflamed arterial
on magnetic resonance angiography and has been correlated with segments
elevation of erythrocyte sedimentation rate/C-reactive protein. The
sensitivity and specificity of PET imaging has not been established;
atherosclerotic lesions may also show increased tracer uptake.[21]
[26] [27]

Differentials
Condition Differentiating signs /
symptoms
Differentiating tests
• Patients are usually older;
• Imaging with CT or magnetic
average age is 74 years.
resonance angiography;
May have polymyalgic
Giant cell arteritis GCA is more likely to have
syndrome with proximal
(GCA) cranial artery involvement
myalgia. Jaw claudication is
and less likely to have lower
common. Lower extremity
extremity involvement.
involvement is less common.
• Intact pulses and the
• Clinical diagnosis.
absence of bruits. No
Essential hypertension • No stenoses on vascular
marked difference in blood
imaging.
pressure between each side.
• Firm, painless ulcer at site of
• Positive syphilis serology.
primary inoculation, usually
• Catheter or CT angiogram:
Syphilis genital region. Symmetrical
typical calcification of the
non-itchy rash accompanies
proximal ascending aorta.
systemic symptoms.
Tuberculosis (TB) • Persistent productive cough. • Mantoux test: elicits delayed
Recent travel to an endemic hypersensitivity reaction,
area. which will be positive in
people with latent infection,
 previously cleared infection,
or in those previously
immunised.
• Chest x-ray: may show
evidence of pulmonary TB
foci.
• Sputum culture: takes 4 to
12 weeks to culture acid
fast bacilli but is diagnostic if
found.
• QuantiFERON® gold test:
blood test to detect interferon
gamma production when
incubated with TB bacilli.
Can identify active and latent
infection.
• Back pain and stiffness
lasting more than 1 hour,
particularly in the mornings.
• X-ray of spine: may
Peripheral arthritis. May
demonstrate sacroiliitis.
be preceded by urethritis
• X-ray of peripheral joint
Spondyloarthropathy or cervicitis in the case
affected by arthritis may
of reactive arthritis.
show periarticular osteolysis
Accompanying symptoms
in psoriatic arthritis.
may include psoriasis,
palmar-plantar pustulosis,
iritis, uveitis, or conjunctivitis.
Condition Differentiating signs /
symptoms
Differentiating tests
• Angiography: reveals
saccular dilation of involved
• A triad of oral and genital
arteries or thrombotic
ulceration with uveitis.
occlusion.
Often accompanied by a
Behçet's disease • Cerebrospinal fluid
peripheral arthritis. May
examination supportive but
have thrombotic arterial and
not diagnostic; increased
venous occlusions.
inflammatory cells and
protein.
• Typically affects children
under age 5 years.
High-grade fever with • Clinical diagnosis using set
strawberry-tongue-marked criteria.
Kawasaki disease lymphadenopathy. Red eyes • Angiography reveals
with uveitis or conjunctivitis. saccular dilation of coronary
Rash and peeling of the skin arteries if affected.
on the palms and soles may
be seen.
Marfan's syndrome • Typically tall people with • Clinical diagnosis.
long limbs. May have a • Family history.
family history of Marfan's • Genetic testing rarely carried
syndrome. Susceptible to out.
lens dislocation.
• Systemic signs and
 symptoms absent.
• Angiography: if vascular wall
• May have hypermobile joints
collagen affected, may reveal
Ehlers-Danlos or paper-thin skin scars.
saccular dilation of involved
syndrome • Systemic signs and
arteries.
symptoms absent.
• Genetic testing.
• More common in men, may
• Angiography: typical abrupt
have associated risk factors
narrowing of artery rather
of hypertension, smoking,
than tapered narrowing.
Atherosclerosis diabetes mellitus, and
Lesions usually at the
raised cholesterol. Typically,
vessel origin and carotid
patients are aged over 40
bifurcations.
years.
• Pulses present but may be
diminished. Hypertension • Angiography: characteristic
Fibromuscular
common and most beading of affected arteries.
dysplasia
commonly affects renal and Aorta not usually involved.
carotid arteries.
Criteria
American College of Rheumatology 1990 criteria for the
classification of Takayasu's arteritis[22]
These are not formal diagnostic criteria but were established to help differentiate Takayasu's
arteritis from
other forms of vasculitis. Imaging may include conventional angiography or magnetic
resonance or computed
tomography angiography. Presence of 3 or more criteria has a sensitivity of 90.5% and a
specificity of 97.8%
for diagnosis of Takayasu's arteritis.
• Age at onset of disease less than or equal to 40 years.
• Claudication of extremities: development and worsening of fatigue and discomfort in
muscles of 1 or
more extremity while in use.
• Decreased brachial artery pulse.
• Systolic blood pressure difference greater than 10 mmHg between arms.
• Bruit over subclavian arteries or abdominal aorta.
• Arteriographic abnormality: narrowing or occlusion of the entire 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.
K. Ishikawa: proposed criteria for the clinical diagnosis of
Takayasu's arteriopathy[28]
Criteria suggested by Ishikawa for diagnosing Takayasu's arteritis were based on
observations in 108
Japanese patients. In addition to the presence of the obligatory criterion, the presence of 2
major, 4 minor,
or 1 major plus 2 minor criteria suggests a high probability of Takayasu's disease with 84%
sensitivity. These
criteria are not widely applied.
Obligatory criterion:
• Age less than or equal to 40 years
Major criteria:
• Lesion of the left mid subclavian artery
• Lesion of the right mid subclavian artery
Minor criteria:
• High erythrocyte sedimentation rate
• Common carotid artery tenderness
• Hypertension
• Aortic regurgitation or annulo-aortic ectasia
• Lesions of the pulmonary artery
• Lesions of the left mid common carotid artery
• Lesions of the distal brachiocephalic trunk
• Lesions of the thoracic aorta
• Lesions of the abdominal aorta.

Approach
The goal of treatment for Takayasu's arteritis is to manage systemic symptoms and
suppress vascular
inflammation to prevent damage to vessels and the tissues they supply. Glucocorticoids are
the mainstay of
treatment, with immunosuppressive agents used for resistant patients or those with
glucocorticoid-related
side effects. Surgical or percutaneous revascularisation procedures may be required to
improve blood
flow or prevent rupture of aneurysms. Low-dose aspirin should be considered to help
prevent ischaemic
complications.
Initial presentation
Oral glucocorticoids should be started. No studies have established the optimal way to taper
glucocorticoids, but most follow the regimen originally described in the cohort from the
National Institutes
of Health (NIH).[6] [29]
Pulse intravenous glucocorticoids have been tried in some patients with central nervous
system
symptoms, but there are no data to support their use.
During treatment, patients should be evaluated regularly by clinical examination and
measurement of
inflammatory markers (i.e., erythrocyte sedimentation rate and C-reactive protein); initially,
this may
be every few days. Vascular imaging studies such as computed tomography or magnetic
resonance
angiography should be performed every 3 to 12 months during the active phase of
treatment and annually
thereafter. Low-dose aspirin should be considered to help prevent ischaemic complications.
A critical issue is in trying to determine whether or not disease is active. Constitutional
symptoms are
frequent when Takayasu's arteritis is active. However, lack of such symptoms does not
mean that the
disease is inactive. New vascular lesions can develop even when no other signs, symptoms,
or laboratory
features of disease activity are present. If new vascular lesions are seen, the disease is
considered to be
active. Conversely, acute phase markers may be elevated from other causes and not
indicate disease
activity. Careful evaluation is required.
Refractory to, or unable to wean from, glucocorticoids
The majority of patients will go into remission with glucocorticoid therapy. However, relapse
occurs in
more than 50% of patients during dose tapering. Therefore, European League Against
Rheumatism
(EULAR) guidelines recommend early initiation of corticosteroid-sparing immunosuppressive
agents such
as methotrexate, leflunomide, azathioprine, or mycophenolate.[30] [31]
In patients with severe or life- or organ-threatening disease, use of cyclophosphamide may
be indicated.
However, the benefit of using cyclophosphamide needs to be considered carefully in the
context of its
known toxicity, particularly premature ovarian failure and long-term risk of secondary
malignancies.[32]
There is no evidence to advise on discontinuation of immunosuppressive therapy, and this
will depend on
individual circumstances.
Refractory to glucocorticoids and additional
immunosuppression
Tumour necrosis factor (TNF)-alpha inhibitors, primarily infliximab, have also been used
successfully in
the management of Takayasu's arteritis when immunosuppressive agents and glucocorticoid
therapy
have failed to control disease activity. These agents are used in addition to glucocorticoids
as a
MANAGEcorticosteroid-sparing agent.[33] [34] [35] Non-biological immunosuppressive
agents may be continued or
tapered.[36]
Symptoms of intermittent claudication or ischaemic organ
dysfunction
Surgical intervention may be required in patients with severe complications of Takayasu's
arteritis.
Vascular lesions are usually not reversible with immunosuppression alone. Therefore,
patients with
significant limb claudication or severe ischaemic organ dysfunction may require surgical
intervention.
Percutaneous angioplasty can be effective in the short term, but re-stenosis is common.[37]
Good longterm outcomes have been reported with vascular bypass surgery.[38] [39]
Patients with progressive
dilation of the aorta may require surgical repair.[40] Except for emergency indications,
vascular
interventions should preferably be performed when the disease is in remission and
inflammation is under
control.
Prevention of complications from long-term glucocorticoid
use
Prolonged glucocorticoid treatment can lead to significant morbidity. Attention to potential
side effects is
critical. Long-term glucocorticoid therapy increases the risk of osteoporosis, and the greatest
amount of
bone loss occurs in the first 6 to 12 months of therapy. Prevention of glucocorticoid-induced
bone loss
by treatment with calcium, vitamin D, and bisphosphonates is recommended.
Glucocorticoid-induced
diabetes mellitus is a potential side effect of therapy, and a high index of suspicion is
required.
Due to the immunosuppressive effects of glucocorticoids, influenza and pneumococcal
vaccination
are recommended, and, while the daily prednisolone (prednisone) dose is greater than 20
mg/day,

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formularies, or locations. Treatment recommendations are specific to patient groups: see
disclaimer

Acute ( summary )
all patients
1st glucocorticoids
plus low-dose aspirin
plus bone protection therapy
adjunct immunosuppressants
adjunct pneumocystis pneumonia prophylaxis
adjunct evaluation for surgery or endovascular
procedure
adjunct tumour necrosis factor (TNF)-alpha
antagonist
rophylaxis for Pneumocystis jirovecii pneumonia with trimethoprim/sulfamethoxazole is
advised

Treatment algorithm
Please note that formulations/routes and doses may differ between drug names and brands,
drug
formularies, or locations. Treatment recommendations are specific to patient groups:

Acute
all patients
glucocorticoids
1s
Primary
t
options
» prednisolone: 1 mg/kg/day orally initially,
then taper according to response, usual
starting dose 40-60 mg/day
» Glucocorticoids are the mainstay of therapy to
suppress vascular inflammation and systemic
inflammatory symptoms. Duration of therapy
varies, but dose can be reduced once signs and
symptoms have diminished and acute phase
markers have normalised.
» A common tapering regimen is to reduce
prednisolone (prednisone) by 5 mg/week until
reaching a dose of 20 mg/day. Thereafter, the
taper rate is decreased to 2.5 mg/week until
reaching a dose of 10 mg/day. Thereafter, the
dose is lowered by 1 mg/day each week, as long
as disease does not become more active.[6] The
2018 European League Against Rheumatism
(EULAR) recommendations for management
of left ventricular volume suggest reducing
prednisolone (prednisone) to a dose of 15-20
mg/day within 2 to 3 months, and then to ≤10
mg/day after 1 year.[31]
» Glucocorticoid tapering may have to be
stopped and the dose increased if there is return
of disease activity.
plus low-dose aspirin
Treatment recommended for ALL patients in
selected patient group
Primary options
» aspirin: 75 mg orally once daily
» Low-dose aspirin is recommended to reduce
the risk of organ damage from vascular
ischaemia. It is usually stopped 1 week prior to
any surgical procedure.
plus bone protection therapy
Treatment recommended for ALL patients in
selected patient group
Primary options
» alendronic acid: 5 mg orally once daily
OR
Acute
» alendronic acid: 35 mg orally once weekly
--AND--
» calcitriol: 0.25 micrograms orally once daily
--AND--
» calcium carbonate: 1000-1500 mg/day
orally given in 2-3 divided doses
» Long-term glucocorticoid therapy increases the
risk of osteoporosis, and the greatest amount
of bone loss occurs in the first 6 to 12 months
of therapy. Risk is proportional to cumulative
glucocorticoid dose, so dose should be reduced
as soon as possible. It is important to prevent
bone loss by ensuring adequate dietary calcium
intake and prophylactic use of bisphosphonates
and vitamin D3/calcium supplementation.
adjunct immunosuppressants
Treatment recommended for SOME patients in
selected patient group
Primary options
» methotrexate: 15-25 mg orally/
subcutaneously once weekly on the same
day each week
--AND--
» folinic acid: 10 mg orally every 6 hours for
10 doses starting 10 hours after methotrexate
dose
-or-
» folic acid: 1 mg orally once daily
Secondary options
» azathioprine: 2 mg/kg/day orally
OR
» mycophenolate mofetil: 1 to 1.5 g orally/
intravenously twice daily
OR
» leflunomide: 20 mg orally once daily
Tertiary options
» cyclophosphamide: 2 mg/kg/day orally
» Relapse occurs in more than 50% of patients
during glucocorticoid tapering. Therefore,
adjunctive use of immunosuppressive agents
such as methotrexate, leflunomide, azathioprine,
Acute
» In an open-label study, methotrexate was
effective as a corticosteroid-sparing agent for a
subset of patients with Takayasu's arteritis.[30]
» Azathioprine or mycophenolate or leflunomide
can be considered for patients who are intolerant
to, or relapse while on, methotrexate.[6] [41]
» In patients with severe or life- or organthreatening disease, use of cyclophosphamide
may be indicated. However, the benefit of
cyclophosphamide needs to be considered
carefully in the context of its known toxicity,
particularly premature ovarian failure, and longterm risk of secondary malignancies.[32]
» There is no evidence to advise on
discontinuation of immunosuppressive therapy,
and this will depend on individual circumstances.
adjunct pneumocystis pneumonia prophylaxis
Treatment recommended for SOME patients in
selected patient group
Primary options
» trimethoprim/sulfamethoxazole: 160/800 mg
orally three times weekly
» While patients are receiving over 20 mg/day
of prednisolone (prednisone), prophylaxis for
pneumocystis pneumonia is recommended.
Trimethoprim/sulfamethoxazole is the
recommended antibiotic.
» Some recommend continuing prophylaxis, as
long as the CD4 lymphocyte count is <200 cells/
mm³.

evaluation for surgery or

adjun
endovascular
ct
procedure
Treatment recommended for SOME patients in
selected patient group
» Vascular lesions are not usually reversible
with immunosuppression alone. Therefore,
patients with significant limb claudication or
severe ischaemic organ dysfunction may
require surgical intervention. Some reports
have indicated good short-term outcomes with
percutaneous intervention for vascular stenoses
in patients with Takayasu's arteritis. However,
re-stenoses are common with this intervention,
and bypass surgery often yields better long-term
results.[6] [37]
» Patients with aneurismal disease of the aorta
may require surgical repair.[40] Except for
emergency indications, vascular interventions or mycophenolate is often necessary.[30] [31]

Acute
should preferably be performed when the
disease is in remission and inflammation is
under control. Patients with active disease
requiring operation are more likely to require
revision.[38] Therefore, control of inflammation
prior to vascular surgery is important to improve
surgical outcome. Long-term complications may
include anastomotic aneurysms and congestive
heart failure.[40]
tumour necrosis factor (TNF)-
adjun
alpha
ct
antagonist
Treatment recommended for SOME patients in
selected patient group
Primary options
» infliximab: 3-5 mg/kg intravenously as a
single dose at 0, 2, and 6 weeks, then every
4-8 weeks thereafter
» TNF-alpha antagonist therapy may be
considered with persistent active disease
despite treatment with glucocorticoids and
immunosuppressive agents.
» In a pilot study of relapsing Takayasu's
arteritis, anti-TNF therapy resulted in
improvement in 93% of patients and sustained
remission in 67%. Most patients in this study
were treated with infliximab.[33]
» Retrospective reviews also support the use of
anti-TNF therapy for refractory disease.[34] [35]
» There is no evidence to advise on
discontinuation of immunosuppressive therapy,
and this will depend on individual circumstances

Emerging
Interleukin-6 (IL-6) inhibitors
IL-6 is thought to play an important role in the pathogenesis of Takayasu's arteritis. Several
small case series
of patients treated with tocilizumab have been reported. In general, most patients have had
favourable
responses, although disease relapse may still occur.[14] [36] Tocilizumab was evaluated in a
double-blind,
placebo-controlled trial in patients with refractory Takayasu's arteritis. The primary endpoint
of the trial (time
to relapse) was not met in the intent-to-treat analysis (P=0.06). However, a favourable
response was seen in
a subset of patients.[42]
Abatacept
T-cell-mediated mechanisms are involved in the pathogenesis of Takayasu's arteritis.
Abatacept inhibits
activation of T cells. However, in one randomised clinical trial, addition of abatacept to a
treatment regimen
with prednisolone (prednisone) did not reduce the risk of relapse in patients with Takayasu's
arteritis.[43]

Secondary prevention
As the precise aetiology of Takayasu's arteritis and causes of flare-ups in disease activity are
unknown,
there are no known specific preventative actions. Management of hypertension is important
to prevent
further vascular damage. Attention to osteoporosis screening and management is crucial,
given the need
for glucocorticoid therapy. Patients require influenza and pneumococcal immunisations
annually. Use
of prophylactic antibiotic therapy to prevent Pneumocystis jirovecii pneumonia is important,
especially
when the prednisolone (prednisone) dose is more than 20 mg daily. Atherosclerotic vascular
disease can
further complicate the vascular damage caused by Takayasu's arteritis; thus, control of
other risk factors is
important.

Patient discussions
Measures to help with control of hypertension, such as following a low-salt diet, are
important to prevent
damage to the arteries leading to stroke, heart attack, or kidney failure. A programme of
gradually
increasing exercise can help form a collateral circulation, which provides new pathways for
blood to
reach organs and limbs and lessens claudication symptoms. Stopping smoking and
controlling blood
fats, including cholesterol, is essential to good general health and to the health of the
arteries. General
health measures also include keeping immunisations up to date, especially if the patient is
maintained on
immunosuppressive therapy. [Vasculitis Foundation] (http://www.vasculitisfoundation.org)
[Medline Plus:
Takayasu arteritis] (http://www.nlm.nih.gov/medlineplus/ency/article/001250.htm)

Monitoring
Monitoring
The monitoring interval should vary inversely with the level of disease activity, being shorter
for those with
more active disease. However, as the disease may become active without new constitutional
symptoms,
regular follow-up is needed. In addition to history and physical examination, erythrocyte
sedimentation
rate, C-reactive protein, and full blood count should be checked at each visit. Vascular
imaging studies
such as computed tomography or magnetic resonance angiography should be performed
every 3 to 12
months during the active phase of treatment and annually thereafter

Complications
Complications Timeframe Likelihood
peripheral vascular ischaemia variable high
Many of the complications of Takayasu's arteritis represent
ischaemic symptoms related to the
development of vascular stenoses and occlusions.
Differentiating between ischaemia resulting from active
vasculitis and ischaemia from vascular damage can be
difficult. Regular vascular imaging studies can help
with follow-up but should also be obtained in the setting of
new ischaemic symptoms. Attempts to control
vascular inflammation are needed to try to minimise long-
term vascular damage.
hypertension variable high
Hypertension is a common complication, usually due to
renal artery or aortic valve stenosis.[6]
osteoporosis secondary to glucocorticoid use variable high
Long-term glucocorticoid therapy increases the risk of
osteoporosis, and the greatest amount of bone loss
occurs in the first 6 to 12 months of therapy. Risk is
proportional to cumulative dose, so glucocorticoid
dose should be reduced as soon as possible.
diabetes mellitus secondary to glucocorticoid use variable medium
Long-term glucocorticoid therapy can cause the
development of diabetes mellitus. A high degree of
vigilance is required.
Pneumocystis jirovecii pneumonia variable medium
Patients require influenza and pneumococcal immunisations
annually. Use of prophylactic antibiotic
therapy to prevent Pneumocystis jirovecii pneumonia is
important, especially when the prednisolone
(prednisone) dose is more than 20 mg daily.
aortic aneurysm variable medium
Most often involves the ascending thoracic aorta.
aortic regurgitation variable medium
Aortic valve insufficiency, usually due to aortic root dilation,
is found in about 25% of patients.[6]
congestive heart failure variable medium
Congestive heart failure occurs in about 25% of patients.[6]
angina variable low
Angina from coronary artery involvement is described in up
to 10% of patients.[6]
stroke variable low
Complications Timeframe Likelihood
Involvement of carotid or vertebral arteries can result in a transient ischaemic attack or
stroke. Visual
disturbance including blurred vision and amaurosis fugax may be present, but permanent
visual loss is
uncommon.[6]

Prognosis
Remission of disease is usually defined as the lack of clinical and laboratory features of
disease, with no
evidence of new vascular lesions on follow-up imaging examinations.[2] [6] Most patients
achieve disease
remission, although the majority require immunosuppressive therapy in addition to
glucocorticoids.[6]
Monophasic disease is described in about 20% of patients.[2] In one series, sustained
remission, lasting for
at least 6 months while on <10 mg of prednisolone (prednisone) daily, was attained by only
28% of patients,
and only 17% remained in remission after prednisolone (prednisone) was discontinued.[6]
Disease relapses occur in >80% of all patients who go into remission.[2] [6] Relapses can
occur despite
ongoing immunosuppressive treatment. Relapses manifest as new vascular lesions on
imaging studies are
typically associated with elevation of acute phase markers, but this laboratory evidence of
active disease can
be lacking.[6] [44]

Mortality and morbidity

Cardiac failure is a common cause of death.[18] Long-term morbidity is related primarily to
complications
from vascular ischaemia. Symptomatic extremity claudication occurs in about 50% of
patients. Upperextremity claudication is more common than lower-extremity symptoms.
Thoracic aortic aneurysm, aortic
valve involvement, and arteritis of coronary and pulmonary arteries are known
complications that are
associated with increased mortality. The 5-year mortality in Takayasu's arteritis is estimated
to be between
70% and 93%.[45]
Pregnancy
Because Takayasu's arteritis is primarily a disease of young women, pregnancy is often a
consideration.
There are few data about pregnancy in patients with Takayasu's arteritis, but successful
pregnancies have
been reported.[6] [46] In one series of patients, the annual incidence of pregnancies fell
after the diagnosis of
Takayasu's arteritis, and the percentage of miscarriages showed an upward trend.[46]
Careful management
of hypertension is necessary during pregnancy.
Diagnostic guidelines
North America
Criteria for the classification of Takayasu arteritis (https://
www.rheumatology.org/Practice-Quality/Clinical-Support/Criteria)
Published by: American College of Rheumatology Last published: 1990

Treatment guidelines
North America
Guideline for the management of giant cell arteritis and Takayasu
arteritis
(https://www.rheumatology.org/Practice-Quality/Clinical-Support/Cli
nicalPractice-Guidelines)
Published by: American College of Rheumatology; Vasculitis
Foundation