1、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,周四下午，风湿专科 54524666转5084肾脏风湿科病房 54524666转,幼年特发性关节炎（JIA),Juvenile Idiopathic ArthritisJuvenile Rheumatic ArthritisJuvenile Chronic Arthritis 2001,JIA has been confirmed by ILAR,Types of Autoimmune Disease,幼年特发性关节炎（JIA),16岁以下儿童长期发热、皮疹淋巴结和肝脾肿大胸膜炎和心包炎反
2、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,感染遗传 1979 Stasty Fink HLA-DW7,DW8寒冷 潮湿 疲劳 营养不良,病因和发病机理,病理变化,关节病变 皮下结节 眼部病变 其他,免疫异常和损伤依据,血IgG IgA IgM 不同程度升高部分患儿补体升高可出现血和关节液RF阳性血和关节液TNF水平增高迟发超敏反应降低,自身抗体的临床价值,在典型风湿病 肯定诊断 （A-dsDNA,ACL)在不典型风湿病 提示诊断 如多关节炎 (CCP抗体阳性)评估预后及指导用药 抗体谱广 + 高滴度 病情
3、重 用药规范,自身抗体的临床价值,新近JIA相关抗体,抗CCP抗体BiP抗体AFA抗GPI抗体抗CB10抗体,临床表现 Manifestation,全身型多关节,RF+ 多关节,RF- 少关节,持续或扩展 银屑病型 附着点关节炎型其他,全身型Systemic onset,急性发病多见于24岁幼儿，JIA 1/51/4反复弛张热随热出现的一过性红色斑疹胸膜炎、心包炎淋巴结及肝脾肿大白细胞计数15X109贫血和血小板升高发热先于关节症状,多关节型,受累关节5个RF阴性和阳性亚型关节梭形肿胀关节积液、晨僵RF及ANA阳性关节病变严重,少关节型,是较多见的JIA受累关节4个主要累及大关节RF阴性可发生
4、虹膜睫状体炎RF阳性可转化为强直性脊柱炎,HLA-B27阳性,免疫检测,血IgG IgM IgA增高 血ANA RF可异常 外周血CD4/CD8 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,血液检查(类白血病，贫血，血小板明显升膏） 免疫检测（series,CCP) 关节腔积液检查（关节穿刺） 骨髓细胞学检查(一般,危重) X线检查(SHARP EVALUATION) MRI(TYPICAL) 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,白细胞升高血小板升高贫血血沉加快CRP升高粘蛋白升高,诊断（ACR
5、),16ys Arthritis 关节炎6mons subtype analysisAccording to new subtypes (JIA)应做鉴别诊断,ACR Clinical Classification Criteria for Juvenile Rheumatoid Arthritis,GENERAL CLASSa. Persistent arthritis of at least six weeks duration in one or more jointsb. Exclusion of other causes of arthritis (see list of exclu
6、sions+) onset subtypes-determined by manifestations during the first six months of disease although manifestations more closely resembling another subtype may appear later Systemic onset JRA*subtypes:PolyarthritisOligoarthritis,ACR Clinical Classification Criteria for Juvenile Rheumatoid Arthritis,*
7、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. Pauciarticular*subtypes:Antinuclear antibody (ANA) positive-chronic uveitisRheumatoid factor (RF) positiveSeronegati
8、ve, B27 positiveNot otherwise classified,ACR Clinical Classification Criteria for Juvenile Rheumatoid Arthritis,*Patients with systemic onset JRA are excluded from this onset subtype. Polyarticularsubtypes:RF positivityNot otherwise classified*Patients with systemic JRA onset are excluded from this
9、subtype.,ACR Clinical Classification Criteria for Juvenile Rheumatoid Arthritis,Other rheumatic diseases Rheumatic fever Systemic lupus erythematosus Ankylosing spondylitis Polymyositis or dermatomyositis Vasculitic syndromes Scleroderma Psoriatic arthritis Reiters syndrome Sjogrens syndrome Mixed c
10、onnective tissue disease Behcets syndrome,ACR Clinical Classification Criteria for Juvenile Rheumatoid Arthritis,Infectious arthritis Inflammatory bowel disease Neoplastic diseases including leukemia Nonrheumatic conditions of bones and joints Hematologic diseases Psychogenic arthralgia Miscellaneou
11、s Sarcoidosis Hypertrophic osteoarthropathy Villonodular synovitis Chronic active hepatitis Familial Mediterranean fever,ACR Clinical Classification Criteria for Juvenile Rheumatoid Arthritis,Reference: JRA Criteria Subcommittee of the Diagnostic and Therapeutic Criteria Committee of the American Rh
12、eumatism 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,Growth failureMAS Server infection TB infectionSide effects by steriod and immune inhib
13、itor 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,非甾体类药物(NASID) 布洛芬 扶他林尼美舒利萘普生阿司匹林以上药物FDA通过可在儿童应用,布洛芬,1964年由英国Boots分司开发成功1995年美国FDA批准布洛芬混悬液为OTC1989年布洛芬缓释胶囊进入中国,病情缓解药 (DMARD),甲氨蝶呤来氟米特,金制剂青霉胺,羟氯喹柳氮磺胺吡啶,羟氯喹作用于抗原呈递环节,羟氯喹作用,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）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,全身治疗眼科治疗关节腔治疗,其他免疫抑制剂,AZA CTXCSAMMF其他新型免疫抑制剂,酶酚酸酯,总结,长期随访，规则治疗循证原则选择安全有效的药物治疗进行统一的评价体系分析个体化治疗合理诱导、巩固和维持治疗,新医院,展望未来,
