257 results found
Porter A, Youngstein T, Tombetti E, et al., Biologic therapy in supra-aortic Takayasu arteritis can improve symptoms of cerebral ischaemia without surgical intervention, Rheumatology, ISSN: 0080-2727
Background: Takayasu arteritis typically results in severe arterial injury with stenoses, occlusions and occasionally aneurysms. Involvement of the supra-aortic arteries is common, and in its most severe form may compromise cerebral blood supply, resulting in signs of cerebral ischaemia including visual impairment, dysphasia, hemiparesis, loss of consciousness and stroke. In addition to combination immunosuppression, the management paradigm for symptomatic cerebral ischaemia includes revascularisation. The invasive nature of this surgery, the risk of complications and the relatively high rate of re-stenosis is of concern to patients and physicians alike.The aim of this study was to determine whether combined immunosuppression with early escalation to biologic therapy improved outcomes and reduced the need for high risk surgical intervention Methods: A retrospective review of 145 Takayasu arteritis patients attending Imperial College Healthcare between 2010-2018 was conducted to identify those with cerebral ischaemia secondary to supra-aortic disease and to analyse their treatment and outcomes. Results: Eight patients (5.5%) were identified. Seven received long-term combined immunosuppressive therapy and six were prescribed biologics. The data revealed a higher than expected comprehensive response to therapy, with significant falls in disease activity, cerebral ischaemia score and prednisolone dose required, over a median follow-up of 37 months. Serial imaging analysis detected no arterial disease progression after the initiation of optimal therapy. Only one patient required surgical intervention for persistent neurological symptoms. Conclusion: Early use of biologic therapy in those with supra-aortic Takayasu arteritis presenting with cerebral ischaemia may reduce the numbers of patients requiring surgical intervention and improve outcomes.
Peghaire C, Dufton N, Lang M, et al., 2019, The transcription factor ERG regulates a low shear stress-induced anti-thrombotic pathway in the microvasculature, Nature Communications, Vol: 10, ISSN: 2041-1723
Endothelial cells actively maintain an anti-thrombotic environment; loss of this protective function may lead to thrombosis and systemic coagulopathy. The transcription factor ERG is essential to maintain endothelial homeostasis. Here we show that inducible endothelial ERG deletion (ErgiEC-KO) in mice is associated with spontaneous thrombosis, hemorrhages and systemic coagulopathy. We find that ERG drives transcription of the anti-coagulant thrombomodulin (TM), as shown by reporter assays and chromatin immunoprecipitation. TM expression is regulated by shear stress (SS) via Krüppel-like factor 2 (KLF2). In vitro, ERG regulates TM expression under low SS conditions, by facilitating KLF2 binding to the TM promoter. However, ERG is dispensable for TM expression in high SS conditions. In ErgiEC-KO mice, TM expression is decreased in liver and lung microvasculature exposed to low SS but not in blood vessels exposed to high SS. Our study identifies an endogenous, vascular bed- specific anti-coagulant pathway in microvasculature exposed to low SS.
Poo SX, Tham CSW, Smith C, et al., 2019, IgG4-related disease in a multi-ethnic community: Clinical characteristics and association with malignancy, QJM: An International Journal of Medicine, Vol: 112, Pages: 763-769, ISSN: 1460-2393
BackgroundImmunoglobulin-G4-related disease (IgG4-RD) is a recently recognised fibro-inflammatory condition that can affect multiple organs. Despite growing interest in this condition, the natural history and management of IgG4-RD remain poorly understood.AimTo describe the clinical characteristics, treatment and outcomes of IgG4-RD in a multi-ethnic UK cohort, and investigate its possible association with malignancy.DesignRetrospective analysis of case-note and electronic data.MethodsCases were identified from sub-specialty cohorts and a systematic search of an NHS trust histopathology database using ‘IgG4’ or ‘inflammatory pseudotumour’ as search terms. Electronic records, imaging and histopathology reports were reviewed.Results66 identified cases of IgG4-RD showed a similar multi-ethnic spread to the local population of North West London. The median age was 59 years and 71% of patients were male. Presenting symptoms relating to mass effect of a lesion were present in 48% of cases and the mean number of organs involved was 2.4. 10 patients had reported malignancies with 6 of these being haematological. 83% of those treated with steroids had good initial response, however 50% had relapsing-remitting disease. Rituximab was administered in 11 cases and all achieved an initial serological response. Despite this, 7 patients subsequently relapsed after a mean duration of 11 months and 4 progressed despite treatment.ConclusionsWe report a large UK-based cohort of IgG4-RD that shows no clear ethnic predisposition and a wide range of affected organs. We discuss the use of serum IgG4 concentrations as a disease marker in IgG4-RD, the association with malignant disease and outcomes according to differing treatment regimens.
Tarkin JM, Mason JC, Fayad ZA, 2019, Imaging at the inter-face of inflammation and angiogenesis by 18F-fluciclatide PET., Heart
Boyle J, Seneviratne A, Hyde G, et al., 2019, METFORMIN DIRECTLY SUPPRESSES ATHEROSCLEROSIS IN NORMOGLYCEMIC MICE VIA HAEMATOPOIETIC ADENOSINE MONOPHOSPHATE-ACTIVATED PROTEIN KINASE (AMPK), 87th Congress of the European-Atherosclerosis-Society (EAS), Publisher: ELSEVIER IRELAND LTD, Pages: E45-E46, ISSN: 0021-9150
Boyle J, Seneviratne A, Han Y, et al., 2019, VERTEBRATE HEMATOMA RESOLUTION IS DIRECTED BY ACTIVATING TRANSCRIPTION FACTOR 1 (ATF1) AND ADENOSINE-MONOPHOSPHATE-ACTIVATED-PROTEIN-KINASE (AMPK), 87th Congress of the European-Atherosclerosis-Society (EAS), Publisher: ELSEVIER IRELAND LTD, Pages: E246-E246, ISSN: 0021-9150
Coath F, Gillbert K, Griffiths B, et al., 2019, Corrigendum: Giant cell arteritis: new concepts, treatments and the unmet need that remains, Rheumatology, Vol: 58, Pages: 1123-1125, ISSN: 1462-0324
This is a correction to: Rheumatology, Volume 58, Issue 7, July 2019, Pages 1123–1125, https://doi.org/10.1093/rheumatology/key326
Coath F, Gillbert K, Hall F, et al., 2019, Giant cell arteritis: new concepts, treatments and the unmet need that remains, Rheumatology, Vol: 58, Pages: 1123-1125, ISSN: 1462-0324
Nadkarni S, Lashin H, Hollywood J, et al., 2019, Identification of an activated neutrophil phenotype in polymyalgia rheumatica during steroid treatment: a potential involvement of immune cell cross-talk, Clinical Science, Vol: 133, Pages: 839-851, ISSN: 0143-5221
We have reported the existence of a distinct neutrophil phenotype in giant cell arteritis (GCA) patients arising at week 24 of steroid treatment. In the present study, we investigated whether longitudinal analysis of neutrophil phenotype in patients with polymyalgia rheumatica (PMR) could reveal a novel association with disease status and immune cell cross-talk. Thus, we monitored PMR patient neutrophil phenotype and plasma microvesicle (MV) profiles in blood aliquots collected pre-steroid, and then at weeks 1, 4, 12 and 24 post-steroid treatment.Using flow cytometric and flow chamber analyses, we identified 12-week post-steroid as a pivotal time-point for a marked degree of neutrophil activation, correlating with disease activity. Analyses of plasma MVs indicated elevated AnxA1+ neutrophil-derived vesicles which, in vitro, modulated T-cell reactivity, suggesting distinct neutrophil phenotypic and cross-talk changes at 24 weeks, but not at 12-week post-steroid.Together, these data indicate a clear distinction from GCA patient neutrophil and MV signatures, and provide an opportunity for further investigations on how to ‘stratify’ PMR patients and monitor their clinical responses through novel use of blood biomarkers.
Shah K, Mason JC, 2019, REAL LIFE EXPERIENCE OF TOCILIZUMAB FOR TAKAYASU ARTERITIS, Annual Conference of the British-Soceity-for-Rheumatology, Publisher: OXFORD UNIV PRESS, Pages: 158-158, ISSN: 1462-0324
Mason J, Olabi B, Farah Z, 2019, Cutaneous polyarteritis nodosa presenting atypically with severe pharyngeal ulceration, Case Reports in Rheumatology, Vol: 2019, ISSN: 2090-6889
Polyarteritis nodosa (PAN) is a multisystem, necrotising vasculitis of small- and medium-sized arteries with a predilection for the visceral vessels. Cutaneous PAN is a rare variant with symptomatic vasculitis limited to the skin, typically presenting as nodular lesions on the extremities with a propensity to ulcerate. We describe a rare case of histologically confirmed cutaneous PAN presenting in a 55-year-old Ghanaian woman with severe oropharyngeal ulceration. This was associated with dysphagia and significant weight loss. Oesophagoduodenoscopy showed that the ulceration extended throughout the oropharynx. Systemic polyarteritis nodosa was ruled out with magnetic resonance angiography. Our patient was treated successfully with corticosteroids and methotrexate. This case suggests that cutaneous PAN should be considered in the differential diagnosis of patients with oropharyngeal ulceration and that histological assessment is pivotal in establishing the diagnosis early in order to instigate appropriate therapy.
Tombetti E, Mason JC, 2019, Takayasu arteritis: advanced understanding is leading to new horizons, Rheumatology, Vol: 58, Pages: 206-219, ISSN: 1462-0324
Although outcomes in Takayasu arteritis (TAK) are improving, diagnosis is typically delayed and significant arterial injury accrues. While wider use of non-invasive imaging is impacting this, the onus remains with clinicians to consider a diagnosis of TAK earlier. Meanwhile, morbidity and mortality in TAK remains increased. Herein we review the current situation, outline recent advances and summarize remaining challenges. Understanding of disease pathogenesis remains poor. However, recent genetic data and identification of pathogenic cytokines may facilitate the search for biomarkers capable of distinguishing active and inactive disease, inflammatory and non-inflammatory arterial remodelling. Imaging is critical for TAK, and each modality has important strengths and limitations. Dependence upon CS therapy remains too high. However, the impact of combination immunosuppressive therapy is now recognized, biologic therapies are increasingly available and new agents offer promise. Multicentre clinical trials are now required, and these will depend upon development of defined clinical and imaging end-points.
Tombetti E, Godi C, Ambrosi A, et al., 2018, Novel angiographic scores for evaluation of large vessel vasculitis, Scientific Reports, Vol: 8, ISSN: 2045-2322
Arterial involvement is the cardinal feature of large-vessel vasculitis (LVV) and prevention of disease progression is the principal therapeutic goal. However, development of tools for its evaluation represents a major unmet need. To address this, a widely-applicable imaging tool for LVV, analysing arterial involvement in 17 arterial territories, has been developed and validated. Individual stenosis and dilation scores were generated and combined in a composite score. The methodology was validated cross-sectionally and longitudinally in 131 patients, 96 Takayasu arteritis (TA), 35 large-vessel giant-cell arteritis (LV-GCA). In total, 4420 arterial segments from 260 imaging studies were evaluated. The new scores allowed quantitative grading of LVV arterial involvement with high consistency, revealing inter-patient differences. TA had higher stenosis and composite scores and lower dilation scores than LV-GCA. Baseline stenotic and composite scores reflected arterial damage rather than disease-activity. Longitudinal changes in all three scores correlated with disease activity and mirrored arterial disease evolution, reflecting both progressive injury and lesion improvement. Increases ≥1 in any score were specific for arterial disease progression. The scores objectively quantify arterial involvement in LVV, providing precise definition of disease phenotype and evolution. We propose that they represent novel vascular outcome measures essential for future clinical trials.
Pearson JD, Mason JC, 2018, Reactive oxygen species as drivers of autoimmune pathology: an introduction to special issue “Oxidative stress and altered redox signalling in autoimmune and connective tissue diseases”, Free Radical Biology and Medicine, Vol: 125, Pages: 1-2, ISSN: 0891-5849
Mason JC, 2018, Surgical intervention and its role in Takayasu arteritis, Best Practice and Research: Clinical Rheumatology, Vol: 32, Pages: 112-124, ISSN: 1521-6942
Vascular surgery remains an important option in the management of Takayasu arteritis (TA). Its use is predominantly confined to the treatment of symptomatic organ ischaemia or life-threatening aneurysm formation. In most cases, this follows the failure of medical therapy to prevent arterial injury. Open surgery and endovascular approaches are used. The choice between them, at least in part, is determined by the site and nature of the lesion. Open surgery, although more invasive, offers enhanced duration of arterial patency, whereas for endovascular intervention, primary angioplasty without stenting is preferred, with stenting reserved for primary or secondary angioplasty failures. Although there is increasing interest in the role of stent grafts and tailor-made endovascular stents, long-term outcomes remain to be reported. Interventional outcomes are improved and complications reduced by therapeutic control of disease activity before and after surgery. The wider use of combined immunosuppression and the introduction of biologic therapy for refractory TA may reduce future requirements for surgical intervention.
Alrashed F, Calay D, Lang M, et al., 2018, Celecoxib exerts protective effects in the vascular endothelium via COX-2-independent activation of AMPK-CREB-Nrf2 signalling, Scientific Reports, Vol: 8, ISSN: 2045-2322
Although concern remains about the athero-thrombotic risk posed by cyclo-oxygenase (COX)-2-selective inhibitors, recent data implicates rofecoxib, while celecoxib appears equivalent to NSAIDs naproxen and ibuprofen. We investigated the hypothesis that celecoxib activates AMP kinase (AMPK) signalling to enhance vascular endothelial protection. In human arterial and venous endothelial cells (EC), and in contrast to ibuprofen and naproxen, celecoxib induced the protective protein heme oxygenase-1 (HO-1). Celecoxib derivative 2,5-dimethyl-celecoxib (DMC) which lacks COX-2 inhibition also upregulated HO-1, implicating a COX-2-independent mechanism. Celecoxib activated AMPKα(Thr172) and CREB-1(Ser133) phosphorylation leading to Nrf2 nuclear translocation. Importantly, these responses were not reproduced by ibuprofen or naproxen, while AMPKα silencing abrogated celecoxib-mediated CREB and Nrf2 activation. Moreover, celecoxib induced H-ferritin via the same pathway, and increased HO-1 and H-ferritin in the aortic endothelium of mice fed celecoxib (1000 ppm) or control chow. Functionally, celecoxib inhibited TNF-α-induced NF-κB p65(Ser536) phosphorylation by activating AMPK. This attenuated VCAM-1 upregulation via induction of HO-1, a response reproduced by DMC but not ibuprofen or naproxen. Similarly, celecoxib prevented IL-1β-mediated induction of IL-6. Celecoxib enhances vascular protection via AMPK-CREB-Nrf2 signalling, a mechanism which may mitigate cardiovascular risk in patients prescribed celecoxib. Understanding NSAID heterogeneity and COX-2-independent signalling will ultimately lead to safer anti-inflammatory drugs.
Mason JC, Vascular cytoprotection, autoimmune disease and premature atherosclerosis, Indian Journal of Rheumatology, ISSN: 0973-3698
A healthy vascular endothelium is critical to health and interference with endothelial homeostasis disrupts haemostasis, regulation of vascular tone and blood pressure, leukocyte trafficking, angiogenesis and tissue repair. Endothelial injury and apoptosis leads to endothelial dysfunction, which is closely associated with increased generation of reactive oxygen species, reduced endothelial nitric oxide synthase, increased consumption and impaired synthesis of nitric oxide. Systemic inflammatory diseases including rheumatoid arthritis and systemic lupus erythematosus are associated with endothelial dysfunction and increased aortic stiffness, states closely associated with atherogenesis. Premature cardiovascular disease is well recognised feature of many rheumatic diseases. The cell and molecular mechanisms related to this remain poorly understood. Specific diseases display individual and common attributes that likely influence cardiovascular risk. A key challenge is the development of the means by which those at highest risk can be identified. Likewise, the ability of current therapies to mitigate risk and the identification of novel vasculoprotective therapies represent important areas of research focus. Similarly close liaison between rheumatologists and cardiologists is essential to minimise the cardiovascular impact on patients and to ensure that patients with rheumatic disease and co-existent coronary heart disease receive appropriate therapy. Identification of safe therapeutic approaches that combine the targeted immunosuppression required, along with comprehensive vascular protection to control the primary disease and prevent secondary complications over the longer term, remains the ultimate challenge.
Aydin SZ, Direskeneli H, Merkel PA, et al., 2017, Assessment of Disease Activity in Large-vessel Vasculitis: Results of an International Delphi Exercise., J Rheumatol, Vol: 44, Pages: 1928-1932, ISSN: 0315-162X
OBJECTIVE: To arrive at consensus for candidate outcomes for disease activity assessment in large-vessel vasculitis (LVV) in clinical trials. METHODS: A Delphi survey including 99 items was circulated among international experts for 3 rounds. RESULTS: Fifty-seven items were accepted for both giant cell arteritis and Takayasu arteritis. Sixty-seven percent of experts voted to have a common approach for both diseases with additional disease-specific items such as weight loss, scalp tenderness/necrosis, morning stiffness, dizziness, visual symptoms, and imaging. CONCLUSION: This study highlights similarities and differences in experts' perspectives for assessing clinical activity in LVV and may guide a consensus-driven core set of validated outcomes.
Dufton NP, peghaire CR, Osuna-Almagro L, et al., 2017, Dynamic regulation of canonical TGFβ signaling by endothelial transcription factor ERG protects from liver fibrogenesis, Nature Communications, Vol: 8, ISSN: 2041-1723
The role of the endothelium in protecting from chronic liver disease and TGFβ-mediated fibrosis remains unclear. Here we describe how the endothelial transcription factor ETS-related gene (ERG) promotes liver homoeostasis by controlling canonical TGFβ-SMAD signalling, driving the SMAD1 pathway while repressing SMAD3 activity. Molecular analysis shows that ERG binds to SMAD3, restricting its access to DNA. Ablation of ERG expression results in endothelial-to-mesenchymal transition (EndMT) and spontaneous liver fibrogenesis in EC-specific constitutive hemi-deficient (ErgcEC-Het) and inducible homozygous deficient mice (ErgiEC-KO), in a SMAD3-dependent manner. Acute administration of the TNF-α inhibitor etanercept inhibits carbon tetrachloride (CCL4)-induced fibrogenesis in an ERG-dependent manner in mice. Decreased ERG expression also correlates with EndMT in tissues from patients with end-stage liver fibrosis. These studies identify a pathogenic mechanism where loss of ERG causes endothelial-dependent liver fibrogenesis via regulation of SMAD2/3. Moreover, ERG represents a promising candidate biomarker for assessing EndMT in liver disease.
Dejaco C, Brouwer E, Mason JC, et al., 2017, Giant cell arteritis and polymyalgia rheumatica: current challenges and opportunities, NATURE REVIEWS RHEUMATOLOGY, Vol: 13, Pages: 578-592, ISSN: 1759-4790
The fields of giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) have advanced rapidly, resulting in a new understanding of these diseases. Fast-track strategies and improved awareness programmes that prevent irreversible sight loss through early diagnosis and treatment are a notable advance. Ultrasonography and other imaging techniques have been introduced into routine clinical practice and there have been promising reports on the efficacy of biologic agents, particularly IL-6 antagonists such as tocilizumab, in treating these conditions. Along with these developments, which should improve outcomes in patients with GCA and PMR, new questions and unmet needs have emerged; future research should address which pathogenetic mechanisms contribute to the different phases and clinical phenotypes of GCA, what role imaging has in the early diagnosis and monitoring of GCA and PMR, and in which patients and phases of these diseases novel biologic drugs should be used. This article discusses the implications of recent developments in our understanding of GCA and PMR, as well as the unmet needs concerning epidemiology, pathogenesis, imaging and treatment of these diseases.
Ribeiro-Rodrigues TM, Laundos TL, Pereira-Carvalho R, et al., 2017, Exosomes secreted by cardiomyocytes subjected to ischaemia promote cardiac angiogenesis, CARDIOVASCULAR RESEARCH, Vol: 113, Pages: 1338-1350, ISSN: 0008-6363
Lynskey NN, Reglinski M, Calay D, et al., 2017, Multi-functional mechanisms of immune evasion by the streptococcal complement inhibitor C5a peptidase, PLOS Pathogens, Vol: 13, ISSN: 1553-7366
The complement cascade is crucial for clearance and control of invading pathogens, and as such is a key target for pathogen mediated host modulation. C3 is the central molecule of the complement cascade, and plays a vital role in opsonization of bacteria and recruitment of neutrophils to the site of infection. Streptococcal species have evolved multiple mechanisms to disrupt complement-mediated innate immunity, among which ScpA (C5a peptidase), a C5a inactivating enzyme, is widely conserved. Here we demonstrate for the first time that pyogenic streptococcal species are capable of cleaving C3, and identify C3 and C3a as novel substrates for the streptococcal ScpA, which are functionally inactivated as a result of cleavage 7 amino acids upstream of the natural C3 convertase. Cleavage of C3a by ScpA resulted in disruption of human neutrophil activation, phagocytosis and chemotaxis, while cleavage of C3 generated abnormally-sized C3a and C3b moieties with impaired function, in particular reducing C3 deposition on the bacterial surface. Despite clear effects on human complement, expression of ScpA reduced clearance of group A streptococci in vivo in wildtype and C5 deficient mice, and promoted systemic bacterial dissemination in mice that lacked both C3 and C5, suggesting an additional complement-independent role for ScpA in streptococcal pathogenesis. ScpA was shown to mediate streptococcal adhesion to both human epithelial and endothelial cells, consistent with a role in promoting bacterial invasion within the host. Taken together, these data show that ScpA is a multi-functional virulence factor with both complement-dependent and independent roles in streptococcal pathogenesis.
Tombetti E, Mason JC, 2017, Application of imaging techniques for Takayasu arteritis, La Presse medicale, Vol: 46, Pages: e215-e223, ISSN: 0032-7867
Arterial injury with subsequent remodelling and predisposition to arterial stenosis and/or dilation are the hallmarks of Takayasu arteritis. The degree of arterial damage closely aligns with prognosis and therefore its prevention is the predominant aim of therapy. Non-invasive imaging has greatly improved our ability to identify the extent and severity of disease and to monitor its progress. However, many questions remain concerning the optimal use of individual modalities at different stages of disease. Imaging methods for the quantification of arterial damage are lacking. Likewise, no single technique can accurately determine disease activity within the arterial wall or distinguish inflammatory and non-inflammatory disease progression. The aim of this review is to outline current imaging strategies in Takayasu arteritis, their individual roles in diagnosis and disease monitoring and potential future advances.
Shah AV, Birdsey GM, Peghaire C, et al., 2017, The endothelial transcription factor ERG mediates Angiopoietin-1-dependent control of Notch signalling and vascular stability, Nature Communications, Vol: 8, ISSN: 2041-1723
Notch and Angiopoietin-1 (Ang1)/Tie2 pathways are crucial for vascular maturation and stability. Here we identify the transcription factor ERG as a key regulator of endothelial Notch signalling. We show that ERG controls the balance between Notch ligands by driving Delta-like ligand 4 (Dll4) while repressing Jagged1 (Jag1) expression. In vivo, this regulation occurs selectively in the maturing plexus of the mouse developing retina, where Ang1/Tie2 signalling is active. We find that ERG mediates Ang1-dependent regulation of Notch ligands and is required for the stabilizing effects of Ang1 in vivo. We show that Ang1 induces ERG phosphorylation in a phosphoinositide 3-kinase (PI3K)/Akt-dependent manner, resulting in ERG enrichment at Dll4 promoter and multiple enhancers. Finally, we demonstrate that ERG directly interacts with Notch intracellular domain (NICD) and β-catenin and is required for Ang1-dependent β-catenin recruitment at the Dll4 locus. We propose that ERG coordinates Ang1, β-catenin and Notch signalling to promote vascular stability.
Alrashed F, Calay D, Thornton CC, et al., 2017, SELECTIVE ACTIVATION OF AN AMPK-CREB-NRF2-DEPENDENT PATHWAY BY CELECOXIB INDUCES VASCULOPROTECTIVE GENES AND MITIGATES AGAINST CARDIOVASCULAR RISK, Annual European Congress of Rheumatology, Publisher: BMJ PUBLISHING GROUP, Pages: 219-219, ISSN: 0003-4967
Mason JC, Youngstein T, Tombetti E, et al., 2017, PET Imaging in Takayasu Disease Requiring Arterial Grafts REPLY, JACC: Cardiovascular Imaging, Vol: 10, Pages: 607-608, ISSN: 1936-878X
Bechman K, Gopalan D, Nihoyannopoulos P, et al., 2017, A cohort study reveals myocarditis to be a rare and life-threatening presentation of large vessel vasculitis, Seminars in Arthritis and Rheumatism, Vol: 47, Pages: 241-246, ISSN: 1532-866X
BackgroundThe predominant forms of adult large vessel vasculitis (LVV) are giant cell arteritis (GCA) and Takayasu arteritis (TA). Cardiac involvement in LVV is a cause of morbidity and mortality, particularly in TA. Cardiac failure is most commonly secondary to uncontrolled arterial hypertension or myocardial ischaemia. Pulmonary hypertension and aortic valve incompetence following ascending aortic dilatation represent other serious cardiovascular complications. However, cardiac failure as a consequence of myocarditis is rarely reported, principally in single case reports or in autopsy studies.MethodsThe Imperial College LVV database was, retrospectively, reviewed to identify patients with cardiac involvement at presentation. Patients with evidence for myocarditis were identified. The cardiac presentation, imaging studies and subsequent medical and surgical management were reviewed in detail.ResultsThe cohort included 139 patients with TA and 24 with GCA. Sixteen presented with cardiac failure without a history of ischaemic coronary heart disease, 14 (10%) with TA and 2 (8.3%) with GCA. Cardiovascular disease identified at presentation included aortic regurgitation (n = 11), myocarditis (n = 4) and hypertensive cardiomyopathy secondary to renal artery stenosis (n = 1). Those patients with evidence of myocarditis at presentation (2.8%) underwent transthoracic echocardiography and cardiac magnetic resonance imaging (CMR). These non-invasive techniques were sufficient for diagnosis of clinically significant myocarditis. Furthermore, they were subsequently used to monitor response to treatment, with serial improvement in left ventricular ejection fraction (LVEF) observed in all 4 patients (p < 0.05). Prednisolone plus cyclophosphamide (CyC) therapy was associated with significant improvement in heart failure symptoms and LVEF in 3 cases. In one case where CyC was contraindicated, tocilizumab treatment led to marked improvement in cardiac symptoms.ConclusionClinicall
Mason JC, Tombetti E, 2017, Pathophysiology of Vasculitis, The ESC Textbook of Vascular Biology, Editors: Krams, Back, Publisher: Oxford University Press, Pages: 253-274
Incerti E, Tombetti E, Fallanca F, et al., 2017, F-18-FDG PET reveals unique features of large vessel inflammation in patients with Takayasu's arteritis, European Journal of Nuclear Medicine and Molecular Imaging, Vol: 44, Pages: 1109-1118, ISSN: 1619-7070
PurposeThe object of this study was to assess whether 18F-fluorodeoxyglucose PET/CT (FDG PET/CT) provides novel information in patients with Takayasu’s arteritis (TA) in addition to that provided by current activity assessment, to analyse the effects of possible confounders, such as arterial grafts, and to verify whether PET/CT could be informative in lesions <4 mm thick.MethodsWe studied 30 patients with TA, evaluated from October 2010 to April 2014 by both PET/CT and magnetic resonance imaging (MRI). All arterial lesions were evaluated by PET both qualitatively (positive/negative) and semiquantitatively (maximum standardized uptake value, SUVmax), and the thickness of lesions in the MRI field of view was evaluated. In a per-patient analysis, the relationships between the PET data and acute-phase reactants and NIH criteria for active TA were evaluated. In a per-lesion analysis, the relationships between the PET features of each lesion and MRI morphological data were evaluated. The effects of the presence of arterial grafts were also evaluated.ResultsIncreased FDG uptake was seen in 16 of 30 patients (53%) and in 46 of 177 vascular lesions (26%). Significant periprosthetic FDG uptake was seen in 6 of 7 patients (86%) with previous vascular surgery and in 10 of 11 of grafts (91%). Graft-associated uptake influenced the PET results in three patients (10%) and the SUVmax values in five patients (17%). Of 39 lesions with significant FDG uptake, 15 (38%) were <4 mm thick. Lesion thickness was correlated with lesion SUVmax in FDG-avid lesions only. FDG arterial uptake was not associated with systemic inflammation or NIH criteria.ConclusionsPET/CT reveals unique and fundamental features of arterial involvement in TA. PET/CT may be useful in the assessment of local inflammatory and vascular remodelling events independent of systemic inflammation during follow-up, even in lesions in which the arterial wall is <4 mm. The presence of arterial grafts is a potenti
Krams CIMBR, Back M, Back SCICM, 2017, ESC Textbook of Vascular Biology, Publisher: Oxford University Press, USA, ISBN: 9780198755777
The official publication of the ESC Working Group on Arthrosclerosis and Vascular Biology, this print edition comes with access to the online version on Oxford Medicine Online, for as long as the edition is published by Oxford University ...
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