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Unique Case of Takayasu Arteritis with Severe Distal Aortic Stenosis and Iliac Thrombosis
Accepted Manuscript Unique case of Takayasu arteritis with severe distal aortic stenosis and iliac thrombosis Claire A. Ostertag-Hill, Ameen K. Abdo, Jason Q. Alexander, Nedaa Skeik PII:
S0890-5096(16)00039-X
DOI:
10.1016/j.avsg.2015.10.021
Reference:
AVSG 2650
To appear in:
Annals of Vascular Surgery
Received Date: 4 August 2015 Revised Date:
13 October 2015
Accepted Date: 15 October 2015
Please cite this article as: Ostertag-Hill CA, Abdo AK, Alexander JQ, Skeik N, Unique case of Takayasu arteritis with severe distal aortic stenosis and iliac thrombosis, Annals of Vascular Surgery (2016), doi: 10.1016/j.avsg.2015.10.021. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Unique case of Takayasu arteritis with severe distal aortic stenosis and iliac thrombosis Claire A. Ostertag-Hill, Ameen K. Abdo, Jason Q. Alexander, Nedaa Skeik
RI PT
Abstract
Takayasu arteritis is a rare, chronic large vessel vasculitis of unknown etiology which
predominantly affects women younger than 40 years of age. Symptoms are highly variable based
SC
on the location and extent of the stenosis, arterial occlusion, aneurysm, and thrombosis.
Diagnosis is based on clinical presentation, relevant laboratory work-up, and imaging findings of
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wall thickening and stenosis of medium and large vessels. Management includes glucocorticoid therapy, frequently paired with adjunctive immunosuppressants and sometimes surgical intervention in severe cases. Here, we present a unique case of Takayasu arteritis with critical distal aortic stenosis with very severe wall thickening involving the bilateral common iliac artery
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and leading to left iliac artery thrombosis. Based on our literature review, our paper represents a very rare presentation of Takayasu arteritis with severe iliac artery thrombosis.
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Keywords: Takayasu arteritis, aortic stenosis, thrombosis
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Case Report A 48-year old woman with a past medical history of tobacco abuse and obesity presented with acute onset of purple discoloration of left third and fifth toes and heel. She had a one-month
RI PT
preceding history of malaise and progressive intermittent bilateral hip and buttock pain with walking.
Vital signs revealed a right arm blood pressure of 132/89 mm Hg with no significant
SC
difference between both arms, a heart rate of 119 beats/min, and a temperature of 36.6°C.
Physical examination revealed purple discoloration of the plantar surface of the left third and
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fifth toes and lateral aspect of the left heel, along with weak bilateral femoral and non-palpable bilateral popliteal, dorsalis pedis (DP), and posterior tibial (PT) pulses. The rest of the physical examination was unremarkable including bilateral radial and ulnar pulses. Arterial duplex ultrasound revealed a moderately reduced resting ankle-brachial index
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(ABI) of 0.71 bilaterally and no significant stenosis but mono-phasic waveform at the bilateral common femoral, superficial femoral, popliteal, PT, and DP arteries consistent with aortoiliac disease. Computed tomography angiogram (CTA) of the abdomen and pelvis revealed critical
EP
infrarenal aortic stenosis caused by underlying severe inflammation with wall thickening of 13mm involving the distal aorta and extending to the bilateral iliac arteries (Figure 1A, B, C).
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Magnetic resonance angiogram (MRA) of the chest did not reveal any other vascular involvement including the major proximal aortic branches. A complete blood cell count and complete metabolic profile were normal, except for
elevated glucose of 160 mg/dL (65-100 mg/dL). Further pertinent work-up revealed an elevated erythrocyte sedimentation rate (ESR) of 36 mm/hr (<21 mm/hr) and an elevated C-reactive protein (CRP) level of 2.76 mm/dL (<.50 mg/dL). A lipid panel revealed elevated cholesterol of
2
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221 mg/dl (100-199 mg/dL), elevated triglycerides of 272 mg/dL (<150 mg/dL), low highdensity lipoprotein (HDL) cholesterol of 29mg/dL (>40 mg/dL), and elevated low-density lipoprotein (LDL) cholesterol of 138 mg/dL (<130 mg/dL). Laboratory workup for
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immunoglobin G subclasses, complement components 3 and 4, antineutrophil cytoplasmic
antibodies (ANCA) vasculitis panel, and antinuclear antibodies was unremarkable. Anti-Human Immunodeficiency Virus (HIV) antibodies, syphilis, and viral hepatitis work-up was also
SC
negative.
Based on the clinical presentation, laboratory work-up and imaging findings, the
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diagnosis of inflammatory aortitis was made. Given the patient’s gender and the presence of severe stenosis of the distal aorta, Takayasu arteritis was considered as the etiology. Medical management with prednisone 60 mg daily, aspirin 81 mg daily, and atorvastatin 40 mg every evening was promptly started. The patient’s ischemic symptoms improved over the remainder of
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the hospitalization, and MRA performed two days later revealed stable aortoiliac findings, and so she was discharged on the above medication regiment. Three weeks later, the patient presented with sudden onset of left leg pain. Physical
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examination revealed cold bilateral feet, non-palpable left DP and PT pulses, and livedo reticularis along plantar and lateral aspects of the left foot. Acute critical limb ischemia was
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considered, and management was immediately started with a therapeutic dose of intravenous (IV) unfractionated heparin. Computed tomography angiogram revealed improvement in the aortic wall thickness (10mm) and inflammatory rind but new thrombosis of the left common iliac artery and embolic occlusion of the distal popliteal and tibiofibular trunk (Figure 2A, B, C). Catheter-based lytic therapy using tissue plasminogen activator (tPA) was combined with aspiration thrombectomy resulting in significant reduction of the clot burden at the left common
3
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iliac artery. However, the procedure was complicated by right iliac artery dissection which was managed by bare-metal stenting. The patient continued to improve on prednisone, atorvastatin, and aspirin, and heparin was bridged to a therapeutic dose of warfarin.
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At a two month follow-up visit, the patient’s ischemic symptoms have resolved but has encountered significant steroid side effects. Repeat laboratory workup revealed normalized ESR (18mm/hr) and improved CRP (.83mg/dL). Repeat CTA revealed further improvement of
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infrarenal aortic inflammation (Figure 3A, B, C) with wall thickening measuring 8mm and patent right external iliac artery stent. Arterial duplex showed a significant improvement of resting ABI
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of 0.94 on the left and 1.10 on the right. Due to improvement in clinical presentation, laboratory and imaging findings, prednisone continued to be slowly tapered.
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Discussion
Takayasu arteritis is a rare, chronic large vessel vasculitis of undetermined etiology that primarily affects the aorta, aortic arch, and large vessels.1,2 Typical manifestation of this disease
EP
occurs before age 40,3 and it is approximately 8.5 times more common among females than males.4 Prevalence of Takayasu arteritis is highest in the populations of Japan, Southeast Asia,
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India, and Mexico.5 Specifically, Japan reports an estimated 150 new cases per year, compared to an incidence of 1 to 3 new cases per million persons per year in the United States and Europe.6–8 Clinical presentation of Takayasu arteritis is highly heterogeneous.9 Early systemic
symptoms of Takayasu arteritis may include fever, night sweats, malaise, weight loss, arthralgia, myalgia, and mild anemia.5 Disease progression can be manifested by diminished or absent pulses associated with blood pressure discrepancies and limb claudication, vascular bruits, and
4
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sometimes hypertension due to renal artery stenosis.3,5 Other systemic manifestations include headaches, carotodynia, erythema nodosum, and neurological features such as postural dizziness, seizures, and amaurosis fugax secondary to hypertension and/or ischemia.5 Cardiovascular
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complications may include aneurysms, pulmonary hypertension, aortic rupture, and thrombosis.9,10
Diagnosis relies on clinical presentation and imaging of the arterial tree by ultrasound,
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computed tomography, magnetic resonance, or catheter-based angiography showing stenoses of medium and large vessels.1,11 18-fluorodeoyxglucose (18F-FDG) positron emission tomography
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may also be helpful for initial diagnosis and monitoring of disease activity.12,13 Laboratory findings such as elevated ESR and CRP may reflect inflammation underlying Takayasu arteritis, but these alone are unreliable in identifying disease activity.9
Angiographic findings have been used to develop multiple systems of classification for
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Takayasu arteritis, with the most recent being advanced at the 1994 Tokyo International Conference on Takayasu arteritis.14 According to this classification, Takayasu arteritis can be classified as Type I, IIa, IIb, III, IV, or V (Table 1). The global prevalence of each type based on
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our literature review is summarized in Table 2.15 Takayasu arteritis classification is beneficial for planning surgical intervention and studying patient characteristics based on vessel involvement.5
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Although the pathogenesis of Takayasu arteritis remains unclear, it is believed to be an
antigen-driven, cell-mediated autoimmune process.24 Takayasu arteritis involves adventitial thickening, focal leukocytic infiltration of the tunica media, and intimal hyperplasia, thereby predisposing for stenosis, arterial occlusion, aneurysmal formation, and thrombosis in affected vessels.5,9 It is hypothesized that an unknown stimulus triggers expression of the 65kDa heat shock protein in aortic tissue.25 This protein is recognized by subsets of T lymphocytes,
5
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including γδ T lymphocytes, which in conjunction with macrophages produce pro-inflammatory cytokines resulting in active vascular inflammation.25,26 Takayasu arteritis has also been associated with various human leukocyte antigen (HLA) alleles in different populations.27
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Glucocorticoid therapy is the primary treatment modality for Takayasu arteritis, aimed at inducing and maintaining disease remission.28 Adjunctive, steroid-sparing immunosuppressants such as methotrexate, mycophenolate mofetil, and azathioprine, are frequently paired with
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glucosteriods to treat refractory disease and minimize steroid adverse events.9,24 More recent therapy, including disease modifying anti-rheumatic agent (leflunomide), tumor necrosis factor
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(TNF)-α antagonists (infliximab), Interleukin-6 Receptor Antagonist (tocilizumab), and antiCD20 (rituximab) have shown some promise for patients with refractory Takayasu arteritis.29,30 However, randomized clinical trials are needed to develop a better understanding of these novel agents.29 Surgical intervention is usually reserved for patients with severe symptomatic stenosis
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or occlusion of arteries leading to ischemic complications at different locations.5,9,31 The diagnosis of Type IV Takayasu arteritis in our patient was based on the clinical presentation and CTA revealing critical infrarenal aortic inflammation and stenosis extending to
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the bilateral iliac arteries, in conjunction with elevated inflammatory markers. The patient’s gender is also suggestive of Takayasu arteritis. Our patient’s age at presentation was slightly
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older than usual for Takayasu arteritis. However, given the severity of the inflammation and stenosis, we believe that the inflammation had started much earlier than the manifested symptoms. Giant cell arteritis was not considered given the patient’s age, and IgG4-related disease was also excluded given the absence of its other systemic manifestations and normal IgG4 titers.
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Our patient’s disease course was complicated by thrombosis of her left iliac artery with embolization to the popliteal artery shortly after starting treatment. Takayasu arteritis promotes a hypercoagulable state and thereby thrombus formation by significantly increasing platelet and
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coagulation activity.32 Although Takayasu-associated thrombosis has been reported in various inflamed vessels including the aorta,24 subclavian artery,33 and common mesenteric arterty,34 we were unable to find any cases of Takayasu arteritis complicated by thrombosis of the iliac artery.
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Our paper represents a rare case of Takayasu arteritis Type IV with impressive distal aortic inflammation and stenosis extending to the bilateral iliac arteries, complicated by iliac
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thrombosis and embolization to the popliteal artery. Considering that each aspect of our patient’s presentation is quite uncommon, this paper calls for more research in this field to better
Bibliography:
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understand and manage Takayasu arteritis and its complications.
1. Skeik, N., Rodriguez, A. & Engstrom, B. Rare Case of Takayasu Arteritis with Concurrent
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Aneurysmal Dilation and Stenosis. Int. J. Angiol. (2015). 2. Skeik, N. et al. Concurrent Takayasu arteritis with common variable immunodeficiency and
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moyamoya disease. Ann. Vasc. Surg. 27, 240.e13–18 (2013). 3. Arend, W. P. et al. The American College of Rheumatology 1990 criteria for the classification of Takayasu arteritis. Arthritis Rheum. 33, 1129–1134 (1990). 4. Lupi-Herrera, E. et al. Takayasu’s arteritis. Clinical study of 107 cases. Am. Heart J. 93, 94– 103 (1977).
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5. Johnston, S. L., Lock, R. J. & Gompels, M. M. Takayasu arteritis: a review. J. Clin. Pathol. 55, 481–486 (2002). 6. Koide, K. Takayasu arteritis in Japan. Heart Vessels. Suppl. 7, 48–54 (1992).
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7. Hall, S. et al. Takayasu arteritis. A study of 32 North American patients. Medicine (Baltimore) 64, 89–99 (1985).
8. Reinhold-Keller, E., Herlyn, K., Wagner-Bastmeyer, R. & Gross, W. L. Stable incidence of
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primary systemic vasculitides over five years: results from the German vasculitis register. Arthritis Rheum. 53, 93–99 (2005).
Rheumatol. 6, 406–415 (2010).
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9. Mason, J. C. Takayasu arteritis--advances in diagnosis and management. Nat. Rev.
10. Tann, O. R., Tulloh, R. M. R. & Hamilton, M. C. K. Takayasu’s disease: a review. Cardiol. Young 18, 250–259 (2008).
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11. Kissin, E. Y. & Merkel, P. A. Diagnostic imaging in Takayasu arteritis. Curr. Opin. Rheumatol. 16, 31–37 (2004).
12. Kobayashi, Y. et al. Aortic wall inflammation due to Takayasu arteritis imaged with 18F-
922 (2005).
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FDG PET coregistered with enhanced CT. J. Nucl. Med. Off. Publ. Soc. Nucl. Med. 46, 917–
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13. Buckley, A. et al. The role of ultrasound in evaluation of Takayasu’s arteritis. J. Rheumatol. 18, 1073–1080 (1991).
14. Hata, A., Noda, M., Moriwaki, R. & Numano, F. Angiographic findings of Takayasu arteritis: new classification. Int. J. Cardiol. 54 Suppl, S155–163 (1996). 15. Schmidt, J. et al. Diagnostic features, treatment, and outcomes of Takayasu arteritis in a US cohort of 126 patients. Mayo Clin. Proc. 88, 822–830 (2013).
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16. Singh, A. P. et al. Angiographic profile and endovascular interventions in Takayasu’s arteritis. J. Invasive Cardiol. 27, 8–13 (2015).
in Turkey. Arthritis Res. Ther. 14, R27 (2012).
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17. Sahin, Z. et al. Takayasu’s arteritis is associated with HLA-B*52, but not with HLA-B*51,
18. Cong, X.-L. et al. Takayasu’s arteritis: clinical features and outcomes of 125 patients in China. Clin. Rheumatol. 29, 973–981 (2010).
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19. Kechaou, M., Frigui, M., Ben Hmida, M. & Bahloul, Z. Takayasu arteritis in southern
Tunisia: a study of 29 patients. Presse Médicale Paris Fr. 1983 38, 1410–1414 (2009).
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20. Petrovic-Rackov, L., Pejnovic, N., Jevtic, M. & Damjanov, N. Longitudinal study of 16 patients with Takayasu’s arteritis: clinical features and therapeutic management. Clin. Rheumatol. 28, 179–185 (2009).
21. Park, M.-C., Lee, S.-W., Park, Y.-B., Chung, N. S. & Lee, S.-K. Clinical characteristics and
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outcomes of Takayasu’s arteritis: analysis of 108 patients using standardized criteria for diagnosis, activity assessment, and angiographic classification. Scand. J. Rheumatol. 34, 284–292 (2005).
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22. Sato, E. I., Hatta, F. S., Levy-Neto, M. & Fernandes, S. Demographic, clinical, and angiographic data of patients with Takayasu arteritis in Brazil. Int. J. Cardiol. 66 Suppl 1,
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S67–70; discussion S71 (1998).
23. Suwanwela, N. & Piyachon, C. Takayasu arteritis in Thailand: clinical and imaging features. Int. J. Cardiol. 54 Suppl, S117–134 (1996). 24. Gornik, H. L. & Creager, M. A. Aortitis. Circulation 117, 3039–3051 (2008). 25. Arnaud, L., Haroche, J., Mathian, A., Gorochov, G. & Amoura, Z. Pathogenesis of Takayasu’s arteritis: a 2011 update. Autoimmun. Rev. 11, 61–67 (2011).
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26. Seko, Y. et al. Perforin-secreting killer cell infiltration and expression of a 65-kD heat-shock protein in aortic tissue of patients with Takayasu’s arteritis. J. Clin. Invest. 93, 750–758 (1994).
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27. Terao, C., Yoshifuji, H. & Mimori, T. Recent advances in Takayasu arteritis. Int. J. Rheum. Dis. 17, 238–247 (2014).
28. Koening, C. L. & Langford, C. A. Takayasu’s arteritis. Curr. Treat. Options Cardiovasc.
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Med. 10, 164–172 (2008).
29. Clifford, A. & Hoffman, G. S. Recent advances in the medical management of Takayasu
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arteritis: an update on use of biologic therapies. Curr. Opin. Rheumatol. 26, 7–15 (2014). 30. Alibaz-Oner, F., Aydin, S. Z. & Direskeneli, H. Advances in the diagnosis, assessment and outcome of Takayasu’s arteritis. Clin. Rheumatol. 32, 541–546 (2013). 31. Mason, J. C. Takayasu arteritis: surgical interventions. Curr. Opin. Rheumatol. 27, 45–52
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(2015).
32. Akazawa, H., Ikeda, U., Yamamoto, K., Kuroda, T. & Shimada, K. Hypercoagulable state in patients with Takayasu’s arteritis. Thromb. Haemost. 75, 712–716 (1996).
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33. Purkayastha, S., Jayadevan, E. R., Kapilamoorthy, T. R. & Gupta, A. K. Suction thrombectomy of thrombotic occlusion of the subclavian artery in a case of Takayasu’s
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arteritis. Cardiovasc. Intervent. Radiol. 29, 289–293 (2006). 34. Silver, M. Takayasu’s Arteritis - An Unusual Cause of Stroke in a Young Patient. West. J. Emerg. Med. 13, 484–487 (2012).
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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
Thoracic descending aorta, abdominal aorta, and/or renal
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Type III
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Type
arteries
Abdominal aorta and/or renal arteries
Type V
Combined features of types IIb and IV
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Type IV
*Involvement of the coronary or pulmonary arteries should be indicated as C (+) or P (+), respectively
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Table 1: Angiographic classification of Takayasu arteritis (based on the 1994 Tokyo International Conference on Takayasu Arteritis)14
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Type I
Type IIa
Type IIb
Type III
Type IV
Type V
India
32.2%
8.1%
1.6%
3.2%
17.7%
37.1%
Schmidt et al.
United
20%
6%
7%
5%
5%
57%
(2013)15
States
Sahin et al. (2012)17
Turkey
39.4%
6.4%
2.7%
Cong et al. (2010)18
China
40%
4.8%
1.6%
Kechauo et al.
Tunisia
67.7%
0%
10.7%
Serbia
50%
19%
South
36.1%
2.8%
Singh et al. (2015)16
Petrovic-Rackov et al. (2009)20 Park et al. (2005)21
Suwanwela et al.
4.5%
43%
2.4%
20.8%
30.4%
0%
3.6%
25%
0%
0%
0%
31%
4.6%
7.4%
15.8%
33.3%
Brazil
21%
4%
0%
4%
14%
57%
Thailand
0%
0%
11.1%
3.2%
19%
66.7%
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(1996)23
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Korea Sato et al. (1998)22
3.9%
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(2009)19
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Location
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Study
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Table 2: Global prevalence of Takayasu arteritis by type based on our literature review
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A
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B
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C
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Figure 1. Computed tomography angiogram transverse (A, B) and coronal (C) images showing significant infrarenal aortic stenosis extending to the bilateral iliac artery (arrows)
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A
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B
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C
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Figure 2. Computed tomography angiogram transverse (A, B) and coronal (C) images showing improvement in aortic wall thickness but new thrombosis of the left common iliac artery (arrows)
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A
AC C
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B
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C
AC C
EP
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Figure 3. Computed tomography angiogram transverse (A, B) and coronal (C) images showing further improvement of infrarenal aortic inflammation and bilateral iliac artery stenosis (arrows)
S0890-5096(16)00039-X
DOI:
10.1016/j.avsg.2015.10.021
Reference:
AVSG 2650
To appear in:
Annals of Vascular Surgery
Received Date: 4 August 2015 Revised Date:
13 October 2015
Accepted Date: 15 October 2015
Please cite this article as: Ostertag-Hill CA, Abdo AK, Alexander JQ, Skeik N, Unique case of Takayasu arteritis with severe distal aortic stenosis and iliac thrombosis, Annals of Vascular Surgery (2016), doi: 10.1016/j.avsg.2015.10.021. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Unique case of Takayasu arteritis with severe distal aortic stenosis and iliac thrombosis Claire A. Ostertag-Hill, Ameen K. Abdo, Jason Q. Alexander, Nedaa Skeik
RI PT
Abstract
Takayasu arteritis is a rare, chronic large vessel vasculitis of unknown etiology which
predominantly affects women younger than 40 years of age. Symptoms are highly variable based
SC
on the location and extent of the stenosis, arterial occlusion, aneurysm, and thrombosis.
Diagnosis is based on clinical presentation, relevant laboratory work-up, and imaging findings of
M AN U
wall thickening and stenosis of medium and large vessels. Management includes glucocorticoid therapy, frequently paired with adjunctive immunosuppressants and sometimes surgical intervention in severe cases. Here, we present a unique case of Takayasu arteritis with critical distal aortic stenosis with very severe wall thickening involving the bilateral common iliac artery
TE D
and leading to left iliac artery thrombosis. Based on our literature review, our paper represents a very rare presentation of Takayasu arteritis with severe iliac artery thrombosis.
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EP
Keywords: Takayasu arteritis, aortic stenosis, thrombosis
1
ACCEPTED MANUSCRIPT
Case Report A 48-year old woman with a past medical history of tobacco abuse and obesity presented with acute onset of purple discoloration of left third and fifth toes and heel. She had a one-month
RI PT
preceding history of malaise and progressive intermittent bilateral hip and buttock pain with walking.
Vital signs revealed a right arm blood pressure of 132/89 mm Hg with no significant
SC
difference between both arms, a heart rate of 119 beats/min, and a temperature of 36.6°C.
Physical examination revealed purple discoloration of the plantar surface of the left third and
M AN U
fifth toes and lateral aspect of the left heel, along with weak bilateral femoral and non-palpable bilateral popliteal, dorsalis pedis (DP), and posterior tibial (PT) pulses. The rest of the physical examination was unremarkable including bilateral radial and ulnar pulses. Arterial duplex ultrasound revealed a moderately reduced resting ankle-brachial index
TE D
(ABI) of 0.71 bilaterally and no significant stenosis but mono-phasic waveform at the bilateral common femoral, superficial femoral, popliteal, PT, and DP arteries consistent with aortoiliac disease. Computed tomography angiogram (CTA) of the abdomen and pelvis revealed critical
EP
infrarenal aortic stenosis caused by underlying severe inflammation with wall thickening of 13mm involving the distal aorta and extending to the bilateral iliac arteries (Figure 1A, B, C).
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Magnetic resonance angiogram (MRA) of the chest did not reveal any other vascular involvement including the major proximal aortic branches. A complete blood cell count and complete metabolic profile were normal, except for
elevated glucose of 160 mg/dL (65-100 mg/dL). Further pertinent work-up revealed an elevated erythrocyte sedimentation rate (ESR) of 36 mm/hr (<21 mm/hr) and an elevated C-reactive protein (CRP) level of 2.76 mm/dL (<.50 mg/dL). A lipid panel revealed elevated cholesterol of
2
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221 mg/dl (100-199 mg/dL), elevated triglycerides of 272 mg/dL (<150 mg/dL), low highdensity lipoprotein (HDL) cholesterol of 29mg/dL (>40 mg/dL), and elevated low-density lipoprotein (LDL) cholesterol of 138 mg/dL (<130 mg/dL). Laboratory workup for
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immunoglobin G subclasses, complement components 3 and 4, antineutrophil cytoplasmic
antibodies (ANCA) vasculitis panel, and antinuclear antibodies was unremarkable. Anti-Human Immunodeficiency Virus (HIV) antibodies, syphilis, and viral hepatitis work-up was also
SC
negative.
Based on the clinical presentation, laboratory work-up and imaging findings, the
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diagnosis of inflammatory aortitis was made. Given the patient’s gender and the presence of severe stenosis of the distal aorta, Takayasu arteritis was considered as the etiology. Medical management with prednisone 60 mg daily, aspirin 81 mg daily, and atorvastatin 40 mg every evening was promptly started. The patient’s ischemic symptoms improved over the remainder of
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the hospitalization, and MRA performed two days later revealed stable aortoiliac findings, and so she was discharged on the above medication regiment. Three weeks later, the patient presented with sudden onset of left leg pain. Physical
EP
examination revealed cold bilateral feet, non-palpable left DP and PT pulses, and livedo reticularis along plantar and lateral aspects of the left foot. Acute critical limb ischemia was
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considered, and management was immediately started with a therapeutic dose of intravenous (IV) unfractionated heparin. Computed tomography angiogram revealed improvement in the aortic wall thickness (10mm) and inflammatory rind but new thrombosis of the left common iliac artery and embolic occlusion of the distal popliteal and tibiofibular trunk (Figure 2A, B, C). Catheter-based lytic therapy using tissue plasminogen activator (tPA) was combined with aspiration thrombectomy resulting in significant reduction of the clot burden at the left common
3
ACCEPTED MANUSCRIPT
iliac artery. However, the procedure was complicated by right iliac artery dissection which was managed by bare-metal stenting. The patient continued to improve on prednisone, atorvastatin, and aspirin, and heparin was bridged to a therapeutic dose of warfarin.
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At a two month follow-up visit, the patient’s ischemic symptoms have resolved but has encountered significant steroid side effects. Repeat laboratory workup revealed normalized ESR (18mm/hr) and improved CRP (.83mg/dL). Repeat CTA revealed further improvement of
SC
infrarenal aortic inflammation (Figure 3A, B, C) with wall thickening measuring 8mm and patent right external iliac artery stent. Arterial duplex showed a significant improvement of resting ABI
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of 0.94 on the left and 1.10 on the right. Due to improvement in clinical presentation, laboratory and imaging findings, prednisone continued to be slowly tapered.
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Discussion
Takayasu arteritis is a rare, chronic large vessel vasculitis of undetermined etiology that primarily affects the aorta, aortic arch, and large vessels.1,2 Typical manifestation of this disease
EP
occurs before age 40,3 and it is approximately 8.5 times more common among females than males.4 Prevalence of Takayasu arteritis is highest in the populations of Japan, Southeast Asia,
AC C
India, and Mexico.5 Specifically, Japan reports an estimated 150 new cases per year, compared to an incidence of 1 to 3 new cases per million persons per year in the United States and Europe.6–8 Clinical presentation of Takayasu arteritis is highly heterogeneous.9 Early systemic
symptoms of Takayasu arteritis may include fever, night sweats, malaise, weight loss, arthralgia, myalgia, and mild anemia.5 Disease progression can be manifested by diminished or absent pulses associated with blood pressure discrepancies and limb claudication, vascular bruits, and
4
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sometimes hypertension due to renal artery stenosis.3,5 Other systemic manifestations include headaches, carotodynia, erythema nodosum, and neurological features such as postural dizziness, seizures, and amaurosis fugax secondary to hypertension and/or ischemia.5 Cardiovascular
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complications may include aneurysms, pulmonary hypertension, aortic rupture, and thrombosis.9,10
Diagnosis relies on clinical presentation and imaging of the arterial tree by ultrasound,
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computed tomography, magnetic resonance, or catheter-based angiography showing stenoses of medium and large vessels.1,11 18-fluorodeoyxglucose (18F-FDG) positron emission tomography
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may also be helpful for initial diagnosis and monitoring of disease activity.12,13 Laboratory findings such as elevated ESR and CRP may reflect inflammation underlying Takayasu arteritis, but these alone are unreliable in identifying disease activity.9
Angiographic findings have been used to develop multiple systems of classification for
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Takayasu arteritis, with the most recent being advanced at the 1994 Tokyo International Conference on Takayasu arteritis.14 According to this classification, Takayasu arteritis can be classified as Type I, IIa, IIb, III, IV, or V (Table 1). The global prevalence of each type based on
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our literature review is summarized in Table 2.15 Takayasu arteritis classification is beneficial for planning surgical intervention and studying patient characteristics based on vessel involvement.5
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Although the pathogenesis of Takayasu arteritis remains unclear, it is believed to be an
antigen-driven, cell-mediated autoimmune process.24 Takayasu arteritis involves adventitial thickening, focal leukocytic infiltration of the tunica media, and intimal hyperplasia, thereby predisposing for stenosis, arterial occlusion, aneurysmal formation, and thrombosis in affected vessels.5,9 It is hypothesized that an unknown stimulus triggers expression of the 65kDa heat shock protein in aortic tissue.25 This protein is recognized by subsets of T lymphocytes,
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including γδ T lymphocytes, which in conjunction with macrophages produce pro-inflammatory cytokines resulting in active vascular inflammation.25,26 Takayasu arteritis has also been associated with various human leukocyte antigen (HLA) alleles in different populations.27
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Glucocorticoid therapy is the primary treatment modality for Takayasu arteritis, aimed at inducing and maintaining disease remission.28 Adjunctive, steroid-sparing immunosuppressants such as methotrexate, mycophenolate mofetil, and azathioprine, are frequently paired with
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glucosteriods to treat refractory disease and minimize steroid adverse events.9,24 More recent therapy, including disease modifying anti-rheumatic agent (leflunomide), tumor necrosis factor
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(TNF)-α antagonists (infliximab), Interleukin-6 Receptor Antagonist (tocilizumab), and antiCD20 (rituximab) have shown some promise for patients with refractory Takayasu arteritis.29,30 However, randomized clinical trials are needed to develop a better understanding of these novel agents.29 Surgical intervention is usually reserved for patients with severe symptomatic stenosis
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or occlusion of arteries leading to ischemic complications at different locations.5,9,31 The diagnosis of Type IV Takayasu arteritis in our patient was based on the clinical presentation and CTA revealing critical infrarenal aortic inflammation and stenosis extending to
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the bilateral iliac arteries, in conjunction with elevated inflammatory markers. The patient’s gender is also suggestive of Takayasu arteritis. Our patient’s age at presentation was slightly
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older than usual for Takayasu arteritis. However, given the severity of the inflammation and stenosis, we believe that the inflammation had started much earlier than the manifested symptoms. Giant cell arteritis was not considered given the patient’s age, and IgG4-related disease was also excluded given the absence of its other systemic manifestations and normal IgG4 titers.
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Our patient’s disease course was complicated by thrombosis of her left iliac artery with embolization to the popliteal artery shortly after starting treatment. Takayasu arteritis promotes a hypercoagulable state and thereby thrombus formation by significantly increasing platelet and
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coagulation activity.32 Although Takayasu-associated thrombosis has been reported in various inflamed vessels including the aorta,24 subclavian artery,33 and common mesenteric arterty,34 we were unable to find any cases of Takayasu arteritis complicated by thrombosis of the iliac artery.
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Our paper represents a rare case of Takayasu arteritis Type IV with impressive distal aortic inflammation and stenosis extending to the bilateral iliac arteries, complicated by iliac
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thrombosis and embolization to the popliteal artery. Considering that each aspect of our patient’s presentation is quite uncommon, this paper calls for more research in this field to better
Bibliography:
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understand and manage Takayasu arteritis and its complications.
1. Skeik, N., Rodriguez, A. & Engstrom, B. Rare Case of Takayasu Arteritis with Concurrent
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Aneurysmal Dilation and Stenosis. Int. J. Angiol. (2015). 2. Skeik, N. et al. Concurrent Takayasu arteritis with common variable immunodeficiency and
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moyamoya disease. Ann. Vasc. Surg. 27, 240.e13–18 (2013). 3. Arend, W. P. et al. The American College of Rheumatology 1990 criteria for the classification of Takayasu arteritis. Arthritis Rheum. 33, 1129–1134 (1990). 4. Lupi-Herrera, E. et al. Takayasu’s arteritis. Clinical study of 107 cases. Am. Heart J. 93, 94– 103 (1977).
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5. Johnston, S. L., Lock, R. J. & Gompels, M. M. Takayasu arteritis: a review. J. Clin. Pathol. 55, 481–486 (2002). 6. Koide, K. Takayasu arteritis in Japan. Heart Vessels. Suppl. 7, 48–54 (1992).
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20. Petrovic-Rackov, L., Pejnovic, N., Jevtic, M. & Damjanov, N. Longitudinal study of 16 patients with Takayasu’s arteritis: clinical features and therapeutic management. Clin. Rheumatol. 28, 179–185 (2009).
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33. Purkayastha, S., Jayadevan, E. R., Kapilamoorthy, T. R. & Gupta, A. K. Suction thrombectomy of thrombotic occlusion of the subclavian artery in a case of Takayasu’s
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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
Thoracic descending aorta, abdominal aorta, and/or renal
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Type III
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Type
arteries
Abdominal aorta and/or renal arteries
Type V
Combined features of types IIb and IV
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Type IV
*Involvement of the coronary or pulmonary arteries should be indicated as C (+) or P (+), respectively
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Table 1: Angiographic classification of Takayasu arteritis (based on the 1994 Tokyo International Conference on Takayasu Arteritis)14
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Type I
Type IIa
Type IIb
Type III
Type IV
Type V
India
32.2%
8.1%
1.6%
3.2%
17.7%
37.1%
Schmidt et al.
United
20%
6%
7%
5%
5%
57%
(2013)15
States
Sahin et al. (2012)17
Turkey
39.4%
6.4%
2.7%
Cong et al. (2010)18
China
40%
4.8%
1.6%
Kechauo et al.
Tunisia
67.7%
0%
10.7%
Serbia
50%
19%
South
36.1%
2.8%
Singh et al. (2015)16
Petrovic-Rackov et al. (2009)20 Park et al. (2005)21
Suwanwela et al.
4.5%
43%
2.4%
20.8%
30.4%
0%
3.6%
25%
0%
0%
0%
31%
4.6%
7.4%
15.8%
33.3%
Brazil
21%
4%
0%
4%
14%
57%
Thailand
0%
0%
11.1%
3.2%
19%
66.7%
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(1996)23
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Korea Sato et al. (1998)22
3.9%
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(2009)19
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Location
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Study
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Table 2: Global prevalence of Takayasu arteritis by type based on our literature review
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A
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B
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C
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Figure 1. Computed tomography angiogram transverse (A, B) and coronal (C) images showing significant infrarenal aortic stenosis extending to the bilateral iliac artery (arrows)
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A
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B
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C
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Figure 2. Computed tomography angiogram transverse (A, B) and coronal (C) images showing improvement in aortic wall thickness but new thrombosis of the left common iliac artery (arrows)
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A
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B
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C
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Figure 3. Computed tomography angiogram transverse (A, B) and coronal (C) images showing further improvement of infrarenal aortic inflammation and bilateral iliac artery stenosis (arrows)