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Objective: To develop international consensus-based recommendations for early referral of individuals with suspected polymyalgia rheumatica (PMR)., Methods: A task force including 29 rheumatologists/internists, 4 general practitioners, 4 patients and a healthcare professional emerged from the international giant cell arteritis and PMR study group. The task force supplied clinical questions, subsequently transformed into Population, Intervention, Comparator, Outcome format. A systematic literature review was conducted followed by online meetings to formulate and vote on final recommendations. Levels of evidence (LOE) (1-5 scale) and agreement (LOA) (0-10 scale) were evaluated., Results: Two overarching principles and five recommendations were developed. LOE was 4-5 and LOA ranged between 8.5 and 9.7. The recommendations suggest that (1) each individual with suspected or recently diagnosed PMR should be considered for specialist evaluation, (2) before referring an individual with suspected PMR to specialist care, a thorough history and clinical examination should be performed and preferably complemented with urgent basic laboratory investigations, (3) individuals with suspected PMR with severe symptoms should be referred for specialist evaluation using rapid access strategies, (4) in individuals with suspected PMR who are referred via rapid access, the commencement of glucocorticoid therapy should be deferred until after specialist evaluation and (5) individuals diagnosed with PMR in specialist care with a good initial response to glucocorticoids and a low risk of glucocorticoid related adverse events can be managed in primary care., Conclusions: These are the first international recommendations for referral of individuals with suspected PMR, which complement the European Alliance of Associations for Rheumatology/American College of Rheumatology management guidelines for established PMR., Competing Interests: Competing interests: KKK: Research grants from Independent Research Fund Denmark, Danish Rheumatic Association and Central Denmark Region unrelated to this project. SES: Research grants from Rheumatology Research Foundation, Bristol Myers Squibb Foundation. Clinical trial support from AstraZeneca, GlaxoSmithKline; Consulting fees from Sanofi (funds toward research support); Data Safety Monitoring Board on MINT trial, Advisory Board for Sanofi (funds toward research support). E-MH: Has received grants unrelated to this manuscript from Novo Nordic Foundation, Roche, Novartis; Personal fees from AbbVie, Sanofi, SOBI, Merck Sharp & Dohme and Union Chimique Belge. AD: Consulting fees from Sanofi; Participation on a Data Safety Monitoring Board or Advisory Board for Sanofi; Board member Vasculitis Foundation. LN: Has received Honorarium from Abbvie; Trustee of the charity PMR-GCA Scotland. SM: Consulting fees from Astrazeneca; Honoraria from Vifor. KJW: Grants from Eli Lilly, Kiniksa, BMS; Consulting fees from Amgen, Sanofi. Honoraria from Amgen. CP: Consulting fee from Pfizer. MP: Consulting fee from Novartis; Clinical trial participant for Abbvie, Amgen, AstraZeneca. HIK: Honoraria from Roche, eTherapeutic Guidelines Australia; Board member Australian Rheumatology Association; Clinical trials for Roche, Abbvie, Sun, Emerald, Novartis, Biogen, Sanofi, Syneos. CEO: Consultancy for Abbvie; Speaking honoraria from Abbvie, Janssen, Novartis and Roche; Advisory board for Abbvie. WAS: Has received honoraria from Abbvie, Chugai, GlaxoSmithKline, Medac, Novartis, Roche, Sanofi ; Support for attending meetings/travel from Abbvie, Chugai, GlaxoSmithKline, Medac, Novartis, Roche, Sanofi; Participated in advisory board from Abbvie, GlaxoSmithKline, Novartis, Sanofi; Principle investigator of phases 2 and 3 studies sponsored by Abbvie, GlaxoSmithKlinie, Novartis and Sanofi. EBrouwer: As an employee of the UMCG received a speaker fee for a talk on GCA at a post EULAR symposium in the Netherlands in 2023 which was paid to the UMCG; As an employee of the UMCG received grants from the Dutch Arthritis Society DAS and the EU/EFPIA/Innovative Medicines Initiative 2 Joint Undertaking Immune-Image grant no 831514 which were paid to the UMCG. SM: Consultancy on behalf of her institution for Roche/Chugai, Sanofi, AbbVie, AstraZeneca, Pfizer; Investigator on clinical trials for Sanofi, GSK, Sparrow; speaking/lecturing on behalf of her institution for Roche/Chugai, Vifor, Pfizer, UCB, Novartis and AbbVie; chief investigator on STERLING-PMR trial, funded by NIHR; patron of the charity PMRGCAuk. No personal remuneration was received for any of the above activities. Support from Roche/Chugai to attend EULAR2019 in person and from Pfizer to attend ACR Convergence 2021 virtually. SM is supported in part by the NIHR Leeds Biomedical Research Centre. VD-P has received honorarium from Abbvie, Chugai, Novartis, BMS, Support for attending meetings/travel from Novartis; Participated in advisory borad from Abbvie, Novartis. All other authors have no competing interests., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ on behalf of EULAR.)

Background: Giant cell arteritis is an age-related vasculitis that mainly affects the aorta and its branches in individuals aged 50 years and older. Current options for diagnosis and treatment are scarce, highlighting the need to better understand its underlying pathogenesis. Genome-wide association studies (GWAS) have emerged as a powerful tool for unravelling the pathogenic mechanisms involved in complex diseases. We aimed to characterise the genetic basis of giant cell arteritis by performing the largest GWAS of this vasculitis to date and to assess the functional consequences and clinical implications of identified risk loci., Methods: We collected and meta-analysed genomic data from patients with giant cell arteritis and healthy controls of European ancestry from ten cohorts across Europe and North America. Eligible patients required confirmation of giant cell arteritis diagnosis by positive temporal artery biopsy, positive temporal artery doppler ultrasonography, or imaging techniques confirming large-vessel vasculitis. We assessed the functional consequences of loci associated with giant cell arteritis using cell enrichment analysis, fine-mapping, and causal gene prioritisation. We also performed a drug repurposing analysis and developed a polygenic risk score to explore the clinical implications of our findings., Findings: We included a total of 3498 patients with giant cell arteritis and 15 550 controls. We identified three novel loci associated with risk of giant cell arteritis. Two loci, MFGE8 (rs8029053; p=4·96 × 10 -8 ; OR 1·19 [95% CI 1·12-1·26]) and VTN (rs704; p=2·75 × 10 -9 ; OR 0·84 [0·79-0·89]), were related to angiogenesis pathways and the third locus, CCDC25 (rs11782624; p=1·28 × 10 -8 ; OR 1·18 [1·12-1·25]), was related to neutrophil extracellular traps (NETs). We also found an association between this vasculitis and HLA region and PLG. Variants associated with giant cell arteritis seemed to fulfil a specific regulatory role in crucial immune cell types. Furthermore, we identified several drugs that could represent promising candidates for treatment of this disease. The polygenic risk score model was able to identify individuals at increased risk of developing giant cell arteritis (90th percentile OR 2·87 [95% CI 2·15-3·82]; p=1·73 × 10 -13 )., Interpretation: We have found several additional loci associated with giant cell arteritis, highlighting the crucial role of angiogenesis in disease susceptibility. Our study represents a step forward in the translation of genomic findings to clinical practice in giant cell arteritis, proposing new treatments and a method to measure genetic predisposition to this vasculitis., Funding: Institute of Health Carlos III, Spanish Ministry of Science and Innovation, UK Medical Research Council, and National Institute for Health and Care Research., Competing Interests: Declaration of interests MCC reports support from the Spanish Ministry of Science and Innovation (PID2020-114909RB-I00), Vasculitis Foundation, Agency for the Management of University and Research Grants (2021 SGR 01561), and Kiniksa Pharmaceuticals; consulting fees or honoraria from GSK, CSL Vifor, AbbVie, and AstraZeneca; support for attending meetings from Kiniksa Pharmaceuticals; and participation on a data safety monitoring board or advisory board for GSK, CSL Vifor, and AstraZeneca. GE has acted as a consultant for GSK, AstraZeneca, Sobi, Novartis, Boehringer, and CSL Vifor. AWM reports support from the UK Medical Research Council (MRC), National Institute for Health and Care Research (NIHR), Leeds Care, and Roche Products; and consulting fees or honoraria from CSL Vifor and AstraZeneca. PL reports grants or contracts from the Federal Ministry of Education and Research, German Research Society, German Society for Rheumatology, John Grube Foundation, and CSL Vifor; consulting fees or honoraria from GSK, CSL Vifor, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Forum für medizinische Fortbildung, Janssen, Rheumaakademie, and UCB; support for attending meetings from CSL Vifor; and participation on a data safety monitoring board or advisory board for GSK, CSL Vifor, AbbVie, and Novartis. TW reports consulting fees or honoraria from AbbVie, AstraZeneca, Lilly, UCB, and Novartis; and participation on a data safety monitoring board or advisory board for AbbVie, AstraZeneca, Lilly, UCB, Novartis, and Fresenius. MAG-G reports honoraria from GSK. NK reports grants or contracts from Bristol Myers Squibb, AbbVie, and Sanofi; and consulting fees or honoraria from Roche, Otsuka, GSK, and Mallinckrodt. CAL reports grants or contracts from Bristol Myers Squibb and support from the National Institutes of Health. PAM reports grants, contracts, or consulting fees from AbbVie, Amgen, AstraZeneca, ArGenx, Boehringer Ingelheim, Bristol Myers Squibb, Cabaletta, CSL Behring, Eicos, Electra, Forbius, Genentech–Roche, GSK, HiBio, InflaRx, Janssen, Jubilant, Kyverna, MiroBio, Neutrolis, Novartis, NS Pharma, Q32, Regeneron, Sanofi, Sparrow, Takeda, and Vistera; royalties or licenses from UpToDate; and stock or stock options from Kyverna, Q32, and Sparrow. SLM reports grants or contracts from MRC, NIHR, and CSL Vifor; consulting fees from Roche, Sanofi, AbbVie, AstraZeneca, and Pfizer; payment or honoraria for lectures or educational events from Roche, Pfizer, UCB, CSL Vifor, Fresenius Kabi, and Novartis; support for attending meetings from Pfizer; participation on a data safety monitoring board or advisory board for Collaboration for Leadership in Applied Health Research and Care, Haywood Foundation, and GC-SheaLD; a leadership or fiduciary role in the British Society for Rheumatology Clinical Affairs Committee; participation as an investigator on industry-sponsored clinical trials for Sanofi; and infrastructure support from MRC. LB reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Instrumentation Laboratory SPA and AbbVie; and support for attending meetings from AbbVie and Novartis. EB reports payments or honoraria from EULAR and received grants from the Dutch Arthritis Society DAS and the EU/EFPIA/Innovative Medicines Initiative 2 Joint Undertaking Immune-Image grant no 831514. EB is member of the board of the non-profit organisation, Auto-immune Research Hub, in the Netherlands. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objectives: To investigate the value of [ 18 F]fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) and magnetic resonance imaging (MRI) in predicting relapse after treatment discontinuation in patients with large-vessel giant cell arteritis (LV-GCA)., Methods: This study included patients with LV-GCA whose treatment was discontinued between 2018 and 2023. All patients underwent PET/CT and/or MRI at the time of treatment discontinuation in clinical remission. Qualitative and quantitative PET/CT scores, by measuring standardized uptake values (SUV), and semiquantitative MRI scores of the aorta and supraaortic vessels were compared between patients who relapsed within 4 months after treatment discontinuation and those who did not., Results: Forty patients were included (median age 67.4 years, interquartile range (IQR) 60.8-74.0; 77.5 % females). Eleven patients (27.5 %) relapsed after treatment discontinuation (time to relapse 1.9 months, IQR 1.4-3.3). Patients who relapsed were comparable to those who remained in remission with respect to the presence of active vasculitis on MRI and/or PET/CT (54.5% vs. 58.6 %, p = 1.0), the number of segments with vasculitic findings on MRI (0, IQR 0.0-1.5, vs. 2, IQR 0.0-3.0, p = 0.221) or the highest SUV artery/liver ratio on PET/CT (1.5, IQR 1.4-1.6, vs. 1.3, IQR 1.2-1.6, p = 0.505). The median number of vasculitic segments on PET/CT was 2.5 (IQR 0.5-4.5) in those with vs. 0 (IQR 0.0-1.5, p = 0.085) in those without relapse, and the PET/CT scores 4.5 (IQR 0.75-8.25) vs. 0 (IQR 0.0-3.0, p = 0.172)., Conclusion: PET/CT or MRI at treatment stop did not predict relapse and may not be suited to guide treatment decisions in patients with LV-GCA in remission., Competing Interests: Declaration of competing interest AH is supported by a grant from the Swiss Foundation for Research on Muscle Diseases (FSRMM). DK received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Abbvie, Janssen, Novartis, Pfizer, Roche, and Eli Lilly and support for attending meetings and/or travel from Janssen. DS received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, educational events, or advisory board from Bayer, Pfizer, Bristol-Myers-Squibb, Daiichi-Sankyo, Sanofi, Philips and Bauerfeind AG. TD received payment or honoraria for lectures and advisory boards from Novartis and CSL and holds IIT grants from Novartis and Abbvie. All other authors have no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: To investigate the hypothesis that a history of PMR is associated with a more severe and damaging disease course in newly diagnosed GCA patients., Methods: This was a retrospective analysis of GCA patients diagnosed between December 2006 and May 2021. We compared vascular ultrasound findings (presence of vasculitis and vascular stenosis) in GCA patients with and without prior PMR., Results: Forty-nine of 311 GCA patients (15.8%) had prior PMR in a median of 30.6 (IQR 7.1-67.3) months before GCA diagnosis. Patients with prior PMR more often had large vessel vasculitis (LVV) (51.0% vs 25.0%, P < 0.001) and stenosis within the vasculitic segments (18.4% vs 3.1%, P < 0.001) on ultrasound. In multivariable analysis, prior PMR remained significantly associated with LVV (odds ratio 7.65, 95% CI: 2.72, 23.97, P < 0.001). Polymyalgic symptoms at GCA diagnosis in the patients without prior PMR were not associated with a higher prevalence of LVV (P = 0.156)., Conclusion: Patients with a diagnosis of PMR before GCA diagnosis had two times more often large vessel involvement and significant more vasculitic stenoses on ultrasound examination than patients without prior PMR. Pre-existing PMR is an independent risk factor for more extensive and advanced ultrasound findings at GCA diagnosis. The contribution of subclinical vasculitis to disease associated damage should be further studied., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objectives: We evaluated the feasibility of a rapid glucocorticoid tapering regimen to reduce glucocorticoid exposure in patients with giant cell arteritis (GCA) treated with glucocorticoids only., Methods: Newly diagnosed patients with GCA treated with a planned 26-week glucocorticoid tapering regimen at the University Hospital Basel were included. Data on relapses, cumulative steroid doses (CSD) and therapy-related adverse effects were collected from patients' records., Results: Of 47 patients (64% women, median age 72 years), 32 patients (68%) had relapsed. Most relapses were minor (28/32) and 2/3 of those were isolated increased inflammatory markers (19/32). Among major relapses, one resulted in permanent vision loss. The median time until relapse was 99 days (IQR 71-127) and median glucocorticoid dose at relapse was 8 mg (IQR 5-16). Nine of 47 patients stopped glucocorticoids after a median duration of 35 weeks and did not relapse within 1 year. Median CSD at 12 months was 4164 mg which is lower compared with published data. Glucocorticoid-associated adverse effects occurred in 40% of patients, most frequently were new onset or worsening hypertension (19%), diabetes (11%) and severe infections (11%)., Conclusion: We could demonstrate that 32% of patients remained relapse-free and 19% off glucocorticoids at 1 year after treatment with a rapid glucocorticoid tapering regimen. Most relapses were minor and could be handled with temporarily increased glucocorticoid doses. Consequently, the CSD at 12 months was much lower than reported in published cohorts. Thus, further reducing treatment-associated damage in patients with GCA by decreasing CSD seems to be possible., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims of the Study: To assess current practices in diagnosing, treating, and following-up giant-cell arteritis by specialists in Switzerland and to identify the main barriers to using diagnostic tools., Methods: We performed a national survey of specialists potentially caring for patients with giant-cell arteritis. The survey was sent by email to all members of the Swiss Societies of Rheumatology and for Allergy and Immunology. A reminder was sent to nonresponders after 4 and 12 weeks. Its questions covered the following dimensions: respondents' main characteristics, diagnosis, treatment, and imaging's role during follow-up. The main study results were summarized using descriptive statistics., Results: Ninety-one specialists, primarily aged 46-65 years (n = 53/89; 59%), working in academic or nonacademic hospitals or private practice, and treating a median of 7.5 (interquartile range [IQR]: 3-12) patients with giant-cell arteritis per year participated in this survey. Ultrasound of temporal arteries/large vessels (n = 75/90; 83%) and positron-emission-tomography-computed tomography (n = 52/91; 57%) or magnetic resonance imaging (n = 46/90; 51%) of the aorta/extracranial arteries were the most common techniques used to diagnose giant-cell arteritis with cranial or large vessel involvement, respectively. Most participants reported a short time to obtain imaging tests or arterial biopsy. The glucocorticoid tapering scheme, glucocorticoid-sparing agent, and glucocorticoid-sparing treatment duration varied among the participants. Most physicians did not follow a predefined repeat imaging scheme for follow-up and mainly relied on structural changes (vascular thickening, stenosis, or dilatation) to drive treatment choice., Conclusions: This survey indicates that imaging and temporal biopsy are rapidly accessible for diagnosing giant-cell arteritis in Switzerland but highlights heterogeneous practice in many disease management areas.

Objectives: To develop an Outcome Measures in Rheumatology (OMERACT) ultrasonography score for monitoring disease activity in giant cell arteritis (GCA) and evaluate its metric properties., Methods: The OMERACT Instrument Selection Algorithm was followed. Forty-nine members of the OMERACT ultrasonography large vessel vasculitis working group were invited to seven Delphi rounds. An online reliability exercise was conducted using images of bilateral common temporal arteries, parietal and frontal branches as well as axillary arteries from 16 patients with GCA and 7 controls. Sensitivity to change and convergent construct validity were tested using data from a prospective cohort of patients with new GCA in which ultrasound-based intima-media thickness (IMT) measurements were conducted at weeks 1, 3, 6, 12 and 24., Results: Agreement was obtained (92.7%) for the OMERACT GCA Ultrasonography Score (OGUS), calculated as follows: sum of IMT measured in every segment divided by the rounded cut-off values of IMTs in each segment. The resulting value is then divided by the number of segments available. Thirty-five members conducted the reliability exercise, the interrater intraclass correlation coefficient (ICC) for the OGUS was 0.72-0.84 and the median intrareader ICC was 0.91. The prospective cohort consisted of 52 patients. Sensitivity to change between baseline and each follow-up visit up to week 24 yielded standardised mean differences from -1.19 to -2.16, corresponding to large and very large magnitudes of change, respectively. OGUS correlated moderately with erythrocyte sedimentation rate, C reactive protein and Birmingham Vasculitis Activity Score (corr coeff 0.37-0.48)., Conclusion: We developed a provisional OGUS for potential use in clinical trials., Competing Interests: Competing interests: CDe has received grant support from AbbVie and consulting/speaker’s fees from Abbvie, Eli Lilly, Janssen, Galapagos, Novartis, Pfizer, Sparrow, Roche and Sanofi, all unrelated to this manuscript. CPo is or has been the principal investigator of studies by AbbVie, Sanofi and Novartis and has received consulting/speaker’s fees from Vifor, AstraZeneca, GlaxoSmithKline and Roche, all unrelated to this manuscript. LT received speakers fee from Roche, Novartis, Janssen, Pfizer, UCB and GE. PB received grant support from Pfizer and speaker’s fees from Janssen. CDu has received consultancy or speaker fees and travel expenses from Abbvie, AOP Orphan, Astra-Zeneca, Bristol-Myers-Squibb, Eli-Lilly, Janssen, Galapagos, Merck-Sharp-Dohme, Novartis, Pfizer, Roche, Sandoz, UCB, Vifor and research support from Eli-Lilly, Pfizer, UCB, all unrelated to this manuscript. E-MH has received fees for speaking and/or consulting from Novartis, AbbVie, Sanofi, Sobi; research funding to Aarhus University Hospital from Novo Nordic Foundation, Danish Rheumatism Association, Danish Regions Medicine Grants, Roche, Novartis, AbbVie; travel expenses from Pfizer, Sobi, AbbVie. E-MH has been the principal investigator of studies by SynACT Pharma and involved as site principal investigator in trials by AbbVie, Novartis, Novo and Sanofi, all unrelated to this manuscript. AI received honoraria, advisory boards, speakers’ bureau, educational grants and research support from AbbVie, Alfasigma, Amgen, Biogen, BMS, Celgene, Celltrion, Eli-Lilly, Galapagos, Gilead, MSD, Novartis, Pfizer, Sanofi Genzyme, SOBI and UCB. KDT is or was a research investigator of studies for Novartis, Astra Zeneca, Glaxo SmithKline, Amgen; has received consulting fees from Aurinia, Novartis and Astra Zeneca; and is a contracted researcher of Bioclinica. KSMvdG received a speaker fee from Roche. WAS is or has been the principal investigator of studies by Abbvie, Amgen, GlaxoSmithKline, Novartis, Roche, Sanofi and has received consulting/speaker’s fees from Abbvie, Amgen, Bristol-Myers Squibb, Chugai, GlaxoSmithKline, Johnson & Johnson, Medac, Novartis, Roche and Sanofi, all unrelated to this manuscript. The other authors declare no conflicts of interest., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To characterise factors associated with permanent vision loss (PVL) and potential reasons for the therapeutic delay contributing to PVL in giant cell arteritis (GCA)., Methods: Retrospective analysis of GCA patients diagnosed at the University Hospital Basel between December 2006 and May 2021., Results: Of 282 patients with GCA (64% females), 49 (17.4%) experienced PVL. In 43/49 (87.8%) PVL occurred before treatment. Of these, 24 (55.8%) patients had first non-ocular symptoms and eventually sought consultation when PVL occurred in a median of 21 (IQR 14.75-31.0) days after the first symptoms. Only five of the 24 patients had consulted a physician before PVL, but GCA diagnosis was missed. Treatment was initiated rapidly after diagnosis (median 1 day (IQR 0.0-7.0)). PVL on therapy occurred in six patients in a median of 40 (IQR 20.5-67.3) days after treatment started. In two of those, glucocorticoids were tapered too quickly.In multivariable analysis, patients with PVL were older (OR 1.17, 95% CI 1.07 to 1.29, p=0.001) and reported more frequently jaw claudication (OR 3.52, 95% CI 1.02 to 13.16, p=0.051). PVL was present in 18 (42.9%) of the 42 patients with vasculitic ultrasound findings in all six temporal artery segments. The incidence of PVL over 15 years did not decline (Spearman rank=0.3, p=0.68)., Conclusion: The prevalence of GCA-associated PVL remains high. Associated factors were advanced age, jaw claudication and ultrasound findings consistent with vasculitis in all six temporal artery segments. Despite preceding non-ocular GCA symptoms weeks before the onset of PVL, most patients were not seen by a rheumatologist before PVL occurred., Competing Interests: Competing interests: AKH is supported by a grant from the Swiss Foundation for Research on Muscle Diseases (FSRMM). CTB received a grant from the Swiss National Science Foundation (SNSF). DK received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Abbvie, Janssen, Novartis, Pfizer, Roche and Eli Lilly and support for attending meetings and/or travel from Janssen. All other authors have no competing interests., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To determine the prevalence and predictors of subclinical giant cell arteritis (GCA) in patients with newly diagnosed polymyalgia rheumatica (PMR)., Methods: PubMed, Embase, and Web of Science Core Collection were systematically searched (date of last search July 14, 2021) for any published information on any consecutively recruited cohort reporting the prevalence of GCA in steroid-naïve patients with PMR without cranial or ischemic symptoms. We combined prevalences across populations in a random-effect meta-analysis. Potential predictors of subclinical GCA were identified by mixed-effect logistic regression using individual patient data (IPD) from cohorts screened with PET/(CT)., Results: We included 13 cohorts with 566 patients from studies published between 1965 to 2020. Subclinical GCA was diagnosed by temporal artery biopsy in three studies, ultrasound in three studies, and PET/(CT) in seven studies. The pooled prevalence of subclinical GCA across all studies was 23% (95% CI 14%-36%, I 2 =84%) for any screening method and 29% in the studies using PET/(CT) (95% CI 13%-53%, I 2 =85%) (n=266 patients). For seven cohorts we obtained IPD for 243 patients screened with PET/(CT). Inflammatory back pain (OR 2.73, 1.32-5.64), absence of lower limb pain (OR 2.35, 1.05-5.26), female sex (OR 2.31, 1.17-4.58), temperature >37° (OR 1.83, 0.90-3.71), weight loss (OR 1.83, 0.96-3.51), thrombocyte count (OR 1.51, 1.05-2.18), and haemoglobin level (OR 0.80, 0.64-1.00) were most strongly associated with subclinical GCA in the univariable analysis but not C-reactive protein (OR 1.00, 1.00-1.01) or erythrocyte sedimentation rate (OR 1.01, 1.00-1.02). A prediction model calculated from these variables had an area under the curve of 0.66 (95% CI 0.55-0.75)., Conclusion: More than a quarter of patients with PMR may have subclinical GCA. The prediction model from the most extensive IPD set has only modest diagnostic accuracy. Hence, a paradigm shift in the assessment of PMR patients in favour of implementing imaging studies should be discussed., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Subcutaneous tocilizumab (TCZ SC) is approved globally for giant cell arteritis (GCA). This phase Ib study investigated the pharmacokinetics, pharmacodynamics, safety, and exploratory efficacy of intravenous (IV) TCZ 6 and 7 mg/kg in patients with GCA. This study explored an IV dose resulting in a minimum exposure level within the range of effective trough concentrations achieved with TCZ SC dosing in GCA and not exceeding the exposure of the well-tolerated 8 mg/kg IV every 4 weeks (Q4W) in rheumatoid arthritis (RA)., Methods: Patients with GCA who had received ≥ 5 doses of TCZ IV 8 mg/kg Q4W and achieved remission were enrolled. Patients received 5 doses of TCZ IV 7 mg/kg Q4W in period 1 and, if still in remission, 5 doses of 6 mg/kg Q4W in period 2. Pharmacokinetic endpoints were maximum concentration (C max ), minimum concentration (C trough ), area under the curve over a dosing interval (AUC τ ), and mean concentration (C mean ) of TCZ after the last dose of each period. Other endpoints included pharmacodynamic markers, safety, and exploratory efficacy., Results: In 24 patients, the median (range) age was 65.5 (57-90) years, and 62.5% were female. TCZ exposures (C max and AUC τ ) were 11.2% and 20.0% lower at the 6- than 7-mg/kg dose. The mean interleukin 6 (IL-6) serum concentrations were elevated at baseline and remained elevated, with slightly higher concentrations in period 1 than in period 2. The mean serum soluble IL-6 receptor concentrations were elevated at baseline and comparable between the 2 doses at steady state. C-reactive protein levels and most erythrocyte sedimentation rates were within normal ranges throughout the study. Overall, 22 patients (91.7%) had ≥ 1 adverse event, and 4 (16.7%) had a serious adverse event. No patients experienced a GCA flare, and all remained in remission throughout the study., Conclusions: Both doses of TCZ IV Q4W were generally well tolerated in patients with GCA. The C max and C mean achieved with 6 mg/kg IV Q4W in patients with GCA were similar to those in patients with RA treated with 8 mg/kg IV Q4W, and C trough was within the range observed in patients with GCA treated with SC dosing every week or every 2 weeks., Trial Registration: ClinicalTrials.gov , NCT03923738., (© 2022. The Author(s).)

Aims: To describe the feasibility and diagnostic accuracy of 18F-FDG positron emission tomography-computed tomography (PET/CT) of the temporal artery compared with temporal artery ultrasound and histology of the temporal artery in patients with suspicion of having giant cell arteritis (GCA)., Materials and Methods: Patients with suspected GCA were included. PET/CT standard uptake value ratios and the compression sign on ultrasound were assessed for the trunk, and parietal and frontal branches of the temporal artery. Temporal artery biopsies were systematically re-assessed, if available., Results: In 17/34 patients, GCA was confirmed. Temporal artery PET/CT confirmed vasculitis in 9/17 patients and was negative in all 17 controls. Nineteen of 34 subjects had a temporal artery biopsy, which was positive in 7 patients. Five of these seven were negative in the preceding PET/CT. Ultrasound confirmed vasculitis in 9/17 patients and was negative in 16/17 controls. In 7/17 patients, PET/CT and ultrasound were positive for temporal arteritis. Two patients had positive findings only on temporal artery PET/CT and two patients showed vasculitis only on temporal artery ultrasound. No temporal artery segments &lt;1.4 mm were positive on PET/CT. The parietal branches were PET/CT-positive in two patients only. In contrast, on ultrasound vasculitic findings were equally distributed amongst all branches. Sensitivity and specificity for identification of temporal artery involvement was 53% and 100% for PET/CT, and 53% and 94% for ultrasound, respectively., Conclusions: Assessment of the temporal artery with PET/CT is a valuable extension in the diagnostic workup for GCA. PET/CT and ultrasound have comparable diagnostic accuracy, but differ on a segment and a patient level and may thus be used as complementary tests. PET/CT has a lower sensitivity for the parietal branch than ultrasound and histology.

Competing Interests: Competing interests: None declared.

Objectives: [18F]Fluorodeoxyglucose (FDG)-PET/CT and US are both well established for diagnosing GCA. The present study investigates their accuracy and whether they provide overlapping or complementary information in a cohort of patients presenting with suspicion of GCA., Methods: We selected consecutive patients from our cohort of suspected GCA cases that underwent both extended vascular US and PET/CT for diagnostic work-up between December 2006 and August 2012., Results: A total of 102 patients were included. Diagnosis of GCA was confirmed in 68 patients and excluded in 34 patients (controls). Vasculitic changes in US were most often found in the temporal artery with 32 positive findings on each side, followed by the popliteal artery (10 right, 9 left) and the subclavian/axillary artery (7 right, 8 left). By contrast, PET/CT showed vasculitis most frequently in the vertebral (23 right, 33 left) and common carotid arteries (32 right, 24 left), followed by the subclavian arteries (16 right, 18 left), and the thoracic (17) and abdominal aorta (23). In 37/68 GCA patients PET/CT and US both revealed vasculitic findings, 11/68 had positive findings in US only and 14/68 in PET/CT only. Specificity of US was higher (one false-positive vs five false-positive in PET/CT). On a single segment level, only 20 of 136 positive segments were positive in both imaging modalities., Conclusion: PET/CT measuring vessel wall metabolism and US vessel wall morphology showed a comparable diagnostic accuracy for GCA. However PET/CT and US were often discrepant within single vascular regions. Thus PET/CT and US should be considered as complementary methods, with a second imaging modality increasing the diagnostic yield by 16-20%., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: To assess changes of arterial vessel wall morphology in large vessel GCA patients (LV-GCA) by repeated US., Methods: Patients with LV-GCA on US examination were followed up 6, 12 and 24 months after diagnosis by US of the temporal, vertebral, carotid (common, internal, external), subclavian, axillary, femoral (deep, superficial and common) and popliteal arteries. Clinical and laboratory data were assessed at each visit. Vessel wall thickening was classified as moderate, marked or arteriosclerotic., Results: A total of 42 patients (26 female) with a median age of 75 years at diagnosis had in median 2 (range 1-3) US follow-up exams. Twenty-eight had both LV and temporal artery involvement and 14 had LV-GCA only. The common carotid, subclavian, axillary, popliteal and/or superficial femoral artery were most commonly involved. Reduction of LV wall thickening occurred in 45% of patients during follow-up, corresponding to 71 of the 284 (25%) initially 'vasculitic' LV segments. In contrast, a reduction of vessel wall thickening in the temporal artery was found in 85% of patients. Of the LVs, the vertebral, axillary, subclavian and deep femoral arteries were most likely to improve. There was no difference in relapses or the received cumulative steroid dose between patients with or without a reduction of vessel wall thickening (temporal artery or LV) during follow-up., Conclusion: Regression of wall thickening within the LV is significantly less common than in the temporal artery and irrespective of clinical remission. Morphological regression does not seem to be a useful predictor for relapses., (© The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Historically, giant cell arteritis (GCA) was considered to be synonymous with temporal arteritis. However, the disease spectrum of GCA extends much further, and includes vasculitis of the aorta and its branches with or without involvement of the temporal arteries. Imaging is crucial for the diagnosis and follow-up of GCA patients. Large vessel GCA (LV-GCA) often presents as an inflammatory syndrome and is only detected by imaging modalities such as: colour duplex sonography (CDS), computed tomography (CT) / CT angiography (CTA), magnetic resonance imaging (MRI) or 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) / CT. Deciding which imaging modality to use in different clinical situations remains a matter of debate. CDS and MRI enable assessment of the temporal arteries with a presumably higher sensitivity than histology. In the context of a typical presentation, CDS can replace a biopsy. In about a third of patients, the temporal arteries are not involved, thus PET/CT, MRI, CT, or CDS of larger arteries is needed to diagnose GCA. The sensitivity of all modalities is affected by glucocorticoid therapy. Therefore, without delaying therapy, imaging should be performed within a few days of treatment initiation. The use of PET/CT for the work-up of inflammatory syndromes in the elderly reveals vasculitis in approximately 20% of examined patients and uncover relevant diagnoses in the majority of remaining patients. The aorta should be routinely assessed in all GCA patients at diagnosis and during follow-up. MRA or CTA are best suited to characterise structural damage of larger arteries. The role of imaging in monitoring GCA disease activity still needs to be further defined.

Aims: The usefulness of [18F] fluorodeoxyglucose-positron emission tomography/computed tomography ([18F]FDG-PET/CT) for diagnosing giant cell arteritis (GCA) has been previously reported. Yet, the interpretation of PET scans is not clear-cut. The present study aimed at determining the best method to analyse PET/CT in a large, real-life cohort of patients presenting with suspicion of GCA., Methods and Results: One hundred and three patients with clinical suspicion of GCA undergoing PET/CT between 2006 and 2012 were included. Clinical data were retrieved from patients' charts. PET/CT was categorized by visual scoring of the uptake and by the artery/liver standardized uptake values (SUV) ratios. Diagnosis of GCA was confirmed in 68 patients and excluded in 35 patients, which served as the controls. GCA patients were older (median age 75 vs. 68 years), and presented more often with ischaemic symptoms. The best discrimination between GCA patients and controls was achieved for PET/CT findings within the supra-aortic arteries (sensitivity 0.71, specificity 0.91 for a SUV/LE cut-off value of 1.0). Specificity of PET/CT for the aorta and the iliofemoral arteries was lower (<0.34). Visual scoring correlated poorly to SUV measurements (Kendall Tau-b 0.13-0.55) and had a lower diagnostic accuracy (sensitivity 0.77, specificity 0.75). Prednisone treatment for ≥10 days significantly reduced PET/CT sensitivity (P = 0.009)., Conclusion: SUV based analysis of PET/CT enhances diagnostic accuracy with best discrimination in the supra-aortic region, particularly in steroid naïve patients. For discrimination based on the aorta and the iliofemoral region, higher cut-off values have to be applied, resulting in lower sensitivities for diagnosing GCA.

Objectives: Autoantibodies are useful biomarkers for diagnosing and monitoring treatment in some autoimmune diseases. Antibodies against isoforms of 14-3-3 protein have been proposed as biomarkers for the presence of aortic aneurysm in large-vessel vasculitis (LVV). Here, we aimed to evaluate the diagnostic role and potential immunopathological involvement of anti-14-3-3 antibodies in newly diagnosed LVV patients., Methods: Antibodies against three isoforms of 14-3-3 (γ, ɛ and ζ) were measured in 90 subjects: 48 GCA and 3 Takayasu's arteritis (TA) patients, and 39 controls (non-inflammatory and inflammatory diseases), using a multiplexed bead-based immunoassay and immunoprecipitation studies. The positive cut-off value was defined based on young healthy controls. Anti-14-3-3 IgG antibodies in LVV patients were compared with those in controls in order to assess their diagnostic performance, and the relationship of anti-14-3-3 IgG antibodies to the immunohistopathology of artery explants was assessed., Results: Antibodies against all three 14-3-3 isoforms were detected in LVV patients as well as in age-matched inflammatory and non-inflammatory controls. Among LVV patients, detection of antibodies targeting 14-3-3 ɛ and ζ was associated with more severe disease. Detection of antibodies against 14-3-3 γ was linked to latent Toxoplasma gondii infection, a parasite that secrets a 14-3-3 homologue, suggesting potential cross-reactivity., Conclusion: Detection of antibodies against 14-3-3 proteins at the time of LVV diagnosis is not disease-specific. Their presence at high levels in LVV patients with stroke, aortitis and-in a previous study-aneurysm formation may indicate an association with extensive tissue destruction. The relevance of 14-3-3 antibodies in non-LVV patients needs to be investigated in larger cohorts., (© The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com)

Giant cell arteritis (GCA) is the most common form of vasculitis in individuals older than 50 years in Western countries. To shed light onto the genetic background influencing susceptibility for GCA, we performed a genome-wide association screening in a well-powered study cohort. After imputation, 1,844,133 genetic variants were analyzed in 2,134 case subjects and 9,125 unaffected individuals from ten independent populations of European ancestry. Our data confirmed HLA class II as the strongest associated region (independent signals: rs9268905, p = 1.94 × 10 -54 , per-allele OR = 1.79; and rs9275592, p = 1.14 × 10 -40 , OR = 2.08). Additionally, PLG and P4HA2 were identified as GCA risk genes at the genome-wide level of significance (rs4252134, p = 1.23 × 10 -10 , OR = 1.28; and rs128738, p = 4.60 × 10 -9 , OR = 1.32, respectively). Interestingly, we observed that the association peaks overlapped with different regulatory elements related to cell types and tissues involved in the pathophysiology of GCA. PLG and P4HA2 are involved in vascular remodelling and angiogenesis, suggesting a high relevance of these processes for the pathogenic mechanisms underlying this type of vasculitis., (Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Objectives: To compare the diagnostic performance between a vascular specialist and a rheumatologist not familiar with vascular ultrasound when applying the compression sign for the diagnosis of temporal arteritis., Methods: Sixty consecutive patients with suspicion of giant cell arteritis were examined by both examiners. Compression of the temporal artery on both sides (stem and both branches) was performed to define whether signs of vasculitis, no vasculitis or an indefinite result were present. Each examiner was blinded to the result of the other., Results: In 59/60 patients, the examiners found an identical result. The interobserver agreement (Krippendorf alpha) was 0.92., Conclusions: The new compression sign for the diagnosis of temporal arteritis is a simple and robust sonographic marker with an excellent interobserver agreement.

Objectives: Pneumocystis jiroveci pneumonia (PCP) is a life-threatening opportunistic infection. Few PCP cases in giant cell arteritis (GCA) have been described, but it remains unknown, which patients need PCP prophylaxis., Methods: Sixty-two patients with GCA from a prospective cohort were studied to identify treatment-related predictors of PCP infection., Results: Four PCP infections occurred, all in patients treated with methotrexate in addition to prednisone. Moreover, PCP is associated with higher cumulative PDN doses and severe lymphocytopenia (<400/μl)., Conclusions: Our findings support PCP-prophylaxis in GCA patients who are treated with methotrexate and PDN, and need high prednisone doses to achieve remission, or develop severe lymphocytopenia.

Background: The aim of this study was to determine subclinical ocular ischemia related to giant cell arteritis (GCA) by means of retinal oximetry (RO) measurements., Patients and Methods: Four test-retest RO images per eye were taken with the retinal vessel analyser (IMEDOS Systems UG, Jena). RO measurements in arterial (A-SO2) and venous (V-SO2) retinal vessels and their difference (A-V SO2) were calculated in GCA patients and compared to those of age-matched controls., Results: GCA biopsy and duplex sonography positive patients (n=8, 13 eyes) from the Basler Riesenzellarteriitis Kohorte study (BARK) were recruited. In controls (n=6, 10 eyes), the mean (± SD) A-SO2 and V-SO2 were measured at 93.89% (± 3.0) and at 55.60% (± 3.4), respectively. In the GCAs, a reduction in the A-SO2 to 93.37% (± 3.3) and an increase in V-SO2 to 61.13% (± 3.6) were found. The A-V SO2 difference was reduced in the GCAs to 32.24% (± 3.8) whereas in the controls the difference was 38.31% (± 2.8)., Conclusions: Oxygen metabolism is affected in cases with GCA. Thus, RO may provide additional data in the diagnosis of GCA, even when no ophthalmic symptoms have been reported., (Georg Thieme Verlag KG Stuttgart · New York.)

Purpose: In patients with suspected giant cell arteritis (GCA), a search for the perivascular halo sign, a sophisticated color duplex ultrasound (CDU) finding, at experienced centers reliably identifies inflamed temporal arteries (TA). We tested whether TA compression in patients with GCA, a simple, largely operator-independent maneuver, elicits contrasting echogenicity between the diseased artery wall and the surrounding tissue (compression sign)., Materials and Methods: 80 individuals with suspected GCA were prospectively enrolled in this single-center study. In all study participants, bilateral ultrasound examination of the TA established the presence/absence of the halo and compression sign. A positive compression sign was defined as visibility of the TA upon transducer-imposed compression of the artery. Based on ACR criteria, a team of specialized physicians independently grouped patients as GCA versus non-GCA., Results: 43/80 study participants were grouped as GCA. Both the halo sign and the compression sign were positive in 34/43 patients in the GCA group, and negative in all 37/37 of the non-GCA group, resulting in a sensitivity of 79 % and a specificity of 100 % for both the halo and the compression sign., Conclusion: In this cohort of individuals with suspected GCA, the halo sign and the compression sign were equal in their diagnostic performance. The simplicity of the compression sign suggests a level of reliability warranting further evaluation., (© Georg Thieme Verlag KG Stuttgart · New York.)

Fever of unknown origin (FUO) is a common medical diagnosis by exclusion. In these cases, fever is the predominant symptom of an underlying disease. We describe the case of a 60-year old patient with FUO. Intensive search for the causative disease was carried out. Unfortunately all the investigations remained fruitless. Eventually, the patient was discharged with the diagnosis of common variable immunodeficiency, based on hypogammaglobulinemia and Cytomegalovirus replication. Two weeks after discharge, the patient presented in the outpatient clinic with the typical symptoms of giant cell arteriitis (GCA). The diagnosis was confirmed by a repeated ultrasound imaging and biopsy findings. The clinical condition of the patient improved rapidly after beginning of treatment with steroids. This case illustrates the importance of a longitudinal observation of patients presenting with FUO if the diagnosis remains unclear after intensive investigations.

Giant cell arteritis (GCA) is the most common of the vasculitis syndromes and, being a disease of the elderly, its incidence is increasing with the general ageing of the population. GCA is most feared for its early complications, namely blindness and stroke, resulting from inflammation and subsequent occlusion of ocular and extra cranial arteries, respectively. More recently, however, GCA has been recognised to also affect limb arteries and the aorta with a high prevalence. These newly recognised features of GCA pose diagnostic, therapeutic and prognostic challenges to treating physicians. Here, recent developments in the field of GCA are summarised and discussed.

Objective: To define the specificity and extent of duplex sonography (DS) findings suggestive of vessel wall inflammation in patients with giant cell arteritis (GCA)., Methods: Patients admitted between December 2006 and April 2009 to the University Hospital Basel with a suspicion of GCA were eligible for the study. DS of 2x11 arterial regions was performed in all study participants, and American College of Rheumatology criteria were applied to classify patients into GCA or non-GCA groups., Results: GCA was diagnosed in 38 of the 72 participants (53%). A DS pattern suggestive of vessel wall inflammation was not observed in any of the patients in the non-GCA group but, in 21 of the 38 patients with GCA (55%), DS signs suggestive of vessel wall inflammation of > or =1 vessel region were detected. In 12 of the 38 patients with GCA (32%), DS signs of large vessel vasculitis (LVV) were found in > or =1 vessel region(s) of both upper and lower limb vessels. Follow-up DS was performed 6 months after the baseline examination in 9 of the 12 patients with LVV and showed the persistence of most findings despite normalised signs of systemic inflammation., Conclusion: DS detects changes in the vessel wall that appear to be specific for GCA; they can be present in upper and lower limb arteries of patients with GCA. Surprisingly, DS-detectable LVV and signs of systemic inflammation are largely dissociated.

Objective: Vision loss and ischaemic stroke are feared complications in GCA. We investigated how platelet count and size and platelet inhibition with ASA relate to ischaemic complications in patients with GCA., Methods: Charts of patients with GCA were retrospectively analysed. Jaw claudication, amaurosis fugax, blurred vision, ischaemic stroke and permanent visual loss were classified as 'ischaemic events'; ischaemic stroke and permanent visual loss were sub-grouped as 'severe ischaemic events'. The incidence of ischaemia and the association to the pre-defined covariates age, fever, ESR, platelet count and size and ASA treatment were assessed., Results: Eighty-five patients (mean age 73 yrs, 60% women, 78% biopsy-proven) were included in the analysis. Of the 85 patients, 62 (73%) presented with ischaemic events, 29/85 patients (34%) with severe ischaemic events. At the time of diagnosis 22/85 patients (26%) were treated with ASA. Of these 22 patients, 15 (68%) presented with ischaemic events, 7/22 patients (32%) with severe ischaemic events. In multivariate analysis, neither platelet count nor size or ASA treatment were significantly associated with ischaemic or severe ischaemic events., Conclusions: The incidence of severe ischaemic events in patients with GCA was high, irrespective of platelet count and size and established ASA treatment.