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

Objective: To develop a new disease activity assessment tool with high accuracy for Takayasu arteritis. Methods: Individual 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 ß 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). Results: The multivariable model yielding the highest accuracy consisted of a high erythrocyte sedimentation rate (ESR), NIH criteria 1 and 4, and carotidynia. Using simplified ß 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. Conclusion: A 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.

Left ventricular function assessment after aortic and renal intervention in Takayasu arteritis by speckle tracking echocardiography: A pilot study.

BACKGROUND: Overt left ventricular (LV) dysfunction and congestive heart failure are known entities in Takayasu arteritis (TA). Subclinical LV dysfunction may develop in these patients despite normal LV ejection fraction (LVEF). Moreover, effect of treatment of aortic or renal artery narrowing in such patients is unknown. METHODS: This study included 15 angiographically confirmed TA patients undergoing aortic and/or renal intervention. A comprehensive clinical, biochemical and echocardiographic (2-dimensional, speckle tracking and tissue doppler imaging) evaluation were done at baseline, 72 h, and six months post intervention. RESULTS: Six patients (40%) had reduced LVEF (<50%) at baseline while rest 9 (60%) patients had reduced global longitudinal strain (GLS) but normal EF. Diastolic filling pattern was abnormal in all the patients. In patients with baseline reduced EF, mean EF improved from 24.62 ± 12.14% to 45.6 ± 9.45% (p = 0.001), E/e' ratio decreased from 15.15 ± 3.19 to 10.8 ± 2.56 (p = 0.005) and median NT pro BNP decreased from 1673 pg/ml (970-2401 pg/ml) to 80 pg/ml (40-354 pg/ml) (p = 0.001) at 6 months after interventional procedure. In patients with baseline normal EF, median NT pro BNP decreased from 512 pg/ml (80-898.5 pg/ml) to 34 pg/ml (29-70.8 pg/ml) (p < 0.01), mean GLS improved from -8.80 ± 0.77% to -16.3 ± 0.78% (p < 0.001) and mean E/e' decreased from 12.93 ± 2.63 to 7.8 ± 2.73 (p = 0.005) at 6 months follow up. CONCLUSION: LV dysfunction is common in patients with TA and obstructive lesions in aorta or renal arteries. GLS can be used to assess subclinical systolic dysfunction in these patients. Timely intervention can improve LV dysfunction and can even reverse the subclinical changes.

Pentraxin 3 is more accurate than C-reactive protein for Takayasu arteritis activity assessment: A systematic review and meta-analysis.

AIMS: Whether the circulating levels of pentraxin 3 (PTX3), an acute phase reactant (APR), are higher in active Takayasu arteritis (TAK), and if so, whether PTX3 is more accurate than C-reactive protein (CRP) in TAK activity assessment has been investigated in this study. STUDY DESIGN: Research works such as PubMed, Embase, ScienceDirect, Cochrane Library, and two Chinese literature databases (CNKI and WanFang) were searched for studies conducted till August 30th, 2019. Two investigators searched the studies independently, who evaluated the quality of the study using the Newcastle-Ottawa scale (NOS) and extracted data. Pooled standard mean difference (SMD) and diagnostic indexes, with a 95% confidence interval (CI), were calculated using a random-effect model. RESULTS: Totally, 8 studies involving 473 TAK (208 active and 265 inactive TAK) patients and 252 healthy controls were eventually included in the meta-analysis. PTX3 level in the blood in active TAK patients were found to be higher than that in dormant TAK with pooled SMD of 0.761 (95% CI = 0.38-1.14, p<0.0001; I2 = 68%, p of Q test = 0.003). And there was no publication bias. Among the 8 studies, 5 studies identified active TAK with both PTX3 and CRP. The pooled sensitivity, specificity, and AUC values of PTX3 in active TAK diagnosis were higher than those of CRP (0.78 [95% CI = 0.65-0.87] vs. 0.66 [95% CI = 0.53-0.77], p = 0.012; 0.85 [95% CI = 0.77-0.90] vs. 0.77 [95% CI = 0.56-0.90], p = 0.033; 0.88 [95% CI = 0.85-0.90] vs. 0.75 [95% CI = 0.71-0.79], p < 0.0001). It showed potential publication bias using Egger's test (p of PTX3 = 0.031 and p of CRP = 0.047). CONCLUSIONS: PTX3 might be better than CRP in the assessment of TAK activity. Yet, it should be cautious before clinical use for moderate heterogeneity and potential publication bias of the meta-analysis.

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

BACKGROUND: Patients with Takayasu's arteritis (TA) experience important changes in lifestyle, quality of life, and functional status due to ischemic symptoms or treatment toxicity. PURPOSE: 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. METHODS: 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. RESULTS: Fifteen women were included, with a median age of 41 years (interquartile range (IQR) 30-45) and disease duration of 108 months (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. CONCLUSIONS: It is important to identify disease-specific outcomes of interest to the patients to develop tools that assess them with a holistic approach.

Comparison of Clinical Features at the Onset of Takayasu's Arteritis According to Age and Sex.

BACKGROUND: Takayasu's arteritis (TA) is a large-vessel vasculitis that predominantly affects the aorta, pulmonary artery, and its main branches. The cause of TA is still unclear. OBJECTIVE: To identify the clinical characteristics of TA at onset in different patient groups. METHODS: The clinical manifestations, laboratory, and angiographic findings of 53 patients with TA based on age at onset and sex were retrospectively analysed. RESULTS: The ratio of the incidence of TA in males and females was 1:4. Chest pain, reduced glomerular filtration rate (GFR), and multivessel involvement were the most common symptoms at TA onset in male patients. 17% of patients had an onset age >40 years, and the percentage of TA patients >40 years old with chest pain was significantly higher [6 (66.7%) vs 13 (29.5%) and p=0.031] than that in TA patients <40 years old. However, their renal artery involvement [1 (11.1%) vs 21 (47.7%)), p=0.042], abdominal aorta lesion [0 (0.0%) vs 16 (38.1%), p=0.030], and multiple vessel involvement [2 (22.2%) vs. 32 (72.7%), p=0.004] were significantly less evident. Multivariate analysis showed that hypertension and thoracic aortic lesion were predisposing factors for TA diagnosis [odds ratio (OR)=3.918, 95% confidence interval (CI)=1.616-1566.185, p=0.026]. For patients with aortic insufficiency (OR=3.674, 95% CI=2.734-567.621, p=0.007) or aneurysm formation (OR=7.255, 95% CI=1.23-1628.614, p=0.044), ascending aortic lesion was an independent risk factor. Furthermore, patients >40 years with chest pain but no brachial pulse should be suspected to have TA. CONCLUSION: Hypertension and thoracic aortic lesion are predisposing factors for the diagnosis of TA. Male with TA was more prone to present with chest pain, multivessel involvement, and reduced GFR.

PET/MRI in large-vessel vasculitis: clinical value for diagnosis and assessment of disease activity.

Diagnosis of large vessel vasculitis (LVV) and evaluation of its inflammatory activity can be challenging. Our aim was to investigate the value of hybrid positron-emission tomography/magnetic resonance imaging (PET/MRI) in LVV. All consecutive patients with LVV from the Department of Internal Medicine who underwent PET/MRI were included. Three PET/MRI patterns were defined: (i) "inflammatory," with positive PET (>liver uptake) and abnormal MRI (stenosis and/or wall thickening); (ii) "fibrous", negative PET (≤liver uptake) and abnormal MRI; and (iii) "normal". Thirteen patients (10 female; median age: 67-years [range: 23-87]) underwent 18 PET/MRI scans. PET/MRI was performed at diagnosis (n = 4), at relapse (n = 7), or during remission (n = 7). Among the 18 scans, eight (44%) showed an inflammatory pattern and three (17%) a fibrous pattern; the other seven were normal. The distribution of the three patterns did not differ between patients with Takayasu arteritis (TA, n = 10 scans) and those with giant cell arteritis (GCA, n = 8 scans). PET/MRI findings were normal in 2/10 (20%) TA scans vs. 5/8 (62%) GCA scans (p = 0.3). Median SUVmax was 4.7 [2.1-8.6] vs. 2 [1.8-2.6] in patients with active disease vs. remission, respectively (p = 0.003). PET/MRI is a new hybrid imaging modality allowing comprehensive and multimodal analysis of vascular wall inflammation and the vascular lumen. This technique offers promising perspectives for the diagnosis and monitoring of LVV.

Assessment of disease activity in Takayasu arteritis: A quantitative study with computed tomography angiography.

BACKGROUND: Identifying disease activity in Takayasu arteritis (TAK) is challenging. This study aimed to investigate the value of quantitative characterization with computed tomography angiography in the assessment of disease activity in patients with TAK. METHODS: We retrospectively analysed the data on 162 aortic CT angiography from 140 TAK patients. Patients were categorized based on disease activity according to the National Institutes of Health criteria into two groups: active disease group (n = 65) and inactive disease group (n = 97). RESULTS: Patients with active TAK had a thicker wall compared with patients with inactive TAK (5.2 ±â€¯2.4 mm vs. 2.5 ±â€¯0.8 mm, p < 0.001). The relative post-contrast enhancement ratio of the thickened wall was higher in active TAK than in inactive TAK (1.5 ±â€¯0.3 vs. 1.1 ±â€¯0.2, p < 0.001). Given a thickness cutoff of 3.3 mm, sensitivity for active-phase TAK was 83.1%, specificity 89.7%, positive predictive value 84.4%, and negative predictive value 88.8%. With a relative post-contrast enhancement ratio cutoff of 1.2, sensitivity for active-phase TAK was 89.2%, specificity 76.3%, positive predictive value 71.6%, and negative predictive value 91.3%. In receiver-operating characteristic curves comparison, maximal wall thickness and relative post-contrast enhancement ratio were superior to C-reactive protein and erythrocyte sedimentation rate for determining active phase disease (p < 0.05). CONCLUSIONS: Quantitative characterization with CT angiography was a useful tool to assess disease activity in TAK patients. Maximal wall thickness and relative post-contrast enhancement ratio have a high sensitivity and specificity for detecting TAK activity.

The "Eternal Recurrence" of Arteritis. Suggesting Autoimmunity Underlining Friedrich Nietzsche's Challenging Clinical Case.

Friedrich Wilhelm Nietzsche (Röcken 1844 -Weimar 1900), the philosopher who theorized the concept of "eternal recurrence", suffered a lifelong multifaceted chronic illness that started in pediatric age with severe headaches and ended up with stroke at the age of 56. Even though many hypothetical diagnosis have been proposed in recent years, they all failed to explain the totality of clinical conditions that co-occurred in the philosopher's extremely challenging case, and debate on the matter is still open. In this report, we suggest an autoimmune condition, specifically Takayasu's arteritis, as a possible etiology of the philosopher's illness, which could not only potentially fit all available clinical data but also be the medical counterpart of Nietzsche's philosophical thought: could eternal recurrence of arteritis explain Zarathustra's destiny? If so, could a vascular surgeon, at this time in future, be so superhuman to change it?

Imaging modalities for the diagnosis and disease activity assessment of Takayasu's arteritis: A systematic review and meta-analysis.

BACKGROUND: Early diagnosis of Takayasu's Arteritis (TAK) and detection of disease activity may reduce the risk of vascular complications. The objective of this study was to determine the effectiveness of imaging modalities for the management of TAK. METHODS: MEDLINE and EMBASE were searched for studies of patients undergoing various imaging modalities for TAK diagnosis or to assess disease activity. We excluded case reports, reviews and case series with <10 patients. The methodologic quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). Random effects meta-analyses with inverse-variance weighting were performed. RESULTS: From the 1126 citations screened, 57 studies met our inclusion criteria. Many of the studies were of small sample size (average N=27), cross-sectional design and low methodological quality. Ultrasound (US) had a lower pooled sensitivity (SN) of 81% (95% CI: 69-89%) than Magnetic Resonance Angiography (MRA) with SN=92% (95% CI: 88-95%) for TAK diagnosis (by clinical criteria and/or X-Ray angiography). Both had high specificities (SP) of >90% for TAK diagnosis. Fewer studies investigated computed tomography angiography (CTA), but SN and SP for TAK diagnosis was high (>90%). The utility of vessel wall thickening and enhancement by MRA and CTA to predict disease activity varied across studies. The pooled SN and SP of 18F-fluorodeoxyglucose-Positron Emission Tomography (FDG-PET) for disease activity was 81% (95% CI: 69-89%) and 74% (95% CI: 55-86%), respectively. CONCLUSION: US, CTA and/or MRA are effective for the diagnosis of TAK. The utility of these imaging modalities for assessing disease activity remains unclear.

Assessment of Disease Activity in Large-vessel Vasculitis: Results of an International Delphi Exercise.

OBJECTIVE: To arrive at consensus for candidate outcomes for disease activity assessment in large-vessel vasculitis (LVV) in clinical trials. METHODS: A Delphi survey including 99 items was circulated among international experts for 3 rounds. RESULTS: Fifty-seven items were accepted for both giant cell arteritis and Takayasu arteritis. Sixty-seven percent of experts voted to have a common approach for both diseases with additional disease-specific items such as weight loss, scalp tenderness/necrosis, morning stiffness, dizziness, visual symptoms, and imaging. CONCLUSION: This study highlights similarities and differences in experts' perspectives for assessing clinical activity in LVV and may guide a consensus-driven core set of validated outcomes.

Multimodality assessment of left ventricular dysfunction in Takayasu arteritis and familial hypercholesterolaemia.

Although left ventricular (LV) systolic dysfunction in patients suffering from Takayasu arteritis (TA) has been reported, little is known regarding the development of heart failure in these patients. We report a novel finding of active TA and familial hypercholesterolaemia presenting with severe LV dysfunction through multimodality assessments of LV systolic dysfunction.

Outcome assessment in Takayasu arteritis.

Takayasu arteritis (TAK) is a systemic granulomatous large-vessel vasculitis with a phenotype that overlaps with GCA and defined by the 1993 and 2012 Chapel Hill Consensus Conference statements. However, the diagnosis of TAK is often delayed since TAK patients may be asymptomatic or have non-specific symptoms. Once a diagnosis is made, it is difficult to judge remission or recurrence since there are no reliable assessment tools. With the availability of newer agents, such as cytokine blockade, which are being evaluated in GCA, there is the potential for real advances in TAK patient management. Without reliable assessment tools it will be difficult to introduce newer agents in an organized way or to optimally benefit patients in the future. In this article we review the use and performance of disease indicators in TAK clinical trials as a basis for the further development of assessment tools for this disease.

Assessment of Patients with Takayasu Arteritis in Routine Practice with Indian Takayasu Clinical Activity Score.

OBJECTIVE: To assess the Indian Takayasu Clinical Activity Score (ITAS2010) in followup of Takayasu arteritis (TA). METHODS: ITAS2010 forms were filled in prospectively (n = 144). Clinical activity was assessed with physician's global assessment (PGA) and criteria defined by Kerr, et al. RESULTS: ITAS2010 was significantly higher in patients with active disease. Total agreement between ITAS2010 and PGA was 66.4%, and between ITAS2010 and Kerr, et al was 82.8%. During followup, 14 of 15 patients showing vascular progression with imaging were categorized as having inactive disease according to ITAS2010. CONCLUSION: ITAS2010 was discriminatory for activity during the followup, but the agreement between PGA and ITAS2010 was moderate. Future work should include the incorporation of advanced vascular imaging and demonstration of ITAS2010 as a scalable measure and not simply a dichotomous measure of activity/flare versus remission.

[PET-CT with ¹8F-FDG in the diagnosis of Takayasu's arteritis and the assessment of response to therapy]. / PET-TAC con ¹8F-FDG en el diagnóstico de la arteritis de Takayasu y la valoración del tratamiento.

We present a patient without specific symptoms of vasculitis, with normal acute phase reactants, but with the pathological diagnosis of Takayasu' arteritis that was referred for a PET-CT with (18)F-FDG. Scan findings showed inflammatory activity in the vessel walls of the aorta and after the appropriate treatment, a second scan with (18)F-FDG, correctly assessed the therapeutic response. We discuss the contributions of PET-CT with (18)F-FDG in the management of this pathological entity.

Advances in the diagnosis, assessment and outcome of Takayasu's arteritis.

Takayasu's arteritis (TAK) is a rare, chronic large-vessel vasculitis (LVV) that predominantly affects aorta, its major branches, and the pulmonary arteries. Segmental stenosis, occlusion, dilatation, or aneurysm formation may occur in the vessel wall during the course of the disease. The vascular involvement can be shown with different imaging modalities to make the diagnosis of TAK. Conventional angiography, the gold standard method for initial diagnosis, seems to be replaced with the new imaging modalities such as magnetic resonance angiography (MRA) and (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) in recent years. The data coming from the new studies support that MRA and FDG-PET are also promising for the assessment of disease activity. Prognosis is possibly getting better with lower mortality in recent years; however, it is difficult to assess the widely different vascular intervention rates among the clinical series. Leflunomide, TNF-α antagonists, and tocilizumab are new options in patients resistant to conventional therapies. There is a clear need to develop a validated set of outcome measures for use in clinical trials of TAK. The OMERACT Vasculitis Working Group has taken on this task and aims to develop a core set of outcomes for LVV.

Diagnosis and assessment of Takayasu arteritis by multiple biomarkers.

BACKGROUND: Patients with Takayasu arteritis (TA) often show recurrence under steroid treatment without an elevation of C-reactive protein (CRP). There is a report that matrix metalloproteinase (MMP)-2, MMP-3, MMP-9 and pentraxin3 (PTX3) could be sensitive biomarkers, but the characteristics of these biomarkers have not been established. METHODS AND RESULTS: We enrolled 45 consecutive patients; 28 were grouped in an active phase as evidenced by clinical recurrence within 2 years of blood sampling. Circulating levels of high-sensitivity (hs)CRP, MMPs, and PTX3 were determined. Patients in an active phase showed higher levels of hsCRP, MMP-9, and PTX3. Area under the receiving operating characteristics curves of hsCRP and PTX3 were significantly higher than that of MMP-9. Among the 28 patients with active TA, 71% was positive for hsCRP and 82% for PTX3. Patients without recurrence showed significantly higher plasma levels of MMP-9. There was a positive correlation between the plasma MMP-3 level and the prednisolone dose. However, PTX3 and MMP-9 levels did not have such a correlation. CONCLUSIONS: PTX3 and MMP-9, which are not affected by prednisolone, could be sensitive biomarkers for assessing TA activity. Evaluation of MMP-9 may suggest prior existence of TA.

Performance of Birmingham Vasculitis Activity Score and disease extent index in childhood vasculitides.

OBJECTIVES: To evaluate the performance of the Birmingham Vasculitis Activity Score (BVAS) v3 and the Disease Extent Index (DEI) for the assessment of disease activity in 4 primary childhood (c-) systemic vasculitides. METHODS: Patients fulfilling the EULAR/PRINTO/PRES (Ankara) c-vasculitis classification criteria for Henoch-Schönlein purpura (HSP), childhood (c) polyarteritis nodosa (c-PAN), c-Wegener's granulomatosis (c-WG) and c-Takayasu arteritis (c-TA) with disease duration at the time of diagnosis ≤3 months were extracted from the PRINTO database. The performance of the BVAS and DEI were examined by assessing convergent validity, the pattern of disease involvement, and responsiveness. We also evaluated alternative unweighted scoring methods for both tools. RESULTS: The analysis set included 796 patients with 669 HSP, 80 c-PAN, 25 c-WG and 22 c-TA. The median age at diagnosis was 6.9 years (6.6-12) and median delay in making the diagnosis from the onset of signs/symptoms was 0.01 (0.003-0.027) years. A strong correlation was found between the BVAS and DEI (rs=0.78) while correlation with the physician global assessment was moderate (rs=0.48) with BVAS and poor with DEI (rs=0.25). Both the BVAS and DEI sub-scores and total scores were able to descrive the disease involvement in the 4 childhood vasculitides. Responsiveness was large (>1.5) for both tools. The performance characteristics of the BVAS and DEI with the unweighted methods were comparable. CONCLUSIONS: This study demonstrates that both the BVAS and DEI are valid tools for the assessment of the level of disease activity in a large cohort of childhood acute and chronic vasculitides.

Takayasu arteritis: assessment of response to medical therapy based on clinical activity criteria and imaging techniques.

In this retrospective longitudinal cohort study we included 52 patients with Takayasu arteritis (TA) who were on regular follow-up at the Vasculitis Unit of Universidade Federal de São Paulo between 2003 and 2009. The mean age at study was 38 years and the mean age at diagnosis was 29 years. Patients were followed for a mean 74.3 months. A relapse-remitting course was observed in 41 patients (78.8%) whereas 9 (17.3%) had a monophasic course and only 2 (3.8%) patients were chronic-active. Disease remission was achieved in 50 patients (96.2%). Angiographic type V was observed in 42.3% of TA patients at diagnosis and in 61.5% during follow-up. The most affected arteries were the abdominal aorta (63.5%) and left subclavian (60.6%). Prednisone was used by 94% of TA patients and immunosuppressive agents were prescribed for 51 (98%) patients. Methotrexate was used by 82.7%, followed by cyclophosphamide (26.9%), azathioprine (25.0%), anti-TNFα agents (5.8%) and leflunomide (5.8%). Although, forty patients (76.9%) used prednisone and methotrexate as initial treatment, 75% of them developed new vascular lesions along follow-up. Eighteen TA patients (34.6%) needed to change immunosuppressive therapy due to failure or toxicity, among them 83.3% presented new lesions. Surgical treatment was performed in 34.6% of patients and restenosis was observed in 13.5% in a median time of 11 months after surgery. In conclusion besides prednisone and methotrexate is largely used in TA, the majority of patients still develop new arterial lesions along time.