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.

Potential Application of Diffusion-Weighted Whole-Body Imaging with Background Body Signal Suppression for Disease Activity Assessment in Takayasu Arteritis-In Search of the "Golden Mean": Case Report.

The case report describes our first experience of "diffusion-weighted whole-body imaging with background body signal suppression" (DWIBS) application for disease activity assessment in a young female patient with Takayasu arteritis (TA). Despite the normal level of inflammatory markers, clinical signs of disease recurrence were present. In our case, DWIBS did not only help to identify the disease recurrence in the patient with false-negative inflammatory markers but also revealed new foci involved in the TA process. DWIBS can be a potentially new imaging method, useful during the follow-up in patients with TA.

Diagnostic accuracy of positron emission tomography for assessment of disease activity in large vessel vasculitis.

AIM: To determine the diagnostic yield of 18 F-fluorodeoxyglucose positron emission tomography (PET) in disease activity assessment of large vessel vasculitides (LVV). METHODS: Patients with LVV who had undergone PET (between 2004 and June 2010) or PET co-registered with computed tomography (PET/CT; since June 2010) were identified. Clinical disease activity was assessed using established scoring systems. PET images were reviewed by two blinded nuclear medicine physicians. Uptake of the aortic wall was compared to the liver uptake utilizing a visual 4-point score, with a vessel wall uptake similar or higher than liver uptake considered as active disease. Various target-to-background ratios were calculated. Receiver operator characteristics analysis was applied to determine the diagnostic accuracy of PET for detecting clinically active disease. Interobserver agreement of visual readings was measured with Cohen´s kappa. RESULTS: Eighty examinations in 62 patients were analyzed, with a mean time between diagnosis and PET of 106 ± 171 weeks. Fifty-seven cases were finally classified as clinically active and 23 cases as clinically inactive. With a cut-off value of 1.3, the aorta-to-liver ratio yielded a sensitivity and specificity of 84.2% and 82.6% (area under the curve 0.9). Overall, sensitivity and specificity of visual analysis were 68.4% and 91.3%, but sensitivity decreased to 54% in patients treated for more than 3 months. Interobserver agreement of visual rating was excellent (κ: 0.93). CONCLUSION: Positron emission tomography is specific and reliable in disease activity assessment of LVV, but lacks sensitivity for detecting active disease in patients under long-term immunosuppressive treatment.

Correlating MRI with clinical evaluation in the assessment of disease activity of Takayasu's arteritis.

OBJECTIVES: To correlate magnetic resonance imaging (MRI) assessment of disease activity in patients with Takayasu's arteritis with the Indian Takayasu's activity score (ITAS). DESIGN, MATERIALS AND METHODS: We prospectively assessed 20 patients with Takayasu's arteritis from November 2010 to September 2011. RESULTS: We found a statistically significant association between MRI assessment of disease activity and ITAS with a P-value of 0.01. The MRI features suggesting active disease included wall thickening and enhancement. We also analyzed the association between MRI and clinical assessment which was also statistically significant at P = 0.037. CONCLUSION: Our study suggests that there is an association between MRI assessment of disease activity and the ITAS. MRI evaluation of disease activity of Takayasu's arteritis therefore goes hand in hand with ITAS 2010, ITAS - A, erythrocyte sedimentation rate and C-reactive protein. However this needs further investigation from future studies using serial assessments.

Clinical assessment in Takayasu's arteritis: major challenges and controversies.

Takayasu's arteritis (TAK) is a rare, chronic, large-vessel vasculitis (LVV) that predominantly affects aorta, its major branches and the pulmonary arteries. Recent controversial issues in the diagnosis, disease assessment and prognosis in TAK are discussed in this review. In recent years, conventional angiography, the standard method for the initial diagnosis, seems to have been replaced by the new imaging modalities, such as MRI and 18F-FDG-PET. Less invasive techniques (CT/MRI) are now suggested first, compared to conventional angiography, and MRI is preferable to CT with less contrast load/radiation. Ultrasound is useful for carotid assessment, but being a user-dependent technique, imaging of deeper vessels (subclavian and aorta) are not reliable. 18F-FDG-PET is useful especially in patients with no vascular symptoms/signs, fever of unknown origin or unexplained acute-phase response. MRI and 18F-FDG-PET are also promising for the assessment of disease activity. New tools for disease assessment such as Indian Takayasu Arteritis Score (ITAS2010) aim to better characterise and quantify disease activity. Prognosis is recently possibly getting better with lower mortality, but a substantial damage is present even in early cases. There is a clear need to develop a validated set of outcome measures to be used in clinical trials of TAK. The OMERACT Vasculitis Working Group has taken on this task, finished a Delphi exercise with experts 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.

[Disease activity assessment in large vessel vasculitis]. / Valutazione dell'attività di malattia nelle vasculiti dei grandi vasi.

Disease activity assessment in large vessel vasculitis (LVV) is often challenging for physicians. In this study, we compared the assessment of disease activity based on inflammatory markers, clinical indices (Indian Takayasu Activity Score [ITAS] and the Kerr/National Institute of Health indices [Kerr/NIH]), and 18F-Fluorodesossiglucose (FGD) vascular uptake at positron emission tomography (Pet). We found that Pet results did not statistically correlate with the clinical indices ITAS and Kerr/NIH, because FDG uptake was increased (grade>2 on a 0-3 scale in at least one evaluated vascular segment) in many patients with inactive disease according to clinical and laboratory parameters (i.e., negative ITAS and Kerr/NIH indices as well as normal erythrocyte sedimentation rate (ESR) and C-reactive protein (PCR)). Similarly, interleukin- 6 and its soluble receptor did not statistically correlate with disease activity. In contrast, clinical indices showed a significant correlation between each other and with inflammatory markers (VES and PCR). These data suggest that while clinical indices and inflammatory markers may be useful to assess disease activity, Pet may be more sensitive.

Cyclophosphamide for large vessel vasculitis: assessment of response by PET/CT.

OBJECTIVES: Glucocorticosteroids (GC) are the standard treatment for large vessel vasculitis, but some patients are refractory. Cyclophosphamide (CYC) has been shown to be effective in autoimmune diseases. METHODS: The study consisted of a retrospective analysis of 10 patients with active large vessel arteritis who received pulse CYC after failure of GC or because of organ threatening stenosis. CYC pulse therapy was started with a dose of 750mg/m² body surface every 3 weeks and increased if necessary. Clinical response was assessed by the Birmingham Vasculitis Activity Score (BVAS), the C-reactive protein and the erythrocyte sedimentation rate (ESR). PET/CT was performed at baseline and during treatment to determine disease activity. RESULTS: The median BVAS at the time of the initial PET/CT was 6.5 (5-13). The median ESR was 42mm/h (6-94mm/h), and the medium CRP was 4.6mg/dl (0.18-11.8mg/dl). All but one patient experienced a complete clinical remission during CYC treatment after a median of 10 cycles. PET/CT confirmed the efficacy of the treatment by normalisation of FDG uptake during therapy. One patient with persisting inflammation was lost to follow-up. One patient experienced a relapse after 21 months. The remaining 8 patients are still in remission with low-dose GC and a maintenance therapy (azathioprine, methotrexate or mycophenolate) after a median follow-up of 45 months. CONCLUSIONS: Pulse cyclophosphamide is effective in patients with large vessel vasculitis resistant to glucocorticosteroids. The high rate of sustained response in our patients suggests that treatment decisions based on clinical parameters combined with PET/CT may have a beneficial effect on the clinical outcome.