Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Primer
  • Published:

Large-vessel vasculitis

Abstract

Large-vessel vasculitis (LVV) manifests as inflammation of the aorta and its major branches and is the most common primary vasculitis in adults. LVV comprises two distinct conditions, giant cell arteritis and Takayasu arteritis, although the phenotypic spectrum of primary LVV is complex. Non-specific symptoms often predominate and so patients with LVV present to a range of health-care providers and settings. Rapid diagnosis, specialist referral and early treatment are key to good patient outcomes. Unfortunately, disease relapse remains common and chronic vascular complications are a source of considerable morbidity. Although accurate monitoring of disease activity is challenging, progress in vascular imaging techniques and the measurement of laboratory biomarkers may facilitate better matching of treatment intensity with disease activity. Further, advances in our understanding of disease pathophysiology have paved the way for novel biologic treatments that target important mediators of disease in both giant cell arteritis and Takayasu arteritis. This work has highlighted the substantial heterogeneity present within LVV and the importance of an individualized therapeutic approach. Future work will focus on understanding the mechanisms of persisting vascular inflammation, which will inform the development of increasingly sophisticated imaging technologies. Together, these will enable better disease prognostication, limit treatment-associated adverse effects, and facilitate targeted development and use of novel therapies.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Disease classification and arterial involvement in LVV.
Fig. 2: Global incidence of large-vessel vasculitis.
Fig. 3: Proposed factors contributing to a loss of immune tolerance of large arteries and initiation of inflammation in LVV.
Fig. 4: Mediators of inflammation in large-vessel vasculitis.
Fig. 5: Investigation and diagnosis of LVV.
Fig. 6: Longitudinal follow-up imaging using FDG-PET.
Fig. 7: PET–MRI in large-vessel vasculitis.
Fig. 8: Management of LVV.

Similar content being viewed by others

References

  1. Jennette, J. C. et al. 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum. 65, 1–11 (2013).

    CAS  PubMed  Google Scholar 

  2. Horton, B. T., Magath, T. B. & Brown, G. E. Arteritis of the temporal vessels: a previously undescribed form. Arch. Intern. Med. 53, 400–409 (1934).

    Google Scholar 

  3. Kogstad, O. A. Polymyalgia rheumatica and its relation to arteritis temporalis. Acta Med. Scand. 178, 591–598 (1965).

    CAS  PubMed  Google Scholar 

  4. Gilmour, J. R. Giant cell chronic arteritis. J. Pathol. Bacteriol. 53, 263–277 (1941).

    Google Scholar 

  5. Hamrin, B., Jonsson, N. & Hellsten, S. Polymyalgia arteritica. Ann. Rheum. Dis. 27, 397–405 (1968).

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Blockmans, D. et al. Repetitive 18F-fluorodeoxyglucose positron emission tomography in giant cell arteritis: a prospective study of 35 patients. Arthritis Rheum. 55, 131–137 (2006).

    PubMed  Google Scholar 

  7. Schmidt, W. A., Natusch, A., Moller, D. E., Vorpahl, K. & Gromnica-Ihle, E. Involvement of peripheral arteries in giant cell arteritis: a color Doppler sonography study. Clin. Exp. Rheumatol. 20, 309–318 (2002).

    CAS  PubMed  Google Scholar 

  8. Hellmich, B. et al. 2018 Update of the EULAR recommendations for the management of large vessel vasculitis. Ann. Rheum. Dis. 79, 19–30 (2020). These guidelines provide a framework for the diagnosis and management of LVV based on the best available evidence.

    PubMed  Google Scholar 

  9. Takayasu, M. A case with peculiar changes of the retinal central vessels [Japanese]. Acta Soc. Ophthal Jpn. 12, 554–555 (1908).

    Google Scholar 

  10. Nasu, T. Pathology of pulseless disease. A systematic study and critical review of twenty-one autopsy cases reported in Japan. Angiology 14, 225–242 (1963).

    CAS  PubMed  Google Scholar 

  11. Gonzalez-Gay, M. A. et al. Giant cell arteritis in northwestern Spain: a 25-year epidemiologic study. Medicine 86, 61–68 (2007).

    PubMed  Google Scholar 

  12. Salvarani, C., Crowson, C. S., O’Fallon, W. M., Hunder, G. G. & Gabriel, S. E. Reappraisal of the epidemiology of giant cell arteritis in Olmsted County, Minnesota, over a fifty-year period. Arthritis Rheum. 51, 264–268 (2004). This study is an important example of epidemiological research in GCA.

    PubMed  Google Scholar 

  13. Kermani, T. A. et al. Increase in age at onset of giant cell arteritis: a population-based study. Ann. Rheum. Dis. 69, 780–781 (2010).

    PubMed  Google Scholar 

  14. Gran, J. T. & Myklebust, G. The incidence of polymyalgia rheumatica and temporal arteritis in the county of Aust Agder, south Norway: a prospective study 1987-94. J. Rheumatol. 24, 1739–1743 (1997).

    CAS  PubMed  Google Scholar 

  15. Gonzalez-Gay, M. A. et al. Epidemiology of giant cell arteritis and polymyalgia rheumatica. Arthritis Rheum. 61, 1454–1461 (2009).

    PubMed  Google Scholar 

  16. Muratore, F. et al. Large-vessel giant cell arteritis: a cohort study. Rheumatology 54, 463–470 (2015).

    PubMed  Google Scholar 

  17. Schmidt, W. A., Seifert, A., Gromnica-Ihle, E., Krause, A. & Natusch, A. Ultrasound of proximal upper extremity arteries to increase the diagnostic yield in large-vessel giant cell arteritis. Rheumatology 47, 96–101 (2008).

    CAS  PubMed  Google Scholar 

  18. Boesen, P. & Sorensen, S. F. Giant cell arteritis, temporal arteritis, and polymyalgia rheumatica in a Danish county. A prospective investigation, 1982–1985. Arthritis Rheum. 30, 294–299 (1987).

    CAS  PubMed  Google Scholar 

  19. Salvarani, C. et al. Epidemiologic and immunogenetic aspects of polymyalgia rheumatica and giant cell arteritis in northern Italy. Arthritis Rheum. 34, 351–356 (1991).

    CAS  PubMed  Google Scholar 

  20. Kobayashi, S. et al. Clinical and epidemiologic analysis of giant cell (temporal) arteritis from a nationwide survey in 1998 in Japan: the first government-supported nationwide survey. Arthritis Rheum. 49, 594–598 (2003).

    PubMed  Google Scholar 

  21. Tam, S. & Wong, T. C. Temporal arteritis in Hong Kong. Int. J. Rheum. Dis. 11, 163–169 (2008).

    Google Scholar 

  22. Sharma, A., Mohammad, A. J. & Turesson, C. Incidence and prevalence of giant cell arteritis and polymyalgia rheumatica: a systematic literature review. Semin. Arthritis Rheum. 50, 1040–1048 (2020).

    PubMed  Google Scholar 

  23. Koide, K. Takayasu arteritis in Japan. Heart Vessel. Suppl. 7, 48–54 (1992).

    CAS  Google Scholar 

  24. Watts, R., Al-Taiar, A., Mooney, J., Scott, D. & Macgregor, A. The epidemiology of Takayasu arteritis in the UK. Rheumatology 48, 1008–1011 (2009).

    PubMed  Google Scholar 

  25. Dreyer, L., Faurschou, M. & Baslund, B. A population-based study of Takayasu s arteritis in eastern Denmark. Clin. Exp. Rheumatol. 29, S40–S42 (2011).

    PubMed  Google Scholar 

  26. Mohammad, A. J. & Mandl, T. Takayasu arteritis in southern Sweden. J. Rheumatol. 42, 853–858 (2015).

    PubMed  Google Scholar 

  27. Gudbrandsson, B., Molberg, O., Garen, T. & Palm, O. Prevalence, incidence, and disease characteristics of Takayasu Arteritis by ethnic background: data from a large, population-based cohort resident in southern Norway. Arthritis Care Res. 69, 278–285 (2017).

    Google Scholar 

  28. Arnaud, L. et al. Takayasu arteritis in France: a single-center retrospective study of 82 cases comparing white, North African, and black patients. Medicine 89, 1–17 (2010).

    PubMed  Google Scholar 

  29. Rutter, M., Bowley, J., Lanyon, P. C., Grainge, M. J. & Pearce, F. A. A systematic review and meta-analysis of the incidence rate of Takayasu arteritis. Rheumatology 60, 4982–4990 (2021).

    PubMed  PubMed Central  Google Scholar 

  30. Goel, R. 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. 47, 718–726 (2018).

    CAS  PubMed  Google Scholar 

  31. Danda, D. et al. Clinical course of 602 patients with Takayasu’s arteritis: comparison between childhood-onset versus adult onset disease. Rheumatology 60, 2246–2255 (2020).

    PubMed Central  Google Scholar 

  32. Zhang, Z. et al. An observational study of sex differences in Takayasu arteritis in china: implications for worldwide regional differences. Ann. Vasc. Surg. 66, 309–317 (2020).

    PubMed  Google Scholar 

  33. Watanabe, Y., Miyata, T. & Tanemoto, K. Current clinical features of new patients with Takayasu arteritis observed from cross-country research in Japan: age and sex specificity. Circulation 132, 1701–1709 (2015).

    PubMed  Google Scholar 

  34. Aeschlimann, F. A. et al. Presentation and disease course of childhood-onset versus adult-onset Takayasu arteritis. Arthritis Rheumatol. 71, 315–323 (2019).

    PubMed  Google Scholar 

  35. Quinn, K. A. et al. Patterns of clinical presentation in Takayasu’s arteritis. Semin. Arthritis Rheum. 50, 576–581 (2020).

    PubMed  Google Scholar 

  36. Tomelleri, A. et al. Gender differences in clinical presentation and vascular pattern in patients with Takayasu arteritis. Scand. J. Rheumatol. 48, 482–490 (2019).

    CAS  PubMed  Google Scholar 

  37. Carmona, F. D., Gonzalez-Gay, M. A. & Martin, J. Genetic component of giant cell arteritis. Rheumatology 53, 6–18 (2014).

    CAS  PubMed  Google Scholar 

  38. Mattey, D. L. et al. Association of giant cell arteritis and polymyalgia rheumatica with different tumor necrosis factor microsatellite polymorphisms. Arthritis Rheum. 43, 1749–1755 (2000).

    CAS  PubMed  Google Scholar 

  39. Salvarani, C. et al. Intercellular adhesion molecule 1 gene polymorphisms in polymyalgia rheumatica/giant cell arteritis: association with disease risk and severity. J. Rheumatol. 27, 1215–1221 (2000).

    CAS  PubMed  Google Scholar 

  40. Rueda, B. et al. A functional variant of vascular endothelial growth factor is associated with severe ischemic complications in giant cell arteritis. J. Rheumatol. 32, 1737–1741 (2005).

    CAS  PubMed  Google Scholar 

  41. Palomino-Morales, R. et al. Association between toll-like receptor 4 gene polymorphism and biopsy-proven giant cell arteritis. J. Rheumatol. 36, 1501–1506 (2009).

    CAS  PubMed  Google Scholar 

  42. Serrano, A. et al. Identification of the PTPN22 functional variant R620W as susceptibility genetic factor for giant cell arteritis. Ann. Rheum. Dis. 72, 1882–1886 (2013).

    CAS  PubMed  Google Scholar 

  43. Carmona, F. D. et al. A genome-wide association study identifies risk alleles in plasminogen and P4HA2 associated with giant cell arteritis. Am. J. Hum. Genet. 100, 64–74 (2017). Genome-wide association studies such as this one are providing novel insights into the pathogenesis of GCA.

    CAS  PubMed  Google Scholar 

  44. Weyand, C. & Goronzy, J. Immune mechanisms in medium and large-vessel vasculitis. Nat. Rev. Rheumatol. 9, 731–740 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Renauer, P. & Sawalha, A. H. The genetics of Takayasu arteritis. Presse Med. 46, e179–e187 (2017).

    PubMed  PubMed Central  Google Scholar 

  46. Terao, C. et al. Genetic determinants and an epistasis of LILRA3 and HLA-B*52 in Takayasu arteritis. Proc. Natl Acad. Sci. USA 115, 13045–13050 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  47. 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).

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Renauer, P. A. et al. Identification of susceptibility loci in IL6, RPS9/LILRB3, and an intergenic locus on chromosome 21q22 in Takayasu arteritis in a genome-wide association study. Arthritis Rheumatol. 67, 1361–1368 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Saruhan-Direskeneli, G. et al. Identification of multiple genetic susceptibility loci in Takayasu arteritis. Am. J. Hum. Genet. 93, 298–305 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Terao, C. 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. 93, 289–297 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Ortiz-Fernandez, L. et al. Identification of susceptibility loci for Takayasu arteritis through a large multi-ancestral genome-wide association study. Am. J. Hum. Genet. 108, 84–99 (2021). Genome-wide association studies such as this one are providing novel insights into the pathogenesis of TAK.

    CAS  PubMed  Google Scholar 

  52. Carmona, F. D. et al. Analysis of the common genetic component of large-vessel vasculitides through a meta-Immunochip strategy. Sci. Rep. 7, 43953 (2017).

    PubMed  PubMed Central  Google Scholar 

  53. Smeeth, L., Cook, C. & Hall, A. J. Incidence of diagnosed polymyalgia rheumatica and temporal arteritis in the United Kingdom, 1990–2001. Ann. Rheum. Dis. 65, 1093–1098 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Nordborg, E. & Nordborg, C. Giant cell arteritis: epidemiological clues to its pathogenesis and an update on its treatment. Rheumatology 42, 413–421 (2003).

    CAS  PubMed  Google Scholar 

  55. Ostrowski, R. A., Metgud, S., Tehrani, R. & Jay, W. M. Varicella zoster virus in giant cell arteritis: a review of current medical literature. Neuroophthalmology 43, 159–170 (2019).

    PubMed  PubMed Central  Google Scholar 

  56. Kumar Chauhan, S., Kumar Tripathy, N., Sinha, N., Singh, M. & Nityanand, S. Cellular and humoral immune responses to mycobacterial heat shock protein-65 and its human homologue in Takayasu’s arteritis. Clin. Exp. Immunol. 138, 547–553 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Pedreira, A. L. S. & Santiago, M. B. Association between Takayasu arteritis and latent or active Mycobacterium tuberculosis infection: a systematic review. Clin. Rheumatol. 39, 1019–1026 (2020).

    PubMed  Google Scholar 

  58. Hill, C. L. et al. Risk of mortality in patients with giant cell arteritis: a systematic review and meta-analysis. Semin. Arthritis Rheum. 46, 513–519 (2017).

    PubMed  Google Scholar 

  59. Richards, B. L., March, L. & Gabriel, S. E. Epidemiology of large-vessel vasculidities. Best. Pract. Res. Clin. Rheumatol. 24, 871–883 (2010).

    PubMed  Google Scholar 

  60. Li, K. J., Semenov, D., Turk, M. & Pope, J. A meta-analysis of the epidemiology of giant cell arteritis across time and space. Arthritis Res. Ther. 23, 82 (2021).

    PubMed  PubMed Central  Google Scholar 

  61. Gran, J. T., Myklebust, G., Wilsgaard, T. & Jacobsen, B. K. Survival in polymyalgia rheumatica and temporal arteritis: a study of 398 cases and matched population controls. Rheumatology 40, 1238–1242 (2001).

    CAS  PubMed  Google Scholar 

  62. Yang, L. et al. Clinical manifestations and longterm outcome for patients with Takayasu arteritis in China. J. Rheumatol. 41, 2439–2446 (2014).

    PubMed  Google Scholar 

  63. Soto, M. E., Espinola, N., Flores-Suarez, L. F. & Reyes, P. A. Takayasu arteritis: clinical features in 110 Mexican Mestizo patients and cardiovascular impact on survival and prognosis. Clin. Exp. Rheumatol. 26, S9–S15 (2008).

    CAS  PubMed  Google Scholar 

  64. 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).

    PubMed  Google Scholar 

  65. Park, S. J. et al. Incidence, prevalence, mortality and causes of death in Takayasu arteritis in Korea - a nationwide, population-based study. Int. J. Cardiol. 235, 100–104 (2017).

    PubMed  Google Scholar 

  66. Mirouse, A. et al. Overall survival and mortality risk factors in Takayasu’s arteritis: a multicenter study of 318 patients. J. Autoimmun. 96, 35–39 (2019).

    PubMed  Google Scholar 

  67. Goel, R. et al. Cardiovascular and renal morbidity in Takayasu arteritis: a population-based retrospective cohort study from the united kingdom. Arthritis Rheumatol. 73, 504–511 (2021).

    PubMed  Google Scholar 

  68. Jin, K. et al. NOTCH-induced rerouting of endosomal trafficking disables regulatory T cells in vasculitis. J. Clin. Invest. 131, e136042 (2021).

    CAS  PubMed Central  Google Scholar 

  69. Miyabe, C. et al. An expanded population of pathogenic regulatory T cells in giant cell arteritis is abrogated by IL-6 blockade therapy. Ann. Rheum. Dis. 76, 898–905 (2017).

    CAS  PubMed  Google Scholar 

  70. Samson, M. et al. Improvement of Treg immune response after treatment with tocilizumab in giant cell arteritis. Clin. Transl. Immunol. 10, e1332 (2021).

    Google Scholar 

  71. Weyand, C. M., Berry, G. J. & Goronzy, J. J. The immunoinhibitory PD-1/PD-L1 pathway in inflammatory blood vessel disease. J. Leukoc. Biol. 103, 565–575 (2018).

    CAS  PubMed  Google Scholar 

  72. Zhang, H. et al. Immunoinhibitory checkpoint deficiency in medium and large vessel vasculitis. Proc. Natl Acad. Sci. USA 114, E970–E979 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Daxini, A., Cronin, K. & Sreih, A. G. Vasculitis associated with immune checkpoint inhibitors-a systematic review. Clin. Rheumatol. 37, 2579–2584 (2018).

    PubMed  Google Scholar 

  74. Wen, Z. et al. The microvascular niche instructs T cells in large vessel vasculitis via the VEGF-Jagged1-Notch pathway. Sci. Transl. Med. 9, eaal3322 (2017).

    PubMed  PubMed Central  Google Scholar 

  75. Watanabe, R. et al. MMP (matrix metalloprotease)-9-producing monocytes enable T cells to invade the vessel wall and cause vasculitis. Circ. Res. 123, 700–715 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  76. Segarra, M. et al. Gelatinase expression and proteolytic activity in giant-cell arteritis. Ann. Rheum. Dis. 66, 1429–1435 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Segarra, M. et al. Dual function of focal adhesion kinase in regulating integrin-induced MMP-2 and MMP-9 release by human T lymphoid cells. FASEB J. 19, 1875–1877 (2005).

    PubMed  Google Scholar 

  78. Piggott, K. et al. Blocking the NOTCH pathway inhibits vascular inflammation in large-vessel vasculitis. Circulation 123, 309–318 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Wang, L. et al. ROS-producing immature neutrophils in giant cell arteritis are linked to vascular pathologies. JCI Insight 5, e139163 (2020).

    PubMed Central  Google Scholar 

  80. Cid, M. C. et al. Cell adhesion molecules in the development of inflammatory infiltrates in giant cell arteritis: inflammation-induced angiogenesis as the preferential site of leukocyte-endothelial cell interactions. Arthritis Rheum. 43, 184–194 (2000).

    CAS  PubMed  Google Scholar 

  81. Tombetti, E. & Mason, J. C. Takayasu arteritis: advanced understanding is leading to new horizons. Rheumatology 58, 206–219 (2019).

    CAS  PubMed  Google Scholar 

  82. Coit, P., De Lott, L. B., Nan, B., Elner, V. M. & Sawalha, A. H. DNA methylation analysis of the temporal artery microenvironment in giant cell arteritis. Ann. Rheum. Dis. 75, 1196–1202 (2016).

    CAS  PubMed  Google Scholar 

  83. Mohan, S. V., Liao, Y. J., Kim, J. W., Goronzy, J. J. & Weyand, C. M. Giant cell arteritis: immune and vascular aging as disease risk factors. Arthritis Res. Ther. 13, 231 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Watanabe, R., Berry, G. J., Liang, D. H., Goronzy, J. J. & Weyand, C. M. Pathogenesis of giant cell arteritis and Takayasu arteritis-similarities and differences. Curr. Rheumatol. Rep. 22, 68 (2020).

    PubMed  Google Scholar 

  85. Ma-Krupa, W. et al. Activation of arterial wall dendritic cells and breakdown of self-tolerance in giant cell arteritis. J. Exp. Med. 199, 173–183 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Maleszewski, J. J. et al. Clinical and pathological evolution of giant cell arteritis: a prospective study of follow-up temporal artery biopsies in 40 treated patients. Mod. Pathol. 30, 788–796 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  87. Weyand, C. M. & Goronzy, J. J. Medium- and large-vessel vasculitis. N. Engl. J. Med. 349, 160–169 (2003).

    CAS  PubMed  Google Scholar 

  88. Pryshchep, O., Ma-Krupa, W., Younge, B. R., Goronzy, J. J. & Weyand, C. M. Vessel-specific Toll-like receptor profiles in human medium and large arteries. Circulation 118, 1276–1284 (2008). This study, and others from the same group, used humanized mouse models of GCA to uncover important aspects of disease pathogenesis.

    CAS  PubMed  PubMed Central  Google Scholar 

  89. Kaiser, M., Younge, B., Björnsson, J., Goronzy, J. J. & Weyand, C. M. Formation of new vasa vasorum in vasculitis. Production of angiogenic cytokines by multinucleated giant cells. Am. J. Pathol. 155, 765–774 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  90. Terrier, B. et al. Interleukin-21 modulates Th1 and Th17 responses in giant cell arteritis. Arthritis Rheum. 64, 2001–2011 (2012).

    CAS  PubMed  Google Scholar 

  91. Watanabe, R. et al. GM-CSF is a pro-inflammatory cytokine in experimental vasculitis of medium and large arteries. Arthritis Rheumatol. https://doi.org/10.1038/s41577-020-0357-7 (2019).

    Article  Google Scholar 

  92. Corbera-Bellalta, M. et al. Blocking GM-CSF receptor α with mavrilimumab reduces infiltrating cells, pro-inflammatory markers, and neoangiogenesis in ex-vivo cultured arteries from patients with giant cell arteritis. Ann. Rheum. Dis. 57, 175–184 (2021).

    Google Scholar 

  93. Deng, J., Younge, B. R., Olshen, R. A., Goronzy, J. J. & Weyand, C. M. Th17 and Th1 T-cell responses in giant cell arteritis. Circulation 121, 906–915 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  94. Espígol-Frigolé, G. et al. Increased IL-17A expression in temporal artery lesions is a predictor of sustained response to glucocorticoid treatment in patients with giant-cell arteritis. Ann. Rheum. Dis. 72, 1481–1487 (2013).

    PubMed  Google Scholar 

  95. Saadoun, D. et al. Th1 and Th17 cytokines drive inflammation in Takayasu arteritis. Arthritis Rheumatol. 67, 1353–1360 (2015).

    CAS  PubMed  Google Scholar 

  96. Ciccia, F. et al. Difference in the expression of IL-9 and IL-17 correlates with different histological pattern of vascular wall injury in giant cell arteritis. Rheumatology 54, 1596–1604 (2015).

    CAS  PubMed  Google Scholar 

  97. Zerbini, A. et al. Increased expression of interleukin-22 in patients with giant cell arteritis. Rheumatology 57, 64–72 (2018).

    CAS  PubMed  Google Scholar 

  98. Corbera-Bellalta, M. et al. Blocking interferon γ reduces expression of chemokines CXCL9, CXCL10 and CXCL11 and decreases macrophage infiltration in ex vivo cultured arteries from patients with giant cell arteritis. Ann. Rheum. Dis. 75, 1177–1186 (2016).

    CAS  PubMed  Google Scholar 

  99. Régnier, P. et al. Targeting JAK/STAT pathway in Takayasu’s arteritis. Ann. Rheum. Dis. 79, 951–959 (2020).

    PubMed  Google Scholar 

  100. Zhang, H. et al. Inhibition of JAK-STAT signaling suppresses pathogenic immune responses in medium and large vessel vasculitis. Circulation 137, 1934–1948 (2018).

    CAS  PubMed  Google Scholar 

  101. Maciejewski-Duval, A. et al. mTOR pathway activation in large vessel vasculitis. J. Autoimmun. 94, 99–109 (2018).

    CAS  PubMed  Google Scholar 

  102. Hadjadj, J. et al. mTOR pathway is activated in endothelial cells from patients with Takayasu arteritis and is modulated by serum immunoglobulin G. Rheumatology 57, 1011–1020 (2018).

    CAS  PubMed  Google Scholar 

  103. Kurata, A. et al. Difference in immunohistochemical characteristics between Takayasu arteritis and giant cell arteritis: It may be better to distinguish them in the same age. Mod. Rheumatol. 29, 992–1001 (2019).

    CAS  PubMed  Google Scholar 

  104. Samson, M. et al. Involvement and prognosis value of CD8+ T cells in giant cell arteritis. J. Autoimmun. 72, 73–83 (2016).

    CAS  PubMed  Google Scholar 

  105. Kaiser, M., Weyand, C. M., Björnsson, J. & Goronzy, J. J. Platelet-derived growth factor, intimal hyperplasia, and ischemic complications in giant cell arteritis. Arthritis Rheum. 41, 623–633 (1998).

    CAS  PubMed  Google Scholar 

  106. Lozano, E., Segarra, M., García-Martínez, A., Hernández-Rodríguez, J. & Cid, M. C. Imatinib mesylate inhibits in vitro and ex vivo biological responses related to vascular occlusion in giant cell arteritis. Ann. Rheum. Dis. 67, 1581–1588 (2008).

    CAS  PubMed  Google Scholar 

  107. Planas-Rigol, E. et al. Endothelin-1 promotes vascular smooth muscle cell migration across the artery wall: a mechanism contributing to vascular remodelling and intimal hyperplasia in giant-cell arteritis. Ann. Rheum. Dis. 76, 1624–1634 (2017).

    PubMed  Google Scholar 

  108. Le Joncour, A. et al. Mast cells drive pathologic vascular lesions in Takayasu arteritis. J. Allergy Clin. Immunol. https://doi.org/10.1016/j.jaci.2021.05.003 (2021).

    Article  PubMed  Google Scholar 

  109. Hu, D. et al. Artery tertiary lymphoid organs control aorta immunity and protect against atherosclerosis via vascular smooth muscle cell lymphotoxin β receptors. Immunity 42, 1100–1115 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  110. Graver, J. C. et al. Massive B-cell infiltration and organization into artery tertiary lymphoid organs in the aorta of large vessel giant cell arteritis. Front. Immunol. 10, 83 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  111. Inder, S. J. et al. Immunophenotypic analysis of the aortic wall in Takayasu’s arteritis: involvement of lymphocytes, dendritic cells and granulocytes in immuno-inflammatory reactions. Cardiovasc. Surg. 8, 141–148 (2000).

    CAS  PubMed  Google Scholar 

  112. van der Geest, K. S. et al. Disturbed B cell homeostasis in newly diagnosed giant cell arteritis and polymyalgia rheumatica. Arthritis Rheumatol. 66, 1927–1938 (2014).

    PubMed  Google Scholar 

  113. Mutoh, T. et al. Identification of two major autoantigens negatively regulating endothelial activation in Takayasu arteritis. Nat. Commun. 11, 1253 (2020). This study implicates distinct anti-endothelial cell antibodies in the pathogenesis of TAK.

    CAS  PubMed  PubMed Central  Google Scholar 

  114. Desbois, A. C. et al. Specific follicular helper T cell signature in Takayasu arteritis. Arthritis Rheumatol. 73, 1233–1243 (2021).

    CAS  PubMed  Google Scholar 

  115. Mackie, S. L. et al. British Society for Rheumatology guideline on diagnosis and treatment of giant cell arteritis. Rheumatology 59, e1–e23 (2020).

    PubMed  Google Scholar 

  116. Diamantopoulos, A. P., Haugeberg, G., Lindland, A. & Myklebust, G. The fast-track ultrasound clinic for early diagnosis of giant cell arteritis significantly reduces permanent visual impairment: towards a more effective strategy to improve clinical outcome in giant cell arteritis? Rheumatology 55, 66–70 (2016).

    PubMed  Google Scholar 

  117. Parikh, M. et al. Prevalence of a normal C-reactive protein with an elevated erythrocyte sedimentation rate in biopsy-proven giant cell arteritis. Ophthalmology 113, 1842–1845 (2006).

    PubMed  Google Scholar 

  118. Furuta, S., Cousins, C., Chaudhry, A. & Jayne, D. Clinical features and radiological findings in large vessel vasculitis: are Takayasu arteritis and giant cell arteritis 2 different diseases or a single entity? J. Rheumatol. 42, 300–308 (2015).

    PubMed  Google Scholar 

  119. Luqmani, R. et al. The Role of Ultrasound Compared to Biopsy of Temporal Arteries in the Diagnosis and Treatment of Giant Cell Arteritis (TABUL): a diagnostic accuracy and cost-effectiveness study. Health Technol. Assess. 20, 1–238 (2016). This landmark study evaluated the diagnostic accuracy of ultrasonography and TAB in GCA.

    PubMed  PubMed Central  Google Scholar 

  120. Dejaco, C. et al. EULAR recommendations for the use of imaging in large vessel vasculitis in clinical practice. Ann. Rheum. Dis. 77, 636–643 (2018).

    PubMed  Google Scholar 

  121. Turesson, C., Borjesson, O., Larsson, K., Mohammad, A. J. & Knight, A. Swedish Society of Rheumatology 2018 guidelines for investigation, treatment, and follow-up of giant cell arteritis. Scand. J. Rheumatol. 48, 259–265 (2019).

    CAS  PubMed  Google Scholar 

  122. Maz, M. et al. 2021 American College of Rheumatology/Vasculitis Foundation guideline for the management of giant cell arteritis and Takayasu arteritis. Arthritis Rheumatol. 73, 1349–1365 (2021).

    PubMed  Google Scholar 

  123. Duftner, C. et al. Imaging in diagnosis, outcome prediction and monitoring of large vessel vasculitis: a systematic literature review and meta-analysis informing the EULAR recommendations. RMD Open 4, e000612 (2018).

    PubMed  PubMed Central  Google Scholar 

  124. Barra, L., Kanji, T., Malette, J. & Pagnoux, C. Imaging modalities for the diagnosis and disease activity assessment of Takayasu’s arteritis: a systematic review and meta-analysis. Autoimmun. Rev. 17, 175–187 (2018).

    PubMed  Google Scholar 

  125. Yamada, I. et al. Takayasu arteritis: diagnosis with breath-hold contrast-enhanced three-dimensional MR angiography. J. Magn. Reson. Imaging 11, 481–487 (2000).

    CAS  PubMed  Google Scholar 

  126. Lariviere, D. et al. Positron emission tomography and computed tomography angiography for the diagnosis of giant cell arteritis: A real-life prospective study. Medicine 95, e4146 (2016).

    PubMed  PubMed Central  Google Scholar 

  127. Stellingwerff, M. D. et al. Different scoring methods of FDG PET/CT in giant cell arteritis: need for standardization. Medicine 94, e1542 (2015).

    PubMed  PubMed Central  Google Scholar 

  128. Grayson, P. C. et al. (18)F-fluorodeoxyglucose-positron emission tomography as an imaging biomarker in a prospective, longitudinal cohort of patients with large vessel vasculitis. Arthritis Rheumatol. 70, 439–449 (2018). This study attempted to define the role of PET imaging in LVV disease monitoring and produced PETVAS.

    PubMed  PubMed Central  Google Scholar 

  129. Soussan, M. et al. Management of large-vessel vasculitis with FDG-PET: a systematic literature review and meta-analysis. Medicine 94, e622 (2015).

    PubMed  PubMed Central  Google Scholar 

  130. Sammel, A. M. et al. Diagnostic accuracy of positron emission tomography/computed tomography of the head, neck, and chest for giant cell arteritis: a prospective, double-blind, cross-sectional study. Arthritis Rheumatol. 71, 1319–1328 (2019).

    PubMed  Google Scholar 

  131. Nielsen, B. D. et al. Simple dichotomous assessment of cranial artery inflammation by conventional 18F-FDG PET/CT shows high accuracy for the diagnosis of giant cell arteritis: a case-control study. Eur. J. Nucl. Med. Mol. Imaging 46, 184–193 (2019).

    CAS  PubMed  Google Scholar 

  132. Dellavedova, L. et al. The prognostic value of baseline 18F-FDG PET/CT in steroid-naïve large-vessel vasculitis: introduction of volume-based parameters. Eur. J. Nucl. Med. Mol. Imaging 43, 340–348 (2016).

    CAS  PubMed  Google Scholar 

  133. Nielsen, B. D. et al. Three days of high-dose glucocorticoid treatment attenuates large-vessel 18F-FDG uptake in large-vessel giant cell arteritis but with a limited impact on diagnostic accuracy. Eur. J. Nucl. Med. Mol. Imaging 45, 1119–1128 (2018).

    CAS  PubMed  Google Scholar 

  134. Einspieler, I. et al. Imaging large vessel vasculitis with fully integrated PET/MRI: a pilot study. Eur. J. Nucl. Med. Mol. Imaging 42, 1012–1024 (2015).

    CAS  PubMed  Google Scholar 

  135. Martin, O. et al. PET/MRI Versus PET/CT for whole-body staging: results from a single-center observational study on 1,003 sequential examinations. J. Nucl. Med. 61, 1131–1136 (2020).

    CAS  PubMed  Google Scholar 

  136. Wei, W. et al. ImmunoPET: concept, design, and applications. Chem. Rev. 120, 3787–3851 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  137. Pugliese, F. et al. Imaging of vascular inflammation with [11C]-PK11195 and positron emission tomography/computed tomography angiography. J. Am. Coll. Cardiol. 56, 653–661 (2010).

    PubMed  Google Scholar 

  138. Kermani, T. A. et al. Disease relapses among patients with giant cell arteritis: a prospective, longitudinal cohort study. J. Rheumatol. 42, 1213–1217 (2015).

    PubMed  PubMed Central  Google Scholar 

  139. Alba, M. A. et al. Relapses in patients with giant cell arteritis: prevalence, characteristics, and associated clinical findings in a longitudinally followed cohort of 106 patients. Medicine 93, 194–201 (2014).

    PubMed  PubMed Central  Google Scholar 

  140. Labarca, C. et al. Predictors of relapse and treatment outcomes in biopsy-proven giant cell arteritis: a retrospective cohort study. Rheumatology 55, 347–356 (2016).

    PubMed  Google Scholar 

  141. Comarmond, C. et al. Long-term outcomes and prognostic factors of complications in Takayasu arteritis: a multicenter study of 318 patients. Circulation 136, 1114–1122 (2017).

    PubMed  Google Scholar 

  142. Weyand, C. M., Fulbright, J. W., Hunder, G. G., Evans, J. M. & Goronzy, J. J. Treatment of giant cell arteritis: interleukin-6 as a biologic marker of disease activity. Arthritis Rheum. 43, 1041–1048 (2000).

    CAS  PubMed  Google Scholar 

  143. Rimland, C. A. et al. Outcome measures in large-vessel vasculitis: relationship between patient, physician, imaging, and laboratory-based assessments. Arthritis Care Res. 72, 1296–1304 (2019).

    Google Scholar 

  144. Matsuyama, A. et al. Matrix metalloproteinases as novel disease markers in Takayasu arteritis. Circulation 108, 1469–1473 (2003).

    CAS  PubMed  Google Scholar 

  145. Dagna, L. et al. Pentraxin-3 as a marker of disease activity in Takayasu arteritis. Ann. Intern. Med. 155, 425–433 (2011).

    PubMed  Google Scholar 

  146. Baldini, M. et al. Selective up-regulation of the soluble pattern-recognition receptor pentraxin 3 and of vascular endothelial growth factor in giant cell arteritis: relevance for recent optic nerve ischemia. Arthritis Rheum. 64, 854–865 (2012).

    CAS  PubMed  Google Scholar 

  147. Tombetti, E., Hysa, E., Mason, J. C., Cimmino, M. A. & Camellino, D. Blood biomarkers for monitoring and prognosis of large vessel vasculitides. Curr. Rheumatol. Rep. 23, 17 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  148. Soriano, A. et al. Visual loss and other cranial ischaemic complications in giant cell arteritis. Nat. Rev. Rheumatol. 13, 476–484 (2017).

    PubMed  Google Scholar 

  149. Macchioni, P. et al. Survival predictors in biopsy-proven giant cell arteritis: a northern Italian population-based study. Rheumatology 58, 609–616 (2019).

    CAS  PubMed  Google Scholar 

  150. Delaval, L. et al. Large-vessel vasculitis diagnosed between 50 and 60years: case-control study based on 183 cases and 183 controls aged over 60years. Autoimmun. Rev. 18, 714–720 (2019).

    PubMed  Google Scholar 

  151. Robson, J. C. et al. The relative risk of aortic aneurysm in patients with giant cell arteritis compared with the general population of the UK. Ann. Rheum. Dis. 74, 129–135 (2015).

    PubMed  Google Scholar 

  152. Proven, A., Gabriel, S. E., Orces, C., O’Fallon, W. M. & Hunder, G. G. Glucocorticoid therapy in giant cell arteritis: duration and adverse outcomes. Arthritis Rheum. 49, 703–708 (2003).

    CAS  PubMed  Google Scholar 

  153. Maksimowicz-McKinnon, K., Clark, T. M. & Hoffman, G. S. Limitations of therapy and a guarded prognosis in an American cohort of Takayasu arteritis patients. Arthritis Rheum. 56, 1000–1009 (2007).

    PubMed  Google Scholar 

  154. Chanouzas, D. et al. Intravenous pulse methylprednisolone for induction of remission in severe ANCA associated Vasculitis: a multi-center retrospective cohort study. BMC Nephrol. 20, 58 (2019).

    PubMed  PubMed Central  Google Scholar 

  155. Christ, L. et al. Tocilizumab monotherapy after ultra-short glucocorticoid administration in giant cell arteritis: a proof-of-concept trial. Lancet Rheumatol. https://doi.org/10.1016/S2665-9913(21)00152-1 (2021).

    Article  Google Scholar 

  156. Wilson, J. C. et al. Serious adverse effects associated with glucocorticoid therapy in patients with giant cell arteritis (GCA): a nested case-control analysis. Semin. Arthritis Rheum. 46, 819–827 (2017).

    CAS  PubMed  Google Scholar 

  157. Águeda, A. F. et al. Management of Takayasu arteritis: a systematic literature review informing the 2018 update of the EULAR recommendation for the management of large vessel vasculitis. RMD Open 5, e001020 (2019).

    PubMed  PubMed Central  Google Scholar 

  158. Mainbourg, S. et al. Prevalence of giant cell arteritis relapse in patients treated with glucocorticoids: a meta-analysis. Arthritis Care Res. 72, 838–849 (2020).

    CAS  Google Scholar 

  159. Mukhtyar, C. et al. Development of an evidence-based regimen of prednisolone to treat giant cell arteritis - the Norwich regimen. Rheumatol. Adv. Pract. 3, rkz001 (2019).

    PubMed  PubMed Central  Google Scholar 

  160. Hoffman, G. S. et al. Infliximab for maintenance of glucocorticosteroid-induced remission of giant cell arteritis: a randomized trial. Ann. Intern. Med. 146, 621–630 (2007).

    PubMed  Google Scholar 

  161. Stone, J. H. et al. Trial of tocilizumab in giant-cell arteritis. N. Engl. J. Med. 377, 317–328 (2017). The GiACTA study evaluated the role of tocilizumab in GCA.

    CAS  PubMed  Google Scholar 

  162. Nakaoka, Y. et al. Efficacy and safety of tocilizumab in patients with refractory Takayasu arteritis: results from a randomised, double-blind, placebo-controlled, phase 3 trial in Japan (the TAKT study). Ann. Rheum. Dis. 77, 348–354 (2018).

    CAS  PubMed  Google Scholar 

  163. Langford, C. A. et al. A randomized, double-blind trial of abatacept (CTLA-4Ig) for the treatment of Takayasu arteritis. Arthritis Rheumatol. 69, 846–853 (2017). Although the results did not demonstrate efficacy, this was the first randomized controlled trial conducted in TAK, demonstrating feasibility.

    CAS  PubMed  PubMed Central  Google Scholar 

  164. Strehl, C. et al. Defining conditions where long-term glucocorticoid treatment has an acceptably low level of harm to facilitate implementation of existing recommendations: viewpoints from an EULAR task force. Ann. Rheum. Dis. 75, 952–957 (2016).

    CAS  PubMed  Google Scholar 

  165. Barra, L. et al. Variations in the clinical practice of physicians managing Takayasu arteritis: a nationwide survey. Open Access. Rheumatol. 9, 91–99 (2017).

    PubMed  PubMed Central  Google Scholar 

  166. Jover, J. A. et al. Combined treatment of giant-cell arteritis with methotrexate and prednisone. a randomized, double-blind, placebo-controlled trial. Ann. Intern. Med. 134, 106–114 (2001).

    CAS  PubMed  Google Scholar 

  167. Hoffman, G. S. et al. A multicenter, randomized, double-blind, placebo-controlled trial of adjuvant methotrexate treatment for giant cell arteritis. Arthritis Rheum. 46, 1309–1318 (2002).

    CAS  PubMed  Google Scholar 

  168. Spiera, R. F. et al. A prospective, double-blind, randomized, placebo controlled trial of methotrexate in the treatment of giant cell arteritis (GCA). Clin. Exp. Rheumatol. 19, 495–501 (2001).

    CAS  PubMed  Google Scholar 

  169. Mahr, A. D. et al. Adjunctive methotrexate for treatment of giant cell arteritis: an individual patient data meta-analysis. Arthritis Rheum. 56, 2789–2797 (2007).

    CAS  PubMed  Google Scholar 

  170. Gérard, A. L. et al. Efficacy and safety of steroid-sparing treatments in giant cell arteritis according to the glucocorticoids tapering regimen: a systematic review and meta-analysis. Eur. J. Intern. Med. 88, 96–103 (2021).

    PubMed  Google Scholar 

  171. Koster, M. J. et al. Efficacy of methotrexate in real-world management of giant cell arteritis: a case-control study. J. Rheumatol. 46, 501–508 (2019).

    CAS  PubMed  Google Scholar 

  172. Diamantopoulos, A. P., Hetland, H. & Myklebust, G. Leflunomide as a corticosteroid-sparing agent in giant cell arteritis and polymyalgia rheumatica: a case series. Biomed. Res. Int. 2013, 120638 (2013).

    PubMed  PubMed Central  Google Scholar 

  173. Karabayas, M. et al. Evaluation of adjunctive mycophenolate for large vessel giant cell arteritis. Rheumatol. Adv. Pract. 4, rkaa069 (2020).

    PubMed  PubMed Central  Google Scholar 

  174. Ly, K. H. et al. Steroid-sparing effect and toxicity of dapsone treatment in giant cell arteritis: a single-center, retrospective study of 70 patients. Medicine 95, e4974 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  175. Monti, S. et al. Systematic literature review informing the 2018 update of the EULAR recommendation for the management of large vessel vasculitis: focus on giant cell arteritis. RMD Open 5, e001003 (2019).

    PubMed  PubMed Central  Google Scholar 

  176. de Boysson, H. et al. Is there a place for cyclophosphamide in the treatment of giant-cell arteritis? A case series and systematic review. Semin. Arthritis Rheum. 43, 105–112 (2013).

    PubMed  Google Scholar 

  177. Misra, D. P., Wakhlu, A., Agarwal, V. & Danda, D. Recent advances in the management of Takayasu arteritis. Int. J. Rheum. Dis. 22, 60–68 (2019).

    CAS  PubMed  Google Scholar 

  178. Villiger, P. M. et al. Tocilizumab for induction and maintenance of remission in giant cell arteritis: a phase 2, randomised, double-blind, placebo-controlled trial. Lancet 387, 1921–1927 (2016).

    CAS  PubMed  Google Scholar 

  179. Strand, V. et al. Health-related quality of life in patients with giant cell arteritis treated with tocilizumab in a phase 3 randomised controlled trial. Arthritis Res. Ther. 21, 64 (2019).

    PubMed  PubMed Central  Google Scholar 

  180. Calderón-Goercke, M. et al. Tocilizumab in giant cell arteritis. Observational, open-label multicenter study of 134 patients in clinical practice. Semin. Arthritis Rheum. 49, 126–135 (2019).

    PubMed  Google Scholar 

  181. Unizony, S. et al. Clinical outcomes of patients with giant cell arteritis treated with tocilizumab in real-world clinical practice: decreased incidence of new visual manifestations. Arthritis Res. Ther. 23, 8 (2021).

    CAS  PubMed  PubMed Central  Google Scholar 

  182. Calderón-Goercke, M. et al. Tocilizumab in giant cell arteritis: differences between the GiACTA trial and a multicentre series of patients from the clinical practice. Clin. Exp. Rheumatol. 38, 112–119 (2020).

    PubMed  Google Scholar 

  183. Clément, J. et al. Real-world risk of relapse of giant cell arteritis treated with tocilizumab: a retrospective analysis of 43 patients. J. Rheumatol. 48, 1435–1441 (2021).

    PubMed  Google Scholar 

  184. Stone, J. H. et al. Long-term effect of tocilizumab in patients with giant cell arteritis: open-label extension phase of the Giant Cell Arteritis Actemra (GiACTA) trial. Lancet Rheumatol. 3, E328–E336 (2021).

    Google Scholar 

  185. Stone, J. H. et al. Glucocorticoid dosages and acute-phase reactant levels at giant cell arteritis flare in a randomized trial of tocilizumab. Arthritis Rheumatol. 71, 1329–1338 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  186. Unizony, S. et al. Tocilizumab for the treatment of large-vessel vasculitis (giant cell arteritis, Takayasu arteritis) and polymyalgia rheumatica. Arthritis Care Res. 64, 1720–1729 (2012).

    CAS  Google Scholar 

  187. Xenitidis, T., Horger, M., Zeh, G., Kanz, L. & Henes, J. C. Sustained inflammation of the aortic wall despite tocilizumab treatment in two cases of Takayasu arteritis. Rheumatology 52, 1729–1731 (2013).

    CAS  PubMed  Google Scholar 

  188. Reichenbach, S. et al. Magnetic resonance angiography in giant cell arteritis: results of a randomized controlled trial of tocilizumab in giant cell arteritis. Rheumatology 57, 982–986 (2018).

    CAS  PubMed  Google Scholar 

  189. Schönau, V. et al. Resolution of vascular inflammation in patients with new-onset giant cell arteritis: data from the RIGA study. Rheumatology 60, 3851–3861 (2021).

    PubMed  Google Scholar 

  190. Sebastian, A. et al. Efficacy and safety of tocilizumab in giant cell arteritis: a single centre NHS experience using imaging (ultrasound and PET-CT) as a diagnostic and monitoring tool. RMD Open 6, e001417 (2020).

    PubMed  PubMed Central  Google Scholar 

  191. Cid, M. C. et al. Mavrilimumab (anti GM-CSF receptor α monoclonal antibody) reduces risk of flare and increases sustained remission in a phase 2 trial of patients with giant cell arteritis. Ann. Rheum. Dis. 80, 31 (2021).

    Google Scholar 

  192. Langford, C. A. et al. A randomized, double-blind trial of abatacept (CTLA-4Ig) for the treatment of giant cell arteritis. Arthritis Rheumatol. 69, 837–845 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  193. US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT04474847 (2021).

  194. Hernández-Rodríguez, J. et al. Tissue production of pro-inflammatory cytokines (IL-1beta, TNFalpha and IL-6) correlates with the intensity of the systemic inflammatory response and with corticosteroid requirements in giant-cell arteritis. Rheumatology 43, 294–301 (2004).

    PubMed  Google Scholar 

  195. García-Martínez, A. et al. Clinical relevance of persistently elevated circulating cytokines (tumor necrosis factor alpha and interleukin-6) in the long-term followup of patients with giant cell arteritis. Arthritis Care Res. 62, 835–841 (2010).

    Google Scholar 

  196. Martínez-Taboada, V. M. et al. A double-blind placebo controlled trial of etanercept in patients with giant cell arteritis and corticosteroid side effects. Ann. Rheum. Dis. 67, 625–630 (2008).

    PubMed  Google Scholar 

  197. Seror, R. et al. Adalimumab for steroid sparing in patients with giant-cell arteritis: results of a multicentre randomised controlled trial. Ann. Rheum. Dis. 73, 2074–2081 (2014).

    CAS  PubMed  Google Scholar 

  198. Brack, A. et al. Giant cell vasculitis is a T cell-dependent disease. Mol. Med. 3, 530–543 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  199. US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT03725202 (2021).

  200. Nakaoka, Y. et al. Long-term efficacy and safety of tocilizumab in refractory Takayasu arteritis: final results of the randomized controlled phase 3 TAKT study. Rheumatol 59, 2427–2434 (2020).

    CAS  Google Scholar 

  201. Mekinian, A. et al. Efficacy of biological-targeted treatments in Takayasu arteritis: multicenter, retrospective study of 49 patients. Circulation 132, 1693–1700 (2015).

    CAS  PubMed  Google Scholar 

  202. Misra, D. P., Rathore, U., Patro, P., Agarwal, V. & Sharma, A. Disease-modifying anti-rheumatic drugs for the management of Takayasu arteritis-a systematic review and meta-analysis. Clin. Rheumatol. 40, 4391–4416 (2021).

    PubMed  Google Scholar 

  203. Youngstein, T. et al. Serial analysis of clinical and imaging indices reveals prolonged efficacy of TNF-α and IL-6 receptor targeted therapies in refractory Takayasu arteritis. Clin. Exp. Rheumatol. 32, S11–S18 (2014).

    PubMed  Google Scholar 

  204. Gudbrandsson, B., Molberg, Ø. & Palm, Ø. TNF inhibitors appear to inhibit disease progression and improve outcome in Takayasu arteritis; an observational, population-based time trend study. Arthritis Res. Ther. 19, 99 (2017).

    PubMed  PubMed Central  Google Scholar 

  205. Mekinian, A. et al. Efficacy and safety of TNF-α antagonists and tocilizumab in Takayasu arteritis: multicenter retrospective study of 209 patients. Rheumatology https://doi.org/10.1093/rheumatology/keab635 (2021).

    Article  PubMed  Google Scholar 

  206. Terao, C. et al. Ustekinumab as a therapeutic option for Takayasu arteritis: from genetic findings to clinical application. Scand. J. Rheumatol. 45, 80–82 (2016).

    CAS  PubMed  Google Scholar 

  207. Yachoui, R., Kreidy, M., Siorek, M. & Sehgal, R. Successful treatment with ustekinumab for corticosteroid- and immunosuppressant-resistant Takayasu’s arteritis. Scand. J. Rheumatol. 47, 246–247 (2018).

    CAS  PubMed  Google Scholar 

  208. Pazzola, G. et al. Rituximab therapy for Takayasu arteritis: a seven patients experience and a review of the literature. Rheumatology 57, 1151–1155 (2018).

    CAS  PubMed  Google Scholar 

  209. Kuwabara, S., Tanimura, S., Matsumoto, S., Nakamura, H. & Horita, T. Successful remission with tofacitinib in a patient with refractory Takayasu arteritis complicated by ulcerative colitis. Ann. Rheum. Dis. 79, 1125–1126 (2020).

    PubMed  Google Scholar 

  210. Saadoun, D. et al. Retrospective analysis of surgery versus endovascular intervention in Takayasu arteritis: a multicenter experience. Circulation 125, 813–819 (2012).

    CAS  PubMed  Google Scholar 

  211. Park, H. S. et al. Long term results of endovascular treatment in renal arterial stenosis from Takayasu arteritis: angioplasty versus stent placement. Eur. J. Radiol. 82, 1913–1918 (2013).

    PubMed  Google Scholar 

  212. Jeong, H. S., Jung, J. H., Song, G. G., Choi, S. J. & Hong, S. J. Endovascular balloon angioplasty versus stenting in patients with Takayasu arteritis: a meta-analysis. Medicine 96, e7558 (2017).

    PubMed  PubMed Central  Google Scholar 

  213. US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT04366596 (2021).

  214. Perera, A. H. et al. Optimizing the outcome of vascular intervention for Takayasu arteritis. Br. J. Surg. 101, 43–50 (2014).

    CAS  PubMed  Google Scholar 

  215. Assie, C., Janvresse, A., Plissonnier, D., Levesque, H. & Marie, I. Long-term follow-up of upper and lower extremity vasculitis related to giant cell arteritis: a series of 36 patients. Medicine 90, 40–51 (2011).

    PubMed  Google Scholar 

  216. Le Hello, C. et al. Symptomatic lower-limb giant-cell arteritis: Characteristics, management and long-term outcome. J. Med. Vasc. 42, 148–156 (2017).

    PubMed  Google Scholar 

  217. Alba, M. A. et al. Central nervous system vasculitis: still more questions than answers. Curr. Neuropharmacol. 9, 437–448 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  218. Guerrero, A. M. et al. Intracranial internal carotid artery angioplasthy and stenting in giant cell arteritis. J. Neuroimaging 25, 307–309 (2015).

    PubMed  Google Scholar 

  219. Tomasson, G. et al. Risk for cardiovascular disease early and late after a diagnosis of giant-cell arteritis: a cohort study. Ann. Intern. Med. 160, 73–80 (2014).

    PubMed  PubMed Central  Google Scholar 

  220. Ray, J. G., Mamdani, M. M. & Geerts, W. H. Giant cell arteritis and cardiovascular disease in older adults. Heart 91, 324–328 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  221. Amiri, N., De Vera, M., Choi, H. K., Sayre, E. C. & Avina-Zubieta, J. A. Increased risk of cardiovascular disease in giant cell arteritis: a general population-based study. Rheumatol 55, 33–40 (2016).

    CAS  Google Scholar 

  222. Pujades-Rodriguez, M. et al. Associations between polymyalgia rheumatica and giant cell arteritis and 12 cardiovascular diseases. Heart 102, 383–389 (2016).

    CAS  PubMed  Google Scholar 

  223. Pujades-Rodriguez, M., Morgan, A. W., Cubbon, R. M. & Wu, J. Dose-dependent oral glucocorticoid cardiovascular risks in people with immune-mediated inflammatory diseases: a population-based cohort study. PLoS Med. 17, e1003432 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  224. Ben-Shlomo, Y. et al. Aortic pulse wave velocity improves cardiovascular event prediction: an individual participant meta-analysis of prospective observational data from 17,635 subjects. J. Am. Coll. Cardiol. 63, 636–646 (2014).

    PubMed  Google Scholar 

  225. Ng, W. F. et al. Takayasu’s arteritis: a cause of prolonged arterial stiffness. Rheumatology 45, 741–745 (2006).

    CAS  PubMed  Google Scholar 

  226. Seyahi, E. et al. Atherosclerosis in Takayasu arteritis. Ann. Rheum. Dis. 65, 1202–1207 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  227. Narváez, J. et al. Impact of antiplatelet therapy in the development of severe ischemic complications and in the outcome of patients with giant cell arteritis. Clin. Exp. Rheumatol. 26, S57–S62 (2008).

    PubMed  Google Scholar 

  228. de Souza, A. W. et al. Antiplatelet therapy for the prevention of arterial ischemic events in Takayasu arteritis. Circ. J. 74, 1236–1241 (2010).

    PubMed  Google Scholar 

  229. Abularrage, C. J. et al. Quality of life of patients with Takayasu’s arteritis. J. Vasc. Surg. 47, 131–136 (2008). discussion 136-7.

    PubMed  Google Scholar 

  230. Akar, S. et al. Quality of life in patients with Takayasu’s arteritis is impaired and comparable with rheumatoid arthritis and ankylosing spondylitis patients. Clin. Rheumatol. 27, 859–865 (2008).

    PubMed  Google Scholar 

  231. Rimland, C. A. et al. Outcome measures in large vessel vasculitis: relationship between patient-, physician-, imaging-, and laboratory-based assessments. Arthritis Care Res. 72, 1296–1304 (2020).

    Google Scholar 

  232. Hellmann, D. B. et al. Domains of health-related quality of life important to patients with giant cell arteritis. Arthritis Rheuma. 49, 819–825 (2003).

    Google Scholar 

  233. Sreih, A. G. et al. Health-related outcomes of importance to patients with Takayasu’s arteritis. Clin. Exp. Rheumatol. 36, 51–57 (2018).

    PubMed  Google Scholar 

  234. Aydin, S. Z., Direskeneli, H. & Merkel, P. A. Assessment of disease activity in large-vessel vasculitis: results of an international Delphi exercise. J. Rheumatol. 44, 1928–1932 (2017).

    PubMed  PubMed Central  Google Scholar 

  235. Aitken, M. & Basu, N. Improving quality of life in vasculitis patients. Rheumatology 59, iii132–iii135 (2020).

    CAS  PubMed  Google Scholar 

  236. Barra, L. et al. Impact of vasculitis on employment and income. Clin. Exp. Rheumatol. 36, 58–64 (2018).

    PubMed  PubMed Central  Google Scholar 

  237. Koster, M. J., Warrington, K. J. & Matteson, E. L. Morbidity and mortality of large-vessel vasculitides. Curr. Rheumatol. Rep. 22, 86 (2020).

    PubMed  Google Scholar 

  238. Wen, Z. et al. NADPH oxidase deficiency underlies dysfunction of aged CD8+ Tregs. J. Clin. Invest. 126, 1953–1967 (2016).

    PubMed  PubMed Central  Google Scholar 

  239. Nadkarni, S. et al. Investigational analysis reveals a potential role for neutrophils in giant-cell arteritis disease progression. Circ. Res. 114, 242–248 (2014).

    CAS  PubMed  Google Scholar 

  240. Kong, X. & Sawalha, A. H. Takayasu arteritis risk locus in IL6 represses the anti-inflammatory gene GPNMB through chromatin looping and recruiting MEF2-HDAC complex. Ann. Rheum. Dis. 78, 1388–1397 (2019).

    CAS  PubMed  Google Scholar 

  241. Keser, G., Aksu, K. & Direskeneli, H. Discrepancies between vascular and systemic inflammation in large vessel vasculitis: an important problem revisited. Rheumatology 57, 784–790 (2018).

    CAS  PubMed  Google Scholar 

  242. Guleria, A. et al. NMR-based serum metabolomics discriminates Takayasu arteritis from healthy individuals: a proof-of-principle study. J. Proteome Res. 14, 3372–3381 (2015).

    CAS  PubMed  Google Scholar 

  243. Cui, X. et al. Novel biomarkers for the precisive diagnosis and activity classification of Takayasu arteritis. Circ. Genom. Precis. Med. 12, e002080 (2019).

    CAS  PubMed  Google Scholar 

  244. Bolha, L. et al. Identification of microRNAs and their target gene networks implicated in arterial wall remodelling in giant cell arteritis. Rheumatology 59, 3540–3552 (2020).

    CAS  PubMed  Google Scholar 

  245. Grayson, P. C. et al. 18F-fluorodeoxyglucose-positron emission tomography as an imaging biomarker in a prospective, longitudinal cohort of patients with large vessel vasculitis. Arthritis Rheumatol. 70, 439–449 (2018).

    PubMed  PubMed Central  Google Scholar 

  246. Youngstein, T. et al. FDG uptake by prosthetic arterial grafts in large vessel vasculitis is not specific for active disease. JACC 10, 1042–1052 (2017).

    PubMed  Google Scholar 

  247. Ćorović, A., Wall, C., Mason, J. C., Rudd, J. H. F. & Tarkin, J. M. Novel positron emission tomography tracers for imaging vascular inflammation. Curr. Cardiol. Rep. 22, 119 (2020).

    PubMed  PubMed Central  Google Scholar 

  248. Lamare, F. et al. Detection and quantification of large-vessel inflammation with 11C-(R)-PK11195 PET/CT. J. Nucl. Med. 52, 33–39 (2011).

    PubMed  Google Scholar 

  249. Pugliese, F. et al. Imaging of vascular inflammation with [11C]-PK11195 and PET/CT angiography. J. Am. Coll. Cardiol. 56, 33–39 (2010).

    Google Scholar 

  250. Tarkin, J. M. et al. Novel approach to imaging active Takayasu arteritis using somatostatin receptor positron emission tomography/magnetic resonance imaging. Circ. Cardiovasc. Imaging 13, e010389 (2020).

    PubMed  PubMed Central  Google Scholar 

  251. US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT04071691 (2021).

  252. Tombetti, E. et al. Novel angiographic scores for evaluation of large vessel vasculitis. Sci. Rep. 8, 15979 (2018).

    PubMed  PubMed Central  Google Scholar 

  253. Nakagomi, D. et al. Development of a score for assessment of radiologic damage in large-vessel vasculitis (Combined Arteritis Damage Score, CARDS). Clin. Exp. Rheumatol. 35, 139–145 (2017).

    PubMed  Google Scholar 

  254. Goel, R. et al. Derivation of an angiographically based classification system in Takayasu’s arteritis: an observational study from India and North America. Rheumatology 59, 1118–1127 (2020).

    CAS  PubMed  Google Scholar 

  255. Gribbons, K. B. et al. Patterns of arterial disease in Takayasu’s arteritis and giant cell arteritis. Arthritis Care Res. 72, 1615–1624 (2020).

    Google Scholar 

  256. Tarzi, R. M., Mason, J. C. & Pusey, C. D. Issues in trial design for ANCA-associated and large-vessel vasculitis. Nat. Rev. 10, 502–510 (2014).

    CAS  Google Scholar 

  257. Sreih, A. G. et al. Development of a core set of outcome measures for large-vessel vasculitis: report from OMERACT 2016. J. Rheumatol. 44, 1933–1937 (2017). The OMERACT group are attempting to define outcome measures for use in LVV clinical studies.

    PubMed  PubMed Central  Google Scholar 

  258. Luqmani, R. A. et al. Birmingham Vasculitis Activity Score (BVAS) in systemic necrotizing vasculitis. QJM 87, 671–678 (1994).

    CAS  PubMed  Google Scholar 

  259. Kerr, G. S. et al. Takayasu arteritis. Ann. Intern. Med. 120, 919–929 (1994).

    CAS  PubMed  Google Scholar 

  260. Aydin, S. Z. et al. Assessment of disease activity and progression in Takayasu’s arteritis with Disease Extent Index-Takayasu. Rheumatology 49, 1889–1893 (2010).

    PubMed  Google Scholar 

  261. Misra, R. et al. Development and initial validation of the Indian Takayasu Clinical Activity Score (ITAS2010). Rheumatology 52, 1795–1801 (2013).

    PubMed  Google Scholar 

  262. Gribbons, K. B. et al. Diagnostic assessment strategies and disease subsets in giant cell arteritis: data from an international observational cohort. Arthritis Rheumatol. 72, 667–676 (2020).

    PubMed  PubMed Central  Google Scholar 

  263. Grayson, P. C. et al. Distribution of arterial lesions in Takayasu’s arteritis and giant cell arteritis. Ann. Rheum. Dis. 71, 1329–1334 (2012).

    PubMed  Google Scholar 

  264. Mader, T. H., Werner, R. P., Chamberlain, D. G. & Doornbos, D. Giant cell arteritis in Alaska Natives. Can. J. Ophthalmol. 44, 53–56 (2009).

    PubMed  Google Scholar 

  265. Smith, C. A., Fidler, W. J. & Pinals, R. S. The epidemiology of giant cell arteritis. Report of a ten-year study in Shelby County, Tennessee. Arthritis Rheum. 26, 1214–1219 (1983).

    CAS  PubMed  Google Scholar 

  266. Hall, S. et al. Takayasu arteritis. A study of 32 North American patients. Medicine 64, 89–99 (1985).

    CAS  PubMed  Google Scholar 

  267. Ing, E. B. et al. The incidence of giant cell arteritis in Ontario, Canada. Can. J. Ophthalmol. 54, 119–124 (2019).

    PubMed  Google Scholar 

  268. Martinez, P. & et al. Incidence and prevalence of polymyalgia rheumatic and giant cell arteritis: a 15-year study in a health care management organization [abstract]. Arthritis Rheumatol. 68 (Suppl. 10), 1190 (2016).

    Google Scholar 

  269. Brekke, L. K. et al. Incidence of giant cell arteritis in Western Norway 1972-2012: a retrospective cohort study. Arthritis Res. Ther. 19, 278 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  270. Tomasson, G., Bjornsson, J., Zhang, Y., Gudnason, V. & Merkel, P. A. Cardiovascular risk factors and incident giant cell arteritis: a population-based cohort study. Scand. J. Rheumatol. 48, 213–217 (2019).

    CAS  PubMed  Google Scholar 

  271. Dreyer, L., Faurschou, M. & Baslund, B. A population-based study of Takayasu´s arteritis in eastern Denmark. Clin. Exp. Rheumatol. 29, S40–S42 (2011).

    PubMed  Google Scholar 

  272. Catanoso, M. et al. Incidence, prevalence, and survival of biopsy-proven giant cell arteritis in northern Italy during a 26-year period. Arthritis Care Res. 69, 430–438 (2017).

    Google Scholar 

  273. Pucelj, N. P. et al. The incidence of giant cell arteritis in Slovenia. Clin. Rheumatol. 38, 285–290 (2019).

    PubMed  Google Scholar 

  274. Romero-Gómez, C. et al. Epidemiological study of primary systemic vasculitides among adults in southern Spain and review of the main epidemiological studies. Clin. Exp. Rheumatol. 33 (Suppl. 89), S-11-8 (2015).

    PubMed  Google Scholar 

  275. Saritas, F., Donmez, S., Direskeneli, H. & Pamuk, O. N. The epidemiology of Takayasu arteritis: a hospital-based study from northwestern part of Turkey. Rheumatol. Int. 36, 911–916 (2016).

    PubMed  Google Scholar 

  276. Friedman, G., Friedman, B. & Benbassat, J. Epidemiology of temporal arteritis in Israel. Isr. J. Med. Sci. 18, 241–244 (1982).

    CAS  PubMed  Google Scholar 

  277. Bas-Lando, M. et al. The incidence of giant cell arteritis in Jerusalem over a 25-year period: annual and seasonal fluctuations. Clin. Exp. Rheumatol. 25, S15–S17 (2007).

    CAS  PubMed  Google Scholar 

  278. Nesher, G., Ben-Chetrit, E., Mazal, B. & Breuer, G. S. The incidence of primary systemic vasculitis in Jerusalem: a 20-year hospital-based retrospective study. J. Rheumatol. 43, 1072–1077 (2016).

    PubMed  Google Scholar 

  279. el-Reshaid, K., Varro, J., al-Duwairi, Q. & Anim, J. T. Takayasu’s arteritis in Kuwait. J. Trop. Med. Hyg. 98, 299–305 (1995).

    CAS  PubMed  Google Scholar 

  280. Dunstan, E. et al. Epidemiology of biopsy-proven giant cell arteritis in South Australia. Intern. Med. J. 44, 32–39 (2014).

    CAS  PubMed  Google Scholar 

  281. Makin, K., Isbel, M. & Nossent, J. Frequency, presentation, and outcome of Takayasu arteritis in Western Australia. Mod. Rheumatol. 27, 1019–1023 (2017).

    PubMed  Google Scholar 

  282. Abdul-Rahman, A. M., Molteno, A. C. & Bevin, T. H. The epidemiology of giant cell arteritis in Otago, New Zealand: a 9-year analysis. N. Z. Med. J. 124, 44–52 (2011).

    PubMed  Google Scholar 

  283. Li, L., Neogi, T. & Jick, S. Mortality in patients with giant cell arteritis: a cohort study in UK primary care. Arthritis Care Res. 70, 1251–1256 (2018).

    Google Scholar 

  284. Ben-Shabat, N. et al. Mortality among patients with giant cell arteritis: a large-scale population-based cohort study. J. Rheumatol. 47, 1385–1391 (2020).

    PubMed  Google Scholar 

  285. Kermani, T. A. et al. Large-vessel involvement in giant cell arteritis: a population-based cohort study of the incidence-trends and prognosis. Ann. Rheum. Dis. 72, 1989–1994 (2013).

    PubMed  Google Scholar 

  286. Michailidou, D. et al. Clinical symptoms and associated vascular imaging findings in Takayasu’s arteritis compared to giant cell arteritis. Ann. Rheum. Dis. 79, 262–267 (2020).

    CAS  PubMed  Google Scholar 

  287. Uy, C. P. et al. The impact of integrated noninvasive imaging in the management of Takayasu arteritis. JACC Cardiovasc. Imaging 14, 495–500 (2021).

    PubMed  Google Scholar 

  288. Spira, D., Xenitidis, T., Henes, J. & Horger, M. MRI parametric monitoring of biological therapies in primary large vessel vasculitides: a pilot study. Br. J. Radiol. 89, 20150892 (2016).

    PubMed  PubMed Central  Google Scholar 

  289. Quinn, K. A. et al. Comparison of magnetic resonance angiography and (18)F-fluorodeoxyglucose positron emission tomography in large-vessel vasculitis. Ann. Rheum. Dis. 77, 1165–1171 (2018).

    PubMed  Google Scholar 

  290. Prieto-González, S. et al. Effect of glucocorticoid treatment on computed tomography angiography detected large-vessel inflammation in giant-cell arteritis. A prospective, longitudinal study. Medicine 94, e486 (2015).

    PubMed  PubMed Central  Google Scholar 

  291. Dweck, M. R. et al. Hybrid magnetic resonance imaging and positron emission tomography with fluorodeoxyglucose to diagnose active cardiac sarcoidosis. JACC Cardiovasc. Imaging 11, 94–107 (2018).

    PubMed  Google Scholar 

  292. Abgral, R. et al. Clinical utility of combined FDG-PET/MR to assess myocardial disease. JACC Cardiovasc. Imaging 10, 594–597 (2017).

    PubMed  Google Scholar 

  293. Laurent, C. et al. PET/MRI in large-vessel vasculitis: clinical value for diagnosis and assessment of disease activity. Sci. Rep. 9, 12388 (2019).

    PubMed  PubMed Central  Google Scholar 

  294. US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT02902731 (2020).

  295. Weyand, C. M., Hicok, K. C., Hunder, G. G. & Goronzy, J. J. Tissue cytokine patterns in patients with polymyalgia rheumatica and giant cell arteritis. Ann. Intern. Med. 121, 484–491 (1994).

    CAS  PubMed  Google Scholar 

  296. US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT04930094 (2021).

  297. US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT04633447 (2021).

  298. Espígol-Frigolé, G. et al. Expression and function of IL12/23 related cytokine subunits (p35, p40, and p19) in giant-cell arteritis lesions: contribution of p40 to Th1- and Th17-mediated inflammatory pathways. Front Immunol. 9, 809 (2018).

    PubMed  PubMed Central  Google Scholar 

  299. Espígol-Frigolé, G. et al. Identification of IL-23p19 as an endothelial proinflammatory peptide that promotes gp130-STAT3 signaling. Sci. Signal. 9, ra28 (2016).

    PubMed  PubMed Central  Google Scholar 

  300. US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT03711448 (2021).

  301. Conway, R. et al. Ustekinumab for refractory giant cell arteritis: a prospective 52-week trial. Semin. Arthritis Rheum. 48, 523–528 (2018).

    CAS  PubMed  Google Scholar 

  302. Matza, M. A., Fernandes, A. D., Stone, J. H. & Unizony, S. H. Ustekinumab for the treatment of giant cell arteritis. Arthritis Care Res. 73, 893–897 (2020).

    Google Scholar 

  303. US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT03841734 (2021).

  304. US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT03892785 (2021).

  305. Schmidt, W. A. et al. A multicentre, randomised, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of sirukumab in the treatment of giant cell arteritis. Rheumatol. Ther. 7, 793–810 (2020).

    PubMed  PubMed Central  Google Scholar 

  306. US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT04299971 (2021).

  307. US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT04161898 (2021).

  308. US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT04882072 (2021).

  309. US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT04564001 (2020).

Download references

Acknowledgements

D.P. and M.K. are funded by Clinical Academic Fellowships from the Chief Scientist Office, Scotland (CAF/19/01 and CAF/21/05, respectively). M.C.C. is funded by the Ministerio de Ciencia e Innovación/AEI//10.13039/501100011033 (PID2020-114909RB-I00) and the International Vasculitis Foundation. N.D. is supported by a Senior Clinical Research Fellowship from the Chief Scientist Office (SCAF/19/02). J.C.M., S.P.M. and T.Y. acknowledge infrastructure support from the Imperial National Institute for Health Research (NIHR) Biomedical Research Centre. P.C.G. is supported by the Intramural Research Program at the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

Author information

Authors and Affiliations

Authors

Contributions

Introduction (N.D., D.P., J.C.M. and T.Y.); Epidemiology (N.D., D.P., R.G., S.P.M. and T.Y.); Mechanisms/pathophysiology (N.D., D.P., M.K., C.S.G., C.M.W. and T.Y.); Diagnosis/screening/prevention (N.D., D.P., P.C.G. and T.Y.); Management (N.D., D.P., N.B., M.C.C. and T.Y.); Quality of life (N.D., D.P., R.G., S.P.M., C.O. and T.Y.); Outlook (N.D., D.P., J.C.M. and T.Y.); Overview of the Primer (N.D., D.P., J.C.M. and T.Y.).

Corresponding author

Correspondence to Neeraj Dhaun.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Peer review information

Nature Reviews Disease Primers thanks Christian Dejaco, who co-reviewed with Milena Bond; David Saadoun; Maxime Samson; and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pugh, D., Karabayas, M., Basu, N. et al. Large-vessel vasculitis. Nat Rev Dis Primers 7, 93 (2021). https://doi.org/10.1038/s41572-021-00327-5

Download citation

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1038/s41572-021-00327-5

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing