微小病变型肾病综合征发病机制的新进展

微小病变型肾病综合征(Minimal changednephmtic syndmme，MCNS)是肾病综合征常见的病理组织类型，在儿童发病率高，但由于其发病机制尚不明确，故无特异针对病因的治疗。现有治疗方案存在疗程长、副作用多、易复发、患者依从性差等缺点，严重威胁患儿的健康，因此，为了预防本病的发生以及在治疗上取得突破，其发病机制的研究至关重要。现将近年来有关微小病变型肾病综合征发病机制的新进展综述如下。     

微小病变型肾病综合征与淋巴因子（综述）

微小病变型肾病综合征(MCNS)的发病机理至今不清,新近研究表明,异常活化T细胞释放的淋巴因子与本病的免疫功能低下及肾小球滤过膜电荷屏障丧失相关,所以有学者称MCNS为淋巴因子相关性疾病,现将研究进展介绍如下。     

病毒基因反式激活在微小病变型肾病发病中的作用

病毒基因反式激活是病毒影响细胞基因表达、诱发疾病发生的形式之一。微小病变型肾病综合征是小儿常见疾病,其病因和发病机制目前尚未完全阐明,而呼吸道病毒感染与本病的触发密切相关。本文就呼吸道病毒基因反式激活在该病触发中的作用作一综述。     

儿童微小病变型肾病综合征的诊断和治疗

微小病变型肾病综合征（MCNS）对糖皮质激素敏感,但极易复发,可转变为对激素依赖或激素耐药,治疗非常棘手。该病诊断标准国内外基本一致,但均无最优治疗方案。本文介绍国内外诊断标准,并重点比较治疗方案。国外所选药物与国内基本一致,但剂量和疗程差异较大。建议个体化及综合治疗,根据不同个体或同一个体不同病程、病理类型改变、药物反应、药物不良反应来不断调整用药,特别要强调坚持治疗和随访的重要性。     

儿童脂蛋白肾病1例报告并文献复习

目的探讨儿童脂蛋白肾病(LPG)的临床及预后。方法回顾性分析1例儿童LPG的临床资料,归纳总结国内外报道的儿童LPG的临床特点及预后。结果患儿,女,9岁,以尿频起病,初次尿检提示菌尿、血尿、蛋白尿,规律抗感染治疗1周后,仍有血尿、蛋白尿,血清白蛋白轻度降低,高脂血症,轻度贫血;肾脏组织活检,镜下可见肥大肾小球,扩张的肾小球毛细血管管腔,其内充以脂蛋白栓子,油红O染色阳性;电镜下多见层状或簇状"栓子"内含颗粒状脂质空泡。基因检测APOE Tokyo(Leu141-Lys143→0)。诊断为LPG,给予降脂治疗后病情明显缓解。结论儿童LPG罕见,血脂水平显著增高,激素治疗无效,肾脏穿刺活检是确诊的主要依据,基因检测提示其遗传背景;降脂治疗可缓解病情进展。     

儿童低凝血酶原血症-狼疮抗凝物综合征2例报告并文献复习

目的对儿童低凝血酶原血症-狼疮抗凝物综合征(hypoprothrombinemia-lupus anticoagulant syndrome,HLAS)的临床特点进行总结,以提高对该病的认识。方法回顾性分析收治的2例HLAS患儿及医学引文索引(Medline)检索到的27例HLAS患儿的临床资料,总结其临床特点。结果 HLAS女性多发;可继发于病毒感染(14/29,48.2%)或系统性红斑狼疮(14/29,48.2%);临床主要表现为不同程度的出血,以中重度出血多见(25/29,86.2%),出血严重程度与原发病及凝血酶原活性无明显相关性;29例HLAS患儿中未经特殊治疗缓解者12例(41.4%),经过替代和(或)免疫性治疗缓解者15例(51.7%),病情仍有波动2例(6.9%)。结论 HLAS极其罕见,常继发于病毒感染或系统性红斑狼疮,临床表现为出血及低凝血酶原血症,大部分患儿预后良好。掌握其临床特点及诊断流程有助于早期诊断,避免误诊。     

儿童微小病变型肾病综合征致病相关基因筛查

目的比较微小病变型肾病综合征(MCNS)患儿与正常健康儿童外周血单个核细胞(PBMC)的基因表达谱变化,筛查MCNS相关致病基因,为揭示MCNS的发病分子机制和临床治疗提供线索。方法原发性MCNS患儿7例,正常同年龄对照组7例,Trizol法抽提PBMC总RNA;采用人类基因组表达谱芯片检测MCNS及正常健康儿童PBMC基因mRNA水平;采用逆转录-聚合酶链反应(RT-PCR)和荧光定量PCR检测部分基因转录水平,鉴定芯片相关检测结果。结果在33 000个基因转录本中,有969个转录本在MCNS患儿PBMC中存在表达差异,其中表达上调552个,表达下调417个。RT-PCR和荧光定量PCR检测结果与基因芯片较为一致。结论采用人类基因组表达谱芯片可快速有效地检测MCNS患儿PBMC中基因表达谱的变化,进而证实MCNS的发生、发展是涉及多基因改变的复杂过程。     

儿童 IgA 肾病合并膀胱血管瘤 1 例报告并文献复习

目的探讨儿科临床血尿性疾病的诊断思路。方法总结分析1例IgA肾病合并多发性膀胱血管瘤患儿的临床资料。结果女性患儿,9岁,临床表现为多次呼吸道感染后诱发间断肉眼血尿、持续性镜下血尿,伴尿中血凝块6年余,尿常规蛋白+++,RBC满视野/HP;24 h尿蛋白定量0.54~1.02 g,肾早期损伤指标以微量白蛋白为主;腹部、泌尿系超声未见异常;泌尿系增强CT扫描未见异常;肾动脉造影未见动静脉畸形或瘘;肾活检病理诊断为局灶增生性IgA肾病;膀胱镜检查提示多发性血管瘤。结论儿童膀胱血管瘤临床较为罕见,对于表现为肉眼血尿伴血凝块,影像学检查无明确异常或其他疾病者,如IgA肾病诊断后治疗不满意,应行膀胱镜检查,以除外膀胱血管瘤的可能。     

先天性肾病综合征芬兰型1例基因突变报告并文献复习

目的探讨先天性肾病综合征芬兰型(CNF)的临床表现及NPHS1基因突变类型。方法回顾分析1例CNF患儿的临床特点、患儿和父母NPHS1基因检测结果,并复习相关文献。结果患儿男性,34周早产,出生后即发病,临床表现为肾病综合征,血清病原学检查均为阴性,无家族史。患儿存在NPHS1基因突变c. 741GA,p.(Trp247*), c.928GA,p.(Asp310Asn),确诊为CNF。其中c. 741GA,p.(Trp247*),国内外均未见报道。结论新发现c. 741GA无义突变,丰富了NPHS1基因的突变谱。     

以血液系统损害为首发症状的儿童系统性红斑狼疮

目的探讨以血液系统改变为首发或主要表现的儿童SLE的临床特点、治疗方案及预后。方法对2005年6月-2011年6月收治以血液系统改变为主并最终确诊为SLE的38例患儿进行回顾性分析。其血液学改变按白细胞改变、贫血及血小板减少进行分析,并随访6～40个月。结果本组患儿血液系统改变中贫血28例(73.7%)、白细胞改变24例(63.2%)、血小板减少15例(39.5%),距确诊SLE的平均时间为8.5(0～24)个月。针对患儿不同症状选择免疫治疗,本组30例患儿SLE基本无活动,6例轻度活动,2例中度活动,无重度活动。15例PLT减少患儿中10例恢复正常,5例PLT维持在安全水平,8例已停药观察。16例自身免疫性溶血性贫血患儿中13例未再出现溶血发作,死亡1例;另2例患儿间断有轻度溶血发作。2例SLE相关再生障碍性贫血治疗显效。1例SLE相关纯红细胞再生障碍性贫血得到有效控制。结论儿童SLE很隐匿,初期常表现为血液系统损害,值得重视,对治疗效果欠佳患儿或青春期前后女童应警惕SLE,延长随访期限,评估病情以选择治疗方案和疗程。     

儿童系统性红斑狼疮国内外诊断标准比较

系统性红斑狼疮是一种全身多系统损害的自身免疫性疾病,预后欠佳,早期诊断非常重要。本文将1982年和1997年美国风湿病学会修订的诊断标准、1982年我国风湿病学会修订的标准（北京标准）及1987年上海风湿病学会修订的标准（上海标准）进行比较,了解各自的特点、敏感性和特异性,以便提高临床医师的诊断水平。     

Nephrotic syndrome in mesangial proliferative lupus nephritis

Renal involvement is a major complication of systemic lupus erythematosus (SLE) and occurs in 30-70% of patients with SLE. Lupus nephritis is classified into six classes (I-VI) by the International Society of Nephrology and Renal Pathology Society (ISN/RPS). Although nephrotic syndrome is commonly associated with diffuse (ISN/RPS class IV) or membranous (ISN/RPS class V) lupus nephritis, several reports have described nephrotic syndrome in adult patients with minimal mesangial lupus nephritis (ISN/RPS class I) or mesangial proliferative lupus nephritis (ISN/RPS class II). However, nephrotic syndrome in mesangial proliferative lupus nephritis has rarely been reported in children. Although the pathogenesis of nephrotic syndrome with mesangial lupus nephritis is incompletely understood, three potential mechanisms have been postulated including lupus nephritis itself, non-steroidal anti inflammatory drug (NSAID)-induced minimal change nephrotic syndrome (MCNS) and coincidental occurrence of MCNS. We describe here a child with mesangial proliferative lupus nephritis who developed MCNS.     

儿童系统性红斑狼疮伴肺间质病变的临床特征

目的了解儿童系统性红斑狼疮伴肺间质病变（SLE-ILD）的发生情况、特征。方法系统性红斑狼疮（SLE）患儿52例进行胸部X线和肺高分辨率CT（HRCT）检查,由2名以上放射科医师阅片,描述影像表现性质、程度。同时结合临床表现、血清学检查进行相关因素分析。结果SLE患儿出现ILD占26.9%,肺HRCT在发现SLE-ILD病变时优于普通胸片;根据患儿的临床表现、胸片、肺HRCT等,可将SLE-ILD患儿分为临床前期型12例（85.7%）,急性肺泡炎型2例（14.3%）,未发现有慢性ILD病变型病例;SLE-ILD患儿并浆膜炎发生率明显升高,而并肾损害发生率却明显降低（P〈0.05）;SLE-ILD患儿抗SSA抗体的阳性率明显高于无ILD组（P〈0.05）。结论儿童SLE-ILD的发生在儿童中并不少见,SLE-ILD更易出现在并浆膜炎、无肾损害及抗SSA抗体阳性患儿。肺HRCT对发现早期肺间质病变有诊断意义,对SLE-ILD患儿进行临床分型对预后判断和指导治疗有重要的价值。     

狼疮抗凝集物检测在系统性红斑狼疮、原发性血小板减少症中的临床应用

目的通过对系统性红斑性狼疮(SLE)310例和原发性血小板减少症(ITP)249例狼疮抗凝集物(LAC)和抗心磷脂抗体亚型(aCL-IgG、IgM、IgA)的测定,研究其与SLE临床表现的关系及LAC在ITP转归中的意义。方法采用脑磷脂-白陶土法(KCCT)及校正试验检测患儿血浆LAC;采用酶联免疫吸附试验(ELISA)测定息儿血清aCL-IgG,IgM、IgA。结果SLE 组中,66.1%显示体内存在高含量LAC,其中45.9%并狼疮肾炎;46.8?L抗体升高,其中90.2%为IgG和(或)IgM,分别有46.9%和11.7%是狼疮并中枢神经系统及血液系统病变。ITP组105例LAC阳性患儿中36.2%经抗核抗体(ANA)检测确诊为SLE,7.6%在2个月-2.4年后发展为SLE。结论LAC和aCL抗体亚型的水平与SLE临床表现密切相关,LAC在狼疮并肾脏病变中为优势病理性自身抗体;aCL抗体亚型的水平则与狼疮性血栓性血管炎性病变有相关关系。对单纯患有ITP的患儿应进行LAC动态观察,可及早确定疾病的转归。     

Systemic Lupus Erythematosus and Congenital Anomalies,Focusing on Neonatal Lupus Erythematosus and Anti-SS-A/SS-B Antibodies*

SLE is a representative autoimmune disease which develops preferentially in women of childbearing age. Its frequent occurrence makes the coincidence of SLE and pregnancy an important clinical problem. SLE is thought to be multifactorial disease. A familial prevalence was found to be 3% which was significantly higher when compared with Japanese prevalence of SLE. When women with SLE become pregnant, the fetus is at high risk and is adversely affected showing the high prevalence of fetal loss. Antiphospholipid antibodies were thought to be one of the causative factors. Ne-onetal lupus erythematosus (NLE) including lupus like skin lesions and congenital complete heart block (CCHB) is associated with maternal anti-SS-A and SS-B antibodies. The disease resolves with normalization of the maternal antibodies by the 8th month after delivery with the exception of the CCHB which is almost universally irriversible. When the sera from 4 maternal patients with NLE and 32 patients with normal delivery were analyzed by immunoblotting using recombinant 60 and 52 kD SS-A, and SS-B purified from calf thymus extract, the frequency of anti-52 kD SS-A and SS-B in patients with NLE was significantly higher than that of patients with normal delivery. Anti-SS-A/SS-B antibodies may react with the SS-A/SS-B antigens in fetal heart tissue as fetal levels of IgG increases which is almost simultaneously as when the SS-A/SS-B antigens appear in the fetal heart tissue. The pathogenesis of tissue damage mediated by autoimmune mechanisms specifically dependent on the biology of pregnancy is recognized to be due to passively acquired autoimmune injury. congenital complete heart block, anti-SS-A antibodies, anti-SS-B antibodies.     

儿童期系统性红斑狼疮与巨噬细胞活化综合征

在儿童,巨噬细胞活化综合征是风湿性疾病(特别是全身型幼年特发性关节炎)或炎症性疾病严重的、有时是致死性的并发症。然而,系统性红斑狼疮合并巨噬细胞活化综合征的临床报告多见于成人。文章重点对巨噬细胞活化等相关概念、感染致病、临床识别和治疗予以介绍。     

Myelopathy, Ascites and Pleural Effusion in Systemic Lupus Erythematosus

A 12-year-old girl with transverse myelopathy, massive pleural effusion and ascites as the presenting features of systemic lupus erythematosus (SLE), is described. All these features developed within a week, but other manifestations of SLE such as malar rash and arthritis were not seen during the illness. Investigations revealed positive direct Coombs' test, high titer of antinuclear antibodies, elevation of serum anti-DNA antibodies, depressed complement activity, thrombocytopenia and proteinuria, indicating that she had SLE. A week after starting treatment with prednisolone 35 mg/day, the thrombocytopenia improved, and following an increase in dosage to 60 mg/day the pleural effusion and ascites diminished after two weeks, and the serological abnormalities improved after two months. The neurological disturbances were unchanged in spite of injections of methylprednisolone 1 g/day for three days from the 89th day of her illness. Review of other cases reported to be improved neurologically, suggested that the earlier initiation of corticosteroids in higher dosage might be beneficial in transverse myelopathy m SLE.     

Acute Myocardial Infarction as the Presenting Symptom of Systemic Lupus Erythematosus

We report a case of acute myocardial infarction due to non-antiphospholipid-related coronary artery thrombosis as the presenting manifestation of systemic lupus erythematosus in a young patient. We present the acute workup and the results of successful transcatheter coronary intervention. The causes of acute myocardial infarction and coronary artery thrombosis in pediatric patients are reviewed.