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吴振彪

乌镇互联网医院

擅长对疑难危重风湿病如系统性红斑狼疮,类风湿关节炎,脊柱关节炎,血管炎,硬皮病,干燥综合征,肌炎,肺动脉高压及变态反应性疾病、免疫功能低下、病毒性肝炎等的诊治。

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发热作为SpA首发表现的回顾性研究

编者:韩青,西京医院临床免疫科 目 的用脊柱关节炎国际协会评估(ASAS)分类标准评估成人脊柱关节炎(SpA)以发热为首发表现的临床特征。方 法本研究回顾性分析2010年1月至2016年5月在韩国首尔Severance医院住院患者的电子病历。作为对照组,还招募了100个SpA的患者。比较两组患者的临床特征和实验室结果。结 果 26例SpA患者首发症状为发热(反应性关节炎50%,未分化SpA26.9%,AS15.4%,炎性肠病关节炎3.8%,银屑病性关节炎3.8%)。外周型SpA患者中发热患者比对照组更为常见(65.4% vs 24.0%,p < 0.001)。发热型SpA患者HLA- B27阳性率低于对照组患者(52.2% vs 77.0%,p < 0.05)。基线期发热型SpA患者系统性炎症标记物明显升高(白细胞计数11.57 vs 7.81cell/μL,p < 0.001;血沉69.2 vs 41.0 mm/ h,p<0.001;c-反应蛋白109.6 vs 15.3 mg/ L,p <0.001)。发热型SpA患者中,使用类固醇治疗的患者比例明显高(57.7% vs 11.0%,p < 0.001)。发热型SpA患者中就诊于风湿病专科的患者比例明显低于对照组(7.7%与59.0%,p < 0.001)。结 论SpA的各种亚型均可以发热为首发症状,发热型SpA患者全身炎症表现突出,早期就诊风湿科的概率较低。当评估发热型患者同时具备SpA任一临床特征时,临床医生应该考虑以SpA为主进行评估,包括HLA-B27或骶髂关节放射学的检查。 参考文献:Fever as an initialmanifestation of spondyloarthritis: A retrospective study.ByunSJ.et alAbstractOBJECTIVES:We aimed to evaluatea wide spectrum of clinical features of adult patients with spondyloarthritis(SpA) whose initial manifestation was fever, using the Assessment ofSpondyloArthritis international Society (ASAS) classification criteria.METHODS:We retrospectivelycollected the electronic medical records of hospitalized SpA patients whoinitially presented to the Severance Hospital (Seoul, Korea) with fever fromJanuary 2010 to May 2016. As a control group, we also recruited one-hundredconsecutive patients who were diagnosed with SpA in our outpatient clinic.Clinical features and laboratory findingswere compared in two patient groups.RESULTS:There were 26patients who had fever as initial presentation of SpA (reactive arthritis 50%,undifferentiated SpA 26.9%, ankylosing spondylitis 15.4%,enteropathic arthritis 3.8%, psoriatic arthritis 3.8%). Peripheral SpA was morecommon in febrile SpA patients than in control SpA patients (65.4% vs 24.0%,p<0.001). Febrile SpA patients were less frequently HLA-B27 positive thancontrol SpA patients (52.2% vs 77.0%, p<0.05). At baseline, systemicinflammatory markers were significantly higher in the febrile SpA patients(white blood cell count, 11.57 vs 7.81 cells/μL, p<0.001; erythrocytesedimentation rate, 69.2 vs 41.0 mm/h, p<0.001; C-reactive protein, 109.6 vs15.3 mg/L, p<0.001). The proportion of patients treated with systemicsteroids was significantly higher in febrile SpA patients (57.7% vs. 11.0%,p<0.001). The proportion of patients who visited rheumatology specialty wassignificantly lower in febrile SpA patients than in control SpA patients (7.7%vs 59.0%, p<0.001).CONCLUSION:Various subgroups ofSpA can be presented with fever as an initial manifestation. Febrile SpApatients demonstrated higher systemic inflammation and a lower chance to visitrheumatology in early stage. When evaluating febrile patients with any clinicalfeatures of SpA, clinicians are advised to consider performing SpA-focusedevaluation including HLA-B27 or a simple sacroiliac joint radiograph.PLoS One. 2017 Sep 14;12(9):e0184323.

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在2018年,狼疮中肠道的菌群的角色,我们有知道多少?

翻译者:赵倩倩,西京医院临床免疫科人类肠道微生物群在维持健康生理状况中的作用以及其与疾病发展的关系仍有待澄清。目前的证据表明,肠道微生物可能参与自身免疫性疾病的发生和发展,包括类风湿关节炎和系统性红斑狼疮(SLE)。尽管最近在了解这些微生物如何影响狼疮的病理生理学方面取得了进展,但研究仍然有限。涵盖的领域:在这篇综述中,我们试图总结最相关的研究结果,这些研究结果有助于我们理解人类肠道微生物群与狼疮发展之间的联系。我们还描述了个体微生物参与者在狼疮生理学中的潜在作用,以及它们如何塑造相关的免疫反应。专家评论:基于大规模测序的独立于培养的技术是解开肠道微生物生物活性的有力工具。目前的数据表明,根据肠道微生物的模式或特定细菌的存在,可以触发与狼疮生理学相关的不同反应。 粪便微生物群移植,活体生物治疗或针对微生物群的饮食干预可能会成为SLE的治疗方法。参考文献:The role of gut microbiota in lupus: what we knowin 2018?The role of the human intestinalmicrobiota in the maintenance of a healthy physiological condition, as well asits relation to the development of disease, remains to be clarified. Currentevidence suggests that intestinal microbes could be involved in the initiationand amplification of autoimmune diseases, including rheumatoid arthritis and systemiclupus erythematosus (SLE). Despite recent progress in understanding how thesemicrobes influence the pathophysiology of lupus, studies are still limited.Areas covered: In this review, we have tried to summarize the most relevantfindings that have contributed to our understanding of the links between thehuman intestinal microbiota and the development of lupus. We also describe thepotential role of individual microbial players in the physiology of lupus, andhow they can shape relevant immune responses. Expert commentary:Culture-independent techniques based on massive sequencing represent a powerfultool to unravel the biological activity of gut microbes. Current datademonstrates that, depending on the pattern of intestinal microorganisms or thepresence of specific bacteria, different responses related to lupus physiologycan be triggered. Fecal microbiota transplantation, live biotherapeutics, ordietary interventions targeting the microbiota will likely become a treatmentfor SLE.

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甲襞毛细血管镜检查-应检查多少根手指?

翻译者:符亚璐,西京医院临床免疫科目  的:风湿病专科医生在诊断系统性硬化症时越来越多地使用甲襞毛细血管镜检查。然而,在繁忙的门诊对所有甲周进行评估可能非常耗时。我们的研究目的是临床医生应该常规评估多少(或哪些)手指以准确捕捉真实病情。方  法:来自173名参与者(101名系统性硬化症,22名原发雷诺症和50名健康对照)的1600张图像(由国际专家观察小组)共计2994次评估纳入该分析。然后测试7个单指或手指组合(来自中指和无名指)对毛细血管两个指标异常[大毛细血管存在和系统性硬化等级(早期,活动或晚期)]的敏感性,并与八个手指相比较。结  果:对于八指检测,和诊断标准相比,敏感性为74.6%。仅检查一个手指的灵敏度较低(从31.7%到左46.6%)。检查两个无名指是59.8%的灵敏度,而检查两个环指和中指的四指组合给出66.7%的灵敏度。结  论:在常规毛细血管镜检查期间,理想情况下应检查所有八个甲床(不包括拇指),否则会遗漏一些异常情况。仅检查四个手指会降低毛细血管镜检查的灵敏度。参考文献:Rheumatology (Oxford). 2018 Sep 21. doi:10.1093/rheumatology/key293. [Epub ahead of print]Nailfoldcapillaroscopy-how many fingers should be examined to detect abnormality?

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类风湿关节炎与粘膜起源假说:保护转化为破坏

编译者:李英,西京医院临床免疫科摘  要  血清中存在高信息量和预测性的RA相关自身抗体,特别是抗瓜氨酸蛋白抗体(ACPAS)的存在,可为类风湿关节炎(RA)的高风险患者进行翻译研究和疾病预防研究。在无关节炎的血清学阳性个体中,已证实存在与局部ACPA产生相关的黏膜炎症过程。在其他高危人群中,即使没有血清自身抗体,也存在与RA相关的自身抗体产生。此外,有一部分处于危险中的个体在肺中表现出局部粘膜ACPA的产生,以及X线小气道疾病、痰液高细胞性和增加中性粒细胞胞外陷阱的形成。在高危人群中的其他粘膜部位也表现出自身抗体的产生、炎症和/或失调的迹象。由于表现出这种局部炎症相关ACPA产生的个体比例大大高于个体发展为未来RA的可能性,这一发现提出了黏膜ACPA具有生物学相关性保护作用的假设。找出促进外部聚焦的粘膜ACPA产生和丢失的机制,促进全身自身抗体的表达,最终促进关节炎的发展,将为预防RA的新治疗方法提供深入的见解。关键点  最终发展为血清阳性类风湿关节炎(RA)的患者会经历一段时期RA相关的自身抗体阳性,这与细胞因子和趋化因子水平的增加有关。不同的黏膜过程会影响全身免疫和自身免疫的发展。对RA的未来发展有很高风险的个体显示出慢性系统性炎症和黏膜炎症的证据。免疫球蛋白A(IgA)抗瓜氨酸蛋白抗体(ACPA)通常是在局部产生的,而不是反映瓜氨酸抗原耐受性的丧失;系统性IgG反应可能是由于外部聚焦的分隔丧失所致。目前正在进行的研究将黏膜失调、炎症和自身抗体产生的发展与系统性自身免疫的下一个发展阶段联系起来。新的自身免疫促进过程很可能在RA的临床前阶段主要或完全发挥作用,并可能成为新的预防策略的目标。 参考文献:Review Article | Published: 15 August 2018Rheumatoidarthritis and the mucosal origins hypothesis: protection turnsto destructionV. Michael Holers, M. Kristen Demoruelle, Kristine A. Kuhn, Jane H. Buckner, William H. Robinson, Yuko Okamoto, Jill M. Norris & Kevin D. DeaneNature Reviews Rheumatologyvolume 14, pages542–557 (2018)AbstractIndividuals at high risk of developing seropositiverheumatoid arthritis (RA) can be identified for translational research anddisease prevention studies through the presence of highly informative andpredictive patterns of RA-related autoantibodies, especially anti-citrullinatedprotein antibodies (ACPAs), in the serum. In serologically positive individualswithout arthritis, designated ACPA positive at risk, the presence of mucosalinflammatory processes associated with the presence of local ACPA productionhas been demonstrated. In other at-risk populations, local RA-relatedautoantibody production is present even in the absence of serum autoantibodies.Additionally, a proportion of at-risk individuals exhibit local mucosal ACPAproduction in the lung, as well as radiographic small-airway disease, sputumhypercellularity and increased neutrophil extracellular trap formation. Othermucosal sites in at-risk individuals also exhibit autoantibody production,inflammation and/or evidence of dysbiosis. As the proportion of individuals whoexhibit such localized inflammation-associated ACPA production is substantiallyhigher than the likelihood of an individual developing future RA, this findingraises the hypothesis that mucosal ACPAs have biologically relevant protectiveroles. Identifying the mechanisms that drive both the generation and loss ofexternally focused mucosal ACPA production and promote systemic autoantibodyexpression and ultimately arthritis development should provide insights intonew therapeutic approaches to prevent RA.Key pointsPatients who eventually developseropositive rheumatoid arthritis (RA) pass through a period of RA-relatedautoantibody positivity that is associated with increased levels of cytokinesand chemokines.Various mucosal processes can influence thedevelopment of systemic immunity and autoimmunity.Individuals who are at high risk of thefuture development of RA demonstrate evidence of chronic systemic and mucosalinflammation.Rather than reflecting a loss ofcitrullinated antigen tolerance, immunoglobulin A (IgA) anti-citrullinatedprotein antibodies (ACPAs) are normally produced locally; a systemic IgGresponse likely results from loss of externally focused compartmentalization.Ongoing studies are linking the developmentof mucosal dysbiosis, inflammation and autoantibody production to the nextstages of development of systemic autoimmunity.Novel autoimmune-promoting processes arelikely to be identified that function primarily, or exclusively, in thepreclinical period of RA and could be the targets for new preventionstrategies.

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IL-23-IL-17通路对脊柱关节炎患者骨的影响

编译者:牛敏,西京医院临床免疫科摘  要  在过去的几年中,IL-23-IL-17通路在人类疾病中的病理生理作用已经被确定。IL-23主要由活化的髓样细胞产生,而IL-17主要由T细胞和固有淋巴细胞产生。有几条证据支持IL-23-IL-17通路在银屑病性关节炎(PsA)和强直性脊柱炎(AS)发病中的作用。PsA和AS中发生的骨改变包括全身骨丢失、关节侵蚀和跟骨形成,反映了IL-23和IL-17的联合作用。IL-17A通过产生或诱导核因子受体激活因子-κB配体(RANKL)的表达,直接或间接地促进破骨细胞的发生,而IL-23对破骨细胞的作用是多元化的。IL-17A对成骨细胞前体细胞向成骨细胞的成熟有不同的影响,这取决于细胞前体的分化阶段。IL-17A阻断剂能抑制关节骨侵蚀,也可能延缓PsA和AS的全身骨丢失和PsA中苔藓样增生的形成。遗传证据将IL-23-IL-17通路与这些风湿病的炎症联系在一起,来自小鼠的数据支持IL-23-IL-17通路的激活在炎症的发展和骨髓炎的形成中起着重要的作用。此外,对人体组织样本的分析以及临床试验的数据也支持了IL-23-IL-17通路在这些疾病中的激活作用。PsA和AS中独特的骨表型是全身骨丢失与骨膜和骨膜骨形成的惊人共存,很可能是IL-23和/或IL-17作用于骨的结果。然而,这些细胞因子对骨细胞的影响是复杂的,它们在与PsA和AS相关的特定骨微环境中的确切作用仍存在争议。 参考文献:Nature ReviewsRheumatology (2018) Review Article | Published: 28 September 2018

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抗NXP2抗体阳性皮肌炎患者的系统性钙质沉着病例

翻译者:高洁,西京医院临床免疫科42岁的妇女因腹痛和口腔不适而进入急诊科。该患者8年前被确诊皮肌炎,抗NXP-2抗体阳性。在过去的3年中,尽管使用强的松联合几种免疫抑制药物(甲氨蝶呤、环孢素、利妥昔单抗和γ-球蛋白)以及抗再吸收疗法,皮肤钙质沉着症仍然发展(图1A,箭头)并恶化。由于临床怀疑肠梗阻,进行了腹部CT扫描,显示小肠扩张和腹膜钙质病变(图1B和C,箭头)。剖腹探查见无明显梗阻点,活检显示脂肪坏死和营养不良钙化。由于手术和组织学发现,笔者怀疑患者此次发病为皮肌炎有关的肠道侵犯。患者临床状况改善,静脉注射250mg甲基强的松龙连续3天,同时每两周静脉注射0.5g环磷酰胺。抗NXP2抗体最近已被鉴定与成人皮肌炎伴严重皮肤钙化有关。此外,这种抗体在青少年皮肌炎中出现,并且可与腹部症状有关,可有多种表现:肠道血管炎、溃疡、出血、吞咽困难等。治疗无规范。虽然在青少年皮肌炎中有成功使用γ-球蛋白的案例,但该患者对这种疗法表现出难治性。为此,我们选择糖皮质激素和环磷酰胺进行积极的免疫抑制治疗。治疗后的临床改善证实了该患者肠道疾病发病机制中炎症成分参与的假设。参考文献:SystemicCalcinosis in NXP2-Dermatomyositis42-year-old woman went to the emergencydepartment due to abdominal pain and oral intolerance. She had been diagnosedwith dermatomyositis 8 years ago, with a positive anti- NXP2 antibody. Duringthe previous 3 years, calcinosis cutis developed (Fig. 1A, arrows) and worseneddespite the use of prednisone combined with several immunosuppressive drugs(methotrexate, cyclosporine, rituximab, and gamma-globulin)and anti-resorptivetherapy.Due to clinical suspicion of intestinalobstruction, an abdominal CT-scan was performed, showing small bowel dilation,and calcium lesions in the peritoneum (Fig. 1B and C, arrows). Surgery teamperformed laparotomy with no evident point of obstruction, and biopsies takenshowed fat necrosis and dystrophic calcification. Because of surgical andhistological findings, we suspected intestinal involvement related todermatomyositis. The patient’s clinical statusimproved with intravenous pulsesof 250 mg of methylprednisolone three consecutive days combined with pulseintravenous of 0.5 g cyclophosphamide fortnightly, to maintain the response.Anti-NXP2 antibodies have recently beencharacterized and are associated with dermatomyositis in adults with a clinicalcourse with severe cutaneous calcification. Also, this antibody appears in juvenile dermatomyositis, and it isassociated with abdominal involvement with several manifestations: intestinalvasculitis, ulcers, bleeding, dysphagia, etc.Treatment is not well established.Although successful gamma-globulins were used in juvenile dermatomyositis, ourpatienthad shownrefractoriness to this therapy. For this reason, we chose aggressiveimmunosup- pressive therapy with corticosteroids and cyclophosphamide. Clinicalimprovement reinforces the hypothesis of an inflammatory component in thepathogenesis of the intestinal process.

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微生物群与HLA-B27相关急性前葡萄炎

编译者:李英,西京医院临床免疫科摘  要  急性前葡萄膜炎(AAU)和脊椎炎(SpA)亚型强直性脊柱炎、反应性关节炎和银屑病性关节炎是受肠道微生物生物学影响的炎症性疾病。急性前葡萄膜炎(AAU)是强直性脊柱炎最常见的临床表现。AAU和强直性脊柱炎与HLA-B27密切相关。HLA-B27会影响肠道微生物群的组成,这反过来又会改变免疫系统,从而影响健康和疾病。肠道微生物群与AAU和强直性脊柱炎的发病机制密切相关。虽然肠道微生物群引起AAU和强直性脊柱炎的机制尚不完全清楚,但通过改变微生物体来治疗或预防强直性脊柱炎和AAU有很大的潜力。本文综述了AAU、SpA与微生物群的关系,重点讨论了AAU的主要SPA危险基因HLA-B27及其与肠耐受性和眼免疫特权丧失的关系。我们提供了四种可能的机制来解释失调、屏障功能和免疫反应如何促进眼部炎症的发展和AAU的发病机制。最后,概述了AAU和SpA的临床治疗中潜在的针对微生物区系的治疗途径。 参考文献:Review Article | Published: 09October 2018Nature Reviews Rheumatology (2018)

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关节功能锻炼对类风湿关节炎患者关节功能的影响

编者:王卫涛,西京医院临床免疫科类风湿关节炎( rheumatoid arthritis,RA)是一种主要以关节炎性改变为主要特征的慢性自身免疫性疾病。其主要的表现为关节功能的受累,特别是中晚期患者出现严重关节破坏,关节畸形,使患者丧失生活能力,很大程度地影响了患者的生活质量,增加了家庭及社会的负担。数据显示:RA的全球发病率为0.5%-1.0%,我国大陆地区发病率为0.42%,总患病人数约500万。国内一项调查报告显示,我国病程1-5年、5-10年、10-15年及>15年的RA患者的致残率分别为18.6%、43.5%、48.1%、61.3%,而且随着病程的延长,残疾及功能受限的发生率还将不断升高。而诸多的实验研究表明,适当加强关节功能锻炼,能很大程度改善患者关节功能,一定程度预防或延缓关节畸形的发生。《类风湿关节炎患者的慢病管理专家共识(2014版)》中提到,适当的体力活动和锻炼有助于提高患者肌力,维护关节功能,延缓病情进展。然而,王秀丽等2016年的研究结果显示,70.29%的RA患者从未进行功能锻炼,92%的患者得不到医护人员的指导,临床对不同时期患者的锻炼方法存在较大差异。很多研究证实:1.水中锻炼比陆地锻炼对RA患者疾病的改善作用更大,对抗炎止痛药物的依赖性更低,关节肿胀、关节疼痛、病情恶化的发生率更低;2.功能锻炼不仅对局部关节功能有显著效果,更重要的是可调节患者的整体生存状态。《2018年中国类风湿关节炎诊疗指南》中就强调应积极鼓励患者每周坚持1-2次的有氧运动(非高强度的体育运动),建议条件适合的患者应当鼓励患者进行慢跑、骑车等有氧运动,可有效减轻RA患者的心血管并发症的发生;3.功能锻炼可以降低RA患者的关节疼痛感,减少晨僵时间,并可以缓解患者病情,对改善关节功能、提高患者生存质量都有积极作用。 参考文献:王莉、陈立红等《功能锻炼对类风湿关节炎患者效果评价的Meta分析》,(北京大学学报),2018-11-9   

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应用心血管磁共振技术评估强直性脊柱炎患者主动脉僵硬度

编者:韩青,西京医院临床免疫科摘  要:评估强直性脊柱炎(AS)患者的主动脉僵硬度,并评估其与AS特征及左室(LV)重建的相关性。在这项前瞻性研究中, 14例AS患者分别与没有心血管症状或已知的心血管疾病的对照组相匹配,进行CMR成像(1.5T)评估主动脉弓脉搏波速度(PWV)。为了提高样品的可比性,对样品进行了评估严格筛选。只有超声心动图检查有异常发现的患者才纳入本研究。Cine CMR用于评估LV的几何结构和收缩功能,并进行后期钆(gá)增强以确定心肌超增强信号的存在(如纤维化)。与对照组相比,AS组患者主动脉弓PWV明显增高(中值9.7 m/s, [IQR] 7.1-11.8 vs.6.1 m/s, IQR 4.6-7.6 m/s;P < 0.001)。PWV与BASFI测量的功能障碍呈正相关(R: 0.62;p =0.018)。与11例没有超增强的患者相比(9.0 m/s, IQR 6.6到10.5 m/s;p = 0.022) ,3例(21%)患者非缺血模式的超增强显示PWV增加(11.7, 12.3和16.5 m/s)。PWV与LV射血分数呈负相关(R: - 0.63;p =0.015),但未发现与LV体积或质量相关。主动脉弓中PWV的升高与功能障碍、非缺血超增强的存在、左心室收缩功能的降低有关。 参考文献: Assessment ofaortic stiffness in patients with ankylosingspondylitis using cardiovascular magnetic resonance.Biesbroek PS .et alAbstractTo evaluate aortic stiffness in patients with ankylosing spondylitis (AS)using cardiovascular magnetic resonance (CMR) and to assess its associationwith AS characteristics and left ventricular (LV) remodeling. In thisprospective study, 14 consecutive AS patients were each matched to two controlswithout cardiovascular symptoms or known cardiovascular disease who underwentCMR imaging for the assessment of aortic arch pulse wave velocity (PWV) at 1.5Tesla. To enhance comparability of the samples, matching was done withreplacement resulting in 20 unique controls. Only AS patients with abnormalfindings on screening echocardiography were included in this exploratory study.Cine CMR was used to assess LV geometry and systolic function, and lategadolinium enhancement was performed to determine the presence of myocardialhyperenhancement (i.e., fibrosis). Aortic arch PWV was significantly higher inthe AS group compared with the control group (median 9.7 m/s, interquartilerange [IQR] 7.1 to 11.8 vs. 6.1 m/s, IQR 4.6 to 7.6 m/s; p < 0.001). PWV waspositively associated with functional disability as measured by BASFI (R: 0.62;p = 0.018). Three patients (21%) with a non-ischemic pattern ofhyperenhancement showed increased PWV (11.7, 12.3, and 16.5 m/s) as compared tothe 11 patients without hyperenhancement (9.0 m/s, IQR 6.6 to 10.5 m/s;p = 0.022). PWV was inversely associated with LV ejection fraction (R: - 0.63;p = 0.015), but was not found to be statistically correlated to LV volumes ormass. Aortic arch PWV was increased in our cohort of patients with AS. HigherPWV in the aortic arch was associated with functional disability, the presenceof non-ischemic hyperenhancement, and reduced LV systolic function.Clin Rheumatol. 2018 May 12. doi:10.1007/s10067-018-4135-x. [Epub ahead of print]

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2010/2011纤维肌痛综合征诊断标准的2016修订

编译者:谢荣华,西京医院临床免疫科目  的:2010年美国风湿病学会(ACR)的暂行标准和2011年用于调查和临床研究的自我报告修订被广泛用于纤维肌痛综合征的诊断。为了该确定标准的有效性、有用性、潜在问题和需要修改的地方,评估了2010-2016年发表的多个研究报告,以便对标准进行2016年的更新。方  法:回顾了14项验证研究,这些研究将2010/2011年的标准与ACR 1990年的分类和临床标准进行了比较,同时也回顾了流行病学、临床和数据库研究,这些研究均强调了重要的标准级别变量。基于1990年和2010/2011年标准之间的定义差异,我们将85%的敏感性和90%的特异性解释为极好的一致性。结  果:与1990年和临床标准相比,2010/2011年标准的中位敏感性和特异性分别为86%和90%。2010/2011标准在应用于区域疼痛综合征时导致了错误的分类,但是当加入一个修改的广泛疼痛标准(“广义疼痛标准”)时,错误的分类被消除了。基于上述数据和临床使用数据,我们对2010/2011年纤维肌痛症标准进行了(2016)修订。结  论:纤维肌痛症诊断标准具有良好的敏感性和特异性。这一修订结合了医生和患者问卷标准,最大限度地减少了对区域疼痛障碍的错误分类,并消除了以前令人困惑的关于排除诊断的建议。以医生为基础的标准对个别病人的诊断是有效的,该标准的自我报告版本对个别患者的临床诊断无效,但对研究研究有效。这些变化允许这些标准作为诊断标准,同时仍然对分类有用。 文献来源: Semin Arthritis Rheum. 2016 Dec;46(3):319-329. doi:10.1016/j.semarthrit.2016.08.012. Epub 2016 Aug 30.2016 Revisions to the 2010/2011fibromyalgia diagnostic criteria.Wolfe F1, Clauw DJ2, Fitzcharles MA3, Goldenberg DL4, Häuser W5, Katz RL6, Mease PJ7, Russell AS8, Russell IJ9, Walitt B10.AbstractOBJECTIVES: The provisional criteria of theAmerican College of Rheumatology (ACR) 2010 and the 2011 self-reportmodification for survey and clinical research are widely used for fibromyalgiadiagnosis. To determine the validity, usefulness, potential problems, and modificationsrequired for the criteria, we assessed multiple research reports published in2010-2016 in order to provide a 2016 update to the criteria.METHODS: We reviewed 14 validation studiesthat compared 2010/2011 criteria with ACR 1990 classification and clinicalcriteria, as well as epidemiology, clinical, and databank studies thataddressed important criteria-level variables. Based on definitional differencesbetween 1990 and 2010/2011 criteria, we interpreted 85% sensitivity and 90%specificity as excellent agreement.RESULTS: Against 1990 and clinicalcriteria, the median sensitivity and specificity of the 2010/2011 criteria were86% and 90%, respectively. The 2010/2011 criteria led to misclassification whenapplied to regional pain syndromes, but when a modified widespread paincriterion (the "generalized pain criterion") was addedmisclassification was eliminated. Based on the above data and clinic usagedata, we developed a (2016) revision to the 2010/2011 fibromyalgia criteria.Fibromyalgia may now be diagnosed in adults when all of the following criteriaare met: CONCLUSIONS: The fibromyalgia criteria have good sensitivity andspecificity. This revision combines physician and questionnaire criteria,minimizes misclassification of regional pain disorders, and eliminates thepreviously confusing recommendation regarding diagnostic exclusions. Thephysician-based criteria are valid for individual patient diagnosis. Theself-report version of the criteria is not valid for clinical diagnosis in individualpatients but is valid for research studies. These changes allow the criteria tofunction as diagnostic criteria, while still being useful for classification.

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干燥综合征相关肺动脉高压的特征及危险因素

翻译者:谢荣华,西京医院临床免疫科目  的:目的探讨原发性干燥综合征(pSS)患者右心导管插入术(RHC)证实的肺动脉高压(PAH)的基线特征,探讨pSS中PAH的危险因素。方  法:该病例对照研究以2007年至2015年住院的pSS-PAH患者为研究对象,无PAH的pSS患者(比例为4:1)作为对照。所有患者均符合2002年欧美共识组pSS-PAH分类标准,该标准是基于RHC欧洲心脏病学会/欧洲呼吸学会指南确定。用单变量二元logistic回归分析相关变量,以确定PAH的可能危险因素。结  果:总共29例经RHC证实的 pSS-PAH(包括平均发病年龄,38.4±8.3年;平均pSS持续时间54.6个月)患者纳入研究。12例pSS患者初始表现为肺动脉高压是(41.4%),气短是最常见的症状(29/29,100%)。平均肺动脉压力为51.8±10.0mmHg,心脏指数是2.3±0.8 L/min/m2,肺血管阻力是13.0±6.0Wood单位。治疗包括免疫抑制剂(93.1%)和PAH靶向治疗(86.2%)。研究发现了四个独立的pSS-PAH风险因素:包括雷诺氏现象(OR= 9.660,P = 0.000),类风湿因子≥200 U /ml (OR= 6.691,P = 0.001),肝脏损伤(OR= 3.284,P = 0.008)和心包积液(OR= 3.279,P = 0.016)。结  论:PAH可能是pSS的首发表现,pSS患者出现雷诺症、高滴度类风湿因子、肝损伤或心包积液时应早期筛查肺动脉高压。参考文献:Int J Rheum Dis. 2018 May;21(5):1068-1075. Epub2018 Apr 6.Characteristics and risk factorsof pulmonary arterial hypertension in patients with primary Sjögren's syndrome.Yan S1,2, Li M2, Wang H3, Yang X2, Zhao J2, Wang Q2, Liu Y3, Lai J3, Tian Z3, Song H1, Zhao Y2, Zeng X2.AbstractAIM: Todescribe baseline characteristics of patients with primary Sjögren's syndrome(pSS) with right heart catheterization (RHC)-confirmed pulmonary arterialhypertension (PAH) and explore risk factors for PAH in pSS.METHODS: Thiscase-control study included consecutive patients hospitalized with pSS-PAH from2007 to 2015, and pSS patients without PAH (in a 4 : 1 ratio) as controls. Allpatients fulfilled the 2002 American-European Consensus Group classificationcriteria for pSS-PAH was defined according to RHC-based European Society ofCardiology/European Respiratory Society guidelines. Associated variables wereanalyzed by univariate binary logistic regression to identify possible riskfactors for PAH.RESULTS: Twenty-ninepatients with RHC-confirmed pSS-PAH were included (mean age at onset, 38.4 ±8.3 years; mean pSS duration, 54.6 months). PAH was the initial manifestationof pSS in 12 patients (41.4%), and shortness of breath was the most commonsymptom (29/29, 100%). Mean pulmonary arterial pressure was 51.8 ± 10.0 mmHg,mean cardiac index was 2.3 ± 0.8 L/min/m2 , and mean pulmonary vascularresistance was 13.0 ± 6.0 Wood units in this group. Treatments includedimmunosuppressive agents (93.1%) and PAH-targeted therapies (86.2%). Weidentified four independent risk factors for PAH in pSS: Raynaud's phenomenon(odds ratio [OR] = 9.660, P = 0.000), rheumatoid factor ≥ 200 U/mL (OR = 6.691,P = 0.001), hepatic injury (OR = 3.284, P = 0.008) and pericardial effusion (OR= 3.279, P = 0.016).CONCLUSIONS: PAH can be the firstmanifestation of pSS. The pSS patients with Raynaud's phenomenon, high-titerrheumatoid factor, hepatic injury or pericardial effusion should be screenedfor PAH.

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系统性红斑狼疮、原发性抗磷脂综合征和继发抗磷脂综合妇女妊娠期间动静脉血栓形成、胎儿死亡和死产的差异:系统回顾和分析

翻译者:谢荣华,西京医院临床免疫科背 景:我们旨在比较系统性红斑狼疮(SLE)、原发性抗磷脂综合征(PAPS)和继发抗磷脂综合症(SAPS)三个疾病之间妊娠期间动静脉血栓形成、胎儿死亡和死产的差异。方 法:搜索在线数据库有关比较SLE与PAPS和/或SAPS有关妊娠方面的文献。文献包括:妊娠妇女SLE与APS比较(SLE 和 PAPS、SLE和SAPS或SLE分别与PAPS和SAPS比较),同时这些文献报告了具体的不良后果,包括动脉/静脉血栓形成、胎儿丢失和死产。风险比率(RR)和95%的可信区间(CIs)作为统计参数,分析由RevMan 5.3软件进行。结 果:共有941名孕妇参加,其中556名是SLE患者,200名是PAPS患者,还有185名是SAPS患者。APS与显著增加的胎儿丢失风险有关(RR:4.49,95%Cl:2.0-9.64;P = 0.0001)。此外,死产和动脉/静脉血栓形成在APS也显著增加(RR:6.65,95%CI:2.14-20.60; P=0.001)和(RR:3.95,95%CI:1.28-12.16;P=0.02)。当PAPS患者与仅患有SLE的患者进行比较时,胎儿丧失和动脉/静脉血栓形成的比例在PAPS仍然高得多。当SAPS与SLE(没有抗磷脂抗体)进行比较时,动脉/静脉血栓形成、死产以及胎儿丢失在SAPS仍然显著增加。但是,动脉/静脉血栓和胎儿丢失在PAPS和SAPS之间没有差异。结 论:与SLE相比较,PAPS和SAPS患者动静脉血栓、胎儿丢失和死产显著增加。但是PAPS和SAPS之间无明显差异。 参考文献:Arterial/venousthrombosis, fetal loss andstillbirth in pregnant women with systemiclupus erythematosus versus primary andsecondary antiphospholipid syndrome: asystematic review and meta-analysisPravesh Kumar Bundhun1, Mohammad Zafooruddin Sani Soogund2 and Feng Huang3*AbstractBundhunetal. BMC Pregnancy and Childbirth (2018) 18:212

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修订的EULAR关于纤维肌痛综合征治疗建议

编译者:谢荣华,西京医院临床免疫科目 的:最初的欧洲抗风湿病联盟关于治疗纤维肌痛综合征的建议评估了截至2005年的证据。由于研究资料的缺乏,因此意味着大多数建议都来自于“专家意见”。方 法:来自12个国家的多学科小组对证据参与了评估,重点是对纤维肌痛综合征的药理学以及非药理学管理的系统回顾和荟萃分析。2015年5月的一项审查确定了符合条件的出版杂志以及根据疼痛、疲劳、睡眠和日常功能等评估的关键结果。建议的评估、发展和评价体系的分级被用于指定建议。结 果:2979个题目被识别出来:从275篇完整的论文中挑选出来进行评审,107篇(和/N荟萃分析)评审合格。根据荟萃分析,指南中唯一“强有力”的基于治疗的建议是锻炼。根据专家意见,分阶段的方法,以下四个主要阶段的建议主要与患者共同决策。初始治疗应包括患者教育和非药物治疗。对于治疗不佳的患者,进一步治疗(基于荟萃分析,所有都被评估为“弱” )应根据个人的特定需求和可能涉及的心理疗法(情绪障碍和无益的应对策略)、药物治疗(严重疼痛或睡眠障碍)和/或多种方法的康复计划(严重残疾)。结 论:这些建议以高质量的审查和荟萃分析为基础,大多数治疗的效果是相对温和的。该研究提出了研究的重点是要阐明谁将受益于具体的干预措施以及它们在组织卫生保健系统优化结果方面的作用。 推荐意见总原则证据级别 分级推荐强度同意%及时诊断,全面了解患者疼痛、功能和心理状态;该病的特征为疼痛处理异常及其他伴随问题;FM管理治疗应采取分级方式。IVD100治疗应以提高与健康相关的生活质量为目标;多学科多方法结合、非药物学和药物治疗方式;治疗根据疼痛强度、功能、相关特点(抑郁症、疲劳、睡眠障碍、患者偏好和合并症)以及与患者协商而定;初期治疗应侧重于非药物治疗。IVD100具体建议非药物治疗 有氧力量训练IaA强100 认知行为治疗IaA弱100 多种治疗IaA弱93 物理治疗:针灸、水疗IaA弱93 冥想运动疗法(气功、瑜伽、太级)和正念减压IaA弱71-73药物治疗 阿米替林(低剂量)IaA弱100 度洛西汀或米那普仑IaA弱100 曲马多IbA弱100 普瑞巴林IaA弱94 环苯扎林IaA弱75文献来源:Ann Rheum Dis2016;0:1–11. doi:10.1136/annrheumdis-2016-209724.EULAR revised recommendations forthe management of fibromyalgia.Macfarlane GJ1, Kronisch C1,2, Dean LE1, Atzeni F3, Häuser W4,5, Fluß E1, Choy E6, Kosek E7, Amris K8, Branco J9, Dincer F10, Leino-Arjas P11, Longley K12, McCarthy GM13, Makri S14, Perrot S15, Sarzi-Puttini P16, Taylor A17, Jones GT1.AbstractOBJECTIVE: The original European LeagueAgainst Rheumatism recommendations for managing fibromyalgia assessed evidenceup to 2005. The paucity of studies meant that most recommendations were 'expertopinion'.METHODS: A multidisciplinary group from 12countries assessed evidence with a focus on systematic reviews andmeta-analyses concerned with pharmacological/non-pharmacological management forfibromyalgia. A review, in May 2015, identified eligible publications andkeyoutcomes assessed were pain, fatigue, sleep and daily functioning. The Gradingof Recommendations Assessment, Development and Evaluation system was used formaking recommendations.RESULTS: 2979 titles were identified: fromthese 275 full papers were selected for review and 107 reviews (and/ormeta-analyses) evaluated as eligible. Based on meta-analyses, the only 'strongfor' therapy-based recommendation in the guidelines was exercise. Based onexpert opinion, a graduated approach, the following four main stages aresuggested underpinned by shared decision-making with patients. Initialmanagement should involve patient education and focus on non-pharmacologicaltherapies. In case of non-response, further therapies (all of which wereevaluated as 'weak for' based on meta-analyses) should be tailored to thespecific needs of the individual and may involve psychological therapies (formood disorders and unhelpful coping strategies), pharmacotherapy (for severepain or sleep disturbance) and/or a multimodal rehabilitation programme (forsevere disability).CONCLUSIONS: These recommendations areunderpinned by high-quality reviews and meta-analyses. The size of effect formost treatments is relatively modest. We propose research priorities clarifyingwho will benefit from specific interventions, their effect in combination andorganisation of healthcare systems to optimise outcome.

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与你的肠道对话:口腔-肠道微生物组轴及其在类风湿关节炎病因学中的免疫调节作用

翻译者:赵倩倩,西京医院临床免疫科摘  要:栖息在人体内的微生物群落,统称为微生物群,是免疫的关键调节剂。微生物组的变化与特定的自身免疫疾病之间的联系支撑了这一观点。具体地,在类风湿关节炎中,全世界最常发生的自身免疫疾病之一,口腔和肠道微生物组的变化涉及对自身抗原的耐受性丧失和促进关节损伤的增加的炎症事件。在本综述中,我们重点介绍了最近对微生物在类风湿关节炎病因学中的作用的见解。此外,我们还讨论了重要的免疫调节过程,包括生物膜形成和中性粒细胞功能,这些过程与类风湿性关节炎相关的宿主 - 微生物相互作用有关。最后,我们介绍了新兴基于微生物组的治疗方法的开发和评估的最新进展。总之,我们得出结论,揭示类风湿关节炎的发病机理的关键在于口腔和肠道微生物组的免疫调节功能。参考文献:Talk to your gut: the oral-gut microbiome axis andits immunomodulatory role in the etiology ofrheumatoid arthritis.AbstractMicrobialcommunities inhabiting the human body, collectively called the microbiome, arecritical modulators of immunity. This notion is underpinned by associationsbetween changes in the microbiome and particular autoimmune disorders.Specifically, in rheumatoid arthritis, one of the most frequentlyoccurring autoimmune disorders worldwide, changes in the oral and gut microbiomeshave been implicated in the loss of tolerance against self-antigens and inincreased inflammatory events promoting the damage of joints. In the presentreview, we highlight recently gained insights in the roles of microbes in theetiology of rheumatoid arthritis. In addition, we address importantimmunomodulatory processes, including biofilm formation and neutrophilfunction, which have been implicated in host-microbe interactions relevantfor rheumatoid arthritis. Lastly, we present recent advances in the developmentand evaluation of emerging microbiome-based therapeutic approaches. Altogether,we conclude that the key to uncovering the etiopathogenesis ofrheumatoidarthritis will lie in the immunomodulatory functions of the oraland gut microbiomes.

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类风湿关节炎中的抗甲状腺抗体和甲状腺功能障碍:患病率和临床价值

翻译者:赵倩倩,西京医院临床免疫科目  的:本研究的目的是评估甲状腺功能以及类风湿关节炎(RA)患者抗甲状腺抗体的流行和临床价值。 方  法:对70例活动性RA患者(ACR标准),男性9例,女性61例,平均年龄47岁(范围15-77)进行分析。使用放射免疫测定法测试抗甲状腺过氧化物酶(TPOAb)和抗甲状腺球蛋白抗体(TgAb)。使用电免疫化学发光(ECLIA,Elecsys Roche)测量游离甲状腺素(FT4)和游离三碘甲腺原氨酸(FT3)和促甲状腺激素(TSH)血清水平。关节疼痛和肿胀关节计数,红细胞沉降率(ESR),C反应蛋白(CRP),类风湿因子(RF),抗CCP抗体和抗核抗体(ANA)也被评估。统计数据由Windows的SPSS统计软件执行。 结  果:26例RA患者(37%)TPOAb阳性,TgAb阳性16例(23%)。在5例(7.1%)患者中,TSH水平略微升高,范围在4.52和15.65 UI / ml之间。TSH水平升高与正常FT4相关3例(4.2%),FT4降低2例(2.8%)。一名患者(1.5%)具有低TSH血清值以及正常FT4。在观察到抗甲状腺阳性和阴性患者之间的临床和血清学数据没有差异。 结  论:我们的研究显示,RA患者的抗甲状腺抗体的患病率增加。然而,抗甲状腺抗体似乎不能识别任何特殊的RA表型。参考文献:Anti-thyroidantibodies and thyroid dysfunction in rheumatoid arthritis: Prevalence andclinical value Objectives:The aim of this study was to assess thyroid function as well as the prevalenceand clinical value of anti-thyroid antibodies in patients with rheumatoidarthritis (RA).Methods: Seventypatients with active RA (ACR criteria), 9 males and 61 females, mean age 47years (range 15–77) were analyzed. Anti-thyroperoxidase (TPOAb) andanti-thyroglobulin antibodies (TgAb) were tested using radioimmunoassay. Freethyroxine (FT4) and free triiodothyronine (FT3) and thyroid-stimulating hormone(TSH) serum levels were measured using electro-immunochemiluminescence (ECLIA,Elecsys Roche). Clinical variables, including tender and swollen joint count,erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoidfactor (RF), anti-cyclic citrullinated peptide antibody (anti-CCP) andantinuclear antibodies (ANA) were also evaluated. Statistics were performed by theSPSS statistical software for Windows.Results:Twenty-six patients (37%) with RA were positive for TPOAb and 16 (23%) forTgAb. In 5 (7.1%) patients TSH level was slightly elevated, ranging between4.52 and 15.65 UI/ml. The increase of TSH levels was associated with normal  FT4 in 3 cases (4.2%) and with reduced FT4 in2 cases (2.8%). One patient (1.5%) had low TSH serum value along with normalFT4. No differences in clinical and serological data between anti-thyroidpositive and negative patients were observed.Conclusion: Our study shows an increased prevalence ofanti-thyroid antibodies in RA patients with a low prevalence of  hormonal alterations. However, anti-thyroidantibodies do not seem to identify any peculiar RA phenotype。

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DM、PM钙质沉着的临床和实验室预测指标及治疗选择

翻译者:高洁,西京医院临床免疫科目  标:为已诊断是多发性肌炎(PM)和皮肌炎(DM)的患者确定提示可能出现钙质沉着的临床和实验室预测因子。方  法:回顾性分析2013年1月和2014年5月之间就诊笔者诊所的肌炎患者。结  果:本文报告74例PM(30例)、DM(30例)、重叠综合征(13例)、包涵体肌炎(1例)。钙质沉着症16例(21.6%),发生于诊断为PM/DM平均43.7个月后。在多元分析中,与不伴有钙质沉着症的患者相比,钙质沉着症患者经历更长的随访时间(p=0.006)、抗-PM/Scl(p=0.033)和抗-NXP2(p=0.024)阳性率也高于无钙质沉着的患者。此外,抗-NXP-2阳性C+患从一开始即表现为弥漫性钙质沉着,但呼吸道受累频率较低。在治疗钙质沉着症方面,目前尚没有单一药物或药物联合使用明确有效者。结  论:随访时间长、诊断为皮肌炎者和PM/Scl或NXP-2阳性均可被认为是预测钙质沉着症发展的危险因素。此外,认为NXP-2抗体的阳性为钙质沉着症的特异性抗体,有发病早、进展迅速的特点。参考文献:Clin Exp Rheumatol. 2017 Mar-Apr;35(2):303-308. Epub 2016Nov 14. Calcinosis inpoly-dermatomyositis: clinical and laboratory predictors and treatment optionsOBJECTIVES:We aimed to identify the possible clinical andlaboratory predictors of calcinosis in a cohort of patients with adiagnosis of polymyositis (PM) and dermatomyositis (DM).METHODS:We carried out a retrospective analysis of acohort of myositis patients attending our clinic between January 2013 and May2014.RESULTS:74 patients (58 females, 16 males) with PM (30cases), DM (30 cases), overlap syndrome (13 cases) and inclusion body myositis(1 case) were enrolled. Sixteen patients (21.6%) had calcinosis thatoccurred a mean of 43.7 months after diagnosis of PDM. At multivariateanalysis, patients with calcinosis experienced longer follow-upduration (p=0.006), anti-PM/Scl (p=0.033) and anti-NXP2 (p=0.024) positivitycompared to patients without calcinosis. Furthermore, anti-NXP-2 positiveC+ showed a diffuse form of calcinosis from the beginning and lowerfrequency of respiratory tract involvement. No single drug or associations ofdrugs was found effective in the treatment of calcinosis.CONCLUSIONS:A longer follow-up period of time, DM diagnosisand positivity for PM/Scl and NXP-2 could all be considered risk factors whichforesee the development of calcinosis. Moreover, the positivity forantibodies to NXP-2 depicts a distinct phenotype of calcinosis with anearly onset and quick widespread dissemination.

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炎症(RA)在精神疾病中的作用

翻译者:戎梦瑶,西京医院临床免疫科炎症过程在常见精神疾病(尤其是抑郁症)病因学中的作用,经过越来越多研究证实,现在已成为精神病学研究重点。 在一项实时系统评价中,Matcham等人使用成对和网状荟萃分析来评估和比较生物DMARDs(bDMARDs)和传统合成DMARDs(csDMARDs)对RA患者心理健康的影响。在回顾性研究了71例经DMARDs治疗的有精神情绪问题的RA患者,所有的研究都使用了36项简短的健康调查(SF-36)问卷。使用两个相互关联的SF-36问卷进行总结得分,结论是:DMARDs一组对心理健康结果影响很小,对身体健康结果的影响稍大的药物。当比较bDMARDs与安慰剂(SMD= 0.27)和csDMARDs(SMD= 0.19-0.30)时,也观察到类似的结果。结论是“单独的药物治疗不太可能显着改善大多数RA患者的心理健康”。Matcham等人通过这种方法,他们证明了无论何种作用方式,bDMARDs(包括TNF抑制剂、B细胞抑制剂、T细胞抑制剂、IL-6阻滞剂和Janus激酶抑制剂)在改善精神(和身体)健康方面都比csDMARDs好。尽管不同bDMARD之间对患者的心理健康影响没有显着差异。因此,心理健康症状可能是RA病理的一个内在组成部分,无论是作为合并症,还是作为RA的炎症过程的一个组成部分,这些患者的心理健康症状仍然难以识别和管理,可能需要进一步的基础研究和临床研究。参考文献:Interoceptionandinflammation in psychiatric disorders. Biol. Psychiatry Cogn.Neurosci.Neuroimag. 2018.

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