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IntroductionGiant cell arteritis (GCA) is a vision-threatening systemic vasculitis for which no universally accessible diagnostic tool exists. Optic nerve sheath diameter (ONSD), measurable via ultrasound, has emerged as a promising, non-invasive biomarker of cranial GCA. The Sonographic Assessment of the Optic Nerve Sheath in Giant Cell Arteritis (SONIC-GCA) aims to validate ONSD ultrasound as a diagnostic and monitoring tool in GCA.Methods and analysisSONIC-GCA is a prospective, multicentre study enrolling patients referred for the evaluation of suspected GCA. A total of 285 participants will undergo optic nerve sheath ultrasound and digital retinal funduscopy, followed by a standardised GCA assessment. All participants will be followed for a minimum of 6 months, at which time an external adjudication committee will confirm the diagnosis of GCA. Those diagnosed with GCA will be followed for 2 years, with repeated optic nerve sheath ultrasound and digital retinal funduscopy at months 3, 6, 12, 18, 24 and at relapse, if applicable.The primary outcome is the diagnostic accuracy of ONSD to detect GCA, which will be evaluated using receiver operating characteristic curve analysis, with adjudicated GCA status serving as the reference standard. Secondary outcomes will address several complementary domains: its value for relapse monitoring will be assessed through time-dependent Cox proportional hazards models, examining whether baseline or longitudinal ONSD predicts relapse risk; intraobserver and interobserver reliability will be determined using intraclass correlation coefficients, providing quantitative estimates of measurement reproducibility; and its association with retinal findings will be evaluated by correlating ONSD measurements with ocular imaging and clinical retinal outcomes. Together, these analyses will comprehensively determine the diagnostic, prognostic and operational utility of ONSD in GCA.Ethics and disseminationThe study has been peer-reviewed by the scientific committee and approved by the CIUSSS du Nord-de-l’Île-de-Montréal Research Ethics Board. Each participating site will obtain local ethics approval prior to enrolment. All participants will provide informed consent. Results will be disseminated through peer-reviewed publications, conference presentations and webinars.Trial registration numberNCT05749094.

The loss of efferocytosis-the phagocytic clearance of apoptotic cells-is an initiating event in atherosclerotic plaque formation. While the loss of macrophage efferocytosis is a prerequisite for advanced plaque formation, the transcriptional and cellular events in the pre-lesion site that drive these defects are poorly defined. Transcriptomic analysis of macrophages recovered from early-stage human atherosclerotic lesions identified a 50-fold increase in the expression of GATA2, a transcription factor whose expression is normally restricted to the hematopoietic compartment. GATA2 overexpression recapitulated many of the functional defects reported in patient macrophages, including deficits at multiple stages in the efferocytic process. These findings included defects in the uptake of apoptotic cells, efferosome maturation, and in phagolysosome function. These efferocytic defects were a product of GATA2-driven alterations in the expression of key regulatory proteins, including Src-family kinases, Rab7 and components of both the vacuolar ATPase and NADPH oxidase complexes. In summary, these data identify a mechanism by which efferocytic capacity is lost in the early stages of plaque formation, thus setting the stage for the accumulation of uncleared apoptotic cells that comprise the bulk of atherosclerotic plaques.

Objectives The cerebral vessels may be affected in primary systemic vasculitis (PSV), but little is known about cerebrovascular events (CVEs) in this population. This study aimed to determine the frequency of CVEs at the time of diagnosis of PSV, to identify factors associated with CVEs in PSV, and to explore features and outcomes of stroke in patients with PSV. Methods Data from adults newly diagnosed with PSV within the Diagnostic and Classification Criteria in VASculitis (DCVAS) study were analysed. Demographics, risk factors for vascular disease, and clinical features were compared between patients with PSV with and without CVE. Stroke subtypes and cumulative incidence of recurrent CVE during a prospective 6-month follow-up were also assessed. Results The analysis included 4828 PSV patients, and a CVE was reported in 169 (3.50%, 95% CI 3.00–4.06): 102 (2.13% 95% CI 1.73–2.56) with stroke and 81 (1.68% 95% CI 1.33–2.08) with transient ischemic attack (TIA). The frequency of CVE was highest in Behçet’s disease (9.5%, 95% CI 5.79–14.37), polyarteritis nodosa (6.2%, 95% CI 3.25–10.61), and Takayasu’s arteritis (6.0%, 95% CI 4.30–8.19), and lowest in microscopic polyangiitis (2.2%, 95% CI 1.09–3.86), granulomatosis with polyangiitis (2.0%, 95% CI 1.20–3.01), cryoglobulinaemic vasculitis (1.9%, 95% CI 0.05–9.89), and IgA-vasculitis (Henoch-Schönlein) (0.4%, 95% CI 0.01–2.05). PSV patients had a 11.9% cumulative incidence of recurrent CVE during a 6-month follow-up period. Conclusion CVEs affect a significant proportion of patients at time of PSV diagnosis, and the frequency varies widely among different vasculitis, being higher in Behçet’s. Overall, CVE in PSV is not explained by traditional vascular risk factors and has a high risk of CVE recurrence.

ObjectiveTo develop and validate updated classification criteria for giant cell arteritis (GCA).MethodsPatients with vasculitis or comparator diseases were recruited into an international cohort. The study proceeded in six phases: (1) identification of candidate items, (2) prospective collection of candidate items present at the time of diagnosis, (3) expert panel review of cases, (4) data‐driven reduction of candidate items, (5) derivation of a points‐based risk classification score in a development data set and (6) validation in an independent data set.ResultsThe development data set consisted of 518 cases of GCA and 536 comparators. The validation data set consisted of 238 cases of GCA and 213 comparators. Age ≥50 years at diagnosis was an absolute requirement for classification. The final criteria items and weights were as follows: positive temporal artery biopsy or temporal artery halo sign on ultrasound (+5); erythrocyte sedimentation rate ≥50 mm/hour or C reactive protein ≥10 mg/L (+3); sudden visual loss (+3); morning stiffness in shoulders or neck, jaw or tongue claudication, new temporal headache, scalp tenderness, temporal artery abnormality on vascular examination, bilateral axillary involvement on imaging and fluorodeoxyglucose–positron emission tomography activity throughout the aorta (+2 each). A patient could be classified as having GCA with a cumulative score of ≥6 points. When these criteria were tested in the validation data set, the model area under the curve was 0.91 (95% CI 0.88 to 0.94) with a sensitivity of 87.0% (95% CI 82.0% to 91.0%) and specificity of 94.8% (95% CI 91.0% to 97.4%).ConclusionThe 2022 American College of Rheumatology/EULAR GCA classification criteria are now validated for use in clinical research.

ObjectiveTo develop and validate classification criteria for microscopic polyangiitis (MPA).MethodsPatients with vasculitis or comparator diseases were recruited into an international cohort. The study proceeded in five phases: (1) identification of candidate items using consensus methodology, (2) prospective collection of candidate items present at the time of diagnosis, (3) data-driven reduction of the number of candidate items, (4) expert panel review of cases to define the reference diagnosis and (5) derivation of a points-based risk score for disease classification in a development set using least absolute shrinkage and selection operator logistic regression, with subsequent validation of performance characteristics in an independent set of cases and comparators.ResultsThe development set for MPA consisted of 149 cases of MPA and 408 comparators. The validation set consisted of an additional 142 cases of MPA and 414 comparators. From 91 candidate items, regression analysis identified 10 items for MPA, 6 of which were retained. The final criteria and their weights were as follows: perinuclear antineutrophil cytoplasmic antibody (ANCA) or anti-myeloperoxidase-ANCA positivity (+6), pauci-immune glomerulonephritis (+3), lung fibrosis or interstitial lung disease (+3), sino-nasal symptoms or signs (−3), cytoplasmic ANCA or anti-proteinase 3 ANCA positivity (−1) and eosinophil count ≥1×109/L (−4). After excluding mimics of vasculitis, a patient with a diagnosis of small- or medium-vessel vasculitis could be classified as having MPA with a cumulative score of ≥5 points. When these criteria were tested in the validation data set, the sensitivity was 91% (95% CI 85% to 95%) and the specificity was 94% (95% CI 92% to 96%).ConclusionThe 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for MPA are now validated for use in clinical research.

IgG4-related disease (IgG4-RD) can cause fibroinflammatory lesions in nearly any organ. Correlation among clinical, serological, radiological and pathological data is required for diagnosis. This work was undertaken to develop and validate an international set of classification criteria for IgG4-RD. An international multispecialty group of 86 physicians was assembled by the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR). Investigators used consensus exercises; existing literature; derivation and validation cohorts of 1879 subjects (1086 cases, 793 mimickers); and multicriterion decision analysis to identify, weight and test potential classification criteria. Two independent validation cohorts were included. A three-step classification process was developed. First, it must be demonstrated that a potential IgG4-RD case has involvement of at least one of 11 possible organs in a manner consistent with IgG4-RD. Second, exclusion criteria consisting of a total of 32 clinical, serological, radiological and pathological items must be applied; the presence of any of these criteria eliminates the patient from IgG4-RD classification. Third, eight weighted inclusion criteria domains, addressing clinical findings, serological results, radiological assessments and pathological interpretations, are applied. In the first validation cohort, a threshold of 20 points had a specificity of 99.2% (95% CI 97.2% to 99.8%) and a sensitivity of 85.5% (95% CI 81.9% to 88.5%). In the second, the specificity was 97.8% (95% CI 93.7% to 99.2%) and the sensitivity was 82.0% (95% CI 77.0% to 86.1%). The criteria were shown to have robust test characteristics over a wide range of thresholds. ACR/EULAR classification criteria for IgG4-RD have been developed and validated in a large cohort of patients. These criteria demonstrate excellent test performance and should contribute substantially to future clinical, epidemiological and basic science investigations.

ObjectiveTo develop and validate new classification criteria for Takayasu arteritis (TAK).MethodsPatients with vasculitis or comparator diseases were recruited into an international cohort. The study proceeded in six phases: (1) identification of candidate criteria items, (2) collection of candidate items present at diagnosis, (3) expert panel review of cases, (4) data‐driven reduction of candidate items, (5) derivation of a points‐based classification score in a development data set and (6) validation in an independent data set.ResultsThe development data set consisted of 316 cases of TAK and 323 comparators. The validation data set consisted of an additional 146 cases of TAK and 127 comparators. Age ≤60 years at diagnosis and imaging evidence of large‐vessel vasculitis were absolute requirements to classify a patient as having TAK. The final criteria items and weights were as follows: female sex (+1), angina (+2), limb claudication (+2), arterial bruit (+2), reduced upper extremity pulse (+2), reduced pulse or tenderness of a carotid artery (+2), blood pressure difference between arms of ≥20 mm Hg (+1), number of affected arterial territories (+1 to +3), paired artery involvement (+1) and abdominal aorta plus renal or mesenteric involvement (+3). A patient could be classified as having TAK with a cumulative score of ≥5 points. When these criteria were tested in the validation data set, the model area under the curve was 0.97 (95% CI 0.94 to 0.99) with a sensitivity of 93.8% (95% CI 88.6% to 97.1%) and specificity of 99.2% (95% CI 96.7% to 100.0%).ConclusionThe 2022 American College of Rheumatology/EULAR classification criteria for TAK are now validated for use in research.

The most likely diagnosis is rheumatoid arthritis. A thorough history and physical examination are important in distinguishing rheumatoid arthritis from other causes of polyarthritis, such as systemic lupus erythematosus and other connective tissue diseases, spondyloarthritis with peripheral joint involvement, joint infections, crystalline arthritis and osteoarthritis. Rheumatoid arthritis should be suspected on the basis of clinical findings: bilateral and symmetric peripheral joint pain and swelling, particularly in small joints, and morning stiffness for more than 30 minutes.1 The classification criteria for rheumatoid arthritis were revised in 2010 to increase the chances of early detection (Box 1).1 In a study involving 2258 patients with early rheumatoid arthritis, the new criteria had a sensitivity of 71%-84% and a specificity of 60%- 74% for detection.2 This implies that there are risks of false-negative and false-positive diagnoses, particularly when the probablity of having the disease is low in a primary care setting. Therefore, the criteria may serve as a guide but should not be used in isolation. Consensus statements recommend measuring the erythrocyte sedimentation rate or the C-reactive protein level or both in cases of suspected rheumatoid arthritis; however, these tests are nonspecific. 1,4 Detecting the presence of the antibodies associated with rheumatoid arthritis, such as rheumatoid factor (RF) and anticitrullinated peptide antibody (commonly measured as anticyclic citrullinated peptide antibody [anti-CCP2]) is also recoimnended to aid in diagnosis.1 Systematic reviews of the diagnostic value of antibodies in undifferentiated inflammatory arthritis showed that antibodies associated with rheumatoid arthritis are predictive of the disease ( positive likelihood ratio 1.1-13.5 for rheumatoid factor and 12.7 for anti-CCP2).5,6 However, rheumatoid factor can be found in other conditions, such as bacterial endocarditis, hepatitis C virus infection and primary biliary cirrhosis, whereas anti-CCP2 has a higher specificity for rheumatoid arthritis (96% v. 86%).6 Testing for anti-CCP2 and rheumatoid factor is not helpful for ruling out disease, because up to 50% of patients with rheumatoid arthritis are antibody-negative.6 It should be performed only if persistent synovitis is present, and antibody status should not be used in isolation to rule in or rule out the disease.7

Takayasu arteritis (TAK) is a large vessel vasculitis that predominately affects young women and can cause severe ischemic complications. Given the rarity of TAK, the management of this condition is challenging. We aim to describe current rheumatologist practices for the management of TAK and identify discrepancies and gaps in knowledge. An online survey (developed by the Canadian Vasculitis Network and approved by the Canadian Rheumatology Association) containing 48 questions with regard to the diagnosis, monitoring and treatment of TAK was distributed to 495 Canadian adult and pediatric rheu-matologists by email. Sixty-six rheumatologists completed the survey (13% response rate): the majority (73%) were from academic centers and ≤25% reported managing more than ten patients in their career. For establishing the diagnosis of TAK, they relied on a combination of signs and symptoms of ischemia, elevations of inflammatory markers and vascular imaging (typically computed tomography and magnetic resonance angiography). The frequency of monitoring for disease activity and the methods employed (clinical, laboratory or imaging) were variable. All physicians used corticosteroids for the treatment of TAK, but 42% would treat for at least 6-12 months, 26% for 12-24 months and 23% would never stop corticosteroids. Fifty-three percent would always use an immunosuppressant (most commonly methotrexate or azathioprine) in addition to corticosteroids and the remainder would only start an immunosuppressant in patients with refractory or relapsing disease. Physician practices for the management of TAK are variable, suggesting that there are knowledge gaps, which may impact outcomes in patients with TAK.