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Nature Reviews. Disease Primers Jan 2022Large-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... (Review)
Review
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.
Topics: Adult; Aorta; Giant Cell Arteritis; Humans; Takayasu Arteritis
PubMed: 34992251
DOI: 10.1038/s41572-021-00327-5 -
Turkish Journal of Medical Sciences Aug 2018Takayasu arteritis (TAK) is a challenging chronic, granulomatous, large-vessel systemic vasculitis, mostly due to difficulties in early diagnosis and assessing actual... (Review)
Review
Takayasu arteritis (TAK) is a challenging chronic, granulomatous, large-vessel systemic vasculitis, mostly due to difficulties in early diagnosis and assessing actual disease activity. Since there are no specific diagnostic laboratory tests, biomarkers, or autoantibodies, many patients experience considerable delay in diagnosis. Remembering the possibility of TAK together with the use of acute phase responses and appropriate imaging studies may be helpful for early diagnosis. Since there may be discrepancies between systemic and vascular wall inflammation, using only acute phase responses is not reliable in assessing current disease activity. Therefore, physical examination and new imaging findings should also be used to assess current disease activity. Despite its limitations, the Indian Takayasu Clinical Activity Score (ITAS2010) may also be helpful for this purpose. The rationale of medical treatment is to suppress both vascular and systemic inflammation with appropriate systemic immunosuppression, including corticosteroids and conventional immunosuppressive agents. In cases of refractory disease activity, leflunomide and biologic agents such as TNF inhibitors and tocilizumab may be tried. In selected cases with persistent lesions that cannot be reversed with medical treatment, endovascular interventions including balloon angioplasty, stent and stent graft replacement, or surgery may be tried. However, such procedures should be performed after suppression of inflammation, i.e. during inactive disease. Prognosis of TAK is probably getting better with lower mortality rates reported in recent years, probably due to the use of more effective medical treatments as well as the use of endovascular interventions when necessary and available.
Topics: Antibodies, Monoclonal, Humanized; Biomarkers; Endovascular Procedures; Guidelines as Topic; Humans; Immunosuppressive Agents; Leflunomide; Physical Examination; Prognosis; Radiology, Interventional; Takayasu Arteritis
PubMed: 30114347
DOI: 10.3906/sag-1804-136 -
Current Rheumatology Reports Aug 2020Giant cell arteritis (GCA) and Takayasu arteritis (TAK) are auto-inflammatory and autoimmune diseases with a highly selective tissue tropism for medium and large... (Review)
Review
PURPOSE OF REVIEW
Giant cell arteritis (GCA) and Takayasu arteritis (TAK) are auto-inflammatory and autoimmune diseases with a highly selective tissue tropism for medium and large arteries. In both diseases, CD4 T cells and macrophages form granulomatous lesions within the arterial wall, a tissue site normally protected by immune privilege. Vascular lesions can be accompanied by an extravascular component, typically an intense hepatic acute phase response that produces well-known laboratory abnormalities, e.g., elevated ESR and CRP. It is unclear whether GCA and TAK lie on a spectrum of disease or whether they represent fundamentally different disease processes.
RECENT FINDINGS
GCA and TAK share many clinical features, but there are substantial differences in genetics, epidemiology, disease mechanisms, response to treatment, and treatment complications that give rise to different disease trajectories. A significant difference lies in the composition of the wall-infiltrating immune cell compartment, which in TAK includes a significant population of CD8 T cells as well as natural killer cells, specifying disparate disease effector pathways mediating tissue damage and vessel wall remodeling. Despite the similarities in tissue tropism and histomorphology, GCA and TAK are two distinct vasculitides that rely on separate disease mechanisms and require disease-specific approaches in diagnosis and management.
Topics: CD8-Positive T-Lymphocytes; Diagnosis, Differential; Giant Cell Arteritis; Humans; Killer Cells, Natural; Macrophages; Takayasu Arteritis
PubMed: 32845392
DOI: 10.1007/s11926-020-00948-x -
Rheumatology (Oxford, England) Feb 2019Although outcomes in Takayasu arteritis (TAK) are improving, diagnosis is typically delayed and significant arterial injury accrues. While wider use of non-invasive... (Review)
Review
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.
Topics: Antirheumatic Agents; Biological Products; Biomarkers; Computed Tomography Angiography; Disease Progression; Genetic Predisposition to Disease; Humans; Immunosuppressive Agents; Magnetic Resonance Angiography; Severity of Illness Index; Takayasu Arteritis
PubMed: 29635396
DOI: 10.1093/rheumatology/key040 -
Scientific Reports Mar 2021Recent studies have provided evidence of a close link between specific microbiota and inflammatory disorders. While the vessel wall microbiota has been recently...
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.
Topics: Aged; Aged, 80 and over; Biomarkers; Computational Biology; Disease Susceptibility; Female; Giant Cell Arteritis; Humans; Male; Metagenome; Metagenomics; Microbiota; Middle Aged; Sepsis; Takayasu Arteritis
PubMed: 33723291
DOI: 10.1038/s41598-021-84725-5 -
Seminars in Arthritis and Rheumatism Oct 2020Takayasu arteritis (TAK) is a chronic inflammatory vasculitis of unknown origin affecting large vessels, predominantly the aorta and its main branches. TAK usually... (Review)
Review
Takayasu arteritis (TAK) is a chronic inflammatory vasculitis of unknown origin affecting large vessels, predominantly the aorta and its main branches. TAK usually affects young women and the management of pregnancy during this vasculitis may be a challenging situation. After a review of the literature, we analysed the data of 505 pregnancies in 373 TAK patients. We discuss main results to clarify if the pregnancy outcome is affected by TAK, especially during disease clinical onset or disease activity. We also discuss the potential impact of pregnancy on TAK prognosis. Disease activity of TAK appears independently associated with a poor pregnancy outcome. More than 5% of pregnant women with TAK develop a life-threatening maternal cardiovascular complication. A good control of TAK disease activity and arterial hypertension before conception and during pregnancy is critical to improve both maternal and foetal outcomes. Pregnancies in the setting of TAK should be considered high-risk, requiring a close collaboration between specialists involved in the care of TAK and obstetricians.
Topics: Aorta; Female; Humans; Hypertension; Pregnancy; Pregnancy Outcome; Prognosis; Takayasu Arteritis
PubMed: 32911287
DOI: 10.1016/j.semarthrit.2020.08.001 -
International Heart Journal 2023Takayasu arteritis (TA or TAK) is a chronic large vessel vasculitis with predilection to affect the aorta and its branches. The new 2022 ACR/EULAR classification...
Takayasu arteritis (TA or TAK) is a chronic large vessel vasculitis with predilection to affect the aorta and its branches. The new 2022 ACR/EULAR classification criteria for Takayasu arteritis incorporated imaging characteristics as an absolute requirement. ESR and CRP fails in accuracy as disease activity markers. Pentraxin 3 appears to be a relatively superior biomarker, which correlates with ITAS 2010 as per several studies. PET-CT is also increasingly being studied for assessing disease activity with variable results. The management of TAK involves use of steroids with upfront steroid sparing immunosuppressive agents. MMF is one such conventional DMARD/immunosuppressant with good efficacy and better safety profile, as reported in various cohort studies. Tocilizumab is proved to be a rapid remission inducing agent in refractory Takayasu arteritis in observational studies. TNF inhibitors in many uncontrolled studies showed good responses, and there is a need for good RCTs for confirmation. JAK inhibitors have also been used with success in a few reports.
Topics: Humans; Treatment Outcome; Takayasu Arteritis; Positron Emission Tomography Computed Tomography; Immunosuppressive Agents; Steroids
PubMed: 37518335
DOI: 10.1536/ihj.23-195 -
Journal of the American College of... Apr 2022Percutaneous transluminal pulmonary angioplasty (PTPA) is a treatment modality for chronic thromboembolic pulmonary hypertension, but whether it can be applied to...
BACKGROUND
Percutaneous transluminal pulmonary angioplasty (PTPA) is a treatment modality for chronic thromboembolic pulmonary hypertension, but whether it can be applied to Takayasu arteritis-associated pulmonary hypertension (TA-PH), another chronic obstructive pulmonary vascular disease, remains unclear.
OBJECTIVES
This study sought to investigate the efficacy and safety of PTPA for TA-PH.
METHODS
Between January 1, 2016, and December 31, 2019, a total of 50 patients with TA-PH who completed the PTPA procedure (the PTPA group) and 21 patients who refused the PTPA procedure (the non-PTPA group) were prospectively enrolled in this cohort study. The primary outcome was all-cause mortality. The safety outcomes included PTPA procedure-related complications.
RESULTS
Baseline characteristics and medical therapies were similar between the PTPA group and the non-PTPA group. During a mean follow-up time of 37 ± 14 months, deaths occurred in 3 patients (6.0%) in the PTPA group and 6 patients (28.6%) in the non-PTPA group, contributing to the 3-year survival rate of 93.7% in the PTPA group and 76.2% in the non-PTPA group (P = 0.0096 for log-rank test). The Cox regression model showed that PTPA was associated with a significantly reduced hazard of all-cause mortality in TA-PH patients (HR: 0.18; 95% CI: 0.05-0.73; P = 0.017). No periprocedural death occurred. Severe complications requiring noninvasive positive pressure ventilation occurred in only 1 of 150 total sessions (0.7%).
CONCLUSIONS
PTPA tended to be associated with a reduced risk of all-cause mortality with acceptable safety profiles and seemed to be a promising therapeutic option for TA-PH patients.
Topics: Angioplasty; Cohort Studies; Humans; Hypertension, Pulmonary; Pulmonary Arterial Hypertension; Retrospective Studies; Takayasu Arteritis; Treatment Outcome
PubMed: 35422244
DOI: 10.1016/j.jacc.2022.01.052 -
Frontiers in Immunology 2023Arterial wall damage in Takayasu arteritis (TAK) can progress despite immunosuppressive therapy. Vascular fibrosis is more prominent in TAK than in giant cell arteritis... (Review)
Review
Arterial wall damage in Takayasu arteritis (TAK) can progress despite immunosuppressive therapy. Vascular fibrosis is more prominent in TAK than in giant cell arteritis (GCA). The inflamed arterial wall in TAK is infiltrated by M1 macrophages [which secrete interleukin-6 (IL-6)], which transition to M2 macrophages once the inflammation settles. M2 macrophages secrete transforming growth factor beta (TGF-β) and glycoprotein non-metastatic melanoma protein B (GPNMB), both of which can activate fibroblasts in the arterial wall adventitia. Mast cells in the arterial wall of TAK also activate resting adventitial fibroblasts. Th17 lymphocytes play a role in both TAK and GCA. Sub-populations of Th17 lymphocytes, Th17.1 lymphocytes [which secrete interferon gamma (IFN-γ) in addition to interleukin-17 (IL-17)] and programmed cell death 1 (PD1)-expressing Th17 (which secrete TGF-β), have been described in TAK but not in GCA. IL-6 and IL-17 also drive fibroblast activation in the arterial wall. The Th17 and Th1 lymphocytes in TAK demonstrate an activation of mammalian target organ of rapamycin 1 (mTORC1) driven by Notch-1 upregulation. A recent study reported that the enhanced liver fibrosis score (derived from serum hyaluronic acid, tissue inhibitor of metalloproteinase 1, and pro-collagen III amino-terminal pro-peptide) had a moderate-to-strong correlation with clinically assessed and angiographically assessed vascular damage. experiments suggest the potential to target arterial wall fibrosis in TAK with leflunomide, tofacitinib, baricitinib, or mTORC1 inhibitors. Since arterial wall inflammation is followed by fibrosis, a strategy of combining immunosuppressive agents with drugs that have an antifibrotic effect merits exploration in future clinical trials of TAK.
Topics: Humans; Takayasu Arteritis; Interleukin-17; Interleukin-6; Tissue Inhibitor of Metalloproteinase-1; Giant Cell Arteritis; Inflammation; Transforming Growth Factor beta; Fibrosis; Mechanistic Target of Rapamycin Complex 1; Membrane Glycoproteins
PubMed: 37256147
DOI: 10.3389/fimmu.2023.1174249 -
Journal of the American College of... Aug 2022Inflammatory aortitis is most often caused by large vessel vasculitis (LVV), including giant cell arteritis, Takayasu's arteritis, immunoglobulin G4-related aortitis,... (Review)
Review
Inflammatory aortitis is most often caused by large vessel vasculitis (LVV), including giant cell arteritis, Takayasu's arteritis, immunoglobulin G4-related aortitis, and isolated aortitis. There are distinct differences in the clinical presentation, imaging findings, and natural history of LVV that are important for the cardiovascular provider to know. If possible, histopathologic specimens should be obtained to aide in accurate diagnosis and management of LVV. In most cases, corticosteroids are utilized in the acute phase, with the addition of steroid-sparing agents to achieve disease remission while sparing corticosteroid toxic effects. Endovascular and surgical procedures have been described with success but should be delayed until disease control is achieved whenever possible. Long-term management should include regular follow-up with rheumatology and surveillance imaging for sequelae of LVV.
Topics: Aorta; Aortitis; Giant Cell Arteritis; Humans; Immunoglobulin G; Takayasu Arteritis
PubMed: 35981827
DOI: 10.1016/j.jacc.2022.05.046