Skip to main content
SpringerLink
Log in

Aging in Primary Systemic Vasculitis: Implications for Diagnosis, Clinical Manifestations, and Management

  • Review Article
  • Published:
Drugs & Aging Aims and scope Submit manuscript

Abstract

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) usually affect adults and older populations. The well recognized clinical (i.e., granulomatosis with polyangiitis [GPA], microscopic polyangiitis, and eosinophilic GPA) and serological phenotypes (i.e., anti-MPO-ANCA, anti-PR3-ANCA and ANCA negative) within AAV differ substantially for clinical, demographic, and epidemiological features, including age at presentation. Whether and how aging could contribute to the clinical expression of these disease phenotypes is intriguing and still overlooked. In addition, despite being predominantly a disease of the elderly, most of the studies analyzing drug interventions and the clinical trials on AAV explicitly excluded older patients, limiting the understanding of the disease in this subset of patients. In elderly patients induced with cyclophosphamide, a lower dose of treatment for patients aged 60 years or older and with reduced renal function has been recommended. Giant cell arteritis (GCA) and Takayasu’s arteritis (TAK) are two primary systemic vasculitides involving large vessels that differ in age at presentation, with GCA patients being at least 10 years older than TAK patients. Different treatment approaches are effective in these conditions. However, a few authors have suggested that they might be considered expressions of the same clinical syndrome, rather than two different diseases. Novel insights into the role of senescence-related immunological and vascular processes might help to interpret the link between these two conditions. Overall, the impact of aging on all these vasculitides is complex and not easy to analyze. So far, few studies focusing on this topic have been published. We reviewed data on the clinical presentation, epidemiology, therapy, and disease- and treatment-related complications in patients affected by these vasculitides, highlighting the differences in young versus elderly subjects.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Watts RA, Mooney J, Scott DGI. The epidemiology of vasculitis in the UK [abstract no. 339]. Rheumatology. 2014;53(suppl 1):i187-i. https://doi.org/10.1093/rheumatology/keu129.008.

    Article  Google Scholar 

  2. Romero-Gomez C, Aguilar-Garcia JA, Garcia-de-Lucas MD, Cotos-Canca R, Olalla-Sierra J, Garcia-Alegria JJ, et al. Epidemiological study of primary systemic vasculitides among adults in southern Spain and review of the main epidemiological studies. Clin Exp Rheumatol. 2015;33(2 Suppl 89):S-11-8.

    PubMed  Google Scholar 

  3. Batu ED, Sari A, Erden A, Sonmez HE, Armagan B, Kalyoncu U, et al. Comparing immunoglobulin A vasculitis (Henoch-Schonlein purpura) in children and adults: a single-centre study from Turkey. Scand J Rheumatol. 2018. https://doi.org/10.1080/03009742.2018.1448111 (Epub 2018 Jun 18).

    Article  PubMed  Google Scholar 

  4. Sungur G, Hazirolan D, Hekimoglu E, Kasim R, Duman S. Late-onset Behcet’s disease: demographic, clinical, and ocular features. Graefes Arch Clin Exp Ophthalmol. 2010;248(9):1325–30.

    Article  PubMed  Google Scholar 

  5. Iudici M, Quartier P, Pagnoux C, Merlin E, Agard C, Aouba A, et al. Childhood- versus adult-onset polyarteritis nodosa results from the French Vasculitis Study Group Registry. Autoimmun Rev. 2018;17(10):984–9.

    Article  PubMed  Google Scholar 

  6. Jennette JC, Falk RJ, Bacon PA, Basu N, Cid MC, Ferrario F, et al. 2012 revised International Chapel Hill consensus conference nomenclature of vasculitides. Arthritis Rheum. 2013;65(1):1–11.

    Article  CAS  PubMed  Google Scholar 

  7. Jennette JC, Falk RJ. Small-vessel vasculitis. N Engl J Med. 1997;337(21):1512–23.

    Article  CAS  PubMed  Google Scholar 

  8. Yates M, Watts RA, Bajema IM, Cid MC, Crestani B, Hauser T, et al. EULAR/ERA-EDTA recommendations for the management of ANCA-associated vasculitis. Ann Rheum Dis. 2016;75(9):1583–94.

    Article  CAS  PubMed  Google Scholar 

  9. Chen M, Kallenberg CG. ANCA-associated vasculitides—advances in pathogenesis and treatment. Nature Rev Rheumatol. 2010;6(11):653–64.

    Article  CAS  Google Scholar 

  10. Berti A, Cornec D, Crowson CS, Specks U, Matteson EL. The epidemiology of antineutrophil cytoplasmic autoantibody-associated vasculitis in Olmsted County, Minnesota (USA): a twenty-year population-based study. Arthritis Rheumatol. 2017;69(12):2338–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Catanoso M, Macchioni P, Boiardi L, Manenti L, Tumiati B, Cavazza A, et al. Epidemiology of granulomatosis with polyangiitis (Wegener’s granulomatosis) in Northern Italy: a 15-year population-based study. Semin Arthritis Rheum. 2014;44(2):202–7.

    Article  PubMed  Google Scholar 

  12. Watts RA, Lane SE, Bentham G, Scott DG. Epidemiology of systemic vasculitis: a ten-year study in the United Kingdom. Arthritis Rheum. 2000;43(2):414–9.

    Article  CAS  PubMed  Google Scholar 

  13. Koldingsnes W, Nossent H. Epidemiology of Wegener’s granulomatosis in northern Norway. Arthritis Rheum. 2000;43(11):2481–7.

    Article  CAS  PubMed  Google Scholar 

  14. Pearce FA, Lanyon PC, Grainge MJ, Shaunak R, Mahr A, Hubbard RB, et al. Incidence of ANCA-associated vasculitis in a UK mixed ethnicity population. Rheumatology (Oxford). 2016;55(9):1656–63.

    Article  Google Scholar 

  15. Mohammad AJ, Jacobsson LT, Westman KW, Sturfelt G, Segelmark M. Incidence and survival rates in Wegener’s granulomatosis, microscopic polyangiitis. Churg-Strauss syndrome and polyarteritis nodosa. Rheumatology (Oxford). 2009;48(12):1560–5.

    Article  Google Scholar 

  16. Pamuk ON, Donmez S, Calayir GB, Pamuk GE. The epidemiology of antineutrophil cytoplasmic antibody-associated vasculitis in northwestern Turkey. Clin Rheumatol. 2016;35(8):2063–71.

    Article  PubMed  Google Scholar 

  17. Franssen CF, Gans RO, Arends B, Hageluken C, ter Wee PM, Gerlag PG, et al. Differences between anti-myeloperoxidase- and anti-proteinase 3-associated renal disease. Kidney Int. 1995;47(1):193–9.

    Article  CAS  PubMed  Google Scholar 

  18. Chen M, Yu F, Zhang Y, Zhao MH. Antineutrophil cytoplasmic autoantibody-associated vasculitis in older patients. Medicine. 2008;87(4):203–9.

    Article  CAS  PubMed  Google Scholar 

  19. Wang Q, van Timmeren MM, Petersen AH, Yuan J, Moser J, Brouwer E, et al. Age-determined severity of anti-myeloperoxidase autoantibody-mediated glomerulonephritis in mice. Nephrol Dial Transpl. 2017;32(2):254–64.

    CAS  Google Scholar 

  20. Lamprecht P. Off balance: T-cells in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides. Clin Exp Immunol. 2005;141(2):201–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Hilhorst M, van Paassen P, Tervaert JW. Proteinase 3-ANCA vasculitis versus myeloperoxidase-ANCA vasculitis. J Am Soc Nephrol. 2015;26(10):2314–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Cornec D, Cornec-Le Gall E, Fervenza FC, Specks U. ANCA-associated vasculitis - clinical utility of using ANCA specificity to classify patients. Nature Rev Rheumatol. 2016;12(10):570–9.

    Article  CAS  Google Scholar 

  23. Bomback AS, Appel GB, Radhakrishnan J, Shirazian S, Herlitz LC, Stokes B, et al. ANCA-associated glomerulonephritis in the very elderly. Kidney Int. 2011;79(7):757–64.

    Article  PubMed  Google Scholar 

  24. Schirmer JH, Wright MN, Vonthein R, Herrmann K, Nölle B, Both M, et al. Clinical presentation and long-term outcome of 144 patients with microscopic polyangiitis in a monocentric German cohort. Rheumatology. 2016;55(1):71–9.

    Article  PubMed  Google Scholar 

  25. Berti A, Felicetti M, Padoan R, Brunori G, Schiavon F, Paolazzi G. Long-term mortality and complications in young and elderly patients with anca-associated vasculitis [abstract no. FRI0310]. Ann Rheum Dis. 2017;76(Suppl 2):604.

    Google Scholar 

  26. Monti S, Balduzzi S, Cavagna L, Montecucco C, Caporali R. Does the age at disease onset influence the clinical presentation and long-term outcome of anca-associated vasculitides? Results from a single-centre cohort [abstract no. AB0569]. Ann Rheum Dis. 2016;75(Suppl 2):1099.

    Google Scholar 

  27. Weiner M, Goh SM, Mohammad AJ, Hruskova Z, Tanna A, Bruchfeld A, et al. Outcome and treatment of elderly patients with ANCA-associated vasculitis. Clin J Am Soc Nephrol. 2015;10(7):1128–35.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Hoganson DD, From AM, Michet CJ. ANCA vasculitis in the elderly. J Clin Rheumatol. 2008;14(2):78–81.

    Article  PubMed  Google Scholar 

  29. Moutzouris DA, Herlitz L, Appel GB, Markowitz GS, Freudenthal B, Radhakrishnan J, et al. Renal biopsy in the very elderly. Clin J Am Soc Nephrol. 2009;4(6):1073–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Monti S, Craven A, Klersy C, Montecucco C, Caporali R, Watts R, et al. Association between age at diagnosis and clinical presentation and outcomes of anca-associated vasculitis analysis from the dcvas study [abstract no. OP0238]. Ann Rheum Dis. 2018;77(Suppl 2):168.

    Google Scholar 

  31. Mohammad AJ, Segelmark M. A population-based study showing better renal prognosis for proteinase 3 antineutrophil cytoplasmic antibody (ANCA)-associated nephritis versus myeloperoxidase ANCA-associated nephritis. J Rheumatol. 2014;41(7):1366–73.

    Article  PubMed  Google Scholar 

  32. Lionaki S, Blyth ER, Hogan SL, Hu Y, Senior BA, Jennette CE, et al. Classification of antineutrophil cytoplasmic autoantibody vasculitides: the role of antineutrophil cytoplasmic autoantibody specificity for myeloperoxidase or proteinase 3 in disease recognition and prognosis. Arthritis Rheum. 2012;64(10):3452–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Mohammad AJ, Weiner M, Sjowall C, Johansson ME, Bengtsson AA, Stahl-Hallengren C, et al. Incidence and disease severity of anti-neutrophil cytoplasmic antibody-associated nephritis are higher than in lupus nephritis in Sweden. Nephrol Dial Transplant. 2015;30(Suppl 1):i23–30.

    CAS  PubMed  Google Scholar 

  34. Guillevin L, Pagnoux C, Seror R, Mahr A, Mouthon L, Le Toumelin P. The Five-Factor Score revisited: assessment of prognoses of systemic necrotizing vasculitides based on the French Vasculitis Study Group (FVSG) cohort. Medicine. 2011;90(1):19–27.

    Article  PubMed  Google Scholar 

  35. Berti A, Matteson EL, Crowson CS, Specks U, Cornec D. Risk of cardiovascular disease and venous thromboembolism among patients with incident ANCA-associated vasculitis: a 20-year population-based cohort study. Mayo Clin Proc. 2018;93(5):597–606.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Avina-Zubieta JA, Mai A, Amiri N, Dehghan N, Ann Tan J, Sayre EC, et al. Risk of myocardial infarction and stroke in patients with granulomatosis with polyangiitis (Wegener’s): a population-based study. Arthritis Rheumatol. 2016;68(11):2752–9.

    Article  PubMed  Google Scholar 

  37. Suppiah R, Judge A, Batra R, Flossmann O, Harper L, Hoglund P, et al. A model to predict cardiovascular events in patients with newly diagnosed Wegener’s granulomatosis and microscopic polyangiitis. Arthritis Care Res. 2011;63(4):588–96.

    Article  Google Scholar 

  38. McGregor JG, Negrete-Lopez R, Poulton CJ, Kidd JM, Katsanos SL, Goetz L, et al. Adverse events and infectious burden, microbes and temporal outline from immunosuppressive therapy in antineutrophil cytoplasmic antibody-associated vasculitis with native renal function. Nephrol Dial Transpl. 2015;30(Suppl 1):i171–81.

    Article  CAS  Google Scholar 

  39. Sriskandarajah S, Bostad L, Myklebust TÅ, Møller B, Skrede S, Bjørneklett R. Cancer in ANCA-associated glomerulonephritis: a registry-based cohort study. Int J Nephrol. 2017;2017:6013038.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Mohammad AJ, Segelmark M, Smith R, Englund M, Nilsson JA, Westman K, et al. Severe infection in antineutrophil cytoplasmic antibody-associated vasculitis. J Rheumatol. 2017;44(10):1468–75.

    Article  CAS  PubMed  Google Scholar 

  41. Chinar R, E. BA, Sophie-Charlotte W, J. RME, C. HE, Ron W, et al. Incidence of malignancies in patients with antineutrophil cytoplasmic antibody–associated vasculitis diagnosed between 1991 and 2013. Arthritis Rheumatol. 2015;67(12):3270–8.

  42. Jardel S, Puéchal X, Le Quellec A, Pagnoux C, Hamidou M, Maurier F, et al. Mortality in systemic necrotizing vasculitides: a retrospective analysis of the French Vasculitis Study Group registry. Autoimmun Rev. 2018;17(7):653–9.

    Article  PubMed  Google Scholar 

  43. Tan JA, Choi HK, Xie H, Sayre EC, Esdaile JM, Avina-Zubieta JA. All-cause and cause-specific mortality in granulomatosis with polyangiitis: a population-based study. Arthritis Care Res (Hoboken). https://doi.org/10.1002/acr.23587 (Epub 2018 Apr 25).

  44. Flossmann O, Berden A, de Groot K, Hagen C, Harper L, Heijl C, et al. Long-term patient survival in ANCA-associated vasculitis. Ann Rheum Dis. 2011;70(3):488–94.

    Article  PubMed  Google Scholar 

  45. Houben E, Penne EL, Voskuyl AE, van der Heijden JW, Otten RHJ, Boers M, et al. Cardiovascular events in anti-neutrophil cytoplasmic antibody-associated vasculitis: a meta-analysis of observational studies. Rheumatology (Oxford). 2018;57(3):555–62.

    Article  Google Scholar 

  46. Bai YH, Li ZY, Chang DY, Chen M, Kallenberg CG, Zhao MH. The BVAS is an independent predictor of cardiovascular events and cardiovascular disease-related mortality in patients with ANCA-associated vasculitis: a study of 504 cases in a single Chinese center. Semin Arthritis Rheum. 2018;47(4):524–9.

    Article  PubMed  Google Scholar 

  47. Berti A, Campochiaro C, Cavalli G, Pepe G, Praderio L, Sabbadini MG, et al. Giant cell arteritis restricted to the limb arteries: an overlooked clinical entity. Autoimmun Rev. 2015;14(4):352–7.

    Article  PubMed  Google Scholar 

  48. Exley AR, Bacon PA, Luqmani RA, Kitas GD, Gordon C, Savage CO, et al. Development and initial validation of the Vasculitis Damage Index for the standardized clinical assessment of damage in the systemic vasculitides. Arthritis Rheum. 1997;40(2):371–80.

    Article  CAS  PubMed  Google Scholar 

  49. Robson J, Doll H, Suppiah R, Flossmann O, Harper L, Hoglund P, et al. Glucocorticoid treatment and damage in the anti-neutrophil cytoplasm antibody-associated vasculitides: long-term data from the European Vasculitis Study Group trials. Rheumatology (Oxford). 2015;54(3):471–81.

    Article  CAS  Google Scholar 

  50. Robson J, Doll H, Suppiah R, Flossmann O, Harper L, Hoglund P, et al. Damage in the anca-associated vasculitides: long-term data from the European Vasculitis Study Group (EUVAS) therapeutic trials. Ann Rheum Dis. 2015;74(1):177–84.

    Article  PubMed  Google Scholar 

  51. Tarzi RM, Pusey CD. Vasculitis: Risks and rewards of treating elderly patients with vasculitis. Nature Rev Nephrol. 2011;7(5):253–5.

    Article  Google Scholar 

  52. Higgins RM, Goldsmith DJ, Connolly J, Scoble JE, Hendry BM, Ackrill P, et al. Vasculitis and rapidly progressive glomerulonephritis in the elderly. Postgrad Med J. 1996;72(843):41–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. de Groot K, Harper L, Jayne DR, Flores Suarez LF, Gregorini G, Gross WL, et al. Pulse versus daily oral cyclophosphamide for induction of remission in antineutrophil cytoplasmic antibody-associated vasculitis: a randomized trial. Ann Intern Med. 2009;150(10):670–80.

    Article  PubMed  Google Scholar 

  54. Lapraik C, Watts R, Bacon P, Carruthers D, Chakravarty K, D’Cruz D, et al. BSR and BHPR guidelines for the management of adults with ANCA associated vasculitis. Rheumatology (Oxford). 2007;46(10):1615–6.

    Article  CAS  Google Scholar 

  55. De Groot K, Rasmussen N, Bacon PA, Tervaert JW, Feighery C, Gregorini G, et al. Randomized trial of cyclophosphamide versus methotrexate for induction of remission in early systemic antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum. 2005;52(8):2461–9.

    Article  CAS  PubMed  Google Scholar 

  56. Pagnoux C, Mahr A, Hamidou MA, Boffa JJ, Ruivard M, Ducroix JP, et al. Azathioprine or methotrexate maintenance for ANCA-associated vasculitis. N Engl J Med. 2008;359(26):2790–803.

    Article  CAS  PubMed  Google Scholar 

  57. Pagnoux C, Quemeneur T, Ninet J, Diot E, Kyndt X, de Wazieres B, et al. Treatment of systemic necrotizing vasculitides in patients aged sixty-five years or older: results of a multicenter, open-label, randomized controlled trial of corticosteroid and cyclophosphamide-based induction therapy. Arthritis Rheumatol. 2015;67(4):1117–27.

    Article  CAS  PubMed  Google Scholar 

  58. Timlin H, Lee SM, Manno RL, Seo P, Geetha D. Rituximab for remission induction in elderly patients with ANCA-associated vasculitis. Semin Arthritis Rheum. 2015;45(1):67–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Harper L, Savage CO. ANCA-associated renal vasculitis at the end of the twentieth century–a disease of older patients. Rheumatology (Oxford). 2005;44(4):495–501.

    Article  CAS  Google Scholar 

  60. Watts RA, Mahr A, Mohammad AJ, Gatenby P, Basu N, Flores-Suarez LF. Classification, epidemiology and clinical subgrouping of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Nephrol Dial Transplant. 2015;30(Suppl 1):i14–22.

    Article  CAS  PubMed  Google Scholar 

  61. Anderson K, Klassen J, Stewart SA, Taylor-Gjevre RM. Does geographic location affect incidence of ANCA-associated renal vasculitis in northern Saskatchewan, Canada? Rheumatology (Oxford). 2013;52(10):1840–4.

    Article  Google Scholar 

  62. Unizony S, Villarreal M, Miloslavsky EM, Lu N, Merkel PA, Spiera R, et al. Clinical outcomes of treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis based on ANCA type. Ann Rheum Dis. 2016;75(6):1166–9.

    Article  CAS  PubMed  Google Scholar 

  63. Mohammad AJ, Jacobsson LT, Mahr AD, Sturfelt G, Segelmark M. Prevalence of Wegener’s granulomatosis, microscopic polyangiitis, polyarteritis nodosa and Churg-Strauss syndrome within a defined population in southern Sweden. Rheumatology (Oxford). 2007;46(8):1329–37.

    Article  CAS  Google Scholar 

  64. Comarmond C, Pagnoux C, Khellaf M, Cordier JF, Hamidou M, Viallard JF, et al. Eosinophilic granulomatosis with polyangiitis (Churg-Strauss): clinical characteristics and long-term followup of the 383 patients enrolled in the French Vasculitis Study Group cohort. Arthritis Rheum. 2013;65(1):270–81.

    Article  PubMed  Google Scholar 

  65. Tan JA, Dehghan N, Chen W, Xie H, Esdaile JM, Avina-Zubieta JA. Mortality in ANCA-associated vasculitis: a meta-analysis of observational studies. Ann Rheum Dis. 2017;76(9):1566–74.

    Article  PubMed  Google Scholar 

  66. de Joode AA, Sanders JS, Stegeman CA. Renal survival in proteinase 3 and myeloperoxidase ANCA-associated systemic vasculitis. Clin J Am Soc Nephrol. 2013;8(10):1709–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Watts RA, Lane SE, Scott DG, Koldingsnes W, Nossent H, Gonzalez-Gay MA, et al. Epidemiology of vasculitis in Europe. Ann Rheum Dis. 2001;60(12):1156–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Arend WP, Michel BA, Bloch DA, Hunder GG, Calabrese LH, Edworthy SM, et al. The American College of Rheumatology 1990 criteria for the classification of Takayasu arteritis. Arthritis Rheum. 1990;33(8):1129–34.

    Article  CAS  PubMed  Google Scholar 

  69. Hunder GG, Bloch DA, Michel BA, Stevens MB, Arend WP, Calabrese LH, et al. The American College of Rheumatology 1990 criteria for the classification of giant cell arteritis. Arthritis Rheum. 1990;33(8):1122–8.

    Article  CAS  PubMed  Google Scholar 

  70. Richards BL, March L, Gabriel SE. Epidemiology of large-vessel vasculidities. Best Pract Res Clin Rheumatol. 2010;24(6):871–83.

    Article  PubMed  Google Scholar 

  71. Dejaco C, Duftner C, Buttgereit F, Matteson EL, Dasgupta B. The spectrum of giant cell arteritis and polymyalgia rheumatica: revisiting the concept of the disease. Rheumatology (Oxford). 2017;56(4):506–15.

    CAS  Google Scholar 

  72. Maksimowicz-McKinnon K, Clark TM, Hoffman GS. Takayasu arteritis and giant cell arteritis: a spectrum within the same disease? Medicine. 2009;88(4):221–6.

    Article  PubMed  Google Scholar 

  73. Kermani TA. Takayasu arteritis and giant cell arteritis: are they a spectrum of the same disease? Int J Rheumatic Dis. https://doi.org/10.1111/1756-185X.13288 (Epub 2018 Apr 6).

  74. Koster MJ, Matteson EL, Warrington KJ. Large-vessel giant cell arteritis: diagnosis, monitoring and management. Rheumatology. 2018;57(suppl 2):ii32–42.

  75. Schmidt WA, Moll A, Seifert A, Schicke B, Gromnica-Ihle E, Krause A. Prognosis of large-vessel giant cell arteritis. Rheumatology (Oxford). 2008;47(9):1406–8.

    Article  CAS  Google Scholar 

  76. Vaideeswar P, Deshpande JR. Pathology of Takayasu arteritis: a brief review. Ann Pediatr Cardiol. 2013;6(1):52–8.

    Article  PubMed  PubMed Central  Google Scholar 

  77. Miller DV, Maleszewski JJ. The pathology of large-vessel vasculitides. Clin Exp Rheumatol. 2011;29(1 Suppl 64):S92–8.

    PubMed  Google Scholar 

  78. Mohan SV, Liao YJ, Kim JW, Goronzy JJ, Weyand CM. Giant cell arteritis: immune and vascular aging as disease risk factors. Arthritis Res Ther. 2011;13(4):231.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Chen HZ, Wang F, Gao P, Pei JF, Liu Y, Xu TT, et al. Age-associated sirtuin 1 reduction in vascular smooth muscle links vascular senescence and inflammation to abdominal aortic aneurysm. Circ Res. 2016;119(10):1076–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Basta G, Schmidt AM, De Caterina R. Advanced glycation end products and vascular inflammation: implications for accelerated atherosclerosis in diabetes. Cardiovasc Res. 2004;63(4):582–92.

    Article  CAS  PubMed  Google Scholar 

  81. Hoffman GS, Calabrese LH. Vasculitis: determinants of disease patterns. Nature Rev Rheumatol. 2014;10(8):454–62.

    Article  Google Scholar 

  82. Nordborg E, Nordborg C. Giant cell arteritis: epidemiological clues to its pathogenesis and an update on its treatment. Rheumatology (Oxford). 2003;42(3):413–21.

    Article  CAS  Google Scholar 

  83. Dejaco C, Duftner C, Al-Massad J, Wagner AD, Park JK, Fessler J, et al. NKG2D stimulated T-cell autoreactivity in giant cell arteritis and polymyalgia rheumatica. Ann Rheum Dis. 2013;72(11):1852–9.

    Article  CAS  PubMed  Google Scholar 

  84. Coit P, De Lott LB, Nan B, Elner VM, Sawalha AH. DNA methylation analysis of the temporal artery microenvironment in giant cell arteritis. Ann Rheum Dis. 2016;75(6):1196–202.

    Article  CAS  PubMed  Google Scholar 

  85. Jung M, Pfeifer GP. Aging and DNA methylation. BMC Biol. 2015;13:7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Grayson PC, Maksimowicz-McKinnon K, Clark TM, Tomasson G, Cuthbertson D, Carette S, et al. Distribution of arterial lesions in Takayasu’s arteritis and giant cell arteritis. Ann Rheum Dis. 2012;71(8):1329–34.

    Article  PubMed  PubMed Central  Google Scholar 

  87. Germano G, Monti S, Ponte C, Possemato N, Caporali R, Salvarani C, et al. The role of ultrasound in the diagnosis and follow-up of large-vessel vasculitis: an update. Clin Exp Rheumatol. 2017;35(Suppl 103(1)):194–8.

  88. Monti S, Floris A, Ponte C, Schmidt WA, Diamantopoulos AP, Pereira C, et al. The use of ultrasound to assess giant cell arteritis: review of the current evidence and practical guide for the rheumatologist. Rheumatology (Oxford). 2018;57(2):227–35.

    Article  Google Scholar 

  89. Kermani TA, Crowson CS, Muratore F, Schmidt J, Matteson EL, Warrington KJ. Extra-cranial giant cell arteritis and Takayasu arteritis: how similar are they? Semin Arthritis Rheum. 2015;44(6):724–8.

    Article  PubMed  Google Scholar 

  90. Soussan M, Nicolas P, Schramm C, Katsahian S, Pop G, Fain O, et al. Management of large-vessel vasculitis with FDG-PET: a systematic literature review and meta-analysis. Medicine. 2015;94(14):e622.

    Article  PubMed  PubMed Central  Google Scholar 

  91. Monti S, Floris A, Ponte CB, Schmidt WA, Diamantopoulos AP, Pereira C, et al. The proposed role of ultrasound in the management of giant cell arteritis in routine clinical practice. Rheumatology (Oxford). 2018;57(1):112–9.

    Article  Google Scholar 

  92. Santoro L, D’Onofrio F, Bernardi S, Gremese E, Ferraccioli G, Santoliquido A. Temporal ultrasonography findings in temporal arteritis: early disappearance of halo sign after only 2 days of steroid treatment. Rheumatology (Oxford). 2013;52(4):622.

    Article  Google Scholar 

  93. Schmidt WA. Ultrasound in the diagnosis and management of giant cell arteritis. Rheumatology. 2018;57(suppl 2):ii22–31.

  94. Schmidt WA, 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 (Oxford). 2008;47(1):96–101.

    Article  CAS  Google Scholar 

  95. Czihal M, Piller A, Schroettle A, Kuhlencordt P, Bernau C, Schulze-Koops H, et al. Impact of cranial and axillary/subclavian artery involvement by color duplex sonography on response to treatment in giant cell arteritis. J Vasc Surg. 2015;61(5):1285–91.

    Article  PubMed  Google Scholar 

  96. De Miguel E, Beltran LM, Monjo I, Deodati F, Schmidt WA, Garcia-Puig J. Atherosclerosis as a potential pitfall in the diagnosis of giant cell arteritis. Rheumatology (Oxford). 2018;57(2):318–21.

    Article  PubMed  Google Scholar 

  97. Dejaco C, Ramiro S, Duftner C, Besson FL, Bley TA, Blockmans D, et al. EULAR recommendations for the use of imaging in large vessel vasculitis in clinical practice. Ann Rheum Dis. 2018;77(5):636–43.

    Article  PubMed  Google Scholar 

  98. Quinn KA, Ahlman MA, Malayeri AA, Marko J, Civelek AC, Rosenblum JS, et al. Comparison of magnetic resonance angiography and 18F-fluorodeoxyglucose positron emission tomography in large-vessel vasculitis. Ann Rheum Dis. 2018;77(8):1165–71.

    PubMed  PubMed Central  Google Scholar 

  99. Grayson PC, Alehashemi S, Bagheri AA, Civelek AC, Cupps TR, Kaplan MJ, 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. 2018;70(3):439–49.

    Article  PubMed  PubMed Central  Google Scholar 

  100. Kermani TA, Sreih AG, Cuthbertson D, Carette S, Hoffman GS, Khalidi NA, et al. Evaluation of damage in giant cell arteritis. Rheumatology. 2018;57(2):322–8.

    Article  PubMed  Google Scholar 

  101. Omma A, Erer B, Karadag O, Yilmaz N, Alibaz-Oner F, Yildiz F, et al. Remarkable damage along with poor quality of life in Takayasu arteritis: cross-sectional results of a long-term followed-up multicentre cohort. Clin Exp Rheumatol. 2017;35(Suppl 103(1)):77–82.

  102. Robson JC, Kiran A, Maskell J, Hutchings A, Arden N, Dasgupta B, 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. 2015;74(1):129–35.

    Article  PubMed  Google Scholar 

  103. Aouba A, Gonzalez Chiappe S, Eb M, Delmas C, de Boysson H, Bienvenu B, et al. Mortality causes and trends associated with giant cell arteritis: analysis of the French national death certificate database (1980–2011). Rheumatology (Oxford). 2018;57(6):1047–55.

    Article  Google Scholar 

  104. Alibaz-Oner F, Koster MJ, Unal AU, Yildirim HG, Cikikci C, Schmidt J, et al. Assessment of the frequency of cardiovascular risk factors in patients with Takayasu’s arteritis. Rheumatology (Oxford). 2017;56(11):1939–44.

    Article  CAS  Google Scholar 

  105. Comarmond C, Biard L, Lambert M, Mekinian A, Ferfar Y, Kahn JE, et al. Long-term outcomes and prognostic factors of complications in Takayasu arteritis: a multicenter study of 318 patients. Circulation. 2017;136(12):1114–22.

    Article  PubMed  Google Scholar 

  106. Park SJ, Kim HJ, Park H, Hann HJ, Kim KH, Han S, et al. Incidence, prevalence, mortality and causes of death in Takayasu arteritis in Korea - a nationwide, population-based study. Int J Cardiol. 2017;235:100–4.

    Article  PubMed  Google Scholar 

  107. Berti A, Cornec D, Medina Inojosa JR, Matteson EL, Murad MH. Treatments for giant cell arteritis: meta-analysis and assessment of estimates reliability using the fragility index. Semin Arthritis Rheum. 2018;48(1):77–82.

    Article  PubMed  Google Scholar 

  108. Barra L, Yang G, Pagnoux C. Non-glucocorticoid drugs for the treatment of Takayasu’s arteritis: a systematic review and meta-analysis. Autoimmun Rev. 2018;17(7):683–93.

    Article  CAS  PubMed  Google Scholar 

  109. Schmidt J, Smail A, Roche B, Gay P, Salle V, Pellet H, et al. Incidence of severe infections and infection-related mortality during the course of giant cell arteritis: a multicenter, prospective, double-cohort study. Arthritis Rheumatol. 2016;68(6):1477–82.

    Article  CAS  PubMed  Google Scholar 

  110. Chazal T, Lhote R, Rey G, Haroche J, Eb M, Amoura Z, et al. Giant-cell arteritis-related mortality in France: a multiple-cause-of-death analysis. Autoimmun Rev. 2018. https://doi.org/10.1016/j.autrev.2018.06.012 (Epub 2018 Oct 11).

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Rheumatology Department, Santa Chiara Hospital, Largo Medaglie D’oro, 9, 38122, Trento, TN, Italy

    Alvise Berti & Giuseppe Paolazzi

  2. Centre for Integrative Biology, University of Trento, Trento, Italy

    Alvise Berti

  3. Rheumatology Department, Policlinico S. Matteo, Fondazione IRCCS, University of Pavia, Pavia, Italy

    Roberto Caporali, Carlomaurizio Montecucco & Sara Monti

  4. University of Pavia, Pavia, Italy

    Sara Monti

Authors
  1. Alvise Berti
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Roberto Caporali
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Carlomaurizio Montecucco
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Giuseppe Paolazzi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sara Monti
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alvise Berti.

Ethics declarations

Conflict of interest

Alvise Berti, Roberto Caporali, Carlomaurizio Montecucco, Giuseppe Paolazzi, and Sara Monti have no financial or non-financial potential conflicts of interest to declare related to this project. All authors were involved in the writing and editing of the manuscript, and approved the final version.

Funding

The study was not supported by grants from any organization or institution.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Berti, A., Caporali, R., Montecucco, C. et al. Aging in Primary Systemic Vasculitis: Implications for Diagnosis, Clinical Manifestations, and Management. Drugs Aging 36, 53–63 (2019). https://doi.org/10.1007/s40266-018-0617-4

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40266-018-0617-4

Search

Navigation