幼年特发性关节炎复旦大学风湿过敏免疫中心 复旦大学附属儿科医院肾脏风湿科 周利军 fenlin183yahoo.com.cn Introductionn周四下午，风湿专科 54524666转5084n肾脏风湿科病房 54524666转3011nfenlin183yahoo.com.cn幼年特发性关节炎（JIA)nJuvenile Idiopathic ArthritisnJuvenile Rheumatic ArthritisnJuvenile Chronic Arthritis2001,JIA has been confirmed by ILARTypes of Autoimmune Disease幼年特发性关节炎（JIA)n16岁以下儿童n长期发热、皮疹n淋巴结和肝脾肿大n胸膜炎和心包炎n反复发作可致关节畸形幼年特发性关节炎（JIA)3岁男孩，弛张热，肝脾肿大少量心包积液、充血性随热出现 皮疹 疾病？病因和发病机理n感染n遗传 n1979 Stasty Fink nHLA-DW7,DW8n寒冷 潮湿 n疲劳 营养不良病因和发病机理病理变化n关节病变 n皮下结节 n眼部病变 n其他免疫异常和损伤依据n血IgG IgA IgM 不同程度升高n部分患儿补体升高n可出现血和关节液RF阳性n血和关节液TNF水平增高n迟发超敏反应降低自身抗体的临床价值n在典型风湿病 肯定诊断（A-dsDNA,ACL)n在不典型风湿病 提示诊断 n 如多关节炎 (CCP抗体阳性)n评估预后及指导用药 抗体谱广 + 高滴度 病情重 用药规范自身抗体的临床价值新近JIA相关抗体n抗CCP抗体nBiP抗体nAFAn抗GPI抗体n抗CB10抗体临床表现 Manifestationn全身型n多关节,RF+ n多关节,RF- n少关节,持续或扩展 n银屑病型 n附着点关节炎型n其他全身型 Systemic onsetn急性发病n多见于24岁幼儿，JIA 1/51/4n反复弛张热n随热出现的一过性红色斑疹n胸膜炎、心包炎n淋巴结及肝脾肿大n白细胞计数15X109n贫血和血小板升高n发热先于关节症状多关节型n受累关节5个nRF阴性和阳性亚型n关节梭形肿胀n关节积液、晨僵nRF及ANA阳性关节病变严重少关节型n是较多见的JIAn受累关节4个n主要累及大关节nRF阴性可发生虹膜睫状体炎nRF阳性可转化为强直性脊柱炎,HLA-B27阳性免疫检测n血IgG IgM IgA增高 n 血ANA RF可异常n 外周血CD4/CD8n 血HLA-B27（排除诊断强直性脊柱炎，并询问一级亲属家族史）实验室检查n血液检查(类白血病，贫血，血小板明显升膏）n 免疫检测（series,CCP)n 关节腔积液检查（关节穿刺）n 骨髓细胞学检查(一般,危重)n X线检查(SHARP EVALUATION)n MRI(TYPICAL)n 关节镜检查(骨中心）关节镜检查关节镜检查关节镜检查影象评价：病情评估sharp评分血液检查n白细胞升高n血小板升高n贫血n血沉加快nCRP升高n粘蛋白升高诊断（ACR)16ys Arthritis 关节炎 6mons subtype analysis According to new subtypes (JIA)应做鉴别诊断ACR Clinical Classification Criteria for Juvenile Rheumatoid Arthritis nGENERAL CLASS a. Persistent arthritis of at least six weeks duration in one or more joints b. Exclusion of other causes of arthritis (see list of exclusions+) nonset subtypes-determined by manifestations during the first six months of disease although manifestations more closely resembling another subtype may appear later nSystemic onset JRA* subtypes: Polyarthritis OligoarthritisACR Clinical Classification Criteria for Juvenile Rheumatoid Arthritisn*Typical fever and rash will be considered probable systemic onset JRA if not associated with arthritis. Before a definite diagnosis can be made, arthritis, as defined must be present. nPauciarticular* subtypes: Antinuclear antibody (ANA) positive-chronic uveitis Rheumatoid factor (RF) positive Seronegative, B27 positive Not otherwise classifiedACR Clinical Classification Criteria for Juvenile Rheumatoid Arthritisn*Patients with systemic onset JRA are excluded from this onset subtype. nPolyarticular subtypes: RF positivity Not otherwise classifiedn*Patients with systemic JRA onset are excluded from this subtype. ACR Clinical Classification Criteria for Juvenile Rheumatoid Arthritis nOther rheumatic diseases nRheumatic fever nSystemic lupus erythematosus nAnkylosing spondylitis nPolymyositis or dermatomyositis nVasculitic syndromes nScleroderma nPsoriatic arthritis nReiters syndrome nSjogrens syndrome nMixed connective tissue disease nBehcets syndrome ACR Clinical Classification Criteria for Juvenile Rheumatoid ArthritisnInfectious arthritis nInflammatory bowel disease nNeoplastic diseases including leukemia nNonrheumatic conditions of bones and joints nHematologic diseases nPsychogenic arthralgia nMiscellaneous nSarcoidosis nHypertrophic osteoarthropathy nVillonodular synovitis nChronic active hepatitis nFamilial Mediterranean fever ACR Clinical Classification Criteria for Juvenile Rheumatoid ArthritisnReference: JRA Criteria Subcommittee of the Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Association Arthritis Rheum 20(Suppl)195, 1977 ACR Guidelines for Medical Management of Rheumatoid Arthritis (updated April, 2002) 鉴别诊断感染性关节炎风湿性关节炎系统性红斑狼疮过敏性紫癜绒毛膜色素沉着性关节炎急性白血病其他血管炎综合征ComplicationnGrowth failurenMAS nServer infection nTB infectionnSide effects by steriod and immune inhibitor and bioagents JIA治疗目标治疗传统 抗炎药物治疗病程缓解药免疫抑制剂新近治疗生物制剂 造血干细胞移植血液净化 展望治疗 异基因移植治疗抗炎药物治疗n非甾体类药物(NASID) n布洛芬 n扶他林n尼美舒利n萘普生n阿司匹林以上药物FDA通过可在儿童应用布洛芬n1964年由英国Boots分司开发成功n1995年美国FDA批准布洛芬混悬液为OTCn1989年布洛芬缓释胶囊进入中国病情缓解药 (DMARD)甲氨蝶呤甲氨蝶呤 来氟米特来氟米特金制剂金制剂 青霉胺青霉胺羟氯喹羟氯喹 柳氮磺胺吡啶柳氮磺胺吡啶羟氯喹作用于抗原呈递环节羟氯喹作用n羟基氯喹对早期类风湿关节炎患者症状控制有效，（ E.L.Matteson,Rheumatology 2004;43:619-625）n对影像学改变的影响与其他慢作用药相似（Jorg J.Goronzy,Arthr Rheum 2004,50(1);43-54）羟氯喹作用羟氯喹作用羟氯喹不减少幼年特 发性关节炎患儿的 MTX血药浓度羟氯喹与MTX联用是 有效、安全的JRA 治疗方案R 25(5):1621- 2激素n全身治疗n眼科治疗n关节腔治疗其他免疫抑制剂nAZA nCTXnCSAnMMFn其他新型免疫抑制剂 酶酚酸酯MMF MPAesterasesesterases总结n长期随访，规则治疗n循证原则n选择安全有效的药物治疗n进行统一的评价体系分析n个体化治疗n合理诱导、巩固和维持治疗新医院展望未来