Imaging Challenges and Developments in Large-vessel Vasculitis.

Vascular imaging is an integral part of large-vessel vasculitis (LVV) evaluation and management. Several imaging modalities are currently employed in clinical practice including vascular ultrasound, computed tomography angiography, MRI and magnetic resonance angiography, and 18F-fluorodeoxyglucose PET. Well-established roles for imaging in LVV include disease diagnosis and assessment of luminal lesions reflecting vascular damage. The ability of imaging to determine treatment response, monitor disease activity, and predict future arterial damage is an area of active research.

Clinical features, imaging use, and management in giant cell arteritis: a retrospective single-center study.

This study examines the characteristics of patients with giant cell arteritis (GCA), the utilization of imaging in GCA diagnosis, and variations in GCA management among specialties. Subjects were identified from the Dallas VAMC database spanning 2010 to 2021 using ICD-9/10 codes for GCA and polymyalgia rheumatica, and a list of temporal artery biopsies (TAB). Patients lacking sufficient data to meet the ACR 1990 classification criteria for GCA were excluded. Categorical variables were compared using Fisher's exact test. Continuous variables were analyzed with the Kruskal-Wallis test. Among 209 identified patients, 41 were excluded due to insufficient data for ACR classification. The cohort comprised 91.9% males with a median age of 69. Of the remaining 168 patients, 42 received a final diagnosis of GCA, and 15 of these were confirmed with a positive TAB. The most reported initial symptoms were visual disturbances (75.5%) and headaches (67.7%). Ophthalmology was the initial physician for 46% of patients. GCA correlated with co-existing autoimmune diseases, glucocorticoid-sparing treatments, and consultation with a rheumatologist (p < 0.05). There were no significant differences in clinical features or management of the positive and negative TAB GCA groups. GCA presents with heterogeneous symptoms making diagnosis challenging. Scalp tenderness and headaches were significantly higher in GCA patients, but sub-group analysis revealed no significant differences among GCA patients. Vascular assessments and adjunct imaging modalities are underutilized. The establishment of multidisciplinary or fast-track clinics may enhance the optimization of GCA management. Key Points • The most common presenting symptoms were blurry vision/visual loss (75.5%), headache (67.7%), and scalp tenderness (35.9%) in descending order. • In sub-group analysis, no significant differences were found between GCA sub-groups, but when compared to the non-GCA group, were found to have significantly higher rates of headache and scalp tenderness. • Compared to other specialties, rheumatologists were more likely to use advanced imaging, and to prescribe glucocorticoid-sparing treatments. • Systematic and comprehensive assessment and multidisciplinary approach could improve diagnosis and management.

Optic nerve sheath measurement to monitor disease activity in giant cell arteritis: a pilot study.

INTRODUCTION/OBJECTIVES: Optic nerve sheath (ONS) enhancement using magnetic resonance imaging of the orbits was observed in patients with giant cell arteritis (GCA). We previously showed that ONS diameter (ONSD) by bedside ultrasound is increased in patient with active GCA. This study aims to assess whether ONSD decreases with clinical remission in patients with GCA. METHODS: A prospective cohort study was conducted from June 2022 to January 2023. Patients who had an optic nerve ultrasound at GCA diagnosis as part of a previous crosssectional study were eligible. Optic nerve ultrasound was performed by the same investigator at diagnosis and month 3. ONSD (includes the optic nerve and its sheath) and optic nerve diameter (OND) were measured. Descriptive statistics for baseline characteristics and paired sample t-test were performed to assess the mean difference in OND and ONSD between diagnosis and month 3. RESULTS: Nine patients with GCA were included. The median age at disease onset was 79 years (interquartile range (IQR) of 79-82 years), and 7 patients were males. All patients were in clinical remission at month 3 on prednisone (median dose of 15 mg/day, IQR of 10-25 mg). The mean ONSD was lower at month 3 (3.76 mm) compared to baseline (5.98 mm), with a paired mean difference of 2.22 mm (95% CI 1.41-3.03 mm, p < 0.001). As anticipated, OND measurements did not vary between diagnosis and month 3. CONCLUSION: ONSD on ultrasound improves after 3 months of therapy in patients with GCA. A longer prospective study is required to determine if ONSD is useful to assess disease activity in GCA. Key Points • ONS ultrasound can identify patients with active GCA. • The ONSD on ultrasound is dynamic and improved after 3 months of GCA therapy. • ONS ultrasound may be useful to monitor disease activity in GCA.

Clinical Manifestations and Prognosis of Giant Cell Arteritis: A Retrospective Cohort Study.

The aim of the study was to evaluate the clinical manifestations and survival of patients with giant cell arteritis (GCA). MATERIALS AND METHODS: . A retrospective study included 166 patients with newly diagnosed GCA. Clinical, laboratory, and instrumental data and three sets of classification criteria were used to confirm the diagnosis: the American College of Rheumatology (ACR) 1990, the revised ACR criteria of 2016 and/or the new ACR and European Alliance of Rheumatologic Associations (EULAR) 2022 criteria. Some of the patients underwent instrumental investigations: temporal artery ultrasound Doppler (n = 61), contrast-enhanced computed tomography (n = 5), CT angiography (n = 6), magnetic resonance imaging (n = 4), MR angiography (n = 3), and 18F-FDG PET/CT (n = 47). Overall and recurrence-free survival rates were analyzed using survival tables and Kaplan-Meier method. RESULTS: . The most frequent first manifestations of GCA were headache (81.8%), weakness (64%), fever (63.8%), and symptoms of rheumatic polymyalgia (56.6%). Changes in temporal arteries in color duplex scanning were detected in 44 out of 61 patients. GCs therapy was performed in all patients who agreed to be treated (n = 158), methotrexate was used in 49 out of 158 patients, leflunomide in 9 patients. In 45 (28.5%) out of 158 patients, a stable remission was achieved as a result of GC monotherapy; in 120 (75.9%) patients, long-term maintenance therapy with GCs was required to prevent exacerbations, including 71 (44.9%) patients in combination with methotrexate or other immunosuppressive drugs. The follow-up period of patients with a history of relapses was 21.0 (8.0-54.0) months. Relapses developed in 73 (46.2%) patients. The overall one-year survival rate was 97.1% [95% CI 94.3; 99.9], and the five-year survival rate of patients was 94.6% [95% CI 90.2; 99.0]. The one-year relapse-free survival rate was 86.4% [95% CI 80.5; 92.3], and the five-year relapse-free survival rate was 52.4% [95% CI 42.0; 62.8]. Twelve (7.2%) of 166 patients died. The cause of death was myocardial infarction in two patients, stroke in two patients, and breast cancer in one patient; in the remaining seven cases, the cause of death was not determined. CONCLUSIONS: : Given the high frequency of disease exacerbation, patients with GCA require long-term follow-up, especially during the first year after diagnosis.

Ultrasonography of the superficial temporal and axillary arteries in giant cell arteritis diagnosis.

OBJECTIVES: Giant cell arteritis (GCA) is the main systemic vasculitis in individuals aged ≥ 50 years. Color Doppler ultrasound (CDS) has an established role in GCA diagnosis and management. This study aims to assess the clinical characteristics associated with a positive CDS evaluation and the impact of additional axillary artery examination on diagnostic sensitivity. MATERIAL AND METHODS: We conducted a retrospective analysis of patients undergoing CDS of the superficial temporal arteries, with or without axillary artery assessment, at our hospital, between 2009 and 2023. Patients meeting the new 2022 diagnostic criteria for GCA were included and their characteristics were analyzed according to the presence of the halo sign on CDS. RESULTS: Of the 135 included patients (54 % female, mean age 75 ± 8 years), the halo sign was observed in 57 %, correlating with higher systemic symptom prevalence (61 % vs 42 %, p = 0.035), lower hemoglobin (p < 0.001), and higher erythrocyte sedimentation rate (p = 0.028). The halo sign inversely related to prior corticosteroid therapy (p = 0.033). Patients with axillary halo sign had fewer external carotid symptoms and a higher vertebral halo sign prevalence. Vertebral halo sign was associated with posterior circulation ischemic stroke (65 %, p < 0.001). Axillary artery studies improved diagnostic sensitivity by 9 %. CONCLUSION: In our study, the halo sign correlated with higher systemic symptoms and analytical abnormalities. Axillary artery examination enhanced CDS sensitivity, linked to severe outcomes like stroke. Prior corticosteroid therapy reduced CDS sensitivity. The correlation of clinical, laboratory, and ultrasound findings provides a more comprehensive understanding of GCA pathogenesis and evolution.

Evaluation of the extracranial "multifocal arcuate sign," a novel MRI finding for the diagnosis of giant cell arteritis, on STIR and contrast-enhanced T1-weighted images.

BACKGROUND: While early diagnosis of giant cell arteritis (GCA) based on clinical criteria and contrast-enhanced MRI findings can lead to early treatment and prevention of blindness and cerebrovascular accidents, previously reported diagnostic methods which utilize contrast-enhanced whole head images are cumbersome. Diagnostic delay is common as patients may not be aware of initial symptoms and their significance. To improve current diagnostic capabilities, new MRI-based diagnostic criteria need to be established. This study aimed to evaluate the "multifocal arcuate sign" on short tau inversion recovery (STIR) and contrast-enhanced T1-weighted (CE-T1W) images as a novel extracranial finding for the diagnosis of GCA. METHODS: A total of 17 consecutive patients (including five with GCA) who underwent CE-T1W and whole-brain axial STIR imaging simultaneously between June 2010 and April 2020 were enrolled. We retrospectively reviewed their MR images. The "multifocal arcuate sign" was defined as "multiple distant arcuate areas with high signal intensity in extracranial soft tissues such as subcutaneous fat, muscles, and tendons." Extracranial abnormal high-signal-intensity areas were classified as "None," when no lesions were detected; "Monofocal," when lesions were detected only in one place; and "Multifocal," when lesions were detected in multiple places. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of "Multifocal" areas were calculated using cross tabulation. Fisher's exact test was used to compare "Multifocal" areas in five patients with GCA and those with other diseases. In addition, mean Cohen's kappa and Fleiss' kappa statistics were used to compare inter-reader agreement. RESULTS: The sensitivity, specificity, PPV, and NPV of the "multifocal arcuate sign" in patients with GCA were 60%, 92-100%, 75-100%, and 85-86%, respectively. Significantly more patients with GCA had "Multifocal" areas compared to those with other diseases (Fisher's exact test, p = 0.008-0.027). Mean Cohen's kappa and Fleiss' kappa for inter-reader agreement with respect to the five GCA patients were 0.52 and 0.49, respectively, for both STIR and CE-T1W sequences. CONCLUSIONS: The new radiologic finding of "multifocal arcuate sign" on STIR and CE-T1W images may be used as a radiologic criterion for the diagnosis of GCA, which can make plain MRI a promising diagnostic modality.

The utility of 18F-FDG-PET/CT in detecting extracranial large vessel vasculitis in rheumatic polymyalgia or giant cell arteritis. A systematic review and meta-analysis.

OBJECTIVE: Systematic review of current evidence to analyze the prevalence of extracranial large vessel vasculitis (LVV) using 18F-FDG PET/CT in patients with polymyalgia rheumatica (PMR) or giant cell arteritis (GCA). MATERIALS AND METHODS: PubMed and EMBASE were searched and the results were screened by two reviewers. Study quality was assessed using a modified version of the Newcastle-Ottawa scale. Heterogeneity between studies was assessed using the I2 statistic and the Q test. Further subgroup analyses were performed by disease type, study quality, and 18F-FDG PET/CT uptake criteria. Publication bias was assessed by funnel plot and Egger's test. RESULTS: 268 publications were identified, of which 17 met the selection criteria and were included in the meta-analysis. The overall pooled prevalence of extracranial LVV by 18F-FDG PET/CT was 54.5% [95% CI: 42.6%-66.1%]. In patients with GCA the prevalence was significantly higher than in patients with PMR (60.1% vs. 41.8%, P = 0.006). Likewise, studies with a lower risk of bias reported a higher prevalence of extracranial LVV (61.1% vs. 46.9%; P = 0.010). No publication bias was observed. CONCLUSIONS: The 18F-FDG PET/CT test may be useful in the detection of extracranial LVV, both in patients with PMR or GCA. Such involvement is more frequent in patients with GCA, and may vary depending on the quality of the studies.

Evaluation of baseline F-18 FDG positron emission tomography in the diagnosis and assessment of giant cell arteritis.

Background/aim: The aim of this study is to evaluate the baseline F18-FDG PET/CT findings of individuals diagnosed with giant cell arteritis (GCA) and to explore its association with clinical findings and classification criteria. Materials and methods: We analysed data from patients who underwent F18-FDG PET/CT scans to investigate large vessel (LV) involvement between 2010 and 2019. Only patients with a clinical diagnosis of GCA and at least 6 months of follow-up were included. We compared initial clinical features and laboratory findings based on the presence of LV vasculitis on PET/CT and the maximum standard uptake value (SUVmax) of vascular territories. Results: Twenty-nine patients (median age at diagnosis: 70, F/M: 24/5) were included in the study. Among them, 21 patients (72.4%) presented with cranial symptoms, while 8 patients (27.5%) had isolated LV-GCA. Twenty-two patients (75.9%) met the ACR/EULAR 2022 GCA classification criteria. LV vasculitis was detected on PET/CT in 23 patients (79.3%). A positive correlation was observed between SUVmax in the thoracic aorta and both CRP and ESR levels (r = 0.50, p = 0.026 and r = 0.63, p = 0.002, respectively). PET/CT positive patients were found to be younger (p = 0.016) and more frequently female (p = 0.017). They also exhibited fewer headaches (56.5% vs. 100%, p = 0.04), experienced fewer flares during follow-up (p = 0.03), and had a lower cumulative glucocorticoid dose at the 6th month (p = 0.036). Comparison of PET/CT-positive patients (n = 23) based on the fulfilment of the ACR/EULAR 2022 classification criteria revealed that patients who met these criteria were older (p = 0.02) and had significantly lower CRP levels at diagnosis (p = 0.02). Conclusion: The performance of F18-FDG PET/CT in diagnosing LV involvement in GCA is favourable, and the severity of FDG uptake in the vessel wall correlates with the acute phase response. Patients with extracranial involvement on PET/CT exhibit distinct features, including a younger age and female predominance. Additionally, these patients appear to experience fewer relapses and require lower doses of glucocorticoids. However, the clinical significance of PET/CT in patients who met ACR/EULAR classification criteria, predominantly consisting of patients with ischemic cranial symptoms, could not be determined in our study.

Transorbital ultrasound in the diagnosis of giant cell arteritis.

OBJECTIVES: The objective of this study was to prospectively evaluate the diagnostic efficacy of transorbital ultrasound (TOS) in patients newly diagnosed with giant cell arteritis (GCA), presenting with visual symptoms. METHODS: Patients with newly diagnosed, untreated GCA were examined using TOS, assessing central retinal artery flow velocity [peak systolic velocity (PSV), end-diastolic velocity (EDV), resistance index (RI)], and optic nerve diameter (OND). Vascular ultrasound was conducted to evaluate the superficial temporal arteries, their branches, facial, axillary, carotid, and vertebral arteries. RESULTS: We enrolled 54 GCA patients, 27 with visual symptoms, and 27 healthy controls. Eyes of GCA patients with visual symptoms demonstrated significantly lower PSV and EDV (PSV: ß = -1.91; P = 0.029; EDV: ß = -0.57; P = 0.032) and significantly elevated OND (ß = 0.79; P = 0.003) compared with controls. RI did not significantly differ from controls (ß = -0.06, P = 0.129). Vascular ultrasound identified an average of 8.7 (SD ± 2.8) pathological vessels per GCA patient. A significant negative association was observed between the number of affected vessels and both PSV (P = 0.048) and EDV (P = 0.040). No association was found with RI (P = 0.249), while a positive significant association was noted with OND (P < 0.001). CONCLUSIONS: This study pioneers the application of TOS to assess structural eye changes in newly diagnosed, untreated GCA patients with visual symptoms. Our findings suggest reduced central retinal artery flow and increased optic nerve diameter as potential biomarkers for serious ocular involvement in GCA. The detected association between internal and external carotid artery involvement indicates a common pathophysiological mechanism underlying systemic and ocular manifestations of GCA.

Diagnostic Strategy Using Color Doppler Ultrasound of Temporal Arteries in Patients With High Clinical Suspicion of Giant Cell Arteritis : A Prospective Cohort Study.

BACKGROUND: Giant cell arteritis (GCA) is the most prevalent systemic vasculitis in people older than 50 years. Any delay in diagnosis impairs patients' quality of life and can lead to permanent damage, particularly vision loss. OBJECTIVE: To evaluate a diagnostic strategy for GCA using color Doppler ultrasound of the temporal artery as a first-line diagnostic test, temporal artery biopsy (TAB) as a secondary test, and physician expertise as the reference method. DESIGN: Prospective multicenter study with a 2-year follow-up. (ClinicalTrials.gov: NCT02703922). SETTING: Patients were referred by their general practitioner or ophthalmologist to a physician with extensive experience in GCA diagnosis and management in one of the participating centers: 4 general and 2 university hospitals. PATIENTS: 165 patients with high clinical suspicion of GCA, aged 79 years (IQR, 73 to 85 years). INTERVENTION: The diagnostic procedure was ultrasound, performed less than 7 days after initiation of corticosteroid therapy. Only ultrasound-negative patients underwent TAB. MEASUREMENTS: Bilateral temporal halo signs seen on ultrasound were considered positive. Ultrasound and TAB results were compared with physician-diagnosed GCA based on clinical findings and other imaging. RESULTS: Diagnosis of GCA was confirmed in 44%, 17%, and 21% of patients by ultrasound, TAB, and clinical expertise and/or other imaging tests, respectively. Their diagnosis remained unchanged at 1 month, and 2 years for those with available follow-up data. An alternative diagnosis was made in 18% of patients. The proportion of ultrasound-positive patients among patients with a clinical GCA diagnosis was 54% (95% CI, 45% to 62%). LIMITATION: Small sample size, no blinding of ultrasound and TAB results, lack of an objective gold-standard comparator, and single diagnostic strategy. CONCLUSION: By using ultrasound of the temporal arteries as a first-line diagnostic tool in patients with high clinical suspicion of GCA, further diagnostic tests for patients with positive ultrasound were avoided. PRIMARY FUNDING SOURCE: Tender "Recherche CH-CHU Poitou-Charentes 2014."

The Common Carotid Artery in the Ultrasound Evaluation of Giant Cell Arteritis.

OBJECTIVES: Vascular ultrasound is commonly used to diagnose giant cell arteritis (GCA). Most protocols include the temporal arteries and axillary arteries, but it is unclear which other arteries should be included. This study investigated whether inclusion of intima media thickness (IMT) of the common carotid artery (CCA) in the ultrasound evaluation of GCA improves the accuracy of the examination. 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 with the temporal arteries and branches, the axillary artery, and CCA. RESULTS: We compared 57 patients with GCA and 86 patients without GCA. Three patients with GCA had isolated positive CCA between 1 and 1.49 mm, and 21 patients without GCA had isolated positive CCA IMT. At the 1.5-mm CCA cutoff, 4 patients without GCA had positive isolated CCA, and 1 patient with GCA had a positive isolated CCA. The sensitivity of ultrasound when adding carotid arteries to temporal and axillary arteries was 84.21% and specificity 65.12% at an intima media thickness (IMT) cutoff of ≥1 mm and 80.70% and 87.21%, respectively, at a cutoff of ≥1.5 mm. CONCLUSION: Measurement of the CCA IMT rarely contributed to the diagnosis of GCA and increased the rate of false-positive results. Our data suggest that the CCA should be excluded in the initial vascular artery ultrasound protocol for diagnosing GCA. If included, an IMT cutoff of higher than 1.0 mm should be used.

Multimodality imaging to assess diagnosis and evaluate complications of large vesselarteritis.

Different types of vasculitis can be distinguished according to the blood vessel's size that is preferentially affected: large-vessel, medium-vessel, and small-vessel vasculitides. Giant cell arteritis (GCA) and Takayasu's arteritis (TAK) are the main forms of large-vessel vasculitis, and may lead to lumen narrowing. Clinical manifestations of arterial narrowing on the short- and long term include vision loss, stroke, limb ischemia, and heart failure. Imaging tools are well established diagnostic tests for large-vessel vasculitis and may aid therapy monitoring in selected cases while providing important information regarding the occurrence of vascular damage, tissue and organ complications. This review aims to provide the current status of multimodality imaging for the diagnosis and identification of vascular complications in the field of large vessel vasculitis.

Large vessel giant cell arteritis.

Giant cell arteritis is the principal form of systemic vasculitis affecting people over 50. Large-vessel involvement, termed large vessel giant cell arteritis, mainly affects the aorta and its branches, often occurring alongside cranial giant cell arteritis, but large vessel giant cell arteritis without cranial giant cell arteritis can also occur. Patients mostly present with constitutional symptoms, with localising large vessel giant cell arteritis symptoms present in a minority of patients only. Large vessel giant cell arteritis is usually overlooked until clinicians seek to exclude it with imaging by ultrasonography, magnetic resonance angiography (MRA), computed tomography angiography (CTA), or [18F]fluorodeoxyglucose-PET-CT. Although the role of imaging in treatment monitoring remains uncertain, imaging by MRA or CTA is crucial for identifying aortic aneurysm formation during patient follow up. In this Series paper, we define the large vessel subset of giant cell arteritis and summarise its clinical challenges. Furthermore, we identify areas for future research regarding the management of large vessel giant cell arteritis.

Limb arteries involvement assessed by FDG/PET CT at diagnosis of giant cell arteritis and risk of relapse: An observational study.

INTRODUCTION: Steroids and anti-IL6 biotherapy are highly effective in obtaining remission in patients with giant cell arteritis (GCA) but the risk of relapses remains high. We aimed to identify predictors of relapse in GCA. METHODS: All consecutive patients admitted with a new diagnosis of GCA - according to the 2022 American College of Rheumatology/EULAR (ACR/EULAR) classification criteria - between May 2011 and May 2022 were eligible for this study. The primary outcome was the GCA relapse rate over the 36-months follow up. Factors associated with the primary outcome and time to first relapse were analyzed. RESULTS: One hundred and eight patients (74 [69-81] years, 64.8% women) with a new diagnosis of GCA were studied. GCA was biopsy-proven in 65 (60.2%) cases. Ninety-eight (90.7%) FDG/PET CT scans performed at diagnosis were available for review. All patients received steroids given for 21.0 [18.0-28.5] months, associated with methotrexate (n=1, 0.9%) or tocilizumab (n=2, 1.9%). During a median follow-up of 27.5 [11.4-35.0] months, relapse occurred in 40 (37%) patients. Multivariable Cox regression model, including general signs, gender, aortic wall thickness, FDG uptake in arterial wall and IV steroid pulse as covariates, showed that both general signs (HR 2.0 [1.0-4.0, P<0.05) and FDG uptake in limb arteries (HR 2.7 [1.3-5.5], P<0.01) at diagnosis were associated with GCA relapse. CONCLUSION: FDG uptake in limb arteries at diagnosis is a predictor of relapse in newly diagnosed GCA.

Real-world clinical decisions of physicians in the management of Takayasu arteritis and giant cell arteritis in Japan: A cross-sectional web questionnaire survey.

OBJECTIVES: The aim is to access the real-world clinical management of physicians who treat Takayasu arteritis (TAK) and giant cell arteritis (GCA) after the publication of the Japanese Circulation Society (JCS) 2017 Guidelines for the Management of Vasculitis Syndrome. METHODS: This descriptive, cross-sectional study utilized self-administered electronic questionnaires, which were answered in February 2022 by physicians treating TAK or GCA and registered with Macromill Inc. RESULTS: The 329 survey respondents were enrolled. The 2017 JCS Guidelines were the most commonly referenced information source for resolving clinical questions, accessed by 70% of respondents. Ophthalmoscopy was performed in only 50% of patients with TAK and in 70% for GCA. The median percentages of patients who underwent 18F-fluorodeoxyglucose-positron emission tomography/computed tomography for TAK and GCA patients were 23% and 20% at diagnosis, respectively, and 10% each at follow-up within 12 months. Tocilizumab was the most frequently used medication in combination with glucocorticoids for both TAK and GCA, especially in remission induction therapy for relapsed patients. CONCLUSIONS: The majority of physicians treating TAK and GCA referred to the 2017 JCS guidelines. This report clarified the current clinical practice for large vessel vasculitis in Japan, providing information for the next revision of the guidelines.