Takayasu Arteriti
Özet
Takayasu arteriti (TA), esas olarak aort ve subklavyen ile karotis gibi büyük dallarını etkileyen, genç kadınlarda ve 40 yaşın altında daha sık görülen kronik granülomatöz büyük damar vaskülitidir. Hastalığın patogenezinde HLA-B52 genetik yatkınlığı ve IL-6 gibi proinflamatuar sitokinler rol oynar. Klinik seyir, ateş ve halsizlik gibi spesifik olmayan konstitüsyonel semptomlarla sinsi başlayıp, damar inflamasyonunun ilerlemesiyle nabız kaybı, üfürüm, kan basıncı farkı ve ekstremite kladikasyosu gibi tıkayıcı iskemik bulgularla devam eder. Tanıda tek bir spesifik test olmaması gecikmelere yol açarken; konvansiyonel anjiyografi, BTA, PET ve özellikle radyasyonsuz yapısı nedeniyle ilk seçenek olarak önerilen MRA gibi görüntüleme yöntemleri kritik öneme sahiptir. Tedavinin temelini glukokortikoidler oluşturur; steroid dozunu azaltmak ve nüksleri önlemek amacıyla metotreksat ve azatioprin gibi geleneksel immunsüpresif ajanlar eklenir. Dirençli vakalarda ise TNF inhibitörleri ve tocilizumab gibi biyolojik tedaviler tercih edilmektedir. Erken tanı ve etkin inflamasyon kontrolü, prognozu iyileştirmede ve mortaliteyi azaltmada hayati rol oynamaktadır.
Takayasu arteritis (TA) is a chronic granulomatous large-vessel vasculitis that predominantly affects the aorta and its main branches, such as the subclavian and carotid arteries, occurring more frequently in young women under the age of 40. HLA-B52 genetic susceptibility and pro-inflammatory cytokines like IL-6 play a crucial role in its pathogenesis. The clinical course begins insidiously with non-specific constitutional symptoms such as fever and fatigue, progressing to occlusive ischemic manifestations including pulse loss, bruits, blood pressure discrepancies, and extremity claudication as vascular inflammation advances. Diagnosis is often delayed due to the lack of specific laboratory tests; however, advanced imaging techniques like conventional angiography, CTA, PET, and particularly MRA—which is recommended as the first choice due to its non-radiation nature—are critical. Glucocorticoids form the cornerstone of medical therapy, often combined with conventional immunosuppressive agents like methotrexate and azathioprine to reduce steroid dosage and prevent relapses. In refractory cases, biologic therapies including TNF inhibitors and tocilizumab are successfully utilized. Early diagnosis and effective inflammation control are paramount in improving prognosis and reducing mortality risks.
Referanslar
Numano F. The story of Takayasu arteritis. Rheumatology (Oxford). 2002;41(1):103-106. doi:10.1093/rheumatology/41.1.103
Mason JC. Takayasu arteritis--advances in diagnosis and management. Nat Rev Rheumatol. 2010;6(7):406-415. doi:10.1038/nrrheum.2010.82
Brunner J, Feldman BM, Tyrrell PN, et al. Takayasu arteritis in children and adolescents. Rheumatology (Oxford). 2010;49(10):1806-1814. doi:10.1093/rheumatology/keq167
Nazareth R, Mason JC. Takayasu arteritis: severe consequences of delayed diagnosis. QJM. 2011;104(9):797-800. doi:10.1093/qjmed/hcq193
Alibaz-Oner F, Direskeneli H. Update on Takayasu's arteritis. Presse Med. 2015;44(6 Pt 2):e259-e265. doi:10.1016/j.lpm.2015.01.015
Watts R, Al-Taiar A, Mooney J, Scott D, Macgregor A. The epidemiology of Takayasu arteritis in the UK. Rheumatology (Oxford). 2009;48(8):1008-1011. doi:10.1093/rheumatology/kep153
Birlik M, Kücükyavas Y, Aksu K, et al. Epidemiology of Takayasu's arteritis in Turkey. Clin Exp Rheumatol. 2016;34(3 Suppl 97):S33-S39.
Saruhan-Direskeneli G, Hughes T, Aksu K, et al. Identification of multiple genetic susceptibility loci in Takayasu arteritis. Am J Hum Genet. 2013;93(2):298-305. doi:10.1016/j.ajhg.2013.05.026
Terao C, Yoshifuji H, Kimura A, et al. Two susceptibility loci to Takayasu arteritis reveal a synergistic role of the IL12B and HLA-B regions in a Japanese population. Am J Hum Genet. 2013;93(2):289-297. doi:10.1016/j.ajhg.2013.05.024
Keser G, Aksu K, Direskeneli H. Discrepancies between vascular and systemic inflammation in large vessel vasculitis: an important problem revisited. Rheumatology (Oxford). 2018;57(5):784-790. doi:10.1093/rheumatology/kex333
Saadoun D, Garrido M, Comarmond C, et al. Th1 and Th17 cytokines drive inflammation in Takayasu arteritis. Arthritis Rheumatol. 2015;67(5):1353-1360. doi:10.1002/art.39037
Clement M, Galy A, Bruneval P, et al. Tertiary Lymphoid Organs in Takayasu Arteritis. Front Immunol. 2016;7:158. Published 2016 Apr 22. doi:10.3389/fimmu.2016.00158
Goel R, Kabeerdoss J, Ram B, et al. Serum Cytokine Profile in Asian Indian Patients with Takayasu Arteritis and its Association with Disease Activity. Open Rheumatol J. 2017;11:23-29. Published 2017 Feb 28. doi:10.2174/1874312901711010023
Hadjadj J, Canaud G, Mirault T, et al. mTOR pathway is activated in endothelial cells from patients with Takayasu arteritis and is modulated by serum immunoglobulin G. Rheumatology (Oxford). 2018;57(6):1011-1020. doi:10.1093/rheumatology/key017
Vanoli M, Daina E, Salvarani C, et al. Takayasu's arteritis: A study of 104 Italian patients. Arthritis Rheum. 2005;53(1):100-107. doi:10.1002/art.20922
Park MC, Lee SW, Park YB, Chung NS, Lee SK. Clinical characteristics and outcomes of Takayasu's arteritis: analysis of 108 patients using standardized criteria for diagnosis, activity assessment, and angiographic classification. Scand J Rheumatol. 2005;34(4):284-292. doi:10.1080/03009740510026526
Sharma BK, Jain S, Sagar S. Systemic manifestations of Takayasu arteritis: the expanding spectrum. Int J Cardiol. 1996;54 Suppl:S149-S154. doi:10.1016/s0167-5273(96)88784-5
Hata A, Noda M, Moriwaki R, Numano F. Angiographic findings of Takayasu arteritis: new classification. Int J Cardiol. 1996;54 Suppl:S155-S163. doi:10.1016/s0167-5273(96)02813-6
Kerr GS, Hallahan CW, Giordano J, et al. Takayasu arteritis. Ann Intern Med. 1994;120(11):919-929. doi:10.7326/0003-4819-120-11-199406010-00004
Keser G, Aksu K, Direskeneli H. Takayasu arteritis: an update. Turk J Med Sci. 2018;48(4):681-697. Published 2018 Aug 16. doi:10.3906/sag-1804-136
He Y, Lv N, Dang A, Cheng N. Pulmonary Artery Involvement in Patients with Takayasu Arteritis. J Rheumatol. 2020;47(2):264-272. doi:10.3899/jrheum.190045
Esen F, Ergelen R, Alibaz-Öner F, Çelik G, Direskeneli H, Kazokoğlu H. Ocular findings and blood flow in patients with Takayasu arteritis: a cross-sectional study. Br J Ophthalmol. 2019;103(7):928-932. doi:10.1136/bjophthalmol-2018-312580
Francès C, Boisnic S, Blétry O, et al. Cutaneous manifestations of Takayasu arteritis. A retrospective study of 80 cases. Dermatologica. 1990;181(4):266-272. doi:10.1159/000247820
Pascual-López M, Hernández-Núñez A, Aragüés-Montañés M, Daudén E, Fraga J, García-Díez A. Takayasu's disease with cutaneous involvement. Dermatology. 2004;208(1):10-15. doi:10.1159/000075039
Bicakcigil M, Aksu K, Kamali S, et al. Takayasu's arteritis in Turkey - clinical and angiographic features of 248 patients. Clin Exp Rheumatol. 2009;27(1 Suppl 52):S59-S64.
Michailidou D, Rosenblum JS, Rimland CA, Marko J, Ahlman MA, Grayson PC. Clinical symptoms and associated vascular imaging findings in Takayasu's arteritis compared to giant cell arteritis. Ann Rheum Dis. 2020;79(2):262-267. doi:10.1136/annrheumdis-2019-216145
Tombetti E, Mason JC. Application of imaging techniques for Takayasu arteritis. Presse Med. 2017;46(7-8 Pt 2):e215-e223. doi:10.1016/j.lpm.2017.03.022
Dejaco C, Ramiro S, Duftner C, et al. EULAR recommendations for the use of imaging in large vessel vasculitis in clinical practice. Ann Rheum Dis. 2018;77(5):636-643. doi:10.1136/annrheumdis-2017-212649
Yoshida S, Akiba H, Tamakawa M, et al. The spectrum of findings in supra-aortic Takayasu's arteritis as seen on spiral CT angiography and digital subtraction angiography. Cardiovasc Intervent Radiol. 2001;24(2):117-121. doi:10.1007/s002700000368
Seyahi E, Ucgul A, Cebi Olgun D, et al. Aortic and coronary calcifications in Takayasu arteritis. Semin Arthritis Rheum. 2013;43(1):96-104. doi:10.1016/j.semarthrit.2012.11.001
Yamada I, Nakagawa T, Himeno Y, Kobayashi Y, Numano F, Shibuya H. Takayasu arteritis: diagnosis with breath-hold contrast-enhanced three-dimensional MR angiography. J Magn Reson Imaging. 2000;11(5):481-487. doi:10.1002/(sici)1522-2586(200005)11:5<481::aid-jmri3>3.0.co;2-4
Raninen RO, Kupari MM, Hekali PE. Carotid and femoral artery stiffness in Takayasu's arteritis. An ultrasound study. Scand J Rheumatol. 2002;31(2):85-88. doi:10.1080/03009740252937595
Cheng Y, Lv N, Wang Z, Chen B, Dang A. 18-FDG-PET in assessing disease activity in Takayasu arteritis: a meta-analysis. Clin Exp Rheumatol. 2013;31(1 Suppl 75):S22-S27.
Zhang X, Zhou J, Sun Y, Shi H, Ji Z, Jiang L. 18F-FDG-PET/CT: an accurate method to assess the activity of Takayasu's arteritis. Clin Rheumatol. 2018;37(7):1927-1935. doi:10.1007/s10067-017-3960-7
de Leeuw K, Bijl M, Jager PL. Additional value of positron emission tomography in diagnosis and follow-up of patients with large vessel vasculitides. Clin Exp Rheumatol. 2004;22(6 Suppl 36):S21-S26.
Arend WP, Michel BA, Bloch DA, et al. The American College of Rheumatology 1990 criteria for the classification of Takayasu arteritis. Arthritis Rheum. 1990;33(8):1129-1134. doi:10.1002/art.1780330811
Hoffman GS. Determinants of vessel targeting in vasculitis. Clin Dev Immunol. 2004;11(3-4):275-279. doi:10.1080/17402520400001652
Lee KH, Cho A, Choi YJ, et al. The role of (18) F-fluorodeoxyglucose-positron emission tomography in the assessment of disease activity in patients with takayasu arteritis [published correction appears in Arthritis Rheum. 2012 Apr;64(4):1302]. Arthritis Rheum. 2012;64(3):866-875. doi:10.1002/art.33413
Gornik HL, Persu A, Adlam D, et al. First International Consensus on the diagnosis and management of fibromuscular dysplasia [published correction appears in Vasc Med. 2019 Oct;24(5):475] [published correction appears in Vasc Med. 2021 Aug;26(4):NP1]. Vasc Med. 2019;24(2):164-189. doi:10.1177/1358863X18821816
Keser G, Aksu K. Diagnosis and differential diagnosis of large-vessel vasculitides. Rheumatol Int. 2019;39(2):169-185. doi:10.1007/s00296-018-4157-3
Clifford AH, Arafat A, Idrees JJ, et al. Outcomes Among 196 Patients With Noninfectious Proximal Aortitis. Arthritis Rheumatol. 2019;71(12):2112-2120. doi:10.1002/art.40855
Dijkema EJ, Leiner T, Grotenhuis HB. Diagnosis, imaging and clinical management of aortic coarctation [published correction appears in Heart. 2019 Jul;105(14):e6]. Heart. 2017;103(15):1148-1155. doi:10.1136/heartjnl-2017-311173
Liang P, Tan-Ong M, Hoffman GS. Takayasu's arteritis: vascular interventions and outcomes. J Rheumatol. 2004;31(1):102-106.
Keser G, Aksu K. What is new in management of Takayasu arteritis?. Presse Med. 2017;46(7-8 Pt 2):e229-e235. doi:10.1016/j.lpm.2016.11.033
Maksimowicz-McKinnon K, Clark TM, Hoffman GS. Limitations of therapy and a guarded prognosis in an American cohort of Takayasu arteritis patients. Arthritis Rheum. 2007;56(3):1000-1009. doi:10.1002/art.22404
Kötter I, Henes JC, Wagner AD, Loock J, Gross WL. Does glucocorticosteroid-resistant large-vessel vasculitis (giant cell arteritis and Takayasu arteritis) exist and how can remission be achieved? A critical review of the literature. Clin Exp Rheumatol. 2012;30(1 Suppl 70):S114-S129.
Shetty AK, Stopa AR, Gedalia A. Low-dose methotrexate as a steroid-sparing agent in a child with Takayasu's arteritis. Clin Exp Rheumatol. 1998;16(3):335-336.
Nakamura S, Morishita M, Yang CL, et al. An elderly female who survived more than 30 years following a diagnosis of Takayasu's arteritis, complicated by fatal intestinal amyloidosis. Clin Rheumatol. 2006;25(6):907-910. doi:10.1007/s10067-005-0088-y
Hoffman GS, Leavitt RY, Kerr GS, Rottem M, Sneller MC, Fauci AS. Treatment of glucocorticoid-resistant or relapsing Takayasu arteritis with methotrexate. Arthritis Rheum. 1994;37(4):578-582. doi:10.1002/art.1780370420
Valsakumar AK, Valappil UC, Jorapur V, Garg N, Nityanand S, Sinha N. Role of immunosuppressive therapy on clinical, immunological, and angiographic outcome in active Takayasu's arteritis. J Rheumatol. 2003;30(8):1793-1798.
Cash JM, Engelbrecht JA. Takayasu's arteritis in western South Dakota. S D J Med. 1990;43(9):5-9.
Rodríguez-Hurtado FJ, Sabio JM, Lucena J, Jiménez-Alonso J. Ocular involvement in Takayasu's arteritis: response to cyclophosphamide therapy. Eur J Med Res. 2002;7(3):128-130.
Goel R, Danda D, Joseph G, et al. Long-term outcome of 251 patients with Takayasu arteritis on combination immunosuppressant therapy: Single centre experience from a large tertiary care teaching hospital in Southern India. Semin Arthritis Rheum. 2018;47(5):718-726. doi:10.1016/j.semarthrit.2017.09.014
Li J, Yang Y, Zhao J, Li M, Tian X, Zeng X. The efficacy of Mycophenolate mofetil for the treatment of Chinese Takayasu's arteritis. Sci Rep. 2016;6:38687. Published 2016 Dec 7. doi:10.1038/srep38687
Goel R, Danda D, Mathew J, Edwin N. Mycophenolate mofetil in Takayasu's arteritis. Clin Rheumatol. 2010;29(3):329-332. doi:10.1007/s10067-009-1333-6
Fearfield LA, Ross JR, Farrell AM, Costello C, Bunker CB, Staughton RC. Pyoderma gangrenosum associated with Takayasu's arteritis responding to cyclosporin. Br J Dermatol. 1999;141(2):339-343. doi:10.1046/j.1365-2133.1999.02989.x
Ujiie H, Sawamura D, Yokota K, Nishie W, Shichinohe R, Shimizu H. Pyoderma gangrenosum associated with Takayasu's arteritis. Clin Exp Dermatol. 2004;29(4):357-359. doi:10.1111/j.1365-2230.2004.01514.x
Yokoe I, Haraoka H, Harashima H. A patient with Takayasu's arteritis and rheumatoid arthritis who responded to tacrolimus hydrate. Intern Med. 2007;46(22):1873-1877. doi:10.2169/internalmedicine.46.0211
de Souza AW, de Almeida Agustinelli R, de Cinque Almeida H, et al. Leflunomide in Takayasu arteritis - A long term observational study. Rev Bras Reumatol Engl Ed. 2016;56(4):371-375. doi:10.1016/j.rbre.2016.02.003
Cui X, Dai X, Ma L, et al. Efficacy and safety of leflunomide treatment in Takayasu arteritis: Case series from the East China cohort. Semin Arthritis Rheum. 2020;50(1):59-65. doi:10.1016/j.semarthrit.2019.06.009
Molloy ES, Langford CA, Clark TM, Gota CE, Hoffman GS. Anti-tumour necrosis factor therapy in patients with refractory Takayasu arteritis: long-term follow-up. Ann Rheum Dis. 2008;67(11):1567-1569. doi:10.1136/ard.2008.093260
Clifford A, Hoffman GS. Recent advances in the medical management of Takayasu arteritis: an update on use of biologic therapies. Curr Opin Rheumatol. 2014;26(1):7-15. doi:10.1097/BOR.0000000000000004
Goel R, Danda D, Kumar S, Joseph G. Rapid control of disease activity by tocilizumab in 10 'difficult-to-treat' cases of Takayasu arteritis. Int J Rheum Dis. 2013;16(6):754-761. doi:10.1111/1756-185X.12220
Loricera J, Blanco R, Castañeda S, et al. Tocilizumab in refractory aortitis: study on 16 patients and literature review. Clin Exp Rheumatol. 2014;32(3 Suppl 82):S79-S89.
Bredemeier M, Rocha CM, Barbosa MV, Pitrez EH. One-year clinical and radiological evolution of a patient with refractory Takayasu's arteritis under treatment with tocilizumab. Clin Exp Rheumatol. 2012;30(1 Suppl 70):S98-S100.
Tombetti E, Di Chio MC, Sartorelli S, et al. Anti-cytokine treatment for Takayasu arteritis: State of the art. Intractable Rare Dis Res. 2014;3(1):29-33. doi:10.5582/irdr.3.29
Langford CA, Cuthbertson D, Ytterberg SR, et al. A Randomized, Double-Blind Trial of Abatacept (CTLA-4Ig) for the Treatment of Takayasu Arteritis. Arthritis Rheumatol. 2017;69(4):846-853. doi:10.1002/art.40037
Hoyer BF, Mumtaz IM, Loddenkemper K, et al. Takayasu arteritis is characterised by disturbances of B cell homeostasis and responds to B cell depletion therapy with rituximab. Ann Rheum Dis. 2012;71(1):75-79. doi:10.1136/ard.2011.153007
Pazzola G, Muratore F, Pipitone N, et al. Rituximab therapy for Takayasu arteritis: a seven patients experience and a review of the literature. Rheumatology (Oxford). 2018;57(7):1151-1155. doi:10.1093/rheumatology/kex249
Gon Y, Yoshifuji H, Nakajima T, et al. Long-term outcomes of refractory Takayasu arteritis patients treated with biologics including ustekinumab. Mod Rheumatol. 2021;31(3):678-683. doi:10.1080/14397595.2020.1800560
Campochiaro C, Tomelleri A, Sartorelli S, et al. Drug retention and discontinuation reasons between seven biologics in patients with Takayasu arteritis. Semin Arthritis Rheum. 2020;50(3):509-514. doi:10.1016/j.semarthrit.2020.01.005
Schmidt J, Kermani TA, Bacani AK, et al. Diagnostic features, treatment, and outcomes of Takayasu arteritis in a US cohort of 126 patients. Mayo Clin Proc. 2013;88(8):822-830. doi:10.1016/j.mayocp.2013.04.025
Ohigashi H, Haraguchi G, Konishi M, et al. Improved prognosis of Takayasu arteritis over the past decade--comprehensive analysis of 106 patients. Circ J. 2012;76(4):1004-1011. doi:10.1253/circj.cj-11-1108
