西罗莫司治疗儿童蓝色橡皮疱痣综合征2例并文献复习

为探讨口服西罗莫司治疗儿童胃肠道蓝色橡皮疱痣综合征（BRBNS）的疗效,该文回顾性分析了2例BRBNS患儿的临床资料和使用西罗莫司治疗的随访结果。2例伴有消化道出血和贫血的BRBNS患儿,给予口服西罗莫司（初始剂量为1 mg/d）作为治疗方案的一部分,维持血药浓度在2.5~12.0 ng/mL之间,患儿消化道出血消失,贫血和凝血功能改善,治疗期间可停止输血且无明显药物不良反应。在PubMed、万方数据库、中国知网搜索西罗莫司治疗BRBNS的相关文献进行总结。检索文献结果显示,年龄为0~18岁的BRBNS儿童病例共检索出26例,加上该研究中报道的2例,共28例使用西罗莫司治疗均取得满意疗效。西罗莫司在儿童BRBNS患者的治疗中可能是有效和安全的,有待进一步的前瞻性研究来评估这种药物的长期疗效。     

儿童卡梅现象13 例回顾性分析并文献复习

目的讨论卡梅现象(KMP)的临床表现、诊断与治疗。方法回顾分析2010年1月-2016年1月收治的13例卡梅现象患儿的临床资料,并进行文献复习。结果 13例患儿中男10例、女3例,发病年龄均6个月。12例患儿有出血点、瘀斑、黄疸和皮肤包块等皮肤表现,1例表现为胸腔积液;病灶位置分布多样;血小板严重减少,纤维蛋白原减少,D-二聚体升高;起病至确诊中位时间为60天。采用手术及糖皮质激素、心得安、干扰素、西罗莫司等药物治疗,10例缓解、3例死亡,其中6例给予西罗莫司治疗者疗效均满意。结论卡梅现象以血管肿瘤合并严重血小板减少及消耗性凝血异常为特点,发病年龄小,起病至确诊时间较长;手术治疗疗效确切;西罗莫司或可成为卡梅现象的有效治疗手段。     

西罗莫司对Raji细胞增殖、凋亡影响的研究

目的探讨西罗莫司对恶性淋巴瘤细胞的作用及其可能机制。方法实验分为西罗莫司组、阿霉素组、西罗莫司+阿霉素组、对照组,观察各组人非霍奇金淋巴瘤Raji细胞增殖、凋亡及细胞周期分布情况,应用MTT比色法检测细胞生长情况,流式细胞术(FCM)分析细胞凋亡及细胞周期分布的情况;应用FCM和免疫细胞化学染色法检测HIF-1α蛋白在西罗莫司各组中的表达情况。结果(1)西罗莫司和阿霉素对Raji细胞生长具有抑制作用,且在一定范围内呈时间剂量依赖性;(2)西罗莫司+阿霉素组吸光度值(A492)与西罗莫司组、阿霉素组相比差异均有显著性(P<0.05);(3)西罗莫司+阿霉素组凋亡率与对照组、阿霉素组相比差异均有显著性(P<0.05),与西罗莫司组相比差异无显著(P>0.05);(4)西罗莫司+阿霉素组各期细胞比例与对照组、阿霉素组相比,细胞周期分布发生明显变化(P<0.05),与西罗莫司组差异无显著性(P>0.05)。(5)西罗莫司各浓度组HIF-1α蛋白表达率下降,与对照组相比差异有显著性(P<0.05)。结论西罗莫司体外对Raji细胞生长具有明显的抑制作用。西罗莫司通过阻滞Raji细胞G0/G1期抑制Raji细胞增殖,通过下调HIF-1α蛋白的表达诱导Raji细胞凋亡。西罗莫司与阿霉素联合对Raji细胞生长具有明显抑制作用,优于单用西罗莫司,但对Raji细胞凋亡和周期的影响与单用西罗莫司无显著差异。     

西罗莫司在小儿卡波西型血管内皮瘤中的应用进展

卡波西型血管内皮瘤(kaposiform hemangioendothelioma, KHE)是罕见的小儿脉管性肿瘤, 合并卡梅现象(Kasabach-Merritt phenomenon, KMP)时, 可危及生命。药物治疗是KHE的主要治疗方式, 近年来多项研究表明哺乳动物雷帕霉素靶标(mammalian target of rapamycin, mTOR)抑制剂西罗莫司对卡波西型血管内皮瘤合并卡梅现象的治疗效果可靠, 不良反应少, 有望成为一线用药。本文总结了国内外对卡波西型血管内皮瘤治疗的研究进展, 从传统治疗方案的现状和局限、西罗莫司的治疗原理和优势、西罗莫司治疗的瓶颈与未来展开综述。     

胶囊内镜诊断多处肠内病变的儿童蓝色橡皮泡痣综合征1例

蓝色橡皮泡痣综合征(blue rubber bleb nevussyndrome,BRBNS)是一种罕见的疾病,其特征是皮肤和胃肠道多发性静脉畸形,典型的皮肤损伤由易压缩的深蓝色橡胶泡组成[1-2]。胃肠道病变容易引起出血,导致缺铁性贫血[3]。凡有特殊皮肤表现如蓝色斑及消化道出血者均应想到本病。胶囊内镜是诊断疑似小肠出血疾病的重要手段。昆明医科大学第一附属医院儿科于2019年4月收治1例BRBNS患儿,现报道如下。     

儿童过敏性紫癜性肾炎药物治疗的Meta分析

目的 儿童过敏性紫癜性肾炎(HSPN)是儿科常见的继发性肾小球疾病，多发于欧洲及亚洲地区，目前尚无统一治疗方案。应用Meta分析方法评价儿童HSPN药物治疗的疗效，为临床治疗及开展相关研究提供参考和帮助。方法 检索Medline、PubMed、EMBASE、CBM、中国期刊网等数据库、学术会议资料和学位论文等，全面收集有关儿童HSPN药物治疗的文献。制定文献纳入及排除标准，并通过查阅文献制定效应指标的评价标准。由2名研究者分别独立筛选文献，符合纳入标准的文献按Shekelle等建议的标准进行文献质量评估，对照性研究按Juni量表进行质量评价。应用Review Manager 42软件进行Meta分析，计算治疗组与对照组的治愈率及有效率的危险率差（RD）及其95％CI，对不能进行Meta分析的文献进行描述性分析，客观评价各种药物治疗方案的疗效。结果 共检索到HSPH相关中、外文文献1 948篇，从中筛选出儿童HSPN药物治疗的相关文献64篇，其中多中心RCT研究（Ⅰa级）1篇，单中心RCT研究（Ⅰb级）6篇，单中心对照研究（Ⅱa级）10篇，无对照的临床病例观察（Ⅱb级）34篇，病例报道（Ⅲ级）13篇。在各种药物治疗方案中应用最多的是激素联合免疫抑制剂的治疗,共纳入163例患儿，其中对照组87例，治疗组76例，治疗前除对照组16例、治疗组14例患儿有轻微肾脏损伤（B级临床状态）外，其余均有肾病水平蛋白尿（C级临床状态）。治疗组采用激素联合免疫抑制剂治疗，对照组单用激素治疗，Meta分析结果显示治疗组较对照组治愈率及有效率均高（治愈率比较的RD=-0.39, 95% CI：-0.53~-0.25，有效率比较的RD＝-0.43，95％CI： -0.66～-0.20），差异有统计学意义。进一步对激素联合静脉冲击环磷酰胺（CTX）的疗效进行单独分析，共纳入106例患儿，其中对照组57例，治疗组49例，症状均较重，为肾病水平蛋白尿和（或）肾功能下降。治疗组应用激素联合静脉冲击CTX，对照组单用激素治疗，评价结果显示治疗组较对照组治愈率及有效率均高（治愈率比较的RD=-0.48, 95% CI: -0.74～-0.23；有效率比较的RD=-0.60, 95% CI: -0.81～-0.40），差异有统计学意义；1项多中心RCT研究提示，支持治疗加CTX口服较单纯进行支持治疗对于改善儿童HSPN病情差异无统计学意义；此外，激素联合其他免疫抑制剂（硫唑嘌呤、环孢素、霉酚酸酯和长春新碱等）、免疫调节剂、抗凝剂及血浆置换等研究仅限于单个文献的对照研究或非随机非对照的临床病例观察，依据这些证据难以从EBM的角度进行评价，其疗效尚不能肯定。结论 目前儿童HSPN药物治疗种类繁多，缺乏统一方案。本研究分析发现，激素联合免疫抑制剂对于症状较重的HSPN患儿（肾病水平蛋白尿伴或不伴有肾功能不全）的疗效优于单用激素治疗，其中激素联合静脉冲击CTX疗效显著；支持治疗加CTX口服较单纯进行支持治疗对于改善HSPN患儿病情差异无统计学意义；但确切疗效仍有待于临床开展大规模、多中心RCT研究来证实。其他药物的疗效尚不能获得EBM的证据支持。     

内镜下组织粘合剂注射和套扎术治疗儿童食管胃静脉曲张出血24例临床观察

目的评价内镜下组织粘合剂注射和套扎术（EVL）治疗儿童食管胃静脉曲张（GOV）的临床疗效。 方法分析2009年10月至2013年11月在复旦大学附属儿科医院因GOV出血接受内镜下治疗的24例患儿的临床资料,总结治疗后即时止血率、再出血率及并发症情况。 结果24例患儿平均年龄（8.0±3.2）岁,男15例,女9例,其中1型GOV（GOV1）6例、2型GOV（GOV2）18例,平均随访10.5（1~32）个月。共行内镜下EVL治疗24例,平均每例套扎4（2~7）环;组织粘合剂注射治疗19例,平均每例组织粘合剂注射量为1（0.5~1.5） mL。即时止血率为100%,3个月内再出血率16.7%（4/24）,3个月以上再出血率16.7%（4/24）,其中2例于治疗后3个月内死亡,6例（25%）于随访期间因出血复发而再次行内镜下治疗,平均套扎2.8（2~5）次。术后均未见明显并发症。 结论内镜下组织粘合剂注射和EVL治疗GOV疗效确切,并发症少,是治疗儿童GOV的有效措施。     

儿童社区获得性肺炎口服与非口服抗生素疗效比较的Meta分析

目的 采用Meta分析对口服和非口服抗生素在儿童社区获得性肺炎治疗中的疗效进行定量评价.方法 检索MEDLINE、EMBASE数据库和Cochrane Central Register of Controlled Trials(CEN-TRAL),检索时间均从建库至2016年9月,获得口服和非口服抗生素治疗儿童社区获得性肺炎相关的临床随机对照试验(randomized controlled trial,RCT),按照纳入、排除标准进行文献筛选,采用Review Man-ager 5.3对纳入的RCT文献进行Meta分析.结果 共检索到4582篇,最终7篇(n=5030)纳入本研究.口服与非口服抗生素患儿的总体治疗失败率没有显著性差异(OR=0.82,95%CI=0.63-1.08,P<0.01);小于1岁患儿的口服治疗失败率显著高于非口服患儿(OR=2.25,95%CI=1.61-3.14,P<0.01);在纳入研究前1周有抗生素使用史的患儿的治疗失败率显著高于无抗生素使用史的患儿(OR=1.94,95%CI=1.50-2.50,P<0.01);口服抗生素患儿病死率显著低于非口服抗生素患儿(OR=0.31,95%CI=0.11-0.85,P=0.02);两种用药方式治疗的复发率(OR=1.28,95%CI=0.34-4.82)、失访率(OR=1.08,95%CI=0.77-1.51)差异均无统计学意义.结论 社区获得性肺炎患儿口服抗生素与非口服抗生素治疗疗效相似,口服抗生素治疗患儿病死率低于非口服患儿.     

儿童急性荨麻疹伴消化性溃疡大出血2例报告

目的探讨急性荨麻疹伴消化道大出血的临床特征及诊治。方法回顾分析2例在治疗过程中出现消化道大出血的急性荨麻疹患儿的临床资料,并复习相关文献。结果例1男性患儿11岁,例2女性患儿2岁10个月,均表现为皮疹、腹痛、呕血、黑便。经治疗后,例1皮疹基本消退,例2残留少许斑片状皮疹;但仍均有不同程度贫血,胃镜均提示消化性溃疡。2例患儿均出现上消化道大出血,例1经药物治疗、介入治疗、外科急诊手术后仍不能有效止血,后继发弥散性血管内凝血及多器官功能衰竭死亡;例2经内科治疗、介入治疗及外科手术治疗后出血停止。结论急性荨麻疹易并发消化道大出血,经药物、内镜下止血及手术治疗,出血可得到有效控制,否则易发生严重并发症。     

组胺受体阻断药酮替芬治疗儿童食物诱发哮喘的临床观察

目的观察酮替芬治疗儿童食物诱发哮喘(FIA)的疗效。方法31例FIA患儿均口服酮替芬0.03~0.05mg/kg,2次/d,共用4周,观察哮喘患儿临床症状变化及糖皮质激素使用次数,同时观察峰流速(PEF)变化。结果显效12例,有效16例,无效3例。结论酮替芬治疗儿童FIA效果满意。     

Blue rubber bleb nevus syndrome: successful treatment with sirolimus

Blue rubber bleb nevus syndrome (BRBNS) is a rare disorder with characteristic vascular malformations of the skin, gastrointestinal system, and, less often, other organ systems. The characteristic cutaneous lesions consist of deep-blue, soft, rubbery blebs, which are easily compressible. The most serious complication is abundant gastrointestinal bleeding. We describe the case of an 8-year-old girl with diagnosed BRBNS who had multiple venous malformations all over her body, importantly, throughout the gastrointestinal tract, mouth, esophagus, stomach, small bowel, and colon. She presented with recurrent massive gastrointestinal bleeding and soft tissue hematoma despite prednisolone and α-interferon therapy. We started low-dose sirolimus as an antiangiogenic agent. The vascular masses were reduced rapidly and there was no gastrointestinal bleeding and muscular hematoma after sirolimus therapy. There was no drug adverse reaction at 20-month follow-up. To the best of our knowledge, this is the first report related to the use of sirolimus in a patient with BRBNS.     

A new approach to blue rubber bleb nevus syndrome: the role of capsule endoscopy and intra-operative enteroscopy

Blue rubber bleb nevus syndrome (BRBNS) is a rare vascular malformation disorder with cutaneous and visceral lesions frequently associated with serious, even fatal bleeding and anemia. The syndrome is considered to be autosomaly predominantly inherited. Intra-operative enteroscopy (IOE) is the best method of identification of all lesions (particularly the small ones, less than 3 mm) and treatment by endoscopic electro-coagulation or surgical excision. Capsule wireless endoscopy is optimal for screening before the IOE and for monitoring the effect of therapy (in patients with BRBNS). We report two cases of BRBNS. Anemia, gastrointestinal bleeding, gastrointestinal malformations and multifocal venous malformations of the skin were present in both of our cases. Gastrointestinal lesions were identified by gastroscopy, colonoscopy and capsule endoscopy. The multiple venous malformations were treated partly by endoscopic electro-coagulation (lesions up to 4 mm in diameter) and by wedge resection. Both of our patients were 12-year-old girls at the time of operation. In the first patient 31 venous malformations of the small bowel were coagulated, two were resected by the surgeon. In the second patient 20 lesions were coagulated endoscopically and another 31 nevi were resected during an 8 h procedure. The first girl is doing fine 4 years after the procedure, the second was allowed home 2 weeks after the procedure in excellent condition. IOE is a unique method of small bowel investigation and concurrently provides a solution for pathological findings. Capsule endoscopy is a feasible non-invasive screening procedure. We believe that a radical eliminatory approach by means of combined surgery and IOE is indicated for the BRBNS to prevent ongoing gastrointestinal bleeding.     

Sirolimus in blue rubber bleb naevus syndrome: A systematic review

The aim of this study is to review sirolimus as a treatment for blue rubber bleb naevus syndrome (BRBNS). A literature search of Medline, Embase, CINAHL, SCOPUS and Google Scholar was conducted for publications reporting treatment of patients with BRBNS with sirolimus. Of 46 articles identified, 17 studies reporting 23 patients met inclusion criteria. Sirolimus was well tolerated in all but one patient who required treatment cessation; 17/18 patients noted an improvement in gastrointestinal disease where this was reported; 21/22 patients noted an improvement in cutaneous disease where this was reported. Based on these results, sirolimus may be considered a first‐line treatment of BRBNS depending on patient morbidity.     

Diagnosis and treatment of blue rubber bleb nevus syndrome in children

Background  Blue rubber bleb nevus syndrome (BRBNS) is characterized by distinctive vascular malformations of skin and the gastrointestinal tract, often leading to chronic anemia and intestinal bleeding. It usually presents right after birth or during early infancy. Though the disease is inherent, its occurrence is sporadic. Thus it is usually not timely diagnosed. We analyzed the clinical characteristics and treatment of this disorder in order to improve the diagnosis and treatment. Methods  Three patients with BRBNS treated at our hospital during 2002–2003 and 39 patients from the literature reported during 1965–2003 were reviewed in terms of the diagnosis and treatment. BRBNS may be diagnosed as cutaneous cavernous hemangioma associated with the same lesion of the gastrointestinal tract and other organs. Results  Our 3 patients suffered from cutaneous angioma and gastrointestinal hemangioma. In 39 patients reported in the literature, cutaneous angioma was observed in all of them, and gastrointestinal hemangioma in 31. Additionally, the lesions were also found in other organs such as the brain (7 patients), joint (2), liver (2), eye (1), kidney (1) and spleen (1). Cutaneous angioma was located on the surface of the skin, including body (93%), limbs (86%), hip (36%) and face (26%). Gastrointestinal hemangioma was more common in the small intestine (100%) than in the colon (74%) and stomach (26%). When the joint was involved by hemangioma, pathologic fracture or overgrowth of bone needed traction and amputation (1 patient respectively). For significant gastrointestinal bleeding, endoscopic techniques (8 patients), surgical excision (5), or both (1) were performed. Recurrent bleeding was successfully treated by endoscopic laser combined with steroid or interferon in one patient. Conclusions  BRBNS in children presents atypical symptom and systemic complications. It should be dealt with seriously if gastrointestinal bleeding or orthopedic complication occurs. Treatment includes conservative, endoscopic and surgical options. Its recurrence with new angioma in the gastrointestinal tract needs laser-steroid therapy.     

Gastrointestinal bleeding and paraparesis in blue rubber bleb nevus syndrome

Blue rubber bleb nevus syndrome (BRBNS), which consists of cutaneous and visceral hemangiomas, is a rare disease. Complications such as gastrointestinal (GI) bleeding, anemia and coagulopathy have been documented. We report a patient with BRBNS who presented with acute paraparesis in addition to GI bleeding and coagulopathy.     

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??The causes of upper gastrointestinal bleeding in children are numerous and vary with age. According to hemorrhagic causes and pathogenesis??upper gastrointestinal bleeding can be classified into two categories??nonvariceal and variceal. The clinical presentation of gastrointestinal bleeding in children ranges from asymptomatic microcytic anemia to hypovolemic shock. Because of the relatively small blood volume and poor blood loss tolerance of children??even a small amount of bleeding is prone to serious complications??so reasonable diagnosis and treatment are necessary. Endoscopic examination can enable us to make diagnoses and perform hemostasis treatment for children?? which has the advantages of being simple??with little trauma and quick effect. With the development of endoscopic technology??the surgery rate and fatality rate of upper gastrointestinal bleeding have significantly decreased.     

Blue rubber bleb nevus syndrome and gastrointestinal haemorrhage: which treatment?

PURPOSE: To describe a paediatric case of "Blue Rubber Bleb Nevus Syndrome" (BRBNS) or Bean's syndrome, a rare systemic disorder characterised by cutaneous and gastrointestinal vascular malformations that often lead to overt life-threatening gastrointestinal bleeding or occult blood loss with severe anaemia and iron deficiency. CASE REPORT: A 6-year-old girl with multiple characteristic cutaneous vascular lesions was admitted for a massive rectal bleeding. A few months previously she was endoscopically treated for gastric angiomas which developed into melaena. Preoperative investigations revealed the recurrence of gastric lesions. At laparotomy, more than 25 angiomas of the GI tract were found. Multiple intestinal resections were carried out. RESULTS: No intraoperative or postoperative problems occurred and the girl is completely healthy without further bleeding after a follow-up period of three years. CONCLUSIONS: BRBNS belongs to the group of vascular venous malformations. Most of the time it occurs sporadically, but it can be inherited as an autosomal dominant trait. Recent analysis identified a locus on chromosome 9 responsible for venous malformations. BRBNS patients present typical skin lesions, with some lesions having a rubber-like nipple appearance; the number of skin and GI lesions and the severity of anaemia are correlated. Treatment is dependent on the extent of gut involvement and the severity of the clinical picture. In the absence of massive bleeding, a conservative treatment will be sufficient; otherwise resections are mandatory, but additional lesions may subsequently develop. Management with electrocautery or laser photocoagulation are usually not effective even if some reports recommend them. Pharmacological treatment is useless. Prognosis of BRBNS is unknown.     

Unexpected result in the etiological approaching to an anemic case: a leech infestation

One of the causes of the childhood anemia is gastrointestinal system bleeding, which rarely results from parasites. The authors report on a 3-year-old boy with severe anemia and a history of hematemesis. While they were investigating the cause of the anemia and the hematemesis, a leech showing itself in the nasal passage led to a quick and exact treatment. Leeches should be considered for differential diagnosis of anemia and gastrointestinal system bleeding in the children.     

Unexpected Result in the Etiological Approaching to an Anemic Case: A Leech Infestation

One of the causes of the childhood anemia is gastrointestinal system bleeding, which rarely results from parasites. The authors report on a 3-year-old boy with severe anemia and a history of hematemesis. While they were investigating the cause of the anemia and the hematemesis, a leech showing itself in the nasal passage led to a quick and exact treatment. Leeches should be considered for differential diagnosis of anemia and gastrointestinal system bleeding in the children.