Active Large Vessel Vasculitis Research Articles

18F-FDG-PET/MR imaging to monitor disease activity in large vessel vasculitis

Disease-monitoring in large vessel vasculitis (LVV) is challenging. Simultaneous 18F-fluorodeoxyglucose positron emission tomography with magnetic resonance imaging (PET/MRI) provides functional assessment of vascular inflammation alongside high-definition structural imaging with a relatively low burden of radiation exposure. Here, we investigate the ability of PET/MRI to monitor LVV disease activity longitudinally in a prospective cohort of patients with active LVV. We demonstrate that both the PET and MRI components of the scan can distinguish active from inactive disease using established quantification methods. Using logistic-regression modelling of PET/MRI metrics, we devise a novel PET/MRI-specific Vasculitis Activity using MR PET (VAMP) score which is able to distinguish active from inactive disease with more accuracy than established methods and detects changes in disease activity longitudinally. These findings are evaluated in an independent validation cohort. Finally, PET/MRI improves clinicians’ assessment of LVV disease activity and confidence in disease management, as assessed via clinician survey. In summary, PET/MRI may be useful in tracking disease activity and assessing treatment-response in LVV. Based on our findings, larger, prospective studies assessing PET/MRI in LVV are now warranted.

Cytotoxic CX3CR1+ T cells drive vascular inflammation in giant cell arteritis but not in Takayasu's arteritis.

To compare the involvement of cytotoxic CX3CR1+ T cell subsets between giant cell arteritis (GCA) and Takayasu's arteritis (TAK). We examined the proportions of CX3CR1+ CD4+ and CD8+ T cells in whole blood freshly obtained from 30 treatment-naive patients with active large vessel vasculitis (GCA, n=22 and TAK, n=8) and 16 healthy controls (HC). Infiltration of CX3CR1+ T cells into the affected arteries was assessed using immunohistochemical staining. Furthermore, CX3CR1+ CD4+ and CD8+ T cells were followed up after glucocorticoid treatment for longitudinal assessment of both diseases. The proportion of CX3CR1+ CD4+ T cells was significantly higher in GCA than in HC but not in TAK. No differences were observed in the proportions of CX3CR1+ CD8+ T cells among the GCA, TAK, and HC groups. The increased proportion of CX3CR1+ CD4+ T cells in GCA strongly correlated with the severity of systemic inflammation, whereas no significant correlation was found in TAK. Compared to TAK, CX3CR1+ CD4+ T cells from GCA patients showed significantly higher expression of granzyme B and perforin. The inflamed temporal arterial tissues of the GCA were infiltrated by numerous CX3CR1+ T cells, contributing to inflammation, disruption of the elastic lamina, and intimal hyperplasia. In contrast, no infiltration of CX3CR1+ T cells was observed in the aortitis lesions of TAK. Longitudinal analysis of post-glucocorticoid treatment showed a reduction in CX3CR1+ T cells in GCA, whereas no significant change was observed in TAK. Differences in immune mechanisms between GCA and TAK highlight cytotoxic CX3CR1+ T cells as potential drivers for GCA-related inflammation and vessel damage but not for TAK.

E021 A rare case of coexistence of ANCA-associated vasculitis and malignancy

Abstract Background/Aims A 65-year-old man, with a background of COPD, peripheral vascular disease and a neurostimulator in situ for chronic back pain, presented with a range of symptoms initially treated as lower respiratory tract infection in the community. He complained of bitemporal headache, jaw-pain, transient visual loss and had raised inflammatory markers (CRP 157 and ESR 105). He was subsequently treated as giant cell arteritis with 60mg prednisolone daily despite equivocal temporal artery ultrasound. He continued to have drenching sweats, arthralgia, epistaxis, shortness of breath and haemoptysis although inflammatory markers had normalised. Immunology revealed a strongly positive anti-PR3 antibody at > 8 units suggestive of granulomatosis polyangiitis. There was no convincing end organ evidence of vasculitis. CT-chest identified nodules and non-specific inflammatory changes but no cavitation or pulmonary haemorrhage. He was intolerant of steroids with significant insomnia and mood changes therefore they were rapidly tapered to 20mg daily. Methods He was readmitted to hospital on 20mg prednisolone with acute abdominal pain. CT abdomen-pelvis showed a lesion at the hepatic flexure suspicious for colon cancer, and this was confirmed on colonoscopy and biopsy. PET-CT at this time showed no evidence for active large vessel vasculitis. His prednisolone was tapered further and omitted prior to right hemicolectomy. Histology revealed definitive adenocarcinoma along with a focus of necrotising vasculitis and granulomas in the subserosa close to the tumour, with a distant granulomatous lesion at the resected appendix. He developed post-operative ileus and desaturated leading to a CTPA which did not show PE but identified progressive enlargement of the pulmonary nodules reported as suspicious of metastases. Throughout this time PR3 remained elevated and repeat PET-CT off steroids showed increased uptake at the aorta and right common iliac artery suggestive of active vasculitis. The FDG uptake and rate of enlargement of the pulmonary nodules was felt to be out of keeping with metastases and an inflammatory cause was suspected. Results Episodic pyrexia continued with no identifiable infective source and so a decision to commence oral prednisolone 40 mg was made. Repeat PET-CT 4 weeks later showed complete resolution of the inflammation in the aorta and right common iliac and reduction in size of the lung nodules. Unfortunately, the patient developed acute pancreatitis on steroids, so the prednisolone was reduced to 20mg with a view to induction therapy with cyclophosphamide. Conclusion This case highlighted multiple diagnostic challenges with clinical features of large vessel involvement in a patient with a positive ANCA and concomitant occult malignancy. Co-existence of a vasculitis and a neoplastic disease is rare. ANCA positive vasculitis is most commonly reported with haematological malignancies but less so in solid tumours, presenting as a paraneoplastic phenomenon. This case also highlighted the challenges in management when both conditions co-exist. Disclosure S. Ahmed: None. E. Pathan: None. P. Brown: None. J. Heaney: None. A. Pratt: None.

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.

Positron emission tomography-CT scan (PET-CT) in the diagnosis of large vessel vasculitis

Vasculitides are a broad group of diseases that can involve any kind of vessel in any organ. These can be classified according to the size of the affected vessels. The most used classification categorizes them in small, medium, and large vessel vasculitis. Large vessel vasculitis can be further divided in Takayasu arteritis and giant cell arteritis which can sometimes be indistinguishable, even with biopsy. Radiology plays an important role identifying distribution patterns and disease extension18. Fluorine-Fluorodeoxyglucose (FDG) PET-CT shows increased vessel wall FDG uptake in patients with active large vessel vasculitis. Multiple studies show that FDG PET-CT helps to identify the anatomic structures with the disease, as well as evaluate its progression with a high sensibility and specificity in non-treated patients with large vessel vasculitis.

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.

The utility of PET/CT in large vessel vasculitis

18F-FDG PET/CT occupies a growing role in the diagnosis of large vessel vasculitis (LVV), illustrating enhanced uptake in the lining of large vessels. A retrospective single center study was conducted of patients who underwent 18F-FDG PET/CT scans between 2009 and 2019 at Sheba Medical Center, Israel. The imaging results were analyzed for evidence of LVV. We reviewed the PET/CT scans of 126 patients and identified 57 studies that either showed evidence of active LVV or that had been performed in patients previously treated for systemic vasculitis. In 6 patients with fevers of unknown origin and elevated inflammatory markers, PET/CT revealed LVV. Six of 13 patients previously treated for systemic vasculitis demonstrated persistent large vessel uptake. LVV was identified in 8 patients with other autoimmune diseases, and in 4 diagnosed with infectious aortitis. In 26 patients who underwent malignancy surveillance, PET/CT revealed more localized large vessel wall inflammation. Our results illustrate that PET/CT may identify large vessel wall inflammation in patients with a suspicion of LVV, and incidentally in patients who undergo malignancy surveillance. PET/CT may also help delineate the presence and extent of vessel inflammation in patients with LVV and in those with other autoimmune diseases.

16. Checking in with novel cancer therapies: a case of immunotherapy-related large vessel vasculitis

IntroductionImmune checkpoint inhibition has revolutionised the management of patients with cancer. However, many immunotherapy-related adverse events have been recognised, such as colitis and dermatitis. We are increasingly aware of patients presenting to rheumatology with musculoskeletal complaints including polymyalgia-like symptoms or an inflammatory arthritis. More uncommonly, patients can present with large vessel vasculitis. We present a case of immunotherapy-related large vessel vasculitis following treatment with a combination of ipilimumab and nivolumab.Case descriptionA 67-year-old man has been known to the oncology team with prostate cancer since 2014. He developed osteoblastic metastases despite androgen deprivation therapy and he was subsequently enrolled onto the NEPTUNE study which involved a combination of ipilimumab and nivolumab. Three weeks after his first cycle of immunotherapy, he developed fevers, diarrhoea and a macular rash. He was admitted for a flexible sigmoidoscopy and biopsies demonstrated inflammation in keeping with immunotherapy-related colitis. It was also noted that his thyroxine level was 64.7pmol/L with a TSH of 0.02mlU/L and this was thought to be immunotherapy-related thyroiditis. His immunotherapy was discontinued and he was on a weaning course of prednisolone with a good response. Five months after his single cycle of immunotherapy, he began reporting generalised aches which were worse in his chest and radiated to his right scapula. He also had bilateral shoulder pain but no specific stiffness. This pain was more noticeable as he weaned off the prednisolone. He had no claudication, headaches or constitutional symptoms. A CT pulmonary angiogram showed no evidence of pulmonary emboli, but there was an incidental finding of circumferential thickening of the aorta suggestive of a vasculitis. Inflammatory markers were notably raised - ESR 127mm/h and CRP 199mg/L. There was no evidence of infection on cultures.He was referred to the rheumatology team. Examination was unremarkable with no evidence of weak pulses or bruits. Immunology tests were all negative. An urgent PET-CT was organised which demonstrated extensive active large vessel vasculitis involving the aorta, subclavian, axillary, carotid and vertebral arteries. He was given one dose of methylprednisolone (1mg/kg) which resulted in a marked improvement in his pain overnight. He received two further doses of methylprednisolone and his CRP improved to 38mg/L. He continues to improve on a weaning course of prednisolone. DiscussionIpilimumab was the first checkpoint inhibitor approved for cancer in 2010. Immune checkpoint inhibitors have since become an expanding field in oncology, particularly in resistant or advanced cases of melanoma and lung cancer. There are currently six checkpoint inhibitors licensed by the US Food and Drug Administration. These are monoclonal antibodies targeting the checkpoint pathway including CTLA4, PD-1 and PDL-1. There are well documented case series with regard to immunotherapy-related toxicities including colitis, dermatitis and endocrinopathies. More relevant to rheumatologists, checkpoint inhibitors have also been associated with rheumatic presentations including inflammatory arthritis, polymyalgia rheumatica, sicca symptoms, myositis and vasculitis. A review of the literature in 2018 found 53 cases of vasculitis associated with checkpoint inhibition, of which 20 were confirmed. All these cases were resolved by withholding the immune checkpoint inhibitor and where necessary, giving steroid therapy. On the whole, immunotherapy-related vasculitis is not as common as arthritis or polymyalgia. As the use of checkpoint inhibitors becomes more widespread, it is important that as rheumatologists, we are aware of the various rheumatic conditions that they can trigger and how to manage them.Key learning pointsThis single case highlights the wide range of immunotherapy-related adverse events associated with immune checkpoint inhibition. Their use in clinical practice will likely become more widespread owing to their success in treating a variety of advanced or resistant malignancies. Apart from being familiar with the various rheumatic complaints, we should also be aware of the other systems that can become involved, so that the patient is managed holistically. Symptoms will usually improve with termination of the checkpoint inhibitor but steroid therapy is often required. The addition of disease modifying anti-rheumatic drugs should be considered in cases where there are relapsing symptoms whilst weaning steroids. However, this is a decision that requires a multidisciplinary approach since it could affect the prognosis of the underlying malignancy. With more research into this area, there will a better understanding of the true incidence of immunotherapy-related adverse events in these patients and how to reduce these in the future.Conflict of interestThe authors declare no conflicts of interest.

33. A case of ocular ischaemic syndrome caused by severe giant cell arteritis

IntroductionThis case describes a very aggressive form of giant cell arteritis (GCA) complicated by ocular ischaemic syndrome (OIS), complete bilateral visual loss and bilateral scalp muscle necrosis, despite treatment with high dose intravenous steroids. OIS, defined as ischaemia of all intraorbital and intraocular structures, is rare, estimated at 7.5 cases per million. This case also highlights the use of PET CT in management of complex cases of GCA.Case descriptionA 79-year-old lady presented with sudden onset pain above her right eye. A month earlier she had undergone curative surgery for infiltrating adenocarcinoma of the colon. 6 months earlier she had complained of bilateral shoulder pain. A month earlier she had developed pain on chewing and was unable to fully open her mouth. The next day she was reviewed in the eye hospital due to 24hrs of intermittent blurred vision. CT head was normal. Fundoscopy was normal and she was diagnosed with ocular migraine. Later that evening she lost vision in the right eye. Bloods showed CRP 58 and ESR 43. She was given 5 days of IV methylprednisolone (5x1g). Despite this she developed a right 6th nerve palsy. 2 days later her left eye developed visual loss, complete ptosis and loss of eye movements in all directions. MRI head with gadolinium showed temporoparietal juxtacortical diffuse white matter signal abnormalities.She underwent extensive investigation. ANCA was negative, lumbar puncture normal and temporal artery biopsy showed extensive fibrinoid necrosis of the vessel wall, with possible granulomata but no eosinophilia. Oral cyclophosphamide (2mg/kg) was started. 5 days later she developed severe bi-temporal pain and a rash which progressed to severe scalp necrosis. There were no vesicles to suggest shingles. Ten days later she suffered an upper gastro-intestinal bleed requiring a 4 unit transfusion. Gastroscopy showed mild gastritis. After this, cyclophosphamide was withheld, following discharge on steroids alone. Bilateral scalp necrosis remained a problem, complicated by pseudomonas infections. When a decreased left radial pulse was noted a PET CT was arranged. This showed active extensive vasculitis of the aorta. At this point methotrexate 15mg per week was added. The scalp lesions rapidly healed and the radial pulse returned to normal. The CRP has remained consistently below 5. DiscussionAn antiplatelet agent, clopidogrel was started due to the ischaemic cerebral findings on MRI, but it probably contributed, along with steroids, to her upper GI bleed. Antiplatelet therapy is no longer recommended routinely in the management of GCA. However in this case the diagnosis was still uncertain. None of us had ever seen orbital infarction syndrome as a complication of GCA. Perhaps a PET CT earlier on in the course of this lady’s disease would have made us more secure in the diagnosis. It could be argued that given the severity of her disease, methotrexate or even tocilizumab should have been commenced earlier. In fact, cyclophosphamide was used initially as it wasn’t clear if this was a medium vessel vasculitis. This was withheld when she had a large upper GI bleed (Hb dropped to 76). Once recovering, her CRP was down to 10. By this time the temporal artery biopsy was available, the ANCA was negative and GCA was felt to be the most likely diagnosis. It was also felt that given the bilateral visual loss, the most feared complication of GCA had already occurred so what was there to gain by using such strong immunosuppression? Hence cyclophosphamide was discontinued, and she was discharged on steroids alone. The addition of methotrexate had an impressive effect in terms of healing her weeping, secondarily infected scalp necrosis. Methotrexate was added in light of the PET CT which showed active large vessel vasculitis. The scalp necrosis, on reflection was due to an ongoing vasculitis that was being undertreated.There were missed opportunities for starting steroids earlier in the course of the disease: polymyalgic symptoms 6 months earlier, jaw claudication a month earlier. However it remains uncertain whether or not earlier treatment would have altered the course of this aggressive, severe disease. Key learning pointsScalp necrosis, which very easily can be mistaken for shingles or infections complicating steroid treatment, can be a feature of GCA. Orbital infarction syndrome can be a feature of GCA. Early PET CT might have clarified the diagnosis. Methotrexate should probably have been started once the limited response to IV steroids was apparent. Antiplatelet agents are no longer recommended in the updated BSR guidelines for managing GCA.Conflicts of interestThe authors have declared no conflicts of interest.

The utility of fluorine‐18‐fluorodeoxyglucose positron emission tomography in the diagnosis and monitoring of large vessel vasculitis: A South Australian retrospective audit

To investigate the utility of fluorine-18-labelled deoxyglucose positron emission tomography (FDG-PET) in routine clinical practice to diagnose and monitor disease activity and treatment response in large vessel vasculitis in a South Australian cohort. We performed a retrospective clinical audit of adult patients who received a FDG-PET at a tertiary referral center between August 2010 and August 2015, where the term "vasculitis" appeared in either the request or report. A total of 45 patients met the inclusion criteria. Nine patients (20%) had a positive FDG-PET for large vessel vasculitis. FDG-PET was positive in 3/6 (50%) patients who met the American College of Rheumatology (ACR) criteria for giant cell arteritis or Takayasu's arteritis (TA) on retrospective review. A positive FDG-PET for large vessel inflammation assisted the primary clinician in making the diagnosis of unclassified large vessel vasculitis in six patients. Four of the seven patients who had more than one scan for large vessel vasculitis demonstrated normalized FDG uptake on subsequent scans after a period on glucocorticoid treatment. The remaining three patients persisted in having increased FDG uptake on FDG-PET imaging while on active treatment. Fluorine-18-labelled deoxyglucose positron emission tomography has a role in the diagnosis of large vessel vasculitis, particularly in patients with a high suspicion of active large vessel vasculitis who do not meet the ACR criteria. FDG-PET may have a role in monitoring disease activity in selected patients with large vessel vasculitis especially in identifying occult sites of large vessel inflammation or to titrate prednisolone therapy.

F-18 FDG PET for assessment of disease activity of large vessel vasculitis: A systematic review and meta-analysis

BackgroundThe aim of this study is to investigate the performance of F-18 fluorodeoxyglucose positron emission tomography (F-18 FDG PET) or positron emission tomography/computed tomography (PET/CT) for the assessment of disease activity in patients with large vessel vasculitis (LVV) through a meta-analysis. MethodsThe MEDLINE via PubMed and EMBASE were searched for the studies evaluating the performance of F-18 FDG PET or PET/CT in the assessment of disease activity in patients with LVV. Pooled sensitivity, specificity, diagnostic odds ratios (DORs), and summary receiver-operating characteristic (sROC) curve were estimated across the included studies. Possible publication bias was assessed by Deek’s funnel plot asymmetry tests. ResultsA total of 439 PET images from 298 patients pooled from nine studies showed that the pooled sensitivity was 0.88 [95% confidence interval (CI) 0.79-0.93] without heterogeneity (χ2 = 14.42, P = .07) and the pooled specificity was 0.81 (95% CI 0.64-0.91) with heterogeneity (χ2 = 63.72, P = .00) for the detection of active LVV. The pooled DOR was 30 (95% CI 8-107). Hierarchical sROC curve indicates that the area under the curve was 0.91 (95% CI 0.89-0.94). There was no significant publication bias (P = .42), and meta-regression analysis revealed that none of the variables was the source of the study heterogeneity. ConclusionsF-18 FDG PET has a good performance for the detection of active disease status in patients with LVV. Revised criteria for the assessment of disease activity incorporated with F-18 FDG PET or PET/CT should be introduced and validated. Further studies are warranted to determine if PET-based treatment of LVV can improve outcomes.

Clinical value of [18F]FDG-PET/CT and 3D-black-blood 3T-MRI for the diagnosis of large vessel vasculitis and single-organ vasculitis of the aorta.

We aimed to investigate the clinical value of a 3D-T1w turbo-spin-echo (TSE) sequence and [18F]fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG-PET/CT) for the diagnosis of active large vessel vasculitis (LVV) and single-organ vasculitis (SOV) of the aorta. Twenty-four patients with suspected vasculitis who underwent MRI and PET/CT were retrospectively evaluated. MRI was analyzed for concentric contrast enhancement and wall thickening, and flow artifact intensity (4-point-scales). PET/CT analysis comprised qualitative, quantitative and semiquantitative methods. Imaging findings were correlated with final diagnosis derived from the clinical follow-up data. Fifteen of 24 patients had a clinically confirmed active vasculitis, two had inactive vasculitis and 7 no vasculitis. [18F]FDG-PET/CT and 3D-T1w TSE-MRI revealed both a high diagnostic accuracy of 88% and 83%, respectively. In patients in whom both PET/CT and MRI showed concordant findings (19 patients), the accuracy increased to 95% with a high positive predictive value (92%) and negative predictive value (100%); thus, a correct diagnosis was obtained in 18 of 19 patients. Among the five patients with discordant findings PET/CT correctly identified the two patients without active vasculitis while rated false positive on MRI. Of the three remaining patients with active vasculitis, two were correctly identified by MRI and one by PET/CT. 3D-T1w TSE-MRI and [18F]FDG-PET/CT are both useful in the diagnosis of active vasculitis with high diagnostic accuracies. The diagnostic accuracy was even optimized by combining the two analysis methods. Therefore, there might be substantial potential for the application of whole-body hybrid PET/MRI in the evaluation of vasculitis in future studies.

Imaging large vessel vasculitis with fully integrated PET/MRI: a pilot study.

The aim of this study was to evaluate the feasibility of hybrid [(18)F]fluorodeoxyglucose (FDG) positron emission tomography (PET)/MRI in patients with large vessel vasculitis (LVV) by comparing visual and quantitative parameters to that of PET/CT. Furthermore, the value of PET/MRI in disease activity and extent of LVV was assessed. A total of 16 [(18)F]FDG PET/MRI and 12 [(18)F]-FDG PET/CT examinations were performed in 12 patients with LVV. MRI of the vessel wall by T1-weighted and T2-weighted sequences was used for anatomical localization of FDG uptake and identification of morphological changes associated with LVV. In addition, contrast-enhanced (CE) magnetic resonance angiography (MRA) was performed. The vascular FDG uptake in the vasculitis group was compared to a reference group of 16 patients using a four-point visual score. Visual scores and quantitative parameters [maximum standardized uptake value (SUVmax) and target to background ratio (TBR)] were compared between PET/MRI and PET/CT. Furthermore, correlations between C-reactive protein (CRP) and quantitative PET results, as well the extent of vasculitis in PET, MRI/CE-MRA and combined PET/MRI, were analysed. TBRs, SUVmax values and visual scores correlated well between PET/MRI and PET/CT (r = 0.92, r = 0.91; r = 0.84, p < 0.05). There was no significant difference between both modalities concerning SUVmax measurements and visual scores. In PET/MRI, PET alone revealed abnormal FDG uptake in 86 vascular regions. MRI/CE-MRA indicated 49 vessel segments with morphological changes related to vasculitis, leading to a total number of 95 vasculitis regions in combination with PET. Strong and significant correlations between CRP and disease extent in PET alone (r = 0.75, p = 0.0067) and PET/MRI (r = 0.92, p < 0.0001) in contrast to MRI/CE-MRA only were observed. Regarding disease activity, no significant correlations were seen between quantitative PET results and CRP, although there was a trend towards significance (r = 0.55, p = 0.0651). PET/MRI also showed active LVV in 15/16 examinations. Hybrid PET/MRI is feasible in LVV and holds promise for precisely determining disease extent and disease activity.

FRI0247 Black Blood Mri/A for Diagnosis of Large Vessel Vasculitis

BackgroundLarge vessel vasculitis affecting the aorta and its primary branches may present with symptoms and findings that closely mimic other diseases, making the diagnosis difficult. Conventional inflammatory markers may not...

Diagnosis and Assessment of Disease Activity in Takayasu Arteritis: A Childhood Case Illustrating the Challenge

Takayasu Arteritis (TA) is a rare, debilitating large vessel vasculitis occurring in patients of all ages, including infants, but the disease most commonly presents in the third decade. Diagnosis is often delayed and consequently TA is associated with significant morbidity and mortality. Accurate methods of monitoring disease activity or damage are lacking and currently rely on a combination of clinical features, blood inflammatory markers, and imaging modalities. In this report we describe a case of a 14-year-old boy with childhood-onset TA who, despite extensive negative investigations, did indeed have on-going active large vessel vasculitis with fatal outcome. Postmortem analysis demonstrated more extensive and active disease than originally identified. This report illustrates and discusses the limitations of current modalities for the detection and monitoring of disease activity and damage in large vessel vasculitis. Clinicians must be aware of these limitations and challenges if we are to strive for better outcomes in TA.

To stent or not to stent - a challenging decision in a rare condition

Introduction: In this case we discuss the management of a patient with recurrent acute coronary syndrome due to Takayasu arteritis (TA). Case report description: In 2007, a 13-year-old Caucasian male with angina, electrocardiographic and troponin abnormalities consistent with an acute coronary syndrome, and widespread bruits, was found to have multiple arterial stenoses involving the aorta, renal and carotid arteries. The erythrocyte sedimentation rate was 32mm (0-7), C reactive protein 36 mg/L (0-7) with a mild normocytic anaemia. Coronary angiography showed triple vessel disease and he was diagnosed with TA with coronary artery involvement. Coronary artery bypass graft surgery (free left internal mammary graft to the left anterior descending artery and sequential saphenous vein graft to the intermediate and left posterolateral vessels) was performed. The patient received intensive medical therapy and angioplasty for hypertension due to bilateral renal artery stenosis. His condition continued to progress and angina recurred in 2012 with coronary angiography demonstrating occlusion of the vein graft segment to the posterolateral artery. The patient was managed medically but was diagnosed with a non-ST elevation myocardial infarction in 2013 due to occlusion of the vein graft to the intermediate. He suffered ongoing symptoms of cardiac ischaemia and after discussion with the Cardiosurgical team a decision was made to treat the diseased native right coronary artery by percutaneous coronary artery intervention (PCI) with drug eluting stents. Despite this measure the patient has experienced ongoing angina and further PCI to the ungrafted left coronary artery territories is under consideration. Discussion: TA most commonly presents in 20-30 year-old females of East Asian descent and coronary artery involvement in children is very rare. From a cardiac perspective this case highlights the challenge of managing coronary artery disease in the setting of active large vessel vasculitis. Limited data exist to guide clinicians in this setting. Whether redo cardiac surgery at age 18 would be superior to a percutaneous approach is unclear. Implications to clinical practice: 1. Our case highlights the importance of considering vasculitis in the differential diagnosis of a young patient presenting with chest pain. 2. Rare clinical scenarios can pose a management dilemma for the treating physician due to the paucity of supporting research available to direct the decision making process. Treatment strategies should be decided on a case-by-case basis and consensus opinion from the multidisciplinary team is recommended.

Tocilizumab: a novel therapy for patients with large-vessel vasculitis

Treatment of large-vessel vasculitis (LVV) remains challenging. Patients usually respond to glucocorticoid (GC) therapy, but often relapse on tapering of the GC dose or after GC withdrawal. In addition, GCs are fraught with numerous adverse events. The aim of this study was to assess the efficacy and safety of the anti-IL-6 receptor (IL-6R) antibody tocilizumab (TCZ) in patients with LVV. Four patients with active LVV (two with GCA and two with Takayasu arteritis) received monthly TCZ infusions (8 mg/kg bodyweight) for 6 consecutive months. Two patients were treatment naïve, while two had relapsing disease. Disease activity and drug tolerability were assessed clinically and by laboratory tests at study entry and subsequently every month for 6 months of TCZ treatment, while an [(18)F]fluorodeoxyglucose PET (PET/CT) scan was performed before and after treatment. In addition, a semi-quantitative clinical evaluation was performed at baseline and at 3 and 6 months using the Indian Takayasu activity score and the Kerr indices. After TCZ, MTX was used as maintenance therapy. All patients treated with TCZ therapy had a satisfactory clinical and laboratory response, while PET/CT findings significantly improved in all cases. No serious adverse events were noted. Only one patient had a transient increase in liver enzymes. In this small group of patients with LVV, treatment with TCZ was effective and well tolerated. Further, larger studies are required to confirm our findings.

Is Fluorine 18 Fluorodeoxyglucose Positron Emission Tomography Scanning a Suitable Diagnostic Test for Histologically Active Large-Vessel Vasculitis?

Recent publications have highlighted the use of fluorine 18 fluorodeoxyglucose (F-FDG) positron emission tomography (PET) as a moderately sensitive, noninvasive diagnostic test for medium- and large-vessel vasculitis. We report the atypical case of a patient with biopsy-proven granulomatous vasculitis of the aorta in addition to a non-small cell lung cancer, whose whole-body F-FDG PET/computed tomography scan demonstrated metabolic activity within the lung malignancy but was metabolically inactive in the aorta. We submit that F-FDG PET may not be an accurate diagnostic test for histologically active large-vessel vasculitis and should be used with caution.