Development of a diagnostic prediction model for giant cell arteritis by sequential application of Southend Giant Cell Arteritis Probability Score and ultrasonography: a prospective multicentre study.

BACKGROUND: Giant 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. METHODS: This 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. FINDINGS: Between 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. INTERPRETATION: A 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. FUNDING: Royal College of Physicians of Ireland, FOREUM.

Disease stratification in GCA and PMR: state of the art and future perspectives.

Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are closely related conditions characterized by systemic inflammation, a predominant IL-6 signature, an excellent response to glucocorticoids, a tendency to a chronic and relapsing course, and older age of the affected population. This Review highlights the emerging view that these diseases should be approached as linked conditions, unified under the term GCA-PMR spectrum disease (GPSD). In addition, GCA and PMR should be seen as non-monolithic conditions, with different risks of developing acute ischaemic complications and chronic vascular and tissue damage, different responses to available therapies and disparate relapse rates. A comprehensive stratification strategy for GPSD, guided by clinical findings, imaging and laboratory data, facilitates appropriate therapy and cost-effective use of health-economic resources. Patients presenting with predominant cranial symptoms and vascular involvement, who usually have a borderline elevation of inflammatory markers, are at an increased risk of sight loss in early disease but have fewer relapses in the long term, whereas the opposite is observed in patients with predominant large-vessel vasculitis. How the involvement of peripheral joint structures affects disease outcomes remains uncertain and understudied. In the future, all cases of new-onset GPSD should undergo early disease stratification, with their management adapted accordingly.

Role of the halo sign in the assessment of giant cell arteritis: a systematic review and meta-analysis.

OBJECTIVES: This systematic review and meta-analysis aimed to evaluate the diagnostic value of the halo sign in the assessment of GCA. METHODS: A systematic literature review was performed using MEDLINE, EMBASE and Cochrane central register databases up to August 2020. Studies informing on the sensitivity and specificity of the US halo sign for GCA (index test) were selected. Studies with a minimum of five participants were included. Study articles using clinical criteria, imaging such as PET-CT and/or temporal artery biopsy (TAB) as the reference standards were selected. Meta-analysis was conducted with a bivariate model. RESULTS: The initial search yielded 4023 studies. Twenty-three studies (patients n = 2711) met the inclusion criteria. Prospective (11 studies) and retrospective (12 studies) studies in academic and non-academic centres were included. Using clinical diagnosis as the standard (18 studies) yielded a pooled sensitivity of 67% (95% CI: 51, 80) and a specificity of 95% (95% CI: 89, 98%). This gave a positive and negative likelihood ratio for the diagnosis of GCA of 14.2 (95% CI: 5.7, 35.5) and 0.375 (95% CI: 0.22, 0.54), respectively. Using TAB as the standard (15 studies) yielded a pooled sensitivity of 63% (95% CI: 50, 75) and a specificity of 90% (95% CI: 81, 95). CONCLUSION: The US halo sign is a sensitive and specific approach for GCA assessment and plays a pivotal role in diagnosis of GCA in routine clinical practice. REGISTRATION: PROSPERO 2020 CRD42020202179.

Ultrasonographic Halo Score in giant cell arteritis: association with intimal hyperplasia and ischaemic sight loss.

OBJECTIVES: We investigated the relationship between the ultrasonographic Halo Score and temporal artery biopsy (TAB) findings in GCA. METHODS: This is a prospective study including 90 patients suspected of having GCA. Ultrasonography of temporal/axillary arteries and a TAB were obtained in all patients at baseline. An experienced pathologist evaluated whether TAB findings were consistent with GCA, and whether transmural inflammation, giant cells and intimal hyperplasia were present. Ultrasonographic Halo Scores were determined. Receiver operating characteristic analysis was performed. RESULTS: Twenty-seven patients had a positive TAB, while 32 patients with a negative TAB received a clinical diagnosis of GCA after 6 months of follow-up. Patients with a positive TAB showed higher Halo Scores than patients with a negative TAB. The presence of intimal hyperplasia in the biopsy, rather than the presence of transmural inflammation or giant cells, was associated with elevated Halo Scores in patients with GCA. The Halo Score discriminated well between TAB-positive patients with and without intimal hyperplasia, as indicated by an area under the curve of 0.82 in the receiver operating characteristic analysis. Patients with a positive TAB and intimal hyperplasia more frequently presented with ocular ischaemia (40%) than the other patients with GCA (13-14%). CONCLUSION: The ultrasonographic Halo Score may help to identify a subset of GCA patients with intimal hyperplasia, a TAB feature associated with ischaemic sight loss.

Efficacy and safety of tocilizumab in giant cell arteritis: a single centre NHS experience using imaging (ultrasound and PET-CT) as a diagnostic and monitoring tool.

Tocilizumab (TCZ), an IL-6 receptor blocker, is approved for relapsing, refractory giant cell arteritis (GCA). We report real-life clinical experience with TCZ in GCA including assessment of responses on imaging (ultrasound (US) and 18F-Fluorodeoxyglucose Positron Emission Tomography-computed Tomography (18FDG-PET-CT)) during the first year of treatment. We included 22 consecutive patients with GCA treated with TCZ where EULAR core data set on disease activity, quality of life (QoL) and treatment-related complications were collected. Pre-TCZ US and 18FDG-PET/CT findings were available for 21 and 4 patients, respectively, where we determined the effect on US halo thickness, temporal and axillary artery Southend Halo Score and Total Vascular Score on 18FDG-PET-CT. The 22 patients with GCA (10 cranial, 10 large vessel, 2 both) had a median disease duration of 58.5 (range, 1-370) weeks prior to initiation of TCZ. Half had used prior conventional synthetic disease-modifying antirheumatic drug (csDMARDs). TCZ was initiated for refractory (50%), ischaemic (36%) or relapsing (14%) disease. Median follow-up was 43 (12-52) weeks. TCZ was discontinued due to serious adverse events (SAEs) in two patients. On treatment with TCZ, 4 discontinued prednisolone, 11 required doses ≤2.5 mg, 2 required daily dose of 2.5-5 mg and 5 needed prednisolones ≥5 mg daily. QoL improved by 50%. Total US halo thickness decreased in 38 arterial segments, median temporal artery Halo Score decreased from 11 to 0, axillary artery Halo Score remained stable. Median Total Vascular Score on FDG-PET/CT reduced from 11.5 to 6.5. In our experience, TCZ showed an excellent response with acceptable safety in GCA, with improvement on US and FDG-PET/CT imaging.

Probability-based algorithm using ultrasound and additional tests for suspected GCA in a fast-track clinic.

OBJECTIVES: Clinical presentations of giant cell arteritis (GCA) are protean, and it is vital to make a secure diagnosis and exclude mimics for urgent referrals with suspected GCA. The main objective was to develop a joined-up, end-to-end, fast-track confirmatory/exclusionary, algorithmic process based on a probability score triage to drive subsequent investigations with ultrasound (US) and any appropriate additional tests as required. METHODS: The algorithm was initiated by stratifying patients to low-risk category (LRC), intermediate-risk category (IRC) and high-risk category (HRC). Retrospective data was extracted from case records. The Southend pretest probability score (PTPS) overall showed a median score of 9 and a 75th percentile score of 12. We, therefore, classified LRC as PTPS <9, IRC 9-12 and HRC >12. GCA diagnosis was made by a combination of clinical, US, and laboratory findings. The algorithm was assessed in all referrals seen in 2018-2019 to test the diagnostic performance of US overall and in individual categories. RESULTS: Of 354 referrals, 89 had GCA with cases categorised as LRC (151), IRC (137) and HRC (66). 250 had US, whereas 104 did not (score <7, and/or high probability of alternative diagnoses). In HRC, US showed sensitivity 94%, specificity 85%, accuracy 92% and GCA prevalence 80%. In LRC, US showed sensitivity undefined (0/0), specificity 98%, accuracy 98% and GCA prevalence 0%. In IRC, US showed sensitivity 100%, specificity 97%, accuracy 98% and GCA prevalence 26%. In the total population, US showed sensitivity 97%, specificity 97% and accuracy 97%. Prevalence of GCA overall was 25%. CONCLUSIONS: The Southend PTPS successfully stratifies fast-track clinic referrals and excludes mimics. The algorithm interprets US in context, clarifies a diagnostic approach and identifies uncertainty, need for re-evaluation and alternative tests. Test performance of US is significantly enhanced with PTPS.

Halo score (temporal artery, its branches and axillary artery) as a diagnostic, prognostic and disease monitoring tool for Giant Cell Arteritis (GCA).

BACKGROUND: Giant cell arteritis (GCA) is a common large vessel vasculitis of the elderly, often associated with sight loss. Glucocorticoids (GC remain the mainstay of treatment, although biologic treatments have been approved. Biomarkers predicting disease severity, relapse rates and damage are lacking in GCA.EULAR recommends ultrasound (US) as the first investigation for suspected GCA. The cardinal US finding, a non-compressible halo, is currently categorised as either negative or positive. However, the extent and severity of this finding may vary.In this study, we hypothesise whether the extent and severity of the halo sign [calculated as a single composite Halo score (HS)] of temporal and axillary arteries may be of diagnostic, prognostic and monitoring importance; whether baseline HS is linked to disease outcomes, relapses and damage; whether HS can stratify GCA patients for individual treatment needs; whether HS can function as an objective monitoring tool during follow up. METHODS: This is a prospective, observational study. Suspected GCA Participants will be selected from the GCA FTC at the participating centres in the UK. Informed consent will be obtained, and patients managed as part of standard care. Patients with GCA will have HS (temporal and axillary arteries) measured at baseline and months 1,3,6 and 12 long with routine clinical assessments, blood sampling and patient-reported outcomes (EQ5D). Non-GCA patients will be discharged back to the referral team and will have a telephone interview in 6 months.We aim to recruit 272 suspected GCA referrals which should yield 68 patients (25% of referrals) with confirmed GCA. The recruitment will be completed in 1 year with an estimated total study period of 24 months. DISCUSSION: The identification of prognostic factors in GCA is both timely and needed. A prognostic marker, such as the HS, could help to stratify GCA patients for an appropriate treatment regimen. Tocilizumab, an IL-6R blocking agent, switches off the acute phase response (C-Reactive Protein), making it difficult to measure the disease activity. Therefore, an independent HS, and changes in that score during treatment and follow-up, maybe a more objective measure of response compare to patient-reported symptoms and clinical assessment alone.