Indian Takayasu Clinical Activity Score Research Articles

Somatostatin receptor PET/MR imaging of large vessel inflammation in active compared with inactive vasculitis and atherosclerosis

Abstract Background Use of 18F-FDG PET in large vessel vasculitis (LVV) is limited by non-specific uptake due to arterial remodelling and/or atherosclerosis leading to diagnostic uncertainty. Purpose To investigate somatostatin receptor 2 (SST2) as a novel inflammation-specific PET imaging target in LVV. Methods In a prospective observational cohort study, we tested the ability of PET/MRI using two somatostatin receptor tracers (68Ga-DOTATATE and 18F-FET-βAG-TOCA) to differentiate active from inactive LVV, and aortic atherosclerosis in patients with recent myocardial infarction. Ex vivo mapping of the imaging target was performed using immunofluorescence microscopy, imaging mass cytometry, and bulk, single-cell and single-nuclei RNA sequencing of temporal artery biopsies from LVV patients. Results Sixty-one participants were included (LVV, n=27; myocardial infarction ≤2 weeks, n=25; control subjects with an oncological indication for imaging, n=9). LVV patients (mean age 58 [SD 16] years; 78% female; 63% active or grumbling disease) had giant cell arteritis (n=13), Takayasu arteritis (n=13), or unspecified LVV (n=1). Baseline index vessel SST2 PET maximum tissue-to-blood ratio (TBRmax) was 61.8% (95% CI 31.5–99.0%, p<0.0001) higher in patients with active/grumbling LVV than inactive LVV, and 34.6% (95% CI 15.1–57.6%, p=0.0002) higher than recent myocardial infarction (Fig. 1a–c; arrow: PET signal; arrowhead: aortic thickening; asterisk: aortic atherosclerosis), with good diagnostic accuracy (AUC ≥0.86, p<0.001 for both). None of the control subjects without LVV or MI had increased arterial SST2 PET signal (Fig. 1d). Mean aortic TBRmax was strongly correlated with Indian Takayasu Clinical Activity Score (r=0.82 [95% CI 0.46–0.95], p=0.001) and maximum wall thickness on MRI (r=0.68 [95% CI 0.31–0.87], p=0.002). SST2 PET/MRI was generally consistent with 18F-FDG PET/CT in LVV patients with contemporaneous scans (Fig. 1a, b), but with very low background signal in the brain and heart allowing for unimpeded assessment of nearby coronary, myocardial, and intracranial artery involvement. On follow-up imaging after a mean 9.3 (SD 3.2) months, clinically effective treatment for LVV was associated with a 0.49 ±SEM 0.24 (p=0.04; 22.3%) reduction in SST2 PET TBRmax, with good scan-scan repeatability in inactive LVV patients with no change in treatment (ICC 0.86, 95% CI 0.04–0.99). SST2 localised to macrophages, pericytes, and perivascular adipocytes in inflamed arterial specimens (Fig. 2; a: H&E; b: imaging mass cytometry; arrow: SST2/CD68 co-staining). SSTR2-expressing macrophages co-expressed pro-inflammatory markers (S100A8, S100A9). Specific SST2 radioligand binding was confirmed by autoradiography in LVV specimens. Conclusion This is the first study to examine SST2 PET/MRI in LVV and to provide histological and gene expression data for validation. Here we show this novel approach holds major promise for diagnosis and therapeutic monitoring in LVV. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Wellcome Trust; Imperial NIHR Biomedical Research Centre

Characteristics of B cells and immunoglobulin profile in Takayasu's arteritis.

Disorders of humoral immunity in Takayasu's arteritis (TAK) have not been well explored. This study describes the characteristics of B cells and immunoglobulin (Ig) profile in patients with TAK. Peripheral B cell populations assessed using flow cytometry and serum Ig levels assessed using a biochemical analyser in 98 newly diagnosed patients with TAK were analysed and compared with those of 31 patients with systemic lupus erythematosus (SLE) and 60 healthy controls (HCs). CD19+ B cell and IgG infiltration to the aortic tissue was evaluated by immunohistochemical staining. The proportion of peripheral CD3-CD19+ B cells and levels of serum IgG in TAK were lower than those in SLE, but higher than those in HCs. CD3-CD19+ B cell counts were higher in TAK than in HCs. Serum IgG and IgG1 levels were higher in active TAK than in non-active TAK. In TAK, positive correlations of serum IgG levels with erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, Kerr score, and Indian Takayasu Clinical Activity Score (ITAS2010, ITAS-A) were observed before immunotherapy. After 6 months of immunotherapy, serum Ig levels significantly decreased. Positive correlations between the changes in IgG levels and values of ESR, CRP, Kerr score, and ITAS-A were detected. Immunohistochemical staining confirmed CD19+ B cell and IgG infiltration to the aortic wall in patients with TAK. Enhanced B cells might contribute to the pathogenesis of TAK, and serum IgG levels could serve as a simple, useful biomarker to assess disease activity and monitor treatment response in TAK.

Derivation and Validation of a New Disease Activity Assessment Tool With Higher Accuracy for Takayasu Arteritis.

ObjectiveTo develop a new disease activity assessment tool with high accuracy for Takayasu arteritis.MethodsIndividual items from National Institute of Health (NIH) criteria and the Indian Takayasu Clinical Activity Score (ITAS2010) were tested as candidate variables to develop a new disease activity assessment tool in a derivation cohort (N = 100). Physician global assessment on disease activity was used as the gold standard. Multivariable logistic regression models were constructed and the model with the highest accuracy was identified. A formula assessing disease activity was generated using simplified β coefficients (rounded to decimal place). Diagnostic performance was evaluated through estimating the area under the curve (AUC). The new assessment tool was subsequently validated in a validation cohort (N = 46).ResultsThe multivariable model yielding the highest accuracy consisted of a high erythrocyte sedimentation rate (ESR), NIH criteria 1 and 4, and carotidynia. Using simplified β coefficients, the following disease activity assessment tool was developed: high ESR (3 points), NIH criterion 1 (2 points), NIH criterion 4 (4 points), and carotidynia (3 points) (total score ≥5, active; total score <5, inactive). The new disease activity assessment tool had a higher AUC (89.37) for discriminating active and inactive diseases than NIH criteria (AUC 77.96), ITAS2010 (AUC 66.12), ITAS-ESR (AUC 75.58), and ITAS-C-reactive protein (AUC 71.34). The AUC (85.23) of the new assessment tool was similar in the validation cohort.ConclusionA new disease activity assessment tool that consists of high ESR, NIH criteria 1 and 4, and carotidynia had higher accuracy in discriminating active and inactive disease than currently used clinical assessment tools.

P295 Establishing adenosine deaminase 2 activity in a cohort of patients with large vessel vasculitis

Abstract Background/Aims Deficiency of adenosine deaminase 2 (DADA2) leads to a broad phenotype; some patients develope vasculitis and strokes, and others have predominantly haematological manifestations. Small, medium and large vessel vasculitis has been described. In contrast, plasma ADA2 activity is elevated in inflammatory conditions including systemic lupus erythematosus and systemic juvenile idiopathic arthritis with macrophage activation syndrome. The role of ADA2 and how its deficiency associates with the vasculitides is not well understood. Using a well-characterised large vessel vasculitis cohort, we sought to establish the potential role of ADA2 activity. Methods ADA2 activity was measured in adults with Takayasu arteritis (TA), large vessel giant cell arteritis (LV-GCA), intracranial vasculitis (IV) and healthy control (HC) subjects using a coupled spectrophotometric assay. Plasma from 11 patients with genotyped DADA2 and 10 patients heterozygous for pathogenic variants in ADA2 were used to define thresholds for deficiency and carrier status respectively (DADA2 activity 0 - 0.90 U/L, ADA2 carrier activity 2.02 - 10.62 U/L). Activity levels above the upper limit of normal (ULN) were defined as &amp;gt; 99th percentile of the HC activity (30.3U/L). To assess potential associations with TA disease status, ADA2 was measured prospectively in matched active and remission samples. TA disease activity was determined as active, grumbling or stable using clinical and radiological features, physician impression, CRP, ESR and Indian Takayasu clinical Activity Score (ITAS). Results No patients had deficient ADA2 activity while 7 subjects had activity within the carrier range (1 HC [1.9%], 5 TA [3.7%], 1 LV-GCA [2.3%]). Compared to HC levels (17.43 [14.11 - 20.78] U/L), activity in the TA group was significantly increased (TA 19.68U/L, p = 0.0061), while LV-GCA and IV were not significantly different. In 20 cases, activity exceeded the ULN; 16 TA (11.9%, p = 0.044; 4 active, 2 grumbling, 10 stable) and 4 LV-GCA (9.1%, ns). In TA, there was a positive correlation between ADA2 activity and ESR (Spearman R = 0.2863, p = 0.0009) but not with CRP or ITAS score. Subgroup analysis revealed ADA2 activity was most prominently elevated in the stable group relative to HCs (TA stable 20.54 U/L [8.08 - 48.66], median +17.8%, p = 0.0006), but not with active or grumbling disease. Consistent with this, prospective analysis demonstrated a significant increase in ADA2 activity in remission vs active disease (p = 0.024), with activity increasing in 18 (62%) patients achieving remission. Conclusion There were no cases of ADA2 deficiency in this cohort. Consistent with other inflammatory conditions, ADA2 activity was elevated in TA compared to HC subjects. Surprisingly, increased ADA2 activity was linked to stable TA in both cross-sectional and prospective analyses. This may suggest a potential role of ADA2 enzyme activity in vascular repair and regrowth - possibly tying in with known elevated levels of ADA2 activity in growing children. Disclosure A. Porter: None. R. Maughan: None. C. Pericleous: None. A. Kiprianos: None. H. Jee: None. P. Lee: None. T. Youngstein: None. J. Mason: None.

Serum levels of fetuin-A as a novel biomarker for disease activity in patients with Takayasu arteritis and granulomatous polyangiitis.

The aim of the present study was to investigate serum fetuin-A (Fet-A) levels in patients with Takayasu arteritis (TA) and granulomatous polyangiitis (GPA) and to analyze the relationship between serum Fet-A levels and disease activity scores. Thirty-two TA and 28 GPA patients presented to the rheumatology clinic at Gazi University and met the criteria of American College of Rheumatology 1990 and 2012 International Chapell Hill meeting, respectively, and 20 healthy control subjects were included in the present study. We collected data on serum C-reactive protein (CRP), albumin, calcium, and phosphate levels as well as erythrocyte sedimentation rates. Calcification risk index (CRI) was calculated for each patient. The Birmingham Vasculitis Activity Score (BVAS) and Indian Takayasu Clinical Activity Score (ITAS), were used to assess disease activity in GPA and TA patients respectively. Serum Fet-A levels were significantly lower in the overall vasculitis group compared to control group (p = 0.015). In subgroup analysis, Fet-A levels were significantly lower in those with active disease, compared to control group (p = 0.001, for active TA (n = 18) and GPA (n = 17), respectively). However, there was no significant difference in serum Fet-A levels in inactive cases versus control subjects (p = 0.061, for inactive TA (n = 14) and GPA (n = 11), respectively). Serum Fet-A levels negatively correlated with BVAS (r = - 0.675) and ITAS scores (r = - 0.385), as well as with CRP and CRI. Our results suggest that serum Fet-A level could be a novel biomarker for assessment of activity status in patients with GPA or TA. Key Points • Serum Fetuin-A is negative acute phase protein and systemic calcification inhibitor synthesized in hepatocytes and secreted by various inflammation. • Serum Fetuin-A was negatively correlated with CRP, BVAS, and ITAS scores and significantly decreased in vasculitis patients with high disease activity. • Serum Fetuin-A could be a promising and useful biomarker for the assessment of disease activity for vasculitis, also that it might also be a predictor of long-term cardiovascular progression.

Tocilizumab for faster and safer remission of Takayasu's arteritis.

Takayasu's arteritis (TAK) is a large-vessel vasculitis. Glucocorticoids (GCs) combined with cyclophosphamide (CTX) is a common treatment option, but their efficacy is limited. The aim of this retrospective study was to study the efficacy and safety of tocilizumab (TCZ) in the treatment of TAK. A total of 63 patients with TAK were divided into two groups according to different treatment strategies: 31 patients in the TCZ group and 32 patients in the CTX group. After 6 months of treatment, disease activity and side effects were evaluated and were compared between the two groups. After 3 months of treatment, the National Institutes of Health (NIH) score (p = 0.005), Indian Takayasu Clinical Activity Score (ITAS) 2010 (p = 0.043), and the Indian Takayasu Activity Score with the Acute-Phase Response (ITAS.A; p = 0.036) were lower in patients treated with TCZ compared with those treated with CTX. In the TCZ group, the proportion of patients with NIH scores ⩽1 reached 50% after 1 month, 90% after 3 months, and 96% after 6 months of treatment, whereas in the CTX group, these proportion were 36%, 30%, and 78%, respectively. Thus, TCZ treatment of TAK is accompanied with a faster remission rate than CTX treatment. Moreover, the total cumulative incidence of adverse events was lower in the TCZ group than in the CTX group (p = 0.035). TCZ was faster and safer in alleviating TAK.

Pericoronary and periaortic adipose tissue density are associated with inflammatory disease activity in Takayasu arteritis and atherosclerosis.

AimsTo examine pericoronary adipose tissue (PCAT) and periaortic adipose tissue (PAAT) density on coronary computed tomography angiography for assessing arterial inflammation in Takayasu arteritis (TAK) and atherosclerosis.Methods and resultsPCAT and PAAT density was measured in coronary (n = 1016) and aortic (n = 108) segments from 108 subjects [TAK + coronary artery disease (CAD), n = 36; TAK, n = 18; atherosclerotic CAD, n = 32; matched controls, n = 22]. Median PCAT and PAAT densities varied between groups (mPCAT: P < 0.0001; PAAT: P = 0.0002). PCAT density was 7.01 ± standard error of the mean (SEM) 1.78 Hounsfield Unit (HU) higher in coronary segments from TAK + CAD patients than stable CAD patients (P = 0.0002), and 8.20 ± SEM 2.04 HU higher in TAK patients without CAD than controls (P = 0.0001). mPCAT density was correlated with Indian Takayasu Clinical Activity Score (r = 0.43, P = 0.001) and C-reactive protein (r = 0.41, P < 0.0001) and was higher in active vs. inactive TAK (P = 0.002). mPCAT density above −74 HU had 100% sensitivity and 95% specificity for differentiating active TAK from controls [area under the curve = 0.99 (95% confidence interval 0.97–1)]. The association of PCAT density and coronary arterial inflammation measured by 68Ga-DOTATATE positron emission tomography (PET) equated to an increase of 2.44 ± SEM 0.77 HU in PCAT density for each unit increase in 68Ga-DOTATATE maximum tissue-to-blood ratio (P = 0.002). These findings remained in multivariable sensitivity analyses adjusted for potential confounders.ConclusionsPCAT and PAAT density are higher in TAK than atherosclerotic CAD or controls and are associated with clinical, biochemical, and PET markers of inflammation. Owing to excellent diagnostic accuracy, PCAT density could be useful as a clinical adjunct for assessing disease activity in TAK.

Risk factors of avascular necrosis in Takayasu arteritis: a cross sectional study.

Takayasu arteritis (TA) is a large-cell vasculitis, and is not usually associated with avascular necrosis (AVN). The objective of the study was to investigate any association between TA and AVN, including the possible pathogenic effect of glucocorticoid (GCs) use. The study design was retrospective and cross sectional. TA patients were enrolled in the study. Demographic variables, disease activity, treatments, physician global assessment, Indian Takayasu Clinical activity score 2010, and Kerr criteria were recorded. Logistic regression analysis was performed to identify predictors of AVN. A total of 29 patients were assessed. AVN was observed in four (13.8%) patients with TA. Male gender and elevated C-reactive protein (CRP) were found to be significantly associated with AVN (p = 0.001 and p = 0.006, respectively). While type IIb TA was more common in patients with AVN (n = 2, 50%), type V was more likely in the absence of AVN (n = 13, 52%). Descending aorta and thoracic aorta were usually involved in patients with AVN (both, n = 3, 75%). In multivariate logistic regression, increased CRP levels were the only predictor for AVN (OR = 1.183, 95% Cl = 1.025-1.364, p = 0.021). No association was identified between AVN in TA patients and either duration or cumulative dose of GCs. The present study found that higher CRP levels and male gender were associated with AVN in patients with TA.

AB0373 PSYCHOMETRIC PROPERTIES OF OUTCOME MEASUREMENT INSTRUMENTS FOR LARGE VESSEL VASCULITIS: A SYSTEMATIC LITERATURE REVIEW

Background:Giant cell arteritis (GCA) and Takayasu arteritis (TAK) are two forms of chronic progressive large-vessel vasculitis (LVV) of unknown etiology. In 2016, the OMERACT Vasculitis Working Group proposed the development of a Core Domain Set of outcome measures for LVV including organ and arterial function, fatigue, pain, biomarkers, and death (1). Understanding the psychometric properties of outcome measurement instruments is essential when selecting among instruments to use in research; a summary of such properties for measures of LVV has not been developed.Objectives:To systematically review and summarize the psychometric properties of outcome measurement instruments used to measure the domains of the OMERACT core domain set for LVV.Methods:A comprehensive search of several databases (Medline, EMBASE, Cochrane, among others) from inception to July 14, 2020 was conducted. Articles were included if they covered psychometric properties of instruments used in LVV. Following the COSMIN and OMERACT frameworks, different psychometric properties (validity, inter- and intra-observer reliability, sensitivity to change, and feasibility) of outcome measurement instruments used in LVV (GCA and TAK) were assessed. Risk of bias was assessed according to the COSMIN checklist.Results:Among the 3534 articles identified, 15 studies focusing on the development or validation of psychometric properties on LVV met the predefined criteria. Two were development studies and 13 were validation studies. These studies provided information on 13 instruments: 5 instruments specific to TAK, 2 specific to systemic vasculitides, and 6 general, non-disease-specific instruments. No instruments specific to GCA were identified.Of the main psychometric properties assessed in the included studies, 40% had a low, 47% had moderate, and 13% had high risk of bias. Construct validity was the property most frequently assessed (in 93% of the tools) (Figure 1).In TAK, the Indian Takayasu Clinical Activity Score 2010 (ITAS2010) showed good consistency (r=0.97), reliability (intra-observer, ICC=0.60; inter-observer, ICC=0.92) and validity (correlation with Physician Global Assessment (PGA) (r=0.73)) for disease activity. Regarding disease damage, the Disease Extent Index-Takayasu (DEI-Tak) showed good validity (correlation with NIH score 94%, k=0.85). Non-specific vasculitis instruments such as the Vasculitis Damage Index (VDI) and the Birmingham Vasculitis Activity Score (BVAS) showed moderate validity in the assessment of disease damage in GCA (cumulative glucocorticoid dose and disease duration, r=0.30 and r=0.29) and TAK (cumulative glucocorticoid dose and disease duration, r=0.29 and r=0.25) in the former and disease activity in GCA in the later (PGA, r=0.50).Six non-vasculitis-specific patient-reported outcomes (PROs) instruments were identified, all showing low to moderate validity in GCA/TAK.Conclusion:The psychometric properties of 13 outcome measures to study LVV covering the OMERACT domains of disease activity, damage, and patient-reported outcomes were assessed. ITAS2010, DEI-Tak, VDI, and BVAS were the instruments with better psychometric properties for disease activity and/or damage. Disease activity and/or damage instruments specific for GCA, and validated PROs for both GCA and TAK are needed.

Risk factors for cerebral infarction in Takayasu arteritis: a single-centre case-control study.

We aimed to investigate the clinical features of Takayasu arteritis with cerebral infarction, and the risk factors for cerebral infarction. The study analysed 122 consecutive patients with Takayasu arteritis retrospectively. The clinical characteristics of Takayasu arteritis patients with and without cerebral infarction were compared. Binary logistic regression analysis was performed to determine risk factors for cerebral infarction in Takayasu arteritis patients. Cerebral infarction was present in 42 (34.4%) of 122 patients with Takayasu arteritis. There were 33 patients with ischaemic stroke and 11 with asymptomatic lacunar infarction, including two patients with both types of infarction. The cerebral infarction group had a significantly higher proportion of males, higher prevalence of blurred vision, and higher Indian Takayasu Clinical Activity Score (ITAS) 2010 than the non-cerebral infarction group. Binary logistic regression analysis indicated that hyperlipidaemia [odds ratio (OR) 5.549, P=0.021], ITAS 2010 (OR 1.123, P= 0.023), number of involved arteries (OR 1.307, P=0.018), and middle cerebral artery (MCA) involvement (OR 4.013, P=0.029) were significantly associated with cerebral infarction in patients with Takayasu arteritis. Receiver operating characteristic curves indicated fair performance of the ITAS 2010 (>6) and number of involved arteries (> 7) for distinguishing Takayasu arteritis patients at risk of cerebral infarction from those without such risk. Hyperlipidaemia, higher ITAS 2010, larger number of involved arteries, and MCA involvement are independent risk factors for cerebral infarction in Takayasu arteritis patients.

Is there an association between upper limb claudication and handgrip strength in Takayasu arteritis?

Limb vascular claudication and hand muscle weakness are common symptoms of Takayasu arteritis (TAK). However, no studies have correlated these two symptoms. Therefore, the aim of the study was to evaluate handgrip strength and its correlation with both upper-limb vascular claudication and imaging of the vessels. This cross-sectional study compared 36 patients with TAK who were matched by age, gender, and body mass index with 36 individuals without TAK (CTR). Hand strength (assessed with handgrip dynamometer), functional capacity (Health Assessment Questionnaire, HAQ), upper-limb vascular claudication symptoms (patients' selfreported form), and disease activity (Indian Takayasu Clinical Activity Score [ITAS] 2010; Physician Global Assessment [PGA], C-reactive protein, and erythrocyte sedimentation rate) were evaluated as well as vessel imaging (e.g., angiotomography or angioresonance) and blood pressure. The median age of the patients was 42.0 years (35.5-51.5 years), whereas the mean disease duration was 13.1±6.8 years. No patient had active disease. Compared to the CTR, the patients with TAK showed reduced strength in the left-hand (22.9±5.9 vs 26.3±5.6 kg; p=0.014) and increased HAQ scores [0.50 (0.12-0.87) vs 0.00 (0.00-0.00); p<0.001]. Both groups had comparable blood pressure. Among patients with TAK, lefthand strength was inversely correlated with HAQ (Spearman correlation: rho=-0.584; p<0.001) and positively correlated with right-hand strength (rho=0.644; p<0.001). Moreover, neither hand's strengths in the patients were correlated with subclavian stenosis imaging, blood pressure or limb vascular claudication. The reduction of strength in the upper left limb is inversely related to the functional capacity (HAQ score) of TAK. This reduction appears unrelated to classical vascular claudication, vessel imaging or blood pressure.

Childhood-onset versus adult-onset Takayasu arteritis: A study of 141 patients from Turkey

AimTo compare childhood-onset (c-TAK) versus adult-onset Takayasu arteritis (a-TAK) patients for vascular involvement, disease activity, damage, and treatment. MethodsPatient charts from two tertiary-care centers of a pediatric and adult rheumatology clinic were reviewed. Adult patients diagnosed before the age of 18 years were included in the childhood-onset group. The activity was assessed with the physician's global assessment (PGA) and Indian Takayasu Clinical Activity Score (ITAS). The damage was evaluated with Takayasu Arteritis Damage Score (TADS) and Vasculitis Damage Index (VDI). ResultsTwenty-four c-TAK (follow-up duration: 53 months) and 117 a-TAK patients (follow-up duration: 68 months) were analyzed. Aorta involvement was more prevalent (79% vs. 33%), and the median PGA score was higher in the c-TAK group (9 vs. 7), whereas the mean Indian Takayasu Arteritis Score was similar (14 vs. 13) among both groups. Median VDI score was lower for c-TAK patients (4 vs. 5), whereas TADS was similar for children and adults (8 vs. 8). Higher incidence of glucocorticoid related side-effects, a longer time to diagnosis and upper extremity claudication seemed to account for higher VDI scores in adults. ConclusionAorta involvement was more common among children with TAK, whereas upper extremities were relatively spared. Biologic agents were used more commonly among children which may be explained by higher rates of aortic involvement. However, c-TAK patients did not have greater cumulative damage.

Takayasu's Arteritis from the Patients' Perspectives: Measuring the Pulse to the Patient-Reported Outcomes

Patients with Takayasu's arteritis (TA) experience important changes in lifestyle, quality of life, and functional status due to ischemic symptoms or treatment toxicity. To describe the clinical characteristics and the patient-reported outcomes (PROs), such as quality of life, disability, fatigue, and perception/impact of the disease in Mexican patients with TA. Cross-sectional study including patients with established diagnosis of TA recruited at a tertiary care center. Demographics, comorbidities, clinical characteristics, laboratory, imaging, and treatment were retrieved. Disease activity (the Indian Takayasu Clinical Activity Score (ITAS) 2010), damage (Vasculitis Damage Index (VDI)), quality of life (Short Form 36 (SF-36)), disability (Health Assessment Questionnaire Disability Index (HAQ-DI)), fatigue (Multidimensional Fatigue Inventory-20), and patient's disease perceptions were assessed. Fifteen women were included, with a median age of 41years (interquartile range (IQR) 30-45) and disease duration of 108months (IQR 55-197). Median ITAS 2010 and VDI scores were 0 (IQR 0-2) and 3 points (IQR 2-6), respectively. Mean SF-36 score was 71.38±13.39, with mean physical and mental component summaries of 66.52±13.37 and 76.24±14.89, respectively. HAQ-DI mean score was 0.48±0.62, being grip the most affected domain. Among fatigue subscales, the higher scores were present in the physical fatigue (16.3±5.8). Correlations between the HAQ-DI and the VDI score (r=0.64, P=0.03); between the general fatigue, score, and disease duration (r=-0.71, P=0.01); and between the SF-36 total score and the HAQ-DI (r=-0.87, P=0.0004) were found. It is important to identify disease-specific outcomes of interest to the patients to develop tools that assess them with a holistic approach.

Pericoronary adipose tissue density is associated with clinical disease activity in Takayasu arteritis and coronary arterial inflammation measured by 68Ga-DOTATATE PET in atherosclerosis

Abstract Background Coronary artery disease (CAD) is an under-recognized complication of intense arterial inflammation in Takayasu arteritis (TAK). While pericoronary adipose tissue (PCAT) density is associated with arterial inflammation in CAD patients, this relationship has not previously been studied in TAK patients, nor directly compared with coronary arterial inflammation measured by 68Ga-DOTATATE positron emission tomography (PET). Purpose To compare PCAT density with clinical, biochemical and molecular imaging markers of inflammation in TAK and CAD patients. Methods PCAT density was quantified from computed tomography coronary angiography (CTCA) around each of the 17 coronary segments in patients with: (1) TAK and CAD, (2) atherosclerotic CAD, and (3) age and gender-matched healthy controls, using semi-automated software (Autoplaque). In TAK patients, PCAT density was compared to the Indian Takayasu Clinical Activity Score (ITAS) and high-sensitivity C-reactive protein (CRP). In CAD patients, PCAT density was compared to local arterial inflammation measured by coronary motion-frozen 68Ga-DOTATATE PET using image registration software (FusionQuant), and systemic (aortic) inflammation using 18F-fluorodeoxyglucose (FDG) PET. Data was acquired either during routine clinical care or prior research that established 68Ga-DOTATATE as an experimental marker of arterial inflammation that binds macrophage somatostatin receptor-2 in atherosclerotic plaques (NCT02021188). Results 60 patients were included (TAK, n=20; CAD, n=20; healthy, n=20). Non-calcified plaque burden (TAK: 95.2%; CAD: 90.4%, p&amp;lt;0.0001) and CRP (TAK: 25.2 ±SD 16.1 mg/L; CAD: 2.5 ±SD 1.7 mg/L, p=0.04) were greater in TAK than CAD patients. PCAT density varied significantly among the three groups (median [IQR] TAK: −72.9 [−81.2 to -66.1] Hounsfield unit [HU]; CAD: −79.9 [−88.0 to −72.2]; healthy: −83.8 [−90.1 to −75.8] HU, p&amp;lt;0.0001). Figure: box-plot showing the distribution of PCAT values by group, with corresponding representative multiplanar reconstructed and cross-sectional CTCA images with surrounding PCAT density displayed by color table in left anterior descending arteries. PCAT density was significantly associated with ITAS (r=0.61, p=0.004) and CRP (r=0.43, p=0.03) in TAK patients, and coronary 68Ga-DOTATATE maximum tissue-to-blood ratio (r=0.31, p&amp;lt;0.001) in CAD patients. PCAT density was not associated with aortic 18F-FDG uptake in CAD patients, nor subcutaneous (pre-sternal) adipose tissue density in either disease group. No significant patient-level confounders were identified using linear mixed-effects regression modelling. Conclusion PCAT density measured by CTCA is greater in TAK than CAD patients, and is associated with clinical and biochemical markers of disease activity in TAK, and coronary arterial inflammation measured by 68Ga-DOTATATE PET in CAD. PCAT could be a useful, easy to measure marker of coronary inflammation and disease activity in both TAK and CAD. PCAT density is greater in TAK than CAD Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Wellcome Trust

Assessment of inflammatory activity in Takayasu's arteritis: performance of clinical scores and common biomarkers versus 18F-FDG PET/CT.

There is no consensus on how to evaluate inflammatory activity in Takayasu's arteritis (TAK). Here we compare biochemical tests and three clinical scores, which evaluate inflammatory activity (IA) in TAK, versus quantitative 18F-FDG PET/CT as the gold standard. This prospective study included patients with TA diagnosed according to the American College of Rheumatology (ACR) criteria. IA was assessed through laboratory tests, clinical scores of the National Institute of Health (NIH), Dabague-Reyes (DR) and the Indian Takayasu Clinical Activity Score 2010 (ITAS2010), and the result of these assessments was compared against 18F-FDG PET/CT Standardised Uptake Values (SUVmax). A total of 35 patients were studied, 86% were women. SUVmax had positive correlations with acute phase reactants and DR and NIH. Agreement of 18F-FDG PET/CT was significant with erythrocyte sedimentation rate (ESR) and DR score. Receiver Operating Characteristic (ROC) curve analysis showed diagnostic value for inflammatory activity in ESR, DR and NIH scores, which had higher specificity when they were estimated with new cut-off points for the Mexican population. ESR and other phase reactants have good sensitivity but low specificity to evaluate IA in TAK when compared against 18F-FDG PET/CT. Among all the clinical scores, DR had the best diagnostic value, with strong potential as a clinical tool to define the inflammatory status in TAK patients when the study image is not available. However, in complex TAK cases with doubtful diagnosis after assessment by clinical scores or laboratory, 18F-FDG PET/CT remains mandatory.

THU0308 COMPARISON OF CHILDHOOD-ONSET VERSUS ADULT-ONSET TAKAYASU ARTERITIS: A STUDY OF 141 PATIENTS FROM TURKEY

Background:Childhood-onset Takayasu Arteritis (c-TAK) may differ from adult-onset Takayasu Arteritis (a-TAK) in clinical maaifestations and treatment.Objectives:To compare c-TAK with a-TAK patients for vascular involvement, disease activity, damage, and treatment.Methods:Patient charts from two tertiary-care centers of a pediatric and adult clinic were reviewed. Adult patients diagnosed before the age of 18 were included in the c-TAK group. The activity was assessed with the physician’s global assessment (PGA) and Indian Takayasu Clinical Activity Score (ITAS). The damage was evaluated with Takayasu Arteritis Damage Score (TADS) and Vasculitis Damage Index (VDI).Results:Twenty four c-TAK and 121 a-TAK patients were compared. 21 (88%) of the c-TAK group and 104 (89%) of the a-TAK group were female. Age at symptom onset was 14 (IQR: 9-15) for c-TAK and 30 (IQR: 24-43) for a-TAK patients. Diagnostic delay in months was shorter for c-TAK patients [c-TAK: 3 (1-10) vs. a-TAK: 12 (5-58)]. Follow-up duration was similar [53 months (IQR: 16-131) vs. 68 (IQR: 30-102), p=0.763].ITAS was comparable for c-TAK and a-TAK patients on the first visit [14 (SD: 7) vs. 13 (SD: 5), p=0.362, respectively]. However, the PGA score was higher in the c-TAK group compared to the a-TAK group [9 (IQR 7-10) vs. 7 (IQR 6-8), p&lt;0.001].14 (64%) of c-TAK patients and 10 (9%) of a-TAK patients received pulse glucocorticoids, p= 0.002. Cumulative glucocorticoid dose was 10 grams (IQR: 6-13) for c-TAK patients and 7 grams (IQR: 4-12) for a-TAK patients (p=0.128).After diagnosis, children had more vascular interventions than the adults did [9 (38%) vs. 20 (18%), p=0.031, respectively].Rates of achieving at least one remission were lower for c-TAK patients [c-TAK: 12 (50 %) vs. a-TAK: 94 (82%), p=0.001]. c-TAK patients had a PGA score of 6 (IQR 3-8), the PGA score in a-TAK patients was 1 (IQR 1-3), p&lt;0.001. Still, ITAS was similar for both groups [c-TAK: 1 (IQR 0-3) vs. a-TAK: 0 (IQR 0-2), p= 0.579]. 9 (38%) of c-TAK patients had at least one relapse, and the 43 (38%) of a-TAK patients had at least one relapse (p=0.960).TADS was similar [c-TAK: 8 (IQR 4-12), a-TAK: 8 (IQR 6-10), p=0.919]. However, VDI of the a-TAK patients was higher than the c-TAK patients [c-TAK: 4 (IQR 2-5), a-TAK: 5 (IQR 3-7), p=0.017]. Glucocorticoid related damage was higher in a-TAK patients (Diabetes: 8% vs. 4%, avascular necrosis: 6% vs. 0, and cataracts: 11% vs. 0)Conclusion:Aorta involvement, biologic agent use, and vascular interventions were more common in c-TAK patients. However, cumulative damage was not increased for c-TAK patients which may be partly explained by more common corticosteroid related side-effects in adults.Table 1.Baseline symptoms, physical examination findings*c-TAK (n= 24)a-TAK (n= 117)pSYMPTOMSStroke1 (4)8 (7)1Carotidynia019 (16)0.044Upper Extremity Claudication5 (21)72 (62)&lt;0.001Hypertension13 (54)22 (19)&lt;0.001Pulse loss (Radial)8/23 (35)62 (58)0.043BRUITSubclavian8 (35)62 (57)0.054Renal9 (39)15 (14)0.014Abdominal Aorta11 (48)9 (8)&lt;0.001*Values denote the number (%) of patientsFigure 1.Comparison of involved arteries* * Numbers in bars represent percentage of patients in each groupFigure 2.Angiographic classification types according to Hata* * Numbers in bars represent percentage of patients in each group. Type 2a and Type 2b are combined. a-TAK group had no patient with Type 3 diseaseTable 2.Medical treatment*First TreatmentTreated Everc-TAK (n=22)a-TAK (n=115)pc-TAK(n=24)a-TAK (n=114)pMethotrexate5 (23)69 (60)0.00112 (50)76 (67)0.123Azathioprine8 (36)38 (33)0.76321 (88)79 (69)0.070Leflunomide01 (1)13 (13)35 (31)0.070Cyclophosphamide†6 (27)6 (5)0.00412 (50)10 (9)&lt;0.001Biologics10 (42)16 (14)0.004Anti-TNF---4 (17)18 (16)-Tocilizumab---7 (29)4 (4)-*Values denote the number (%) of patients.Disclosure of Interests:None declared

Ayurvedic management for a rare disorder Takayasu arteritis - A case report.

Takayasu arteritis (TA) is a rare disorder and it is a devastating condition of aorta. The presently available treatments for the condition in the modern medicine have limited benefits. This is case of TA which was better managed with Ayurvedic intervention. An Ayurvedic diagnosis for this case was Siragata Vata (vitiated Vata Dosha affecting the blood vessels). A 42-year-old woman was diagnosed with TA and treated on the line of management of Siragata Vata with Shastikashali Pinda Swedana (sudation with bolus of medicated cooked rice) for 16 days, Erandamuladi Niruha Basti (enema mainly with decoction) along with Ashwagandha Taila Anuvasana (enema with medicated oil) for 16 days in Kala Basti Krama (16 days in alternate order of decoction and oleation enema) followed by one day gap and then 7 days of Nasya Karma (nasal therapy) with Triphaladi Taila (oil) on alternate days along with a combination of Ayurvedic oral drugs [Brihadvatachintamani Rasa-125 mg, Dashamula Kwatha-40 ml, Narsinha Churna (powder)-3 g, Yogaraja Guggulu-1g (500mgx2tab) and Shiva Gutika-500 mg, twice a day for 1 month. Same Panchakarma procedures were repeated after 6 months. A similar combination of oral medications were continued in between and during this period. Chyavanaprasha Aveleha in the dose of 10g twice a day with milk were also added after completion of this treatment regime. Patient condition was assessed on Indian Takayasu Clinical Activity Score (ITAS-2010) for disease activity of TA. Satisfactory results were observed in the patient with improvement in ITAS-2010 scoring. TA may be managed with Ayurvedic drugs and Panchakarma procedures.

Circulatory Glutamine/Glucose ratio for evaluating disease activity in Takayasu arteritis: A NMR based serum metabolomics study

Quantitative assessment of disease activity is important for effective care of patients with Takayasu arteritis (TA). Activated glutaminolysis and reduced glycolytic flux is the hallmark of active inflammation. Based on this, we hypothesize that the circulatory Glutamine/Glucose ratio (QGR) can serve as an indicant of active inflammation in TA. To probe this hypothesis, the serum samples were collected from 45 active and 53 inactive TA patients fulfilling American College of Rheumatology (ACR) criteria and assessed for disease activity according to Indian Takayasu Clinical Activity Score (ITAS) using acute phase reactant–erythrocyte sedimentation rate [ITAS-A (ESR)]. The quantitative profiles of circulatory metabolites implicated in glutaminolysis (Glutamine and Glutamate) and those which estimate glycolytic flux (i.e. glucose and lactate) were measured using high field (800 MHz) NMR spectroscopy. The recorded spectra were analyzed using CHENOMX NMR Suite and the estimated concentration profiles were compared and evaluated for their diagnostic potential using Metaboanalyst. Compared to inactive-TA patients, the sera of active-TA patients were characterized by significantly decreased serum levels of glutamine and lactate suggesting that these patients exhibit activated glutaminolysis and reduced glycolytic activity. This is further supported by significantly decreased QGR and lactate to glucose ratio (LGR) levels in active compared to inactive TA patients. The receiver operating characteristic (ROC) curve analysis revealed satisfactory accuracy, sensitivity and specificity for QGR [with area under ROC curve (AUROC) = 0.76 and 95% confidence interval (CI) = 0.66–0.84) compared to that for LGR (with AUROC = 0.67 and CI = 0.561-0.77). Therefore, we believe that the circulatory QGR has the potential to serve as surrogate marker for the assessment of disease activity in TA patients. However, the use of this ratio in clinical settings will require future studies on large patient cohorts and procedural optimization as well to improve accuracy.

Translation and validation of the Indian Takayasu clinical activity score (ITAS2010) for the Brazilian Portuguese language

BackgroundThe Indian Takayasu Clinical Activity Score (ITAS2010) was developed in 2010 as an assessment tool for disease activity in patients with Takayasu arteritis (TA). It has since been widely used in different studies and in clinical practice for the management of patients with TA. The present study aims to translate the ITAS2010 into Brazilian Portuguese language and to validate it for use in clinical practice in Brazil.MethodsFor this cross-sectional study, the ITAS2010 was translated in accordance with the guidelines described by Beaton et al. and then applied with 27 patients with TA on three assessments by two rheumatologists working independently. To measure interrater agreement, the assessments were performed on the same day within approximately 1 hour. One of the rheumatologists performed a second evaluation of patients with TA within 7 to 14 days to measure intrarater agreement.ResultsThe correlation coefficient for the ITAS2010 score between the two raters was high (r = 0.916; p < 0.0001), as well as the intraclass correlation coefficient (ICC) [0.918 with a 95% confidence interval (95CI): 0.828–0.962]. The correlation coefficient and the ICC for intrarater agreement were moderate for ITAS2010 (r = 0.633; p < 0.0001 and ICC = 0.594; 95CI: 0.292–0.790). The ITAS2010 at baseline was compared with the physician’s global assessment (PGA) and with Kerr’s criteria for detecting disease activity in TA. Higher ITAS2010 scores were observed in patients with active and grumbling/persistent disease than in those presenting inactive disease according to the PGA [1.5 (0.0–3.0) vs. 0.0 (0.0–0.0); p = 0.0025]. Patients with active disease according to the Kerr’s criteria had also higher ITAS2010 scores than those considered in remission [3.0 (3.0–7.0) vs. 0.0 (0.0–0.0); p = 0.0068].ConclusionsThe Brazilian Portuguese version of the ITAS2010 is a valid and reproducible tool for the assessment of disease activity in TA and it is an additional tool for the routine evaluation of Brazilian patients with TA.

Serum leptin, a potential predictor of long-term angiographic progression in Takayasu's arteritis.

AimIn patients with Takayasu's arteritis (TA), current biomarkers that properly reflect the progression of the vascular structure remain absent. We aimed to determine the serum leptin level to investigate its relationship with imaging changes and assess its value as a predictor for long‐term radiological progression.MethodThis study included 34 untreated TA patients and 40 age‐matched healthy controls. At baseline and during the 5‐year follow‐up, we assessed disease activity using Kerr's criteria and Indian Takayasu Clinical Activity Score (ITAS2010) and monitored laboratory biomarkers as well as imaging findings. Serum leptin levels were measured by enzyme‐linked immunosorbent assay.ResultsThe baseline serum leptin levels were significantly higher in TA patients than in healthy controls. Leptin was significantly positively correlated with triglyceride and high‐density lipoprotein cholesterol levels and negatively correlated with fibrinogen and C‐reactive protein levels. Patients were subdivided into three groups based on their baseline leptin level. During a 5‐year follow‐up, patients in the high and medium leptin groups showed more radiological progression compared to those in the low leptin group. Cox proportional hazard regression analysis showed that a high serum leptin level was a positive predictor of radiological progression.ConclusionLeptin is a potential biomarker for assessing TA structural progression. Untreated patients with elevated serum leptin levels are at a higher risk of progression in the aorta. Thus, the leptin level can be a predictor of long‐term radiological progression.