481

REVIEW

Takayasu arteritis: a review

S L Johnston, R J Lock, M M Gompels
.............................................................................................................................

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J Clin Pathol 2002;55:481–486

Takayasu arteritis is a well known yet rare form of large Hall et al found the incidence to be 2.6/million/
vessel vasculitis. This review details the history, clinical year.6 The UK incidence is unknown.
features, differential diagnoses, classification, and
CLINICAL FEATURES
immunology of the disorder. Suppression of The clinical features have been well documented
inflammation and preservation of vascular competence by cohort studies of over 570 patients from differ-
are the aims of treatment. As with any rare disease, ent countries.1 6–13 Manifestations range from
asymptomatic disease found as a result of impal-
randomised controlled treatment trials are either lacking pable pulses or bruits, to catastrophic neurologi-
or based on small patient numbers, making cal impairment. A two stage process has been
management decisions difficult. Current evidence based suggested with a “pre-pulseless” phase character-
ised by non-specific inflammatory features, fol-
treatments are presented and discussed. lowed by a chronic phase with the development of
.......................................................................... vascular insufficiency, in some cases accompanied
by intermittent flares, although not all patients
conform to this pattern.6

T
akayasu arteritis, also known as pulseless
disease, occlusive thromboaortopathy, and
Martorell syndrome,1 is a chronic inflamma- “As the inflammation progresses and
tory arteritis affecting large vessels, predomi- stenoses develop, the more characteristic
nantly the aorta and its main branches. Vessel features become apparent, influenced by
inflammation leads to wall thickening, fibrosis, the development of collateral circulation”
stenosis, and thrombus formation. Symptoms
reflect end organ ischaemia. More acute inflam- The disease commonly presents in the 2nd or
mation can destroy the arterial media and lead to 3rd decade of life, often with a delay in diagnosis
aneurysm formation.2 Early reports suggested from the onset of first symptoms of months to
that the disease was confined to females from years. In one of the largest cohorts (n = 107) 80%
Eastern Asia, but it has now been recognised of patients were between 11 and 30 years, 77%
worldwide in both sexes, although disease mani- had disease onset between the ages of 10 and 20
festations vary between populations. The female years, with time from onset of symptoms to diag-
to male ratio appears to decline from Eastern Asia nosis of two to 11 years in 78%.1 A study of 88
towards the West. patients from India9 gave a mean (SD) age at
symptom onset of 24.0 (8.8) years and mean (SD)
HISTORY age at diagnosis of 28.3 (9.9) years. The National
Published descriptions of this arteritis date back Institute of Health study by Kerr et al suggested
as far as 1830.2 Yamamoto described the case of a that the delay in diagnosis was longer in
45 year old man with persistent fever who devel- juveniles, being up to four times that of adult
oped impalpable upper limb and carotid pulses patients.10 However, data from India12 looking at
associated with weight loss and dyspnoea.3 In patients aged under 18 years demonstrated a
1905 Takayasu, professor of ophthalmology at delay of only 2.5 to 5.5 months. This discrepancy
Kanazawa University Japan, presented the case of presumably relates to the difference in disease
a 21 year old woman with characteristic fundal incidence between the two populations, which
arteriovenous anastamoses.4 In the same year, results in differences in awareness. The clinical
Onishi and Kagosha each described similar cases features and progress of young patients with
associated with absent radial pulses.3 In 1920, the Takayasu arteritis appear to be very similar to
first postmortem case of a 25 year old woman those of adults.12
demonstrated panarteritis and suggested that the Non-specific features include fever, night
See end of article for fundal appearances resulted from retinal sweats, malaise, weight loss, arthralgia, myalgia,
authors’ affiliations ischaemia.2 In 1951, Shimizu and Sano summa- and mild anaemia.6 As the inflammation
....................... rised the clinical features of this “pulseless progresses and stenoses develop, the more char-
Correspondence to: disease”.5 acteristic features become apparent, influenced
Dr S L Johnston, by the development of collateral circulation. Sten-
Department of Immunology otic lesions predominate9 10 and tend to be
and Immunogenetics,
INCIDENCE
Southmead Hospital, Takayasu arteritis is rare, but most commonly
Westbury on Trym, Bristol seen in Japan, South East Asia, India, and Mexico.
BS10 5NB, UK; .................................................
In 1990, it was included in the list of intractable
[email protected] Abbreviations: ACR, American College of
Accepted for publication
diseases maintained by the Japanese Rheumatology; CRP, C reactive protein; ESR, erythrocyte
15 January 2002 government,2 and to date 5000 patients have been sedimentation rate; HLA, human leucocyte antigen; IL,
....................... registered. A study of North American patients by interleukin; MRA, magnetic resonance angiography

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482 Johnston, Lock, Gompels

Table 1 1990 ACR criteria for the classification of Takayasu arteritis15

Criterion Definition

Age at disease onset <40 years Development of symptoms or findings related to Takayasu arteritis at age <40 years
Claudication of extremities Development and worsening of fatigue and discomfort in muscles of 1 or more extremity 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 arms

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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 of the entire aorta, its primary branches, or large arteries in the
proximal upper or lower extremities, not caused by arteriosclerosis, fibromuscular dysplasia, or similar causes;
changes usually focal or segmental

A diagnosis of Takayasu arteritis requires that at least 3 of the 6 criteria are met.

bilateral. Nearly all patients with aneurysms also have Assessment of pulmonary vasculature by angiography is not
stenoses and most have extensive vascular lesions. universally recommended, being reserved for patients with
symptoms of pulmonary hypertension.10 Doppler ultrasound is
CHARACTERISTIC FEATURES a useful non-invasive procedure for the assessment of vessel
wall inflammation. In view of the vessels involved, histological
• Diminished or absent pulses in 84–96% of patients1 9 associ- diagnosis is usually impractical and histological assessment is
ated with limb claudication and blood pressure discrepan- limited to those cases undergoing revascularisation proce-
cies. dures.
• Vascular bruits in 80–94% of patients,1 6 10 often multiple, The differential diagnoses include other causes of large ves-
and particularly affecting the carotids, subclavian, and sel vasculitis: inflammatory aortitis (syphilis, tuberculosis,
abdominal vessels. lupus, rheumatoid arthritis, spondyloarthropathies, Behçet’s
• Hypertension in 33–83% of patients,1 6 7 10 12 generally disease, Kawasaki disease, and giant cell arteritis); develop-
reflecting renal artery stenosis, which is seen in 28–75% of mental abnormalities (coarctation of the aorta and Marfan
patients.1 10 12 syndrome), and other aortic pathologies, such as ergotism and
neurofibromatosis. Most of these have specific features that
• Takayasu retinopathy in up to 37% of patients.6 7
• Aortic regurgitation resulting from dilatation of the
ascending aorta, separation of the valve leaflets, and valve
thickening in 20–24%.9 10
• Congestive cardiac failure associated with hypertension,
aortic regurgitation, and dilated cardiomyopathy.9
• Neurological features secondary to hypertension and/or
ischaemia, including postural dizziness, seizures, and
amaurosis.
• Pulmonary artery involvement in 14–100% of patients,
depending on the method used to assess pulmonary vascu-
lature. Oligaemic lung fields on plain chest x ray correlate
with pulmonary vasculopathy in approximately a third of
cases.14 Pulmonary artery disease shows little correlation
with the systemic pattern of arterial involvement,7 14 but can
be useful in the differential diagnosis by helping to confirm
Takayasu arteritis.
• Other symptoms include dyspnoea, headaches, carotody-
nia, myocardial ischaemia, chest wall pain, and erythema
nodosum.

Variable disease presentation between different populations is

well illustrated by Moriwaki et al in their study of Indian and
Japanese patients.11 The Japanese patients (n = 80) were pre-
dominantly female (96%), presenting with dizziness, vertigo,
pulselessness, more prolonged and severe inflammation, and
more aortic regurgitation, reflecting involvement of the aortic
arch and its main branches. This contrasted with the Indian
patients (n = 102), 37% of whom were male. They tended to
present with headache, hypertension, and left ventricular
hypertrophy as a result of vasculitis affecting the abdominal
aorta and renal vessels. However, most patients in both coun-
tries had diffuse disease.

DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS

From the more typical features of Takayasu’s arteritis, the
Figure 1 Arch aortogram demonstrating (A) a severely narrowed
American College of Rheumatology (ACR) defined specific right common carotid artery, (B) occlusion of the left common carotid
diagnostic criteria for this disorder in 1990 (table 1).15 Angio- artery and, (C) proximal stenosis of the left subclavian artery.
graphy remains the gold standard for diagnosis (figs 1, 2). (D) The right vertebral artery provides the dominant cerebral supply.

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Takayasu arteritis 483

Table 2 New angiographic classification of

Takayasu arteritis, Takayasu conference 199411
Type Vessel involvement

Type I Branches from the aortic arch

Type IIa Ascending aorta, aortic arch and its branches
Type IIb Ascending aorta, aortic arch and its branches, thoracic
descending aorta

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Type III Thoracic descending aorta, abdominal aorta, and/or
renal arteries
Type IV Abdominal aorta and/or renal arteries
Type V Combined features of types IIb and IV

According to this classification system, involvement of the coronary or

pulmonary arteries should be designated as C (+) or P (+),
respectively.

Table 3 Ishikawa clinical classification of Takayasu

arteritis7
Group Clinical features

Group I Uncomplicated disease, with or without pulmonary artery

involvement
Group IIA Mild/moderate single complication together with
uncomplicated disease
Group IIB Severe single complication together with uncomplicated
disease
Group III Two or more complications together with uncomplicated
disease

Figure 2 Arch aortogram demonstrating severe involvement of all

extracranial vessels; the descending thoracic aorta appears to be
normal.
The natural history of any disorder can only be elucidated
by following patients in the absence of specific treatment.
enable diagnosis, but tuberculosis has remained an important
Ishikawa defined clinical groups based on the natural history
differential and possible aetiological factor. However, tubercu-
and complications of the disease.7 The four most important
lous aortitis tends to cause erosion of the vessel wall with the
complications were defined as Takayasu retinopathy, second-
formation of true or false aneurysms, particularly affecting
ary hypertension, aortic regurgitation, and aneurysm forma-
the descending thoracic and abdominal aorta. Dissection and
tion, each being graded as mild/moderate or severe at the time
rupture are important complications rather than the stenoses
of diagnosis. Four grades of disease are described (table 3).
typical of Takayasu arteritis. The incidence of rupture and
bleeding complications of aneurysmal Takayasu arteritis is
low. Syphilis tends to affect an older age group, with calcifica- “Tuberculosis has remained an important differential
tion, sparing the descending thoracic aorta, and stenoses are and possible aetiological factor”
not a feature.9 Hypertension as a result of fibromuscular dys-
plasia is an important differential diagnosis. Ishikawa retrospectively studied 54 Japanese patients over
Although similar in many respects, including aortic six months to 18 years of follow up between 1957 and 1975.
involvement in 10–15% of patients with giant cell arteritis, The overall five year survival rate after diagnosis was 83.1%.
Michel et al suggest that giant cell arteritis and Takayasu Seven patients died within five years of diagnosis, all were in
arteritis can be differentiated on clinical grounds. In a study of groups IIB and III, and deaths were mostly from cerebrovas-
280 patients, 217 with giant cell arteritis and 63 with Takayasu cular disease and congestive cardiac failure. All patients with
arteritis identified through the ACR vasculitis criteria data- aortic regurgitation were in group III. The five year survival
bank, they found that age of 40 years at disease onset was the rate in combined groups IIB and III was 70%, compared with
single most discriminatory factor. Excluding age from the 100% in group I. Five acute events occurred in the survivors
analysis, ethnic background and clinical signs of upper limb during follow up, three of five occurring in patients from
vascular insufficiency, shoulder stiffness, and scalp tenderness groups IIB and III. No acute event occurred in patients from
were variables that led to correct diagnoses in 95% of group I. Nineteen of the 54 patients were treated with steroids.
patients.16 The experience from India supports this classification for
prognostic assessment.9 Cumulative survival at five years after
disease onset was 91%, after 10 years the figure was 84%,
CLASSIFICATION whereas event free survival figures were 74.9% and 64%,
An attempt has been made to classify the disease on the basis respectively. Patients with a single mild complication or no
of angiographic findings. The early system, revised by complication at diagnosis had a five year event free survival of
Lupi-Herrera et al in 1977,1 has been superseded by the new 97%, compared with 59.7% in patients with a single severe or
classification of Takayasu arteritis (table 2).11 These systems multiple complications. No deaths occurred in patients in
are useful in that they allow a comparison of patient groups I and IIA, whereas 19.6% of patients in groups IIB and
characteristics according to the vessels involved and are help- III died during follow up, mostly from cerebrovascular disease
ful in planning surgery, but they offer little by way of progno- and cardiac failure. Twenty two major non-fatal events
sis. occurred during follow up, with 20 of 22 occurring in groups
Most patients in the large series studied have diffuse IIB and III. In this study, 63 of 88 patients received no specific
disease. disease modifying treatment. Other studies, which have

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484 Johnston, Lock, Gompels

included patients treated more aggressively, give five year sur- “A study reported in 1998 concluded that no known
vival rates of 90–94%.6 13 Therefore, classification according to serological test was able to supplant vascular
this system appears to give useful prognostic information at histopathology in determining disease activity”
diagnosis and may help to guide treatment.
Several studies have examined the acute phase response in
HISTOLOGY, IMMUNOLOGY, AND PATHOGENESIS Takayasu arteritis. Ishikawa found that the erythrocyte
Macroscopically, in the chronic phase, the aorta is thickened sedimentation rate (ESR) was raised in 29 of 54 patients
secondary to fibrosis of all three vessel layers. The lumen is studied,7 with an equal distribution in the four disease catego-

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narrowed in a patchy distribution, often affecting multiple ries. Higher values were seen in the younger patients, declin-
areas. If disease progression is rapid, fibrosis can be ing with age, perhaps representing the natural history of the
inadequate with subsequent aneurysm formation. The intima disease. Hall et al found that the ESR was raised in three quar-
may be ridged, with a “tree bark” appearance, a feature com- ters of 32 cases, and that it showed an excellent correlation
mon to many aortitides.17 with treatment effect.6 However, Kerr et al concluded that the
Microscopically, the vasculitis may be divided into an acute ESR was not a consistently reliable marker of disease course,
florid inflammatory phase and a healed fibrotic phase. In the being raised in 72% with active disease but also in nearly half
acute phase a vasa vasoritis is seen in the adventitia. The of patients in clinical remission.10 In their study, 44% of arterial
media is infiltrated by lymphocytes and occasional giant cells biopsy specimens obtained from patients with clinically inac-
with neovascularisation. Mucopolysaccharides, smooth mus- tive disease demonstrated vasculitis, suggesting that disease
cle cells, and fibroblasts thicken the intima. In the chronic activity may be underestimated, a view also supported by
phase there is fibrosis with destruction of elastic tissue. Simi- P Bacon (personal communication, 2001).
lar histopathological findings are also seen in giant cell arteri- This inconsistency has led to a search for better serological
tis; therefore, biopsy results may not differentiate between markers. A study reported in 199824 concluded that no known
these two vasculitides. Clinical features usually allow correct serological test was able to supplant vascular histopathology
diagnosis,16 but difficulties can be envisaged in older patients in determining disease activity. This study compared 29
with Takayasu arteritis when the timing of disease onset is patients (22 with clinically inactive disease and seven with
uncertain. clinically active vasculitis) with 26 healthy control volunteers;
Recent investigation of the cellular composition of the aor- no serological test reliably distinguished healthy volunteers
tic wall18 has shown neovessels in the deep intima associated from patients with active disease. The markers assessed
with the adventitial vasa vasorum. T cells and dendritic cells, included ESR, C reactive protein (CRP), tissue factor, von Wil-
with few B cells, granulocytes, and macrophages, surrounded lebrand factor, thrombomodulin, and tissue plasminogen
the vessels. The media contained acellular fibrous tissue, with activator, in addition to various adhesion molecules. The
bundles of neovascularisation and sparse smooth muscle cells. numbers with clinically active disease were small and again
Inflammation was most prominent in the adventitia, with may have been underestimated in the absence of histological
infiltration of B and T cells. In half of the cases these formed assessment. ESR and CRP values were not directly compared.
nodules, with central B cells and peripheral T cells in close Although disease activity may not be discriminated by these
proximity to antigen presenting dendritic cells. Granulocytes markers at a single point in time, for individual patients the
were located outside of the nodules and granulocyte destruc- use of a given parameter longitudinally may still be of value.
tion was observed. No giant cells were seen. Serum concentrations of the pro-inflammatory and chemo-
Infection has been considered to play a role in the tactic cytokines interleukin 1β (IL-1β), IL-6, and RANTES
pathogenesis of Takayasu arteritis. Tuberculosis has been par- have been assessed by enzyme linked immunoabsorbent
ticularly implicated in view of the high prevalence of infection, assay.25 All of 18 patients studied had increased concentrations
of IL-6 and RANTES during active disease compared with
past or present, in affected patients,1 9 largely from endemic
healthy controls, and concentrations parallelled disease activ-
areas. More recently, viral infection is being investigated as a
ity. These cytokines correlated with the ESR but not with CRP
trigger of vasculitis.19
values. This lack of CRP correlation (CRP being driven by IL-1
Seko et al have reported that γδT cells, αβT cells (CD4 and
and IL-6) was not adequately explained. The positive correla-
CD8), and natural killer cells play an important role in the tion with disease activity suggested that these cytokines may
vascular injury.20 The 65 kDa heat shock protein to which γδT contribute to the vasculitis and raised the possibility of their
cells respond is strongly expressed in the aortic tissue of use in monitoring disease and treatment. However, serum
patients with Takayasu arteritis. They have previously found cytokine assays are not necessarily a reflection of tissue cyto-
restricted VαVβ gene usage of the αβT cell receptor, suggesting kine concentrations and may not accurately detect biologically
that a specific antigen was being targeted. More recently, they active cytokine. Their use over and above the ESR remains to
have reported restricted usage of the VγVδ genes in the be established.
infiltrating γδT cells, supporting their hypothesis, along with
the expression of various costimulatory molecules necessary TREATMENT OPTIONS
for T cell activation. Medical treatment
Takayasu arteritis has been associated with different human Steroids have formed the mainstay of treatment for Takayasu
leucocyte antigen (HLA) alleles in different populations.21–23 arteritis and reports of efficacy vary. This may relate to the
For example, in Japan and Korea there is a clear association stage of disease at which treatment is introduced in addition
with the extended haplotype: HLA B*52, DRB1*1502, to disease extent. Early data suggested little benefit,1 with six
DRB5*0102, DQA1*0103, DQB1*0601, DPA1*02-DPB1*0901.21 of eight patients treated showing no improvement. Data from
Sequence analysis has shown that some of the alleles share the USA in 19856 from 29 steroid treated patients demon-
specific epitopes and it may be that the epitopes are more strated a reduction in ESR, a reduction of inflammatory
important as a disease susceptibility factor than the allele in symptoms, and eight of 16 patients with absent pulses were
which they are found. The HLA association is thought by some shown to have a return of a pulse after a delay of several
to strengthen the argument in favour of an autoimmune months. In a later study, of 48 treated patients, remission was
pathogenesis. However, no specific autoantigens have yet been achieved at least once with steroids alone in 60%.10
identified and for any adaptive immune response to occur, It is now accepted that approximately half of patients
whether against exogenous or endogenous antigen, presenta- treated with steroids will respond.8 This lack of universal suc-
tion of antigen to T cells in the context of the major histocom- cess and the side effects associated with steroid use have led to
patibility complex is central. a search for a more effective treatment.

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Takayasu arteritis 485

Comparisons have been made with the treatment of other ever, recent surgical experience of critical thoracic aortic arch
systemic vasculitides, such as Wegener’s granulomatosis.26 stenoses and stroke risk from the National Institutes of
Therefore, immunosuppressive agents including cyclophos- Health, USA32 33 concluded that critical stenoses should be cor-
phamide, azathioprine, and methotrexate have all been tried. rected to prevent stroke, with grafts originating from the
However, the difficulty of comparing Takayasu arteritis with ascending aorta. Renal artery involvement is best treated by
Wegener’s granulomatosis relates not only to the size of vessel percutaneous transluminal angioplasty.33 Stent placement fol-
affected by the disease process, but also to the very different lowing angioplasty for ostial lesions, long segment lesions,
morbidity and mortality associated with these disorders. incomplete relief of stenoses, and dissection is safe and

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Untreated systemic Wegener’s granulomatosis has a mean effective.34 Radical surgical treatment of thoracic aneurysms is
survival from disease onset of five months and a one year recommended if technically possible because more palliative
mortality of 82%,27 which is in sharp contrast to that of procedures fail to prevent recurrent aneurysm formation or to
Takayasu arteritis. minimise risk of later surgery.35
Kerr et al studied 25 steroid unresponsive patients10
receiving cytotoxic medications including cyclophosphamide, PREGNANCY
azathioprine, or methotrexate, although not concurrently. The Because Takayasu arteritis predominantly affects women of
overall remission rate was 33%. Twenty three per cent of all reproductive age, the issue of pregnancy is important. Kerr et
treated patients in their study never achieved remission. al reported five pregnancies in their series of 60 patients, all of
Because no single cytotoxic drug appears to be better than whom had normal deliveries of a normal live infant.10 Only
any other in terms of efficacy, side effect profiles have been an one patient had disease exacerbation during pregnancy.
important driving force in determining treatment. An early A study from Hong Kong in 198336 reported on 13 women
report of methotrexate28 suggested that it was a clinically use- who had experienced a total of 30 pregnancies. Apart from
ful, well tolerated drug. A follow up study of 16 steroid unre- hypertension, there were no major obstetric problems and no
sponsive patients treated with methotrexate and steroid dem-
maternal deaths directly related to pregnancy. Fetal outcome
onstrated remission in 81%.29 However, seven of 16 relapsed as
could be predicted on the basis of maternal vessel involvement
they were weaned off of steroids. Overall, eight patients
(abdominal aorta and renal), severity of maternal hyper-
sustained remissions of four to 34 months and four of these
tension, superimposed pre-eclampsia, and timing of adequate
were able to discontinue treatment altogether. Three of 16
blood pressure control.
progressed despite treatment. A Brazilian study included 12
Maternal complications reported in 12 patients from
patients treated with methotrexate and prednisolone13; 58%
had a good response. Three had to discontinue treatment India37 included superimposed pre-eclampsia, congestive
because of leucopenia or abnormal liver function. cardiac failure, progressive renal impairment, and one case of
postpartum sepsis. Abdominal aortic involvement and a delay
“Because no single cytotoxic drug appears to be better in seeking medical attention predicted a poor perinatal
than any other in terms of efficacy, side effect profiles outcome.
have been an important driving force in determining Fertility is not adversely affected, pregnancy per se does not
appear to exacerbate the disease, but management of
treatment”
hypertension is essential. Hypertension in the second stage of
labour is a risk factor for cerebral haemorrhage; shortening
More recently, three patients have been reported after treat- this stage by use of low forceps delivery or vacuum extraction
ment with mycophenolate mofetil.30 All three showed clinical appears to be a reasonable solution.36 37
benefit, steroids were tapered or discontinued, and no toxicity
was observed. Larger studies will be necessary to confirm LONG TERM FOLLOW UP
these findings and establish the place of this drug in the treat- Takayasu arteritis is a systemic vasculopathy that can progress
ment of Takayasu arteritis. to cause vital organ ischaemia. Therefore, long term follow up
Currently, the best evidence based treatments include ster- is recommended. The limitations of monitoring the acute
oids, to which 50% respond, and methotrexate to which a fur- phase response have been discussed; better tools are required
ther 50% respond. The use of methotrexate as a steroid spar-
and so far these have focused on vascular imaging techniques,
ing drug is logical and safe. Twenty five percent of patients
with non-invasive methods obviously being most appropriate.
with active disease will not respond to current treatments and
Doppler ultrasound is easily applied to extracranial vessels
care should be taken not to expose these patients to the haz-
and can determine vessel wall thickness. Magnetic resonance
ards of prolonged immunosuppression in the absence of clini-
angiography (MRA) is now being investigated in the
cal benefit.
evaluation of large vessel vasculitides.38 It provides high reso-
The other important medical issues relate to the manage-
lution detail of vessel wall thickness and lumen configuration,
ment of hypertension and the prevention and treatment of
thrombosis. Hypertension can be particularly difficult, and and allows the measurement of wall enhancement as a reflec-
worsened by the use of steroids with their fluid retaining side tion of oedema and active inflammation. Compared with the
effects. The use of angiotensin converting enzyme inhibitors gold standard of conventional angiography, approximately 2%
requires careful monitoring in view of the frequency of renal of stenosed arteries are overestimated as occluded on MRA.
artery stenosis.31 The reduction of enhancement on follow up is presumed to
reflect reduced inflammatory activity. Therefore, MRA is likely
Surgical treatment to be used increasingly as an accurate follow up tool.
Indications for surgery include hypertension with critical The management of patients with Takayasu arteritis can be
renal artery stenosis, extremity claudication limiting activities problematic. There may be uncertainty with regard to the
of daily living, cerebrovascular ischaemia or critical stenoses of onset and course of the disease, a poor correlation between
three or more cerebral vessels, moderate aortic regurgitation, clinical assessment and disease activity, poor disease activity
and cardiac ischaemia with confirmed coronary artery markers in peripheral blood, and a lack of useful treatment in
involvement.10 In general, surgery is recommended at a time of up to 25% of patients with progressive disease. The risk of
quiescent disease to avoid complications, which include increased morbidity and mortality means that most patients
restenosis, anastamotic failure, thrombosis, haemorrhage, and who present will ultimately receive immunosuppression. The
infection.6 10 vasculitides, particularly those affecting small vessels, gener-
Surgery may be unnecessary for aortic arch and splanchnic ally require aggressive treatment. The same may not be true of
disease as a result of extensive collateral development.31 How- all patients with Takayasu arteritis despite the angiographic

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486 Johnston, Lock, Gompels

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methotrexate; mycophenolate mofetil may be useful 15 Arend WP, Michel BA, Bloch DA, et al. The American College of
• Treatment should aim to control disease activity and Rheumatology 1990 criteria for the classification of Takayasu arteritis.
preserve vascular competence, with minimal long term side Arthritis Rheum 1990;33:1129–34.
effects; those with disease that carries a good prognosis 16 Michel BA, Arend WP, Hunder GG. Clinical differentiation between
giant cell (temporal) arteritis and Takayasu’s arteritis. J Rheumatol
should not be put at risk by treatment that is more harmful 1996;23:106–11.
than the disease itself 17 Gravanis MB. Giant cell arteritis and Takayasu aortitis: morphologic,
• Fertility is not adversely affected and pregnancy does not pathogenetic and etiologic factors. Int J Cardiol 2000;75:S21–33.
appear to exacerbate the disease, although management 18 Inder SJ, Bobryshev YV, Cherian SM, et al. Immunophenotypic analysis
of hypertension is essential of the aortic wall in Takayasu’s arteritis: involvement of lymphocytes,
dendritic cells and granulocytes in immuno-inflammatory reactions.
Cardiovasc Surg 2000;8:141–8.
19 Numano F. Vasa vasoritis, vasculitis and atherosclerosis. Int J Cardiol
2000;75:S1–8.
appearances. Cohort studies suggest a good prognosis for 20 Seko Y, Takahashi N, Tada Y, et al. Restricted usage of T-cell receptor
those with uncomplicated or monocomplicated disease. Thus, Vγ-Vδ genes and expression of co-stimulatory molecules in Takayasu’s
arteritis. Int J Cardiol 2000;75:S77–83.
the temptation to immunosuppress such patients aggressively 21 Salazar M, Varela A, Ramirez LA, et al. Association of HLA-DRB1*1602
should be questioned. In contrast, early treatment of those and DRB1*1001 with Takayasu arteritis in Colombian mestizos as
with progressive complicated disease may lead to a better markers of Amerindian ancestry. Int J Cardiol 2000;75:S113–16.
22 Vargas-Alarcón G, Zúñiga J, Gamboa R, et al. DNA sequencing of
prognosis for this group. Because inflammation is a risk factor HLA-B alleles in Mexican patients with Takayasu arteritis. Int J Cardiol
for atherosclerosis,2 more atherosclerotic complications are 2000;75:S117–22.
likely in the longer term. 23 Khraishi MM, Gladman DD, Dagenais P, et al. HLA antigens in North
American patients with Takayasu arteritis. Arthritis Rheum
1992;35:573–5.
“Takayasu arteritis is a systemic vasculopathy that can 24 Hoffman GS, Ahmed AE. Surrogate markers of disease activity in
patients with Takayasu arteritis. A preliminary report from The
progress to cause vital organ ischaemia” International Network for the Study of the Systemic Vasculitides (INSSYS).
Int J Cardiol 1998;66:S191–4.
25 Noris M, Daina E, Gamba S, et al. Interleukin-6 and RANTES in
As with any rare disorder, sufficient patient numbers for Takayasu arteritis. A guide for therapeutic decisions? Circulation
randomised controlled treatment trials are lacking. The aim of 1999;100:55–60.
treatment must be the control of disease activity and the pres- 26 Hoffman GS, Kerr GS, Leavitt RY, et al. Wegener granulomatosis: an
analysis of 158 patients. Ann Intern Med 1992;116:488–98.
ervation of vascular competence, with minimal long term side 27 Hoffman GS, Leavitt RY, Fleisher TA, et al. Treatment of Wegener’s
effects. Patients with disease that carries a good prognosis granulomatosis with intermittent high-dose intravenous
should not be put at risk by treatment that is more harmful cyclophosphamide. Am J Med 1990;89:403–10.
28 Hoffman GS, Leavitt RY, Kerr GS, et al. Treatment of Takayasu’s arteritis
than the disease itself. Current evidence favours the use of (TA) with methotrexate (MTX). Arthritis Rheum 1991;34:S74.
steroids and methotrexate, but mycophenolate mofetil may 29 Hoffmann GS, Leavitt RY, Kerr GS, et al. Treatment of
prove to have a role. glucocorticoid-resistant or relapsing Takayasu arteritis with methotrexate.
Arthritis Rheum 1994;37:578–82.
30 Daina E, Schieppati A, Remuzzi G. Mycophenolate mofetil for the
ACKNOWLEDGEMENTS treatment of Takayasu arteritis: report of three cases. Ann Intern Med
1999;130:422–6.
The authors would like to thank Dr M Thornton, Consultant Radiolo- 31 Lagneau P, Baptiste Michel J, Vuong PN. Surgical treatment of
gist, Southmead Hospital, Westbury on Trym, Bristol for help in provi- Takayasu’s disease. Ann Surg 1987;205:157–66.
sion of the radiographic material. 32 Giordano JM, Leavitt RY, Hoffman G, et al. Experience with surgical
treatment of Takayasu’s disease. Surgery 1991;109:252–8.
33 Giordano JM. Surgical treatment of Takayasu’s arteritis. Int J Cardiol
..................... 2000;75:S123–8.
Authors’ affiliations 34 Sharma BK, Jain S, Bali HK, et al. A follow-up study of balloon
angioplasty and de-novo stenting in Takayasu arteritis. Int J Cardiol
S L Johnston, R J Lock, M M Gompels, Department of Immunology and 2000;75:S147–52.
Immunogenetics, Southmead Hospital, Westbury on Trym, Bristol 35 Sasaki S, Kubota S, Kunihara T, et al. Surgical experience of the
BS10 5NB, UK thoracic aortic aneurysm due to Takayasu’s arteritis. Int J Cardiol
2000;75:S129–34.
36 Wong VCW, Wang RYC, Tse TF. Pregnancy and Takayasu’s arteritis.
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