幼年特发性关节炎治疗研究进展

幼年特发性关节炎（JIA）是小儿最常见的慢性风湿性疾病，其临床诊断标准为：①年龄小于16岁；②关节肿、痛、热、紧张或活动受限；③病程持续6周以上；④除外已知病因所致关节炎。JIA曾命名为幼年类风湿性关节炎（JRA），亦称Still病，1997年由国际风湿病学会改名为JIA。共分七型：①全身型（SOJIA）；②少关节炎型，又分为持续性和进展性；⑧多关节炎型（类风湿因子阴性）；④多关节炎型（类风湿因子阳性）；⑤银屑病型（PSOJIA）；⑥附着点相关型（ERA）；⑦其他型。现将近年来JIA治疗进展作一介绍。     

幼年特发性关节炎的诊治

幼年特发性关节炎 (Jl A )又称幼年类风湿性关节炎 (JRA)。近年来 ,本病有增有增多趋势。现将近年来的研究进展介绍如下。1　命名多年来 ,美国风湿病学会把本病命名为 JRA,亦称 Still病 ;。欧洲称为幼年慢性关节炎 (JCA)。 2 0 0 1年国际风湿病学联盟将其命名为 JIA。至今 JRA、JIA两个诊断名称均可使用。作者认为本病应命名为 JIA。2　分类国际风湿病学会把本病分为全身型、多关节型 (又分为类风湿因子阳性、类风湿因子阴性 )、少关节型 (又分为持续型和扩展型 )、银屑病型、附着点相关性关节炎、其他关节炎六型。上述全身型是指…     

幼年特发性关节炎的发病机制

幼年特发性关节炎 (juvenileidiopathicarthritis,JIA)过去美国称幼年类风湿关节炎 ,欧洲称幼年慢性关节炎。 2 0 0 1年国际风湿病学联盟将 16岁以下儿童不明原因关节肿胀 ,持续 6周以上统一命名为幼年特发性关节炎 ,并分为 7种类型[1] 。本文就其发病机制研究进展作一综述。1　人类白细胞抗原研究显示 ,多种人类白细胞抗原 (HLA )与JIA有关[2 ,3 ] :①HLA DRB1的亚型与多种类型JIA有关 ;②HLA A2、DR5、DR8、DPB1 0 2 0 1具有特征性 ,主要见于早发的寡关节型JIA ,多为女性 ,常伴有慢性虹膜睫状体炎 ,抗核抗体阳性 ;③迟发的寡…     

幼年特发性关节炎生物制剂治疗的研究进展

幼年特发性关节炎(iuvenile idiopathic arthritis,JIA)是儿童时期一种常见的结缔组织病,表现为16周岁以前发病,持续时间超过6周,且原因不明的各种关节炎病变.共分为7型:①全身型;②少关节炎型,又分为持续性和进展性;③多关节炎型(类风湿因子阴性);④多关节炎型(类风湿因子阳性);⑤银屑病型;⑥附着点炎相关型;⑦未分类型.有研究证实:约25%～70%的JIA患者在发病后的10年中仍处于疾病活动状态[1],并且这种疾病逐渐成为儿童致残的主要原因之一.目前,JIA的治疗以控制发热和急性期关节症状、维持发育、减少致残为主要目的,但缺乏特异性的治疗方法.     

白芍总苷胶囊治疗儿童特发性关节炎的临床有效性和安全性观察

目的观察白芍总苷胶囊(帕夫林,TGP)治疗幼年型特发性关节炎(JIA)的疗效及安全性。方法2003—2004年在上海4个中心(上海仁济医院、复旦大学附属儿科医院、上海第二军医大学附属长海医院、上海第二医科大学附属儿童医学中心)选择诊断明确的JIA中少关节型、多关节型及全身型三种类型的患儿80例,随机分为治疗组和对照组(采用拆信封法),治疗组给予TGP(朗生医药公司)联合甲氨蝶吟(MTX)治疗,对照组单用MTX治疗,观察患者关节症状改善程度、血沉变化情况以及药物副作用。结果第4周时治疗组患儿关节症状改善50%,明显高于对照组的30%(P<0.05),并且第4周时治疗组有效率为60%,明显高于对照组的37.5%(P<0.05),此外,白芍总苷胶囊与MTX联合应用在治疗初期能较大幅度地降低血沉。在不良反应发生方面,治疗组仅出现轻度的腹泻,且发生率较低(10%),而对照组部分患儿出现了肝功能的异常。结论白芍总苷胶囊与MTX联合应用能较好地缓解JIA患儿的关节症状,缩短患儿症状改善的时间,且不良反应发生率低,患儿耐受性好。     

附着点炎相关关节炎合并过敏性紫癜一例

附着点炎相关关节炎(ERA)为幼年特发性关节炎(JIA) 的亚型之一。过敏性紫癜(HSP)是一种儿童常见的IgA介导的血管炎。而ERA合并HSP尚不多见,现报告1例如下。患者男,16岁。因关节疼痛2年、皮疹3个月、肉眼血尿     

抗环瓜氨酸肽抗体在幼年特发性关节炎中的意义

幼年特发性关节炎(juvenile idiopathic arthritis,JIA)旧称幼年类风湿关节炎,是指16岁以下青少年不明原因的关节肿胀并持续6周以上的关节炎。JIA是儿童时期致残率最高的自身免疫性疾病．以慢性关节滑膜炎症为其主要特征。迄     

中国557例全身型幼年特发性关节炎临床特征和预后分析的多中心研究

目的 探索全身型幼年特发性关节炎(SoJIA)的临床特征和预后转归.方法 收集我国8家医院儿科2001-2011年住院治疗的SoJIA患儿资料,分析其临床特征和预后.结果 8家医院共收治1339例幼年特发性关节炎(JIA)患儿,其中SoJIA患儿557例(41.6％),男∶女平均为1.58,中位发病年龄为6.9岁(年龄0.5～15岁),起病时主要症状为发热557例(100.0％),关节炎355例(63.7％),皮疹319例(57.2％),浆膜腔积液103例(18.5％),肝肿大194例(34.8％),脾肿大7例(12.7％),浅表淋巴结肿大239例(42.9％),病程中并发巨噬细胞活化综合征54例(9.6％).关节炎发生时,累及的关节按发生频率排序为膝、踝、肩、腕.实验室检查白细胞计数升高493/555例(88.8％),红细胞沉降率升高541/554例(97.6％),C反应蛋白升高532/553例(96.2％),CD4/CD8 下降158/310例(51.0％),免疫球蛋白上升221/460例(48.0％),抗核抗体阳性40/455例(8.8％).治疗后,完全缓解232例(50.0％),部分缓解202例(43.5％),未缓解21例(4.6％)和死亡9例(1.9％).结论 中国SoJIA患儿男性多于女性,发病年龄跨度较广,发病高峰集中在5～7岁,关节炎在起病初期可不出现,如有关节炎则最常累及关节为下肢大关节,抗核抗体阳性并不能排除SoJIA的诊断,目前治疗条件下,预后较好.     

全身型幼年特发性关节炎并发巨噬细胞活化综合征研究进展

巨噬细胞活化综合征（macrophage activation syndrome，MAS）是儿童风湿病一个潜在的、威胁生命的并发症，最常并发于全身型幼年特发性关节炎（systemic juvenile idiopathic arthritis，sJIA），以分化良好的巨噬细胞过度活化和增殖为特征，进而导致发热、肝脾淋巴结肿大、全血细胞减少、肝功能紊乱、血管内凝血及中枢神经系统功能障碍等一系列临床表现的疾病。本病在临床上并不多见，临床医生对其往往认识不够充分。据此，本文拟对并发于sJIA的MAS在发病机制及临床诊治方面的进展作一综述。     

全身型幼年特发性关节炎并发巨噬细胞活化综合征2例报告并文献复习

目的探讨全身型幼年特发性关节炎（SOJIA）并发巨噬细胞活化综合征（MAS）的临床特征、诊断及治疗,以提高对该疾病的早期认识,降低病死率。方法分析2例SOJIA并发MAS患儿的临床症状、体征、辅助检查及病情进展、诊断、治疗、预后。结果 2例均有持续高热、肝脏及淋巴结进行性增大、肝功能急剧恶化、凝血功能障碍、外周血细胞骤减、血清铁蛋白急剧升高、中枢神经系统功能障碍、血沉和CRP下降、NK细胞减少等临床特征,经甲强龙冲击、环孢素A及丙种球蛋白静滴治疗后均好转出院。结论 SOJIA并发MAS早期表现为高热及外周血细胞减少等,及早予激素等治疗效果确切;临床医生应提高认识,以达到早期诊治、降低病死率的目的。     

Macrophage activation syndrome in children with systemic onset juvenile idiopathic arthritis: clinical experience from northwest India

The objective of this study is to describe the clinical and laboratory features of macrophage activation syndrome (MAS) in systemic onset juvenile idiopathic arthritis (SOJIA) at a tertiary care center in northwest India. Review of medical records of all children with SOJIA admitted during the period January 1995–December 2008 in Pediatric Allergy and Immunology Unit, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, was done. Six patients (5 boys and 1 girl) with SOJIA and MAS were identified. Mean age at time of disease onset was 6.5 years. MAS was the presenting manifestation of SOJIA in 4 patients. Clinical manifestations included fever (6/6), clinical shock (6/6), encephalopathy (5/6), generalized lymphadenopathy (4/6), hepatosplenomegaly (3/6), jaundice and abdominal tenderness (3/6), cardiac involvement (3/6), and meningeal irritation (2/6). Laboratory findings at onset of MAS included decreasing total leukocyte and platelet counts, coagulopathy, elevated transaminases, hyponatremia, and lipid abnormalities. Hemophagocytosis was demonstrable in the bone marrow in 4 patients and in the lymph node in 1. For treatment, we used intravenous methylprednisolone (4/6), oral prednisolone (2/6), and intravenous immunoglobulin (2/6). Outcome was favorable in all patients except one who died of rapidly progressive disease. This paper describes the experience of JIA-related macrophage activation syndrome in a tertiary Indian center. We have shown that MAS can be the early presenting manifestation of evolving SOJIA. Early diagnosis and aggressive management can have a significant impact on the mortality associated with this syndrome. We stress on the role of glucocorticoids in the management of this condition and believe that glucocorticoids have a far more important role in the management of this condition than what has been previously reported.     

Anakinra treatment for systemic onset juvenile idiopathic arthritis (SOJIA)

SIR, Systemic onset juvenile idiopathic arthritis (SOJIA) accountsfor 10–20% of all patients with JIA, but it accounts forincreased morbidity and mortality compared with other formsof JIA [1]. A significant number of patients have ongoing diseaseactivity despite aggressive treatment. A follow-up study foundthat the probability of disease remission 10 yrs after onsetwas only 37% [2]. Despite a variety of treatments some childrenwith SOJIA have a refractory course with significant morbidity.Pasqual et     

Methotrexate as a possible trigger of macrophage activation syndrome in systemic juvenile idiopathic arthritis

Macrophage activation syndrome (MAS) is a potentially life threatening complication of chronic rheumatic diseases, particularly systemic juvenile idiopathic arthritis (JIA). A number of triggers have been related to the development of MAS, including viral infections, nonsteroidal antiinflammatory drug therapy, and gold salt injections. We describe a patient with systemic JIA who developed MAS shortly after receiving methotrexate, suggesting that this drug can be regarded as a potential trigger of MAS in children with JIA.     

Juvenile idiopathic arthritis

Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatologic disease in childhood, which represents a nonhomogeneous group of disorders that share the clinical manifestation of arthritis lasting at least 6 wk under the age of 16. The exact diagnosis requires exclusion of other diseases that cause arthritis. The exact etiopathogenesis of JIA is still unknown. The interactions between genetic factors, environmental exposures and immune mechanisms are thought to contribute to pathogenesis of the disease. The “International League Against Rheumatism” classification divides JIA into 7 subtypes: oligoarticular JIA, rheumatoid factor (RF) positive polyarticular JIA, RF negative polyarticular JIA, systemic-onset JIA, enthesitis-related arthritis, juvenile psoriatic arthritis and undifferentiated JIA. Each subgroup of JIA is characterized by a different mode of presentation, disease course and outcome. The improvements in treatment of JIA in the last 2 decades, such as the early introduction of intraarticular corticosteroids, methotrexate and biologic agents, have dramatically upgraded the prognosis of the disease. If untreated, JIA may cause devastating results, such as disability from joint destruction, growth retardation, blindness from chronic iridocyclitis, and even multiple organ failure and death in systemic-onset JIA. The aim of treatment is the induction of remission and control the disease activity to minimize the pain and loss of function, and to maximize quality of life. JIA is a disease having a chronic course, which involves active and inactive cycles over the course of years. Recent studies showed that nearly half of the patients with JIA enter adulthood with their ongoing active disease. This review elucidates how recent advances have impacted diagnosis, pathogenesis and current treatment.     

Does red-man reaction stimulate macrophage activation syndrome in children with systemic juvenile idiopathic arthritis?

Macrophage activation syndrome (MAS) is a major cause of death in patients with systemic juvenile idiopathic arthritis (JIA). We describe 4 patients who developed MAS during or after vancomycin treatment. Vancomycin should be used with great care in patients with systemic JIA.     

Autologous hemopoietic stem-cell transplantation for children with refractory autoimmune disease

Autologous stem cell transplantation (ASCT) has been proposed as a possible treatment for severe autoimmune diseases such as rheumatoid arthritis (RA), multiple sclerosis (MS), systemic sclerosis, and systemic lupus erythematosus (SLE). To date, more than 250 patients with various autoimmune disorders have undergone an ASCT since 1996. Among them, there is a very limited number of children. This review summarizes the experience with ASCT for pediatric rheumatic diseases. Most reported cases concern juvenile idiopathic arthritis (JIA). Experience with ASCT for childhood SLE, Scleroderma, or Dermatomyositis is very limited. To date, 12 children with severe systemic or polyarticular JIA, all with progressive disease activity despite the use of corticosteroids, MTX, CsA, or Cyclophosphamide were treated in our center with ASCT. Rheumatologic follow-up at 3-month intervals up to 36 months showed a marked decrease in arthritis severity as expressed by the core-set criteria for juvenile chronic arthritis (JCA) activity. However, these children remain at risk for severe viral infections due to the prolonged lymfopenia. ASCT in this severely ill patient group induces a very significant and drug-free remission of the disease, but carries a significantly risk of developing fatal MAS.     

Early juvenile idiopathic arthritis

Early juvenile idiopathic arthritis (JIA) is important to recognize as timely diagnosis and treatment improves prognosis. It is a misconception that complications of JIA arise only from long-standing disease and that children will outgrow it. Early aggressive treatment is the paradigm as early disease activity has long-term consequences. There are predictors of persistent disease and joint erosions that may identify patients at higher risk. Control of disease activity within the first 6 months of onset confers improved clinical course and outcomes. The treatment perspective is thus one of early aggressive treatment for induction of disease control and ultimately remission.     

Hip involvement in juvenile idiopathic arthritis

We analyzed the clinical, biological, and radiological aspects of hip involvement in juvenile idiopathic arthritis (JIA) in a developing country. The recruited patients fulfilled the International League Against Rheumatism criteria for the diagnosis of the JIA. Clinical, biological, and radiological parameters relating to the JIA were collected. Hip involvement was assessed according to clinical and radiological data related to hip disease. One hundred twenty-one patients were included (68 girls and 53 boys). The mean age of the disease onset was 9 ± 4.2 years (1–16 years).The mean age of the patients at the time of the study was 15 ± 10 years (2–46 years). The duration of the disease was 5 ± 8.5 years (0.5–39 years). Forty cases (33%) of the hip involvement were noted. The mean age was 24 ± 10.03 years (3–46 years); the sex ratio was 1:3. The mean duration of the hip disease was 0.6 ± 3.6 years (3–14 years). Hip arthritis seemed to be more frequent in polyarticular and enthesitis-related arthritis. The severity of the hip involvement was significantly correlated with early disease onset, disease duration, subtypes, and high disability (for all these data p < 0.05). This study suggested that in JIA hip involvement was more frequent in enthesitis-related arthritis and polyarticular subtypes. It was correlated with the severity and the early disease onset of the JIA, which was similar to reported data.     

Temporomandibular involvement in juvenile idiopathic arthritis

OBJECTIVE: To study occurrence as well as clinical signs and symptoms of temporomandibular joint (TMJ) involvement in juvenile idiopathic arthritis (JIA) in a population representing all subtypes of JIA. METHODS: Ninety-seven consecutive children with JIA underwent orthodontic evaluation including an orthopantomogram (OPG). Further evaluation included patient characteristics, disease onset, course, and medical treatment. RESULTS: Forty-five percent of all children had TMJ involvement. Frequencies according to JIA subtypes: systemic 67%, oligoarticular (persistent and extended) 39%, rheumatoid factor (RF) negative polyarticular 59%, RF positive polyarticular 33%, enthesitis related arthritis 13%, psoriatic arthritis 33%, and other arthritis 50%. In children with a polyarticular course, irrespective of their disease onset, TMJ involvement was more frequent (55% vs 31% in oligoarticular course). In children with disease onset at a young age and/or an extended course of the disease, TMJ involvement was also more frequent. Pain during jaw excursion, absence of translation, asymmetry during maximal opening and protrusion, as well as crepitation during evaluation are predictors for TMJ involvement with a good specificity but a low sensitivity. Not all patients with TMJ involvement have clinical signs. CONCLUSION: Because of the high prevalence and discrepancy between clinical signs and presence of arthritis of the TMJ, regular orthodontic evaluation and OPG is recommended to recognize TMJ involvement and enable early intervention.     

上海单中心住院儿童风湿性疾病谱演变

目的:了解上海单中心风湿性疾病住院患儿疾病谱的变化趋势,提高对儿童风湿性疾病的认识。方法:回顾性分析2005—2016年复旦大学附属儿科医院5950例患者的临床资料,采用χ2检验进行发生率的比较和分析。结果:①住院例数位列前3位的分别是:川崎病2633例(44.3%),过敏性紫癜(HSP)2109例(35.4%),幼年特发性关节炎(JIA)574例(9.6%)。②除外HLP,其余病种住院人数均呈上升趋势。③近6年住院的风湿性疾病种类由原来的17种增长到目前37种。④SLE患者逐年增长(112/2348和197/3602,χ2=1.41,P=0.235),重症狼疮患者数亦较前增多(35/112和55/197,χ2=0.38,P=0.536)。⑤风湿性疾病合并巨噬细胞活化综合征(MAS)的发生率为7.2‰(43/5950),幼年型关节炎伴全身发作(sJIA)中有12.9%(26/201)出现过MAS,占风湿性疾病合并MAS总数的60.5%(26/43)。近6年风湿性疾病合并MAS(χ2=14.1,P<0.01),及sJIA合并MAS均明显增多(χ2=11.2,P<0.01)。⑥1.1%(64/5950)风湿性疾病相关肺部病变,幼年型皮肌炎(JDM)中24.4%(20/82)合并风湿性疾病相关肺部病变,占风湿性疾病相关肺部病变总人数的31.3%(20/64)。近6年风湿性疾病并发相关肺部病变及患者明显增多(χ2=5.66,P=0.017)。⑦儿童风湿性疾病病死率为3.7‰(22/5950),45.5%发生于SLE(10/22)。近6年SLE病死率有所下降(5/112和5/197,χ2=0.34,P=0.558)。结论:风湿性疾病住院患者病种及人数由多到少依次为川崎病、HSP、JIA、SLE及JDM。在每年总患者数相对稳定情况下,少见、疑难、危重病种逐年增多。虽近6年SLE仍是风湿性疾病主要死因,但病死率逐年下降。