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02-04-2018 | Giant cell arteritis | Review | Article

Recent Advances in Giant Cell Arteritis

Journal: Current Rheumatology Reports

Authors: M. Guevara, C. S. Kollipara

Publisher: Springer US

Abstract

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.

Summary

This paper is a review of the recent progress in the understanding of GCA pathogenesis, diagnosis, treatment, and prognosis.
Literature
1.
Salvarini C, Macchioni P, et al. Polymyalgia rheumatic and giant cell arteritis. Lancet. 2008;372:234–45.CrossRef
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.CrossRef
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. CrossRefPubMed
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.CrossRefPubMedPubMedCentral
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.CrossRef
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.PubMed
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.CrossRefPubMedPubMedCentral
8.
Gonzales-Gay MA. Genetic epidemiology. Giant cell artheritis and polymyalgia rhuematica. Arthritis Res. 2001;3:154–7.CrossRef
9.
Renauer P, Coit P, et al. Epigenetics and vasculitis: a comprehensive review. Clin Rev Allergy Immunol. 2006;50:357.CrossRef
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.CrossRefPubMed
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.CrossRefPubMed
12.
Ly KH, Regent A, et al. Pathogenesis of giant cell arteritis: more than just an inflammatory condition? Autoimmun Rev. 2010;9:635–45.CrossRefPubMed
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.CrossRefPubMed
14.
Haugeberg G, Bie R, et al. Temporal arterirtis associated with chlamydia pneumonia DNA detected in a artery specimen. J Rheumatol. 2001;28:1738.PubMed
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.CrossRefPubMedPubMedCentral
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.CrossRefPubMed
17.
Piggott K, Biousse V, Newman NJ, Goronzy JJ, Weyand CM. Vascular damage in giant cell arteritis. Autoimmunity. 2009;42:596–604.CrossRefPubMedPubMedCentral
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMedPubMedCentral
21.
Noack M, Miossec P. Th17 and regulatory T cell balance in autoimmune and inflammatory diseases. Autoimmun Rev. 2014;13:668–77.CrossRefPubMed
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.CrossRefPubMed
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.
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.CrossRefPubMedPubMedCentral
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.CrossRefPubMed
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.
27.
Weyand CM, Goronzy JJ. Giant-cell arteritis and polymyalgia rheumatic. Ann Intern Med. 2003;139:505–15.CrossRefPubMed
28.
Galis ZS, Khathri JJ. Matrix metalloproteinases in vascular remodeling and atherogenesis: the good, the bad and the ugly. Circ Res. 2002;90:251.PubMed
29.
Weyand C, Goronzy J. Medium and large vessel vasculitis. N Engl J Med. 2003;349:160–9.CrossRefPubMed
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.CrossRefPubMed
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.CrossRef
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.CrossRef
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.CrossRef
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRef
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.CrossRefPubMed
38.
Nesher G, Breuer G, et al. Giant cell arteritis and polymyalgia Rheumatica update. Rambam Maimonides Med J. 2016;7(4):e0035.CrossRefPubMedCentral
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.PubMed
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.CrossRef
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRef
47.
Prior J, Ranjbar H, et al. Diagnostic delay for giant cell arteritis -a systematic review and metaanalysis. BMC Med. 2017;15:120.CrossRefPubMedPubMedCentral
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMed
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.CrossRefPubMedPubMedCentral
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.CrossRefPubMed
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.CrossRefPubMedPubMedCentral
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.
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.
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.CrossRefPubMed
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.
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.CrossRefPubMed
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.CrossRefPubMed
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.
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.
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.CrossRefPubMedPubMedCentral
67.
Hunder GG. Giant cell arteritis and polymyalgia rheumatica. In: Kelly WN, Harris ED, editors. Textbook of rheumatology. 5th ed. Philadelphia: WB Saunders; 1996.
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.CrossRefPubMed
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.CrossRefPubMed
70.
Lee MS, Smith SD, et al. Antiplatelet and anticoagulation therapy in patients with giant cell arteritis. Arthritis Rheum. 2005;54:3306.CrossRef
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.CrossRefPubMed
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.
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.CrossRef
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.CrossRef
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.CrossRefPubMed
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. CrossRefPubMed
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.CrossRef
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.CrossRefPubMed
79.
Aiello PD, Trautmann JC, McPhee TJ, Kunselman AR, Hunder GG. Visual prognosis in giant cell arteritis. Ophthalmology. 1993;100:550–5.CrossRefPubMed
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.CrossRefPubMedPubMedCentral