Ultrasound evaluation of synovitis in RA: Correlation with clinical disease activity and sensitivity to change in an observational cohort study

ObjectiveTo evaluate the correlation between clinical measures of disease activity and a ultrasound (US) scoring system for synovitis applied by many different ultrasonographers in a daily routine care setting within the Swiss registry for RA (SCQM) and further to determine the sensitivity to change of this US Score.MethodsOne hundred and eight Swiss rheumatologists were trained in performing the Swiss Sonography in Arthritis and Rheumatism (SONAR) score. US B-mode and Power Doppler (PwD) scores were correlated with DAS28 and compared between the clinical categories in a cross-sectional cohort of patients. In patients with a second US (longitudinal cohort), we investigated if change in US score correlated with change in DAS and evaluated the responsiveness of both methods.ResultsIn the cross-sectional cohort with 536 patients, correlation between the B-mode score and DAS28 was significant but modest (Pearson coefficient r = 0.41, P < 0.0001). The same was true for the PwD score (r = 0.41, P < 0.0001). In the longitudinal cohort with 183 patients we also found a significant correlation between change in B-mode and in PwD score with change in DAS28 (r = 0.54, P < 0.0001 and r = 0.46, P < 0.0001, respectively). Both methods of evaluation (DAS and US) showed similar responsiveness according to standardized response mean (SRM).ConclusionsThe SONAR Score is practicable and was applied by many rheumatologists in daily routine care after initial training. It demonstrates significant correlations with the degree of as well as change in disease activity as measured by DAS. On the level of the individual, the US score shows many discrepancies and overlapping results exist.     

Validity of the rheumatoid arthritis impact of disease (RAID) score and definition of cut-off points for disease activity states in a population-based European cohort of patients with rheumatoid arthritis

Objectives

To assess the validity of the rheumatoid arthritis impact of disease (RAID) for measuring disease activity of rheumatoid arthritis (RA) and to determine cut-off values for defining the disease activity states.

Concordance between clinical and ultrasound findings in rheumatoid arthritis

BackgroundClinical joint examination is less time-consuming than ultrasound in rheumatoid arthritis. Knowledge of clinical and ultrasound concordance of joints groups could help in selecting joints for a best ultrasonographic assessment.ObjectiveTo evaluate concordance between clinical examination and ultrasound of joints in a heterogeneous group of patients with rheumatoid arthritis.MethodForty patients were included in a prospective, transversal, single-center study, whatever disease activity, duration or treatment. In each patient, 40 joints were evaluated for a total of 1600 joints. Synovitis was scored using clinical examination, B-mode, power Doppler and both B-mode and power Doppler. Concordance between swelling joint by clinical examination, synovitis thickening by B-mode (grade 1 or higher) and inflammation by power Doppler (grade 1 or higher) was assessed by computing the kappa coefficient.ResultsClinical joint examination and ultrasound concordance was very low at the shoulders and metatarsophalangeal joints (κ < 0.1) and was low at wrists (κ: 0.23 to 0.30). B-mode and power Doppler found 2.4 and 1.4 more synovitis than swollen joint count using clinical examination and up to 30 times more at metatarsophalangeal joints. Concordance was strong at tibio-talar joints (κ: 0.65 to 0.82) and moderate at others joints sites (κ: 0.4 to 0.6).ConclusionAssessment of a heterogeneous group showed that ultrasound adds information to clinical examination, most notably at the shoulders, wrists and metatarsophalangeal joints. Concordance was moderate to strong at other joint sites.     

类风湿关节炎患者骨密度与疾病活动相关性的临床观察

目的探讨类风湿关节炎（RA）患者发生骨量丢失的原因,为早期预防RA患者骨质疏松提供理论依据。方法前瞻性观察86例RA患者,收集患者基线及两年后的一般临床资料和疾病活动相关指标,并同时用双能X线骨密度仪测量患者6个部位的骨密度。结果22例患者（25.6%）有至少一个检测部位骨质疏松;34例患者（39.5%）表现为至少一个检测部位骨量低下。在随访两年中,桡尺骨远端及前臂的BMD明显下降（P〈0.005）;代表局部骨量变化的桡尺骨远端、前臂及手的BMD与代表全身骨量变化的股骨颈、腰椎和全身的BMD有很好的相关性（r：0.599-0.806,P〈0.001）。BMD与疾病活动指标（包括ESR、CRP、HAQ、RAI、DAS、28个关节肿胀指数及ACR功能分级）均无相关性;但多元回归分析示基线RF升高为观察两年后各检测部位骨密度Z值下降的独立危险因素,RF阳性的患者其两年后各部位的Z值均显著低于RF阴性的患者（P〈0.05）。女性在手、桡尺骨远端、前臂的BMD值均低于男性（adjusted R2=0.256-0.398,P〈0.001）。增龄为除了前臂外所有部位BMD降低的独立危险因素（P=0.02-0.000）。小剂量强的松龙（≤5mg/d）与本组患者的BMD变化无相关。结论骨量丢失为RA患者的常见并发症,尤其见于女性及高龄患者;前臂局部的骨量丢失高于全身的骨量丢失。RF升高为引起BMD下降的重要原因之一。     

Enthesopathy in rheumatoid arthritis and spondyloarthritis: An ultrasound study

Objective

We aimed to compare the prevalence of enthesopathy seen on ultrasonography (US) in spondyloarthritis (SpA) and rheumatoid arthritis (RA) and compared it to healthy controls.

Patient-defined flares and disease activity worsening in 222 patients with psoriatic arthritis from 14 countries

ObjectivesTo explore patient-defined flares in psoriatic arthritis (PsA), compared to an increase in disease activity in psoriatic arthritis (DAPSA) and to analyze the validity of a patient-reported flare question.MethodsReFlap (NCT03119805) was a longitudinal study in 14 countries of consecutive patients with definite PsA. Patients were seen twice in the context of usual care, 4.5 ± 2.2 months apart. Flares were reported by patients and physicians at the second visit using a single question. DAPSA worsening was defined as a change to a higher DAPSA category. Agreement between the definitions of worsening was calculated by prevalence adjusted bias adjusted kappa (PABAK). Validity of patient-reported flare was assessed by comparing patients with versus without flare and transition to flares.ResultsIn 222 patients, mean disease duration 10.8 ± 8.3 years, 127 (58.8%) males: disease activity was low (mean DAPSA 11.5 ± 14.0); 63.3% received a bDMARD. Patient-reported flares between the 2 visits were seen in 27% patients (for these patients, mean 2.2 ± 3.7 flares per patient, mean duration 12.6 ± 21.0 days per flare). Physician- reported flares were seen in 17.6% and worsening in DAPSA in 40.1% of patients. Agreement between definitions was moderate (PABAK = 0.32-0.59). Patients in flare had significantly more active disease than patients not in flare for all outcomes (all P < 0.001). At the patient-level, transition to flare state was associated to a worsening in disease activity and impact outcomes.ConclusionsPatient flares were frequent and were associated with active and symptomatic disease. These findings provide preliminary validation for patient-reported flares in PsA.     

Abrupt and unexpected stressful life events are followed with increased disease activity in spondyloarthritis: A two years web-based cohort study

Objective

The contribution of environmental factors to spondyloarthritis (SpA) course remains poorly characterized. We previously reported a possible triggering of disease flares by stressful life events and vaccination. The objective of the present study was to specify the types of vaccine and life event that may influence disease activity.

Early non-response to certolizumab pegol in rheumatoid arthritis predicts treatment failure at one year. Data from a randomised phase III clinical trial

Objectives

To compare different early clinical criteria of non-response determined at three months as predictors of clinical failure at one year in patients with rheumatoid arthritis starting therapy with certolizumab pegol.

Persistence of ultrasound synovitis in patients with rheumatoid arthritis fulfilling the DAS28 and/or the new ACR/EULAR RA remission definitions: Results of an observational cohort study

ObjectiveThe primary aim of the study was to evaluate whether rheumatoid arthritis (RA) patients considered to be in remission according to clinical criteria sets still had persisting ultrasound (US) synovitis. We further intended to evaluate the capacity of our US score to discriminate between the patients with a clinically active disease versus those in remission.MethodsThis is an observational study nested within the Swiss Clinical Quality Management in Rheumatic Diseases (SCQM) rheumatoid arthritis cohort. A validated US score (SONAR score) based on a semi-quantitative B-mode and Doppler (PwD) score as part of the regular clinical workup by rheumatologists in different clinical settings was used. To define clinically relevant synovitis, the same score was applied to 38 healthy controls and the 90st percentile was used as cut-off for ‘relevant’ synovitis.ResultsThree hundred and seven patients had at least one US examination and concomitant clinical information on disease activity. More than a third of patients in both DAS28 and ACR/EULAR remission showed significant gray scale synovitis (P = 0.01 and 0.0002, respectively) and PwD activity (P = 0.005 and 0.0005, respectively) when compared to controls. The capacity of US to discriminate between the two clinical remission groups and patients with active disease was only moderate.ConclusionThis observational study confirms that many patients considered to be in clinical remission according the DAS and the ACR/EULAR definitions still have residual synovitis on US. The prognostic significance of US synovitis and the exact place of US in patients reaching clinical remission need to be further evaluated.     

Association of IL-2RA and IL-2RB genes with erosive status in early rheumatoid arthritis patients (ESPOIR and RMP cohorts)

ObjectivesTo assess the impact of single nucleotide polymorphisms (SNPs) in IL-2RA (rs2104286) and IL-2RB (rs743777 and rs3218253) genes on the risk of erosions in rheumatoid arthritis (RA) patients.MethodsThis work is derived from 2 prospective cohorts of early RA: ESPOIR (n = 439) and RMP (n = 180). The proportions of patients with erosions at baseline and 1 year according to the genotypes of IL2RA (rs2104286) or the haplotypes constructed with the 2 SNPs of IL2RB were compared in the whole population and in ACPA positive patients. A meta-analysis assessing the risk of erosion depending on the haplotypes of the 2 SNPs of IL-2RB was performed using the Mantel-Haenszel method. A multivariate model was used to assess the independent effect of the haplotypes of IL-2RB on the risk of erosions.ResultsThe AC haplotype of IL-2RB carriage was significantly associated with the rate of erosions in ACPA positive patients in ESPOIR cohort (rate of erosions: AC/AC: 78% versus GC or GT/GC or GT: 44%, p = 0.001). A meta-analysis of ESPOIR and RMP cohorts confirmed that the carriage of AC haplotype was significantly associated with the rate of erosions at 1 year in the whole sample (OR[95%CI] = 1.92[1.14–3.22], p = 0.01) and in ACPA positive patients (OR[95%CI] = 3.34[1.68–6.67], p = 0.0006). A multivariate model in ESPOIR cohort demonstrated the independent effect of the carriage of the AC haplotype (6.03[1.94–18.69], p = 0.002) on the risk of erosions in ACPA+ patients.ConclusionA haplotype constructed with 2 SNPs located on IL-2RB gene was associated with erosive status in early RA.     

早期类风湿关节炎患者甲襞微循环积分与病情活动度及骨质疏松的相关性分析

目的探讨早期类风湿关节炎患者甲襞微循环异常与病情活动性及骨质疏松的相关性。方法收集60例早期RA患者及60名健康对照者的血清,测定甲襞微循环积分,酶联免疫法测定其25(OH)D浓度,运用双能X线吸收仪测定RA患者骨密度,详细记录RA患者临床、实验室及影像学资料,计算疾病活动性。影响因素分析采用多元线性回归分析和Logistic回归分析进行统计学分析。结果 (1)RA患者甲襞微循环水平高于健康对照组,差异有统计学意义[(6.13±1.92)与(4.70±1.54),t=3.174,P=0.018];(2)甲襞微循环积分分别与RA患者DAS28积分、ESR、CRP、抗CCP抗体滴度相关(r=0.515、0.579、0.422、0.473,P均0.05)同时,甲襞微循环积分在不同疾病活动度的RA患者中表达差异有统计学意义;(3)线性回归分析提示RA患者血清甲襞微循环积分增高是疾病活动性的危险因素(β=0.376,P=0.013);(4)VEGF水平随25(OH)D减低表现出增高的趋势,但差异无统计学意义(P=0.702);Pearson相关分析显示甲襞微循环积分与25(OH)D水平呈负相关(r=-0.593,P0.001);(5)34例维生素D缺乏的患者均给予2周的阿法骨化醇补充治疗,血清25(OH)D水平从(14.0±3.4)ng/m L增加到(18.0±4.2)ng/m L,同时甲襞微循环评分由(6.68±2.06)下降到(4.62±1.69)。两者治疗前后比较均有统计学意义(t=-11.913,P0.001和t=14.742,P0.001);(6)Logistic回归分析发现甲襞微循环、年龄和DAS28是骨质疏松的危险因素(OR分别为1.632、1.257和1.506;P分别为0.003、0.015、0.047),而25(OH)D是RA患者骨质疏松的保护因素(OR=0.65,95%CI 0.44~0.96,P=0.032)。结论早期RA患者甲襞微循环异常与病情活动度相关;甲襞微循环积分增高是骨质疏松发生的危险因素。对于合并维生素D不足的RA患者,补充维生素D或许有助于微循环功能的改善。     

The impact of diet on disease activity in spondyloarthritis: A systematic literature review

ObjectivesOur study aimed to systematically review the evidence about the effect of diet or dietary supplements on spondyloarthritis (SpA) disease activity.Methodsa systematic literature review (SLR) was conducted in MEDLINE, EMBASE, Cochrane and SCOPUS according to the “PEO” format (Population, Exposure, Outcome). The population was SpA (axial or peripheral, axSpA/pSpA, including Psoriatic Arthritis-PsA); the intervention any kind of diet/dietary supplement; the outcome disease activity. Inclusion criteria were: adult patients, Randomized Controlled Trials (RCTs) and longitudinal studies (so that a pre-and post-intervention assessment were available), papers in English. Risk of bias (RoB) was conducted with different tools according to the design of the study.ResultsLiterature search yielded 1390 publications, of which 15 were finally inlcuded: 12 interventional and 3 observational studies. Among those with the lower RoB: a) 2 RCTs, one at unclear and one at low RoB, failed to show benefit of probiotics in SpA b) Two RCTs at unclear RoB provided evidence that weight loss, but not hypocaloric diet, was associated to MDA achievement in PsA. The remaining interventional studies were at high RoB. Among the observational studies, one study on Mediterranean diet demonstrated an association between diet adherence and a ≥ 20% decrease of ASDAS in axSpA. The other two observational studies were judged of poor quality.Conclusionsweight loss seem to be able to impact disease activity in PsA, while probiotics do not seem useful in SpA; evidence for dietary behaviors is scarce and heterogeneous.     

50例绝经后高疾病活动期的女性类风湿关节炎骨密度的临床观察

目的观察绝经后高疾病活动期的女性类风湿关节炎患者骨矿物质密度水平的变化。方法收集50例绝经后女性RA患者一般临床资料,包括年龄、RA病程、绝经年龄、ESR、CRP、RF、抗CCP抗体、DSA28评分及雌二醇水平,应用双能X线吸收法(DXA)测定50例患者腰椎L_(1-4)和左髋关节部位的骨密度,分析其骨密度(BMD)的情况。结果 1.50例绝经后女性RA的DSA28评分大于5.1,属高疾病活动期,骨质疏松组发生率52%;远高于骨量减少组(30%)及骨密度正常组(18%)。2.骨质疏松组的绝经年龄比非骨质疏松组明显提前(P=0.005),抗CCP抗体水平明显升高(P=0.037),有统计学意义,但在年龄、病程、RF、DSA28评分及雌激素方面两者无统计学差异。3.Logistic回归分析结果显示抗CCP抗体(OR值1.025,P=0.041)是绝经后高疾病活动女性RA骨质疏松的独立危险因素。4.骨质疏松组,腰椎总骨密度较髋关节显著降低(P0.001);腰椎组内比较以腰1椎体BMD最低,而后依次为腰2,腰3、腰4(P=0.0003),左髋关节组内比较以大转子BMD最低,而后依次为股骨颈、小转子(P0.0001)。结论绝经后高疾病活动期的女性RA患者存在明显的骨质疏松,以腰椎骨密度(特别L_1)下降最明显;抗CCP抗体可能是高疾病活动期的女性类RA患者发生骨质疏松的危险因素。     

Predictors of disease flare after discontinuation of concomitant methotrexate in Japanese patients with rheumatoid arthritis treated with tocilizumab

ObjectiveTo investigate predictors of disease flare after methotrexate discontinuation in Japanese rheumatoid arthritis (RA) patients with sustained low disease activity undergoing tocilizumab plus methotrexate combination therapy.MethodsParticipants of this multicenter, open-label, uncontrolled, prospective study were RA patients maintaining low disease activity (Clinical Disease Activity Index [CDAI] ≤ 10) for ≥ 12 weeks with tocilizumab plus methotrexate. Methotrexate was discontinued after 12 weeks of biweekly administration while continuing tocilizumab therapy. Disease flare was defined as either a CDAI score > 10 or intervention with rescue treatments for any reason even if the CDAI score was ≤ 10. The impact of baseline characteristics on disease flare at week 64 (52 weeks after methotrexate discontinuation) was assessed with logistic regression models.ResultsEfficacy analyses were performed in 49 patients, of whom 15 had a disease flare by week 64. The proportion (95% confidence interval [CI]) of patients who maintained low disease activity without a flare at week 64 was 69.4% (54.6–81.8%). The dosing interval of tocilizumab was longer than that described on the drug label in Japan (i.e., intravenously every 4 weeks, or subcutaneously every 2 weeks) in 27% and 6% of patients with and without a flare, respectively. Multivariate analysis revealed that male sex (odds ratio [OR]: 18.00, 95% CI: 2.80–115.56) and extended dosing interval of tocilizumab (OR: 12.00, 95% CI: 1.72–83.80) were independent predictors of disease flare.ConclusionMale patients and those receiving tocilizumab at an extended dosing interval are at high risk of disease flare after discontinuation of concomitant methotrexate.Trial registration numberjRCTs041180071, UMIN000021247.     

甲状腺癌超声介导诊断及临床分期

目的 研究不同病理类型及相关亚型甲状腺癌的声像图特点,并将超声应用于甲状腺癌的临床分期,以实现对甲状腺癌患者术前合理评估、精确分期及个体化治疗.方法 收集2000年1月至2006年6月的甲状腺癌病例407例,分析比较不同病理类型及相关亚型甲状腺癌的声像图特征;同时,将超声应用于甲状腺癌的临床分期和个体化治疗.结果 1.根据不同病理类型甲状腺癌的临床生物学特征,结合其声像图特征,提出甲状腺癌的超声分型(Bus-TC typing),包括①经典型;②低分化型;③微小型;④弥漫硬化型;⑤髓样型;⑥不典型型.2.甲状腺乳头状癌可按其超声表现分为以下8型,包括①经典型;②微小型;③弥漫型;④囊性变型;⑤边缘型;⑥多灶型;⑦侵袭型;⑧合并桥本型.3.甲状腺癌颈部转移性淋巴结可依照其声像图特征分为5型,包括①囊性变型;②钙化型;③巨淋巴结型;④微小型;⑤侵袭型.4.超声诊断甲状腺癌T分期准确率为93.9%;NO期的准确率为86.1%;Nla期的准确率为80.O%;Nlb期的准确率为74.9%.术前超声检查可以发现51.5%的临床触诊漏诊的隐匿性转移淋巴结.结论 超声检查在甲状腺癌的临床诊断中具有独到的优势,对于甲状腺癌的合理评估、精确分期、及时治疗及颈部淋巴结的处理具有不可替代的价值.     

Ultrasonography of shoulders in spondyloarthritis and rheumatoid arthritis: A case-control study

IntroductionShoulders are often involved in spondyloarthritis (SpA) and rheumatoid arthritis (RA). The diagnosis of peripheral SpA and its differential diagnosis with RA could be challenging. A recent ultrasound study showed that ultrasonography (US) of the hands might differentiate psoriatic arthritis to RA. The aim of the study was to compare different US features in SpA, RA and healthy controls.MethodsA total of 38 SpA and 43 RA patients with clinical involvement of shoulders were included and compared to 33 controls. One blinded rheumatologist performed US examinations. The following items were assessed: gleno-humeral effusion, long-head biceps tendon tenosynovitis, subacromial and subdeltoid bursitis, acromio clavicular (AC) synovitis and humeral bone erosion.ResultsThirty-eight SpA (mean age: 49.9 ± 15.4 years, 58% of male), 43 RA patients (52.9 ± 16.6 years, 26% of male) and 33 controls (55.2 ± 16.9 years, 42% of male) were assessed. In comparison to RA, SpA patients had higher frequency of AC synovitis (66% vs 5%, P < 0.0001) but lower prevalence of subacromial and subdeltoid bursitis (39% vs 67%, P = 0.015), gleno-humeral effusion (5% vs 28%, P = 0.008) and humeral bone erosion (10% vs 56%, P < 0.0001). Unilateral abnormalities were found more frequently in SpA patients than in RA (64% vs 26%, P < 0.0001).ConclusionOur results suggest that AC synovitis is highly evocative of SpA in patients with inflammatory painful shoulders. Thus, US might help to diagnose SpA and to differentiate with RA.