Rheumatol Int (2012) 32:1155–1159
DOI 10.1007/s00296-010-1764-z
ORIGINAL ARTICLE
Retrospective evaluation of 22 patients with Takayasu’s arteritis
Nazife Sule Yasar Bilge • Timuçin Kaşifoğlu
Döndü Ü. Cansu • Cengiz Korkmaz
•
Received: 20 August 2010 / Accepted: 30 December 2010 / Published online: 20 January 2011
Ó Springer-Verlag 2011
Abstract Takayasu’s arteritis (TA) is a rare, idiopathic,
inflammatory, granulomatous vasculitis that affects the
aorta and its primary branches. Clinical features and the
pattern of arterial involvement show differences in different regions of the world according to ethnic influences. Our
aim in this retrospective study was to evaluate the demographic, clinic, laboratory, and angiographic findings of 22
patients with TA followed by our clinic and also compare
our results with series from the literature. The hospital files
of the 22 patients followed by our clinic between 1998 and
2009 were retrospectively evaluated. We also compared
our results with the series from the literature that we were
able to reach by US National Library of Medicine, National
Institute of Health. Gender distribution, age at diagnosis,
and type of aortic involvement were similar with the study
from Turkey. Different clinical manifestations of Takayasu’s arteritis have been described in different ethnic
groups. We also want to underline the coincidence of TA
and other rheumatic diseases such as sarcoidosis, SLE, RA,
and psoriatic arthritis, different from other published series.
Keywords Takayasu’s arteritis Vasculitis Pulseless
disease Immunosuppressive treatment
Inflammation may involve entire vessel wall causing stenotic or occlusive lesions in 98% of patients and aneurisms
in 27% [1]. Even TA is most commonly seen in East Asia,
the disease has been reported worldwide [2]. The incidence
ranges between 1.2 and 2.6 cases/million/year [3]. TA
occurs more frequently in women than in men; female to
male ratio is 8–10:1 [4]. Clinical manifestations are nonspecific such as myalgias, arthralgias, fever, weight loss,
carotidynia, and symptoms reflecting stenosis of the
effected arteries [5]. The diagnoses can delay until patients
have symptoms such as transient ischemic attack or stroke,
results in the localized stenosis of the affected artery [1, 2].
Vascular imaging is absolutely necessary for the correct
diagnosis and also to monitorize the disease progression
[2]. Clinical features and arterial involvement patterns
show differences in different regions of the world [6]. The
aim of this retrospective study was to evaluate the demographic, clinic, laboratory, and angiographic findings of 22
patients with TA followed by Eskisehir Osmangazi University, Faculty of Medicine, Division of Rheumatology.
We have also compared our results with the series from
other countries to present the differences and similarities
between populations.
Introduction
Methods
Takayasu’s arteritis (TA) is an uncommon vasculitis that
primarily affects the aorta and its main branches [1, 2].
The hospital files of the 22 patients who fulfilled the
American College of Rheumatology 1990 criteria for the
diagnosis of TA and followed by our clinic between 1998
and 2009 were retrospectively evaluated. Data included
patients’ gender, age, age of disease, symptoms at admission, and laboratory findings including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and
therapy (medical or surgical). The pretreatment and
N. S. Y. Bilge (&) T. Kaşifoğlu D. Ü. Cansu C. Korkmaz
Faculty of Medicine, Internal Medicine,
Division of Rheumatology, Eskişehir Osmangazi University,
Eskişehir, Turkey
e-mail: suleyasar@yahoo.com
123
1156
Rheumatol Int (2012) 32:1155–1159
posttreatment ESR and CRP values were compared with
Wilcoxon signed-rank test. Patients underwent aortic
angiography at the time of diagnosis and were classified
into 6 types using the new classification of Takayasu’s
arteritis according to the international conference on
Takayasu’s arteritis, 1994 [6]. Type I involves branches of
aortic arch; Type IIa involves ascending aorta, aortic arch,
and its branches; Type IIb is a combination of Type IIa plus
involvement of thoracic descending aorta; Type III
involves thoracic descending aorta, abdominal aorta, and/
or renal arteries; Type IV involves only abdominal aorta
and/or renal arteries; Type V is a combination of Type IIb
plus Type IV.
We have also compared our results with the series from
the literature that we were able to reach by US National
Library of Medicine, National Institute of Health, and
written in English.
Results
Demographic and laboratory features
Twenty-two patients were included in the study. Nineteen
of the 22 patients (86.3%) were woman. Mean age of the
patients was 39.6 ± 12.1, age at onset of disease was
30.1 ± 12.3 (ranged between 12 and 60), and average age
at diagnosis was 30.1 ± 12.3. The mean follow-up period
was 4.7 ± 3.2 years changing from 1 month to 10 years
(Table 1).
The mean erythrocyte sedimentation rate (ESR) was
55.6 ± 35.5 mL/h (0–20 mL/h) and mean C-reactive protein (CRP) was 4.6 ± 4.9 mg/dL (0–0.5 mg/dL) before
treatment and 31.1 ± 23.4 mL/h and 1.9 ± 3.4 mg/dL
after treatment, respectively (Table 1).
Both acute-phase reactants decreased after treatment.
The decrease was statistically significant between pretreatment and posttreatment ESR (P = 0.008), but the
difference was insignificant between pretreatment and
posttreatment CRP (P = 0.3).
Comorbid diseases
Some patients had sarcoidosis, systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and psoriatic
arthritis in medical history. Of the patients, 22.7% had
hypertension and 4.5% of them had diabetes mellitus at the
time of diagnosis. One of the patients had bilateral uveitis
at the time of diagnosis.
Clinical features
Clinical features of the patients were nonspecific. Claudication of the extremity was present in 10 patients (45.5%),
and 18.2% of the patients had vertigo. Carotidynia and
fatigue were present in 13.6% of the patients. Visual
symptoms, arthritis, fever, abdominal pain, and diarrhea
were present in 9.1% of the patients. Headache, nausea,
syncope, and raynaud phenomenon were present in 4.5% of
the patients. Loss of hearing was the initial complaint of
one patient (Table 2).
In physical examination, 90.9% of the patients had
murmur in cervical region, 54.5% had murmur in abdominal region, and 33.3% had in both regions.
Type of aortic involvement
Seventeen of the 22 patients had diagnosis by X-ray
angiography, two by MR angiography, two by CT angiography, and one of them was defined with thorax CT.
The most common type of aortic involvement was Type
I arteritis (36.4%); 22.7% had Type IV involvement; and
18.2% had Type V arteritis. Type II aortic involvement was
the least common arteritis (9.1%), and 45.5% of the
Table 2 Clinical features of the patients with TA
Clinical features
Number
of patients
%
Claudication
10
45.5
Vertigo
4
18.2
Carotidynia
3
13.6
Fatigue
3
13.6
Table 1 Demographic and laboratory features of the patients with
TA
Visual symptoms
2
9.1
Arteritis
2
9.1
F/M
19/3
Mean age (years)
39.6 ± 12.1
Fever
Abdominal pain
2
2
9.1
9.1
Age at diagnosis
30.1 ± 12.3
Diarrhea
2
9.1
4.7 ± 3.2 (1–120 months)
Headache
1
4.5
55.6 ± 35.5 mL/h
Nausea
1
4.5
ESR after treatment
30.1 ± 23.4 mL/h
Syncope
1
4.5
CRP before treatment
CRP after treatment
4.6 ± 4.9 mg/dL
1.9 ± 3.4 mg/dL
Raynaud phenomenon
1
4.5
Loss of hearing
1
4.5
Mean follow-up period (years)
ESR before treatment
123
Rheumatol Int (2012) 32:1155–1159
1157
Outcome
Table 3 Type of aortic involvement
Type
Number of patients %
Type I
8
36.4
Type IIa
0
0
Type IIb
2
9.1
Type III
0
0
Type IV
5
22.7
Type V
4
18.2
Involvement of renal arteries 8 (4/4)
(unilateral/bilateral)
One of our patients died in coronary intensive care unit
because of congestive cardiomyopathy. And four of our
patients were lost to follow up.
Discussion
36.4 (18.2/18.2)
patients had renal arterial involvement. Unilateral and
bilateral involvement was equal (18.2%), and 20% of the
patients had aortic aneurism. Three patient’s angiographic
data were missing (Table 3).
Aortic aneurism was seen in three patients. Aneurism
developed in one patient with HT and retinopathy developed in another.
Treatment
Therapeutic approaches to TA patients included both
medical treatment and surgical treatment; 76.2% received
steroids, 52.4% had methotrexate, and 47.6% had azathioprine therapy. The number of patients who had leflunamide or infliximab was 2 (9.5%). The average
therapy period was 3.6 years (1–10 years). Both patients
had infliximab therapy in combination with azathioprine.
One of the patients received methotrexate in addition to
azathioprine. Infliximab was used as an alternative
treatment in patients who were evaluated as resistant to
azathioprine and methotrexate therapies. Surgery was
performed to 7 patients (33.3%); 22.7% had bypass
surgery and stent placement was performed to 9.1% of
them (Table 4). None of the patients had undergone a
second surgical procedure.
Table 4 Therapeutic approaches to the patients
Treatment
Number of
the patients
%
Bypass surgery
5
Stent
2
22.7
9.1
Steroid
16
72.7
Methotrexate
11
50
Azathioprine
10
45.5
Leflunomide
2
9.1
Infliximab
2
9.1
TA has an unpredictable pattern with various clinical
manifestations [2]. Different manifestations of the disease
have been described in different ethnic groups [3]. There
are two series with 45 and 14 patients have been reported
from Turkey previously [3, 7]. In this retrospective study,
we presented demographic, clinical, laboratory, and
angiographic findings of 22 patients with TA followed by
our clinic and compared our results with the other series
published before.
The mean age and clinical features of our patients were
similar with the published series from Serbia, Colombia,
India, North America, Korea, and also from our country
[2, 4, 8–13]. In India, the female:male ratio was 1.58:1 and
2.15:1 in Thailand [9, 13, 14] (Table 5). In many of the
published studies including ours, the female predominance
is more significant. In a study reported by Lupi-Herrera
et al. [10], the onset of age was less than 20, much more
younger than the other series. Diagnosis was delayed
almost 2 years after the beginning of the symptoms like
mentioned in other studies [11]. This is because of the
nonspecificity of the symptoms. The patients can be diagnosed earlier if the clinician is suspicious about TA in
differential diagnosis.
The most common symptom was claudication (45.5%)
same as the patients from Colombia and North America
[8, 11]. In the study by Ureten et al. [4], claudication was
the second common manifestation (44%) following constitutional symptoms (71%).
Of the patients, 90.9% had murmur in the neck, same as
those in the literature [8]. Even this is an important indicator of the disease, it is not diagnostic. Hypertension was
found in a less percentage of patients different from the
series of Colombia, India, North America, and Thailand
[8–11, 14], but HT is a multifactorial originated disease
that can explain the difference.
Type I aortic involvement, involving branches of
aortic arch, was the most common type among the
patients. Same involvement was seen among the patients
from Serbia, Colombia, and Korea, but Type V
involvement was more common in series from Japan,
India, and Thailand [8, 9, 12, 14]. Our results were also
similar to the other studies from Turkey [4]. Renal
arterial involvement was more common among the
Indian patients [9].
123
V (18.2%)
III (0)
IV (22.7%)
V (31%)
IV (4%)
III (0)
IV (0)
IIb (9.1%)
III (22%)
IIb (0)
I (36.4%)
30.1 ± 12.3
IIa (0)
II (18%)
IIa (19%)
I (56%)
I (50%)
V (66.7%)
III (67%)
19/3
8/1
34 (18–59)
34 (19–52)
16/1
2.21/1
3rd–4th decade
3rd decade
6.6/1
V (28.6%)
V (57%)
IV (27.3%)
IV (14%)
V (55.7%)
III (0)
IV (20%)
III (4%)
IIb (5.7%)
IIb (0)
III (3.8%)
IIa (11.4%)
II (4%)
II (6.6%)
I (34.3%)
I (21%)
Type of aortic involvement
I (6.6%)
26/6
27.3 ± 9.2
28.9 (13–47)
27 (10–52)
65/41
26/9
5/1
Age at diagnosis
F/M
45
16
63
129
32
35
123
Number of the patients
73
106
Turkey
[3]
Serbia
[2]
Thailand
[13]
Korea
[12]
North
America [10]
India
[16]
Colombia
[7]
Brasil
[6]
Country
Table 5 Comparision of the series from literature
22
Rheumatol Int (2012) 32:1155–1159
Present
study
1158
We have defined active disease using clinical signs,
symptoms, and increase in acute-phase reactants (ESR and
CRP). Resolution of clinical and laboratory findings were
defined as remission. Using immunosuppressive treatment
provides remission.
Glucocorticoids are the effective palliative agents for
most of the patients. But the addition of the immunosuppressive agents provides remission in higher rates [5, 6],
and in our experience, several patients needed immunosuppressive therapy to control the disease activity. The
most commonly used immunosuppressive drug was methotrexate same as the published studies [6]. In the published
study from Serbia [2], 69% of the patients needed a second
immunosuppressive agent other from glucocorticoids. We
have treated all patients with combination therapy including glucocorticoids and other immunosuppressive agents
same as Ureten et al. [4]. Infliximab was used as an
alternative treatment in resistant patients. There are some
studies in the literature supporting the usage of anti-tumor
necrosis factor therapy in Takayasu’s arteritis and resulted
in remission [15, 16]. Infliximab might be an effective
alternative treatment choice in Takayasu’s arteritis.
Also, in the same study from Serbia, 25% of the patients
required multiple surgical interventions. None of our
patients had undergone a second surgical intervention.
But restenosis was reported in 24.23% of the cases in India
[13].
In conclusion, some of the demographic and clinical
findings of our patients were similar to those reported
before and some of them were different from the published
series. The difference might be related to ethnic influences.
The similarities between our data and Ureten et al.’s results
support this consequence. In addition, we want to underline
the coincidence of TA and other rheumatic diseases. Five
of our patients had TA secondary to a rheumatic disease
such as SLE, RA, sarcoidosis, and psoriatic arthritis. There
are some TA cases that were presented as sarcoidosis, SLE,
and RA [17, 18], but ours had sarcoidosis, SLE, RA, and
psoriatic arthritis and developed TA later on progress.
These uncommon associations of the two such rare diseases in the same person raise questions of common etiologic factors.
References
1. Liang P, Hoffman GS (2005) Advances in the medical and surgical treatment of Takayasu arteritis. Curr Opin Rheumatol
17:16–24
2. Petrovic-Rackov L, Pejnovic N, Jevtic M, Damjanov N (2009)
Longitudinal study of 16 patients with Takayasu’s arteritis:
clinical features and therapeutic management. Clin Rheumatol
28:179–185
Rheumatol Int (2012) 32:1155–1159
3. Andrews J, Al-Nahhas A, Pennell DJ, Hossain MS, Davies KA,
Haskard DO, Mason JC (2004) Non-invasive imaging in the
diagnosis and management of Takayasu’s arteritis. Ann Rheum
Dis 63:995–1000
4. Ureten K, Ozturk MA, Onat MA, Ozturk MA, Ozbalkan Z, Guvener M, Kıraz S, Ertenli I, Calguneri M (2004) Takayasu’s
arteritis: results of a university hospital of 45 patients in Turkey.
Int J Cardiol 96:259–264
5. Kerr GS, Hallahan CW, Giordano J, Leavitt RY, Fauci SA,
Rottem M, Hoffman GS (1994) Takayasu arteritis. Ann Int Med
120(11):919–929
6. Sato EI, Hatta FS, Levy-Neto M, Fernandes S (1998) Demographic, clinical, and angiographic data of patients with Takayasu
arteritis in Brazil. Int J Cardiol 66(Suppl 1):67–70
7. Türkoğlu C, Memiş A, Payzin S, Akin M, Kültüsay H, Akilli A,
Can L, Altintig A (1996) Takayasu arteritis in Turkey. Int J
Cardiol 54(Suppl):S135–S136
8. Cañas CA, Jimenez CA, Ramirez LA, Uribe O, Tobón I, Torrenegra A, Cortina A, Muñoz M, Gutierrez O, Restrepo JF, Peña
M, Iglesias A (1998) Takayasu arteritis in Colombia. Int J Cardiol
66(Suppl 1):73–79
9. Parakh R, Yadav A (2007) Takayasu’s arteritis: an Indian perspective. Eur J Vasc Endovasc Surg 33(5):578–582
10. Lupi-Herrera E, Sánchez-Torres G, Marcushamer J, Mispireta J,
Horwitz S, Vela JE (1977) Takayasu’s arteritis. Clinical study of
107 cases. Am Heart J 93(1):94–103
1159
11. Hall S, Barr W, Lie JT, Stanson AW, Kazmier FJ, Hunder GG
(1985) Takayasu arteritis. A study of 32 North American patients.
Medicine (Baltimore) 64(2):89–99
12. Park YB, Hong SK, Choi KJ, Sohn DW, Oh BH, Lee MM, Choi
YS, Seo JD, Lee YW, Park JH (1992) Takayasu arteritis in
Korea: clinical and angiographic features. Heart Vessels suppl
7:55–59
13. Jain S, Kumari S, Ganguly NK, Sharma BK (1996) Current status
of Takayasu arteritis in India. Int J Cardiol 54(Suppl):111–116
14. Suwanwela N, Piyachon C (1996) Takayasu arteritis in Thailand:
clinical and imaging features. Int J Cardiol 54 suppl:S117–S134
15. Hoffman GS, Merkel PA, Brasington RD, Lenschow DJ, Liang P
(2004) Anti-tumor necrosis factor therapy in patients with difficult to treat Takayasu arteritis. Arthritis Rheum 50(7):2296–2304
16. Karageorgaki ZT, Mavragani CP, Papathanasiou MA, Skopouli
FN (2007) Infliximab in Takayasu arteritis: a safe alternative?
Clin Rheumatol 26(6):984–987
17. Schapiro JM, Shpitzer S, Pinkhas J, Sidi Y, Arber N (1994)
Sarcoidosis as the initial manifestation of Takayasu’s arteritis.
J Med 25(1–2):121–128
18. Kitazawa K, Joh K, Akizawa T (2008) A case of lupus nephritis
coexisting with podocytic infolding associated with Takayasu’s
arteritis. Clin Exp Nephrol 12(6):462–466
123
Cengiz Korkmaz