幼年特发性关节炎课件

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 Introduction n周四下午，风湿专科 54524666转5084 n肾脏风湿科病房 54524666转3011 幼年特发性关节炎（JIA) nJuvenile Idiopathic Arthritis nJuvenile Rheumatic Arthritis nJuvenile Chronic Arthritis 2001,JIA has been confirmed by ILAR Types 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,DW8 n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 nAFA n抗GPI抗体 n抗CB10抗体 临床表现 Manifestation n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 onset n急性发病 n多见于24岁幼儿，JIA 1/51/4 n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15X109 n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JIA n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/CD8 n 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 Oligoarthritis ACR Clinical Classification Criteria for Juvenile Rheumatoid Arthritis n*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 classified ACR Clinical Classification Criteria for Juvenile Rheumatoid Arthritis n*Patients with systemic onset JRA are excluded from this onset subtype. nPolyarticular subtypes: RF positivity Not otherwise classified n*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 Arthritis nInfectious 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 Arthritis nReference: 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 Complication nGrowth failure nMAS nServer infection nTB infection nSide 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OTC n1989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 nCTX nCSA nMMF n其他新型免疫抑制剂 酶酚酸酯 MMF MPA esterasesesterases 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 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