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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 -
Frontiers in Immunology 2022Vasculitis is an inflammation of the blood vessels caused by autoimmunity and/or autoinflammation, and recent advances in research have led to a better understanding of... (Review)
Review
Vasculitis is an inflammation of the blood vessels caused by autoimmunity and/or autoinflammation, and recent advances in research have led to a better understanding of its pathogenesis. Glucocorticoids and cyclophosphamide have long been the standard of care. However, B-cell depletion therapy with rituximab has become available for treating antineutrophil cytoplasmic antibody-associated vasculitis (AAV). More recently, avacopan, an inhibitor of the complement 5a receptor, was shown to have high efficacy in remission induction against AAV. Thus, treatment options for AAV have been expanded. In contrast, in large vessel vasculitis (LVV), including giant cell arteritis and Takayasu arteritis, tocilizumab, an IL-6 receptor antagonist, was shown to be effective in suppressing relapse and has steroid-sparing effects. However, the relapse rate remains high, and other therapeutic options have long been awaited. In the last decade, Janus kinase (JAK) inhibitors have emerged as therapeutic options for rheumatoid arthritis (RA). Their efficacy has been proven in multiple studies; thus, JAK inhibitors are expected to be promising agents for treating other rheumatic diseases, including LVV. This mini-review briefly introduces the mechanism of action of JAK inhibitors and their efficacy in patients with RA. Then, the pathophysiology of LVV is updated, and a rationale for treating LVV with JAK inhibitors is provided with a brief introduction of our preliminary results using a mouse model. Finally, we discuss the newly raised safety concerns regarding JAK inhibitors and future perspectives for treating LVV.
Topics: Arteritis; Giant Cell Arteritis; Humans; Janus Kinase Inhibitors; Recurrence; Takayasu Arteritis
PubMed: 35432355
DOI: 10.3389/fimmu.2022.881705 -
Current Rheumatology Reports Oct 2020Guidelines for the management of large vessel vasculitides have been recently updated by several scientific societies. We have evaluated the current recommendations for... (Review)
Review
PURPOSE OF REVIEW
Guidelines for the management of large vessel vasculitides have been recently updated by several scientific societies. We have evaluated the current recommendations for treatment of giant cell arteritis (GCA) and Takayasu arteritis (TA) and addressed potential future therapeutic strategies.
RECENT FINDINGS
While glucocorticoids (GCs) remain the gold standard for induction of remission, many patients relapse and acquire high cumulative GC exposure. Thus, GC-sparing therapies such as methotrexate are recommended for selected patients with GCA and all patients with TA. Recent high-quality evidence shows that tocilizumab is an effective GC-sparing agent in GCA. Non-biologic and biologic immunomodulators also appear to have GC-sparing properties in TA. Tocilizumab is now considered to be part of the standard treatment for GCA, particularly with relapsing disease, but questions on its use such as length of treatment and monitoring of disease activity remain open. High-quality evidence to guide treatment of TA is still lacking.
Topics: Antibodies, Monoclonal, Humanized; Giant Cell Arteritis; Glucocorticoids; Humans; Methotrexate; Recurrence; Takayasu Arteritis
PubMed: 33044642
DOI: 10.1007/s11926-020-00964-x -
Current Rheumatology Reports Jan 2021The goal of this paper is to review current and future uses of patient-reported outcomes in large vessel vasculitis. The large vessel vasculitides comprise Giant Cell... (Review)
Review
PURPOSE OF REVIEW
The goal of this paper is to review current and future uses of patient-reported outcomes in large vessel vasculitis. The large vessel vasculitides comprise Giant Cell Arteritis and Takayasu arteritis; both are types of systemic vasculitis which affect the larger blood vessels. Patient-reported outcomes (PROs) capture the impact of these diseases on health-related quality of life.
RECENT FINDINGS
Generic PROs such as the SF-36 are currently used to compare HRQOL of people with GCA and TAK within clinical trials and observational studies and to make comparisons with the general population and HRQoL in other diseases. The development of a disease-specific PRO for GCA is currently underway. Beyond clinical trials, there is much interest in the use of PROs within routine clinical care, particularly E-PROs for remote use. Further work will be needed to complete the development of disease-specific PROs for people with large vessel vasculitis and to establish feasibility, acceptability, and utility of E-PROs.
Topics: Giant Cell Arteritis; Humans; Patient Reported Outcome Measures; Quality of Life; Systemic Vasculitis; Takayasu Arteritis
PubMed: 33511455
DOI: 10.1007/s11926-020-00979-4 -
Indian Journal of Ophthalmology Feb 2021Giant cell arteritis (GCA) is the most important medical emergency in ophthalmology, because its most dreaded complication is visual loss, which is preventable if these... (Review)
Review
Giant cell arteritis (GCA) is the most important medical emergency in ophthalmology, because its most dreaded complication is visual loss, which is preventable if these patients are diagnosed early and treated immediately and aggressively. This is a brief review of GCA, its ophthalmic manifestations, and how to diagnose and manage them.
Topics: C-Reactive Protein; Giant Cell Arteritis; Humans; Optic Neuropathy, Ischemic; Vision Disorders
PubMed: 33463564
DOI: 10.4103/ijo.IJO_1681_20 -
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... Jan 2023
Topics: Humans; Cardiovascular Diseases; Child, Orphaned; Cardiovascular System; Heart; Takayasu Arteritis
PubMed: 36599612
DOI: 10.1016/j.jacc.2022.11.003 -
Brazilian Journal of Cardiovascular... Aug 2019The roles that aortitis plays in the development of annuloaortic ectasia (AAE) remain uncertain, while clinical features of AAE in arteritis are largely unknown. This... (Review)
Review
The roles that aortitis plays in the development of annuloaortic ectasia (AAE) remain uncertain, while clinical features of AAE in arteritis are largely unknown. This study was designed to highlight the clinical features of AAE, the treatments of choice, and the causative relations between aortitis and AAE. The morphology of the aortic valve leaflets was normal in half of the patients, while the valves were thin and overstretched in the other half. Most patients had an aortic aneurysm. Half of the patients had severe aortic valve insufficiency, and one-quarter of them had dilation of the sinuses of Valsalva. Takayasu arteritis was prone to develop coronary artery lesions, whereas giant cell arteritis were not. Aortic branch lesions in Takayasu arteritis were stenotic or occlusive in 92.9% of the patients, while in giant cell arteritis, they were all dilated lesions. Most patients (94.7%) required surgical treatment with steroid therapy. However, long-term follow-up results showed a higher anastomotic dehiscence rate, particularly in patients with Takayasu arteritis. Further morphometric and pathological research on AAE in arteritis should be undertaken, and more feasible measures should be warranted for preventing postoperative anastomotic dehiscence.
Topics: Aortic Aneurysm, Thoracic; Giant Cell Arteritis; Humans; Postoperative Complications; Takayasu Arteritis
PubMed: 31454202
DOI: 10.21470/1678-9741-2018-0252 -
Autoimmunity Reviews Jun 2023Giant cell arteritis is the most common form of large vessel vasculitis and preferentially involves large and medium-sized arteries in patients over the age of 50.... (Review)
Review
Giant cell arteritis is the most common form of large vessel vasculitis and preferentially involves large and medium-sized arteries in patients over the age of 50. Aggressive wall inflammation, neoangiogenesis and consecutive remodeling processes are the hallmark of the disease. Though etiology is unknown, cellular and humoral immunopathological processes are well understood. Matrix metalloproteinase-9 mediated tissue infiltration occurs through lysis of basal membranes in adventitial vessels. CD4+ cells attain residency in immunoprotected niches, differentiate into vasculitogenic effector cells and enforce further leukotaxis. Signaling pathways involve the NOTCH1-Jagged1 pathway opening vessel infiltration, CD28 mediated T-cell overstimulation, lost PD-1/PD-L1 co-inhibition and JAK/STAT signaling in interferon dependent responses. From a humoral perspective, IL-6 represents a classical cytokine and potential Th-cell differentiator whereas interferon-γ (IFN- γ) has been shown to induce chemokine ligands. Current therapies involve glucocorticoids, tocilizumab and methotrexate application. However, new agents, most notably JAK/STAT inhibitors, PD-1 agonists and MMP-9 blocking substances, are being evaluated in ongoing clinical trials.
Topics: Humans; Giant Cell Arteritis; Autoimmunity; Programmed Cell Death 1 Receptor; CD4-Positive T-Lymphocytes; Cytokines; Takayasu Arteritis
PubMed: 36990133
DOI: 10.1016/j.autrev.2023.103328 -
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