Association of clinical, imaging and laboratory parameters with adverse effects of glucocorticoid therapy in patients with giant cell arteritis

BackgroundGiant cell arteritis (GCA) is characterized by inflammation of large and medium vessels. First-line therapy for the treatment of GCA are glucocorticoids, which are effective while potential adverse effects should be considered, especially during long-term use. The aim was to investigate the incidence of glucocorticoids’ adverse effects and potential predictors for them.Materials and methods138 GCA patients were retrospectively evaluated for newly developed glucocorticoid adverse effects in 2020. Potential predictors, defined as initial glucocorticoid pulse therapy, relapse of GCA and concomitant polymyalgia rheumatica as well as parameters of inflammation and endothelial dysfunction, including pulse-wave velocity and intima-media-thickness, were measured in 2012.ResultsPotential new glucocorticoid adverse effects per patient was 1 (25th-75th 0–3) of which chronic kidney disease progression (29%), bone fractures (23.2%), cataracts (18.1%), dementia, and arterial hypertension (each at 12.3%) were most commonly recorded. Significant associations were found between occurrence of any relapse and new diabetes mellitus and between initial glucocorticoid pulse therapy and new dementia (all with p < 0.05). In multivariate regression analysis, any relapse was a predictor for developing diabetes mellitus (OR 9.23 [95% CI 1.33–64.05], p = 0.025). However, no correlations were observed between endothelial dysfunction or inflammatory parameters and development of new glucocorticoid adverse effects.ConclusionGCA relapses may be associated for development of diabetes mellitus potentially by increasing glucocorticoid doses. Parameters of inflammation and endothelial dysfunction are not suited predictors for glucocorticoid adverse effects

Diagnostic value of antibodies against a modified citrullinated vimentin in rheumatoid arthritis

Antibodies directed against citrullinated vimentin are members of the family of autoantibodies reactive with citrullinated proteins and are among the most specific serological markers for the diagnosis of rheumatoid arthritis (RA). This study was performed to test the diagnostic value of a newly developed enzyme-linked immunosorbent assay (ELISA) for the detection of antibodies against a genetically modified citrullinated vimentin (anti-MCV) in comparison with a second-generation anti-cyclic citrullinated peptides (anti-CCP2) ELISA test system. Blinded sera from 631 patients (409 consecutive out-patients and 222 randomly selected stored sera) with RA (n = 164) and non-RA (osteoarthritis [n = 120], polymyalgia rheumatica/giant cell arteritis [n = 80], spondyloarthritis [n = 36], and other inflammatory rheumatic or non-inflammatory disease [n = 67]) were tested for the presence of anti-MCV and anti-CCP2 antibodies according to the manufacturers' instructions. The diagnostic performance of the anti-MCV was comparable with the anti-CCP2 assay for the diagnosis of RA according to the calculated area under the curve (0.824; 95% confidence interval (CI) 0.778–0.870 versus 0.818; 95% CI 0.767–0.869) as analysed by receiving operating characteristic curve. When categorised with a cutoff value of 20.0 U/ml (as recommended by the manufacturer), sensitivity and specificity of the anti-MCV ELISA were 69.5% (95% CI 61.9%–76.5%) and 90.8% (86.9%–93.8%), respectively, compared with 70.1% (62.5%–77.0%) and 98.7% (96.7%–99.6%) of the anti-CCP2 assay. Using the cutoff values of 19.0 U/ml and 81.5 U/ml for the anti-MCV test to obtain a sensitivity and specificity identical to the anti-CCP2 assay, showed a reduced specificity (89.8%; 85.8%–92.9%) and sensitivity (53.7%; 45.7%–61.5%), respectively, of the anti-MCV ELISA compared with the anti-CCP2 test. In conclusion, the serum ELISA testing for anti-MCV antibodies as well as the anti-CCP-2 assay perform comparably well in the diagnosis of RA. In the high-specificity range, however, the anti-CCP2 assay appears to be superior to the anti-MCV test

Impact of COVID-19 pandemic on the management of patients with RA: a survey of rheumatologists in six European countries

OBJECTIVE: We aimed to describe, from the perspective of rheumatologists in Europe, how the coronavirus disease 2019 (COVID-19) pandemic has impacted their management of people with RA and the continuing medical education of physicians. METHODS: Rheumatologists participating in the Adelphi RA Disease Specific ProgrammeTM in six European countries were contacted in August and September 2020 for a telephone survey. Rheumatologists were asked seven attitudinal questions on changes to patient management, prescription behaviour and continuing education owing to COVID-19. Results were summarized with descriptive statistics. RESULTS: The telephone survey was completed by 284 rheumatologists. The most commonly reported changes to patient management were increased utilization of video/telephone consultations (66.5% of respondents), fewer visits (58.5%) and limiting physical contact (58.1%). Furthermore, 67.9% of rheumatologists who indicated that prescribing behaviour had changed switched their patients to self-administered medication, and 60.7% reported not starting patients on targeted synthetic DMARDs, biologic originator DMARDs or biosimilar DMARDs. In total, 57.6% of rheumatologists believed that changes in management would persist. Rheumatologists reported that 38.0% of patients expressed concerns about how COVID-19 would impact treatment, including access to treatment and the risk of infection. The biggest impact on rheumatologist education was a switch to online training and conferences. CONCLUSION: All countries saw changes in patient management and prescribing behaviour, including the rapid uptake of telemedicine. It is important that the international rheumatology community learns from these experiences to prepare better for future pandemics and to address ongoing rheumatologist shortages

Disease stratification in giant cell arteritis to reduce relapses and prevent long-term vascular damage

For years, clinicians and researchers working on giant cell arteritis have been battling with the conundrum of a disease that displays a short-term steroid responsiveness but is burdened by a remarkable risk of flares and chronic damage in the long term. This issue should be addressed by a change in the direction of research and clinical practice. Evidence suggests that giant cell arteritis is not a monolithic disease; it varies in extent and severity. Hence, treatment should be guided by disease stratification. The current one-size-fits-all strategy leads to overreliance on glucocorticoids and progression of glucocorticoid-related and disease-related complications. A new approach requires disease stratification using clinical, laboratory, histology, and imaging parameters. A giant cell arteritis registry might offer opportunities to scrutinise disease course and prognostic variables early; however, more studies that directly incorporate disease stratification through the above parameters are required. This Series paper also suggests that future clinical trials should be targeted at patients with different disease strata of giant cell arteritis and should incorporate ultrasound, PET-CT scanning, and other imaging modalities as key outcomes

Systematic literature review informing the 2018 update of the EULAR recommendation for the management of large vessel vasculitis : focus on giant cell arteritis

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.Objectives: To analyse the current evidence for the management of large vessel vasculitis (LVV) to inform the 2018 update of the EULAR recommendations. Methods: Two systematic literature reviews (SLRs) dealing with diagnosis/monitoring and treatment strategies for LVV, respectively, were performed. Medline, Embase and Cochrane databases were searched from inception to 31 December 2017. Evidence on imaging was excluded as recently published in dedicated EULAR recommendations. This paper focuses on the data relevant to giant cell arteritis (GCA). Results: We identified 287 eligible articles (122 studies focused on diagnosis/monitoring, 165 on treatment). The implementation of a fast-track approach to diagnosis significantly lowers the risk of permanent visual loss compared with historical cohorts (level of evidence, LoE 2b). Reliable diagnostic or prognostic biomarkers for GCA are still not available (LoE 3b).The SLR confirms the efficacy of prompt initiation of glucocorticoids (GC). There is no high-quality evidence on the most appropriate starting dose, route of administration, tapering and duration of GC (LoE 4). Patients with GCA are at increased risk of dose-dependent GC-related adverse events (LoE 3b). The addition of methotrexate or tocilizumab reduces relapse rates and GC requirements (LoE 1b). There is no consistent evidence that initiating antiplatelet agents at diagnosis would prevent future ischaemic events (LoE 2a). There is little evidence to guide monitoring of patients with GCA. Conclusions: Results from two SLRs identified novel evidence on the management of GCA to guide the 2018 update of the EULAR recommendations on the management of LVV.info:eu-repo/semantics/publishedVersio

Collateral effects of the SARS-CoV-2 pandemic on oncologic surgery in Bavaria

Background The ongoing SARS-COV-2 pandemic has severe implications for people and healthcare systems everywhere. In Germany, worry about the consequences of the pandemic led to the deferral of non-emergency surgeries. Tumor surgery accounts for a large volume in the field of visceral surgery and cannot be considered purely elective. It is not known how the SARS-COV-2 pandemic has changed the surgical volume in tumor patients. Methods Retrospective analysis of the amount of oncological surgeries in three academic visceral surgery departments in Bavaria, Germany, in 2020. Procedures were split into subgroups: Upper Gastrointestinal (Upper GI), Colorectal, Hepato-Pancreato-Biliary (HPB), Peritoneal and Endocrine. Procedures in 2020 were compared to a reference period from January 1st, 2017 to December 31st 2019. Surgical volume was graphically merged with SARS-COV-2 incidence and the number of occupied ICU beds. Results Surgical volume decreased by 7.6% from an average of 924 oncologic surgeries from 2017 to 2019 to 854 in 2020. The decline was temporally associated with the incidence of infections and ICU capacity. Surgical volume did not uniformly increase to pre-pandemic levels in the months following the first pandemic wave with lower SARS-COV-2 incidence and varied according to local incidence levels. The decline was most pronounced in colorectal surgery where procedures declined on average by 26% following the beginning of the pandemic situation. Conclusion The comparison with pre-pandemic years showed a decline in oncologic surgeries in 2020, which could have an impact on lost life years in non-COVID-19 patients. This decline was very different in subgroups which could not be solely explained by the pandemic

Evaluation of genome-wide loci of iron metabolism in hereditary hemochromatosis identifies PCSK7 as a host risk factor of liver cirrhosis

Genome-wide association studies (GWAS) have revealed genetic determinants of iron metabolism, but correlation of these with clinical phenotypes is pending. Homozygosity for HFE C282Y is the predominant genetic risk factor for hereditary hemochromatosis (HH) and may cause liver cirrhosis. However, this genotype has a low penetrance. Thus, detection of yet unknown genetic markers that identify patients at risk of developing severe liver disease is necessary for better prevention. Genetic loci associated with iron metabolism (TF, TMPRSS6, PCSK7, TFR2 and Chr2p14) in recent GWAS and liver fibrosis (PNPLA3) in recent meta-analysis were analyzed for association with either liver cirrhosis or advanced fibrosis in 148 German HFE C282Y homozygotes. Replication of associations was sought in additional 499 Austrian/Swiss and 112 HFE C282Y homozygotes from Sweden. Only variant rs236918 in the PCSK7 gene (proprotein convertase subtilisin/kexin type 7) was associated with cirrhosis or advanced fibrosis (P = 1.02 × 10−5) in the German cohort with genotypic odds ratios of 3.56 (95% CI 1.29-9.77) for CG heterozygotes and 5.38 (95% CI 2.39-12.10) for C allele carriers. Association between rs236918 and cirrhosis was confirmed in Austrian/Swiss HFE C282Y homozygotes (P = 0.014; ORallelic = 1.82 (95% CI 1.12-2.95) but not in Swedish patients. Post hoc combined analyses of German/Swiss/Austrian patients with available liver histology (N = 244, P = 0.00014, ORallelic = 2.84) and of males only (N = 431, P = 2.17 × 10−5, ORallelic = 2.54) were consistent with the premier finding. Association between rs236918 and cirrhosis was not confirmed in alcoholic cirrhotics, suggesting specificity of this genetic risk factor for HH. PCSK7 variant rs236918 is a risk factor for cirrhosis in HH patients homozygous for the HFE C282Y mutatio

Definitions and reliability assessment of elementary ultrasound lesions in giant cell arteritis: a study from the OMERACT Large Vessel Vasculitis Ultrasound Working Group.

ObjectivesTo define the elementary ultrasound (US) lesions in giant cell arteritis (GCA) and to evaluate the reliability of the assessment of US lesions according to these definitions in a web-based reliability exercise.MethodsPotential definitions of normal and abnormal US findings of temporal and extracranial large arteries were retrieved by a systematic literature review. As a subsequent step, a structured Delphi exercise was conducted involving an expert panel of the Outcome Measures in Rheumatology (OMERACT) US Large Vessel Vasculitis Group to agree definitions of normal US appearance and key elementary US lesions of vasculitis of temporal and extracranial large arteries. The reliability of these definitions on normal and abnormal blood vessels was tested on 150 still images and videos in a web-based reliability exercise.ResultsTwenty-four experts participated in both Delphi rounds. From originally 25 statements, nine definitions were obtained for normal appearance, vasculitis and arteriosclerosis of cranial and extracranial vessels. The halo and compression signs were the key US lesions in GCA. The reliability of the definitions for normal temporal and axillary arteries, the halo sign and the compression sign was excellent with inter-rater agreements of 91-99% and mean kappa values of 0.83-0.98 for both inter-rater and intra-rater reliabilities of all 25 experts.ConclusionsThe halo and the compression signs are regarded as the most important US abnormalities for GCA. The inter-rater and intra-rater agreement of the new OMERACT definitions for US lesions in GCA was excellent

Definitions and reliability assessment of elementary ultrasound lesions in giant cell arteritis: a study from the OMERACT Large Vessel Vasculitis Ultrasound Working Group

Objectives: To define the elementary ultrasound (US) lesions in giant cell arteritis (GCA) and to evaluate the reliability of the assessment of US lesions according to these definitions in a web-based reliability exercise. Methods: Potential definitions of normal and abnormal US findings of temporal and extracranial large arteries were retrieved by a systematic literature review. As a subsequent step, a structured Delphi exercise was conducted involving an expert panel of the Outcome Measures in Rheumatology (OMERACT) US Large Vessel Vasculitis Group to agree definitions of normal US appearance and key elementary US lesions of vasculitis of temporal and extracranial large arteries. The reliability of these definitions on normal and abnormal blood vessels was tested on 150 still images and videos in a web-based reliability exercise. Results: Twenty-four experts participated in both Delphi rounds. From originally 25 statements, nine definitions were obtained for normal appearance, vasculitis and arteriosclerosis of cranial and extracranial vessels. The 'halo' and 'compression' signs were the key US lesions in GCA. The reliability of the definitions for normal temporal and axillary arteries, the 'halo' sign and the 'compression' sign was excellent with inter-rater agreements of 91-99% and mean kappa values of 0.83-0.98 for both inter-rater and intra-rater reliabilities of all 25 experts. Conclusions: The 'halo' and the 'compression' signs are regarded as the most important US abnormalities for GCA. The inter-rater and intra-rater agreement of the new OMERACT definitions for US lesions in GCA was excellent