Large Vessel Vasculitis Patients Research Articles

Fibroblast Activation Protein Inhibitor-Positron Emission Tomography in Aortitis: Fibroblast pathology in active inflammation and remission.

Epigenetically modified fibroblasts contribute to chronicity in inflammatory diseases. Reasons for the relapsing character of large vessel vasculitis (LVV) remain obscure, including the role of fibroblasts, in part due to limited access to biopsies of involved tissue.68Ga FAPI-46 (FAPI)-PET/CT detects activated fibroblasts in vivo. In this exploratory pilot study, we tested the detection of fibroblast activation in vessel walls using FAPI-PET/CT in LVV with aortitis. 8 LVV patients with aortitis and 8 age- and gender-matched controls were included. Distribution of FAPI uptake was evaluated in the aorta and large vessels. FAPI-uptake was compared with MRI inflammatory activity scores. Imaging results were compared with clinical parameters such as serum inflammatory markers, time of remission and medication. Three aortitis patients were clinically active, five in remission. Irrespective of activity, FAPI uptake was significantly enhanced in aortitis compared with controls. Patients in remission had a mean duration of remission of 2.8 years (range 1-4 years), yet significant FAPI uptake in the vessel wall was found.In remitted aortitis, MRI inflammatory scores were close to be negative, while in 4/5 patients visually identifiable FAPI uptake was observed. This pilot feasibility study shows significant tracer uptake in the aortic walls in LVV. FAPI positivity indicates ongoing fibroblast pathology in clinically remitted LVV.

Prevalence and distribution of vascular calcifications at CT scan in patients with and without large vessel vasculitis: a matched cross-sectional study

ObjectivesThe aim of this study was to compare the prevalence, entity and local distribution of arterial wall calcifications evaluated on CT scans in patients with large vessel vasculitis (LVV) and...

OA35 Early identification of large vessel vasculitis: a specific benefit of a non-specific symptom pathway?

Abstract Background/Aims Since December 2020 in Cornwall there has been a Non-Specific Symptom Pathway (NSSP): a 2-week-wait pathway by which GPs can access a CT thorax, abdomen & pelvis (CT-TAP) to assess non-specific symptoms where there is a suspicion of malignancy, but conventional 2-week-wait referral criteria are not met. An unexpected consequence of this pathway was the finding of cases of suspected large vessel vasculitis (LVV) being referred to rheumatology outpatients. Methods Cases with a new diagnosis of LVV or cancer were identified using the NSSP database over the period of December 2021- May 2022. Clinical and laboratory features were analysed and compared. During this time period a Logiq E10 US machine was acquired by the department, enabling axillary US to be performed for some of the suspected LVV cases that were referred to rheumatology. Results Of the 241 accepted referrals, 14 patients (5.81%) had a subsequent definite cancer diagnosis, 6 (2.49%) had LVV diagnosed as a direct consequence of the NSSP. 5 (83%) cases of LVV had CRP >60 versus 4 (33%) of the cancer patients where measured. Mean CRP was 38.9 in cancer patients and 82.3 in LVV (normal 0-5mg/L). Mean platelet count was 401 in cancer patients, 510 in LVV patients (normal 150-400x109). 3 LVV patients had immunoglobulins and serum protein electrophoresis tested, of which 2 had significantly raised IgG and 1 was confirmed as polyclonal. In one case, significant thoracic aneurysmal dilatation was identified; a 59-year-old previously healthy woman presented to primary care with fatigue, night sweats and arm pain. Investigations showed anaemia, thrombocytosis, polyclonal high immunoglobulins, CRP 74. CT-TAP via NSSP revealed thoracic aorta wall thickening with aneurysmal dilatation, diameter being 4.5cm at the aortic arch. Subsequently the patient was referred to vascular surgeons and rheumatology. Rheumatology clinic review noted no symptoms of cranial giant cell arteritis or polymyalgia rheumatica. Examination revealed significant blood pressure discrepancy between right and left arms (diastolic difference of 62mmHg) and bilateral axillary bruits. Bilateral axillary artery ultrasound revealed significant intima-media thickening: right distal 1.19mm, left distal 1.37mm (normal less than 0.9mm) consistent with LVV. 10mg Prednisolone and subsequently leflunomide 10mg were initiated with resolution of inflammatory markers and symptoms. Surgical intervention was not felt to be required but regular surveillance continues. Conclusion Polyclonal raised IgG, unexplained raised CRP and thrombocytosis, arm blood pressure discrepancy and axillary bruits may be useful indicator tests for referral to the NSSP. LVV diagnosis normally requires extensive inpatient investigations in patients with pyrexia-of-unknown-origin and can be challenging in the absence of PMR or cranial GCA symptoms. As well as early identification of cancer, NSSP has the additional benefit of detecting cases of LVV that may have otherwise gone unnoticed, including the cases with secondary aneurysmal change. Disclosure R. Machin: None. M. Hughes: None.

Incidental findings on FDG-PET/CT in large vessel vasculitis.

This study aims to determine the number and type of incidental findings detected on positron emission tomography (PET)/CT in a cohort of patients with large vessel vasculitis (LVV). Reports from PET/CT studies along with the medical charts of a cohort of patients with LVV from a Rheumatology clinic in Edmonton, Alberta, Canada, were retrospectively reviewed. Incidental findings from PET/CT, along with follow-up studies and their diagnosis were documented. The data was analyzed with descriptive statistics. The disease activity of 40 patients, with an average age of 65.8years, was investigated using PET/CT. A statistically significant increase in incidental findings with age was observed. A total of 61 incidental findings were found in 26 (65%) patients. Of these findings, 25 were in the abdomen and pelvis. The most common incidental finding was lymphadenopathy. Follow-up investigations of incidental findings lead to 5 clinically significant findings including metastatic adenocarcinoma, Mycobacterium avium infection, papillary thyroid carcinoma, pheochromocytoma, and stroke. PET/CT is a reliable tool for determining disease activity in LVV patients and the implications of incidental findings need to be discussed with patients by the ordering care provider. This study demonstrates that incidental findings on PET/CT scan are common and increase with age in patients with LVV. A significant number of patients required further investigation for incidental findings. Key Points • Incidental findings on PET/CT scan are common in our patient population with LVV. • Frequency of incidental findings in our patient population with LVV increased with age. • Findings from this study can be used by ordering providers to have an informed conversation with their patient about the frequency of incidental findings on PET/CT scans.

Somatostatin Receptor PET/MR Imaging of Inflammation in Patients With Large Vessel Vasculitis and Atherosclerosis

BackgroundAssessing inflammatory disease activity in large vessel vasculitis (LVV) can be challenging by conventional measures. ObjectivesWe aimed to investigate somatostatin receptor 2 (SST2) as a novel inflammation-specific molecular imaging target in LVV. MethodsIn a prospective, observational cohort study, in vivo arterial SST2 expression was assessed by positron emission tomography/magnetic resonance imaging (PET/MRI) using 68Ga-DOTATATE and 18F-FET-βAG-TOCA. Ex vivo mapping of the imaging target was performed using immunofluorescence microscopy; imaging mass cytometry; and bulk, single-cell, and single-nucleus RNA sequencing. ResultsSixty-one participants (LVV: n = 27; recent atherosclerotic myocardial infarction of ≤2 weeks: n = 25; control subjects with an oncologic indication for imaging: n = 9) were included. Index vessel SST2 maximum tissue-to-blood ratio was 61.8% (P < 0.0001) higher in active/grumbling LVV than inactive LVV and 34.6% (P = 0.0002) higher than myocardial infarction, with good diagnostic accuracy (area under the curve: ≥0.86; P < 0.001 for both). Arterial SST2 signal was not elevated in any of the control subjects. SST2 PET/MRI was generally consistent with 18F-fluorodeoxyglucose PET/computed tomography imaging in LVV patients with contemporaneous clinical scans but with very low background signal in the brain and heart, allowing for unimpeded assessment of nearby coronary, myocardial, and intracranial artery involvement. Clinically effective treatment for LVV was associated with a 0.49 ± 0.24 (standard error of the mean [SEM]) (P = 0.04; 22.3%) reduction in the SST2 maximum tissue-to-blood ratio after 9.3 ± 3.2 months. SST2 expression was localized to macrophages, pericytes, and perivascular adipocytes in vasculitis specimens, with specific receptor binding confirmed by autoradiography. SSTR2-expressing macrophages coexpressed proinflammatory markers. ConclusionsSST2 PET/MRI holds major promise for diagnosis and therapeutic monitoring in LVV. (PET Imaging of Giant Cell and Takayasu Arteritis [PITA], NCT04071691; Residual Inflammation and Plaque Progression Long-Term Evaluation [RIPPLE], NCT04073810)

Somatostatin receptor PET/MR imaging of large vessel inflammation in active compared with inactive vasculitis and atherosclerosis

Abstract Background Use of 18F-FDG PET in large vessel vasculitis (LVV) is limited by non-specific uptake due to arterial remodelling and/or atherosclerosis leading to diagnostic uncertainty. Purpose To investigate somatostatin receptor 2 (SST2) as a novel inflammation-specific PET imaging target in LVV. Methods In a prospective observational cohort study, we tested the ability of PET/MRI using two somatostatin receptor tracers (68Ga-DOTATATE and 18F-FET-βAG-TOCA) to differentiate active from inactive LVV, and aortic atherosclerosis in patients with recent myocardial infarction. Ex vivo mapping of the imaging target was performed using immunofluorescence microscopy, imaging mass cytometry, and bulk, single-cell and single-nuclei RNA sequencing of temporal artery biopsies from LVV patients. Results Sixty-one participants were included (LVV, n=27; myocardial infarction ≤2 weeks, n=25; control subjects with an oncological indication for imaging, n=9). LVV patients (mean age 58 [SD 16] years; 78% female; 63% active or grumbling disease) had giant cell arteritis (n=13), Takayasu arteritis (n=13), or unspecified LVV (n=1). Baseline index vessel SST2 PET maximum tissue-to-blood ratio (TBRmax) was 61.8% (95% CI 31.5–99.0%, p&amp;lt;0.0001) higher in patients with active/grumbling LVV than inactive LVV, and 34.6% (95% CI 15.1–57.6%, p=0.0002) higher than recent myocardial infarction (Fig. 1a–c; arrow: PET signal; arrowhead: aortic thickening; asterisk: aortic atherosclerosis), with good diagnostic accuracy (AUC ≥0.86, p&amp;lt;0.001 for both). None of the control subjects without LVV or MI had increased arterial SST2 PET signal (Fig. 1d). Mean aortic TBRmax was strongly correlated with Indian Takayasu Clinical Activity Score (r=0.82 [95% CI 0.46–0.95], p=0.001) and maximum wall thickness on MRI (r=0.68 [95% CI 0.31–0.87], p=0.002). SST2 PET/MRI was generally consistent with 18F-FDG PET/CT in LVV patients with contemporaneous scans (Fig. 1a, b), but with very low background signal in the brain and heart allowing for unimpeded assessment of nearby coronary, myocardial, and intracranial artery involvement. On follow-up imaging after a mean 9.3 (SD 3.2) months, clinically effective treatment for LVV was associated with a 0.49 ±SEM 0.24 (p=0.04; 22.3%) reduction in SST2 PET TBRmax, with good scan-scan repeatability in inactive LVV patients with no change in treatment (ICC 0.86, 95% CI 0.04–0.99). SST2 localised to macrophages, pericytes, and perivascular adipocytes in inflamed arterial specimens (Fig. 2; a: H&amp;E; b: imaging mass cytometry; arrow: SST2/CD68 co-staining). SSTR2-expressing macrophages co-expressed pro-inflammatory markers (S100A8, S100A9). Specific SST2 radioligand binding was confirmed by autoradiography in LVV specimens. Conclusion This is the first study to examine SST2 PET/MRI in LVV and to provide histological and gene expression data for validation. Here we show this novel approach holds major promise for diagnosis and therapeutic monitoring in LVV. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Wellcome Trust; Imperial NIHR Biomedical Research Centre

The role of PET/CT in disease activity assessment in patients with large vessel vasculitis.

To evaluate the accuracy of PET/CT and of PET vascular activity score (PETVAS) in assessing disease activity and the ability of PETVAS in predicting relapses in a large single-centre cohort of patients with large vessel vasculitis (LVV). We conducted a retrospective cohort study of prospectively collected data of consecutive patients diagnosed with LVV who underwent at least one PET/CT scan between 2007 and 2020. The nuclear medicine physician's interpretation of each PET/CT scan (active/inactive vasculitis) was compared with disease activity clinical judgement (active disease/remission). For each PET/CT scan, the PETVAS score was calculated and its accuracy in assessing disease activity was evaluated. The ability of PETVAS in predicting subsequent relapses was evaluated. A total of 100 consecutive LVV patients (51 large vessel GCA, 49 Takayasu arteritis) underwent a total of 476 PET/CT scans over a mean follow-up period of 97.5 months. Physician-determined PET/CT grading was able to distinguish between clinically active and inactive LVV with a sensitivity of 60% (95% CI 50.9, 68.7) and specificity of 80.1% (95% CI 75.5, 84.1); the area under the curve (AUC )was 0.70 (95% CI 0.65, 0.75). PETVAS was associated with disease activity, with an age and sex-adjusted odds ratio for active disease of 1.15 (95% CI 1.11, 1.19). A PETVAS ≥10 provided 60.8% sensitivity and 80.6% specificity in differentiating between clinically active and inactive LVV; the AUC was 0.73 (95% CI 0.68, 0.79). PETVAS was not associated with subsequent relapses, with an age and sex-adjusted hazard ratio of 1.04 (95% CI 0.97, 1.11). The visual PET/CT grading scale and PETVAS had moderate accuracy to distinguish active LVV from remission. PETVAS did not predict disease relapses.

Clinical features of large vessel vasculitis (LVV): Elderly-onset versus young-onset

Objectives We compared large vessel vasculitis (LVV) clinical features between age groups. Methods We retrospectively examined clinical features and therapies in 41 LVV patients at our hospital from January 2010 to March 2020. We compared two patient groups, elderly (≥50 years) and young (<50 years). Results Of all patients, 29 were elderly and 12 were young. In the younger group, upper extremity symptoms (p <.05), bruits (p <.01), and cardiovascular complications (p <.01) were more common. Of the elderly group, 7 (24%) met classification criteria for giant cell arteritis while none of the younger group met these criteria; however, 10 (83%) of the younger group and 3 (10%) of the elderly group met the ACR classification criteria for Takayasu arteritis (p <.01). In the elderly group, 16 patients (66%) met no criteria (p <.01). There were no significant differences in laboratory findings but imaging showed a significantly higher incidence of head and neck artery lesions in the younger group (p <.05). The younger group was more likely to receive additional tocilizumab (p <.01) and cardiovascular complications were more likely to occur in younger patients (p < .01). Conclusion LVV clinical features differed between elderly- and young-age-onset groups.

Toward Reliable Uptake Metrics in Large Vessel Vasculitis Studies.

The aim of this study is to investigate the influence of sex, age, fat mass, fasting blood glucose level (FBGL), and estimated glomerular filtration rate (eGFR) on blood pool activity in patients with large vessel vasculitis (LVV). Blood pool activity was measured in the superior caval vein using mean, maximum, and peak standardized uptake values corrected for body weight (SUVs) and lean body mass (SULs) in 41 fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) scans of LVV patients. Sex influence on the blood pool activity was assessed with t-tests, while linear correlation analyses were used for age, fat mass, FBGL, and eGFR. Significantly higher SUVs were found in women compared with men, whereas SULs were similar between sexes. In addition, higher fat mass was associated with increased SUVs (r = 0.56 to 0.65; all p < 0.001) in the blood pool, but no correlations were found between SULs and fat mass (r = −0.25 to −0.15; all p > 0.05). Lower eGFR was associated with a higher FDG blood pool activity for all uptake values. In FDG-PET/CT studies with LVV patients, we recommend using SUL over SUV, while caution is advised in interpreting SUV and SUL measures when patients have impaired kidney function.

Imaging Tests in the Early Diagnosis of Giant Cell Arteritis.

Early recognition of giant cell arteritis (GCA) is crucial to avoid the development of ischemic vascular complications, such as blindness. The classic approach to making the diagnosis of GCA is based on a positive temporal artery biopsy, which is among the criteria proposed by the American College of Rheumatology (ACR) in 1990 to classify a patient as having GCA. However, imaging techniques, particularly ultrasound (US) of the temporal arteries, are increasingly being considered as an alternative for the diagnosis of GCA. Recent recommendations from the European League Against Rheumatism (EULAR) for the use of imaging techniques for large vessel vasculitis (LVV) included US as the first imaging option for the diagnosis of GCA. Furthermore, although the ACR classification criteria are useful in identifying patients with the classic cranial pattern of GCA, they are often inadequate in identifying GCA patients who have the extracranial phenotype of LVV. In this sense, the advent of other imaging techniques, such as magnetic resonance imaging (MRI), computed tomography (CT), and positron emission tomography (PET)/CT, has made it possible to detect the presence of extracranial involvement of the LVV in patients with GCA presenting as refractory rheumatic polymyalgia without cranial ischemic manifestations. Imaging techniques have been the key elements in redefining the diagnostic work-up of GCA. US is currently considered the main imaging modality to improve the early diagnosis of GCA.

Usefulness of 18F-Fluorodeoxyglucose Positron Emission Tomography in Diagnosing Polymyalgia Rheumatica and Large-Vessel Vasculitis: A Case-Control Study

Background: Polymyalgia rheumatica (PMR) is a relatively common disease among the elderly. None of the most common imaging techniques provides diagnostic certainty of PMR. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) may be a useful candidate as it can be used to visualize articular and periarticular FDG uptake at different locations, as well as associated large-vessel vasculitis (LVV). However, in the absence of large-scale case-control studies, its usefulness needs to be evaluated. The purpose of this study was to determine the usefulness of FDG-PET/CT in diagnosing PMR and LVV. Methods: We analyzed FDG-PET/CT scans performed between January 2015 and December 2019 on patients diagnosed with PMR. For comparisons, patients with PMR were matched 1:1 to controls according to age and sex. FDG-PET/CT scans had been performed on controls over the same period for diagnosis of cancer-associated stroke. FDG uptake was scored visually for 17 articular or periarticular sites and 13 vascular sites using a semi-quantitative scoring system (score 0-3). The case and control groups were compared using generalized linear mixed models (binomial distribution, logit function) for binary outcomes, and linear mixed models for continuous outcomes, with matched sets as a random effect. Receiver operating characteristics (ROC) curve analysis, based on the area under the ROC curve (AUC), was used to assess the ability of the number of sites with significant hyperfixation (score ≥ 2) and the FDG uptake score to differentiate the two groups. From the ROC curves, we determined optimal threshold values by maximizing the Youden index. Sensitivity and specificity for the optimal threshold were calculated. Results: 81 patients with a diagnosis of PMR and 81 controls were included (mean (SD) age 70.7 (9.8) years; 44.4% women). Significant differences between the PMR and control groups were found at all articular and periarticular sites for: 1) FDG uptake score (p<0.001 for all locations); 2) number of patients per site with significant FDG uptake (score ≥ 2); 3) global FDG articular uptake scores (score 0-51) (31 [IQR, 21 to 37] versus 6 [IQR, 3 to 10], p<0.001); and 4) number of sites with significant FDG uptake (score ≥ 2) (score 0-17) (11 [IQR, 7 to 13] versus 1 [IQR, 0 to 2], p<0.001). ROC curve analysis revealed that the presence of 6 or more sites with significant FDG uptake (≥ 2) was associated with the diagnosis of PMR, with a sensitivity of 84% and a specificity of 96% (AUC 0.90 [95% CI 0.8593-0.95]). No significant differences in global FDG vascular uptake scores (score 0-39) or in number of patients with at least 1 significant vascular uptake site (score ≥ 2) were found between the PMR and control groups (1 [IQR, 0 to 4] versus 4 [IQR, 0 to 6], p=0.06, and 8 (11.3%) versus 10 (14.1%), p=0.62 respectively). Conclusion: Our results demonstrate that the FDG uptake score and the number of sites with significant FDG uptake could be relevant criteria for the diagnosis of PMR. However, unlike other authors, we found no evidence suggesting that FDG-PET/CT may be useful in diagnosing silent underlying LVV in patients with isolated PMR. Funding: None to declare. Declaration of Interest: None to declare. Ethical Approval: Since this is a retrospective study, it did not require ethical committee approval in accordance with the French laws and regulations. Informed consent was obtained from all patients for the FDG-PET/CT scans.

AB0379 BARICITINIB IN POLYMYALGIA RHEUMATICA AND GIANT CELL ARTERITIS: REPORT OF SIX CASES

Background:Glucocorticoids (GC) are the cornerstone of the treatment of polymyalgia rheumatica (PMR) and giant cell arteritis (GCA), but they are associated with several adverse events (AEs). Moreover, a considerable proportion of patients relapse during GC tapering.Objectives:To describe the efficacy and safety of the JAK-inhibitor baricitinib (BARI) in a group of patients with PMR and/or GCA.Methods:Case series of patients with PMR and/or GCA with a refractory disease course, despite several lines of therapy, including methotrexate (MTX) and tocilizumab (TCZ), started treatment with BARI. All patients underwent periodic, standardised clinical and laboratory examinations, and also FDG-PET/CT. PMR-activity score (AS) was calculated at each visit except in patients with isolated large vessel vasculitis (LVV) or GCA.Results:A total of six patients (five females and one male, median age 64 years, range 50-83) were treated with BARI. Two of them had isolated PMR (patients #1 and #6), two had PMR with associated LVV (patients #2 and #5), and one (patient #3) had cranial-GCA. Demographic and clinical characteristics are provided in Table 1. At the time of starting BARI, patients were taking a median prednisone dose of 8.75 mg/day (range 0-25), and the 4 patients with PMR±LVV had a median PMR-activity score (PMR-AS) of 23.3 (indicating high disease activity), which decreased to 1.58 after 6 months of treatment with BARI. Two of them could stop GC and continued BARI monotherapy (in one case, BARI was tapered down to 2 mg/day after 12 months).After starting BARI, patient #3 (GCA) could gradually taper prednisone from 25 mg/day to 10 mg/day in six months, without reporting fever or headache. After one year of treatment, she feels well while taking prednisone 7.5 mg/day.Patient #4 (LVV) remained clinically stable during the treatment with BARI, but a follow-up FDG-PET/CT showed LVV, and we decided to stop BARI and restart TCZ. After 4 months of treatment with BARI, patient #5 suffered from pneumonia, while she was also taking prednisone 15 mg/day. BARI was therefore stopped. No other AEs attributable to BARI were detected.Conclusion:BARI appears as an appealing option for treating patients with PMR and/or GCA. Although these preliminary results should be confirmed by a RCT, BARI lowered rapidly disease activity and exerted a significant steroid-sparing effect, allowing GC withdrawal in 2 out of 6 patients.Table 1.Demographic and clinical characteristics of patients.Patient #SexAgeDiagnosisPrevious treatmentDisease duration (months)PMR-AS1F66PMRMTX, HCQ, SSZ25.540.52F78PMR+LVVTCZ, MTX41.828.83F61GCACYC, MMF, TCZ119.8N/A4F60LVVTCZ16.4N/A5F83PMR+LVVMTX, TCZ24.415.26M50PMRMTX24.617.8CYC: cyclophosphamide, GCA: giant cell arteritis, HCQ: hydroxychloroquine, LVV: large vessel vasculitis, MMF: mycophenolate mofetil, MTX: methotrexate, N/A: not applicable, PMR: polymyalgia rheumatica, PMR-AS: PMR-activity score, SSZ: sulfasalazine, TCZ: tocilizumab.Disclosure of Interests:Dario Camellino Speakers bureau: Medac, Eli Lilly, Paid instructor for: Mylan, Consultant of: Accord, Celgene, Novartis, Sanofi, Christian Dejaco Speakers bureau: Eli Lilly (&lt;10.000€), Andrea Giusti Speakers bureau: UCB, Amgen, Kyowa Kirin, Abiogen Pharma, and Eli Lilly, Consultant of: EffRx, Abiogen Pharma, FRANCO MARTINI: None declared, Renzo Cosso: None declared, Giuseppe Girasole: None declared, Gerolamo Bianchi Speakers bureau: Amgen, MSD, Novartis, Pfizer, Roche, Sanofi, Genzyme, and Servier, Consultant of: Abbvie, Abiogen Pharma, BMS, Celgene, Eli Lilly, GSK, Janssen-Cilag, Medac

A Review on the Value of Imaging in Differentiating between Large Vessel Vasculitis and Atherosclerosis

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.

Specific microbiome profile in Takayasu\u2019s arteritis and giant cell arteritis

Recent studies have provided evidence of a close link between specific microbiota and inflammatory disorders. While the vessel wall microbiota has been recently described in large vessel vasculitis (LVV) and controls, the blood microbiome in these diseases has not been previously reported (LVV). We aimed to analyse the blood microbiome profile of LVV patients (Takayasu’s arteritis [TAK], giant cell arteritis [GCA]) and healthy blood donors (HD). We studied the blood samples of 13 patients with TAK (20 samples), 9 patients with GCA (11 samples) and 15 HD patients. We assessed the blood microbiome profile by sequencing the 16S rDNA blood bacterial DNA. We used linear discriminant analysis (LDA) coupled with linear discriminant effect size measurement (LEfSe) to investigate the differences in the blood microbiome profile between TAK and GCA patients. An increase in the levels of Clostridia, Cytophagia and Deltaproteobacteria and a decrease in Bacilli at the class level were found in TAK patients compared with HD patients (LDA > 2, p < 0.05). Active TAK patients had significantly lower levels of Staphylococcus compared with inactive TAK patients. Samples of GCA patients had an increased abundance of Rhodococcus and an unidentified member of the Cytophagaceae family. Microbiota of TAK compared with GCA patients was found to show higher levels of Candidatus Aquiluna and Cloacibacterium (LDA > 2; p < 0.05). Differences highlighted in the blood microbiome were also associated with a shift of bacterial predicted metabolic functions in TAK in comparison with HD. Similar results were also found in patients with active versus inactive TAK. In conclusion, patients with TAK were found to present a specific blood microbiome profile in comparison with healthy donors and GCA subjects. Significant changes in the blood microbiome profiles of TAK patients were associated with specific metabolic functions.

Interleukin-1 pathway in active large vessel vasculitis patients with a poor prognosis: a longitudinal transcriptome analysis.

ObjectivesLarge vessel vasculitis (LVV) is characterised by a high relapse rate. Because accurate assessment of the LVV disease status can be difficult, an accurate prognostic marker for initial risk stratification is required. We conducted a comprehensive longitudinal investigation of next‐generation RNA‐sequencing data for patients with LVV to explore useful biomarkers associated with clinical characteristics.MethodsKey molecular pathways relevant to LVV pathogenesis were identified by examining the whole blood RNA from patients with LVV and healthy controls (HCs). The data were examined by pathway analysis and weighted gene correlation network analysis (WGCNA) to identify functional gene sets that were differentially expressed between LVV patients and HCs, and associated with clinical features. We then compared the expression of the selected genes during week 0, week 6, remission and relapse.ResultsThe whole‐transcriptome gene expression data for 108 samples obtained from LVV patients (n = 27) and HCs (n = 12) were compared. The pathway analysis and WGCNA revealed that molecular pathway related to interleukin (IL)‐1 was significantly upregulated in LVV patients compared with HCs, which correlated with the positron emission tomography vascular activity score, a disease‐extent score based on the distribution of affected arteries. Further analysis revealed that the expression levels of genes in the IL‐1 signalling pathway remained high after conventional treatment and were associated with disease relapse.ConclusionUpregulation of the IL‐1 signalling pathway was a characteristic of LVV patients and was associated with the extent of disease and a poor prognosis.

Atypical Large Vessel Vasculitis Presenting With Cholestatic Liver Abnormalities: Case-Based Review.

Clinicians usually easily recognize cranial manifestations of giant cell arteritis (GCA) such as new-onset headache, jaw claudication, scalp tenderness, and abrupt changes in visual acuity or blindness; however, when presented with an aberrant clinical course, the diagnosis becomes more elusive. In addition to temporal arteries and other extracranial branches of the carotid arteries, large vessel vasculitis (LVV) can also affect other blood vessels including coronary arteries, aorta with its major branches, intracranial blood vessels, and hepatic arteries.Over time, the scope of the symptoms typically associated with LVV has broadened and includes cases of fever of unknown origin accompanied with other constitutional symptoms that can mimic a range of neoplastic and infectious diseases. In up to half of patients with atypical LVV, liver enzyme level elevations with a cholestatic pattern have been observed. Alkaline phosphatase level and γ-glutamyl transferase level elevations tend to be more prevalent in those LVV patients with vigorous inflammatory responses, particularly in those with fever and other nonspecific constitutional symptoms. These patients also have more profound anemia and thrombocytosis. With the exception of rare instances of vasculitides and granulomas affecting the liver tissue, liver biopsy is generally of little help and primarily shows nonspecific changes of fatty liver.In this article, we review 3 patients who were eventually diagnosed with atypical LVV. The diagnosis was confirmed with temporal artery biopsy in 2 patients and with positron emission tomography/computed tomography in 1 patient. The common hepatic abnormality observed in all patients was the elevation of alkaline phosphatase level, which tended to respond rapidly to initiation of immunosuppressive treatment.

Semiquantitative Interpretation Criteria for Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography in Large-Vessel Vasculitis: Pattern Recognition and Correlation with Polymyalgia Rheumatica.

Background:Fluorine-18-fluorodeoxyglucose (18F-FDG)-positron emission tomography/computed tomography (PET/CT) is emerging as a useful imaging modality in suspected large-vessel vasculitis (LVV), owing to its ability to accumulate at the sites of inflammation within the arterial walls. However, there remains scope for standardization of reporting criteria to ensure reproducibility. Recently, a semiquantitative scoring system called “total vascular score” (TVS) has been suggested as a method to standardize and harmonize FDG PET/CT evaluation in LVV patients. The purpose of this study was to assess the clinical utility of the proposed semiquantitative grading scale in LVV patients.Materials and Methods:Patients presenting with clinical symptoms of vasculitis, who had undergone a baseline FDG-PET/CT were evaluated. 18F-FDG uptake in the major vessels was quantified with standardized uptake values (SUVsmax) using four-point scale by three independent nuclear physicians. TVS was calculated based on the calculation of the vascular uptake values with respect to mediastinal blood pool and liver uptake and the number of vessels involved.Results:A total of 106 PET-positive patients (74 males and 32 females) were evaluated. The most frequently involved vessels were thoracic aorta >abdominal aorta >subclavian arteries with mean SUVmax values of 4.05, 3.12, and 2.70, respectively. Mean TVS was 13.18 ± 3.4 (range 03–19) among 276 involved vessels. TVS showed significant positive correlation with erythrocyte sedimentation rate (r = 0.82; P < 0.005). 18 patients showed periarticular FDG uptake, with shoulder joint being the most commonly involved joint.Conclusion:The simplified visual and semiquantitative grading scale for interpretation and reporting classification provides better objectivity in diagnosis, communication with referring clinicians, and planning in patients of LVV.

Aortic dilatation in patients with large vessel vasculitis: A longitudinal case control study using PET/CT

ObjectiveTo 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. MethodsAll 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. Results93 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. ConclusionsPatients 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.

Predictors of positive 18F-FDG PET/CT-scan for large vessel vasculitis in patients with persistent polymyalgia rheumatica

ObjectivePolymyalgia rheumatica (PMR) is often the presenting manifestation of giant cell arteritis (GCA). Fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) scan often discloses the presence of large vessel vasculitis (LVV) in PMR patients. We aimed to identify predictive factors of a positive PET/CT scan for LVV in patients classified as having isolated PMR according to well-established criteria. MethodsA set of consecutive patients with PMR from a single hospital were assessed. All of them underwent PET/CT scan between January 2010 and February 2018 based on clinical considerations. Patients with PMR associated to other diseases, including those with cranial features of GCA, were excluded. The remaining patients were categorized in classic PMR (if fulfilled the 2012 EULAR/ACR classification criteria at disease diagnosis; n = 84) or atypical PMR (who did not fulfill these criteria; n = 16). Only information on patients with classic PMR was assessed. ResultsThe mean age of the 84 patients (51 women) with classic PMR was 71.4 ± 9.2 years. A PET/CT scan was positive in 51 (60.7%). Persistence of classic PMR symptoms was the most common reason to perform a PET/CT scan. Nevertheless, patients with positive PET/CT scan often had unusual symptoms. The best set of predictors of a positive PET/CT scan were bilateral diffuse lower limb pain (OR = 8.8, 95% CI: 1.7–46.3; p = 0.01), pelvic girdle pain (OR = 4.9, 95% CI: 1.50–16.53; p = 0.01) and inflammatory low back pain (OR = 4.7, 95% CI: 1.03–21.5; p = 0.04). ConclusionInflammatory low back pain, pelvic girdle and diffuse lower limb pain are predictors of positive PET/CT scan for LVV in PMR.

Large-vessel vasculitis in human immunodeficiency virus-infected patients

ObjectiveThe objective of this study was to describe large-vessel vasculitis (LVV) in patients with human immunodeficiency virus (HIV) infection. It is a retrospective single-center study conducted between 2000 and 2015 through a university hospital of 11 HIV-infected patients with LVV. MethodsThe characteristics and outcome of 11 HIV-infected patients with LVV (7 patients fulfilled international criteria for Takayasu arteritis, 5 patients had histologic findings of vasculitis, and 5 patients had imaging features of aortitis) were analyzed and compared with those of 82 patients with LVV but without HIV infection. ResultsConcerning the HIV-infected patients with LVV (n = 11), the mean age was 40 years (range, 36-56 years), and 55% of patients were female. At diagnosis of LLV, the mean initial CD4 cell count was 455 cells/mm3 (range, 166-837 cells/mm3), and the median HIV viral load was 9241 copies. Vascular lesions were located in the aorta (n = 7), in supra-aortic trunks (n = 7), and in digestive arteries (n = 3). Inflammatory aorta infiltrates showed a strong expression of interferon-γ and interleukin 6. In HIV-negative LVV patients (n = 82), the median age was 42 years, and 88% of the patients were women. Thirty patients had an inflammatory syndrome. Seventy patients had been treated with glucocorticosteroids and 57 with immunosuppressive treatments. Compared with their negative counterparts, HIV-positive patients with LVV were more frequently male (P = .014), had more vascular complications (ie, Ishikawa score; P = .017), and had more frequent revascularization (P = .047). After a mean follow-up of 96 months, four relapses of vasculitis were reported, and one patient died. Regardless of the HIV virologic response, antiretroviral therapy improved LVV in only one case. ConclusionsLVV in HIV-infected patients is a rare and severe entity.