儿童NLRP12-自身炎症性疾病临床特征分析

目的探讨儿童NLRP12-自身炎症性疾病(NLRP12-AD)的临床表现、免疫学特点、基因型、诊治过程及预后,加强儿科医师对本病认识。方法回顾性分析2016年深圳市儿童医院诊治NLRP12-AD 1例患儿的临床特征,并以NLRP12-AD为检索词,检索PubMed、中国知网、重庆维普及万方数据库2008年1月至2019年1月相关文献,总结儿童期发病NLRP12-AD患者的临床资料及基因变异特点。结果本组为首例伴发巨噬细胞活化综合征患儿。回顾本组及儿童期发病NLRP12-AD(33例)共34例患儿,总结临床特征如下:儿童期各年龄均可发病,无性别差异,可无阳性家族史。几乎全部以发热为首发症状,近半数由寒冷诱发(44%),常见症状为周期性发热(100%)、肌痛(53%)、皮疹(38%)、关节炎(35%)、腹痛及腹泻(50%),其他症状有头痛、口腔溃疡、淋巴结肿大和肝脾大等。约50%患者发作时红细胞沉降率(ESR)和C反应蛋白(CRP)异常升高,并伴有白介素(IL)-1、IL-6、IL-18升高。约48%患者激素和抗组胺药物治疗有效,但其中5例严重病例单用激素效果不佳,联合使用托珠单抗等新型生物制剂疗效显著。结论儿童NLRP12-AD临床表型多样,易被误诊为全身型幼年特发性关节炎(SoJIA)或感染性疾病,如能早期诊治,大部分患者预后良好。     

儿童NLRP12-自身炎症性疾病临床特征分析

目的　探讨儿童NLRP12-自身炎症性疾病（NLRP12-AD）的临床表现、 免疫学特点、 基因型、 诊治过程及预后， 加强儿科医师对本病认识。方法　回顾性分析2016年深圳市儿童医院诊治NLRP12-AD 1例患儿的临床特征， 并以NLRP12-AD为检索词， 检索PubMed、 中国知网、 重庆维普及万方数据库2008年1月至2019年1月相关文献，总结儿童期发病NLRP12-AD患者的临床资料及基因变异特点。结果　本组为首例伴发巨噬细胞活化综合征患儿。回顾本组及儿童期发病NLRP12-AD（33例）共34例患儿，总结临床特征如下：儿童期各年龄均可发病，无性别差异，可无阳性家族史。几乎全部以发热为首发症状，近半数由寒冷诱发（44%），常见症状为周期性发热（100%）、肌痛（53%）、皮疹（38%）、关节炎（35%）、腹痛及腹泻（50%），其他症状有头痛、口腔溃疡、淋巴结肿大和肝脾大等。约50%患者发作时红细胞沉降率（ESR）和C反应蛋白（CRP）异常升高，并伴有白介素（IL）-1、IL-6、IL-18升高。约48%患者激素和抗组胺药物治疗有效，但其中5例严重病例单用激素效果不佳，联合使用托珠单抗等新型生物制剂疗效显著。结论　儿童NLRP12-AD临床表型多样，易被误诊为全身型幼年特发性关节炎（SoJIA）或感染性疾病，如能早期诊治，大部分患者预后良好。     

儿童不明原因发热357例病因及临床特征分析

目的探讨儿童不明原因发热的病因分布及临床特征, 为儿童不明原因发热的早期诊断提供线索。方法收集2016年1月1日至2020年12月31日复旦大学附属儿科医院357例不明原因发热患儿的病因构成、年龄、性别、病程、住院时间、确诊时间及急性期的炎症因子水平等临床资料行病例对照分析。依据疾病种类分为感染性疾病组(简称感染组)、非感染性炎症性疾病组(简称非感染组)、肿瘤性疾病组(简称肿瘤组)和其他疾病组(简称其他组)。依据年龄分为<1岁组, 1～<3岁组、3～<6岁组、6～<12岁组及12～<18岁组, 组间比较采用Mann-WhitneyU检验、Kruskal-WallisH检验和χ2检验。结果 357例患儿中男217例、女140例, 就诊年龄5.1(2.0, 9.3)岁, 起病年龄3.9(1.3, 9.2)岁, 确诊时间94(66, 213)d, 住院时间8(6, 14)d。感染组163例(45.7%)、非感染组133例(37.2%)、肿瘤组21例(5.9%), 其他组40例(11.2%), 4组间起病年龄差异有统计意义(H=94.01, P<0.01),...     

儿童家族性地中海热2 例报告并文献复习

目的探讨儿童家族性地中海热(FMF)的临床特征及诊治。方法回顾分析2例FMF患儿的临床资料及致病基因MEFV变异情况,并复习相关文献。结果例1,女性,6岁3月龄;例2,男性,3岁。均表现为反复发热,非特异性炎性指标升高。例1患儿经基因测序证实存在MEFV复合杂合变异,给予秋水仙碱治疗后临床症状明显缓解;例2患儿经基因测序证实存在MEFV核酸位点变异,但相应蛋白水平未见变异,给予秋水仙碱治疗后发热症状明显好转。结论对于经常规治疗仍反复发热、非特异性炎性指标升高者,需警惕儿童FMF。     

自身炎症性疾病临床诊断

自身炎症性疾病（autoinflammatory diseases or disorders,AIDs）是一组以反复发热、急性关节炎和急性期蛋白增加为特征的复发性非侵袭性炎症性疾病。以往由于认识不足以及缺乏诊断条件,对这类疾病估计不足。随着基因诊断技术的进步、炎症发生发展机制与信号通路研究的日益进展,近年来对自身炎症性疾病的研究有了飞速进展,这也对临床诊断提出了更新的挑战。     

100例儿童发热待查的临床分析

目的探讨上海及其周围地区儿童不明原因发热的病因,诊断方法及思路。方法将100例自1999年2月~2004年11月在上海儿童医学中心内科住院治疗的发热待查患儿分为小于5岁组(36例)和大于5岁组(64例),进行回顾性分析。结果男64例,女36例,平均年龄6.5岁(35 d~14岁)。<5岁组中感染性疾病29例(80.5%),结缔组织病2例(5.6%),恶性肿瘤、先天性疾病各1例,另有3例(8.3%)未明确诊断。大于5岁组中感染性疾病32例(50%),结缔组织疾病17例(26.6%),恶性肿瘤4例(6.2%),其他疾病1例,病因未明10例(15.6%)。结论感染性疾病,结缔组织疾病,恶性肿瘤是儿童发热待查的主要原因,而感染性疾病是儿童发热待查的最主要原因。其中以呼吸道感染为首位,结缔组织疾病在学龄儿童发病率显著提高。     

Nod样受体家族含pyrin结构域蛋白12在自身炎症性疾病中的研究进展

Nod样受体家族含pyrin结构域蛋白12(NLRP12)作为发现较晚的Nod样受体家族成员, 是重要的模式识别受体之一, 识别多种病原体并启动下游免疫应答, 参与多项机体炎症反应的调控, 与自身炎症性疾病的发生、进展相关。现从其结构、功能及NLRP12相关自身炎症性疾病等方面对NLRP12进行综述, 探讨NLRP12在自身炎症中的作用机制, 为认识、探索、治疗NLRP12相关自身炎症疾病提供新思路。     

反复发热伴MEFV基因突变患儿10例临床分析及文献复习

目的　探讨在非高危人群中家族性地中海热（FMF）的诊断要点及其临床表现与基因型的关系。方法　回顾性分析重庆医科大学附属儿童医院2016-07-27—2017-11-15收治的10例反复发热伴MEFV基因突变患儿的基因检测报告及临床表现,结合国内外FMF相关文献,对诊断要点及其临床表现与基因型进行总结归纳。结果　10例患儿中共发现4个MEFV基因突变,分别为G304R、E148Q、P369S、R408Q,其中纯合突变4例（40.0%）,杂合突变2例（20.0%）,复杂突变4例（40.0%）。10例患儿中9例有反复发热,1例有反复化脓性扁桃体炎。该10例患儿根据Tel Hashomer标准,有1例患儿疑似诊断FMF,有8例患儿临床怀疑FMF;若根据Turkish儿科标准,则有7例患儿可临床诊断FMF。结论　FMF主要依靠临床诊断,可以通过基因检测来支持但不一定排除。携带M694V纯合型突变的FMF患者比其他突变的患者起病年龄更早,临床表现很可能更严重;而E148Q的致病性存在争议,其作为惟一突变时不支持FMF诊断。中国儿童中FMF发病率可能被低估,尚需纳入更多的研究对象,进一步研究。     

317例儿童不明原因发热的临床分析

目的：探讨儿童不明原因发热(FUO)的病因,诊断方法和思维方式。方法：回顾性地总结分析1996年1月至2000年12月符合FUO诊断标准的住院患儿317例。结果：317例中明确诊断有298例,确诊率为94.0%。感染性疾病160例(53.7%),非感染性疾病138例(46.3%),两者之比为1.15∶1。最终确定诊断的方法分别为：临床综合诊断140例(47.0%);血清和骨髓细菌培养检查64例(21.5%);组织活检37例(12.4%);影像学检查35例(11.7%);尸体解剖11例(3.7%);骨髓形态学确诊6例(1.9%);回顾性诊断5例(1.7%)。结论：根据临床经过和必要的实验室检查大部分FUO病例可以明确病因诊断,病理学检查对疑难病例的诊断提供重要依据,极少数病人最终只能依赖尸检明确诊断。感染性疾病、结缔组织病和恶性肿瘤性疾病是该组FUO的主要原因。     

National survey of childhood febrile illness cases with fever of unknown origin in Japan

Background: In Japan, an actual condition survey on childhood febrile diseases with fever of unknown origin has never been performed. We carried out a national survey on childhood febrile illnesses in order to collect useful information for the differential diagnosis. Methods: A nationwide survey using questionnaires was performed on febrile illness cases with fever of unknown origin (FUO) experienced by 2843 pediatrics institutions with sick beds during a 5‐year period before 2007. FUO was defined as a febrile illness of at least 2 weeks' duration with a temperature ≥38°C, and failure to establish a diagnosis in spite of intensive evaluation during seven days' hospitalization. Results: Two hundred fifty‐five of 2843 questionnaire‐surveyed institutions had 960 FUO cases, of which 132 could not be diagnosed, and 828 could be diagnosed after detailed medical examinations. The diagnoses they clarified included infectious diseases in 190 cases (23%), rheumatic diseases in 448 cases (54%), neoplasms in 67 cases (8%), and others in 123 cases (15%). Conclusion: Clarification of illnesses that ought to be differentiated in the diagnostic approach to an FUO case is essential for arriving at its definitive diagnosis by exclusion.     

Fever of unknown origin in 185 paediatric patients: a single-centre experience

Aim: We conducted a prospective study to evaluate the causes and outcome in children with fever of unknown origin (FUO). Methods: From 1990 to 1999, 185 children with FUO were evaluated. Initial evaluation included routine haematological analysis, Epstein-Barr virus (EBV) serology, urine, stool or blood cultures, chest X-ray and tuberculin probe. Results: In 131 (70%) patients diagnosis was established, and 70 (37.8%) had infectious disease. EBV infection was the most common infection followed by visceral leishmaniasis (VL), urinary tract infection (UTI) and tuberculosis. Autoimmune disorders were diagnosed in 24 (12.9%), Kawasaki disease in 12 (6.4%), malignant diseases in 12 (6.4%) and miscellaneous conditions in 15 (8.1%) patients. In the remaining 54 (30%) patients, diagnosis was not established and most of them had self-limited disease. During the investigation, 26 (14%) patients developed serious organ dysfunction and five patients (two with virus-associated haemophagocytic syndrome, one with VL and two unknown) died.

Conclusion: The most important infectious causes of FUO in our study were EBV infection and VL. Kawasaki disease represented a significant cause of FUO at the beginning of our study because it was not recognized by primary-care physicians. We report myelodysplastic syndrome as another emerging cause of paediatric FUO. Repeated clinical examination and careful use of specific laboratory examinations, invasive diagnostic procedures or imaging are crucial in approaching paediatric FUO.     

744例儿童发热待查的临床分析

目的 探讨儿童发热待查病因构成、诊断方法和思路。方法 １９９３年１月１日￣１９９８年１２月３１日符合发热待查诊断标准的住院患儿７４４例,按年龄分为〈３岁,３￣７岁、〉７岁三组,进行回顾性分析。结果：（１）〈３岁组９６例,其中感染性疾病５０例（５２％）（呼吸道感染２１例,２２％）;先天性疾病１４例（１５％）;恶性肿瘤９例（９％）。（２）３￣７岁组１９２例,感染性疾病１１５例（５９．９％）（呼吸道感染     

不明原因长期发热的临床分析

目的 探讨不明原因长期发热患儿的病因及诊断方法。方法 回顾性地总结分析符合ＦＵＯ诊断标准的患儿１１８例。结果 １１８例中晚期诊断有１０７例,确诊率为９０．７５,未能确诊１１例,确诊病例中,感染性疾病３３例,结缔组织病４４例,肿瘤及瘤样病１４例,其他疾病１３例,伪装热３例。最终确定诊断的方法分别为;血清学和细菌学检查７５例,占７０．０％;组织活检１３例,占１２．１％;骨髓检查９例,占８４％,影像学检     

Rheumatoid arthritis during the first year of life

A 20-week-old female, first examined at 14 weeks of age for daily spiking fever and skin rash, subsequently developed signs of rheumatoid arthritis. The onset of rheumatoid arthritis during the first weeks of life is rare and its diagnosis may be difficult. It seems that onset during the later months of the first year is more frequently encountered. A review of the relevant publications in English disclosed that onset during first year was noticed in 1.02 percent of the patients, while in a study from Germany 6 to 9.9 percent of cases started during their first year.     

Evaluation of 80 children with prolonged fever

BACKGROUND: Several studies have been published regarding the etiology and evaluation of a child with prolonged fever, however, the reasons for the prolonged fever have changed during the years. The present study aims to determine the causes of prolonged fever, to investigate the relationship of fever using some basic laboratory tests, and to establish guidelines for the approach in those children. METHODS: The charts of 80 out of 17490 hospitalized children who were seen between 1996 and 2001 with prolonged fever of longer than 2 weeks and unknown origin were reviewed in the university hospital of Izmir, Turkey. Their charts were evaluated in respect of age, sex, growth curves, educational level of their families, the duration and the magnitude of fever, causes of fever, and basic laboratory investigations such as white blood cell, blood smear, hemoglobin, erythrocyte sedimentation rate, and C-reactive protein. RESULTS: Forty-four (55.00%) were boys and 36 (45.00%) were girls. Forty-four children (55.00%) were aged between 1 month and 2 years, 21 (26.25%) were aged 3-6 years, seven (8.75%) were aged 7-10 years, and eight (10.00%) were older than 10 years. The mean age was 3.87 +/- 4.17 years (range 3 months-17 years). Forty-six children (57.50%) had a prolonged fever that had lasted from 15-30 days, 18 (22.50%) from 31-60 days, and 16 (20.00%) had fever lasting more than 60 days. Final diagnosis had been reached in 70 of the 80 children (87.50%). The most common causes were infection (47/80), followed by immune deficiency (6/80), collagen tissue disorder (5/80), neoplasia (2/80), and miscellaneous (10/80) such as central fever in three, diabetes insipidus in two, familial Mediterranean fever in two, Kawasaki disease, foreign body in the respiratory system, and Crohn disease in one patient each. Among the laboratory tests white blood cell count, hemoglobin level and blood smear distribution of infection group were statistically significant. CONCLUSIONS: The most common cause of fever of unknown origin remains infection. The proportion of collagen tissue disorders and neoplasia have been found to be decreased. Unusual reasons such as diabetes insipidus and foreign body in the respiratory system in the miscellaneous group have been detected. Age plays important role in the diagnosis of prolonged fever, while some basic laboratory tests might give clues in the evaluation and may suggest a diagnosis.     

Prolonged follow up of seven patients affected by hepatosplenic granulomata due to cat-scratch disease

This study is a retrospective analysis of seven patients with hypoechogenic lesions in the liver and/or spleen due to Bartonella henselae, who were followed from 1998 through to 2005 by the Department of Pediatrics, Turin University. In addition to showing constitutional symptoms, four children had skin lesions suggestive of injuries inflicted by cats, and one child had a history of exposure to cats. The origin of the infection remained undefined in the other two patients. Humoral tests enabled a precise diagnosis in all children. Treatment with macrolides or combinations of two active antibiotics for at least 2–3 weeks led to the definitive clearance of infection, although residual intraparenchymal lesions persisted in five patients for several months or years. Conclusion B. henselae serology allows an easy diagnosis of multiple hepatosplenic granulomata, a clinical picture that appears to be under-recognized. Macrolides or a combination of two active antibiotics for 2–3 weeks leads to a rapid clinical response and a definitive clearance of infection.