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BackgroundSince the publication of the European League Against Rheumatism (EULAR) recommendations for the management of large vessel vasculitis (LVV) in 2009, several relevant randomised clinical trials and cohort analyses have been published, which have the potential to change clinical care and therefore supporting the need to update the original recommendations.MethodsUsing EULAR standardised operating procedures for EULAR-endorsed recommendations, the EULAR task force undertook a systematic literature review and sought opinion from 20 experts from 13 countries. We modified existing recommendations and created new recommendations.ResultsThree overarching principles and 10 recommendations were formulated. We recommend that a suspected diagnosis of LVV should be confirmed by imaging or histology. High dose glucocorticoid therapy (40–60 mg/day prednisone-equivalent) should be initiated immediately for induction of remission in active giant cell arteritis (GCA) or Takayasu arteritis (TAK). We recommend adjunctive therapy in selected patients with GCA (refractory or relapsing disease, presence of an increased risk for glucocorticoid-related adverse events or complications) using tocilizumab. Methotrexate may be used as an alternative. Non-biological glucocorticoid-sparing agents should be given in combination with glucocorticoids in all patients with TAK and biological agents may be used in refractory or relapsing patients. We no longer recommend the routine use of antiplatelet or anticoagulant therapy for treatment of LVV unless it is indicated for other reasons.ConclusionsWe have updated the recommendations for the management of LVV to facilitate the translation of current scientific evidence and expert opinion into better management and improved outcome of patients in clinical practice.

To describe the clinical features, treatment, and outcomes in a longitudinal cohort of patients with Takayasu arteritis (TAK). We retrospectively studied patients with newly diagnosed TAK evaluated from January 1, 1984, through December 31, 2009. The cohort included 126 patients who were predominantly white (85/103; 82.5%) and female (115/126; 91%). The median age at diagnosis was 31.6 years (interquartile range, 22.9-39.8 years). Median delay in diagnosis was 17.5 months (interquartile range, 7-41.8 months). Thirty-one patients (25%) were 40 years or older at diagnosis. Median delay in diagnosis for patients 40 years or older was 44.8 months compared with 28.3 months for those younger than 40 years (P<.001). Limb claudication was the presenting symptom in 64 of 123 patients (52%). Hata type V arteriographic abnormalities were the most common (57/100; 57%). Renal artery abnormalities were observed in 24 of 41 patients (58%) with new-onset hypertension. Inflammatory markers were elevated at diagnosis in 85 of 119 patients (71%). Vascular interventions were performed in 69 patients (55%). Seventy-nine patients (63%) were followed up for more than 1 year (median follow-up, 5.5 years; interquartile range, 2.9-10.0 years). In this subset, treatment consisted of corticosteroids in 73 patients (92%) and additional immunosuppressants in 52 patients (66%). At 5 years, 96% experienced at least one remission of any duration. The overall survival was 97% at 10 years and 86% at 15 years. Mortality was increased compared with the general population (standardized mortality ratio, 3.0; 95% CI, 1.0-8.9). There continues to be an unacceptably long delay in the diagnosis of TAK. Awareness of TAK in patients older than 40 years is needed. Morbidity was high despite immunosuppressive treatment. Survival was decreased in this cohort.

Primary large-vessel vasculitis encompasses conditions that, despite sharing many common features, constitute distinct entities that have their own prognostic implications. These conditions include giant cell arteritis and Takayasu arteritis, with isolated aortitis being increasingly recognised in the literature and studied within this disease spectrum. Epidemiological studies have evidenced a worldwide distribution of Takayasu arteritis. In giant cell arteritis, distinct clinical phenotypes with specific outcomes (ie, cranial and large vessel forms) have been recognised. The advancements that have been made in vascular imaging have enabled improvement in diagnosis and classification of these diseases, although their value in follow-up continues to be assessed. Targeted therapies that can induce clinical remission with reduced glucocorticoid exposure are emerging. However, many patients develop vascular damage over time, highlighting the need for further understanding of the pathophysiological link between inflammation, vascular injury, and remodelling.

Childhood-onset Takayasu Arteritis (c-TA) is a rare, large-vessel vasculitis seen in children that could predisposing patients to a high risk of mortality. Exercise has the potential to improve overall health in several diseases, but evidence remains scant in c-TA. The main objective of this study was to investigate the safety and potential therapeutic effects of exercise in c-TA. This was a 12-week, multicenter, randomized, controlled trial, to test the effects of a home-based, exercise intervention . standard of care in c-TA patients in remission. The primary outcomes were arterial inflammation, assessed by [ F] FDG- PET/MRI and systemic inflammatory markers. Secondary outcomes included, physical activity levels, functionality, body composition, disease-related parameters, and quality of life. Thirty-seven patients were assessed for eligibility, which represents the total number of c-TA patients being followed by the three specialized medical ambulatory services in Sao Paulo. After exclusions, fourteen c-TA patients (71.4% females) aged 12-25 years were randomly allocated into exercised (n=5) and non-exercised groups (n=9). Exercise did not exacerbate arterial inflammation. In fact, exercised patients had a reduction in the frequency of vessel segments with severe inflammation, whereas the non-exercised patients had an opposite response ( =0.007). Greater improvements in visceral fat, steps per day, functionality and physical component SF-36 were observed in the exercised patients ( 0.05). Exercise is safe and may improve visceral fat, physical activity levels, functionality, and physical component SF-36 in c-TA patients. Thus, exercise arises as a novel, evidence-based intervention to improve general health in c-TA. https://www.clinicaltrials.gov/ct2/show/NCT03494062?term=NCT03494062&draw=2&rank=1, identifier NCT03494062.

Objectives Takayasu arteritis (TAK) is an inflammatory vasculitis that affects the aorta and its primary branches. The pathogenesis of TAK remains elusive, yet identifying key cell types in the aorta of TAK patients is crucial for uncovering cellular heterogeneity and discovering potential therapeutic targets. Methods This study utilized single-cell transcriptome analysis on aortic specimens from three TAK patients, with control data sourced from a publicly available database (GSE155468). Additionally, bulk RNA sequencing was performed on peripheral CD4 + and CD8 + T cells from eight TAK patients and eight matched healthy volunteers. All participants were recruited at Anzhen Hospital, Capital Medical University, China, between January 2020 and December 2023. Results Single-cell transcriptome analysis identified 11 predominant cell types in aortic tissues, with notable differences in proportions between TAK patients and controls. T cells, B cells, macrophages, smooth muscle cells (SMCs), and fibroblasts exhibited subtype-specific gene expression signatures, with notable changes in interactions between T cells, B cells, and monocyte-macrophages, highlighting their active involvement in the pathogenesis of TAK. Bulk RNA-Seq analysis of peripheral blood T cells from TAK patients showed an upregulation of complement system genes, underscoring the significance of the complement signaling pathway in TAK’s immunopathogenesis. Conclusion The findings underscore the active involvement of various immune and structural cells in the aortic tissues of TAK patients and reveal the presence of the complement signaling pathway in peripheral blood T cells. These insights are instrumental for identifying novel therapeutic targets and developing robust disease monitoring methods for TAK.

Giant cell arteritis (GCA) is a granulomatous systemic vasculitis of large- and medium-sized arteries that affects the elderly. In recent years, advances in diagnostic imaging have revealed a greater degree of large vessel involvement than previously recognized, distinguishing classical cranial- from large vessel (LV)- GCA. GCA often co-occurs with the poorly understood inflammatory arthritis/bursitis condition polymyalgia rheumatica (PMR) and has overlapping features with other non-infectious granulomatous vasculitides that affect the aorta, namely Takayasu Arteritis (TAK) and the more recently described clinically isolated aortitis (CIA). Here, we review the literature focused on the immunopathology of GCA on the background of the three settings in which comparisons are informative: LV and cranial variants of GCA; PMR and GCA; the three granulomatous vasculitides (GCA, TAK, and CIA). We discuss overlapping and unique features between these conditions across clinical presentation, epidemiology, imaging, and conventional histology. We propose a model of GCA where abnormally activated circulating cells, especially monocytes and CD4 + T cells, enter arteries after an unknown stimulus and cooperate to destroy it and review the evidence for how this mechanistically occurs in active disease and improves with treatment.

Background Advances in treatment have swiftly alleviated systemic inflammation of Takayasu’s arteritis (TAK), while subclinical vascular inflammation and the ensuing arterial remodeling continue to present unresolved challenges in TAK. The phenotypic switching of vascular smooth muscle cells (VSMC) is regarded as the first step in vascular pathology and contributes to arterial remodeling. Exosomes facilitate the transfer and exchange of proteins and specific nucleic acids, thereby playing a significant role in intercellular communication. Little is known about the modulatory role of serum exosomes in phenotypic switching of VSMC and vascular remodeling in TAK. Methods Serum exosomes isolated from TAK patients were co-cultured with VSMC to identify the modulatory role of exosomes. VSMC were transfected with miR-199a-5p mimic and inhibitor. CCK8 assays and EdU assays were performed to measure proliferative ability. The migration of VSMC was evaluated by scratch assays and transwell migration assays. The flow cytometry was employed to identify apoptosis of VSMC. Dual-luciferase reporter assay, RNA immunoprecipitation assay and fluorescence in situ hybridization were utilized to validate the target gene of miR-199a-5p. The correlational analysis was conducted among exosome miRNA, serum MMP2, TIMP2 and clinical parameters in TAK patients. Results The coculture of VSMC with serum exosome mediated dedifferentiation of VSMC. Through gain- and loss-of-function approaches, miR-199a-5p over-expression significantly increased expression of VSMC marker genes and inhibited VSMC proliferation and migration, whilst the opposite effect was observed when endogenous miR-199a-5p was knocked down. The overexpression of miR-199a-5p suppressed VSMC apoptosis. Further, MMP2 serves as functional target gene of miR-199a-5p. The correlation analyses revealed an inverse correlation between Vasculitis Damage Index and exosome miR-199a-5p level or serum MMP2, which requires validation in a larger cohort. Conclusion Our study indicated that the miR-199a-5p/MMP2 pathway played a role in inhibiting the migration, proliferation and apoptosis of VSMC. The decreased secretion of MMP2 may potentially prompt the intimal infiltration of inflammatory cells within the vascular wall, offering a novel therapeutic opportunity by tackling both inflammatory responses and the neointimal overgrowth associated with TAK arterial damage. Moreover, exosome miR-199a-5p and MMP2 derived from serum possess potential as future biomarkers for vascular injury.

Large-vessel vasculitis (LVV) manifests as inflammation of the aorta and its major branches and is the most common primary vasculitis in adults. LVV comprises two distinct conditions, giant cell arteritis and Takayasu arteritis, although the phenotypic spectrum of primary LVV is complex. Non-specific symptoms often predominate and so patients with LVV present to a range of health-care providers and settings. Rapid diagnosis, specialist referral and early treatment are key to good patient outcomes. Unfortunately, disease relapse remains common and chronic vascular complications are a source of considerable morbidity. Although accurate monitoring of disease activity is challenging, progress in vascular imaging techniques and the measurement of laboratory biomarkers may facilitate better matching of treatment intensity with disease activity. Further, advances in our understanding of disease pathophysiology have paved the way for novel biologic treatments that target important mediators of disease in both giant cell arteritis and Takayasu arteritis. This work has highlighted the substantial heterogeneity present within LVV and the importance of an individualized therapeutic approach. Future work will focus on understanding the mechanisms of persisting vascular inflammation, which will inform the development of increasingly sophisticated imaging technologies. Together, these will enable better disease prognostication, limit treatment-associated adverse effects, and facilitate targeted development and use of novel therapies.Large-vessel vasculitis is the most common primary vasculitis in adults, manifesting as inflammation of the aorta and its major branches. This Primer reviews the epidemiology, pathophysiology, diagnosis and management of this disease, highlights its effects on patient quality of life, and discusses future research questions.

ObjectiveTo investigate the efficacy and safety of the interleukin-6 receptor antibody tocilizumab in patients with Takayasu arteritis (TAK).MethodsPatients with TAK who had relapsed within the previous 12 weeks were induced into remission with oral glucocorticoid therapy. In this double-blind, placebo-controlled trial, patients were randomly assigned 1:1 to receive weekly tocilizumab 162 mg or placebo subcutaneously, and oral glucocorticoids were tapered 10 %/week from week 4 to a minimum of 0.1 mg/kg/day until 19 patients relapsed. The primary endpoint was time to relapse of TAK, defined as ≥2 of the following: objective systemic symptoms, subjective systemic symptoms, elevated inflammation markers, vascular signs and symptoms or ischaemic symptoms.ResultsThe intent-to-treat and safety populations included 18 tocilizumab-treated and 18 placebo-treated patients. The per-protocol set (PPS) included 16 tocilizumab-treated and 17 placebo-treated patients. HRs for time to relapse of TAK were 0.41 (95.41% CI 0.15 to 1.10; p=0.0596) in the intent-to-treat population (primary endpoint) based on relapse in eight tocilizumab-treated and 11 placebo-treated patients and 0.34 (95.41% CI 0.11 to 1.00; p=0.0345) in the PPS. The secondary endpoints, time to relapse assessed by Kerr’s definition and clinical symptoms only, were consistent with the primary endpoint. Serious adverse events were reported in one tocilizumab-treated and two placebo-treated patients. There were no serious infections and no deaths.ConclusionAlthough the primary endpoint was not met, the results suggest favour for tocilizumab over placebo for time to relapse of TAK without new safety concerns. Further investigation is warranted to confirm the efficacy of tocilizumab in patients with refractory TAK.Trial registration numberJapicCTI-142616.

Background Takayasu arteritis, a chronic inflammatory disease predominantly affecting the aorta and major arterial branches, can lead to serious complications such as myocardial infarction and heart failure. Case presentation This case report details a rare initial presentation of a 24-year-old female with acute left heart failure, leading to a diagnosis of Takayasu arteritis. Initial misdiagnosis as viral myocarditis was reconsidered after comprehensive examinations, including echocardiography, vascular ultrasound, and imaging studies, which revealed the disease’s characteristic vascular involvement. The patient was treated with a combination of prednisone acetate, tocilizumab, and supportive therapies, resulting in symptomatic and laboratory improvement by the three-year follow-up. Conclusions The case emphasizes the need for clinicians to recognize atypical presentations of Takayasu arteritis to avoid misdiagnosis and to consider its multifactorial impacts on heart failure.