Pathophysiology, Diagnosis, and Management of Takayasu Arteritis: A Review of Current Advances

Cureus, Journal Year: 2023, Volume and Issue: unknown

Published: July 29, 2023

Takayasu arteritis (TA) is a rare, chronic, inflammatory vasculitis that primarily affects large arteries, causing significant morbidity and mortality. This review provides an overview of the pathophysiology, diagnosis, management TA based on current advances in field. characterized by autoimmune-mediated inflammation, vascular remodeling, endothelial dysfunction. The disease progresses through three stages (active, healing phase) each presenting distinct clinical features. Diagnosis can be challenging due to non-specific manifestations lack specific diagnostic tests. Various imaging modalities, such as angiography, ultrasound, Doppler techniques, play crucial role diagnosis visualizing arterial involvement assessing extent. Management involves multidisciplinary approach, with disease-modifying anti-rheumatic drugs (DMARDs) cornerstone medical therapy. Synthetic biologic DMARDs are used induce remission, control prevent complications. Non-pharmacologic interventions, resistance exercises curcumin supplementation, show potential benefits. Invasive including endovascular therapy open surgery, for managing lesions. However, challenges remain understanding management, heterogeneity presentation standardized treatment guidelines. future lies precision medicine, utilizing biomarkers molecular profiling personalize approaches improve patient outcomes. Further research needed unravel underlying mechanisms develop targeted therapies.

Language: Английский

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Persistent aortic inflammation in patients with giant cell arteritis

Autoimmunity Reviews, Journal Year: 2023, Volume and Issue: 22(9), P. 103411 - 103411

Published: Aug. 18, 2023

Language: Английский

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Deficiency of the CD155-CD96 immune checkpoint controls IL-9 production in giant cell arteritis

Cell Reports Medicine, Journal Year: 2023, Volume and Issue: 4(4), P. 101012 - 101012

Published: April 1, 2023

Loss of function inhibitory immune checkpoints, unleashing pathogenic responses, is a potential risk factor for autoimmune disease. Here, we report that patients with the vasculitis giant cell arteritis (GCA) have defective CD155-CD96 checkpoint. Macrophages from GCA retain checkpoint ligand CD155 in endoplasmic reticulum (ER) and fail to bring it surface. CD155low antigen-presenting cells induce expansion CD4+CD96+ T cells, which become tissue invasive, accumulate blood vessel wall, release effector cytokine interleukin-9 (IL-9). In humanized mouse model GCA, recombinant human IL-9 causes wall destruction, whereas anti-IL-9 antibodies efficiently suppress innate adaptive immunity vasculitic lesions. Thus, surface translocation creates deviate differentiation toward Th9 lineage commitment results vasculitogenic cells.

Language: Английский

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The Contribution of Innate Immunity in Large-Vessel Vasculitis: Detangling New Pathomechanisms beyond the Onset of Vascular Inflammation

Cells, Journal Year: 2024, Volume and Issue: 13(3), P. 271 - 271

Published: Feb. 1, 2024

Large-vessel vasculitis (LVV) are autoimmune and autoinflammatory diseases focused on vascular inflammation. The central core of the intricate immunological molecular network resides in disruption "privileged immune state" arterial wall. outbreak, initially primed by dendritic cells (DC), is then continuously powered a feed-forward loop intimate cooperation between innate adaptive immunity. If role immunity has been largely elucidated, knowledge critical function LVV still fragile. A growing body evidence strengthened active players their key signaling pathways orchestrating complex pathomechanisms underlying LVV. Besides DC, macrophages crucial culprits development participate across all phases inflammation, culminating vessel wall remodeling. In recent years, variety potential pathogenic actors expanded to include neutrophils, mast cells, soluble mediators, including complement system. Interestingly, new insights have recently linked inflammasome paving way for its Overall, these observations encourage conceptual approach that includes more in-depth study guide future targeted therapies.

Language: Английский

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Outcome Measures and Biomarkers for Disease Assessment in Takayasu Arteritis

Diagnostics, Journal Year: 2022, Volume and Issue: 12(10), P. 2565 - 2565

Published: Oct. 21, 2022

Takayasu arteritis (TAK) is a less common large vessel vasculitis where histopathology of involved arteries difficult to access except during open surgical procedures. Assessment disease activity in TAK, therefore, relies on surrogate measures. Clinical measures such as the National Institutes Health (NIH) score, Disease Extent Index TAK (DEI.TAK) and Indian Activity Score (ITAS2010) inconsistently associate with acute phase reactants (APRs). Computerized tomographic angiography (CTA), magnetic resonance (MRA), or color Doppler Ultrasound (CDUS) enables anatomical characterization stenosis, dilatation, wall characteristics. Vascular uptake 18-fluorodeoxyglucose other ligands using positron emission tomography computerized (PET-CT) helps assess metabolic activity, which reflects well subset normal APRs. Angiographic scoring systems quantitate extent vascular involvement have been developed recently. Erythrocyte sedimentation rate C-reactive protein moderate performance distinguishing active TAK. Numerous novel biomarkers are under evaluation Limited literature suggests better assessment by combining APRs, PET-CT, circulating biomarkers. Validated damage indices patient-reported outcome specific lacking. Few evaluated reflect constitute important research agenda.

Language: Английский

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The neutrophil: A key resourceful agent in immune‐mediated vasculitis

Immunological Reviews, Journal Year: 2022, Volume and Issue: 314(1), P. 326 - 356

Published: Nov. 21, 2022

Summary The term “vasculitis” refers to a group of rare immune‐mediated diseases characterized by the dysregulated immune system attacking blood vessels located in any organ body, including skin, lungs, and kidneys. Vasculitides are classified according size vessel that is affected. Although this observation not specific small‐, medium‐, or large‐vessel vasculitides, patients show high circulating neutrophil‐to‐lymphocyte ratio, suggesting direct indirect involvement neutrophils these diseases. As first responders infection inflammation, release cytotoxic mediators, reactive oxygen species, proteases, neutrophil extracellular traps. If controlled, dangerous arsenal can injure vascular system, which acts as main transport route for neutrophils, thereby amplifying initial inflammatory stimulus recruitment cells. This review highlights ability “set tone” cells other wall. Considering both their long‐established newly described roles, we extend functions far beyond host‐damaging potential. We also roles various types primary vasculitis, complex anti‐neutrophil cytoplasmic antibody‐associated polyarteritis nodosa, Kawasaki disease, giant cell arteritis, Takayasu Behçet's disease.

Language: Английский

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Clinical experience and safety of Janus kinase inhibitors in giant cell arteritis: a retrospective case series from Sweden

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: May 25, 2023

The Janus kinase (JAK)-STAT signaling pathway is relevant in both Takayasu and giant cell arteritis (GCA), the use of JAK inhibitors (JAKi) arthritis, psoriasis, inflammatory bowel disease nowadays common. Some evidence clinical efficacy JAKi GCA exists a phase III randomized controlled trial (RCT) upadacitinib currently recruiting. In 2017, we started using barcitinib patient with inadequate response to corticosteroids, later on, treated other 14 patients baricitinib/tofacitinib during intense follow-up. retrospective data these 15 individuals are here summarized. was diagnosed based on ACR criteria and/or imaging techniques combined increased C-reactive protein (CRP) erythrocyte sedimentation rate (ESR) followed by good initial corticosteroids. initiated activity, CRP, presumably dependent symptoms, despite unsatisfying high doses prednisolone. mean age at initiation 70.1 years exposure 19 months. From initiation, significant reductions CRP were seen already 3 (p = 0.02) 6 A slower decrease observed regarding ESR 0.12) Furthermore, daily prednisolone reduced 0.004) No relapses observed. Two affected serious infections, but therapy retained or reintroduced after recovery. We present encouraging observational one hitherto largest case series long-term Our experiences will complement results from awaited RCT.

Language: Английский

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Central Retinal Artery Occlusion: A Review of Pathophysiological Features and Management

Stroke Vascular and Interventional Neurology, Journal Year: 2023, Volume and Issue: 4(1)

Published: Aug. 16, 2023

Central retinal artery occlusion (CRAO) is a form of acute ischemic stroke that results in painless vision loss attributable to infarction. A keen understanding clinical presentation and underlying pathophysiological features key timely intervention development new treatment modalities. In CRAO, the time between initial insult significant because, analogous stroke, duration ischemia inversely related viable tissue. major challenge CRAO delayed presentation, which reduces amount salvageable retina. addition, imaging techniques effectively identify penumbra, or tissue reversibly damaged, are not well established. To compile this narrative review, we conducted systematic search PubMed database relevant articles on including reviews, meta‐analyses, studies, observational trials, randomized trials. The strategy included following keywords: central occlusion, treatment, management, meta‐analysis, study, trial, trial. We also searched for ongoing trials ClinicalTrials.gov. identified studies were then carefully evaluated their relevance topic used compiling review. Intravenous thrombolysis compelling therapeutic approach, with current limited data suggesting early (4.5 hours symptom onset) better patient outcomes. However, assessing comparing different fibrinolytic agents, routes administration (venous versus arterial), timing will provide further insight efficacy modality. parallel, testing aimed at quantifying blood flow viability could improve risk stratification guide treatment. These can be conjunction use conventional therapies, neuroprotectants, thrombolytics management various presentations deployed emergency settings. This article provides review features, factors, emerging CRAO.

Language: Английский

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Arterial wall fibrosis in Takayasu arteritis and its potential for therapeutic modulation

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: May 15, 2023

Arterial wall damage in Takayasu arteritis (TAK) can progress despite immunosuppressive therapy. Vascular fibrosis is more prominent TAK than giant cell (GCA). The inflamed arterial infiltrated by M1 macrophages [which secrete interleukin-6 (IL-6)], which transition to M2 once the inflammation settles. transforming growth factor beta (TGF-β) and glycoprotein non-metastatic melanoma protein B (GPNMB), both of activate fibroblasts adventitia. Mast cells also resting adventitial fibroblasts. Th17 lymphocytes play a role GCA. Sub-populations lymphocytes, Th17.1 interferon gamma (IFN-γ) addition interleukin-17 (IL-17)] programmed death 1 (PD1)-expressing (which TGF-β), have been described but not IL-6 IL-17 drive fibroblast activation wall. Th1 demonstrate an mammalian target organ rapamycin (mTORC1) driven Notch-1 upregulation. A recent study reported that enhanced liver score (derived from serum hyaluronic acid, tissue inhibitor metalloproteinase 1, pro-collagen III amino-terminal pro-peptide) had moderate-to-strong correlation with clinically assessed angiographically vascular damage.

Language: Английский

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Serum IL-6 level trajectory for predicting the effectiveness and safety of tocilizumab in the treatment of refractory Takayasu arteritis

European Journal of Internal Medicine, Journal Year: 2024, Volume and Issue: 126, P. 77 - 82

Published: April 20, 2024

Language: Английский

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