OBJECTIVES:This Delphi survey, involving patients, primary and secondary care clinicians, and experts was conducted to evaluate the giant cell arteritis (GCA)-polymyalgia rheumatica (PMR) spectrum disease (GPSD) and its implications. The GPSD concept proposes a unified framework for diagnosis and treatment of overlapping conditions including cranial and extracranial GCA and PMR. The survey included two rounds and addressed six propositions covering disease nomenclature, phenotypes, imaging, stratification and clinical impact. METHODS:Round 1 achieved consensus across all propositions, with over 75% agreement and several items exceeding 90%. Key areas of agreement included recognition of GPSD (92%), the role of imaging in diagnosis and stratification (100%), and the need for multilevel assessment (100%). Round 2 refined and clarified questions, further strengthening consensus, with some items reaching 100% agreement. Internal consistency analysis confirmed the survey's reliability and validity for future use. RESULTS:The GPSD model promotes comprehensive evaluation of all phenotypes regardless of initial presentation. It advocates early specialist involvement, personalized treatment strategies and improved diagnostic tools. Imaging modalities such as ultrasound and PET are essential for detecting subclinical disease, excluding alternative diagnoses, and guiding management, especially when symptoms are ambiguous. Stratified care in PMR addresses diagnostic uncertainty and highlights emerging therapies like cytokine blockade. CONCLUSION:The model supports prospective studies using baseline imaging and stratified treatment arms to monitor disease control and long-term outcomes. By unifying fragmented care pathways and promoting a spectrum-based approach, GPSD has the potential to improve patient outcomes, reduce misdiagnosis and guide more effective therapeutic strategies across related inflammatory conditions.

OBJECTIVE:Polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) are closely related chronic inflammatory diseases in which macrophages play a central role in the pathogenesis. This study compared macrophage-related immune profiles in subacromial bursal tissues affected by PMR and temporal arteries affected by GCA to identify shared therapeutic targets. METHODS:Subacromial bursa biopsies (SABBs) were obtained from patients with active PMR (n = 11). Temporal artery biopsies (TABs) were collected from 14 patients with GCA. Immunohistochemical staining was performed for macrophage markers [CD68, CD64, CD86, CD206 and folate receptor (FR) β] and macrophage-related cytokines (GM-CSF, IL-6, IL-23, IFN-γ, M-CSF and TNF-α). The percentage of positively stained cells was quantitatively scored. RESULTS:All macrophage-related markers and cytokines were expressed in both PMR-affected SABBs and GCA-affected TABs. The proportions of cells expressing macrophage markers (CD68, CD64, CD86 and CD206) and macrophage-related cytokines (GM-CSF, IL-6, IL-23, IFN-γ, M-CSF and TNF-α) were comparable between the two tissue types. However, the expression of FRβ was relatively higher in GCA TABs than in PMR SABBs. CONCLUSION:The macrophage immune profiles are remarkably similar in PMR SABBs and GCA TABs. This study underscores the concept of PMR and GCA as a disease spectrum and identifies shared therapeutic targets for both PMR and GCA.

BACKGROUND:Polymyalgia rheumatica is a common inflammatory disease characterized by pain and stiffness in the shoulders and hips. Glucocorticoids are the first-line treatment, but relapses and glucocorticoid-related toxic effects are common, which underscores the need for effective alternatives. Secukinumab is a fully human monoclonal antibody that selectively inhibits interleukin-17A. METHODS:We enrolled patients with recently relapsed polymyalgia rheumatica and randomly assigned them, in a 1:1:1 ratio, to receive secukinumab at a dose of 300 mg (SEC-300 group), secukinumab at a dose of 150 mg (SEC-150 group), or placebo for 52 weeks. Patients in all the groups also received prednisone on a tapering schedule for 24 weeks. The primary outcome was sustained remission at week 52, defined as remission (the absence of signs or symptoms attributable to polymyalgia rheumatica and no new diagnosis of giant-cell arteritis that warranted escape or rescue treatment) that was sustained from week 12 until week 52. The annual cumulative glucocorticoid dose was a secondary outcome. Safety was also assessed. RESULTS:A total of 381 patients underwent randomization, and 127 were assigned to each group. At 52 weeks, sustained remission was observed in 41.2% (95% confidence interval [CI], 32.8 to 49.7) of the patients in the SEC-300 group, in 40.6% (95% CI, 32.2 to 49.0) of those in the SEC-150 group, and in 20.4% (95% CI, 13.6 to 27.2) of those in the placebo group (P<0.001 for the comparison of each secukinumab dose with placebo). The mean adjusted annual cumulative glucocorticoid dose was 1603.7 mg in the SEC-300 group, 1683.2 mg in the SEC-150 group, and 2093.0 mg in the placebo group. Serious adverse events occurred in 13.5% of the patients in the SEC-300 group, in 15.9% in the SEC-150 group, and in 14.2% in the placebo group. Nasopharyngitis, hypersensitivity reactions, urinary tract infections, fungal infections, and back pain were more common in the secukinumab groups than in the placebo group. CONCLUSIONS:Among patients with relapsed polymyalgia rheumatica, treatment with secukinumab plus a 24-week glucocorticoid taper resulted in a higher percentage of patients with remission and in lower cumulative glucocorticoid doses than a glucocorticoid taper alone. (Funded by Novartis; REPLENISH ClinicalTrials.gov number, NCT05767034.).

ObjectivePolymyalgia rheumatica (PMR) is an inflammatory disorder of the elderly characterized by girdle pain and stiffness. Obesity has an influence on disease activity and outcome in rheumatic diseases like osteoarthritis and rheumatoid arthritis. We aimed to investigate the relationship between high BMI and the severity and outcome of PMR, which is incompletely understood.MethodsIn a post hoc analysis, 83 patients with recent-onset PMR were studied over 6 months using clinical examination, laboratory evaluation, and girdle ultrasound (US). The modified Health Assessment Questionnaire (mHAQ), 36-item Short Form Health Survey (SF-36), and PMR visual analog scale (VAS) scores, as well as prednisone therapy data, were recorded. Patients were grouped according to their BMI.ResultsAt baseline, the 12 patients with obesity had significantly more shoulder pain (P= 0.03), global pain (P= 0.03), PMR VAS (P< 0.01), and fatigue (P= 0.03); higher mHAQ (P= 0.01); and lower SF-36 physical component summary (P= 0.048) and SF-36 pain index (P< 0.001). The mean initial prednisone dose was similar among groups, but patients with obesity received a lower dose/kg (1.9 [SD 0.7] mg vs 2.2 [SD 0.7] mg;P< 0.01). At 6 months, patients with obesity were being treated with higher mean daily prednisone doses (8.5 [SD 3.2] mg/d vs 6.2 [SD 5.2] mg/d;P= 0.02), and 40% of them were receiving higher daily prednisone doses than the standard protocol compared with 14% patients without obesity (P= 0.048). Clinical features, laboratory results, and US results were similar between patients with and without obesity.ConclusionObesity affects both symptom severity and prednisone utilization in patients with PMR. The reason for this may relate to different subjective pain perception rather than increased inflammation in patients with obesity. BMI should be considered when interpreting symptoms in patients with PMR and deciding their prednisone doses.

BACKGROUND:Sarilumab is approved for adult patients with polymyalgia rheumatica who have had an inadequate response to corticosteroids or who cannot tolerate corticosteroid taper. We aimed to evaluate the effect of sarilumab on patient-reported outcomes. METHODS:This phase 3, double-blind, randomised controlled trial was done in 60 centres in 17 countries. Eligible patients were adults aged 50 years or older who had at least one episode of disease flare during a glucocorticoid taper (at a dose of ≥7·5 mg per day or prednisone dose equivalent) within 12 weeks before screening and had a history of at least 8 weeks of glucocorticoid treatment (≥10 mg per day or prednisone dose equivalent). All the patients had symptoms of polymyalgia rheumatica and an erythrocyte sedimentation rate >30 mm/h or a C-reactive protein concentration of at least 10 mg/L within 12 weeks before screening. Patients were randomly assigned (1:1) to receive either subcutaneous sarilumab 200 mg once every 2 weeks with a 14-week glucocorticoid taper or matching placebo with a 52-week glucocorticoid taper. Patients and investigators were masked to treatment allocation. The patient-reported outcomes measured were Health Assessment Questionnaire Disability Index (HAQ-DI), Patient Global Assessment of Health Visual Analog Scale (VAS), Pain VAS, Short Form Health Survey (SF-36 v2), EuroQoL 5-Dimensions 3-Levels (EQ-5D including the descriptive system and the VAS), and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F). Patient-reported outcomes were analysed until week 52 as changes from baseline. Post-hoc analyses included proportions of patients reporting improvements of at least minimum clinically important difference and scores of at least normative values. p values were nominal. Analyses were done in the intention-to-treat population. There was no involvement of people with lived experience at any stage of the study. This trial is registered with ClinicalTrials.gov, NCT03600818. FINDINGS:Between Oct 9, 2018, and July 15, 2020, 118 patients were enrolled and randomly assigned to receive sarilumab (n=60) or placebo (n=58). Of these, 117 patients received treatment (59 in the sarilumab group and 58 in the placebo group). One patient assigned to the sarilumab group did not receive treatment. Mean age was 68·9 years (SD 8·1). 82 (69%) of 118 patients were female and 36 (31%) were male, and 98 (83%) were White. At baseline, moderate-to-severe fatigue was reported by 43 (73%) of 59 patients in the sarilumab group and 43 (74%) of 58 patients in the placebo group. At week 52, patients in the sarilumab group reported greater improvements than patients in the placebo group in SF-36 Physical Component Summary (PCS; least-squares mean [LSM] change 7·65 vs 2·87, p=0·020) and Mental Component Summary (MCS; 3·04 vs -1·71, p=0·030) scores, and in five of eight domains. Sarilumab showed greater improvements in EQ-5D utility index (0·11 vs -0·02, p=0·034) and VAS scores (8·37 vs -0·46, p=0·084), FACIT-F (7·91 vs 4·17, p=0·060), HAQ-DI (-0·39 vs -0·15, p=0·054), Pain VAS (-20·57 vs -12·04, p=0·20), and Patient Global Assessment VAS (-15·01 vs -6·08, p=0·13). More patients in the sarilumab group than in the placebo group reported improvements of minimum clinically important difference or greater in SF-36 PCS scores (odds ratio 3·46 [95% CI 1·16-10·62], p=0·020). More than 50% of patients in the sarilumab group reported scores of at least normative values for SF-36 MCS and four domain scores, whereas this was not the case for any domain in the placebo group. INTERPRETATION:Patients with relapsing polymyalgia rheumatica have impaired health-related quality of life. The use of sarilumab 200 mg once every 2 weeks with a 14-week glucocorticoid taper led to clinically important improvements in health-related quality of life and patient-reported outcomes versus placebo with a 52-week glucocorticoid taper. Improvements were highest in patients with most severe disease. These findings provide support for the use of sarilumab in patients with polymyalgia rheumatica whose disease activity and health-related quality of life is not adequately managed by glucocorticoid monotherapy according to treat-to-target principles. FUNDING:Sanofi and Regeneron Pharmaceuticals.

We propose a novel hybrid physical and virtual training method, complemented by online learning, as an effective method to teach and acquire ultrasound skills. We aim to illustrate this through our experience with a remote ultrasound training module for giant cell arteritis scanning. The significance of this innovation is the ability to mitigate the challenges faced by ultrasound training during pandemic-times, including the need for physical distancing, group size limitation and overseas travel restrictions. Furthermore, the hybrid training provides an invaluable access to distant specialist cognitive and procedural expertise when conventional means may not be feasible. Although this form of ultrasound training has limitations, such as diminished face-to-face contact, we were able to resume training despite the unfavourable circumstances. By harnessing virtual technology for hands-on training, we can strive to reduce worldwide training inequalities, particularly in areas requiring highly specialised skills where expertise may not be available locally. Even as the world has moved out of ‘lockdown’, the pandemic has serendipitously provided novel ways of doing things; the lessons learnt here can be utilised for future hybrid training models, especially where hands-on experience is crucial.

OBJECTIVES:Insight into the immunopathology of polymyalgia rheumatica (PMR) is scarce and mainly derived from peripheral blood studies. The limited data available point towards macrophages as potential key players in PMR. This study aimed to identify the factors driving proinflammatory macrophage development and their functions in the immunopathology of PMR. METHODS:Monocyte phenotypes were investigated by flow cytometry in peripheral blood (PMR, n = 22; healthy controls, n = 20) and paired subacromial-subdeltoid (SASD) bursal fluid (PMR, n = 9). Macrophages in SASD bursa were characterised by immunohistochemistry and immunofluorescence (PMR, n = 12; controls undergoing shoulder replacement surgery, n = 10). The functions of cytokines expressed in PMR-affected tissue were examined using macrophage differentiation cultures (PMR, n = 7; healthy controls, n = 7). RESULTS:Monocytes (CD14highCD16- and CD14highCD16+) were increased in blood of PMR patients and activated in bursal fluid. Macrophages dominated immune infiltrates in PMR-affected tissue, expressing various proinflammatory cytokines. While interleukin (IL)-6 and interferon-gamma (IFN-γ) expression was abundant in both PMR and control tissue, granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF) were significantly increased in PMR tissue. Macrophages in PMR-affected tissue showed an elevated CD206/folate receptor β ratio, reflecting a GM-CSF skewed signature. A combination of GM-CSF/M-CSF/IFN-γ significantly boosted IL-6 production in vitro, while limited IL-6 production was observed without GM-CSF. CONCLUSIONS:The monocyte compartment is expanded and activated in PMR. Macrophages in PMR-affected tissue produce abundant proinflammatory cytokines such as IL-6. A network of locally expressed cytokines, including GM-CSF, M-CSF, and IFN-γ, may drive the proinflammatory functions of these macrophages. Overall, macrophages may constitute key therapeutic targets for PMR.

Polymyalgia rheumatica (PMR) is one of the most common inflammatory rheumatic diseases in people aged ≥50 years and is characterised by neck pain, bilateral shoulder and hip girdle pain, and morning stiffness. It is closely interlinked with giant cell arteritis (GCA) (potentially considered the GCA-PMR spectrum) and rheumatoid arthritis and shares a common immunopathophysiology with both. Glucocorticoids (GCs) have been the standard of care for PMR for several decades (American College of Rheumatology/European Alliance of Associations for Rheumatology guidelines); however, >50% of patients cannot successfully taper GCs, and long-term treatment is associated with considerable GC-related adverse events. Immunohistological studies using biopsies from subacromial bursae have indicated that various cytokines and cells, including macrophages, interleukin-6 (IL-6), and fibroblast-like synoviocytes (FLS), play an integral role in the immunopathophysiology of PMR. Proinflammatory cytokines, including IL-1, IL-6, IL-17, and tumour necrosis factor-alpha, activate FLS which then secrete IL-6 that can further promote FLS proliferation. Activation of synoviocytes in bursae may result in bursitis which can lead to a high concentration of acute-phase reactants and systemic inflammation. IL-6 also plays a role in sleep disturbances, mood disorders, pain, and fatigue; it is often seen in PMR, via disruption of the hypothalamic-pituitary-adrenal axis, and actions on the peripheral and central pain pathways. Given the diverse roles of IL-6 in the immunopathophysiology of PMR, targeted molecular therapies such as IL-6 receptor inhibitors offer promising alternatives for disease management, distinct from the nonspecific immunosuppressive effects of GCs. In this review, we describe the immunopathophysiology of PMR and discuss unmet medical needs and therapeutic options for PMR.

Sarilumab (interleukin‐6 receptor inhibitor) is approved in the United States and Europe for polymyalgia rheumatica (PMR). This study characterized sarilumab pharmacokinetics (PK) and assessed the influence of intrinsic and extrinsic factors on PK in patients with PMR and giant cell arteritis (GCA). Exposure‐responses analyses were conducted to evaluate the PK‐pharmacodynamic (PD) relationships of sarilumab with key efficacy and safety endpoints in patients with PMR (NCT03600818). Population (Pop) PK analysis was conducted using pooled PK data from two phase III studies including 58 patients with PMR and 40 with GCA (NCT03600805). This Pop PK model was developed by re‐estimating parameters from a previous rheumatoid arthritis (RA) model. The main source of intrinsic PK variability in patients with PMR was body weight, with decreasing weight causing increased sarilumab exposure. The population mean apparent clearance for patients with PMR was lower than for patients with RA due to higher albumin, lower creatinine clearance, and lower C‐reactive protein (CRP) in PMR than in RA. Individual exposures at steady state overlapped among patients with PMR, GCA, and RA. PK‐PD relationships showed that greater sarilumab C trough in patients with PMR were associated with increasing total sIL‐6Rα and decreasing CRP. There was a slight increase in patients achieving sustained remission at Week 52 and a decrease in absolute neutrophil count with increasing sarilumab C trough plateauing at 20‐25 mg/L. The PD effect of sarilumab plateaued at C trough of 20‐25 mg/L for target saturation, efficacy, and safety endpoints, supporting a dosage of 200 mg every 2 weeks for PMR.

Objective To test the reliability of the Outcome Measures in Rheumatology Giant cell arteritis (GCA) Ultrasonography Score (OGUS) and other composite scores in a patient-based exercise involving experts and non-experts in vascular ultrasonography.Methods Six GCA patients were scanned twice (two rounds separated ≥3 hours) by 12 experts and 12 non-experts. Non-experts received 90 min of theoretical and 240 min of practical training between rounds 1 and 2. Ultrasonography was conducted on temporal arteries (common superficial, frontal and parietal branches) and axillary arteries bilaterally to calculate the OGUS, the Southend score and the Halo count. Inter-reader and intra-reader reliability were assessed by intraclass correlation coefficient (ICC).Results Mean age of GCA patients was 78±5.1 years, 2 (33.3%) were women, and all were in clinical remission. Expert inter-reader ICC of the OGUS was 0.60 in both rounds, 0.40 in round 1 and 0.51 in round 2 for the Southend score and 0.45 and 0.52, respectively, for the Halo count. Median ICCs for intra-reader reliability were 0.86, 0.73 and 0.65 for the OGUS, Southend score and Halo count, respectively.For non-experts, inter-reader ICCs in round 1 were 0.20 for the OGUS, 0.20 for a normalised Southend score (=score divided by available segments) and 0.35 for a normalised Halo count. After training, inter-reader reliability ICCs improved to 0.52, 0.29 and 0.54, respectively.Conclusion Inter-reader reliability was fair to moderate, and intra-reader reliability was good for OGUS, Southend score and Halo count among experts. Inter-reader reliability of non-experts in vascular ultrasonography improved after the training.

The use of ultrasound (US) has increasingly become an established part of routine clinical practice in rheumatology. However, there is still a debate over whether all rheumatologists should learn US examination skills. Nonetheless, all rheumatologists should be able to understand the place of the US, when to request it, and what potential value it adds. Point of Care US (POCUS) has recently emerged as an adjunct to clinical reasoning and rapid decision-making in areas of acute medicine, such as vascular, cardiac, urological, and other emergencies.1 We coined the term POCRUS (point of care rheumatology US) to describe its similar application in rheumatology. APLAR recently trialed a new model for teaching the US, focusing on applying the US in clinical practice using an evidence-based probability approach. The sessions were organized around the management of clinical scenarios rather than using a traditional system of evaluating each joint or each disease process separately. The model reinforced the importance of clinical history and physical examination in decisions and helped learners consider the additional value of the US in a range of scenarios. The course was delivered online in 2022–2023. The course was grounded on the US prediction tool previously developed for diagnosing giant cell arteritis (GCA) and large vessel vasculitis (LVV). EULAR recommendations for LVV2 and polymyalgia rheumatica (PMR) criteria3, 4 demonstrate that the sequential application of clinical assessment with US examination leads to robust prediction of post-test probability diagnostic sensitivity and specificity. Clinical decision-making in rheumatology is often associated with a degree of uncertainty, and the US offers a rapid means of either confirming or refuting a diagnostic hypothesis. The US improves diagnostic accuracy and clinical confidence and facilitates earlier prompt and appropriate treatment while simultaneously ruling out serious mimics like infection, cancer, and metabolic conditions, as well as less serious mimics such as osteoarthritis and chronic pain. While inflammatory rheumatological conditions may show distinct sonographic abnormalities, others show a combination of features, the interpretation of which requires some guidance. We developed an online course under the aegis of APLAR to apply these principles in the diagnosis of inflammatory arthritic conditions. In this POCRUS course, the faculty grouped common rheumatology scenarios into five categories: oligoarthralgia, monoarthralgia, polyarthralgia, polymyalgia, and GCA/LVV. The course was presented in six 2-h online sessions. During the overview session, the attendees were introduced to a probability-based approach for managing inflammatory diseases, which had been previously reported for GCA. They were taught the role of POCRUS in the probability-based algorithm for individual scenarios by recognizing specific and sensitive US signs/patterns of disease. The attendees were further taught about the sensitivity/specificity and the linked negative/positive predictive values, which helped them to confirm/exclude target conditions by applying POCRUS findings. A predictive approach was recently published for suspected GCA in a fast-track clinic. GCA has a wide range of symptoms that can be difficult to distinguish from other conditions. A probability-based approach is used to predict the likelihood of GCA by applying SGCAPS (Southend GCA probability score) and vascular US (halo count, halo score). This approach stratifies patients into low, intermediate, and high-risk categories.5, 6 A nomogram has been developed to provide a numerical post-test predictive value.7 The significance of the US findings of oligoarthritis, enthesitis,8, 9 tenosynovitis,10 pulley abnormalities,11 and dactylitis (Figure 1) was introduced at the second session. This session also covered inflammation and structural damage, scoring, tight control monitoring, patient education, adherence, persistence, and compliance issues. Three different case scenarios were discussed, and a panel discussion with faculty members allowed for a synthesis of the salient messages. The third session began with a lecture on an approach to acute monoarthritis, which included sensitive and specific US findings of gout,12-16 the application of a probability-based approach to gout and acute monoarthritis (Figure 2), and several case presentations. Participants were asked about the probability and urgency of differential diagnoses, the potential benefit of US, and the need for arthrocentesis. They also used the 2015 ACR/EULAR Classification Gout Criteria17, 18 to calculate pre- and post-test probability. When the clinical features, pretest probability, and US results are inconsistent (for example, fluid collection without a Doppler signal in an unwell patient), participants were encouraged to consider alternative diagnostic procedures as an alert for serious conditions such as tumors. In the fourth session, the value of POCRUS for small joint polyarthralgia, a common presentation to early arthritis clinics, was explored. The talk mainly focused on rheumatoid, psoriatic arthritis, and osteoarthritis and highlighted the ability of US to detect several inflammatory and structural lesions, which can provide alternative explanations. This can occur when a scan is normal, such as in chronic pain syndromes or when pathology not previously considered is seen, such as an enlarged median nerve. However, it was noted that the presence of a lesion without associated symptoms in a normal population is not always diagnostic. In such cases, US findings like grade 2–3 Doppler signals or size of erosions may add specificity. The fifth session covered the importance of POCRUS in fast-track GCA clinics (already used), including scanning techniques, interpretation of US images, and the application of SGCAPS. Three cases were used to illustrate the spectrum of GCA and LVV and its differentials, including ANCA-associated vasculitis. The diagnostic approach to PMR using US characteristics of PMR and the evolution of classification criteria is featured in the sixth session. Anatomical areas that should be the focus of US examination for PMR19 were detailed to differentiate PMR from other inflammatory disorders such as rheumatoid arthritis and spondyloarthropathy. PET and MRI-based studies20-23 were quoted alongside US research to support the proposed approach. Case presentations highlighted the overlap with differential diagnoses such as crystal deposition disease, inflammatory arthritis and the GCA-PMR spectrum. The scenario-based, probability-directed education in POCRUS, organized by APLAR, received positive feedback when targeted at participants with beginner to intermediate competency. Attendees appreciated the break-out sessions and panel discussions as they allowed them to ask the expert facilitators questions and discuss cases to identify the role of US in their clinical practice. During the sessions, participants discussed scenarios involving US use and identified the perceived barriers to its implementation. Our pre- and post-course questionnaire surveys helped us identify the barriers to the inclusion of US in rheumatology practice (Table 1). With the increased availability of cost-effective portable US equipment and the easier accessibility of US training courses/workshops for rheumatologists, POCRUS is expected to assist in overcoming these barriers. However, almost all participants reported that US had helped them improve the diagnosis and management of rheumatic disease by adding to post-test probability. Ideally, in the future, live demonstrations and hands-on face-to-face teaching can be incorporated into the program. By allowing more time for each module, a formal knowledge assessment before and after sessions helps to assess the teaching effectiveness. A follow-up evaluation after 6 months will further confirm knowledge retention in the participants. We can potentially improve rheumatology practice using our probability-directed POCRUS approach as it reduces subjective variations in clinical evaluations and minimizes diagnostic errors. This approach can lead to more seamless and streamlined one-stop consultations in early arthritis, fast-track, and other urgent clinics. Additionally, it can objectively determine diagnostic uncertainty, which can encourage timely additional tests, improve patient communication, and optimize expectations (Box 1). The approach also serves as a real-time imaging tool for illustrating the underlying cause of disease symptoms to patients. This should facilitate informed decision-making, choice, and adherence to therapy, which can often be challenging to understand. Categorize pre-test probability Assess specific/sensitive patterns Categorize post-test probability Uncertain disease Our POCRUS teaching model has significant implications for research in facilitating the development of algorithms for diagnosing inflammatory rheumatic and musculoskeletal diseases (RMDs). We propose to conduct a standard pre-test clinical assessment, which takes into account the international classification criteria for different RMDs as probability scores. Subsequently, a standardized US assessment is performed to confirm or exclude the target RMD condition. We believe the scenario-based, probability-directed POCRUS approach is an effective teaching method that helps improve understanding and reinforce the diagnostic value of specific US findings. This method should be considered alongside other theories and practical instructions. Its unique capabilities will significantly contribute to the field and enhance the learning experience for students and professionals alike. BD provided the initial idea for the course. All authors participated in designing, planning, conceptualising, and organising the curriculum, pedagogy, and teaching of the online course. All authors wrote and critically revised the manuscript for important intellectual content. All authors have read and approved the submitted manuscript. We acknowledge the APLAR Academy, APLAR Education Committee, and APLAR Secretariat for providing the necessary funding, opportunity, and support to organize and report this Webinar series. We extend our heartfelt thanks to the late Professor Debashish Danda, Immediate Past President of APLAR, and Professor Lai Shan Tam, Convenor of APLAR Academy, for their encouragement and unwavering support toward this course. None declared. Only the course attendants can access the recording of the online course materials. The corresponding author, KOK, can provide all other data supporting the findings in this paper upon request.

Objectives To update the EULAR recommendations for the use of imaging modalities in primary large vessel vasculitis (LVV). Methods A systematic literature review update was performed to retrieve new evidence on ultrasound, MRI, CT and [ 18 F]-fluorodeoxyglucose positron emission tomography (FDG-PET) for diagnosis, monitoring and outcome prediction in LVV. The task force consisted of 24 physicians, health professionals and patients from 14 countries. The recommendations were updated based on evidence and expert opinion, iterating until voting indicated consensus. The level of agreement was determined by anonymous votes. Results Three overarching principles and eight recommendations were agreed. Compared to the 2018 version, ultrasound is now recommended as first-line imaging test in all patients with suspected giant cell arteritis, and axillary arteries should be included in the standard examination. As an alternative to ultrasound, cranial and extracranial arteries can be examined by FDG-PET or MRI. For Takayasu arteritis, MRI is the preferred imaging modality; FDG-PET, CT or ultrasound are alternatives. Although imaging is not routinely recommended for follow-up, ultrasound, FDG-PET or MRI may be used for assessing vessel abnormalities in LVV patients with suspected relapse, particularly when laboratory markers of inflammation are unreliable. MR-angiography, CT-angiography or ultrasound may be used for long-term monitoring of structural damage, particularly at sites of preceding vascular inflammation. Conclusions The 2023 EULAR recommendations provide up-to-date guidance for the role of imaging in the diagnosis and assessment of patients with LVV.

BackgroundGiant cell arteritis is a critically ischaemic disease with protean manifestations that require urgent diagnosis and treatment. European Alliance of Associations for Rheumatology (EULAR) recommendations advocate ultrasonography as the first investigation for suspected giant cell arteritis. We developed a prediction tool that sequentially combines clinical assessment, as determined by the Southend Giant Cell Arteritis Probability Score (SGCAPS), with results of quantitative ultrasonography.MethodsThis prospective, multicentre, inception cohort study included consecutive patients with suspected new onset giant cell arteritis referred to fast-track clinics (seven centres in Italy, the Netherlands, Spain, and UK). Final clinical diagnosis was established at 6 months. SGCAPS and quantitative ultrasonography of temporal and axillary arteries with three scores (ie, halo count, halo score, and OMERACT GCA Score [OGUS]) were performed at diagnosis. We developed prediction models for diagnosis of giant cell arteritis by multivariable logistic regression analysis with SGCAPS and each of the three ultrasonographic scores as predicting variables. We obtained intraclass correlation coefficient for inter-rater and intra-rater reliability in a separate patient-based reliability exercise with five patients and five observers.FindingsBetween Oct 1, 2019, and June 30, 2022, we recruited and followed up 229 patients (150 [66%] women and 79 [34%] men; mean age 71 years [SD 10]), of whom 84 were diagnosed with giant cell arteritis and 145 with giant cell arteritis mimics (controls) at 6 months. SGCAPS and all three ultrasonographic scores discriminated well between patients with and without giant cell arteritis. A reliability exercise showed that the inter-rater and intra-rater reliability was high for all three ultrasonographic scores. The prediction model combining SGCAPS with the halo count, which was termed HAS-GCA score, was the most accurate model, with an optimism-adjusted C statistic of 0·969 (95% CI 0·952 to 0·990). The HAS-GCA score could classify 169 (74%) of 229 patients into either the low or high probability groups, with misclassification observed in two (2%) of 105 patients in the low probability group and two (3%) of 64 of patients in the high probability group. A nomogram for easy application of the score in daily practice was created.InterpretationA prediction tool for giant cell arteritis (the HAS-GCA score), combining SGCAPS and the halo count, reliably confirms and excludes giant cell arteritis from giant cell arteritis mimics in fast-track clinics. These findings require confirmation in an independent, multicentre study.FundingRoyal College of Physicians of Ireland, FOREUM.

Background: Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are considered to belong to a spectrum of inflammatory diseases with a broad overlap in clinical presentation called GPSD (GCA-PMR Spectrum Disease) [1]. Soft tissue abnormalities around the joints in patients with GPSD have already been detected using [18F]FDG PET/CT [2]. However, the resolution is limited for methodological reasons and soft tissue structures are often difficult to impossible to differentiate. Magnetic resonance imaging (MRI) offers the possibility of examining soft tissue structures with high resolution to better differentiate which structures are affected. Objectives: The aim of our study was therefore to analyze typical predilection sites of the soft tissue in GPSD with high-resolution MRI. Methods: Retrospective analysis of MRI examinations of patients with newly diagnosed GPSD according to current recommendations. High-resolution contrast-enhanced MRI was performed on a 3 Tesla scanner, using a T1-weighted VIBE sequence. The following structures were analyzed separately by two experienced radiologists, blinded to clinical data: Shoulders on both sides with glenohumeral joints, periarticular tendons, cervical spine. Enhancement was judged in a 4-point Lickert scale reaching from “no inflammation” to “surely inflamed” (0=no signs of inflammation, 1=mild contrast enhancement, unclear whether degenerative or inflammatory genesis, 2=accentuated contrast enhancement, suspicious of inflammatory changes, 3=strong contrast enhancement, highly suspicious of inflammatory changes). The analysis with regard to inflammatory changes was carried out in binary form; 0 and 1 were considered inflammation negative, 2 and 3 were considered inflammation positive. Results: 78 patients with GPSD [mean age 72±8 years; predominant vasculitis: 43(55.1%); predominant PMR 19(24.4%); overt symptoms of GCA and PMR 16(20.5%)] were analyzed. Analysis of the shoulders and spine revealed significant enhancement indicative of inflammatory activity in 51%, while only 44.9% had corresponding clinical symptoms. In detail, analysis revealed signs of glenohumeral synovitis in 27 patients (27/78=35%, 24 left side, 24 right side, 21 bilateral), shoulder joint effusion in 5 patients (5/78=6%, 5 left side, 4 right side, 4 bilateral), enhancement of the long biceps tendon in 20 patients (20/78=26%, 16 left side, 18 right side, 14 bilateral), enhancement of the subscapularis tendon in 33 patients (33/78=42%, 33 left side, 33 right side, 33 bilateral) and enhancement of the supraspinous ligament in 23 patients (23/78=29%) (Table 1). Conclusion: Signs of inflammation were found in more than half of the GPSD patients. Due to the high resolution of the MRI, various inflamed articular structures could be identified, including glenohumeral joints and various tendons. A new finding is that tendinitis can also be detected. MRI provides a differentiated overview of inflamed soft tissue structures in GPSD. REFERENCES: [1] Tomelleri, A., et al., Disease stratification in GCA and PMR: state of the art and future perspectives. Nat Rev Rheumatol, 2023. 19(7): p. 446-459.[2] Fröhlich, M., et al., Whole-Body [(18)F]FDG PET/CT Can Alter Diagnosis in Patients with Suspected Rheumatic Disease. Diagnostics (Basel), 2021. 11(11). Acknowledgements: NIL. Disclosure of Interests: Konstanze V. Guggenberger: None declared, Matthias Fröhlich: None declared, Marc Schmalzing BMS, Novartis, AbbVie, AstraZeneca, Chugai/Roche, Janssen-Cilag, Gilead,Boehringer/Ingelheim, Mylan, onkowissen.de, Galapagos, EUSA-Pharma, Chugai/Roche, Hexal/Sandoz, Gilead, AbbVie, Janssen-Cilag, Boehringer/Ingelheim, onkowissen.de, EUSA-Pharma, Novartis, AstraZeneca, Amgen, medac, Lilly, Galapagos, UCB, Chugai, Novartis, Bhaskar Dasgupta: None declared, Michael Gernert: None declared, Patrick P. Strunz: None declared, Hannah Labinsky: None declared, Sebastian E. Serfling: None declared, Rudolf A. Werner: None declared, Torsten Bley: None declared.Table 1Examined soft tissue structures in magnetic resonance imaging (MRI) in patients with giant cell arteritis (GCA) and/or polymyalgia rheumatica (PMR), i.e. GCA-PMR spectrum diseases (GPSD), and frequency of contrast-agent enhancement, indicative for inflammation.Inflamed soft tissue structuresleft (%)right (%)bilateral(%)glenohumeral synovitis24 (31)24 (31)21 (27)shoulder joint effusion5 (6)4 (5)4 (5)enhancement long biceps tendon16 (20)18 (23)14 (18)Enhancement subscapularis tendon33 (42)33 (42)33 (42)Enhancement supraspinous ligament23 (29)

Objectives Ultrasound has a paramount role in the diagnostic assessment of giant cell arteritis (GCA); Southend halo score (HS), halo count (HC), and OMERACT GCA Ultrasonography Score (OGUS) are the first quantitative scores proposed in this setting. The aim of this study was therefore to assess the diagnostic accuracy of these scores in a real-life scenario, as well as to evaluate their optimal cutoff, also with respect to disease extent, sex, and age. Methods We retrospectively collected clinical, serological, and US findings of all patients referred for the first time to our vasculitis clinic in the suspicion of GCA. Results A total of 79 patients were included, and a definite diagnosis of GCA was made in 43 patients. For OGUS, the ROC curve showed an optimal cut point of 0.81 (sensitivity 79.07% and specificity 97.22%). For HC and HS, the optimal cutoff values were > 1.5 (sensitivity 76.7% and specificity 97.2%) and > 14.5 (sensitivity 74.4% and specificity 97.2%), respectively. No relevant differences were assessed when patients were stratified according to disease extent, age, and sex. Compression sign (CS) was positive in 34 of 38 patients with cranial GCA and negative in all controls and LV-GCA. Conclusion All three scores display good sensitivity and excellent specificity, although the cutoff was slightly different than proposed. In particular, for OGUS, a threshold of 0.81 could be employed for diagnostic purposes, although it was developed solely for monitoring. Due to its high sensitivity and specificity, CS should be always assessed in all patients referred with a suspicion of cranial GCA.

Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are common conditions in older adults. Their clinical connection has been recognized over time, with many patients experiencing both conditions separately, simultaneously or in temporal sequence to each other. Early GCA detection is essential to prevent vascular damage, but identifying subclinical GCA in PMR patients remains a challenge and routine screening is not standard practice. Subclinical GCA prevalence in newly diagnosed PMR patients ranges from 23 to 29%, depending on the screening method. Vessel wall imaging and temporal artery biopsy can detect subclinical GCA. Epidemiology and trigger factors show similarities between the two conditions, but PMR is more common than GCA. Genetic and pathogenesis studies reveal shared inflammatory mechanisms involving dendritic cells, pro-inflammatory macrophages, and an IL-6 signature. However, the inflammatory infiltrates differ, with extensive T cell infiltrates seen in GCA while PMR shows an incomplete profile of T cell and macrophage-derived cytokines. Glucocorticoid treatment is effective for both conditions, but the steroid requirements vary. PMR overall mortality might be similar to the general population, while GCA patients with aortic inflammatory aneurysms face increased mortality risk. The GCA-PMR association warrants further research. Considering their kinship, recently the term GCA-PMR Spectrum Disease (GPSD) has been proposed.