Recent Advances in Giant Cell Arteritis

  • M. Guevara
  • C. S. Kollipara
Vasculitis (L Espinoza, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Vasculitis


Purpose of Review

Giant cell arteritis (GCA) is the most common systemic vasculitis. GCA is categorized as a granulomatous vasculitis of large and medium size vessels. Majority of the symptoms and signs of GCA result from involvement of the aorta and its branches intra- and extracranial. Temporal artery biopsy continues to be the cardinal diagnostic procedure despite new imaging modalities for diagnosing GCA with cranial involvement. Great advances in awareness have led to improvement in preventing irreversible vision loss due to early diagnosis.

Recent Findings

The cause of GCA has not been elucidated but major progress has been made in the knowledge of its pathogenesis leading to new therapeutic targets, particularly inhibition of interleukin 6. IL 6 plays a key role in the regulation of TH17/Tregs imbalance in GCA and appears to correlate with clinical disease activity in GCA. All of this has led to the first FDA (food and drug administration) approved treatment for GCA, Tocilizumab. Abatacept and Ustekinumab are promising targets for therapy in LVV but still need further research.


This paper is a review of the recent progress in the understanding of GCA pathogenesis, diagnosis, treatment, and prognosis.


Review of epidemiology Pathophysiology Diagnosis Treatment and prognosis for GCA 


Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Salvarini C, Macchioni P, et al. Polymyalgia rheumatic and giant cell arteritis. Lancet. 2008;372:234–45.CrossRefGoogle Scholar
  2. 2.
    Salvarani C, Macchioni P, et al. Epidemiologic and immunogenetic aspects of polymyalgia rheumatic and giant cell arteritis in northern Italy. Arthritis Rheum. 1991;32:351.CrossRefGoogle Scholar
  3. 3.
    •• Samson M, Corbera-Bellata M, et al. Recent advances in our understanding of giant cell arteritis pathogenesis. Autoimmun Rev. 2017;16:833–44. This study provides a detailed review about all the advances in pathophysiology of GCA. CrossRefPubMedGoogle Scholar
  4. 4.
    Crowson CS, Matteson EL, Myasoedova E, Michet CJ, Ernste FC, Warrington KJ, et al. The lifetime risk of adult onset rheumatoid arthritis and other inflammatory autoimmune rheumatic diseases. Arthritis Rheum. 2011;63:633–9.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Salvarini C, Crowson CS, et al. Reappraisal of the epidemiology of giant cell arteritis in Olmsted County, Minnesota, over a fifty year period. Arthritis Rheum. 2004;51:264–8.CrossRefGoogle Scholar
  6. 6.
    Combe B, Sany J, et al. Distribution of HLA-DRB1 alleles of patients with polymyalgia rheumatic and giant cell arteritis in a Mediterranean population. J Rheumatol. 1998;25:94.PubMedGoogle Scholar
  7. 7.
    Weyand CM, Hicok KC, Hunder GG, Goronzy JJ. The HLA-DRB1 locus a genetic component in giant cell arteritis. J Clin Invest. 1992;90:2355–61.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Gonzales-Gay MA. Genetic epidemiology. Giant cell artheritis and polymyalgia rhuematica. Arthritis Res. 2001;3:154–7.CrossRefGoogle Scholar
  9. 9.
    Renauer P, Coit P, et al. Epigenetics and vasculitis: a comprehensive review. Clin Rev Allergy Immunol. 2006;50:357.CrossRefGoogle Scholar
  10. 10.
    Li Y, Liu Y, Strickland FM, Richardson B. Age-dependent decreases in DNA methyl-transferase levels and low transmethylation micronutrient levels synergize to promote overexpression of genes implicated in autoimmunity and acute coronary syndromes. Exp Gerontol. 2010;45:312–22.CrossRefPubMedGoogle Scholar
  11. 11.
    Coit P, De Lott B, et al. DNA methylation analysis of the temporal artery microenviroment in giant cell arteritis. Ann Rheum Dis. 2016;75:1196–202.CrossRefPubMedGoogle Scholar
  12. 12.
    Ly KH, Regent A, et al. Pathogenesis of giant cell arteritis: more than just an inflammatory condition? Autoimmun Rev. 2010;9:635–45.CrossRefPubMedGoogle Scholar
  13. 13.
    Gabriel SE, Espy M, Erdman DD, Bjornsson J, Smith TF, Hunder GG. The role of parvovirus B19 in the pathogenesis of giant cell arteritis. Arthritis Rheum. 1999;42:1255–8.CrossRefPubMedGoogle Scholar
  14. 14.
    Haugeberg G, Bie R, et al. Temporal arterirtis associated with chlamydia pneumonia DNA detected in a artery specimen. J Rheumatol. 2001;28:1738.PubMedGoogle Scholar
  15. 15.
    Pryshchep O, Ma-Krupa W, Younge BR, Goronzy JJ, Weyand CM. Vessel-specific toll-like receptor profiles in human medium and large arteries. Circulation. 2008;118:1276–84.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Weyand CM, Schonberger J, et al. Distinct vascular lesions in giant cell arteritis share identical T cell clonotypes. J Exp Med. 1994;179:951–60.CrossRefPubMedGoogle Scholar
  17. 17.
    Piggott K, Biousse V, Newman NJ, Goronzy JJ, Weyand CM. Vascular damage in giant cell arteritis. Autoimmunity. 2009;42:596–604.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Samson M, Audia S, Fraszczak J, Trad M, Ornetti P, Lakomy D, et al. Th1 and Th17 lymphocytes expressing CD161 are implicated in giant cell arteritis and polymyalgia rheumatic pathogenesis. Arthritis Rheum. 2012;64:3788–98.CrossRefPubMedGoogle Scholar
  19. 19.
    Terrier B, Geri G, Chaara W, Allenbach Y, Rosenzwajg M, Costedoat-Chalumeau N, et al. Interleukin-21 modulates Th1 and Th17 responses in giant cell arteritis. Arthritis Rheum. 2012;64:2001–11.CrossRefPubMedGoogle Scholar
  20. 20.
    Deng J, Younge BR, Olshen RA, Goronzy JJ, Weyand CM. Th17 and Th1 cell responses in giant cell arteritis. Circulation. 2010;121:906–15.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Noack M, Miossec P. Th17 and regulatory T cell balance in autoimmune and inflammatory diseases. Autoimmun Rev. 2014;13:668–77.CrossRefPubMedGoogle Scholar
  22. 22.
    Samson M, Audia S, Janikashvili N, Ciudad M, Trad M, Fraszczak J, et al. Brief report: inhibition of IL6 function corrects Th17/Treg cell imbalance in patients with rheumatoid arthritis. Arthritis Rheum. 2012;64:2499–503.CrossRefPubMedGoogle Scholar
  23. 23.
    • Miyabe C, Miyabe Y, et al. An expanded population of pathogenic regulatory T cells in giant cell arteritis is abrogated by IL6 blockade therapy. Ann Rheum Dis. 2016. This article provides important information about the role of IL 6 in the imbalance of TH17/TH regulatory cells in the pathophysiology of GCA. Google Scholar
  24. 24.
    Zhang H, Watanabe R, Berry GJ, Vaglio A, Liao YJ, Warrington KJ, et al. Immunoinhibitory checkpoint deficiency in medium and large vessel vasculitis. Proc Natl Acad Sci U S A. 2017;114:E970–9.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Goldstein BL, Gedmintas L, Todd DJ. Drug associated polymyalgia rheumatica/giant cell arteritis occurring in two patients after treatment with ipilimumab, an antagonist of ctl-4. Arthritis Rheumatol. 2014;66:768–9.CrossRefPubMedGoogle Scholar
  26. 26.
    Corbera-Bellalta M, Planas-Rigol E. Blocking interferon gamma 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. 2015.Google Scholar
  27. 27.
    Weyand CM, Goronzy JJ. Giant-cell arteritis and polymyalgia rheumatic. Ann Intern Med. 2003;139:505–15.CrossRefPubMedGoogle Scholar
  28. 28.
    Galis ZS, Khathri JJ. Matrix metalloproteinases in vascular remodeling and atherogenesis: the good, the bad and the ugly. Circ Res. 2002;90:251.PubMedGoogle Scholar
  29. 29.
    Weyand C, Goronzy J. Medium and large vessel vasculitis. N Engl J Med. 2003;349:160–9.CrossRefPubMedGoogle Scholar
  30. 30.
    Brack A, Martinez-Taboada V, Stanson A, Goronzy JJ, Weyand CM. Disease pattern in cranial and large-vessel giant cell arteritis. Arthritis Rheum. 1999;42(2):311–7.CrossRefPubMedGoogle Scholar
  31. 31.
    Nuenninghoff DM, Hunder GG, Christianson TJ, McClelland RL, Matteson EL. Incidence and predictors of large-artery complication (aortic aneurysm, aortic dissection, and/or large-artery stenosis) in patients with giant cell arteritis: a population-based study over 50 years. Arthritis Rheum. 2003;4(8):3522–31.CrossRefGoogle Scholar
  32. 32.
    Gonzalez-Gay MA, Lopez-Diaz MJ, Barros S, Garcia-Porrua C, Sanchez-Andrade A, Paz-Carreira J, et al. Giant cell arteritis: laboratory tests at the time of diagnosis in a series of 240 patients. Medicine (Baltimore). 2005;84(5):277–90.CrossRefGoogle Scholar
  33. 33.
    Nesher G, Berkun Y, Mates M, Baras M, Nesher R, Rubinow A, et al. Risk factors for cranial ischemic complications in giant cell arteritis. Medicine (Baltimore). 2004;83(2):114–22.CrossRefGoogle Scholar
  34. 34.
    Cid MC, Font C, Oristrell J, de la Sierra A, Coll-Vinent B, López-Soto A, et al. Association between strong inflammatory response and low risk of developing visual loss and other cranial ischemic complications in giant cell (temporal) arteritis. Arthritis Rheum. 1998;41(1):26–32.CrossRefPubMedGoogle Scholar
  35. 35.
    Muratore F, Boiardi L, Cavazza A, Aldigeri R, Pipitone N, Restuccia G, et al. Correlation between histopathological findings and clinical manifestations in biopsy-proven giant cell arteritis. J Autoimmun. 2016;69:94–101.CrossRefPubMedGoogle Scholar
  36. 36.
    González-Gay MA, García-Porrúa C, Llorca J, Hajeer AH, Brañas F, Dababneh A, et al. Visual manifestations of giant cell arteritis. Trends and clinical spectrum in 161 patients. Medicine (Baltimore). 2000;79(5):283–92.CrossRefGoogle Scholar
  37. 37.
    Font C, Cid MC, Coll-Vinent B, Lopez-Soto A, Grau JM. Clinical features in patients with permanent visual loss due to biopsy-proven giant cell arteritis. Br J Rheumatol. 1997;36:251–4.CrossRefPubMedGoogle Scholar
  38. 38.
    Nesher G, Breuer G, et al. Giant cell arteritis and polymyalgia Rheumatica update. Rambam Maimonides Med J. 2016;7(4):e0035.CrossRefPubMedCentralGoogle Scholar
  39. 39.
    Lensen KD, Voskuyl AE, Comans EF, van der Laken C, Smulders YM. Extracranial giant cell arteritis: a narrative review. Neth J Med. 2016;74(5):182–92.PubMedGoogle Scholar
  40. 40.
    Gonzalez-Gay MA, Vasquez-Rodriquez TR, Gomez-Acebo I, et al. Strokes at time of disease diagnosis in a series of 287 patients with biopsy proven giant cell arteritis. Medicine (Baltimore). 2009;88(4):227–35.CrossRefGoogle Scholar
  41. 41.
    Agard C, Barrier JH, Dupas B, Ponge T, Mahr A, Fradet G, et al. Aortic involvement in recent-onset giant cell (temporal) arteritis: a case-control prospective study using helical aortic computed tomodensitometric scan. Arthritis Rheum. 2008;59:670–6.CrossRefPubMedGoogle Scholar
  42. 42.
    Prieto-Gonzalez S, Depetris M, et al. Positron emission tomography assessment of large vessel inflammation in patients with newly diagnosed, biopsy-proven giant cell arteritis: a prospective, case-control study. Ann Rheum Dis. 2014;73(7):1388–92.CrossRefPubMedGoogle Scholar
  43. 43.
    Evans JM, O'Fallon WM, Hunder GG, et al. Increased incidence of aortic aneurysm and dissection in giant cell (temporal) arteritis. A population-based study. Ann Intern Med. 1995;122(7):502–7.CrossRefPubMedGoogle Scholar
  44. 44.
    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.CrossRefPubMedGoogle Scholar
  45. 45.
    Prieto-González S, Arguis P, García-Martínez A, Espígol-Frigolé G, Tavera-Bahillo I, Butjosa M, et al. Large vessel involvement in biopsy-proven giant cell arteritis: prospective study in 40 newly diagnosed patients using CT angiography. Ann Rheum Dis. 2012;71(7):1170–6.CrossRefPubMedGoogle Scholar
  46. 46.
    Gonzalez-Gay MA, Garcia-Porrua C, Piñeiro A, Pego-Reigosa R, Llorca J, Hunder GG. Aortic aneurysm and dissection in patients with biopsy-proven Giant cell arteritis from northwestern Spain: a population-based study. Medicine (Baltimore). 2004;83(6):335–41.CrossRefGoogle Scholar
  47. 47.
    Prior J, Ranjbar H, et al. Diagnostic delay for giant cell arteritis -a systematic review and metaanalysis. BMC Med. 2017;15:120.CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    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;33:1122–8.CrossRefPubMedGoogle Scholar
  49. 49.
    Laria A, Zoli A, Bocci M, Castri F, Federico F, Ferraccioli GF. Systematic review of the literature and a case report informing biopsy-proven giant cell arteritis(GCA) with normal C-reactive protein. Clin Rheumatol. 2012;31(9):1389–93.CrossRefPubMedGoogle Scholar
  50. 50.
    Kermani TA, Schmidt J, Crowson CS, Ytterberg SR, Hunder GG, Matteson EL, et al. Utility of erythrocyte sedimentation rate and C-reactive protein for the diagnosis of giant cell arteritis. Semin Arthritis Rheum. 2012;41(6):866–71.CrossRefPubMedGoogle Scholar
  51. 51.
    Roche NE, Fulbright JW, Wagner AD, Hunder GG, Goronzy JJ, Weyand CM. Correlation of interleukin-6 production and disease activity in polymyalgia rheumatica and giant cell arteritis. Arthritis Rheum. 1993;36(9):1286–94.CrossRefPubMedGoogle Scholar
  52. 52.
    Martinez-Taboada VM, Alvarez L, RuizSoto M, Marin-Vidalled MJ, Lopez-Hoyos M. Giant cell arteritis and polymyalgia rheumatica: role of cytokines in the pathogenesis and implications for treatment. Cytokine. 2008;44(2):207–20.CrossRefPubMedGoogle Scholar
  53. 53.
    Ball EL, Walsh SR, Tang TY, Gohil R, Clarke JM. Role of ultrasonography in the diagnosis of temporal arteritis. Br J Surg. 2010;97(12):1765–71.CrossRefPubMedGoogle Scholar
  54. 54.
    Grossman C, Barshack I, Koren-Morag N, Ben-Zvi I, Bornstein G. Baseline clinical predictors of an ultimate giant cell arteritis diagnosis in patients referred for a temporal artery biopsy. Clin Rheumatol. 2016;35:1817–22.CrossRefPubMedGoogle Scholar
  55. 55.
    Jakobsson K, Jacobsson L, Mohammad AJ, Nilsson JÅ, Warrington K, Matteson EL, et al. The effect of clinical features and glucocorticoids on biopsy findings in giant cell arteritis. BMC Musculoskelet Disord. 2016;17(1):363.CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Chatelain D, Duhaut P, Schmidt J, Bosshard S, Guernou M, Pellet H, et al. Pathological features of temporal arteries in patients with giant cell arteritis presenting with permanent visual loss. Ann Rheum Dis. 2009;68:84–8.CrossRefPubMedGoogle Scholar
  57. 57.
    Ing EB, Lahaie Luna G, Toren A, Ing R, Chen JJ, Arora N, et al. Multivariable prediction model for suspected giant cell arteritis: development and validation. Clin Ophthalmol. 2017;11:2031–42.CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Perez-Lopez J, Solans Laque R, et al. Colour-duplex ultrasonography of the temporal and ophthalmic arteries in the diagnosis and follow up of giant cell arteritis. Clin Exp Rheumatol. 2009;27:311–7.Google Scholar
  59. 59.
    Ghinoi A, Pipitone N, Nicolini A, Boiardi L, Silingardi M, Germano G, et al. Large-vessel involvement in recent onset giant cell arteritis: a case-control colour Doppler sonography study. Rheumatology (Oxford). 2012;36(9):730–4.Google Scholar
  60. 60.
    Loffler C, Hoffend J, Benck U, Kramer B, Bergner R. The value of ultrasound in diagnosing extracranial large vessel vasculitis compared to FDG-PET/CT: a retrospective study. Clin Rheumatol. 2017;36:2079–86.CrossRefPubMedGoogle Scholar
  61. 61.
    Mackie SL, Hensor EM, et al. Should I send my patient with previous giant cell arteritis for imaging of the thoracic aorta? A systematic literature review and meta-analysis. Ann Rheum Dis. Published Online First 22 Dec 2012.Google Scholar
  62. 62.
    Brodmann M, Lipp RW, Passath A, Seinost G, Pabst E, Pilger E. The role of 2-18F-fluoro-2-deoxy-d-glucose positron emission tomography in the diagnosis of giant cell arteritis of the temporal arteries. Rheumatology. 2004;43:241–2.CrossRefPubMedGoogle Scholar
  63. 63.
    Blockmans D, de Ceuninck L, et al. Repetitive 18F-fluorodeoxyglucose positron emission tomography in giant cell arteritis: a prospective study of 35 patients. Arthritis Rheum. 2006;55:131–7.CrossRefPubMedGoogle Scholar
  64. 64.
    Grayson PC, Alehashemi S, Bagheri AA, Civelek AC, 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. 2017.Google Scholar
  65. 65.
    Salvarini C, Macchioni PL, et al. Polymyalgia rheumatic and giant cell arteritis : 5 year epidemiologic and clinical study Reggio Emilia, Italy. Clin Exp Rheum. 1987;5:205.Google Scholar
  66. 66.
    Delecoeuillerie G, Joly P, Cohen de Lara A, Paolaggi JB. Polymyalgia rheumatic and temporal arteritis: a retrospective analysis of prognosis features and different corticosteroids regimens. Ann Rheum Dis. 1988;47:733–9.CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Hunder GG. Giant cell arteritis and polymyalgia rheumatica. In: Kelly WN, Harris ED, editors. Textbook of rheumatology. 5th ed. Philadelphia: WB Saunders; 1996.Google Scholar
  68. 68.
    Hoffman GS, Cid MC, Hellmann DB, Guillevin L, Stone JH, Schousboe J, et al. A multicenter, randomized, double-blind placebo-controlled trial of adjuvant methotrexate treatment for giant cell arteritis. Arthritis Rheum. 2002;46:1309–18.CrossRefPubMedGoogle Scholar
  69. 69.
    Mazlumzadeh M, Hunder GG, Easley KA, Calamia KT, Matteson EL, Griffing WL, et al. Treatment of giant cell arteritis using induction therapy with high dose glucocorticoids: a double-blind, placebo controlled, randomized prospective clinical trial. Arthritis Rheum. 2006;54:3310–8.CrossRefPubMedGoogle Scholar
  70. 70.
    Lee MS, Smith SD, et al. Antiplatelet and anticoagulation therapy in patients with giant cell arteritis. Arthritis Rheum. 2005;54:3306.CrossRefGoogle Scholar
  71. 71.
    Jover JA, Hernandez-Garcia C, et al. Combined treatment of giant cell arteritis with methotrexate and prednisone. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 2001;134:106–14.CrossRefPubMedGoogle Scholar
  72. 72.
    Spiera RF, Mitnick HJ, et al. A prospective, double-blind, randomized, placebo controlled trial of methotrexate in the treatment of giant cell arteritis. Clin Exp Rheum. 2001;19:495.Google Scholar
  73. 73.
    Mahr AD, Jover JA, et al. Adjunctive methotrexate for treatment of giant cell arteritisL an individual patient data meta-analysis. Arthritis Rheum. 2007;56:1677.CrossRefGoogle Scholar
  74. 74.
    Koster M, Matteson E, et al. Recent advances in the clinical management of giant cell arteritis and takayasu arteritis. Curr Opin Rheum. 2016;28:211–7.CrossRefGoogle Scholar
  75. 75.
    Villiger PM, Adler S, Kuchen S, Wermelinger F, Dan D, Fiege V, et al. Tocilizumab for induction and maintenance of remission in giant cell arteritis: a phase 2,randomised, double-blind, placebo-controlled trial. Lancet. 2016;387:1921–7.CrossRefPubMedGoogle Scholar
  76. 76.
    •• Stone JH, Tuckwell K, Dimonaco S, Klearman M, Aringer M, Blockmans D, et al. Trial of tocilizumab in giant cell arteritis. N Engl J Med. 2017;377:317–28. This study provided the knowledge necessary to lead to the first FDA approved treatment as steroid sparing agent in GCA. CrossRefPubMedGoogle Scholar
  77. 77.
    Langford CA, Cuthbertson D, Ytterberg SR, Khalidi N, Monach PA, Carette S, et al. A randomized, double-blind trial of Abatacept (CTLA-4Ig) for the treatment of giant cell arteritis. Arth Rheum. 2017;69:837–45.CrossRefGoogle Scholar
  78. 78.
    Matteson EL, Gold KN, Bloch DA, Hunder GG. Long term survival of patients with giant cell arteritis in the American College of Rheumatology giant cell arteritis classification criteria cohort. Am J Med. 1996;100:193–6.CrossRefPubMedGoogle Scholar
  79. 79.
    Aiello PD, Trautmann JC, McPhee TJ, Kunselman AR, Hunder GG. Visual prognosis in giant cell arteritis. Ophthalmology. 1993;100:550–5.CrossRefPubMedGoogle Scholar
  80. 80.
    Tomasson G, Peloquin C, et al. Risk for cardiovascular disease early and late after a diagnosis of giant cell arteritis: a cohort study. Ann Intern Med. 2014;160:73.CrossRefPubMedPubMedCentralGoogle Scholar

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Authors and Affiliations

  1. 1.Division of Rheumatology Louisiana State UniversityNew OrleansUSA

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