Review: What Is the Current Evidence for Disease Subsets in Giant Cell Arteritis?
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SUBMITTER: van der Geest KSM
PROVIDER: S-EPMC6175064 | biostudies-literature | 2018 Sep
REPOSITORIES: biostudies-literature
Publications
Review: What Is the Current Evidence for Disease Subsets in Giant Cell Arteritis?
van der Geest Kornelis S M KSM Sandovici Maria M van Sleen Yannick Y Sanders Jan-Stephan JS Bos Nicolaas A NA Abdulahad Wayel H WH Stegeman Coen A CA Heeringa Peter P Rutgers Abraham A Kallenberg Cees G M CGM Boots Annemieke M H AMH Brouwer Elisabeth E
Arthritis & rheumatology (Hoboken, N.J.) 20180730 9
Giant cell arteritis (GCA) is an autoimmune vasculitis affecting large and medium-sized arteries. Ample evidence indicates that GCA is a heterogeneous disease in terms of symptoms, immune pathology, and response to treatment. In the current review, we discuss the evidence for disease subsets in GCA. We describe clinical and immunologic characteristics that may impact the risk of cranial ischemic symptoms, relapse rates, and long-term glucocorticoid requirements in patients with GCA. In addition, ...[more]
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Project description:Glucocorticoids remain the cornerstone of medical therapy in giant cell arteritis (GCA) and should be started immediately to prevent severe consequences of the disease, such as blindness. However, glucocorticoid therapy leads to significant toxicity in over 80% of the patients. Various steroid-sparing agents have been tried, but robust scientific evidence of their efficacy and safety is still lacking. Tocilizumab, a monoclonal IL-6 receptor blocker, has shown promising results in a number of case series and is now being tested in a multi-centre randomized controlled trial. Other targeted treatments, such as the use of abatacept, are also now under investigation in GCA. The need for surgical treatment is rare and should ideally be performed in a quiescent phase of the disease. Not all patients follow the same course, but there are no valid biomarkers to assess therapy response. Monitoring of disease progress still relies on assessing clinical features and measuring inflammatory markers (C-reactive protein and erythrocyte sedimentation rate). Imaging techniques (e.g., ultrasound) are clearly important screening tools for aortic aneurysms and assessing patients with large-vessel involvement, but may also have an important role as biomarkers of disease activity over time or in response to therapy. Although GCA is the most common form of primary vasculitis, the optimal strategies for treatment and monitoring remain uncertain.
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Project description: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.
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Project description:ObjectiveTo explore the association between giant cell arteritis (GCA) and subsequent cardiovascular disease in older adults.DesignPopulation based retrospective cohort study.SettingThe entire province of Ontario, Canada.ParticipantsPatients aged 66 years and older with newly diagnosed GCA (n = 1141), osteoarthritis (n = 172,953), or neither (n = 200,000). Patients with neither were randomly selected from the general population and formed the control group.Main outcome measuresThe primary composite outcome was based on a subsequent diagnosis or surgical treatment for coronary artery disease, stroke, peripheral arterial disease, or aneurysm or dissection of the aorta.ResultsThe composite end point was more common in seniors with GCA (12.1/1000 person-years) than in patients with osteoarthritis (7.3/1000 person-years) or neither condition (5.3/1000 person-years). The adjusted hazard ratio for cardiovascular disease was 1.6 (95% confidence interval (CI) 1.1 to 2.2) in patients with GCA versus patients with osteoarthritis, and 2.1 (95% CI 1.5 to 3.0) in patients with GCA versus unaffected controls.ConclusionsOlder adults with GCA appear to be at increased risk for developing cardiovascular disease. Whether an aggressive approach to cardiovascular risk factor modification is particularly beneficial in these patients remains to be determined.
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Project description:Giant cell arteritis (GCA) and Takayasu Arteritis (TAK) are two systemic granulomatous vasculitides affecting medium- and large-sized arteries. Similarities in GCA and TAK regarding the clinical presentation, the systemic inflammatory response and the distribution of the arterial lesions, have triggered a debate over the last decade about whether GCA and TAK represent two different diseases, or are age-associated different clinical phenotypes of the same disease. On the other hand, there are differences regarding epidemiology, several clinical features (eg, polymyalgia rheumatica in GCA) and treatment. The aim of this review is to present the latest data regarding this question and to shed some light on the differences and similarities between GCA and TAK regarding epidemiology, genetics, pathogenesis, histopathology, clinical presentation, imaging and treatment. The existing data in literature support the opinion that GCA and TAK are different clinical entities.
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