儿童原发性免疫缺陷病的临床特点

目的了解儿童原发性免疫缺陷病(PID)的临床特点,以助于早期识别和诊断。方法对本院儿科住院诊断为PID的26例病例进行回顾性分析,记录病史、出生史、家族史、临床表现、实验室检查、诊断、治疗和转归等情况。结果PID中选择性IgA缺乏症6例,普通变异性免疫缺陷病、婴儿暂时性低丙种球蛋白血症各5例,T、B细胞联合免疫缺陷病、湿疹血小板减少伴免疫缺陷综合征各4例,慢性肉芽肿病2例。25例临床表现为反复感染,感染部位主要是呼吸道和消化道;确定有条件致病菌感染6例,自身免疫性疾病5例,有家族病史6例。住院期间死亡、放弃治疗各1例,其他病情好转出院。结论对反复感染、条件致病菌感染或伴自身免疫性疾病患儿,结合家族史,应尽早行免疫学检查,以早期识别和诊断PID。     

单中心174例原发性免疫缺陷病临床预警症状的初步探讨

目的 分析并总结原发性免疫缺陷病（PID）患儿的临床感染特征和预警症状,了解预警症状对PID早期识别的应用价值。方法 参考2011年免疫学会国际联合会(IUIS)PID分类委员会公布的方案、泛美免疫缺陷病组(PAGID)和欧洲免疫缺陷病协会(ESID)提出的PID诊断和分类标准,在首都医科大学附属北京儿童医院2000年10月至2011年11月病例检索系统检索出院诊断中含有上述PID分类疾病的病历,对于诊断低丙种球蛋白血症和联合免疫缺陷的患儿除外继发性免疫缺陷病,逐份查阅病历重新诊断,并做出明确、可以和可能诊断,以明确、可以诊断的病例进行预警症状的分析。结果 ①174例PID患儿进入分析,男女比例为4.4∶1,其中抗体缺陷为主的免疫缺陷101例(58.0%),严重联合免疫缺陷病（SCID）34例(19.5%),吞噬细胞功能缺陷19例(10.9%),定义明确的免疫缺陷综合征10例(5.7%),免疫失调性疾病10例(5.7%)。②75例(43.1%)存在反复呼吸道感染,以抗体缺陷为主的免疫缺陷最为常见,与SCID间差异有统计学意义;卡介苗接种后异常反应在慢性肉芽肿病（CGD）中最多见,与抗体缺陷为主的免疫缺陷和SCID比较差异有统计学意义;腹泻病在定义明确的免疫缺陷综合征中较常见,败血症在SCID和CGD患儿中较常见,但PID各类型间比较差异无统计学意义。③72例(41.4%)患儿存在营养发育落后,PID各类型间差异无统计学意义;淋巴结、肝和脾肿大以CGD和免疫失调性疾病最为常见;鹅口疮在SCID中常见,与抗体缺陷为主的免疫缺陷差异有统计学意义;肛周脓肿以CGD多见,与其他PID类型比较差异有统计学意义。107例(61.5%)有明确微生物学证据。④PID患儿共电话随访到85例(48.8%),其中死亡28例(32.9%)。⑤124例为明确和可以诊断PID,其中106例(85.5%)具备≥2条预警症状。静脉应用抗生素清除病灶(96.0%)、体重不增或生长发育极度迟缓(41.1%)、反复呼吸道感染(41.9%)和PID家族史(22.6%)在不同类型PID中均占有较高的比例。结论 预警症状对PID有着很好的提示作用,需要静脉应用抗生素清除病灶、体重不增或生长发育极度迟缓和PID家族史对PID有预警意义,中耳炎、中枢神经系统感染和反复呼吸道感染在抗体缺陷为主的免疫缺陷中较为多见, 深部脓肿、卡介苗接种后异常反应对CGD有预警意义。慢性反复发作性腹泻对PID预警作用值得进一步关注。     

儿童MSN基因突变致原发性免疫缺陷病1例并文献复习

目的：报告儿童MSN基因突变致原发性免疫缺陷病的临床特征及免疫表型。方法：总结分析1例MSN基因突变致原发性免疫缺陷病患儿的临床资料、免疫表型及治疗,并复习相关文献。结果：患儿男,8岁,临床表现为生后反复呼吸道和消化道感染,反复皮肤湿疹,频发足癣。中性粒细胞、淋巴细胞、单核细胞均降低,免疫球蛋白IgG、IgA和IgM低下,T、B和NK淋巴细胞计数降低,CD4+/CD8+比例倒置,DNT细胞比例增高,基因检测发现MSN基因外显子5有1个半合子、错义突变位点（c.511C＞T：p.R171W),为自发突变。在PubMed、Web of Science、中国知网、维普数据库和万方数据库中检索儿童Moesin（MSN）基因突变或缺陷,检索时间均从建库至2017年6月30日。共检索到相关文献2篇,均为英文文献,总结包括本文1例在内的6例MSN基因突变患儿的临床和免疫特点;临床均表现为生命早期发生反复感染,累及呼吸道、消化道和皮肤等,对细菌、真菌和病毒均易感,水痘-带状疱疹病毒感染尤为突出,易累及多系统。免疫表型方面,CD8+T细胞过量表达衰老细胞标志物CD57;给予免疫蛋白替代治疗以及预防性抗生素,可有效减少感染发生。结论：MSN基因突变所致免疫缺陷病表现为2岁以内即发生的反复感染,白细胞降低,低丙种球蛋白血症。     

原发性免疫缺陷患儿呼吸道合胞病毒感染情况分析

目的 了解原发性免疫缺陷（primary immunodeficiency,PID）患儿呼吸道合胞病毒（RSV）感染情况及临床特征。方法 收集2009年4月至2010年9月于重庆医科大学附属儿童医院就诊的PID患儿鼻咽吸取物30份,采用荧光定量PCR（ real-time RT-PCR ）方法检测RSV,对阳性标本进行病毒分离;并收集临床资料,分析其临床特征。结果 30份标本中检测出11份RSV,阳性率为36.7%。其中无感染症状2例（18.2%）,支气管炎3例（27.3%）,肺炎6例（54.5%）。2例无症状患儿近期均静脉滴注丙种球蛋白（IVIG）。结论 PID患儿更易感染RSV;IVIG应用于免疫缺陷患儿能够降低RSV肺炎的发生率。     

发热与原发性免疫缺陷病

住院医师汇报病史：患儿，男，7岁，体重22№。因“发现免疫功能异常3年，发热、咳嗽1个月”于2014年4月2日入院。患儿4月龄起有反复呼吸道感染病史，3年前因反复化脓性中耳炎在当地住院，多次查免疫功能提示免疫球蛋白IgM增高，外院诊断为原发性免疫缺陷病（高IgM血症），之后每月输注静脉丙种球蛋白替代治疗。1个月前患儿无明显诱因下出现发热，伴咳嗽、流涕，热峰40．5℃，     

儿童肺隐球菌病6例诊断和治疗分析

目的　探讨儿童肺隐球菌病的诊断与治疗。方法　回顾性分析北京儿童医院 2 0 0 0～ 2 0 0 2年收治的 6例肺隐球菌病患儿的临床资料、影像学表现、免疫状态、诊断方法、治疗和转归。结果　 6例均起病缓慢、病史长 ,症状为发热、咳嗽。肺部查体 5例正常 ,1例闻及干性音和中水泡音。 4例体液和细胞免疫功能检查正常 ,1例人类免疫缺陷病毒阳性 ,1例为X 连锁低丙种球蛋白血症。 6例患儿均发生血行播散 ,其中 5例合并脑膜炎。 2例应用二性霉素B和氟康唑治疗后 ,肺隐球菌病控制 ,脑膜炎好转 ;3例放弃治疗 ;1例合并肝脾和淋巴结隐球菌病 ,应用氟康唑治愈。结论　儿童肺隐球菌病可发生于免疫功能正常的儿童 ,其临床和影像学表现无特异性 ,诊断依赖于对该病的警惕和认识及隐球菌检查。儿童肺隐球菌病易发生血行播散应及时予抗真菌治疗。     

原发性免疫缺陷病诊断筛查步骤（草案）

原发性免疫缺陷病诊断筛查步骤（草案）（１９９５年１１月于重庆第四届全国小儿免疫学术会议）一、详细询问病史家族中曾有因感染死于婴幼儿时期者或有反复感染者是原发性免疫缺陷病的重要线索。感染发生于生后者，应疑为联合免疫缺陷病；生后６个月才发生反复化脓性感染...     

原发性免疫缺陷病感染防治措施概述

原发性免疫缺陷病（PID）患儿易发生反复、严重、持续或致死性感染。熟悉PID感染防治措施有利于对这类疾病患儿进行慢病化管理及改善预后。本文主要介绍PID感染防治措施中的一般措施、疫苗接种、抗生素应用及静脉注射丙种球蛋白替代治疗。     

原发性免疫缺陷病临床发病情况回顾

目的了解原发性免疫缺陷病的临床发病情况,加强临床医师对该类疾病的认识,促进今后防治工作的开展.方法回顾性分析1974年1月至2003年12月我院93例原发性免疫缺陷病患儿的临床资料.结果93例原发性免疫缺陷病患儿中,以抗体缺陷为主者占39.8%（37/93）;以联合免疫缺陷者占22.6%（21/93）;以T淋巴细胞缺陷为主者占14.0%（13/93）;其他明确的免疫缺陷综合征者占12.9%（12/93）;吞噬功能缺陷者占9.7%（9/93）;补体缺陷者占1.1%（1/93）.从年度诊断的原发性免疫缺陷病病例数来看有逐年增多的趋势,1996年以后诊断例数呈现大幅度上升,共诊断50例.死亡病例共计16例,以联合免疫缺陷病为主.男：女=3：1.结论我国各类原发性免疫缺陷病均有发病,并且随着诊断技术水平的不断提高,临床诊断的病例日益增多,已成为临床,特别是儿内科的一组重要的疾病,应引起全国临床医师的注意.     

儿童免疫缺陷病的诊断与治疗

免疫缺陷病临床分为原发性免疫缺陷病(PID)和继发性免疫缺陷病(SID),前者为单基因遗传病,某种免疫应答反应完全缺失,后者继发于某些疾病或特殊生理时期,免疫应答反应呈一般性低下。PID分为8大类型,诊断以临床表现、免疫功能缺陷和基因检测为依据。普通儿科医师应掌握诊断逻辑程序和筛选方法,学会检索及网上咨询。PID治疗以对症、替代治疗和干细胞移植为主要手段。SID的诊断以原发疾病为线索,反复感染为特征,免疫功能检测较困难,常为一般性降低。SID治疗以根治原发病,改善全身器官功能状态为本,有针对性选用免疫调节剂可能有帮助。     

Immunological investigations in children with recurrent respiratory infections

Respiratory tract infections are common diseases in childhood. Most children with recurrent respiratory infections do not have an immunodeficiency. If they do, this is often due to an antibody deficiency. An important point in the investigation of a child with recurrent respiratory infections is to assess whether the child is thriving. If not, an underlying disease should be sought. Immunological investigations are useful if other, more frequent, underlying diseases have been ruled out. Early immunological screening is mandatory if there is a family history of immunodeficiency. In this review, a protocol is described which identifies children with severe antibody deficiency by simple screening tests before recurrent infections have caused irrepairable damage to the lungs. More elaborate tests are used to detect milder antibody deficiencies. These are reserved for those children in whom symptoms persist.     

儿童原发免疫缺陷病72例临床分析

目的了解儿童原发免疫缺陷病的临床特点。方法回顾分析2000-10—2006-10在北京儿童医院病房收治的原发免疫缺陷病患儿的临床资料。结果72例原发免疫缺陷患儿中以抗体缺陷为主的免疫缺陷病41例(57·0%),联合免疫缺陷病16例(22·2%),吞噬细胞数量和(或)功能缺陷8例(11·1%),以T细胞缺陷为主的免疫缺陷病4例(5·6%),定义明确的免疫缺陷综合征3例(4·2%)。其共同特点为反复的、严重的、持久的感染,但病因不同,又有其各自的特点。如寻常变异型免疫缺陷病病史长者易合并肝脾大及关节炎。严重联合免疫缺陷病发病年龄小,病死率高,除呼吸道感染外,迁延性腹泻较多见;而慢性肉芽肿病以反复的皮肤、淋巴结脓肿及易发生卡介苗播散性疾病为特点。结论原发免疫缺陷病以抗体缺陷为主。部分类型有其独有特点,根据症状、体征可进行相应的检查以明确诊断。约1/4患儿有阳性家族史,对此类患儿应慎重预防接种,以免为患儿造成不必要的痛苦。目前原发免疫缺陷病患儿管理仍极不完善,大量患儿失访或放弃治疗,形势严峻,亟待改善。     

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目的 分析儿童原发性免疫缺陷病(PID)的临床发病及诊断情况,增强儿科医师对该类疾病的认识.方法 回顾性分析重庆医科大学附属儿童医院1993年5月至2007年12月诊断的135例PID患儿的临床资料,包括发病时症状体征、性别、发病年龄、家族史、免疫学结果 及诊断情况.结果 135例患儿中以抗体缺陷最多,占34.8%.吞噬细胞缺陷占18.5%,其他明确的免疫缺陷综合征占14.8%,联合免疫缺陷占11.9%,免疫失调性疾病占5.9%,补体缺陷占0.7%,其他PID占13.3%.男女比例为110:25,临床诊断与基因诊断比例为98:37.1993-1996年诊断9例,1997-2000年诊断23例,2001-2003年诊断31例,2004-2007年诊断72例,诊断病例数逐年增加.其中2001-2003年基因诊断7例,2004-2007年基因诊断30例.结论 PID为一组主要见于婴幼儿的遗传病,是引起儿童反复、严重、致残、致死性感染的重要原因.近年来诊断的PID病例数逐年增加,基因分析是确诊该类疾病的重要手段.     

Defects of IgG subclasses as a cause of severe, recurrent respiratory tract infection

IgG Immunoglobulins can be differentiated into four subclasses with different structures and functions. Partial or complete defects of one or two subclasses can be related to an impaired immune defence. We describe four children with severe recurrent bacterial airway infections. Two children had developed bronchiectasia following recurrent bronchopulmonary inflammation. Prior to diagnosis of IgG subclass deficiency other common causes of recurrent airway infections were excluded. Defects of IgG 2 or IgG 4 antibodies as well as of both classes were found with compensatory elevation of IgG 1 and IgG 3. In repeated sputum cultures haemophilus influenzae and staphylococcus aureus were isolated. This might be due to an impaired antibody production against special antigens as alpha-toxin of staphylococcus or capsular polysaccharide of haemophilus influenzae. The four cases demonstrate that in children with severe recurrent airway infections including bronchiectasia and otitis media defects of IgG subclasses have to be considered. Diagnosis should be proved by repeated determinations of blood levels after exclusion of other common causes for infections. Diminution of IgG subclasses without clinical symptoms of airway infections is also possible. If diagnosis seems to be certain intravenous substitution with 7 s gammaglobulin beside symptomatic antibiotic therapy is recommended.     

Consensus Document on the differential diagnosis and therapeutic approach to recurrent fever by the Paediatric Infectology Society and the Paediatric Rheumatology Society

Recurrent fever is a relatively common problem during childhood. Diagnosis is often easy and related to mild viral infections. However a small proportion of these cases originate from an underlying non-infectious process that is generally difficult to diagnose. In this paper we describe the differential diagnosis of recurrent or periodic fever versus other processes, with especial attention to autoinflammatory disorders (AD). AD are alterations of innate immunity, and they have been recently classified as an immunodeficiency. Anyhow, since infections are not present, these processes are different to the classic primary immunodeficiency. An important part of AD is of known genetic aetiology. The symptoms originate from an underlying inflammatory process and can have different clinical expressions. One of the most relevant groups is the hereditary syndromes of periodic fever. This group of diseases associates recurrent fever and several clinical symptoms with a relative periodicity, separated by intervals free or almost free of symptoms. We include the diagnostic criteria for some processes as well as the characteristics that should, eventually, lead to a genetic study. Although treatment should be individualised, we also include some general recommendations.     

Spectrum of primary immunodeficiencies in a tertiary hospital over a period of 10 years

IntroductionMore than 200 primary immunodeficiencies (PID) have been described and about 60% present during childhood. Early diagnosis and treatment have been shown to improve patient outcome.AimAnalysis of patients with a PID diagnosed in a paediatric tertiary care hospital-referral centre over a period of 10 years.Patients and methodsMedical records of all paediatric patients followed up in our unit were retrospectively reviewed. Clinical and epidemiological features, laboratory tests, therapy and outcome were analysed.ResultsOne hundred and eighty nine patients were followed up in this period of time. Antibody disorders were the most common diagnosis. In our series, clinical presentation at diagnosis were: recurrent respiratory infections in selective IgA deficiency and common variable immunodeficiency (CVID) patients, failure to thrive and opportunistic infections (mainly viral infections) in patients with severe combined immunodeficiency (SCID), skin abscesses (Staphylococcus aureus, Serratia spp.) and complicated pneumonia (Aspergillus spp., Rhodococcus equi) in chronic granulomatous disease, congenital heart disease and consistent phenotype in 22q11 deletion syndrome, skin abscesses and ecthyma gangrenosum in severe congenital neutropenia and opportunistic infections and sepsis (Pseudomonas aeruginosa) in children with X-linked agammaglobulinaemia (XLA). Lymphoproliferative disorders were common in CVID. No malignancies were observed during this period. One patient with XLA developed chronic encephalitis.All patients with CVID and XLA were receiving immunoglobulin replacement therapy (8 intravenous and 14 (since 2006) subcutaneous route) and in all but two SCID patients, stem cell transplantation was performed. Outcome was good in most of them except 8 SCID (2 prior and 6 after transplantation), 3 Wiskott-Aldrich syndrome, 1 complete DiGeorge, 1 chronic granulomatous disease and 1 ataxia-telangiectasia patients who died during follow-up.ConclusionThe vast majority of patients included in this series presented with typical clinical features; therefore, basic knowledge of these entities in primary care and collaboration with hospital referral centres should allow a large number of PID in children to be diagnosed at an early stage, leading to proper treatment and monitoring, and therefore improvement of patient prognosis.     

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??Primary immune deficiency??PID?? represents a highly heterogeneous group of disorders from early ages. The clinical manifestations of these diseases were mainly recurrent and severe infections. Because of the difficulty on diagnosis and differential diagnosis and on treatment of recurrent and refractory infections?? most PIDs were intractable cases. Recent advance in the understanding of the immune system have led to the development of novel immunologic assays to aid in the diagnosis of these disorders??and more and more PID patients are diagnosed and have received suitable therapy. In this article??the author reviewed the progress and application of immune functional evaluation in PID??including flow cytometry??FCM????investigating T cell receptor excision circles??TREC????T cell receptor beta-chain variable region??TCRBV?? repertoire diversity.     

Flow cytometric immunophenotyping in the diagnosis and follow-up of immunodeficient children

From time to time, paediatricians are confronted with children who might suffer from a primary immunodeficiency disease. For practical purposes, these children can be divided into four main clinical categories: (1) a relatively large group of children with recurrent ear-nose and throat and lower respiratory tract infections, in some cases caused by deficiencies of antibodies or complement; (2) children with failure to thrive, intractable diarrhoea or an opportunistic infection which can be caused by a T-lymphocyte or combined immunodeficiency; (3) children with infections with pyogenic bacteria or fungi as seen in case of granulocyte/monocyte function deficiency; and (4) a small heterogeneous group of children with recurrence of particular infections. Also, acquired immunodeficiency becomes a more common problem in paediatric practice. Flow cytometric immunophenotyping of leucocytes appears to be an efficient and rapid tool in the diagnosis and follow-up of immunodeficient patients, supporting early recognition, before serious infections have compromised the child's general condition. This technique can now be performed in many hospitals. In this review, we give directions for the use of flow cytometric immunophenotyping of leucocytes in the diagnosis and follow-up of immunodeficient children according to the four main clinical categories.