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A New Era for Giant Cell Arteritis
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A New Era for Giant Cell Arteritis

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Immunology".

Deadline for manuscript submissions: closed (31 March 2022) | Viewed by 33696

Special Issue Editor

Prof. Dr. Bernard Bonnotte

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Guest Editor
1. Department of Internal Medicine and Clinical Immunology, Reference Center for Autoimmune Cytopenias, François Mitterrand University Hospital, Dijon, France
2. INSERM U1098, University of Bourgogne/Franche-Comté, Dijon, France
Interests: giant cell arteritis (GCA); auto-immune cytopenias; immunosuppressive cell therapies; Castleman; immunopathology.

Special Issue Information

Dear Colleagues,

Giant cell arteritis (GCA), the most common form of systemic vasculitis in the elderly, can cause progressive and sometimes devastating complications, including vision loss. For decades, its pathophysiology remained unknown, biopsy of the temporal artery was the only cardinal diagnostic procedure, and its treatment was based on corticosteroids. However, studies in recent years have greatly increased our knowledge of GCA and will change clinical practice. Indeed, recent studies have better characterized the different immune and vascular cells involved in the pathogenesis of this form of vasculitis. The cause of GCA has yet to be elucidated, but major progress has been made in our understanding of its pathogenesis, which has made it possible to define new therapeutic targets. New imaging modalities for the diagnosis of GCA with cranial involvement, allowing for precise and functional mapping of this form of vasculitis, are becoming essential to the diagnostic procedure. In addition, new therapies that precisely act against different inflammatory cytokine pathways have shown spectacular efficacy.

The aim of this Special Issue is to highlight the most recent advances in the pathophysiology, diagnosis, including imaging methods, and clinical management of GCA. I look forward to receiving your contribution. 

Prof. Dr. Bernard Bonnotte
Guest Editor

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Keywords

  • giant cell arteritis
  • pathogenesis
  • diagnosis
  • temporal artery biopsy
  • imaging
  • positron emission tomography
  • ultrasound
  • biologic agents
  • cytokine receptors
  • cytokines

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Published Papers (7 papers)

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Research

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12 pages, 492 KiB  
Article
Impact of Glucocorticoid Cumulative Doses in a Real-Life Cohort of Patients Affected by Giant Cell Arteritis
by Paul Castan, Anael Dumont, Samuel Deshayes, Jonathan Boutemy, Nicolas Martin Silva, Gwénola Maigné, Alexandre Nguyen, Sophie Gallou, Audrey Sultan, Achille Aouba and Hubert de Boysson
J. Clin. Med. 2022, 11(4), 1034; https://doi.org/10.3390/jcm11041034 - 16 Feb 2022
Cited by 20 | Viewed by 2340
Abstract
Objectives: To describe the impact of cumulative glucocorticoid (GC) doses on related adverse events (AEs) in giant cell arteritis (GCA) in a real-life setting. Methods: The medical charts of the last 139 consecutive GCA patients followed in a tertiary centre were retrospectively analysed. [...] Read more.
Objectives: To describe the impact of cumulative glucocorticoid (GC) doses on related adverse events (AEs) in giant cell arteritis (GCA) in a real-life setting. Methods: The medical charts of the last 139 consecutive GCA patients followed in a tertiary centre were retrospectively analysed. The cumulative GC doses were calculated, and the main GC-related AEs were collected during the follow-up. Results: After a median follow-up duration of 35.6 (2–111) months, the median cumulative GC dose in the 139 patients was 9184 (1770–24,640) mg, and 131 patients (94%) presented at least one GC-related AE. Infections (63%) were the most frequently reported GC-related AE, followed by metabolic events (63%), including weight gain in 51% of them. Cardiovascular and neuropsychiatric events occurred in 51% and 47% of patients, respectively. Osteoporotic fractures, muscular involvement, digestive events, geriatric deterioration, skin fragility, ophthalmologic complications and hypokalaemia were reported in <35% of patients. Cardiovascular events (p = 0.01), osteoporotic fractures (p = 0.004), cataract occurrence (p = 0.03), weight gain (p = 0.04) and infections (p = 0.01) were significantly associated with GC cumulative doses > 9 g. Longer GC durations were associated with cataract occurrence (p = 0.01), weight gain (p = 0.03) and all-grade infections (p = 0.048), especially herpes zoster occurrence (p = 0.003). Neuropsychiatric and metabolic events appeared within the first months after GC introduction, whereas herpes zoster recurred, and most cardiovascular AEs emerged after 1 year. Geriatric events, especially osteoporotic fractures, occurred 2 years after GC introduction. Conclusion: This study highlights how frequent GC-related AEs are and the impact of prolonged GC and cumulative doses. Full article
(This article belongs to the Special Issue A New Era for Giant Cell Arteritis)
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Review

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22 pages, 3291 KiB  
Review
New Insights into the Pathogenesis of Giant Cell Arteritis: Mechanisms Involved in Maintaining Vascular Inflammation
by Hélène Greigert, Coraline Genet, André Ramon, Bernard Bonnotte and Maxime Samson
J. Clin. Med. 2022, 11(10), 2905; https://doi.org/10.3390/jcm11102905 - 20 May 2022
Cited by 33 | Viewed by 5698
Abstract
The giant cell arteritis (GCA) pathophysiology is complex and multifactorial, involving a predisposing genetic background, the role of immune aging and the activation of vascular dendritic cells by an unknown trigger. Once activated, dendritic cells recruit CD4 T cells and induce their activation, [...] Read more.
The giant cell arteritis (GCA) pathophysiology is complex and multifactorial, involving a predisposing genetic background, the role of immune aging and the activation of vascular dendritic cells by an unknown trigger. Once activated, dendritic cells recruit CD4 T cells and induce their activation, proliferation and polarization into Th1 and Th17, which produce interferon-gamma (IFN-γ) and interleukin-17 (IL-17), respectively. IFN-γ triggers the production of chemokines by vascular smooth muscle cells, which leads to the recruitment of additional CD4 and CD8 T cells and also monocytes that differentiate into macrophages. Recent data have shown that IL-17, IFN-γ and GM-CSF induce the differentiation of macrophage subpopulations, which play a role in the destruction of the arterial wall, in neoangiogenesis or intimal hyperplasia. Under the influence of different mediators, mainly endothelin-1 and PDGF, vascular smooth muscle cells migrate to the intima, proliferate and change their phenotype to become myofibroblasts that further proliferate and produce extracellular matrix proteins, increasing the vascular stenosis. In addition, several defects in the immune regulatory mechanisms probably contribute to chronic vascular inflammation in GCA: a defect in the PD-1/PD-L1 pathway, a quantitative and qualitative Treg deficiency, the implication of resident cells, the role of GM-CSF and IL-6, the implication of the NOTCH pathway and the role of mucosal-associated invariant T cells and tissue-resident memory T cells. Full article
(This article belongs to the Special Issue A New Era for Giant Cell Arteritis)
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12 pages, 772 KiB  
Review
Ocular Complications of Giant Cell Arteritis: An Acute Therapeutic Emergency
by Emmanuel Héron, Neila Sedira, Ouassila Dahia and Céline Jamart
J. Clin. Med. 2022, 11(7), 1997; https://doi.org/10.3390/jcm11071997 - 2 Apr 2022
Cited by 7 | Viewed by 3701
Abstract
The risk of blindness, due to acute ischemic ocular events, is the most feared complication of giant cell arteritis (GCA) since the middle of the 20th century. A decrease of its rate has occurred after the advent of corticoid therapy for this vasculitis, [...] Read more.
The risk of blindness, due to acute ischemic ocular events, is the most feared complication of giant cell arteritis (GCA) since the middle of the 20th century. A decrease of its rate has occurred after the advent of corticoid therapy for this vasculitis, but it seems to have stabilized since then. Early diagnosis and treatment of GCA is key to reducing its ocular morbidity. However, it is not uncommon for ophthalmological manifestations to inaugurate the disease, and the biological inflammatory reaction may be mild, making its diagnosis more challenging. In recent years, vascular imaging has opened up new possibilities for the rapid diagnosis of GCA, and ultrasound has taken a central place in fast-track diagnostic processes. Corticosteroid therapy remains the cornerstone of treatment and must begin immediately in patients with visual symptoms and suspicion of GCA. In that situation, the administration route of corticotherapy, intravenous or oral, is less important than its speed of delivery, any hour of delay worsening the prognosis. Full article
(This article belongs to the Special Issue A New Era for Giant Cell Arteritis)
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13 pages, 536 KiB  
Review
Treatment of Giant Cell Arteritis (GCA)
by Alexis Régent and Luc Mouthon
J. Clin. Med. 2022, 11(7), 1799; https://doi.org/10.3390/jcm11071799 - 24 Mar 2022
Cited by 10 | Viewed by 8033
Abstract
Giant cell arteritis (GCA) is the most frequent primary large-vessel vasculitis in individuals older than 50. Glucocorticoids (GCs) are considered the cornerstone of treatment. GC therapy is usually tapered over months according to clinical symptoms and inflammatory marker levels. Considering the high rate [...] Read more.
Giant cell arteritis (GCA) is the most frequent primary large-vessel vasculitis in individuals older than 50. Glucocorticoids (GCs) are considered the cornerstone of treatment. GC therapy is usually tapered over months according to clinical symptoms and inflammatory marker levels. Considering the high rate of GC-related adverse events in these older individuals, immunosuppressive treatments and biologic agents have been proposed as add-on therapies. Methotrexate was considered an alternative option, but its clinical impact was limited. Other immunosuppressants failed to demonstrate a significant favourable benefit/risk ratio. The approval of tocilizumab, an anti-interleukin 6 (IL-6) receptor inhibitor brought significant improvement. Indeed, tocilizumab had a noticeable effect on cumulative GCs’ dose and relapse prevention. After the improvement in pathophysiological knowledge, other targeted therapies have been proposed, with anti-IL-12/23, anti-IL-17, anti-IL-1, anti-cytotoxic T-lymphocyte antigen 4, Janus kinase inhibitors or anti-granulocyte/macrophage colony stimulating factor therapies. These therapies are currently under evaluation. Interestingly, mavrilimumab, ustekinumab and, to a lesser extent, abatacept have shown promising results in phase 2 randomised controlled trials. Despite this recent progress, the value, specific condition and optimal application of each treatment remain undecided. In this review, we discuss the scientific rationale for each treatment and the therapeutic strategy. Full article
(This article belongs to the Special Issue A New Era for Giant Cell Arteritis)
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13 pages, 299 KiB  
Review
An Updated Review of Cardiovascular Events in Giant Cell Arteritis
by Hubert de Boysson and Achille Aouba
J. Clin. Med. 2022, 11(4), 1005; https://doi.org/10.3390/jcm11041005 - 15 Feb 2022
Cited by 19 | Viewed by 4364
Abstract
Giant cell arteritis (GCA) is a systemic vasculitis with a direct and indirect increased risk of acute and chronic vascular events, affecting large and medium vessels, and responsible for most of the morbidity and mortality of this disease. We aimed in this review [...] Read more.
Giant cell arteritis (GCA) is a systemic vasculitis with a direct and indirect increased risk of acute and chronic vascular events, affecting large and medium vessels, and responsible for most of the morbidity and mortality of this disease. We aimed in this review to provide an updated synthesis of knowledge regarding cardiovascular events observed in GCA. By definition, GCA patients are over 50 and often over 70 years old, and subsequently also present age-related cardiovascular risk factors. In addition, the systemic and vascular inflammation as well as glucocorticoids (GC) probably contribute to an accelerated atherosclerosis and to vascular changes leading to arterial stenoses and aortic dilations and/or dissections. GCA-related ischemic complications, especially ophthalmologic events, stroke or myocardial infarcts are mostly observed within the first months after the diagnosis, being mainly linked to the vasculitic process. Conversely, aortic complications, including dilations or dissections, generally occur several months or years after the diagnosis, mainly in patients with large-vessel vasculitis. In these patients, other factors such as atherosclerosis, GC-related endothelial damage and vascular wall remodeling/healing probably contribute to the vascular events. GCA management includes the detection and treatment of these previous and newly induced cardiovascular risk factors. Hence, the use of cardiovascular treatments (e.g., aspirin, anticoagulation, statins, anti-hypertensive treatments) should be evaluated individually. Aortic structural changes require regular morphologic evaluations, especially in patients with previous aortitis. The initial or secondary addition of immunosuppressants, especially tocilizumab, an anti-IL-6 receptor antibody, is discussed in patients with GCA-related cardiovascular complications and, more consensually, to limit GC-mediated comorbidities. Full article
(This article belongs to the Special Issue A New Era for Giant Cell Arteritis)
19 pages, 1597 KiB  
Review
Functionally Heterogenous Macrophage Subsets in the Pathogenesis of Giant Cell Arteritis: Novel Targets for Disease Monitoring and Treatment
by Idil Esen, William F. Jiemy, Yannick van Sleen, Kornelis S.M. van der Geest, Maria Sandovici, Peter Heeringa, Annemieke M. H. Boots and Elisabeth Brouwer
J. Clin. Med. 2021, 10(21), 4958; https://doi.org/10.3390/jcm10214958 - 26 Oct 2021
Cited by 19 | Viewed by 4580
Abstract
Giant cell arteritis (GCA) is a granulomatous large-vessel vasculitis that affects adults above 50 years of age. In GCA, circulating monocytes are recruited to the inflamed arteries. With cues from the vascular microenvironment, they differentiate into macrophages and play important roles in the [...] Read more.
Giant cell arteritis (GCA) is a granulomatous large-vessel vasculitis that affects adults above 50 years of age. In GCA, circulating monocytes are recruited to the inflamed arteries. With cues from the vascular microenvironment, they differentiate into macrophages and play important roles in the pathogenesis of GCA via pro-inflammatory cytokine production and vascular remodeling. However, a deeper understanding of macrophage heterogeneity in GCA pathogenesis is needed to assist the development of novel diagnostic tools and targeted therapies. Here, we review the current knowledge on macrophage heterogeneity and diverse functions of macrophage subsets in the pathogenesis of GCA. We next discuss the possibility to exploit their heterogeneity as a source of novel biomarkers and as targets for nuclear imaging. Finally, we discuss novel macrophage-targeted therapies and future directions for targeting these cells in GCA. Full article
(This article belongs to the Special Issue A New Era for Giant Cell Arteritis)
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11 pages, 1188 KiB  
Review
Imaging Tests in the Early Diagnosis of Giant Cell Arteritis
by Diana Prieto-Peña, Santos Castañeda, Isabel Martínez-Rodríguez, Belén Atienza-Mateo, Ricardo Blanco and Miguel A. González-Gay
J. Clin. Med. 2021, 10(16), 3704; https://doi.org/10.3390/jcm10163704 - 20 Aug 2021
Cited by 27 | Viewed by 3865
Abstract
Early recognition of giant cell arteritis (GCA) is crucial to avoid the development of ischemic vascular complications, such as blindness. The classic approach to making the diagnosis of GCA is based on a positive temporal artery biopsy, which is among the criteria proposed [...] Read more.
Early recognition of giant cell arteritis (GCA) is crucial to avoid the development of ischemic vascular complications, such as blindness. The classic approach to making the diagnosis of GCA is based on a positive temporal artery biopsy, which is among the criteria proposed by the American College of Rheumatology (ACR) in 1990 to classify a patient as having GCA. However, imaging techniques, particularly ultrasound (US) of the temporal arteries, are increasingly being considered as an alternative for the diagnosis of GCA. Recent recommendations from the European League Against Rheumatism (EULAR) for the use of imaging techniques for large vessel vasculitis (LVV) included US as the first imaging option for the diagnosis of GCA. Furthermore, although the ACR classification criteria are useful in identifying patients with the classic cranial pattern of GCA, they are often inadequate in identifying GCA patients who have the extracranial phenotype of LVV. In this sense, the advent of other imaging techniques, such as magnetic resonance imaging (MRI), computed tomography (CT), and positron emission tomography (PET)/CT, has made it possible to detect the presence of extracranial involvement of the LVV in patients with GCA presenting as refractory rheumatic polymyalgia without cranial ischemic manifestations. Imaging techniques have been the key elements in redefining the diagnostic work-up of GCA. US is currently considered the main imaging modality to improve the early diagnosis of GCA. Full article
(This article belongs to the Special Issue A New Era for Giant Cell Arteritis)
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