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Imaging of giant cell arteritis – recent advances
Abstract
Imaging is increasingly being used to guide clinical decision-making in patients with giant cell arteritis (GCA). While ultrasound has been rapidly adopted in fast-track clinics worldwide as an alternative to temporal artery biopsy for the diagnosis of cranial disease, whole-body PET/CT is emerging as a potential gold standard test for establishing large vessel involvement. However, many unanswered questions remain about the optimal approach to imaging in GCA. For example, it is uncertain how best to monitor disease activity, given there is frequent discordance between imaging findings and conventional disease activity measures, and imaging changes typically fail to resolve completely with treatment. This chapter addresses the current body of evidence for the use of imaging modalities in GCA across the spectrum of diagnosis, monitoring disease activity, and long-term surveillance for structural changes of aortic dilatation and aneurysm formation and provides suggestions for future research directions.
... For both diseases, no consensus exists on the definition of remission or relapse, and studies informing the measurement properties of routinely employed disease activity instruments are lacking [7,8]. Despite its clear potential utility, substantive questions exist about the routine use of imaging for monitoring either disease [9]. The artificial impact of common therapies on systemic inflammatory markers and imaging, independent of actual disease activity, complicates this further. ...
Objective
Blindness is a feared complication of giant cell arteritis (GCA). However, the spectrum of pathologic orbital imaging findings on magnetic resonance imaging (MRI) in GCA is not well understood. In this study, we assess inflammatory changes of intraorbital structures on black blood MRI (BB-MRI) in patients with GCA compared to age-matched controls.
Methods
In this multicenter case-control study, 106 subjects underwent BB-MRI. Fifty-six patients with clinically or histologically diagnosed GCA and 50 age-matched controls without clinical or laboratory evidence of vasculitis were included. All individuals were imaged on a 3-T MR scanner with a post-contrast compressed-sensing (CS) T1-weighted sampling perfection with application-optimized contrasts using different flip angle evolution (SPACE) BB-MRI sequence. Imaging results were correlated with available clinical symptoms.
Results
Eighteen of 56 GCA patients (32%) showed inflammatory changes of at least one of the intraorbital structures. The most common finding was enhancement of at least one of the optic nerve sheaths ( N = 13, 72%). Vessel wall enhancement of the ophthalmic artery was unilateral in 8 and bilateral in 3 patients. Enhancement of the optic nerve was observed in one patient. There was no significant correlation between imaging features of inflammation and clinically reported orbital symptoms ( p = 0.10). None of the age-matched control patients showed any inflammatory changes of intraorbital structures.
Conclusions
BB-MRI revealed inflammatory findings in the orbits in up to 32% of patients with GCA. Optic nerve sheath enhancement was the most common intraorbital inflammatory change on BB-MRI. MRI findings were independent of clinically reported orbital symptoms.
Key Points
• Up to 32% of GCA patients shows signs of inflammation of intraorbital structures on BB-MRI.
• Enhancement of the optic nerve sheath is the most common intraorbital finding in GCA patients on BB-MRI.
• Features of inflammation of intraorbital structures are independent of clinically reported symptoms.
Objective
To develop and validate updated classification criteria for giant cell arteritis (GCA).
Methods
Patients with vasculitis or comparator diseases were recruited into an international cohort. The study proceeded in six phases: (1) identification of candidate items, (2) prospective collection of candidate items present at the time of diagnosis, (3) expert panel review of cases, (4) data‐driven reduction of candidate items, (5) derivation of a points‐based risk classification score in a development data set and (6) validation in an independent data set.
Results
The development data set consisted of 518 cases of GCA and 536 comparators. The validation data set consisted of 238 cases of GCA and 213 comparators. Age ≥50 years at diagnosis was an absolute requirement for classification. The final criteria items and weights were as follows: positive temporal artery biopsy or temporal artery halo sign on ultrasound (+5); erythrocyte sedimentation rate ≥50 mm/hour or C reactive protein ≥10 mg/L (+3); sudden visual loss (+3); morning stiffness in shoulders or neck, jaw or tongue claudication, new temporal headache, scalp tenderness, temporal artery abnormality on vascular examination, bilateral axillary involvement on imaging and fluorodeoxyglucose–positron emission tomography activity throughout the aorta (+2 each). A patient could be classified as having GCA with a cumulative score of ≥6 points. When these criteria were tested in the validation data set, the model area under the curve was 0.91 (95% CI 0.88 to 0.94) with a sensitivity of 87.0% (95% CI 82.0% to 91.0%) and specificity of 94.8% (95% CI 91.0% to 97.4%).
Conclusion
The 2022 American College of Rheumatology/EULAR GCA classification criteria are now validated for use in clinical research.
Objective
To develop and validate updated classification criteria for giant cell arteritis (GCA).
Methods
Patients with vasculitis or comparator diseases were recruited into an international cohort. The study proceeded in 6 phases: 1) identification of candidate items, 2) prospective collection of candidate items present at the time of diagnosis, 3) expert panel review of cases, 4) data‐driven reduction of candidate items, 5) derivation of a points‐based risk classification score in a development data set, and 6) validation in an independent data set.
Results
The development data set consisted of 518 cases of GCA and 536 comparators. The validation data set consisted of 238 cases of GCA and 213 comparators. Age ≥50 years at diagnosis was an absolute requirement for classification. The final criteria items and weights were as follows: positive temporal artery biopsy or temporal artery halo sign on ultrasound (+5); erythrocyte sedimentation rate ≥50 mm/hour or C‐reactive protein ≥10 mg/liter (+3); sudden visual loss (+3); morning stiffness in shoulders or neck, jaw or tongue claudication, new temporal headache, scalp tenderness, temporal artery abnormality on vascular examination, bilateral axillary involvement on imaging, and fluorodeoxyglucose–positron emission tomography activity throughout the aorta (+2 each). A patient could be classified as having GCA with a cumulative score of ≥6 points. When these criteria were tested in the validation data set, the model area under the curve was 0.91 (95% confidence interval [95% CI] 0.88–0.94) with a sensitivity of 87.0% (95% CI 82.0–91.0%) and specificity of 94.8% (95% CI 91.0–97.4%).
Conclusion
The 2022 American College of Rheumatology/EULAR GCA classification criteria are now validated for use in clinical research.
Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are two interrelated inflammatory diseases affecting patients above 50 years of age. Patients with GCA suffer from granulomatous inflammation of medium- to large-sized arteries. This inflammation can lead to severe ischemic complications (e.g., irreversible vision loss and stroke) and aneurysm-related complications (such as aortic dissection). On the other hand, patients suffering from PMR present with proximal stiffness and pain due to inflammation of the shoulder and pelvic girdles. PMR is observed in 40–60% of patients with GCA, while up to 21% of patients suffering from PMR are also affected by GCA. Due to the risk of ischemic complications, GCA has to be promptly treated upon clinical suspicion. The treatment of both GCA and PMR still heavily relies on glucocorticoids (GCs), although novel targeted therapies are emerging. Imaging has a central position in the diagnosis of GCA and PMR. While [18F]fluorodeoxyglucose (FDG)-positron emission tomography (PET) has proven to be a valuable tool for diagnosis of GCA and PMR, it possesses major drawbacks such as unspecific uptake in cells with high glucose metabolism, high background activity in several non-target organs and a decrease of diagnostic accuracy already after a short course of GC treatment. In recent years, our understanding of the immunopathogenesis of GCA and, to some extent, PMR has advanced. In this review, we summarize the current knowledge on the cellular heterogeneity in the immunopathology of GCA/PMR and discuss how recent advances in specific tissue infiltrating leukocyte and stromal cell profiles may be exploited as a source of novel targets for imaging. Finally, we discuss prospective novel PET radiotracers that may be useful for the diagnosis and treatment monitoring in GCA and PMR.
Objectives:
There are limited data on the additional diagnostic yield of axillary artery ultrasound (axUS) in addition to temporal artery ultrasound (tempUS) for the diagnosis of giant cell arteritis (GCA).
Methods:
Retrospective study of consecutive patients with suspected GCA who underwent a standardized axUS and tempUS between 01/2015 and 03/2017. The diagnostic yield of axUS in addition to ultrasound of the temporal arteries with respect to the final clinical diagnosis was assessed, with a positive axUS defined as circumferential, hypoechogenic thickening of the far wall axillary artery intima media thickness (axIMT) ≥1.3 mm. A subgroup of patients underwent PET-CT within one week before or after the sonographic study. Separate analyses were performed regarding certain subgroups according to clinical presentation and to clinical pre-test probability for cranial GCA.
Results:
Out of 228 patients, 92 received a final diagnosis of GCA. From the 92 patients with a final diagnosis of GCA, 50 (54.3%), 13 (14.1%) and 15 (16.3%) had a positive tempUS, positive axUS, and combined positive tempUS and axUS, respectively. The sensitivity of sonographic imaging for the final diagnosis of GCA increased from 69.6% to 84.8%, when axUS results were considered in addition to tempUS, while the specificity remained high (no false positive axUS). The diagnostic yield of axUS was highest in patients with a low clinical probability of cranial GCA and lowest in patients with symptoms of ocular ischemia. We observed a substantial rate (42.1%) of discordant results between axUS and PET-CT in a subgroup of 38 patients.
Conclusions:
In conclusion, axUS offers a substantial diagnostic yield in addition to tempUS in subjects with suspected GCA, mainly in those subjects with low clinical probability for cranial GCA.
Objective:
To evaluate the diagnostic performance of an extended ultrasound protocol in patients referred under the suspicion of giant cell arteritis (GCA).
Methods:
Consecutive patients with suspected GCA were examined with an extended color duplex ultrasound (CDU) protocol during a period of 2 years. The extended CDU protocol included temporal, axillary, subclavian, brachiocephalic, and carotid arteries. The reference was clinically diagnosed GCA, confirmed after ≥6-month follow-up. Hypo- or medium-echogenic, circumferential, homogenous wall thickening, and/or a positive compression sign in temporal arteries, were regarded as typical signs of arteritis.
Results:
Of the eligible 201 patients, 83 (41%) received a clinical GCA diagnosis at follow-up ≥6 months post CDU examination. Among these cases, 48 (58%) demonstrated inflammation solely in temporal arteries, 8 (10%) showed abnormalities restricted to extra-cranial vessels, and 23 (28%) patients displayed inflammatory changes in both temporal and extra-cranial arteries. Color duplex ultrasound of temporal arteries yielded a diagnostic sensitivity and specificity [95% confidence intervals (CI)] of 86% (76-92%) and 99% (95-99%), respectively. By adding axillary artery examination, the sensitivity increased to 92% (83-97%) while the specificity remained unchanged. Further, inclusion of subclavian artery marginally increased the sensitivity by 1%. Finally, by also including brachiocephalic and common carotid arteries resulted in a sensitivity of 95% (88-99%) and a specificity of 98% (94-99%).
Conclusions:
Color duplex ultrasound examination demonstrated a high accuracy in diagnosing patients both with cranial and extra-cranial GCA. Further examination of brachiocephalic and common carotid arteries can increase the sensitivity without affecting the specificity when temporal and axillary findings are indecisive. Finally, the extended CDU protocol allows measurement of the general burden of inflammation, which could be relevant for future monitoring purposes.
Aims:
To describe the feasibility and diagnostic accuracy of 18F-FDG positron emission tomography-computed tomography (PET/CT) of the temporal artery compared with temporal artery ultrasound and histology of the temporal artery in patients with suspicion of having giant cell arteritis (GCA).
Materials and methods:
Patients with suspected GCA were included. PET/CT standard uptake value ratios and the compression sign on ultrasound were assessed for the trunk, and parietal and frontal branches of the temporal artery. Temporal artery biopsies were systematically re-assessed, if available.
Results:
In 17/34 patients, GCA was confirmed. Temporal artery PET/CT confirmed vasculitis in 9/17 patients and was negative in all 17 controls. Nineteen of 34 subjects had a temporal artery biopsy, which was positive in 7 patients. Five of these seven were negative in the preceding PET/CT. Ultrasound confirmed vasculitis in 9/17 patients and was negative in 16/17 controls. In 7/17 patients, PET/CT and ultrasound were positive for temporal arteritis. Two patients had positive findings only on temporal artery PET/CT and two patients showed vasculitis only on temporal artery ultrasound. No temporal artery segments <1.4 mm were positive on PET/CT. The parietal branches were PET/CT-positive in two patients only. In contrast, on ultrasound vasculitic findings were equally distributed amongst all branches. Sensitivity and specificity for identification of temporal artery involvement was 53% and 100% for PET/CT, and 53% and 94% for ultrasound, respectively.
Conclusions:
Assessment of the temporal artery with PET/CT is a valuable extension in the diagnostic workup for GCA. PET/CT and ultrasound have comparable diagnostic accuracy, but differ on a segment and a patient level and may thus be used as complementary tests. PET/CT has a lower sensitivity for the parietal branch than ultrasound and histology.
Objectives
To characterize the effect of ultra-short glucocorticoids followed by Tocilizumab monotherapy on the intima-media thickness (IMT) in GCA.
Methods
18 GCA patients received 500mg methylprednisolone intravenously on days 0-2, followed by Tocilizumab (8mg/kg) intravenously on day 3 and thereafter weekly subcutaneous Tocilizumab injections (162 mg) over 52 weeks. Ultrasound of temporal (TA), axillary (AA) and subclavian (SA) arteries was performed at baseline, on days 2-3, at week 4, 8, 12, 24 and 52. The largest IMT of all segments and IMT at landmarks of AA/SA were recorded. IMT was scaled by mean normal values and averaged. Each segment was classified according to diagnostic cut-offs.
Results
16 patients had TA and 6 had extracranial large artery involvement. The IMT showed a sharp decline on day 2/3 in the TA and AA/SA. In TA, this was followed by an increase to baseline levels at week 4 and a subsequent slow decrease, which was paralleled by decreasing symptoms and achievement of clinical remission. The AA/SA showed a new signal of vasculitis at week 4 in three patients with an IMT increase up to week 8.
Conclusions
Glucocorticoid pulse therapy induced a transient decrease of the IMT in TA and AA/SA. Tocilizumab monotherapy resulted in a slow and steady decrease in IMT of the TA and a smaller and delayed effect on the AA/SA. The data strongly support a remission-inducing effect of Tocilizumab and argue for an important role of ultrasound in monitoring disease activity in GCA.
The large vessel vasculitides comprise giant cell arteritis (GCA), Takayasu arteritis (TAK), and chronic periaortitis. The diagnostic approach to these conditions involves the correct use and interpretation of clinical criteria, imaging techniques, and, in case of GCA, temporal artery biopsy. Ultrasound, magnetic resonance imaging (MRI), and computed tomography (CT) reveal a homogeneous, concentric, thickening of the arterial wall. MRI and CT may also reveal aneurysms and stenoses. 18F-Fluorodeoxyglucose (FDG)-PET shows increased FDG uptake of inflamed artery walls delineating increased metabolic activity. Ultrasound, FDG-PET, and MRI are the recommended imaging techniques in GCA and TAK. In patients with a high suspicion of GCA who present with visual disturbances, initiation of high-dose intravenous corticosteroids should not be delayed by imaging. Extracranial large vessel vasculitis may be confirmed by all three modalities, particularly by FDG-PET in case of atypical clinical pictures. In this article, we review the role of the GCA and TAK ACR classification criteria, temporal artery biopsy, conventional angiography, ultrasound, MRI, magnetic resonance angiography (MRA), CT angiography (CTA), and FDG-PET in the diagnostic approach of large vessel vasculitis.
Purpose
Monitoring disease activity in patients with large vessel vasculitis (LVV) can be challenging. [18F]FDG-PET/CT is increasingly used to evaluate treatment response in LVV. In this systematic review and meta-analysis, we aimed to summarize the current evidence on the value of [18F]FDG-PET/CT for treatment monitoring in LVV.
Methods
PubMed/MEDLINE and the Cochrane library database were searched from inception through October 21, 2020. Studies containing patients with LVV (i.e. giant cell arteritis, Takayasu arteritis and isolated aortitis) that received treatment and underwent [18F]FDG-PET/CT were included. Screening, full-text review and data extraction were performed by 2 investigators. The risk of bias was examined with the QUADAS-2 tool. Meta-analysis of proportions and diagnostic test accuracy was performed by a random-effects model and bivariate model, respectively.
Results
Twenty-one studies were included in the systematic review, of which 8 studies were eligible for meta-analysis. Arterial [18F]FDG uptake decreased upon clinical remission in longitudinal studies. High heterogeneity ( I ² statistic 94%) precluded meta-analysis of the proportion of patients in which the scan normalized during clinical remission. Meta-analysis of cross-sectional studies indicated that [18F]FDG-PET/CT may detect relapsing/refractory disease with a sensitivity of 77% (95%CI 57–90%) and specificity of 71% (95%CI 47–87%). Substantial heterogeneity was observed among the cross-sectional studies. Both variation in clinical aspects and imaging procedures contributed to the heterogeneity.
Conclusion
Treatment of LVV leads to reduction of arterial [18F]FDG uptake during clinical remission. [18F]FDG-PET/CT has moderate diagnostic accuracy for detecting active LVV. [18F]FDG-PET/CT may aid treatment monitoring in LVV, but its findings should be interpreted in the context of the clinical suspicion of disease activity. This study underlines the relevance of published procedural recommendations for the use of [18F]FDG-PET/CT in LVV.
Imaging is becoming increasingly important for the diagnosis of large vessel vasculitis (LVV). Atherosclerosis may be difficult to distinguish from LVV on imaging as both are inflammatory conditions of the arterial wall. Differentiating atherosclerosis from LVV is important to enable optimal diagnosis, risk assessment, and tailored treatment at a patient level. This paper reviews the current evidence of ultrasound (US), 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography (FDG-PET), computed tomography (CT), and magnetic resonance imaging (MRI) to distinguish LVV from atherosclerosis. In this review, we identified a total of eight studies comparing LVV patients to atherosclerosis patients using imaging—four US studies, two FDG-PET studies, and two CT studies. The included studies mostly applied different methodologies and outcome parameters to investigate vessel wall inflammation. This review reports the currently available evidence and provides recommendations on further methodological standardization methods and future directions for research.
Background
Giant cell arteritis (GCA) is frequently associated with aortic involvement that is likely to cause life-threatening structural complications (aneurysm, dissection). Few studies have investigated the occurrence of these complications, and no predictive factor has been identified so far. The aim of this study was to investigate factors associated with the risk of aortic complications in a cohort of GCA aortitis.
Methods
Data of all patients managed with aortitis (CT or 18 FDG PET) at the diagnosis of GCA in five hospitals from May 1998 and April 2019 were retrospectively collected. Clinical features were compared according to the presence of aortitis symptoms. The predictive factors of occurrence or aggravation of aortic structural abnormalities were investigated.
Results
One hundred and seventy-one patients with GCA aortitis were included; 55 patients (32%) had symptoms of aortitis (dorsal/lumbar/abdominal pain, aortic insufficiency) at diagnosis. The median follow-up was 38 months. Aortic complications occurred after a median time of 32 months. There were 19 new aortic aneurysms or complications of aneurysm and 5 dissections. Survival without aortic complication was significantly different between the symptomatic and non-symptomatic groups (Log rank, p = 0.0003). In multivariate analysis the presence of aortitis symptoms at diagnosis (HR 6.64 [1.95, 22.6] p = 0.002) and GCA relapse (HR 3.62 [1.2, 10.9] p = 0.02) were factors associated with the occurrence of aortic complications.
Conclusion
In this study, the presence of aortitis symptoms at the diagnosis of GCA aortitis and GCA relapse were independent predictive factors of occurrence of aortic complications during follow-up.
Objectives
Predictive data for the development of aortic dilatation (AD) in giant-cell arteritis (GCA) are controversial. The aim was to investigate by computed tomography (CT) the prevalence of AD in a consecutive cohort of GCA patients and controls, and to identify possible predictors for AD.
Methods
GCA patients and controls were identified by electronic search and underwent aortic contrast enhanced CT defining AD by aortic diameter adjusted to age, gender and body surface area. Pulse-wave velocity, intima-media thickness (IMT) and laboratory studies including lymphocyte subsets were conducted identifying potential factors associated with AD. Clinical and laboratory parameters at disease onset, occurrence of aortic rupture/dissection before and up to five years after study visit were retrieved by chart review.
Results
144 GCA patients and 115 controls were included. GCA patients developed more frequently AD of the ascending and thoracic descending aorta compared to controls (OR 2.60, p = 0.016; OR 3.65, p = 0.005, respectively). Factors associated with AD development of thoracic descending aorta, but not of the ascending aorta, were higher percentages of circulating CD3+CD4+ cells, higher CD4/CD8 ratio, presence of polymyalgia rheumatica and increased carotid IMT at disease onset (OR range 1.10-3.11, all with p < 0.05). During follow-up, no GCA patient required surgical aortic repair or suffered aortic rupture/dissection.
Conclusions
Thoracic but not abdominal ADs occur more commonly in GCA patients, however, the subsequent risk for aortic repair, rupture or dissection is low. Changes of T-cell subsets, presence of polymyalgia rheumatica and increased carotid IMT at disease onset are associated with AD development.
Background and aim
Assessing cranial artery inflammation plays an important role in the diagnosis of cranial giant cell arteritis (C-GCA). However, current diagnostic tests are limited. The use of fluorine-18-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT imaging is an established tool for assessing large vessel inflammation but is currently not used for assessment of the cranial arteries. This study aimed to evaluate the accuracy of FDG-PET/CT in the diagnosis of biopsy proven C-GCA and its relation to clinical presentation.
Methods
This retrospective case control study included temporal artery biopsy (TAB) positive C-GCA patients and age- and sex-matched controls. FDG-PET/CT scans were performed according to EANM/EARL guidelines, visually assessed by an experienced nuclear medicine physician, and semiquantitatively assessed using the maximum standardised uptake value (SUVmax). The visual and semiquantitative assessments were performed on the temporal arteries, maxillary arteries, vertebral arteries, and occipital arteries. Clinical signs and symptoms were scored for comparison.
Results
A total of 24 C-GCA patients and 24 controls were included in the study. Visual analysis revealed an 83% sensitivity and a 75% specificity. Receiver operating characteristic (ROC) analysis of the semiquantitative assessment revealed a 79% sensitivity and a 92% specificity when measuring SUVmax in the cranial arteries. Visual and semiquantitative assessments showed moderate agreement (Fleiss kappa 0.55). There was a positive correlation between the number of cranial symptoms and the SUVmax in the vertebral artery.
Conclusion
FDG-PET/CT can reliably diagnose C-GCA by assessing cranial artery inflammation using SUVmax. Extending the use of FDG-PET/CT to include assessment of the cranial arteries may improve its diagnostic value in GCA and provide a suitable alternative to TAB. Moderate agreement between visual and semiquantitative assessment methods suggest diagnostic accuracy may be improved by further standardisation.
Objectives:
To compare colour duplex ultrasonography (CDU) findings with axillary 18F-fluorodeoxyglucose (FDG) PET/CT findings and to compare the diagnostic performance of temporal and axillary artery CDU with temporal artery CDU alone.
Methods:
Patients suspected of GCA were retrospectively included. Presence of a halo or occlusion was considered a positive CDU finding. FDG-PET/CT-assessed axillary artery involvement was defined as axillary artery FDG uptake higher than liver uptake. The reference was the clinical diagnosis after 6 months, which was based on symptomatology and additional diagnostic tests, with the exception of CDU.
Results:
Of the 113 included patients, GCA was diagnosed in 41. Twenty-eight out of 41 GCA patients underwent a FDG-PET/CT. FDG-PET-assessed extra-cranial GCA was present in 20/41 patients, of which 13 showed axillary involvement on FDG-PET/CT. An axillary halo was found in eight of these 13 patients. Six out of the 20 patients with FDG-PET-assessed GCA showed no axillary involvement on CDU or FDG-PET/CT. Five of them had single artery involvement on FDG-PET/CT (two aorta; three vertebral artery). One patient had an axillary occlusion on CDU, consistent with FDG-PET/CT results. Overall, sensitivity and specificity of temporal artery CDU was 52% (95% CI: 35, 67) and 93% (95% CI: 84, 97), respectively. Adding axillary artery results improved sensitivity to 71% (95% CI: 55, 84), while specificity did not change.
Conclusion:
Presence of an axillary halo or occlusion on CDU is consistent with axillary artery FDG-PET/CT results, but a negative CDU does not rule out axillary involvement. Adding axillary artery assessment to temporal artery assessment may substantially increase the diagnostic performance of CDU.
Background:
Sometimes, the underlying causes of inflammation cannot be established despite meticulous investigation, including medical history, physical examination, laboratory tests, and radiologic procedures. Rheumatologists are often faced with patients whose condition is known as inflammation of unknown origin (IUO). Differential diagnosis of IUO is diverse, and investigation of these cases is challenging and time-consuming.
Objective:
The study aimed to assess the diagnostic role of positron emission tomography/computed tomography (PET/CT) in the evaluation of patients with IUO.
Methods:
The study sample consisted of 97 adult patients with IUO who have not been previously diagnosed with an infectious, inflammatory, or malignant disease. The necessary data were collected from January 2015 to June 2018 with a 6-month follow-up period. The patients were screened using PET/CT after a specific diagnosis could not be established with detailed laboratory and radiologic evaluations.
Results:
A final diagnosis was established at follow-up, and 47 (54%) of the 97 patients had inflammatory diseases, 30 (34.4%) had malignancies, and 10 (11.4%) had infections. Despite meticulous investigation, 10 patients were left undiagnosed in the follow-up. PET/CT aided diagnosis in 59 patients (60.8%), but it was not helpful in 38 patients (39.2%). PET/CT was positive in 30 (63%) of the 47 patients with inflammatory diseases, whose final diagnosis was inflammatory rheumatic disease, as follows: large-vessel vasculitis in 19 patients, polymyalgia rheumatica in 7 patients, and seronegative arthritis or other rare miscellaneous diseases in 4 patients. The sensitivity of PET/CT was 67% with a specificity and diagnostic accuracy of 100% and 71%, respectively.
Conclusions:
Investigation of the underlying etiology of IUO is time-consuming and challenging. PET/CT may help identify the final diagnosis more quickly by locating an obscure inflammatory site; thus, it may reduce the number of unnecessary biopsies, diagnostic time, anxiety, work loss, morbidity, and mortality.
PurposeTo evaluate the sensitivity and specificity of PET/CT findings in PMR and generate a diagnostic algorithm utilizing a minimum number of musculoskeletal sites.Methods
Steroid-naïve patients with newly diagnosed PMR (2012 EULAR/ACR classification criteria) were prospectively recruited to undergo whole-body 18F−FDG PET/CT. Each PMR case was age- and sex-matched to four PET/CT controls. Control scan indication, diagnosis and medical history were extracted from the clinical record. Qualitative and semi-quantitative scoring (maximum standardized uptake value [SUVmax]) of abnormal 18F-FDG uptake at 21 musculoskeletal sites was undertaken for cases and controls. Results informed the development of a novel PET/CT diagnostic algorithm using a classification and regression trees (CART) method.ResultsThirty-three cases met the inclusion criteria and were matched to 132 controls. Mean age was 68.6 ± 7.4 years for cases compared with 68.2 ± 7.3 for controls, and 54.5% were male. Median CRP was 49 mg/L (32–65) and ESR 41.5 mm/h (24.6–64.4) in the PMR group. The predominant control indication for PET/CT was malignancy (63.6%). Individual musculoskeletal sites proved insufficient for diagnostic purposes. A novel algorithm comprising 18F-FDG uptake ≥ 2 adjacent to the ischial tuberosities in combination with either abnormalities at the peri-articular shoulder or interspinous bursa achieved a sensitivity of 90.9% and specificity of 92.4% for diagnosing PMR.Conclusions
The presence of abnormal 18F-FDG uptake adjacent to the ischial tuberosities together with findings at the peri-articular shoulder or interspinous bursa on whole-body PET/CT is highly sensitive and specific for a diagnosis of PMR.Trial registrationClinical Trial Registration: Australian New Zealand Clinical Trials Registry, http://www.anzctr.org.au, ACTRN1261400696695
Objectives
To analyse the current evidence for the management of large vessel vasculitis (LVV) to inform the 2018 update of the EULAR recommendations.
Methods
Two systematic literature reviews (SLRs) dealing with diagnosis/monitoring and treatment strategies for LVV, respectively, were performed. Medline, Embase and Cochrane databases were searched from inception to 31 December 2017. Evidence on imaging was excluded as recently published in dedicated EULAR recommendations. This paper focuses on the data relevant to giant cell arteritis (GCA).
Results
We identified 287 eligible articles (122 studies focused on diagnosis/monitoring, 165 on treatment). The implementation of a fast-track approach to diagnosis significantly lowers the risk of permanent visual loss compared with historical cohorts (level of evidence, LoE 2b). Reliable diagnostic or prognostic biomarkers for GCA are still not available (LoE 3b).
The SLR confirms the efficacy of prompt initiation of glucocorticoids (GC). There is no high-quality evidence on the most appropriate starting dose, route of administration, tapering and duration of GC (LoE 4). Patients with GCA are at increased risk of dose-dependent GC-related adverse events (LoE 3b). The addition of methotrexate or tocilizumab reduces relapse rates and GC requirements (LoE 1b). There is no consistent evidence that initiating antiplatelet agents at diagnosis would prevent future ischaemic events (LoE 2a). There is little evidence to guide monitoring of patients with GCA.
Conclusions
Results from two SLRs identified novel evidence on the management of GCA to guide the 2018 update of the EULAR recommendations on the management of LVV.
Background
Since the publication of the European League Against Rheumatism (EULAR) recommendations for the management of large vessel vasculitis (LVV) in 2009, several relevant randomised clinical trials and cohort analyses have been published, which have the potential to change clinical care and therefore supporting the need to update the original recommendations.
Methods
Using EULAR standardised operating procedures for EULAR-endorsed recommendations, the EULAR task force undertook a systematic literature review and sought opinion from 20 experts from 13 countries. We modified existing recommendations and created new recommendations.
Results
Three overarching principles and 10 recommendations were formulated. We recommend that a suspected diagnosis of LVV should be confirmed by imaging or histology. High dose glucocorticoid therapy (40–60 mg/day prednisone-equivalent) should be initiated immediately for induction of remission in active giant cell arteritis (GCA) or Takayasu arteritis (TAK). We recommend adjunctive therapy in selected patients with GCA (refractory or relapsing disease, presence of an increased risk for glucocorticoid-related adverse events or complications) using tocilizumab. Methotrexate may be used as an alternative. Non-biological glucocorticoid-sparing agents should be given in combination with glucocorticoids in all patients with TAK and biological agents may be used in refractory or relapsing patients. We no longer recommend the routine use of antiplatelet or anticoagulant therapy for treatment of LVV unless it is indicated for other reasons.
Conclusions
We have updated the recommendations for the management of LVV to facilitate the translation of current scientific evidence and expert opinion into better management and improved outcome of patients in clinical practice.
Objective
The purpose of our study was to assess the diagnostic performance of ¹⁸F-FDG PET-CT for large vessel involvement in patients with suspected giant cells arteritis (GCA) and a negative temporal artery biopsy (TAB).
Methods
We conducted a retrospective study in a cohort of patients with suspected GCA and negative TAB who underwent an ¹⁸F-FDG PET-CT. Ten vascular segments were studied using a visual score and a semi-quantitative method based on SUVmax ratio with respect to liver uptake. The diagnosis of GCA was established during a mean follow-up of 42 months, based on the presence of clinical symptoms, laboratory results, and imaging data compatible with GCA, good response to corticosteroid therapy, and no differential diagnosis after a follow-up of at least 18 months.
Results
We included 63 patients (30 men and 33 women, aged 67 ± 12 years). ¹⁸F-FDG PET-CT showed large vessel involvement in 22 patients, 14 of whom were finally diagnosed with GCA. Forty-one patients were ¹⁸F-FDG PET-CT negative, 9 of whom were finally diagnosed with GCA. Overall, ¹⁸F-FDG uptake by large vessel yielded 61% sensitivity, 80% specificity, 64% positive predictive value, 78% negative predictive value, and 73% diagnostic accuracy. A significant number of patients were treated by corticosteroids before ¹⁸F-FDG PET-CT. However, corticosteroid therapy did not impact significantly the diagnostic performance, although there was a trend to a lower sensitivity in patients receiving corticosteroid therapy for more than 3 days.
Conclusions
¹⁸F-FDG PET-CT is a useful imaging technique to assess large vessel involvement in patients with suspected GCA and negative TAB.
Objective
The OMERACT Vasculitis Working Group seeks to develop validated outcome measures for use in trials for large-vessel vasculitis (LVV).
Methods
An international Delphi exercise conducted among investigators identified items considered important to measure active disease. In parallel, qualitative research with patients was conducted, including interviews and focus groups.
Results
Next steps prioritized by the group for LVV include i) defining disease states (remission, flare, and patient-acceptable symptom state); and ii) selection of patientreported outcome tools.
Conclusion
The ultimate goal is to develop an OMERACT-endorsed Core Set of outcome measures for use in clinical trials of LVV.
Objective
Positron emission tomography/computed tomography (PET/CT) has not been well studied as a first‐line test for giant cell arteritis (GCA), due, in part, to historical limitations in visualizing the cranial arteries. The Giant Cell Arteritis and PET Scan (GAPS) study was therefore carried out to assess the accuracy of a newer generation PET/CT of the head, neck, and chest for determining a diagnosis of GCA.
Methods
In the GAPS study cohort, 64 patients with newly suspected GCA underwent time‐of‐flight PET/CT (1‐mm slice thickness from the vertex to diaphragm) within 72 hours of starting glucocorticoids and before undergoing temporal artery biopsy (TAB). Two physicians with experience in PET reviewed the patients’ scans in a blinded manner and reported the scans as globally positive or negative for GCA. Tracer uptake was graded across 18 artery segments. The clinical diagnosis was confirmed at 6 months’ follow‐up.
Results
In total, 58 of 64 patients underwent TAB, and 12 (21%) of the biopsies were considered positive for GCA. Twenty‐one patients had a clinical diagnosis of GCA. Compared to TAB, the sensitivity of PET/CT for a diagnosis of GCA was 92% (95% confidence interval [95% CI] 62–100%) and specificity was 85% (95% CI 71–94%). The negative predictive value (NPV) was 98% (95% CI 87–100%). Compared to clinical diagnosis, PET/CT had a sensitivity of 71% (95% CI 48–89%) and specificity of 91% (95% CI 78–97%). Interobserver reliability was moderate (κ = 0.65). Among the enrolled patients, 20% had a clinically relevant incidental finding, including 7 with an infection and 5 with a malignancy. Furthermore, 5 (42%) of 12 TAB‐positive GCA patients had moderate or marked aortitis.
Conclusion
The high diagnostic accuracy of this PET/CT protocol would support its use as a first‐line test for GCA. The NPV of 98% indicates the particular utility of this test in ruling out the condition in patients considered to be at lower risk of GCA. PET/CT had benefit over TAB in detecting vasculitis mimics and aortitis.
Purpose of the review
The two main forms of large-vessel vasculitis (LVV) are giant cell arteritis (GCA) and Takayasu’s arteritis (TAK). Vascular imaging can characterize disease activity and disease extent in LVV. This review critically analyzes the clinical utility of vascular imaging in LVV and highlights how imaging may be incorporated into the management and study of these conditions.
Recent findings
There are multiple imaging modalities available to assess LVV including ultrasonography, CT angiography (CTA), magnetic resonance angiography (MRA), and ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET). As these techniques are refined, imaging may be increasingly useful to evaluate the cranial arteries and the aorta and its primary branches. In addition, vascular imaging may be useful to monitor disease activity and may have prognostic value to predict future clinical events.
Summary
There are strengths and weaknesses associated with vascular imaging that should be considered when evaluating patients with LVV. Vascular imaging will likely play an increasingly important role in the clinical management of patients and the conduct of research in LVV and may ultimately be incorporated as outcome measures in clinical trials in these conditions.
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Arterial involvement is the cardinal feature of large-vessel vasculitis (LVV) and prevention of disease progression is the principal therapeutic goal. However, development of tools for its evaluation represents a major unmet need. To address this, a widely-applicable imaging tool for LVV, analysing arterial involvement in 17 arterial territories, has been developed and validated. Individual stenosis and dilation scores were generated and combined in a composite score. The methodology was validated cross-sectionally and longitudinally in 131 patients, 96 Takayasu arteritis (TA), 35 large-vessel giant-cell arteritis (LV-GCA). In total, 4420 arterial segments from 260 imaging studies were evaluated. The new scores allowed quantitative grading of LVV arterial involvement with high consistency, revealing inter-patient differences. TA had higher stenosis and composite scores and lower dilation scores than LV-GCA. Baseline stenotic and composite scores reflected arterial damage rather than disease-activity. Longitudinal changes in all three scores correlated with disease activity and mirrored arterial disease evolution, reflecting both progressive injury and lesion improvement. Increases ≥1 in any score were specific for arterial disease progression. The scores objectively quantify arterial involvement in LVV, providing precise definition of disease phenotype and evolution. We propose that they represent novel vascular outcome measures essential for future clinical trials.
Purpose:
To estimate the diagnostic accuracy of conventional 18F-FDG PET/CT of cranial arteries in the diagnosis of giant cell arteritis (GCA).
Methods:
The study was a retrospective case-control study. The reference diagnosis was fulfillment of the 1990 ACR criteria for GCA. All patients had new-onset GCA. Conventional 18F-FDG PET/CT was performed before glucocorticoid treatment. Controls were age- and sex-matched patients with a previous history of malignant melanoma (MM) undergoing surveillance PET/CT >6 months after MM resection. PET images were evenly cropped to include only head and neck and were assessed in random order by four nuclear medicine physicians blinded to reference diagnosis. Temporal (TA), maxillary (MA) and vertebral (VA) arteries were visually rated for 18F-FDG uptake. Interreader agreement was evaluated by Fleiss kappa.
Results:
A total of 44 patients and 44 controls were identified. In both groups, the mean age was 69 years (p = 0.45) and 25/44 were women. 35/41 GCA patients were temporal artery biopsy positive (TAB). Considering only FDG uptake in TA and/or MA, diagnostic sensitivity and specificity was 64 and 100%. Including VA, sensitivity increased to 82% and specificity remained 100%. Interreader agreement was 91% and Fleiss kappa 0.82 for the PET diagnosis based on the cranial arteries.
Conclusion:
Conventional 18F-FDG PET/CT is an accurate and reliable tool to diagnose cranial arteritis in glucocorticoid-naïve GCA patients. The high diagnostic specificity suggests that TAB can be omitted in patients with 18F-FDG uptake in cranial arteries. 18F-FDG PET/CT performed in patients with suspected vasculitis should always include the head and neck.
PurposeTo evaluate the in-treatment diagnostic accuracy of FDG PET/CT in large-vessel giant cell arteritis (LV-GCA) by serial scans before and after a short course of high-dose glucocorticoid treatment. Methods
Twenty-four glucocorticoid-naïve patients with new-onset PET/CT verified LV-GCA (pre-treatment baseline PET) were prospectively included. Excluded were patients with a previous history of GCA or polymyalgia rheumatica, LV-GCA-mimicking conditions and patients on immunosuppressive therapy. All patients were treated with 60 mg of oral prednisolone daily and assigned for in-treatment FDG PET/CT after either 3 (PET3) or 10 days (PET10). Two experienced nuclear medicine physicians, blinded to patients’ clinical data, reviewed the FDG PET/CT images. A visual semi-quantitative approach was used. Segmental and homogenous FDG uptake in the wall of the aorta and/or supra-aortic branches with higher uptake intensity than liver was considered consistent with vasculitis. Inter-reader reliability was evaluated. ResultsAlthough glucocorticoid treatment attenuated FDG uptake in large vessels, LV-GCA was accurately diagnosed in 10/10 patients after 3 days of treatment, but only in 5/14 patients after 10 days of treatment (p < 0.001). Interrater reliability was substantial (agreement 87%, Cohen’s weighted kappa 0.70). No correlation between CRP and FDG uptake was found. Conclusions
Within 3 days of high-dose glucocorticoid treatment, FDG PET/CT can diagnose LV-GCA with high sensitivity. This window of opportunity ensures that prompt glucocorticoid treatment can be initiated to avoid debilitating GCA complications with a limited effect on diagnostic accuracy. After 10 days of treatment, FDG PET/CT sensitivity decreases significantly.
Objectives
To perform a systematic literature review on imaging techniques for diagnosis, outcome prediction and disease monitoring in large vessel vasculitis (LVV) informing the European League Against Rheumatism recommendations for imaging in LVV.
Methods
Systematic literature review (until 10 March 2017) of diagnostic and prognostic studies enrolling >20 patients and investigating ultrasound, MRI, CT or positron emission tomography (PET) in patients with suspected and/or established primary LVV. Meta-analyses were conducted, whenever possible, obtaining pooled estimates for sensitivity and specificity by fitting random effects models.
Results
Forty-three studies were included (39 on giant cell arteritis (GCA), 4 on Takayasu arteritis (TAK)). Ultrasound (‘halo’ sign) at temporal arteries (8 studies, 605 patients) and MRI of cranial arteries (6 studies, 509 patients) yielded pooled sensitivities of 77% (95% CI 62% to 87%) and 73% (95% CI 57% to 85%), respectively, compared with a clinical diagnosis of GCA. Corresponding specificities were 96% (95% CI 85% to 99%) and 88% (95% CI 81% to 92%). Two studies (93 patients) investigating PET for GCA diagnosis reported sensitivities of 67%–77% and specificities of 66%–100% as compared with clinical diagnosis or temporal artery biopsy. In TAK, one study each evaluated the role of magnetic resonance angiography and CT angiography for diagnostic purposes revealing both a sensitivity and specificity of 100%. Studies on outcome prediction and monitoring disease activity/damage were limited and mainly descriptive.
Conclusions
Ultrasound and MRI provide a high diagnostic value for cranial GCA. More data on the role of imaging for diagnosis of extracranial large vessel GCA and TAK, as well as for outcome prediction and monitoring in LVV are warranted.
Objectives
To develop an Outcome Measures in Rheumatology (OMERACT) ultrasonography score for monitoring disease activity in giant cell arteritis (GCA) and evaluate its metric properties.
Methods
The OMERACT Instrument Selection Algorithm was followed. Forty-nine members of the OMERACT ultrasonography large vessel vasculitis working group were invited to seven Delphi rounds. An online reliability exercise was conducted using images of bilateral common temporal arteries, parietal and frontal branches as well as axillary arteries from 16 patients with GCA and 7 controls. Sensitivity to change and convergent construct validity were tested using data from a prospective cohort of patients with new GCA in which ultrasound-based intima–media thickness (IMT) measurements were conducted at weeks 1, 3, 6, 12 and 24.
Results
Agreement was obtained (92.7%) for the OMERACT GCA Ultrasonography Score (OGUS), calculated as follows: sum of IMT measured in every segment divided by the rounded cut-off values of IMTs in each segment. The resulting value is then divided by the number of segments available. Thirty-five members conducted the reliability exercise, the interrater intraclass correlation coefficient (ICC) for the OGUS was 0.72–0.84 and the median intrareader ICC was 0.91. The prospective cohort consisted of 52 patients. Sensitivity to change between baseline and each follow-up visit up to week 24 yielded standardised mean differences from −1.19 to −2.16, corresponding to large and very large magnitudes of change, respectively. OGUS correlated moderately with erythrocyte sedimentation rate, C reactive protein and Birmingham Vasculitis Activity Score (corr coeff 0.37–0.48).
Conclusion
We developed a provisional OGUS for potential use in clinical trials.
Objective:
Vascular ultrasound has been increasingly used to diagnose giant cell arteritis (GCA). The temporal and axillary arteries are commonly evaluated. However, the usefulness of including the subclavian artery remains unclear. This study investigated whether inclusion of the subclavian artery in addition to the temporal and axillary arteries in the ultrasound evaluation of GCA improves the accuracy of the examination beyond ultrasonography of the temporal and axillary arteries alone.
Methods:
We formed a fast-track clinic to use ultrasound to rapidly evaluate patients with suspected GCA. In this cohort study, patients referred for new concern for GCA received a vascular ultrasound for GCA. Subclavian intima-media thickness (IMT) cutoffs of 1.0 and 1.5 mm were retrospectively assessed.
Results:
Two hundred thirty-seven patients were referred to the fast-track clinic from November 2017 to August 2021. One hundred sixty-eight patients received an ultrasound for concern for new GCA. With a subclavian IMT cutoff of 1.5 mm, inclusion of the subclavian artery did not identify any patients with GCA who were not otherwise found to have positive temporal and/or axillary artery examinations, and at this cutoff, there was 1 false-positive result. A subclavian IMT cutoff of 1.0 mm identified several subjects diagnosed with GCA who had otherwise negative ultrasounds, but most subjects with an isolated subclavian IMT greater than 1.0 mm had false-positive results, and the specificity of this cutoff was poor.
Conclusion:
Inclusion of the subclavian artery in the ultrasound assessment of GCA at 2 different cutoffs rarely contributed to the accurate diagnosis of GCA and increased the rate of false-positive results.
In the absence of risk factors like bicuspid aortic valve, connective tissue disorder, or family history of aortic dissections, degenerative thoracic aortic aneurysm appears to be an indolent disease. Most American and European societies recommend yearly or biannual imaging of the thoracic aorta with computed tomographic (CT) imaging, magnetic resonance (MRI) imaging, and transthoracic echocardiographic (TTE) examination. We aimed to identify the rate of progression and predictors of early degenerative aortic root dilatation (ARD) and ascending aortic dilatation (AAD) over a period of 10 years on the basis of echocardiographic measurements. A retrospective chart analysis was performed on 340 patients (mean age 67.4 ± 11.6 years; 85.6% men; 83.8% White) with known ARD and AAD. Aortic root and ascending aorta measurements were followed by serial echocardiograms from the time of the first diagnosis for a total of 10 years. During this time, the mean change in ARD was 0.28 ± 0.71 mm and AAD was 0.15 ± 0.18 mm. On multivariate regression after adjusting for baseline demographics, risk factors, and medication use, there was no statistically significant increase in their unit change in mean ARD or AAD. In conclusion, mild to moderate degenerative thoracic aortic aneurysm has a minimal change in dimensions over time, and current guidelines recommending yearly surveillance imaging of ARD and AAD need to be revisited to allow a more liberal follow-up interval.
Objective
To identify the clinical, laboratory, and histopathological features that may predict the diagnosis of giant cell arteritis (GCA).
Methods
A retrospective chart review was performed on patients who underwent temporal artery biopsy (TAB) between January 1, 2011 and March 31, 2019. Patient demographics, clinical characteristics, laboratory features, histopathological features, and biopsy results were collected. GCA status was determined by a neuro-ophthalmologist (OOA). Stepwise logistic regression analysis was performed to identify features that predict GCA status.
Results
Of 101 patients who underwent TAB, 31 (31%) were diagnosed with GCA. Age was found to be statistically significant for the diagnosis of GCA (P = 0.009), with an average age of 74.4 years (± 8.1) in those with GCA vs. 68.9 years (± 10.0) in those without. The incidence of transient vision loss was higher in GCA than non-GCA patients (P=0.005). Anterior arteritic ischemic optic neuropathy (n=3), ophthalmic artery occlusion (n=2), and posterior ischemic optic neuropathy (n=1) were seen only in the GCA group. Of the 31 GCA patients, 15 had active GCA (48%), 3 (10%) had healed temporal arteritis (HTA), 8 (26%) had suggested HTA, and 5 (16%) had false negative biopsies. Of the 70 non-GCA patients, 63 (90%) had negative biopsies, 2 (3%) had HTA, and 5 (7%) had suggested HTA. Histopathological analysis revealed that CD68 staining had a sensitivity of 69% and specificity of 86%. Both presence of multinucleated giant cells (MNGC) and transmural inflammation had 100% specificity, however sensitivity was ≤ 50%. In patients with negative TABs and complete risk factor data available (n=66), the odds of GCA increased 2.16-fold every 5 years of age, and 1.08-fold every mg/day of oral steroid use, A biopsy result of HTA had an odds ratio of 84.7 and suggested HTA of 49.2 against a negative TAB for diagnosis of GCA.
Conclusion
Age at time of biopsy, HTA, and suggested HTA are predictive for the diagnosis of GCA. Transient vision loss is more commonly seen in GCA, and anterior arteritic ischemic optic neuropathy, ophthalmic artery occlusion, and posterior ischemic optic neuropathy are important ophthalmic manifestations of GCA. CD68 staining is more sensitive but less specific for diagnosing GCA in comparison to other histopathologic findings such as presence of MNGC and transmural inflammation. Further work is recommended to investigate the importance of the specific histopathologic finding of CD68 staining in the diagnosis of GCA.
Objectives:
This study was designed to evaluate the performance of high-resolution magnetic resonance imaging (HR-MRI) in detecting giant cell arteritis (GCA), evaluate superficial extracranial artery and other MRI abnormalities, and compare three-dimensional (3D) and two-dimensional (2D) techniques.
Methods:
PubMed, Web of Science, and Cochrane Library were screened up to March 7, 2021, and further selection was performed according to the eligibility criteria. Quality Assessment of Diagnostic Accuracy Studies-2 was used for quality assessment, and heterogeneity assessment and statistical calculations were also performed.
Results:
In total, 1851 records were retrieved from online databases, and 15 studies were finally included. Regarding the performance of HR-MRI, the superficial extracranial artery had 75% sensitivity and 89% specificity, respectively, with an area under the receiver operating characteristic curve (AUC) of 0.91. Positive and negative post-test possibilities were 86% and 20%, respectively, with clinical diagnosis as reference. When referenced with temporal artery biopsy, the sensitivity was 91%, specificity was 78%, AUC was 0.92, and positive and negative post-test possibilities were 78% and 10%, respectively. 3D HR-MRI and 2D HR-MRI had 70% and 72% sensitivity, respectively, and 91% and 84% specificity, respectively.
Conclusions:
HR-MRI is a valuable imaging modality for GCA diagnosis. It provided high accuracy in the diagnosis of GCA and played a potential role in identifying GCA-related ischemic optic neuropathy. 3D HR-MRI had better specificity than 2D HR-MRI.
Key points:
HR-MRI helps clinicians to diagnose GCA. Superficial extracranial arteries and other MRI abnormalities can be assessed with HR-MRI. HR-MRI can help in assessing GCA-related optic neuropathy.
The many forms of vasculitis are characterized by inflammation of blood vessels, leading to potentially long-term sequelae including vision loss, aneurysm formation and kidney failure. Accurate estimation of the incidence and prevalence has been hampered by the absence of reliable diagnostic criteria and the rarity of these conditions; however, much progress has been made over the past two decades, although data are still lacking from many parts of the world including the Indian subcontinent, China, Africa and South America. Giant cell arteritis occurs in those aged 50 years and over and seems to mainly affect persons of northern European ancestry, whereas Takayasu arteritis occurs mainly in those aged under 40 years. By contrast, Kawasaki disease mainly occurs in children aged under 5 years and is most common in children of Asian ancestry, and IgA vasculitis occurs in children and adolescents. Although much less common than giant cell arteritis, the different forms of antineutrophil cytoplasmic antibody-associated vasculitis are being increasingly recognized in most populations and occur more frequently with increasing age. Behçet syndrome occurs most commonly along the ancient silk road between Europe and China. Much work needs to be done to better understand the influence of ethnicity, geographical location, environment and social factors on the development of vasculitis.
C-Reactive protein and erythrocyte sedimentation rate are crucial parameters used to monitor giant cell arteritis (GCA). Given that tocilizumab is approved for the treatment of GCA, these parameters are less sensitive because of the effects of interleukin-6 receptor blockade. Thus, the optimal method for monitoring GCA patients undergoing tocilizumab therapy, especially patients exhibiting a persistent thickened vessel wall in large vessels, remains unclear. Contrast-enhanced ultrasonography (CEUS) can increase the visibility of tissue perfusion by slow blood flow, which cannot be detected by power color doppler. We used CEUS to investigate patients with active and inactive GCA of the large vessels (active large vessel arteritis [aLVV]/inactive large vessel arteritis [iLVV]) who were not administered tocilizumab in this proof-of-concept study. After injection of the ultrasound contrast agent, the contrasted area (CA) of large vessels in a transverse section was calculated twice: first when the lumen was contrasted completely and once again 4–8 s later. We investigated the value of increase in CA that exhibited the best sensitivity and specificity for aLVV. Twenty-four patients were included in this study: 15 with aLVV and 9 with iLVV. The CA increased from 32.2 ± 16.8 to 52.5 ± 21.3 mm² (p < 0.0001) in aLVV. The mean CA remained unchanged in iLVV. The best cutoff value to differentiate between aLVV and iLVV was a ≥25% increase in CA with a sensitivity and specificity of 91.7% and 100%, respectively. Our study indicates that CEUS can detect aLVV with high sensitivity and specificity. Incorporation of CEUS into routine clinical practice might result in a good method for monitoring disease activity in LVV in GCA patients. The limitation of our study was the small number of patients and the lack of investigator blinding to clinical data.
Objectives
To assess the sensitivity to change of ultrasound halo features and their association with disease activity and glucocorticoid (GC) treatment in patients with newly diagnosed giant cell arteritis (GCA).
Methods
Prospective study of patients with ultrasound-confirmed GCA who underwent serial ultrasound assessments of the temporal artery (TA) and axillary artery (AX) at fixed time points. The number of segments with halo and maximum halo intima–media thickness (IMT) was recorded. Time points in which >80% of patients were assessed were considered for analysis. Halo features at disease presentation and first relapse were compared.
Results
49 patients were assessed at 354 visits. Halo sensitivity to change was assessed at weeks 1, 3, 6, 12 and 24 and showed a significant standardised mean difference between all time points and baseline for the TA halo features but only after week 6 for the AX halo features. The number of TA segments with halo and sum and maximum TA halo IMT showed a significant correlation with erythrocyte sedimentation rate (0.41, 0.44 and 0.48), C reactive protein (0.34, 0.39 and 0.41), Birmingham Vasculitis Activity Score (0.29, 0.36 and 0.35) and GC cumulative dose (−0.34, −0.37 and −0.32); no significant correlation was found for the AX halo features. Halo sign was present in 94% of first disease relapses but with a lower mean number of segments with halo and sum of halo IMT compared with disease onset (2.93±1.59 mm vs 4.85±1.51 mm, p=0.0012; 2.01±1.13 mm vs 4.49±1.95 mm, p=0.0012).
Conclusions
Ultrasound is a useful imaging tool to assess disease activity and response to treatment in patients with GCA.
Objectives:
Efficacy evaluation of giant cell arteritis (GCA) treatment is primarily based on non-specific symptoms and laboratory markers. We aimed to assess the change in vascular inflammation in patients with large vessel (LV)-GCA under different treatments using [18F]FDG PET/CT.
Methods:
Observational study on patients with new-onset, active LV-GCA starting treatment with either prednisolone monotherapy (PRED) or combination with methotrexate (MTX) or tocilizumab (TOC). All patients underwent baseline and follow-up PET/CT. The aorta and its major branches were assessed using PET vascular activity score (PETVAS) by independent readers. Cumulative glucocorticoid doses and cessation of glucocorticoid treatment were documented in all patients.
Results:
We included 88 LV-GCA patients, 27 were treated with PRED, 42 with MTX, and 19 with TOC. PETVAS decreased from 18.9-8.0 units at follow-up in the overall population (p< 0.001). PETVAS changes were numerically higher in patients receiving MTX (-12.3 units) or TOC (-11.7 units) compared with PRED (-8.7). Mean cumulative prednisolone dosages were 5637, 4418, and 2984 mg in patients treated with PRED, MTX, and TOC (p= 0.002). Risk ratios for glucocorticoid discontinuation at the time of follow-up PET/CT were 6.77 (95%CI 1.01-45.29; p= 0.049) and 16.25 (95%CI 2.60-101.73; p= 0.003) for MTX and TOC users compared with PRED users.
Conclusion:
Treatment of LV-GCA inhibits vascular inflammation in the aorta and its major branches. While similar control of vascular inflammation was achieved with PRED, MTX, and TOC treatments, TOC showed a strong glucocorticoid sparing effect, supporting the concept of initial combination therapy.
Background
The combination of tocilizumab plus a glucocorticoid taper is effective in maintaining clinical remission without requiring additional glucocorticoid therapy in patients with giant cell arteritis, as shown in part one of the Giant Cell Arteritis Actemra (GiACTA) trial. However, the duration of the tocilizumab effect after discontinuation is unknown. Here, we explored the maintenance of efficacy 1 year after discontinuation of tocilizumab treatment, the effectiveness of retreatment with tocilizumab after relapse, and the long-term glucocorticoid-sparing effect of tocilizumab.
Methods
In part one of the GiACTA trial, 251 patients were randomly assigned (2:1:1:1) to receive subcutaneous tocilizumab (162 mg) once a week or every other week, combined with a 26-week prednisone taper, or placebo combined with a prednisone taper over a period of either 26 weeks or 52 weeks. Patients in clinical remission stopped masked injections at 1 year (the conclusion of part one). In part two, treatment was at the investigators' discretion and could consist of no treatment, tocilizumab, glucocorticoids, methotrexate, or combinations of these, for two years. Maintenance of efficacy as assessed by clinical remission (defined as absence of relapse determined by the investigator), cumulative glucocorticoid dose, and long-term safety were exploratory objectives in part two of the trial. This trial is registered at ClinicalTrials.gov, NCT01791153.
Findings
215 patients participated in part two of the trial; 81 patients who were randomly assigned to tocilizumab once a week in part one were in clinical remission after 1 year, of whom 59 started part two on no treatment. 25 of these 59 patients (42%) maintained tocilizumab-free and glucocorticoid-free clinical remission throughout part two. Median (95% CI) cumulative glucocorticoid doses over 3 years were 2647 mg (1987–3507) for tocilizumab once a week, 3948 mg (2352–5186) for tocilizumab-every-other-week, 5277 mg (3944–6685) for placebo with a 26-week prednisone taper, and 5323 mg (3900–6951) for placebo with a 52-week prednisone taper (van Elteren p≤0·001, tocilizumab once a week vs placebo groups; p<0·05, tocilizumab-every-other-week vs placebo groups). Tocilizumab-based regimens restored clinical remission among patients who experienced relapse in part two and were treated (median time to remission: 15 days for tocilizumab alone [n=17]; 16 days for tocilizumab plus glucocorticoids [n=36]; and 54 days for glucocorticoids alone [n=27]). No new or unexpected safety findings were reported over the full 3 years of the study.
Interpretation
Giant cell arteritis remains a chronic disease that entails ongoing management and careful vigilance for disease relapse, but continuous indefinite treatment with immunosuppressive drugs is not required for all patients. A substantial proportion of patients treated with tocilizumab for one year maintain drug-free remission during the two years after tocilizumab cessation. For patients who experience relapse, tocilizumab can be used to manage relapses, but it remains prudent to include prednisone for patients who experience relapse because of the risk for vision loss.
Funding
F Hoffmann-La Roche.
Objectives
To evaluate the time-dependent effects of tocilizumab on vascular inflammation as measured by 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in giant cell arteritis (GCA).
Methods
Patients with GCA treated with tocilizumab were selected from a prospective, observational cohort. Patients underwent FDG-PET at the baseline visit prior to initiation of tocilizumab and at subsequent follow-up visits performed at 6-month intervals. All imaging findings were interpreted blinded to clinical data. The PET vascular activity score (PETVAS) was used to quantify arterial FDG uptake. Wilcoxon signed rank test was used to compare change in PETVAS between visits. Linear regression was used to determine change in PETVAS over multiple timepoints.
Results
Twenty-five patients with GCA were included. All patients had physician-determined active vasculitis at the baseline visit by clinical assessment and FDG-PET interpretation. PETVAS was significantly reduced in association with tocilizumab treatment from the baseline to the most recent follow-up visit [24.0 (IQR 22.3–27.0) vs 18.5 (IQR 15.3–23.8); p< 0.01]. A significant reduction in PETVAS was observed over a two-year treatment period (p< 0.01 for linear trend), with a similar degree of improvement in both the first and second years of treatment. Repeat FDG-PET scans after tocilizumab discontinuation showed worsening PET activity in five out of six patients, with two patients subsequently experiencing clinical relapse.
Conclusion
Treatment of patients with GCA with tocilizumab was associated with both clinical improvement and reduction of vascular inflammation as measured by serial FDG-PET. Future clinical trials in GCA should study direct treatment effect on vascular inflammation as an outcome measure.
High-quality aortic imaging plays a central role in the management of patients with thoracic aortic aneurysm. Computed tomography angiography and magnetic resonance angiography are the most commonly used techniques for thoracic aortic aneurysm diagnosis and imaging surveillance, with each having unique strengths and limitations that should be weighed when deciding patient-specific applications. To ensure optimal patient care, imagers must be familiar with potential sources of artifact and measurement error, and dedicate effort to ensure high-quality and reproducible aortic measurements are generated. This review summarizes the imaging evaluation and underlying pathology relevant to the diagnosis of thoracic aortic aneurysm.
Objectives. To compare the ultrasound characteristics with clinical features, final diagnosis and outcome; and to evaluate the halo size following glucocorticoid treatment in patients with newly diagnosed GCA.
Methods. Patients with suspected GCA, recruited from an international cohort, had an ultrasound of temporal (TA) and axillary (AX) arteries performed within 7 days of commencing glucocorticoids. We compared differences in clinical features at disease presentation, after 2 weeks and after 6 months, according to the presence or absence of halo sign. We undertook a cross-sectional analysis of the differences in halo thickness using Pearson's correlation coefficient (r) and Analysis of Variance (ANOVA).
Results. A total of 345 patients with 6 months follow-up data were included; 226 (65.5%) had a diagnosis of GCA. Jaw claudication and visual symptoms were more frequent in patients with halo sign (P =0.018 and P =0.003, respectively). Physical examination abnormalities were significantly associated with the presence of ipsilateral halo (P <0.05). Stenosis or occlusion on ultrasound failed to contribute to the diagnosis of GCA. During 7 days of glucocorticoid treatment, there was a consistent reduction in halo size in the TA (maximum halo size per patient: r=-0.30, P =0.001; and all halos r=-0.23, P <0.001), but not in the AX (P >0.05). However, the presence of halo at baseline failed to predict future ischaemic events occurring during follow-up.
Conclusion. In newly diagnosed GCA, TA halo is associated with the presence of ischaemic features and its size decreases following glucocorticoid treatment, supporting its early use as a marker of disease activity, in addition to its diagnostic role.
GCA is the most common form of primary systemic vasculitis affecting older people. It is considered a clinical emergency because it can lead to irreversible blindness in around 20% of untreated cases. High doses of glucocorticoids should be initiated promptly to prevent disease-related complications; however, glucocorticoids therapy usually results in significant toxicity. Therefore, correct diagnosis is crucial. For many years, temporal artery biopsy has been considered the diagnostic 'gold standard' for GCA, but it has many limitations (including low sensitivity). US has proven to be effective for diagnosing GCA and can reliably replace temporal artery biopsy in particular clinical settings. In cases of suspected GCA with large-vessel involvement, other imaging modalities can be used for diagnosis (e.g. CT and PET). Here we review the current evidence for each diagnostic modality and propose an algorithm to diagnose cranial-GCA in a setting with rapid access to high quality US.
Objectives:
To describe the frequency and causes for the presence of a halo sign on the ultrasound of patients without a diagnosis of GCA.
Methods:
In total, 305 patients with temporal artery colour Doppler ultrasound showing the presence of halo sign (intima-media thickness ≥0.34 mm for temporal arteries [TAs] and ≥1 mm for axillary arteries) were included, and their medical records were reviewed. The clinical diagnosis based on the evolution of the patient over at least one year was established as the definitive diagnosis.
Results:
Fourteen of the 305 (4.6%) patients included showed presence of the halo sign without final diagnosis of GCA: 12 patients in the TAs (86%), and two patients with isolated AAs involvement (14%). Their diagnoses were PMR (n = 4, 29%); atherosclerosis (n = 3, 21%); and non-Hodgkin lymphoma type T, osteomyelitis of the skull base, primary amyloidosis associated with multiple myeloma, granulomatosis with polyangiitis, neurosyphilis, urinary sepsis and narrow-angle glaucoma (n = 1 each, 7%).
Conclusion:
The percentage of halo signs on the ultrasound of patients without GCA is low, but it does exist. There are conditions that may also show the halo sign (true positive halo sign), and we must know these and always correlate the ultrasound findings with the patient's clinic records.
Objectives:
Temporal artery biopsy (TAB) is a reference test for the diagnosis of GCA but reveals inflammatory changes only in a subset of patients. The lack of knowledge of TAB sensitivity hampers comparisons with non-invasive techniques such as temporal artery ultrasonography. We performed a systematic literature review and meta-analysis to estimate the sensitivity of TAB in GCA and to identify factors that may influence the estimate.
Methods:
A systematic literature review involved searching electronic databases and cross-references. Eligibility criteria included publications reporting at least 30 GCA cases fulfilling the original or modified 1990 ACR classification criteria. The pooled proportion of TAB-positive GCA cases was calculated by using aggregated-data meta-analysis with a random-effects model and assessment of heterogeneity with the I2 statistic. Subgroup analyses and meta-regression were used to examine the effect of patient and study characteristics on TAB positivity.
Results:
Among 3820 publications screened, 32 studies (3092 patients) published during 1993-2017 were analysed. The pooled proportion of TAB-positive GCA cases was 77.3% (95% CI: 71.8, 81.9%), with high between-study heterogeneity (I2 = 90%). The proportion of TAB-positive cases was slightly higher in publications before than in 2012 and after (P = 0.001).
Conclusion:
The estimated sensitivity of 77% provides indirect evidence that TAB is not less sensitive than temporal artery imaging. The unexplained high between-study heterogeneity could result from differences in TAB sampling, processing or interpretation. The decrease in TAB-positive GCA cases over time could reflect an increasing propensity for clinicians to accept a GCA diagnosis without proof by TAB.
Objectives:
To assess changes of arterial vessel wall morphology in large vessel GCA patients (LV-GCA) by repeated US.
Methods:
Patients with LV-GCA on US examination were followed up 6, 12 and 24 months after diagnosis by US of the temporal, vertebral, carotid (common, internal, external), subclavian, axillary, femoral (deep, superficial and common) and popliteal arteries. Clinical and laboratory data were assessed at each visit. Vessel wall thickening was classified as moderate, marked or arteriosclerotic.
Results:
A total of 42 patients (26 female) with a median age of 75 years at diagnosis had in median 2 (range 1-3) US follow-up exams. Twenty-eight had both LV and temporal artery involvement and 14 had LV-GCA only. The common carotid, subclavian, axillary, popliteal and/or superficial femoral artery were most commonly involved. Reduction of LV wall thickening occurred in 45% of patients during follow-up, corresponding to 71 of the 284 (25%) initially 'vasculitic' LV segments. In contrast, a reduction of vessel wall thickening in the temporal artery was found in 85% of patients. Of the LVs, the vertebral, axillary, subclavian and deep femoral arteries were most likely to improve. There was no difference in relapses or the received cumulative steroid dose between patients with or without a reduction of vessel wall thickening (temporal artery or LV) during follow-up.
Conclusion:
Regression of wall thickening within the LV is significantly less common than in the temporal artery and irrespective of clinical remission. Morphological regression does not seem to be a useful predictor for relapses.
Objective:
To evaluate aortic diameter and predictors of aortic dilatation using 18FDG-PET/CT in a longitudinally followed cohort of patients with large vessel vasculitis (LVV) compared with controls.
Methods:
All consecutive patients with LVV who underwent at least 2 PET/CT scans between January 2008 and May 2015 were included. The first and last PET/CT study was evaluated by a radiologist and a nuclear medicine physician. Diameter and FDG uptake of the aorta was measured at 4 different levels: ascending, descending thoracic, suprarenal and infrarenal abdominal aorta. Twenty-nine age- and sex-matched patients with lymphoma who underwent at least 2 PET/CT scans in the same time interval were selected as controls.
Results:
93 patients with LVV were included in the study. In the time interval between first and last PET/CT study (median time 31 months), the diameter of the ascending, descending thoracic and suprarenal abdominal aorta significantly increased in LVV patients but not in controls. At last PET/CT, patients with LVV compared with controls had higher diameter of ascending [35.41 (5.54) vs 32.97 (4.11) mm, p = 0.029], descending thoracic [28.42 (4.82) vs 25.72 (3.55) mm, p = 0.007] and suprarenal abdominal aorta, mean [25.34 (7.01) vs 22.16 (3.26) mm, p = 0.005] and more frequently had aortic dilatation [19% vs 3%, p = 0.023]. Significant predictors of aortic dilatation were male sex [OR 7.27, p = 0.001] and, only for GCA, hypertension [OR 6.30, p = 0.031]. Finally, GCA patients with aortic FDG uptake grade 3 at first PET/CT, compared to those with aortic FDG uptake ≤2, had significantly higher aortic diameter.
Conclusions:
Patients with LVV are at increased risk of aortic dilatation compared with age- and sex-matched controls. Significant predictors of aortic dilatation are male sex and, only for GCA, hypertension. GCA patients with aortic FDG uptake grade 3 are at increased risk of aortic dilatation.
Objectives:
Arteritic anterior ischemic optic neuropathy (A-AION) caused by inflammatory occlusion of the posterior ciliary arteries is the most common reason for irreversible vision loss in patients with giant cell arteritis. Atypical clinical presentation and negative funduscopy can delay systemic high-dose corticosteroid therapy to prevent impending permanent blindness and involvement of the contralateral eye.The purpose of this study was to assess the diagnostic accuracy of 3-dimensional (3D) high-resolution T1-weighted black-blood magnetic resonance imaging (T1-BB-MRI) for the detection of posterior ciliary artery involvement in patients with giant cell arteritis and funduscopic A-AION.
Materials and methods:
After institutional review board approval and informed consent, 27 patients with suspected giant cell arteritis and vision disturbances were included in this monocentric prospective cohort study. Giant cell arteritis was diagnosed in 18 patients according to the diagnostic reference standard (6 men, 73.8 [69.0-78.0] years); 14 of those were positive for A-AION. Precontrast and postcontrast 3D T1-BB-MRI was performed in all 27 patients. Two radiologists separately assessed image quality and local fat suppression (4-point scale), visual contrast enhancement (3-point scale), and diagnostic confidence (5-point scale) regarding arteritic posterior ciliary artery involvement. Magnetic resonance imaging findings were assessed in comparison to funduscopy. Statistical analysis included accuracy parameters and interrater agreement.
Results:
Sensitivity of 3D T1-BB-MRI was 92.9% (95% confidence interval, 66.1%-99.8%) and specificity was 92.3% (95% confidence interval, 64.0%-99.8%) for detection of A-AION-positive patients. Image quality and local fat suppression were assessed with 3.2 ± 0.8 (median 3) and 3.8 ± 0.5 (median 4). Visual contrast enhancement with 2.3 ± 0.8 (median 3) and diagnostic confidence was rated at 4.7 ± 0.5 (median 5). Interrater agreement was high (κ = 0.85, P < 0.001). Three-dimensional T1-BB-MRI displayed bilateral findings in 50% of the cases, whereas only unilateral A-AION was detected in funduscopy as a possible indication for the contralateral eye at risk.
Conclusions:
Three-dimensional T1-BB-MRI allows accurate detection of arteritic posterior ciliary artery involvement in patients with A-AION. Further, 3D T1-BB-MRI seems to display arteritic involvement of the posterior ciliary arteries earlier than funduscopy and might, therefore, display "vision-at-risk" in patients with visual impairment and suspected giant cell arteritis but unremarkable funduscopy.
In diagnosing and following patients with acute aortic syndromes and thoracic aortic aneurysms, high-quality imaging of the thoracic aorta is indispensable. Mainstay modalities for thoracic aortic imaging are echocardiography, computed tomographic angiography, and magnetic resonance angiography. For any given clinical scenario, the imaging modality and protocol chosen will have a significant impact on sensitivity and specificity for the aortic diagnosis of concern. Imaging can also provide important ancillary information regarding myocardial performance, aortic valve morphology and function, and end-organ perfusion. Surveillance of patients following thoracic aortic surgery with serial imaging studies can identify complications that may require reintervention, and imaging has played an integral role in development of new surgical and interventional methods. Emerging techniques in thoracic aortic imaging include positron emission tomography, which addresses vessel wall inflammation, and 4-dimensional magnetic resonance angiography, which illustrates flow dynamics.
Objectives To define the elementary ultrasound (US) lesions in giant cell arteritis (GCA) and to evaluate the reliability of the assessment of US lesions according to these definitions in a web-based reliability exercise.
Methods Potential definitions of normal and abnormal US findings of temporal and extracranial large arteries were retrieved by a systematic literature review. As a subsequent step, a structured Delphi exercise was conducted involving an expert panel of the Outcome Measures in Rheumatology (OMERACT) US Large Vessel Vasculitis Group to agree definitions of normal US appearance and key elementary US lesions of vasculitis of temporal and extracranial large arteries. The reliability of these definitions on normal and abnormal blood vessels was tested on 150 still images and videos in a web-based reliability exercise.
Results Twenty-four experts participated in both Delphi rounds. From originally 25 statements, nine definitions were obtained for normal appearance, vasculitis and arteriosclerosis of cranial and extracranial vessels. The ‘halo’ and ‘compression’ signs were the key US lesions in GCA. The reliability of the definitions for normal temporal and axillary arteries, the ‘halo’ sign and the ‘compression’ sign was excellent with inter-rater agreements of 91–99% and mean kappa values of 0.83–0.98 for both inter-rater and intra-rater reliabilities of all 25 experts.
Conclusions The ‘halo’ and the ‘compression’ signs are regarded as the most important US abnormalities for GCA. The inter-rater and intra-rater agreement of the new OMERACT definitions for US lesions in GCA was excellent.
Objectives:
To assess agreement between interpretation of magnetic resonance angiography (MRA) and 18F-fluorodeoxyglucose positron emission tomography (PET) for disease extent and disease activity in large-vessel vasculitis (LVV) and determine associations between imaging and clinical assessments.
Methods:
Patients with giant cell arteritis (GCA), Takayasu's arteritis (TAK) and comparators were recruited into a prospective, observational cohort. Imaging and clinical assessments were performed concurrently, blinded to each other. Agreement was assessed by per cent agreement, Cohen's kappa and McNemar's test. Multivariable logistic regression identified MRA features associated with PET scan activity.
Results:
Eighty-four patients (GCA=35; TAK=30; comparator=19) contributed 133 paired studies. Agreement for disease extent between MRA and PET was 580 out of 966 (60%) arterial territories with Cohen's kappa=0.22. Of 386 territories with disagreement, MRA demonstrated disease in more territories than PET (304vs82, p<0.01). Agreement for disease activity between MRA and PET was 90 studies (68%) with Cohen's kappa=0.30. In studies with disagreement, MRA demonstrated activity in 23 studies and PET in 20 studies (p=0.76). Oedema and wall thickness on MRA were independently associated with PET scan activity. Clinical status was associated with disease activity by PET (p<0.01) but not MRA (p=0.70), yet 35/69 (51%) patients with LVV in clinical remission had active disease by both MRA and PET.
Conclusions:
In assessment of LVV, MRA and PET contribute unique and complementary information. MRA better captures disease extent, and PET scan is better suited to assess vascular activity. Clinical and imaging-based assessments often do not correlate over the disease course in LVV.
Trial registration number:
NCT02257866.
Objective:
To analyse magnetic resonance angiographic (MRA) vessel wall signals from a randomized controlled trial of tocilizumab (TCZ) to treat GCA.
Methods:
Participants were assigned in a 2:1 ratio to receive either TCZ + glucocorticoids (GCs) or placebo + GC infusions at 4-week intervals for 52 weeks. GCs were started at 1 mg/kg/day, then tapered to 0.1 mg/kg/day at week 12 and thereafter down to zero. Patients with initial positive MRA findings underwent control MRA at weeks 12 and 52. Vessel wall signals were scored from 0 (normal) to 3 (intense late enhancement). Outcomes were the number of patients with complete MRA remission at weeks 12 and 52, and changes in vasculitis score, vessel anatomy and atherosclerosis.
Results:
Of the 30 randomized participants, nine TCZ and two placebo patients had no vessel wall enhancement on initial MRA. At week 12, MRAs were performed in nine TCZ and four placebo patients (nine and three in clinical remission, respectively). Three (33%) TCZ patients showed normalization of vessel wall signals compared with one (25%) placebo patient. At week 52, there was additional MRA improvement in some TCZ patients, but one-third showed persistent or increased late vessel wall enhancement. There was no formation of aneurysms or stenosis and no increase in atherosclerosis.
Conclusions:
Although TCZ resulted in complete clinical and laboratory remission of GCA over 52 weeks, MRA signals in vessel walls normalized in only one-third of patients. Whether these signals are of prognostic importance remains to be determined.