不同剂量甲氨蝶呤联合不同剂量叶酸治疗活动期类风湿关节炎的临床研究

摘要 目的：探讨不同剂量甲氨蝶呤（MTX）联合不同剂量的叶酸治疗活动期类风湿关节炎（RA）的疗效与安全性。方法：选取100例符合纳入、排除标准的RA患者,按照28关节疾病活动指数（DAS28）分为高疾病活动度组（使用MTX 15 mg 每周1次）50例和低疾病活动度组（使用MTX 10 mg 每周1次）50例。高疾病活动度组按叶酸使用10 mg 每周1次 或5 mg 每周1次随机分为两组。低疾病活动度组按叶酸使用5 mg 每周1次或不使用随机分为两组,对比治疗6个月后的临床疗效和安全性。结果：治疗后,高疾病活动度叶酸5 mg组DAS28评分、视觉模拟评分量表（VAS）评分、血沉（ESR）、超敏C反应蛋白（hs-CRP）以及总有效率均优于叶酸10 mg组（P<0.05）,但是两组健康评定问卷（HAQ）评分、不良反应发生率和MTX浓度比较无明显差异（P>0.05）。低疾病活动度叶酸5 mg 组与无叶酸组患者治疗后hs-CRP、ESR、MTX浓度比较差异有统计学意义（P<0.05）,但是两组总有效率和不良反应发生率比较无明显差异（P>0.05）。结论：RA高疾病活动时,使用MTX 15 mg 每周1次联合叶酸5 mg 每周1次疗效更优,且不良反应发生率及MTX浓度变化不明显。RA低疾病活动时,MTX 10 mg 每周1次,与是否使用叶酸在疗效和安全性上无显著差异,但未使用叶酸患者的MTX浓度更高。     

类风湿性关节炎活动性病变MRI征象及其与FIB、FDP、D-D的相关性研究

摘要 目的：探讨类风湿性关节炎（RA）活动性病变磁共振成像（MRI）征象及其与纤维蛋白原（FIB）、纤维蛋白(原)降解产物（FDP）、D-二聚体（D-D）的相关性研究。方法：选取2020年1月-2021年2月期间我院诊治的61例RA患者,根据28个关节疾病活动指数（DAS28）评分将其分为活动组（35例）和稳定组（26例）。对比两组MRI征象,血清FIB、FDP、D-D水平。采用Spearman相关性分析RA活动期患者MRI各征象间的相关性及MRI各征象与血清FIB、FDP、D-D水平间的相关性。结果：活动组滑膜增厚或滑膜炎、骨髓水肿、软骨及骨侵蚀、腱鞘炎或周围软组织受累、关节腔积液征象人数占比均高于稳定组（P＜0.05）。活动组患者血清FIB、FDP、D-D水平均高于稳定组（P＜0.05）。Spearman相关性分析结果显示,RA活动期患者滑膜增厚或滑膜炎征象与骨髓水肿、软骨及骨侵蚀、关节腔积液征象均呈正相关（P＜0.05）,骨髓水肿征象与软骨及骨侵蚀征象呈正相关（P＜0.05）;RA活动期患者滑膜增厚或滑膜炎、骨髓水肿、关节腔积液征象与血清FIB、FDP、D-D水平均呈正相关（P＜0.05）,软骨及骨侵蚀征象与FIB呈正相关（P＜0.05）。结论：MRI征象可清晰显示RA患者的滑膜、骨质、关节腔及周围肌腱、软组织等异常改变,且MRI征象之间具有相关性,可在一定程度上反映RA的病理改变;血清FIB、FDP、D-D的检测有助于反映RA活动情况;MRI征象与血清FIB、FDP、D-D水平间具有相关性,二者联合应用有助于进一步评估RA活动情况。     

补肾通络汤联合甲氨蝶呤对类风湿关节炎患者炎症细胞因子、骨代谢标志物及血管新生相关因子的影响

摘要 目的：探究补肾通络汤联合甲氨蝶呤治疗类风湿关节炎患者的临床效果。方法：选取2017年9月到2018年6月我院收治并确诊的79例类风湿关节炎患者,按照随机数字表法将其分为对照组39例和研究组40例,对照组仅接受甲氨蝶呤治疗,研究组在对照组基础上联合补肾通络汤治疗,治疗3个月后比较临床疗效、炎症细胞因子、骨代谢标志物、血管新生相关因子水平、28个关节疾病活动度积分(DAS28)及不良反应。结果：研究组治疗总有效率为90.00%,明显高于对照组的71.79%（P＜0.05）;研究组治疗3个月后白细胞介素-1(IL-1)、白细胞介素-6(IL-6) 、肿瘤坏死因子-α(TNF-α)、骨碱性磷酸酶 (B-ALP)、碱性成纤维细胞生长因子（bFGF）、血管内皮生长因子（VEGF）水平以及DAS28积分均低于对照组（P＜0.05）;研究组治疗3个月后25羟维生素D［25( OH) D］、Ⅰ型前胶原羧基端前肽 (PICP)、甲状旁腺激素(PTH)、转化生长因子-β1（TGF-β1）水平高于对照组;研究组不良反应发生率为17.50%,与对照组的25.64%比较无差异（P＞0.05）。结论：补肾通络汤联合甲氨蝶呤治疗类风湿关节炎患者能够有效控制炎性反应,实现对骨代谢的调节,且能够对新生血管增生形成有效抑制,同时不会增加不良反应,值得推广应用。     

温针灸联合平衡针刀对椎动脉型颈椎病患者椎动脉血流、颈椎关节活动度及生活质量的影响

摘要 目的：探讨椎动脉型颈椎病（CSA）患者应用温针灸联合平衡针刀治疗对椎动脉血流、颈椎关节活动度及生活质量的影响。方法：选取首都医科大学附属北京中医医院于2020年1月-2023年1月收治的150例CSA患者,按治疗方案的不同进行分组,对照组（75例）行温针灸治疗,研究组（75例）行温针灸联合平衡针刀治疗,对比两组疗效、生活质量、颈椎关节活动度、颈椎功能、椎动脉血流指标。结果：研究组96.00%（72/75）治疗总有效率高于对照组81.33%（61/75）（P＜0.05）;研究组治疗后左椎动脉收缩期峰值血流速度、右椎动脉收缩期峰值血流速度高于对照组（P＜0.05）;研究组治疗后3周屈伸活动角度、旋转活动角度高于对照组（P＜0.05）;研究组治疗后1周、2周及3周NDI评分较对照组均更低（P＜0.05）;研究组治疗后健康调查简表（SF-36）各项评分高于对照组（P＜0.05）。结论：CSA应用温针灸联合平衡针刀治疗,可改善颈椎关节活动度,促进颈椎功能恢复,有利于椎动脉血流状况改善,并提高生活质量。     

痛风性关节炎急性期、缓解期超声特征及与血清IL-22、IL-37水平的相关性研究

摘要 目的：探讨痛风性关节炎（GA）急性期、缓解期超声特征及与血清白细胞介素（IL）-22、IL-37水平的相关性。方法：选取从2019年7月至2021年3月期间，在我院诊断为GA的患者64例作为痛风组，及同期在我院体检的健康志愿者32例作为正常对照组。经过超声检查、血清样品实验后，观察受试者的超声特征，比较受试者血清IL-22、IL-37的水平，采用Spearman检验分析GA患者血清IL-22、 IL-37水平与超声特征的相关性。比较超声特征、IL-22和IL-37水平单一或联合应用对GA急性期、缓解期的诊断价值。结果：痛风组急性期血清IL-22水平显著高于缓解期及正常对照组(P＜0.05)；痛风组急性期及缓解期血清IL-37水平均显著高于正常对照组，且缓解期高于急性期(P＜0.05)。64例GA患者中有29例存在痛风石；60例在急性期存在关节积液，至缓解期有22例吸收至正常积液量；有52例在急性期关节滑膜增生，至缓解期有14例得以缓解;有29例存在"双轨征"，仅1例在缓解期消失;有14例发生骨侵蚀，在缓解期均未见明显改善；缓解期积液厚度、滑膜厚度均明显小于急性期(P＜0.05)。无论急性期还是缓解期，GA患者血清IL-22水平与关节积液均呈正相关(P＜0.05)。超声检查联合血清IL-22、IL-37水平检测用于诊断无论在急性期还是缓解期，其敏感性及特异性均较高。结论：IL-22水平不论在急性期还是缓解期，与超声下关节积液均呈正相关。血清IL-22、IL-37检测与超声检查联合可提高急性期及缓解期GA的诊断效能。     

温针灸对寒湿痹阻型类风湿关节炎患者血清CXCR16、CCL19和TLR4/NF-κB信号通路的影响

摘要 目的：观察温针灸对寒湿痹阻型类风湿关节炎（RA）患者血清CXC趋化因子配体16（CXCR16）、趋化因子配体19(CCL19)和Toll样受体 4/核转录因子-κB（TLR4/NF-κB）信号通路的影响。方法：选择2020年6月~2022年6月期间佛山健翔骨伤医院收治的80例RA患者。按照随机数字表法将患者分为对照组（接受常规西医治疗,40例）和研究组（对照组的基础上结合温针灸治疗,40例）。对比两组评分[中医证候积分、28个关节疾病活动性评分（DAS28）]、实验室指标[RF、C反应蛋白（CRP）、红细胞沉降率（ESR）、抗环瓜氨酸抗体（抗CCP抗体）]、血清CXCR16、CCL19和TLR4/NF-κB信号通路相关指标的变化情况。结果：治疗后,两组中医证候积分、DAS28评分均下降,且研究组低于对照组,差异有统计学意义（P<0.05）。治疗后,两组类风湿因子（RF）、C反应蛋白（CRP）、红细胞沉降率（ESR）、抗环瓜氨酸抗体（抗CCP抗体）下降,且研究组低于对照组,差异有统计学意义（P<0.05）。治疗后,两组CXCR16、CCL19下降,且研究组低于对照组,差异有统计学意义（P<0.05）。治疗后,两组TLR4信使核糖核酸（mRNA）、NF-κB mRNA下降,且研究组低于对照组,差异有统计学意义（P<0.05）。结论：温针灸能够显著改善寒湿痹阻型RA患者的临床症状,调节血清CXCR16、CCL19水平,同时还可抑制TLR4/NF-κB信号通路激活。     

枸橼酸托法替布片联合仙灵骨葆胶囊对类风湿性关节炎合并骨质疏松患者血清炎症细胞因子、骨强度及骨代谢水平影响

摘要 目的：探讨枸橼酸托法替布片联合仙灵骨葆胶囊对类风湿性关节炎（RA）合并骨质疏松患者血清炎症细胞因子、骨强度及骨代谢水平影响。方法：纳入2021年8月至2022年8月期间徐州医科大学附属连云港医院诊治的80例RA合并骨质疏松患者。根据随机数字表法将患者分为对照组（雷公藤多苷片联合仙灵骨葆胶囊治疗）和实验组（枸橼酸托法替布片联合仙灵骨葆胶囊治疗）,各为40例。对比两组疗效、炎症细胞因子、骨强度及骨代谢指标,观察两组不良反应发生率。结果：实验组的临床总有效率高于对照组（P<0.05）。实验组治疗后巨噬细胞集落刺激因子（M-CSF）、白细胞介素-1β（IL-1β）、环氧合酶-2（COX-2）低于对照组同期（P<0.05）。实验组治疗后横截面积（CSA）、横截面转动惯量（CSMI）、截面系数（Z）、皮质厚度（CT）高于对照组同期（P<0.05）。实验组治疗后骨钙素N端中分子（N-MID）、总Ⅰ型胶原氨基端延长肽（T-PINP）、骨钙素（BGP）、Ⅰ型胶原羧基端前肽（PICP）高于对照组同期,β-胶原降解产物（β-CTX）低于对照组同期（P<0.05）。两组治疗后腰椎骨密度和股骨颈骨密度较治疗前升高,且实验组高于对照组同期（P<0.05）。两组治疗后血沉（ESR）、C反应蛋白（CRP）、类风湿关节炎患者病情（DAS28）评分下降,且实验组低于对照组同期（P<0.05）。两组不良反应发生率组间对比无统计学差异（P>0.05）。结论：枸橼酸托法替布片联合仙灵骨葆胶囊应用于RA合并骨质疏松患者,可有效调节骨代谢水平,增强骨强度,降低血清炎症细胞因子水平。     

腺苷脱氨酶及同工酶对自身免疫病诊断和病情监测的作用

摘要 目的：检测腺苷脱氨酶(ADA)及其同工酶在自身免疫病患者血清中的变化,探讨其诊断和病情监测作用。方法：收集70例系统性红斑狼疮（SLE）、114例类风湿性关节炎(RA)、55例强直性脊柱炎(AS)、及其年龄性别对应的健康血清标本。测定血清总ADA（tADA）、ADA1及ADA2活性。ROC曲线分析其诊断价值。结果：与健康对照相比,ADA活性在SLE患者血清中显著升高[tADA：15（12,20）vs 8（7,10）U/L;ADA1：3.5（2,5）vs 3（2,3）U/L;ADA2：11（8,15）vs 6（5,7）U/L;P<0.01）]。与健康对照相比,RA患者血清中tADA和ADA1活性无显著变化(P>0.05),ADA2活性水平升高[8（5.25,10）vs 7（5,9）U/L,P<0.05）];与健康对照相比,AS患者血清中tADA和ADA1活性无显著变化(P>0.05),ADA2活性升高[7（5,9）vs 6（5,7）U/L,P<0.05）]。ROC分析显示tADA及ADA2对SLE具有较好诊断价值（tADA：88.6%特异性、77.1%敏感性;ADA2：92.9%特异性、68.6%敏感性）。ADA活性对RA及AS患者无诊断价值。spearman相关性分析显示,tADA活性与SLE患者疾病活动度有一定正相关性（r=0.303,P=0.011)。结论：血清tADA活性检测可作为SLE辅助诊断和病情监测指标。     

超声引导下隐神经联合IPACK阻滞对老年全膝关节置换术患者应激反应、炎性细胞因子及膝关节活动度的影响

摘要 目的：探讨超声引导下隐神经联合腘动脉与膝关节后囊间隙（IPACK）阻滞对老年全膝关节置换术（TKA）患者应激反应、炎性细胞因子及膝关节活动度的影响。方法：根据随机数字表法,将无锡市中医医院2021年3月~2022年9月期间收治的102例初次行TKA的老年患者分为观察组（超声引导下隐神经联合IPACK阻滞镇痛处理）和对照组（超声引导下隐神经镇痛处理）,每组各51例。对比两组疼痛情况、炎性细胞因子、应激反应指标、不良反应发生率、膝关节活动度。结果：观察组术后6 h、术后12 h、术后24 h视觉模拟评分法（VAS）评分低于对照组（P<0.05）。观察组术后48 h肿瘤坏死因子-α（TNF-α）、白细胞介素（IL）-6、IL-1β、β-淀粉样蛋白（Aβ）低于对照组（P<0.05）。观察组术后48 h血管紧张素Ⅱ（AngⅡ）、皮质醇（COR）低于对照组（P<0.05）。观察组术后24 h、术后48 h膝关节活动度大于对照组（P<0.05）。两组不良反应发生率对比无差异（P>0.05）。结论：超声引导下隐神经联合IPACK阻滞用于TKA患者,具有较好的镇痛效果,可减轻应激反应,抑制炎性细胞因子过度分泌,改善膝关节活动度,麻醉效果较好。     

微型钢板内固定与克氏针内固定治疗掌指关节周围骨折临床疗效的回顾性研究

摘要 目的：对比掌指关节周围骨折采用克氏针内固定或微型钢板内固定治疗后的临床疗效。方法：回顾性分析2019年8月~2022年12月期间江南大学附属医院收治的掌指关节周围骨折97例患者的临床资料。按照不同的内固定方式将患者分为A组（克氏针内固定治疗,47例）和B组（微型钢板内固定,50例）。对比两组治疗指标[手术时间、骨折愈合时间、住院时间、功能锻炼开始时间]、术后指标[指关节总活动度、手总主动活动度评分]、手功能[手指总主动屈曲度量表（TAFS）评分]、手部疼痛,同时观察两组术后并发症发生情况。结果：B组的功能锻炼开始时间、骨折愈合时间均短于A组,手术时间长于A组（P<0.05）,两组住院时间组间对比无差异（P>0.05）。B组的指关节总活动度大于A组,手总主动活动度评分高于A组（P<0.05）。治疗3个月后,两组手部疼痛视觉模拟量表（VAS）评分下降,且B组低于A组（P<0.05）。B组手功能TAFS评分优良率为92.00%,高于A组74.47%（P<0.05）。B组的术后并发症发生率低于A组（P<0.05）。结论：相对于克氏针内固定治疗,微型钢板内固定治疗掌指关节周围骨折,可缩短愈合时间、功能锻炼开始时间,提高手功能,指关节总活动度以及手总主动活动度评分,减轻手疼痛,降低并发症发生率,但其手术时间更长。     

Serum calprotectin (S100A8/9): an independent predictor of ultrasound synovitis in patients with rheumatoid arthritis

IntroductionCalprotectin, a heterodimeric complex of S100A8/9 (MRP8/14), has been proposed as an important serum biomarker that reflects disease activity and structural joint damage in rheumatoid arthritis (RA). The objective of this cross-sectional study was to test the hypothesis that calprotectin is associated with clinical and ultrasound-determined disease activity in patients with RA.MethodsA total of 37 patients with RA (including 24 females, a mean disease duration of 20 months) underwent a clinical examination and 7-joint ultrasound score (German US-7) of the clinically dominant hand and foot to assess synovitis by grey-scale (GS) and synovial vascularity by power Doppler (PD) ultrasound using semiquantitative 0–3 grading. The levels of serum calprotectin and C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were determined at the time of the ultrasound assessment. We analysed the relationship between serum calprotectin level, traditional inflammatory markers, and ultrasound-determined synovitis.ResultsThe levels of serum calprotectin were significantly correlated with swollen joint count (r = 0.465, p < 0.005), DAS28-ESR (r = 0.430, p < 0.01), ESR (r = 0.370, p < 0.05) and, in particular, CRP (r = 0.629, p < 0.001). Calprotectin was significantly associated with GS (r = 0.359, p < 0.05) and PD synovitis scores (r = 0.497, p < 0.005). Using multivariate regression analysis, calprotectin, adjusted for age and sex, was a better predictor of PD synovitis score (R² = 0.765, p < 0.001) than CRP (R² = 0.496, p < 0.001).ConclusionsThe serum levels of calprotectin are significantly associated with clinical, laboratory and ultrasound assessments of RA disease activity. These results suggest that calprotectin might be superior to CRP for monitoring ultrasound-determined synovial inflammation in RA patients.     

Ultrasonographic assessment reveals detailed distribution of synovial inflammation in Blau syndrome

Introduction

Arthritis is the most frequent manifestation of Blau syndrome, an autoinflammatory disorder caused by the genetic mutation of NOD2. However, detailed information on arthritis in Blau syndrome on which the therapeutic strategy should be based on is lacking. This multi-center study aimed to accurately characterize the articular manifestation of Blau syndrome and also to demonstrate the utility of musculoskeletal ultrasound in Blau syndrome.

Methods

Patients who had been diagnosed with Blau syndrome by genetic analysis of NOD2 were recruited. A total of 102 synovial sites in 40 joints were assessed semiquantitatively by ultrasound for gray-scale synovitis and synovial power Doppler (PD) signal.

Results

In total, 10 patients whose age ranged from 10 months to 37 years enrolled in this study. Although only 4 joints (0.8%) were tender on physical examination, 81 joints (16.9%) were clinically swollen. Moreover, 240 (50.0%), and 124 (25.8%) joints showed gray-scale (GS) synovitis and synovial PD signal on ultrasound, respectively. Importantly, GS synovitis was present in 168 out of 399 non-swollen joints, in which 61 also exhibited synovial PD signal. Among 40 joint regions, the ankle, the wrist, and the proximal interphalangeal joints were the most frequently and severely affected joints. Comparisons between different synovial tissues demonstrated a significantly higher proportion of the joints with tenosynovitis as compared with that with intra-articular synovitis (41.5% versus 27.9%, P < 0.0001). In respect of age and treatment, synovial PD signals were minimal in the youngest patient and in the oldest two patients, and were relatively mild in patients receiving treatment with methotrexate plus TNF antagonists. In two patients who underwent the second ultrasound examination, total PD scores markedly decreased after initiating the treatment with a tumor necrosis factor (TNF) antagonist.

Conclusions

The detailed information on synovial inflammation obtained by ultrasound confirms the dissociation between pain and inflammation and the frequently involved joint regions and synovial tissue in the arthritis of Blau syndrome. Our data also demonstrate that ultrasonography can be a potent tool in monitoring the activity of synovial inflammation and in investigating the pathophysiology of arthritis in this rare but archetypical autoinflammatory condition.     

Ultrasound power Doppler synovitis is associated with plasma IL-6 in established rheumatoid arthritis

Background and objective: Cytokines have an important role in the pathogenesis of rheumatoid arthritis (RA). Although plasma levels of IL-6 have been related to musculoskeletal ultrasound (MSUS) synovitis in early DMARD-naïve RA, there are no similar studies in established disease. Methods: 64 RA patients treated with non-biological DMARDs and 30 healthy controls were included in this prospective cross-sectional study. A blood sample was taken before evaluation of disease activity (DAS28) and ultrasonography (all tests performed in a blinded fashion). MSUS was performed by one of two ultrasound-trained rheumatologists on 10 joints of both hands. Gray scale (GS) and pD (power Doppler) synovitis were evaluated using a semi-quantitative scale (0–3) in individual joints, and their sum (score 10) was calculated. Plasma cytokines (IL-2, IL-4, IL-6, IL-10, IL-17, TNF, IFN-γ, and VEGF) were quantified by flow cytometry. Results: Levels of all cytokines, excepting VEGF, were significantly higher in RA patients than in controls (P ⩽ 0.05). In RA patients, IL-6, but not other cytokines, correlated positively with DAS28 and swollen joint count (P ⩽ 0.01), as well as with 10-joint pD score, and GS and pD of both wrists (P < 0.01 for all tests). In multiple linear regression, the association of IL-6 with 10-joint pD score was maintained even after adjustment for DAS28. However, there was no correlation of IL-6 with tender joint count, 10-joint GS score, or presence of erosions. Conclusion: We demonstrated an association of inflammatory findings on MSUS and plasma IL-6 independently of DAS28 in established RA.     

Low-dose oral prednisone improves clinical and ultrasonographic remission rates in early rheumatoid arthritis: results of a 12-month open-label randomised study

IntroductionIn early rheumatoid arthritis (RA), low-dose oral prednisone (PDN) co-medication yields better clinical results than monotherapy with disease-modifying anti-rheumatic drugs (DMARDs). In addition, ultrasonography (US) evaluation reveals rapid and significant effects of glucocorticosteroids on subclinical synovitis. No data currently exist that examine the clinical and US results offered by glucocorticoid co-medication over DMARD monotherapy in early RA patients.MethodsTwo hundred and twenty patients with early RA (< 1 year from clinical onset) were treated according to a low disease activity (LDA) targeted step-up protocol including methotrexate (MTX) and, in the active treatment arm, low-dose (6.25 mg/day) oral PDN over 12 months. Clinical disease activity measures were collected at baseline, 2, 4, 6, 9 and 12 months, and US examination of hands was performed at baseline, 6 and 12 months. Grey-scale and power Doppler (PD) synovitis were scored (0 to 3) for each joint. At 12 months, clinical remission according to the disease activity score among 28 joints was defined as the clinical outcome, and a total joint PD score of 0 (PD negativity) as the imaging outcome.ResultsEach group included 110 patients with comparable demographic, clinical, laboratory and US characteristics. At 12 months, the LDA rate was similar in the two groups, whilst the clinical remission rate (risk ratio = 1.61 (95% confidence interval = 1.08, 2.04)) and PD negativity rate (risk ratio = 1.31 (95% confidence interval = 1.04, 1.64)) were significantly higher in the MTX+PDN group.ConclusionIn early RA, despite a similar response rate in terms of LDA, low-dose oral PDN co-medication led to a higher proportion of clinical remission and PD negativity compared with MTX monotherapy, thus ensuring a better disease activity control.

Trial registration number

Current Controlled Trials ISRCTN2486111     

Aldolase predicts subsequent myopathy occurrence in systemic sclerosis

Introduction

In early rheumatoid arthritis (RA), low-dose oral prednisone (PDN) co-medication yields better clinical results than monotherapy with disease-modifying anti-rheumatic drugs (DMARDs). In addition, ultrasonography (US) evaluation reveals rapid and significant effects of glucocorticosteroids on subclinical synovitis. No data currently exist that examine the clinical and US results offered by glucocorticoid co-medication over DMARD monotherapy in early RA patients.

Methods

Two hundred and twenty patients with early RA (< 1 year from clinical onset) were treated according to a low disease activity (LDA) targeted step-up protocol including methotrexate (MTX) and, in the active treatment arm, low-dose (6.25 mg/day) oral PDN over 12 months. Clinical disease activity measures were collected at baseline, 2, 4, 6, 9 and 12 months, and US examination of hands was performed at baseline, 6 and 12 months. Grey-scale and power Doppler (PD) synovitis were scored (0 to 3) for each joint. At 12 months, clinical remission according to the disease activity score among 28 joints was defined as the clinical outcome, and a total joint PD score of 0 (PD negativity) as the imaging outcome.

Results

Each group included 110 patients with comparable demographic, clinical, laboratory and US characteristics. At 12 months, the LDA rate was similar in the two groups, whilst the clinical remission rate (risk ratio = 1.61 (95% confidence interval = 1.08, 2.04)) and PD negativity rate (risk ratio = 1.31 (95% confidence interval = 1.04, 1.64)) were significantly higher in the MTX+PDN group.

Conclusion

In early RA, despite a similar response rate in terms of LDA, low-dose oral PDN co-medication led to a higher proportion of clinical remission and PD negativity compared with MTX monotherapy, thus ensuring a better disease activity control.

Trial registration number

Current Controlled Trials ISRCTN2486111     

Is Ultrasound a Better Target than Clinical Disease Activity Scores in Rheumatoid Arthritis with Fibromyalgia? A Case-Control Study

Objectives

Our goal is to study the correlations among gray-scale seven-joint ultrasound score (GS-US7), power Doppler seven-joint ultrasound score (PD-US7), disease activity score-28 joints (DAS28), simplified disease activity index (SDAI) and clinical disease activity index (CDAI) in patients with and without fibromyalgia (FM).

Methods

A matched case-control study included all patients consecutively seen in the Rheumatoid Arthritis (RA) Clinic. Participants were allocated into one of two groups: RA with FM and RA without FM. Ultrasound (US) and clinical scoring were blinded for the presence of FM. Medians and proportions were compared by Mann-Whitney’s test and McNemar’s test, respectively. Spearman’s rank correlation coefficients (r_s) were calculated among clinical and US scores and differences were tested by r-to-z transformation test.

Results

Seventy-two women were included, out of 247 RA patients, mostly white, with median (IQR) age of 57.5 (49.3–66.8) years, with RA symptoms for 13.0 (6.0–19.0) years and FM symptoms for 6.0 (2.0–15.0) years. Disease-modifying antirheumatic drugs, non-steroidal anti-inflammatory drugs and prednisone use was comparable between groups. Objective activity parameters were not different between groups. RA patients with FM had greater DAS28, SDAI and CDAI but similar GS-US7 and PD-US7. GS-US7 correlated with DAS28, SDAI and CDAI in patients with and without FM (r_s = 0.36–0.57), while PD-US7 correlated with clinical scores only in patients without FM (r_s = 0.35–0.38).

Conclusion

To our knowledge, this is the first study to demonstrate that ultrasound synovitis scores are not affected by FM in RA patients. PD-US7 performed better than GS-US7 in long-standing RA patients with DAS28, SDAI or CDAI allegedly overestimated due to FM. Since sonographic synovitis predicts erosion better than swollen joint count, C-reactive protein and erythrocyte sedimentation rate, US should be considered a promising treatment target in RA patients with FM.     

Serum levels of CXCL13 are associated with ultrasonographic synovitis and predict power Doppler persistence in early rheumatoid arthritis treated with non-biological disease-modifying anti-rheumatic drugs

Introduction

Biological markers specifically reflecting pathological processes may add value in the assessment of inter-individual variations in the course of rheumatoid arthritis (RA). The current study was undertaken to investigate whether baseline serum levels of the chemokine CXCL13 might predict clinical and ultrasonographic (US) outcomes in patients with recent-onset RA.

Methods

The study included 161 early RA patients (disease duration < 12 months) treated according to a disease activity score (DAS) driven step-up protocol aiming at DAS < 2.4. Clinical disease activity measures were collected at baseline, 2, 4, 6, 9 and 12 months, and US examination of the hands was performed at baseline, 6 and 12 months. Grey-Scale (GS) and Power Doppler (PD) synovitis were scored (0 to 3), with overall scores as the sum of each joint score. CXCL13 levels were measured at baseline by enzyme-linked immunosorbent assay and evaluated in relation to the achievement of low disease activity (LDA, DAS < 2.4) and US residual inflammation (PD ≤ 1) at 12 months.

Results

Baseline levels of CXCL13 were significantly higher in RA compared to healthy controls (n = 19) (P = 0.03) and correlated with measures of synovitis, such as the swollen joint count (R 0.28, P < 0.001), the US-GS (R 0.27, P = 0.003) and US-PD (R 0.26, P = 0.005) score. Although CXCL13 did not predict the likelihood of achieving clinical LDA at 12 months within a structured treat-to-target protocol, elevated levels of CXCL13 were associated with more frequent increases of methotrexate dosage (P < 0.001). Using adjusted analyses, the highest levels of CXCL13 (> 100 pg/ml) were the only independent predictor of residual imaging inflammation (P = 0.005), irrespective of initial US-PD scores, disease activity status, acute phase reactants and autoantibodies. Among the patients in clinical LDA at 12 months, US-PD scores ≤ 1 were less frequently achieved in the high baseline CXCL13 (> 100 pg/ml) group, with an adjusted OR = 0.06 (95% CI 0.01 to 0.55, P = 0.01).

Conclusions

CXCL13 emerges as a new biological marker in early RA, accurate in assessing the severity of synovitis and the persistence of US-PD activity over time in response to conventional treatments.     

类风湿关节炎拇长屈肌腱病变的超声特点

目的:总结类风湿关节炎(RA)患者拇长屈肌腱(FHL)病变的超声特点及二者间的相关性。方法:回顾性分析2010年2月至2011年6月因足部疼痛于我院就诊的60例(120足)RA患者资料。应用彩色多普勒超声诊断仪探查拇长屈肌腱,根据超声探查拇长屈肌腱病变情况的结果将患者分为3组:肌腱完整组(A组,45足),肌腱周围炎症组(B组,49足),肌腱断裂组(C组,26足)。对拇长屈肌腱病变的特点及部位进行描述,并将拇长屈肌腱病变严重程度与患者年龄及病程进行相关性分析。结果:45足肌腱完整,49足出现不同部位的肌腱周围炎症(内踝转折处17足,henrry’s结节处11足,第一跖趾关节跖侧21足),26足发生肌腱断裂(9足发生于内踝转折处,17足发生于跖趾关节跖侧)。肌腱病变的发生率71%。A组平均年龄49.9±9.2岁,病程4.7±2.6年;B组平均年龄56.2±9.2岁,病程16.2±7.4年;C组平均年龄54.7±8.0岁,病程20.9±4.4年。三组间上述参数差异具有统计学意义(P0.05)。结论:拇长屈肌腱是类风湿关节炎足部结构的常见受累部位,其病变多发生于内踝转折处,henrry's结节处及第一跖趾关节跖侧,但henrry’s结节处的断裂少见。在对类风湿关节炎平足患者进行肌腱转位手术时,应充分考量拇长屈肌腱的病变。     

Three Groups in the 28 Joints for Rheumatoid Arthritis Synovitis – Analysis Using More than 17,000 Assessments in the KURAMA Database

Rheumatoid arthritis (RA) is a joint-destructive autoimmune disease. Three composite indices evaluating the same 28 joints are commonly used for the evaluation of RA activity. However, the relationship between, and the frequency of, the joint involvements are still not fully understood. Here, we obtained and analyzed 17,311 assessments for 28 joints in 1,314 patients with RA from 2005 to 2011 from electronic clinical chart templates stored in the KURAMA (Kyoto University Rheumatoid Arthritis Management Alliance) database. Affected rates for swelling and tenderness were assessed for each of the 28 joints and compared between two different sets of RA patients. Correlations of joint symptoms were analyzed for swellings and tenderness using kappa coefficient and eigen vectors by principal component analysis. As a result, we found that joint affected rates greatly varied from joint to joint both for tenderness and swelling for the two sets. Right wrist joint is the most affected joint of the 28 joints. Tenderness and swellings are well correlated in the same joints except for the shoulder joints. Patients with RA tended to demonstrate right-dominant joint involvement and joint destruction. We also found that RA synovitis could be classified into three categories of joints in the correlation analyses: large joints with wrist joints, PIP joints, and MCP joints. Clustering analysis based on distribution of synovitis revealed that patients with RA could be classified into six subgroups. We confirmed the symmetric joint involvement in RA. Our results suggested that RA synovitis can be classified into subgroups and that several different mechanisms may underlie the pathophysiology in RA synovitis.