未分化关节炎学习班

未分化关节炎诊治,北京协和医院风湿免疫科 赵岩,RA治疗2010-EULAR建议要点,目标治疗（Treat-to-Target） 首先使用传统DMARDs 联合用药 危险因素分层治疗 生物制剂的使用,Smolen, et al. Ann Rheum Dis; 2010;69:631637,达到临床缓解或低活动度为首要目标,M F Bakker.Ann Rheum Dis.2007,66:56-60,目标治疗（Treat-to-Target）,Smolen, et al. Ann Rheum Dis; 2010;69:631637,持续缓解非常重要,EULAR 2011治疗RA建议更新,EULAR 2011治疗RA建议更新,强调初始治疗的重要性 强调MTX的剂量：1525 mg/w 主张联合用药，尤其MTX+HCQ 明确LEF的治疗地位 强调激素的重要性 生物制剂：TNFa、IL-6单抗 轻症、早期( MTX5年副作用 = MTX短期副作用 MTX ?,2011-EULAR传统DMARDs更新：MTX,起始10-15mg/w，可用到20-30mg/w 联合用药中，MTX为“锚定”药物 术中使用安全 妊娠前停用3个月 长期维持减至安全剂量（小于15mg/w）,2011-EULAR传统DMARDs更新：皮质激素,减少NSAIDs用量（10mg/d) 减缓骨破坏（10mg/d) 越早使用获益越大 起始剂量不定，根据病情活动度 增加临床缓解的比例，缩短达到临床缓解的时间 减少TNFB的使用（16% vs 35%） 减少副作用：恶心、肝功异常等 风险效益平衡,生物制剂DMARDs,肿瘤：TNFB 1.3 益处 骨质疏松： 动脉硬化: （RR：0.39） （MTX RR：0.94） 妊娠： 增高（儿童）： 经济：？,Ann Rheum Dis April 2011 Vol 70 No 4,未分化关节炎诊疗,未分化关节炎(undifferentiated arthritis，UA)早期关节炎(early arthritis，EA),EA通常是UA。EA可发展为RA或其它已知关节病、可自然缓解、或维持未分化状态。,未分化关节炎诊疗步骤,诊治第一步是明确有无关节炎。 诊治第二步是除外已知关节炎（如SLE、PsA、SpA等）。 诊治第三步是判断关节炎持续性和侵蚀性的可能性，给予合适的治疗方案。,关节炎的自然病程,B.Combe.Ann Rheum Dis.2006,关节炎的发展演变：滑膜炎,第一阶段： 细胞迁徙至滑膜。可完全缓解，也可转为慢性滑膜炎（第二阶段）,第二阶段： 亚急性滑膜炎、细胞集聚（非特异性）,第三阶段： 血管醫、滑膜增生、不可逆骨和软骨破坏（RA）,早期UA病程的变化呈多样化,40-50% of Pts with early UA remit spontaneously,Van Aken, et al, ARD 2006；Hrrison BJ et al, BJR1996；Van Dongen et al, AR 2007,30-50% develop rheumatoid arthritis,Early initiation of DMARDs is beneficial,Need to recognize which UA will develop RA,是否为关节炎,Recommendation 1:Arthritis,1b,B,Arthritis is characterised by the presence of joint swelling, associated with pain or stiffness. Patients presenting with arthritis of more than one joint should be referred to, and seen by, a rheumatologist, ideally within six weeks after the onset of symptoms.,未分化关节炎(UA)或早期关节炎(EA)：,非外伤或骨性肥大所致的关节肿胀提示UA的诊断 两个以上关节受累、晨僵、MCP/MTP受累则更支持诊断诊治第一步是明确有无关节炎。手足关节受累的最好检查是挤压试验（Squeeze test）,关节炎的检查方法,Recommendation 2:Examination,2b,C,Clinical examination is the method of choice for detecting synovitis. In doubtful cases, ultrasound, power Doppler, and MRI might be helpful to detect synovitis.,关节炎的检查：,临床检查仍然是诊断关节炎的“金标准”MRI和US是诊断、预后和监测UA疗效的有前景的方法和手段，有待进一步规范和验证。,早期诊断：MR,早期诊断 ：超声,关节炎的鉴别诊断,Recommendation 3:Exclusion,-,D,Exclusion of diseases other than rheumatoid arthritis requires careful history taking and clinical examination, and ought to include at least the following laboratory tests: complete blood cell count, urinary analysis, transaminases, antinuclear antibodies.,鉴别诊断：,根据不同国家、地区、不同人群尚需查：血尿酸、Lyme病抗体、parvovirus病毒、尿道或宫颈刮片培养、细菌或肝炎病毒检测、胸片等,常见风湿病和少见风湿病的鉴别：太难！,病例：女，45岁，手PIP、MCP和腕关节肿痛6周，RF+，晨僵40分钟ANA1:320(+)，抗SSA(+)，有口眼干2年,肥大性骨关节病,肿瘤骨转移,Ollier Disease (内生软骨瘤):多发骨肿块,增大,变形,边界清楚的溶骨性改变,关节间隙正常,色素绒毛结节性滑膜炎,细小病毒B19感染引起的病毒性关节炎:PIP, MCP,W关节肿胀,病毒性关节炎,反射性交感神经营养不良,弥漫性手肿胀；变形,Dupuytren挛缩,掌筋膜的结节性增厚，最常见于第4,5指，可双侧。与癫痫，糖尿病及酒精肝病相关；也可有家族聚集性。,淀粉样病变,结节病,未分化关节炎的预后,Recommendation 4:Prognostic factors,III,C,In every patient presenting with early arthritis to the rheumatologist, the following factors predicting persistent and erosive disease should be measured: number of swollen and tender joints, ESR or CRP, levels of rheumatoid factor and anti-CCP antibodies, and radiographic erosions.,生物学预测模型？ 生物标记物&高敏影像学的作用？,能否预测那种类型的患者将发展成为持续或骨质破坏性关节炎, 及其治疗的结局？,Biologic Prediction Models,Making a diagnosis of RA continues to be based primarily on clinical grounds,A& R, 2002,56(2):433440,Leiden Prediction Model,RHEUMATOID ARTHRITIS Case,岁女性:腕及足关节痛3周，伴晨僵60分钟 右腕和2nd MCP肿胀压痛, 双侧足MTP(2-5) 压痛有10个关节受累 (只有右手2个关节肿 )ESR 正常, RF 23(临界),抗CCP 16(5), ANA1:80CRP 17 (normal8)手足关节X线无异常MRI:腕关节肿胀,Leiden Model （同样适用于新标准）,70%,6分或以上肯定RA诊断,ACR/EULAR2009年RA诊断标准,肿胀关节数和压痛关节数 CRP和ESR RF和抗CCP抗体滴度 早期发现影像学侵蚀灶 其它：女性患者,B Combe，et al. Ann Rheum Dis, 2007;66:3445,2007 EULAR：回顾早期预测的45项研究下列因子对持续侵蚀性有预测作用,未分化关节炎的治疗,Recommendation 5:Treatment,1a,A,Patients at risk of developing persistent or erosive arthritis should be started with DMARDs as early as possible, even if they do not yet fulfil established classification criteria for inflammatory rheumatological diseases.,465 patients with recent-onset RA randomised to receive initial monotherapy or combination therapy were used. Predictors for RRP (increase in Sharp-van der Heijde score 5 after 1 year) were identified by multivariate logistic regression analysis,RHEUMATOID ARTHRITIS Case,岁女性:腕及足关节痛3周，伴晨僵60分钟 右腕和2nd MCP肿胀压痛, 双侧足MTP(2-5) 压痛有10个关节受累 (只有右手2个关节肿 )ESR 正常, RF 23(临界),抗CCP 16(5), ANA1:80CRP 17 (normal10mg/d长期使用应避免小剂量（5mg/d）长期维持有争议：预防骨质疏松、无高血压、糖尿病等,Pincus T, Sokka T, Stein CM. Are long-term very low doses of prednisone for patients with rheumatoid arthritis as helpful as high doses are harmful? Ann Intern Med 2002;136(1):768.Boers M, et al. Randomised comparison of combined step-down prednisolone, methotrexate and sulphasalazine with sulphasalazine alone in early rheumatoid arthritis. Lancet 1997;350:30918.,COBRA研究：泼尼松60mg/d，6周内减至7.5mg/g,联合MTX/HCQ/SSZ,Boers M, et al. Randomised comparison of combined step-down prednisolone, methotrexate and sulphasalazine with sulphasalazine alone in early rheumatoid arthritis. Lancet 1997;350:30918.,Recommendation 9:DMARDs,1a,A,Among the DMARDs, methotrexate is considered to be the anchor drug, and should be used first in patients at risk of developing persistent disease.,药物选择：MTX首选,MTX：核心药物（Anchor Drug）小剂量（7.5-20mg/w）每周使用是长期最有效和安全的药物大剂量（2030mg/w）时有细胞毒和其它副作用，根据个体差异决定是否使用大剂量初始治疗可单用MTX快加：5mg/w；慢减：2.5mg/w合并使用叶酸明显减少胃肠副作用（2-24小时）,Chan ESL, Cronstein BN. Molecular action of methotrexate in inflammatory diseases. Arthritis Res 2002;4:26673.Donahue KE, et al. Systematic review: comparative effectiveness and harms of disease-modifying medications for rheumatoid arthritis. Ann Intern Med 2008;148(2):12434.Pincus T, Yazici Y, Sokka T. Are excellent systematic reviews of clinical trials useful for patient care? Nat Clin Pract Rheumatol 2008;4(6):2945.,药物选择：传统DMARDs,MTX有禁忌或不能耐受者可选择LEF、SSZ等雷公藤多甙？,Recommendation 10:Treat-to-target,1b,B,The main goal of DMARD treatment is to achieve remission. Regular monitoring of disease activity and adverse events should guide decisions on choice and changes in treatment strategies (DMARDs including biological agents).,目标治疗（Treat-to-Target）,早期强化治疗密切随访，根据病情活动度调整治疗方案（Tight Control），直至临床缓解精确的疾病活动评价体系个体化治疗,严格控制（Tight Control）,密切随访（1-3月）根据病情活动度调整治疗方案达到临床缓解和维持临床缓解同样重要,M F Bakker.Ann Rheum Dis.2007,66:56-60,Recommendation 11:Other interventions,1a,B,Non-pharmaceutical interventions such as dynamic exercises, occ