Diagnostic et extension des artérites à cellules géantes. Apport de l imagerie. Daniel Blockmans Hôpital Universitaire Gasthuisberg Leuven, Belgique

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1 Diagnostic et extension des artérites à cellules géantes. Apport de l imagerie Daniel Blockmans Hôpital Universitaire Gasthuisberg Leuven, Belgique

2 Large vessel vasculitides Giant cell arteritis Takayasu Chronic periaortitis

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5 However Sensitivity of biopsy is not 100 % : skip areas Not every clinical presentation is typical Non-cranial (large vessel) giant-cell arteritis (Brack A, et al 1999) Takayasu arteritis / chronic periaortitis : no arteries easily accessible for biopsy Poor correlation of symptoms, signs and levels of acute-phase reactants with disease activity in 1 out of 2 Takayasu patients

6 Imaging techniques used in LVV Classical angiography (showing stenosis, occlusion or aneurysm formation in latephase Takayasu) Ultrasonography CT scan MRI Isotopic techniques Gallium scintigraphy FDG-PET

7 Color duplex ultrasonography in the diagnosis of GCA Schmidt WA, et al. NEJM 1997; 37:

8 Color duplex ultrasonography in the diagnosis of GCA Schmidt WA, et al. NEJM 1997; 37:

9 Meta-Analysis Ultrasound: Sensitivity / Specificity 1 Study N=751 TA: Studies N=2036 TA:476 Sensitivity Specificity Halo 72 % 55 % 99,5 % 94 % Stenosis Occlusion 75 % 66 % 96 % 95 % All together 88 % 87 % 96 % 96 % Largest series: Schmidt WA, et al. Ann Int Med 2003;138:609 Meta-analysis: analysis: Karassa FB, et al. Ann Int Med 2005;142:359-69

10 Another Meta-Analysis 8 Studies N=575 TA:204 Sensitivity Specificity OR Halo unilateral 68 % 91 % 34 Halo bilateral 43 % 100 % 65 Arida A, et al. BMC Musculoskeletal Disorders 2010;11:44

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12 Temporal artery ultrasonography for diagnosis of GCA : the French experience Maldini Carla, et al. J Rheumatol 2010; 37:

13 Large-Vessel Giant Cell Arteritis Consecutive new patients in GCA clinic LV-GCA TA N Age <0.001 Females 83 % 65 % 0,019 AION 4 % 19 % <0.01 Time diagnosis 7.2 mo. 1.9 mo. <0.001 PMR 45 % 42 % n.s. ESR 76 mm/h 74 mm/h n.s. TA-US path. 62 % 95 % <0.001 TA-Histo path. 67 % 78 % n.s. P Schmidt WA, et al. Rheumatology 2008;47:96-101

14 Axillary Artery Ultrasound Proximal arm artery involvement in LV-GCA Wall swelling (<50%) Axillary a. 98% Subclavian a. 61% Brachial a. 21% Stenosis (>50%)( Occlusion Bilateral: 79% Schmidt WA, et al. Rheumatology 2008;47:96-101

15 Doppler ultrasound in Takayasu Detection of concentric wall thickening in the majority of patients (Sun Y et al. Stroke 1996; 27: ) Maximal wall thickness ranged from 2.0 to 4.5 mm in 9 women with active disease compared with 0.5 to 0.7 mm in 12 controls (Schmidt WA et al. Rheumatology 2002; 41: ) Wall thickness may decrease again during therapy

16 Carotidynia in Takayasu s s Arteritis acute after 3 weeks after 1 year Acute vasculitis exists Darker because of edema Steroid works quickly Schmidt WA, et al. J Rheumatol 2007;34:231-2

17 Helical aortic computed tomodensitometric scan in recent-onset GCA Agard C. et al. Arthritis Rheum 2008; 15:

18 Helical aortic computed tomodensitometric scan in recent-onset GCA Agard C., et al. Arthritis Rheum 2008; 15:

19 CT angiography in newly diagnosed GCA patients Prieto-González S, et al. Ann Rheum Dis 2012.

20 Large vessel involvement in biopsy-proven giant cell arteritis : prospective study in 40 newly diagnosed patients using CT angiography Sergio Prieto-González et al Ann Rheum Dis.

21 CT angiography in newly diagnosed GCA patients Sergio Prieto-González Ann Rheum Dis

22 CT-scan in Takayasu Enhanced CT-scan in early Takayasu : double ring pattern (inside ring represents swelling of the intima, outside ring represents active medial and adventitial inflammatory change) Visualisation of stenosis, dilatation, aneurysms, wall thickening and mural thrombus in late Takayasu; calcifications are easily detected with CT, not with MRI

23 MRI in LVV MR angiography : shows only late stages when intimal changes have occured with development of stenoses, occlusions or dilatations MRI : aortic wall thickening during the early phase (Matsunaga N et al, Radiographics 1997; 17: ) Interval between early and late phases may vary from 1 to 8 years

24 Diagnostic MRI criteria for active vasculitis wall thickening wall edema increased mural Gadolinium-contrast enhancement

25 Distribution of arterial lesions in Takayasu s arteritis and giant cell arteritis Grayson P, et al. Ann Rheum dis 2012; 71: Retrospective study on 145 patients with TAK, 62 patients with GCA from 2 cohorts : the Vasculitis Clinical Research Consortium (VCRC, 6 centers, n = 98) and the Cleveland Clinic Foundation (CCF, n = 109) Presence of abnormal arterial wall thickness was only recorded in the CCF cohort Patients with GCA underwent angiography at the discretion of the physician if there was a clinical suspicion for large vessel disease 97 % of all arterial lesions were stenotic or occlusive, 3 % of all lesions were aneurysmatic (both GCA and TAK)

26 MRA in Takayasu and GCA Grayson P, et al. Ann Rheum Dis 2012; 71:

27 Cluster analysis of arterial involvement in Takayasu arteritis reveals symmetric extension of the lesions in paired arterial beds Arnaud L, et al. Arthritis & Rheum 2011; 63: patients with TAK (9-66 years) Vascular doppler : 79,3 % CT angiography 72,0 % MRI 41,5 % Results : Stenosis : 84,1 % Wall thickening : 72,0 % Occlusion : 51,2 % Dilatation : 17,1 % Aneurysm : 12,2 % 69 % aortic lesions, > 90 % involvement of at least ons primary branch of the aortic arch All paired arterial beds clustered with their contralateral counterpart, except for the internal and external carotid arteries

28 Arnaud et al, Arthritis Rheum 2011; 63:

29 MRI in GCA Cases of sole inflammation of the superficial occipital arteries and spared superficial temporal arteries have been identified by MRI Bley TA et al. Arthritis Rheum 2005; 52: MRI can demonstrate the involvement of intracranial, extradural (e.g. middle meningeal) arteries, vertebral arteries or ophthalmic arteries in GCA Bley TA et al. Ann Rheum Dis 2009; 68: Geiger J et al. Rheumatology 2009; 48: Geiger J et al. Clin Rheumatol 2008; 27: In clinical practice, MRI can be used to identify the most inflamed artery segment, which can decrease the number of false-negative temporal artery biopsies

30 Unaffected vs. Inflamed post contrast T1-w SE, fat-sat no mural inflammation mural inflammatory changes biopsy negative, GCA excluded GCA validated by histology Bley et al., Arthritis & Rheumatism 2005

31 4-Point 3 T - + no mural enhancement slight mural enhancement prominent mural enhancement strong mural enhancement Bley et al., AJNR 2007

32 MRI vs. Clinical Diagnosis (n = 64) Sensitivity 80.6 % Specificity 97.0 % positive predictive value 96.2 % negative predictive value 84.2 % < 10 days of steroids (n = 50) 85.7 % 95.5 % 96.0 % 84.0 % Cohen`s kappa test, inter-observer agreement: substantial strength of agreement: kappa = 0.68 (CI 95% ) Bley et al., AJNR 2007

33 Angeli E, et al. The role of radiology in the diagnosis and management of Takayasu s arteritis. Journal of Nephrology 2001; 14:

34 Takayasu Arteritis : Utility and Limitations of Magnetic Resonance Imaging in Diagnosis and Treatment. 77 MRI studies in 24 Takayasu patients Patients were stratified as having either unequivocally active disease, inactive disease or uncertain disease : vessel wall edema was present in 94 % during periods of active disease but also in 56 % during clinical remission 16 patients underwent several MR studies over time. The presence of edema within vessel walls did not consistently correlate with the occurrence of new anatomical changes found on subsequent studies E. Tso et al, Arthritis Rheum. 2002; 46:

35 Tso L, Flamm SD, White RD et al, Arthritis & Rheumatism 2002; 46:

36 Inconsistencies in the presence or absence of vessel edema and subsequent anatomic changes have cast doubt on the utility of edemaweighted MR imaging as a sole guide to disease activity and treatment in TA. In this study, the greatest utility of MR was in providing a safe, noninvasive means of assessing changes in vascular anatomy. E. Tso et al, Arthritis Rheum. 2002; 46:

37 FDG-PET : Technique 18 F-fluorodeoxyglucose (FDG) is a glucose analog which is transported across the capillary and cellular membranes in proportion to the rate of glucose uptake The normal pattern of FDG-uptake includes high uptake in the brain, heart and kidneys Increased FDG-uptake can be observed in malgnant processes, but also in inflammatory conditions, eg infections, sarcoidosis, vasculitis Positron emission tomography (PET) visualizes FDG consumption throughout the body

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40 Blockmans D, et al. Am J Med 2000; 108: 246-9

41 FDG-uptake in the larger thoracic vessels has a sensitivity of 56 % specificity of 98 % positive predictive value of 93 % negative predictive value of 80 % for GCA/PR FDG-uptake in the vessels of the legs has a sensitivity of 64 % specificity of 77 % positive predictive value of 62 % negative predictive value of 79 % for GCA/PR Blockmans D, et al. Am J Med 2000; 108: 246-9

42 Tato F and Hoffmann U. J Vasc Surg 2006; 44:

43 W. Brodmann et al. Rheumatology 2004; 43:

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45 Cervical interspinous bursitis in active PMR C. Salvarani et al. Ann Rheum Dis 2008; 67:

46 PET-CT in polymyalgia Hiroyuki Yamashita, et al. Mod Rheumatol 2011.

47 Both M, et al. Ann Rheum Dis 2008; 67:

48 Meta-analysis of FDG-PET studies in GCA Besson Florent L, et al. Eur J Nucl Med Mol Imaging 2011; 38:

49 Conclusions on PET in GCA GCA frequently involves large arteries such as the thoracic and abdominal aorta, the subclavian and axillary arteries, etc.. PMR complaints in GCA patients are caused by (peri)synovitis of the shoulders, hips and processi spinosi and not by inflammation of the subclavian or axillary arteries A negative FDG-PET scan does not exclude the diagnosis of GCA (isolated cranial forms) Arthritis Rheum 2006; 55:

50 FDG-PET is probably not superior to sedimentation rate/crp for follow-up of established GCA or PMR Relapses of GCA or PMR cannot be predicted by results of former PET scintigraphies Arthritis Rheum 2006; 55: Rheumatology 2007: 46: 672-7

51 GCA is a strong risk factor for thoracic aortic dilatation, especially at the ascending aorta Those GCA patients with strong aortic FDG uptake at PET-scintigraphy may be especially prone to this complication Rheumatology 2008; 47:

52 J of Comput Assisted Tomogr 1999; 23:16-18.

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55 FDG-PET in Takayasu Earlier studies: good correlation between FDG-PET and clinical activity More recent studies: M. Webb et al, Eur J Nucl Med Mol Imaging 2004; 31: J. Andrews et al. Ann Rheum Dis 2004; 63: Y. Kobayashi et al, J Nucl Med 2005; 46: compared with disease activity assessed by NIH criteria, FDG-PET had a sensitivity of 78% and a specificity of 87% SG Lee et al, Clin Nucl Med 2009; 34: no association between FDG vascular uptake intensity and clinical, biological, or MRI assessment of disease activity L Arnaud et al, Arthritis Rheum 2009; 60:

56 FDG-PET in Takayasu Retrospective study of 53 FDG-PET scans in 38 Takayasu patients Significant association between clinical disaese activity and disease activity judged by FDG-PET (p = 0,008) at baseline In 15 followup scans, the changes in visual grade, areas of active vascular FDG uptake, and SUV intensity refelected changes in clinical disease activity Lee K-H, et al. Arthritis Rheum 2012, 64:

57 FDG-PET in Takayasu Daisuke Tezuka, et al. J Am Coll Cardiol Img 2012; 5:422-9.

58 PET in Takayasu Daisuke Tezuka, et al. J Am Coll Cardiol Img 2012; 5:422-9.

59 Derdelinckx I, et al. Acta cardiol 2000; 55: 193-5

60 Derdelinckx I, et al. Acta cardiol 2000; 55: 193-5

61 Arthritis Rheum 2005; 2:

62 Comparison of different non-invasive modalities Advantages US : Highest resolution : mm Cheap, can be repeated as often as wanted MRI : PET: good resolution : 1 mm Vessel wall edema, thickness and enhancement may point to active lesions One examination visualizes all involved arteries Highly specific for vasculitis Disadvantages US : Low sensitivities in unexperienced hands Aorta and proximal branches are hard to visualize MRI : Expensive No good relation of MRI parameters to later stenotic lesions in Takayasu PET : Expensive, not always available Bad resolution: >4 mm Temporal arteries not visible Meaning of residual FDG-uptake during steroid treatment?

63 Recommendations for clinical practice Diagnosis: typical clinical picture of GCA: perform temporal artery biopsy of clinically involved artery, or guided by ultrasound halo sign aspecific symptoms possibly due to (large vessel) GCA: perform FDG-PET scan clinical picture of PMR: treat immediately with low dose steroids or perform FDG-PET Takayasu: perform MRI and PET

64 Recommendations for clinical practice Follow-up: GCA/PMR: clinical picture and inflammatory parameters; no place for repetitive PET possible relapse of GCA/PMR: PET scan less reliable if still under steroid treatment GCA : yearly X-ray or CT-scan of thorax for detection of aortic dilatation (especially if aorta took up FDG at diagnosis?) Takayasu: no golden standard: combination of clinical symptoms, inflammatory parameters, MRI and PET results

65 Extension des artérites à cellules géantes toutes les modalitées d imagerie ont montré que les deux maladies peuvent attaquer toutes les artères de gros (et moyen) calibre Les artères contralaterales sont presque toujours atteintes, l atteinte de l aorte est continuelle Les différences entre la maladie de Horton et la maladie de Takayasu peuvent être moins importantes et seulement dûes au vieillissement de la paroi artérielle

66 Merci pour votre attention!