以血细胞减少为首发表现的儿童原发性免疫缺陷病23例临床分析

目的回顾血细胞减少为首发表现的原发性免疫缺陷病(PID)的病例资料,了解PID并发免疫性血细胞减少的临床特点,为临床诊疗工作提供帮助。方法收集我院血液肿瘤中心自2012年1月至2014年7月间收治的23例以免疫性血细胞减少为首发表现的PID患儿临床资料并进行回顾性分析。结果23例中男14例,女9例,男:女=1.55:1;中位发病年龄11(1~107)个月,中位病程3个月(2 d~38个月);经过临床及实验室确诊联合免疫缺陷病6例、伴有其他症状的免疫缺陷病(湿疹血小板减少伴免疫缺陷综合征)5例、以抗体缺陷为主的免疫缺陷病(包括选择性IgA缺乏及普通变异型免疫缺陷病)7例、吞噬细胞功能缺陷(先天性中性粒细胞减少)1例、淋巴细胞凋亡缺陷(自身免疫性淋巴增殖性疾病)4例;其中14例进一步得到基因诊断证实。23例中以溶血性贫血为表现者9例、血小板减少9例,两系血细胞减少2例及全血细胞减少3例。对常规免疫治疗有效者4例(17.4%),部分有效者11例(47.8%),复发者3例(13.0%),无效者5例(21.7%,其中死亡1例)。结论PID并发免疫性血细胞减少常于婴儿期起病、男性多见,虽可影响两系及以上血细胞,但以单系免疫性血细胞减少为主;对常规免疫治疗效果欠佳、病程常迁延反复。诊断需结合临床及相关实验室检查,还可借助基因诊断。临床医生对常规免疫治疗效果不佳的儿童(尤其是婴幼儿)免疫性血细胞减少,需要注意存在PID的可能。     

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。     

小儿获得性低巨核细胞性血小板减少性紫癜临床报告

获得性低巨核细胞性血小板减少性紫癜(AATP) ,近年来国内外学者对成人发病屡有报道 ,但有关小儿病例报道较少 ,我院自19 91年～ 1996年收治本病 5例 ,报告如下 :临床资料1.一般资料 :本组 5例均为我院住院患儿 ,并符合朱跃军等提出的诊断标准。男 3例 ,女 2例 ,年龄 7～ 12岁 ;起病至确诊时间1月～ 2年。本文仅有 1例在本院首次确诊 ,余 4例均被误诊为特发性血小板减少性紫癜(ITP) ,并间断地给强的松或强的松及丹那唑治疗 3月～ 2年不等 ,发病前 2例分别患上呼吸道感染、支气管炎 ,伴发烧曾用过小儿APC、安乃近或复方氨基比林 ,余 3例病…     

造血干细胞移植在原发性免疫缺陷病治疗中的进展

原发性免疫缺陷病（PID）是一种以反复感染、易患自身免疫性疾病和恶性肿瘤为特征的免疫系统疾病,该病预后差,生存期短。目前认为,根据发病机制,利用造血干细胞移植以达到免疫重建是根治该病最为有效的方法,国外已有治疗X连锁高IgM血症、重症联合免疫缺陷病、慢性肉芽肿病、湿疹一血小板减少一免疫缺陷综合征、白细胞黏附缺陷症等疾病的相关报道,供体来源、移植前预处理等都对移植的成功有很大影响。2006年9月我国已有首例PID患者接受了骨髓移植治疗,希望今后会有越来越多的PID患者通过骨髓移植治愈。     

Wiskott-Aldrich综合征致病基因的回复突变现象及其临床意义

Wiskott-Aldrich综合征(WAS)即湿疹、血小板减少、免疫缺陷综合征,为x连锁隐性遗传,是以湿疹、血小板减少、反复感染、易患淋巴系统恶性肿瘤和自身免疫性疾病为特征的原发性免疫缺陷病(PID).该病致病基因编码的蛋白质为WASP,是由502个氨基酸构成的富含脯氨酸的蛋白质.WASP表达于所有非红系造血细胞,包括CD28~+干细胞、血小板、淋巴细胞、中性粒细胞、巨噬细胞和树突状细胞,在细胞生长和骨架形成的信号转导过程中发挥重要作用.突变基因在体内发生自发性回复突变,从而导致体细胞嵌合已在多种PID患者中报道,如腺苷脱氨酶缺乏所致的重症联合免疫缺陷(ADA-SCID)~([1])、X连锁的严重联合免疫缺陷(X-SCID)~([2])、白细胞黏附分子缺陷病(LAD)~([3])、因核因子KB必需分子(NEMO)基因突变导致的高IgM综合征和外胚层发育不良~([4-5])等.随着我国基因诊断明确的WAS病例数不断增多,WASP基因的回复突变现象应引起高度关注,现就其发生机制和临床意义综述如下.     

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。     

中国原发性免疫缺陷病现状和展望

1我国对原发性免疫缺陷病认识发展过程自1952年Bruton发现首例反复肺炎、鼻窦炎和中耳炎患儿,伴血浆电泳γ球蛋白带缺乏,而后被命名为X连锁无丙种球蛋白血症以来,人们认识原发性免疫缺陷病(primary immunodeficiency disease,PID)已近60年。我国对PID的认识和研究大致分两个阶段即启蒙阶段和发展阶段,启蒙阶段之前经历了近20年。虽然我国20世纪60年代已有与PID有关的零星病例报道,但直到80年代初天津市儿童医     

非典型川崎病25例临床特点回顾性分析

目的总结非典型川崎病的诊疗经验。方法对25例非典型川崎病患儿的临床资料进行回顾性分析。结果 25例非典型川崎病患儿中,10例误诊为咽结合膜热,5例误诊为淋巴结炎,1例误诊为猩红热,1例误诊为金黄色葡萄球菌烫伤样皮肤综合征,8例拟诊为川崎病。25例患儿均有持续发热,误诊患儿中临床症状、体征可有多变性,体征非持续性。血白细胞、血沉、C反应蛋白、血小板均升高。心脏彩超2例出现冠状动脉改变。经使用阿司匹林和丙种球蛋白联合治疗,25例患儿预后良好,随诊1年无冠状动脉异常发现。结论对于持续发热,抗生素治疗无效的患儿,白细胞、血沉、C反应蛋白、血小板等明显升高,结合多变的临床症状、体征,应警惕川崎病的可能性。阿司匹林和丙种球蛋白联合应用是川崎病的标准治疗方法。     

原发性免疫缺陷病早期识别

原发性免疫缺陷病(primary immunodeficiency disease,PID)是一类以单基因遗传为主的少见免疫缺陷疾病。国外流行病学研究认为,具有临床表现的PID发病率为1/20000～1/5000活产婴。我国目前仅有极少部分PID患儿得到确诊,早期诊断是提高PID患儿生存率和生活质量的关键。本文首先分析国外PID预警症状在PID诊断中的价值,然后根据笔者单位多年来积累的临床经验,结合我国国情,提出PID早期识别线索,以供儿童免疫专科医师讨论和儿科医生参考。     

小儿免疫性和变态反应性疾病诊治进展

现将国内 2 0 0 1年度儿科免疫性和变态反应性疾病诊治进展简述如下。1　原发性免疫缺陷病 (ＰＩＤ)ＰＩＤ仍未能引起临床医师的足够重视。年度内仅有贾月萍等报道选择性ＩｇＡ缺陷合并Ｅｖａｎ综合征及桥本甲状腺炎 1例以及笔者报道的严重联合免疫缺陷病———Ｏｍｅｎｎ综合征 1例。另有张宁[1] 等报道用流式细胞仪检测外周血ＣＤ19+ 细胞 (Ｂ细胞 )数量协助诊断先天性Ｘ 连锁无丙种球蛋白血症 (Ｘ ＬＡ) ,8例血清ＩｇＧ <2 ｇ/Ｌ患儿外周血ＣＤ19+ 细胞 <1%确诊为Ｘ ＬＡ。目前国内已基本具备ＰＩＤ基因筛查与分子诊断能力 ,依靠我国丰富…     

亚历山大病及海绵状脑白质营养不良

亚历山大病(Alexander disease,AD)及海绵状脑白质营养不良(Canavan disease,CD)是遗传性脑白质病中比较少见的两种疾病.自国外首次报道本病以来,AD历经60年,CD历经近80年的观察研究,人类对两病的认识不断深入.本文结合国内外的研究现状和笔者追踪观察临床病例的体会,做一总结分析.     

佩梅病及佩梅样病

佩梅病(Pelizaeus-Merzbaeher disease,PMD)是一种罕见的弥漫性脑白质髓鞘形成障碍的X连锁隐性遗传疾病,属蛋白脂蛋白1(proteolipid protein 1,PLP1)相关的遗传性髓鞘形成障碍疾病谱中的一种.PMD特征性病理改变为神经髓鞘不能正常形成,而非其他遗传性白质脑病那样脱髓鞘改变.     

Autoimmune thyroid disease and celiac disease in children

BACKGROUND: Celiac disease (CD) may be associated with other immunologic disorders in adults and children. Previous studies linking CD and autoimmune thyroid disease in children have included very few patients with limited biochemical and immunologic screening tests. The aim of this multicenter study was to establish the prevalence of autoimmune thyroid involvement in a large series of pediatric patients with CD. METHODS: Five hundred seventy-three consecutive pediatric patients were enrolled from clinics in Torino, Bologna, Foggia, Rome (two clinics), Naples, and Bari. Three hundred forty-three patients with CD were studied, 230 girls and 113 boys (median age, 8.5 years). Two hundred fifty-six of the patients with CD (median age, 9 years) had been following a gluten-free diet for 3 months to 16 years; 87 patients were untreated (median age, 6.2 years). The diagnosis of CD was made using the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) criteria. A control group of 230 subjects (median age, 8.3 years) was enrolled. Serum free triiodothyronine, free thyroxine, and thyroid-stimulating hormone (TSH), antithyroperoxidase, antithyroglobulin, anti-TSH receptor antibodies, and thyroid echographic pattern were considered. RESULTS: Autoimmune thyroid disease was found in 90 of 343 (26.2%) patients with CD (62 on a gluten-free diet) and in 20 (10%) of the control subjects (P = 0.001). Fifty-four (15.7%) patients with CD and autoimmune markers had normal thyroid function (euthyroidism) as did 12 (6.0%) of the control subjects; hypothyroidism was observed in 28 (8.1%) patients with CD and in 7 (3.5%) of the control subjects. Hyperthyroidism was diagnosed in four patients with CD and in none of the control subjects with autoimmune markers. An abnormal echographic pattern was seen in 37 patients with CD (16.8%) and only in 1 (1.6%) of the control subjects (P = 0.002). CONCLUSIONS: The high frequency of autoimmune thyroid disease found among patients with CD, even those on a gluten-free diet, may justify a thyroid status assessment at diagnosis and at follow-up evaluation of children with CD.     

Probable autoimmune thyroid disease and combined immunodeficiency disease

An 8-year-old girl with combined immunodeficiency secondary to adenosine deaminase deficiency developed thyroid failure of probable autoimmune origin manifested by linear growth deceleration, marked bone-age delay, and myxedema. To our knowledge, this association has not been previously reported. Immunologic abnormalities included absolute T-cell lymphopenia and markedly reduced in vitro lymphocyte responses to phytohemagglutinin and to alloantigen in the mixed lymphocyte reaction. The diagnosis of autoimmune thyroid disease was suggested by the presence of antithyroglobulin antibodies in the serum and by decreased, patchy uptake of iodine 123 on a thyroid scan. Autoimmune thyroid disease may have developed because the immunodeficient state, with its greater deficiency of suppressor/cytotoxic T cells, allowed expression of a clone of helper T lymphocytes specific for thyroidal antigens. Thus, autoimmune disease may be more common in immunodeficient states and appropriate surveillance should be instituted.     

Bone disease in infants and children with hepatobiliary disease

Radiological studies of bone were performed in infants and children with hepatobiliary disease. Rickets was found in 23 out of 39 patients (59%) with surgically unrepaired biliary atresia, in 4 out of 15 (27%) with surgically repaired biliary atresia, in 11 out of 21 (52%) with neonatal hepatitis, and in 2 out of 4 (50%) with intrahepatic cholestasis. Osteoporosis was found in 23 out of 39 (59%) with unrepaired biliary atresia, in 3 out of 15 (20%) with repaired biliary atresia, in 5 out of 21 (24%) with neonatal hepatitis, and in 1 out of 4 (25%) with intrahepatic cholestasis. 2 girls with Byler disease and 1 infant with choledochal cyst showed no radiological evidence of bone disease.In unrepaired biliary atresia comparative studies of biochemical data in the groups with and without bone disease showed the following. Serum calcium levels were reduced in the patients with bone disease compared with those in the group without it. Serum magnesium levels were markedly reduced in the groups with and without bone disease. The product of serum calcium and phosphorus was reduced in the group with osteoporosis compared with that in the group without it. The raised levels of serum alkaline phosphatase were unrelated to the presence or absence of bone disease.     

The relationship of juvenile lumbar disc disease and Scheuermann's disease

Between 1969 and 1979 five children were found to have lumbar disc disease and were evaluated for clinically unsuspected thoracic spine abnormalities. Of these five children, two had Scheuermann's disease and one had disc space narrowing associated with Schmorl's nodes. One other had narrowed disc spaces without bony defects, and one had a normal thoracic spine. A unitary concept of childhood lumbar disc disease, Schmorl's nodes and Scheuermann's disease is suggested.