播散性卡介苗感染18例分析

目的 探讨播散性卡介苗感染的临床表现、免疫学异常以及治疗转归.方法 回顾性分析2000年1月至2007年12月首都医科大学附属北京儿童医院收治的18例播散性卡介苗感染患儿的临床资料.结果 18例患儿中男13例,女5例,播散首先发生于接种部位同侧腋下淋巴结,同时播散至肺15例次,纵隔和腹腔淋巴结18例次,皮肤和软组织5例次,骨骼4例次,肝4例次,脾8例次,肾和肾上腺各1例次,脑膜1例次.18例中诊断原发免疫缺陷病12例,其中严重联合免疫缺陷病3例,慢性肉芽肿(CGD)7例,白细胞介素12/干扰素γ通路缺陷2例.18例中11例死亡,7例随访1～9年仍存活,其中4例有反复活动性皮肤和骨结核表现,3例易患反复其他病原感染.结论 播散性卡介苗感染患儿多存在原发免疫缺陷病,其中CGD和IL-12/IFN-γ通路缺陷在此类患儿中比例较高,对此类患儿应进行特殊免疫功能检查.患儿多数预后不良,应尽早明确免疫缺陷类型,并进行针对性免疫治疗.     

Inherited disorders of the IL-12-IFN-γ axis in patients with disseminated BCG infection

Disseminated BCG infection is a rare complication of vaccination that occurs in patients with impaired immunity. In recent years, a series of inherited disorders of the IL-12-IFN- axis have been described that predispose affected individuals to disseminated disease caused by BCG, environmental Mycobacteria, and non-typhoidal Salmonella. The routine immunological work-up of these patients is normal and the diagnosis requires specific investigation of the IL-12-IFN- circuit. We report here the first two such patients originating from and living in Iran. The first child is two years old and suffers from complete IFN- receptor 2 deficiency and disseminated BCG infection. He is currently in clinical remission thanks to prolonged multiple antibiotic therapy. The other, a 28-year-old adult, suffers from IL-12p40 deficiency and presented with disseminated BCG infection followed by recurrent episodes of systemic salmonellosis. He is now doing well. A third patient of Iranian descent, living in North America, was reported elsewhere to suffer from IL-12R1 deficiency. These three patients thus indicate that various inherited defects of the IL-12-IFN- circuit can be found in Iranian people. In conclusion we recommend to consider the disorders of the IL-12-IFN- circuit in all patients with severe BCG infection, disseminated environmental mycobacterial disease, or systemic non-typhoidal salmonellosis, regardless of their ethnic origin and country of residence.     

Clinical presentation of Bacillus Calmette-Guérin infections in patients with immunodeficiency syndromes

Nine children with immunodeficiency syndromes who developed persistent or disseminated Bacillus Calmette-Guérin (BCG) infections after BCG vaccination at birth were observed in Santiago, Chile, over a period of 10 years. This represents a risk for persistent or disseminated BCG infections of 3.4/1,000,000 vaccinated newborns. This may closely reflect the incidence of severe combined immunodeficiency syndromes, cellular immunodeficiency syndromes and chronic granulomatous disease in the study area. The clinical presentation and course of the infection varied considerably depending on the underlying immunodeficiency syndrome. Two patients with severe combined immunodeficiency presented with cutaneous nodules in the absence of any local reaction at the site of BCG vaccination. Both patients died of disseminated BCG infection within the first year of life. Four patients with cellular immunodeficiency syndromes presented with regional lymphadenitis resistant to treatment after the fifth month of life. Three of these patients had specific unresponsiveness to tuberculin and survived from 5 to 6 years of age. Two boys with X-linked chronic granulomatous disease presented with regional lymphadenitis in the first 3 months of life. A girl with autosomal recessive chronic granulomatous disease presented at 18 months of age with regional lymphadenitis. All three patients with chronic granulomatous disease had positive tuberculin reactions and died from infections other than BCG.     

Fatal outcome of disseminated Mycobacterium avium infection in childhood. A case of primary incompetent monocyte/macrophage function?

Disseminated BCG infection rarely heals, and disseminated disease caused by the Mycobacterium avium complex usually has a poor prognosis with a short time to death. The case of a boy who died after 9 years of diagnosed disseminated M. avium complex infection is described. He showed no signs of previously known immunodeficiency except an incompetent primary monocyte/macrophage function. This case has been commented on in Acta Paediatrica Scandinavia (1982) as "the first infant to survive a generalized BCG infection"     

The impact of a change in bacille Calmette-Guérin vaccine policy on tuberculosis incidence in children in Cape Town, South Africa

BACKGROUND: A decision by the South African National Department of Health to change the route of administration and strain of bacille Calmette-Guérin (BCG) vaccine was implemented in Cape Town, South Africa, between July and December 2000. This provided an opportunity to compare the incidence of tuberculosis and proportion with disseminated disease in children less than 2 years old before and after the changeover from percutaneous (PC) Tokyo 172 BCG to intradermal (ID) 1331 Danish BCG immunization. METHODS: Clinical records of all tuberculosis patients aged less than 2 years at diagnosis and born between January 1, 1999, and June 30, 2000 (PC cohort) and between January 1, 2001, and June 30, 2002 (ID cohort) were collected. All cases were reviewed for likelihood of TB, its severity and disease dissemination. RESULTS: The number of reported patients with tuberculosis in the PC cohort was 1369 and in the ID cohort 1397, giving incidence rates of 866 (95% confidence interval [CI], 821-913) and 858 (95% CI, 814-904) per 100,000 person-years, respectively. The proportion who had disseminated disease (meningitis and/or miliary spread) was significantly lower in the ID cohort (4.7%) than in the PC cohort (8.6%) (relative risk, 0.54; 95% CI, 0.40-0.72). Those not vaccinated had a significantly higher proportion of disseminated disease cases (29.2%) than the PC and ID groups combined (6.6%) (relative risk, 4.4; 95% CI, 2.7-6.7). CONCLUSION: A program using Danish 1331 BCG given intradermally did not prevent more tuberculosis cases in children overall as compared with a program using Tokyo 172 BCG given percutaneously but reduced the proportion with disseminated disease.     

Disseminated Bacillus Calmette-Guérin infection in a girl with hyperimmunoglobulin E syndrome

Disseminated Bacillus Calmette-Guérin infection occurs in few well-defined immunodeficiencies, such as severe combined immunodeficiency, chronic granulomatous disease and paediatric acquired immunodeficiency syndrome. This severe complication of immunization against tuberculosis has been lethal in the majority of children who had primary immunodeficiency. Our patient, a 9-y-old girl with hyperimmunoglobulin E syndrome developed disseminated Bacillus Calmette-Guerin infection in infancy. Patients with hyperimmunoglobulin E syndrome (HIES) are susceptible to serious staphylococcal and fungal infections. Disseminated Bacillus Calmette-Guerin infection has not previously been reported in this rare immunodeficiency.     

Spectrum of primary immune deficiency at a tertiary care hospital

Objective  To report various primary immune deficiencies diagnosed in children at a tertiary care hospital, their clinical manifestations and laboratory profile. Methods  Case records of children diagnosed to have primary immunodeficiency disorders over a period of 24 months at a tertiary care hospital in northern India were evaluated. Results  Twenty-seven children (M: F=3.5: 1) with mean age of 5.4 ± 4.6 yrs (2mo-16yr) were diagnosed to have primary immunodeficiency. Thirteen children had chronic granulomatous disease (CGD), 4 had severe combined immunodeficiency (SCID), 4 had hypogammaglobulinemia, 2 had Ataxia telangiectasia, and one each had DiGeorge syndrome, Wiskott Aldrich syndrome, hyper IgM syndrome and leukocyte adhesion defect. Common mode of presentation were recurrent/ persistent pneumonia in 19, recurrent/ persistent diarrhea in 10, deep seated abscesses in 8, allergy in 3, disseminated tuberculosis infection in 2, extensive fungal infections in 2 and 1 each of disseminated cytomegalovirus (CMV) infection, disseminated BCG disease, otitis media and meningitis. Family history of sibling deaths was elicited in 2 families. Infectious agents were isolated in 16 cases. Conclusion  From a single center 27 patients with primary immune deficiency could be identified by chart review, suggesting need for high index of suspicion for diagnosis of primary immune deficiency in India. Though the exact prevalence is not known there is need to make a registry to document the magnitude of problem of these disorders.     

Disseminated cryptococcal infection in patient with novel JAK3 mutation severe combined immunodeficiency, with resolution after stem cell transplantation

Disseminated cryptococcal infection is the second most common cause of death after tuberculosis in acquired immune deficiency syndrome patients. Surprisingly, it has been reported only in few patients with primary immunodeficiency diseases. Herein, we report the clinical presentation and outcome of a 23-month-old boy with novel JAK3 mutation severe combined immunodeficiency disease complicated by severe disseminated cryptococcal infection.     

IFNGR1基因突变致分枝杆菌易感性疾病2例病例报告

目的：探讨IFNGR1基因突变致分枝杆菌易感性疾病（MSMD）的临床特征。方法：总结2例IFNGR1基因突变MSMD患儿的临床特征,ELISA方法检测干扰素-γ（IFN-γ）释放功能,流式细胞术检测IFNGR1蛋白表达,Sanger测序方法分析IFNGR1基因突变。结果：①2例患儿均生后3月龄内出现卡介苗病,以卡介苗接种侧腋下淋巴结肿大为初始表现,并逐渐播散累及肺部、肠道、中枢和骨髓。确诊年龄分别为4岁和6岁。常规免疫功能（淋巴细胞亚群、免疫球蛋白、中性粒细胞呼吸爆发功能和补体）评估未见缺陷。②2例患儿的IFN-γ释放能力明显低下、IFNGR1蛋白表达均低于正常。③1例存在c.665 G>A（p.G219R）纯合突变,其父母均为c.665 G>A（p.G219R）杂合突变;1例存在c.665 G>A（p.G219R）和c.310 C>A（p.A104N）复合杂合突变,分别遗传自患儿母亲［c.665 G>A（p.G219R）杂合突变］及父亲［c.310 C>A（p.A104N）杂合突变］。其中1例患儿的突变为新发突变,既往无文献报道。④2例患儿在确诊前抗痨治疗效果不佳,确诊后加用IFN-γ,卡介苗感染得到控制,未见其他不良反应。结论：IFNGR1基因突变可导致MSMD。卡介苗病患儿常规免疫评估无缺陷时,需考虑该病可能,相关蛋白检测、IFN-γ释放实验和基因分析有助于诊断。IFN-γ治疗有一定疗效。     

Idiopathic disseminated bacillus Calmette–Guerin infection in three infants

We describe the cases of three infants between 4 and 9 months of age with disseminated bacillus Calmette–Guerin (BCG) infection who developed persistent fever, skin rash, and multiple chest nodules visible on computed tomography 22–34 days after BCG vaccination. These infants were healthy before inoculation, and their detailed immunological profiles, including T cell and neutrophil levels, were within normal range. Most reported BCG cases involve impaired immunity, such as children with chronic granulomatous disease, severe combined immunodeficiency, or human immunodeficiency virus infections. Because of their immature immune systems, BCG vaccination can be hazardous even in early infants without immune abnormalities. Hence, we advise caution when administering BCG vaccines to early infants.     

Shaken baby syndrome masquerading as apparent life threatening event

Disseminated cryptococcosis is a rare and often fatal disease in children. The majority of cases usually occur in individuals with defective cell-mediated immunity, most commonly due to HIV infection. The authors here in report an 8-year-old girl from Nepal who presented with fever, cough, headache, lymphadenopathy, hepatosplenomegaly and cutaneous lesions. Lymph node biopsy revealed multiple granulomas composed of histiocytes and epitheliold cells along with numerous yeast forms of cryptococcus. Cultures of CSF, sputum and urine yielded cryptococcus neoformans. Surprisingly,the immune function in terms of T-cell number, CD4 : CD8 ratio, serum immunoglobulins and HIV serology was normal. After the diagnosis of disseminated cryptococcosis was established, the patient was treated with 5-fluorocytosine (100 mg/kg/day) for initial two weeks and amphotericin B (1 mg/kg/day) for 13 weeks. Patient responded well to the treatment with disappearance of presenting symptoms, cutaneous lesions, and lymphadenopathy, though she still had hepatosplenomegaly, which also decreased. Unfortunately, she developed loss of vision in 10th week of therapy. The patient was discharged on oral fluconazole (6 mg/kg/day) and no recurrence was found during the follow-up period of more than 9 months. This is the first case of disseminated cryptococcosis with no detectable immune deficit, from India.     

Langerhans' cell histiocytosis: experience from a single center

Clinical profile, disease-distribution and outcome of Langerhans cell histiocytosis (LCH) is presented in this retrospective analysis. There were 69 children with LCH from January 1986 to December 2004. Diagnosis was presumptive in the majority. The age ranged from 2 months to 12 years. Multisystem disease was documented in 48 (69.6%) children. Evidence of hepatic dysfunction was detected in 25 (36.2%). An elevated serum alkaline phosphatase was a prominent observation in patients with hepatic involvement. Children with localized disease received oral steroids, while cases with disseminated/multi-system disease were treated with prednisolone and, vinblastine or etoposide. 20 (54%) children with disseminated disease and organ dysfunction died. A favorable outcome was documented in all but one case with localized disease. Portal hypertension developed in 3 cases, all of whom had a fatal outcome. Twelve (17.4%) patients had diabetes insipidus. Disseminated disease with organ dysfunction was observed to be a predictor of fatal outcome.     

儿童侵袭性肺炎链球菌病的临床特征及耐药性分析

目的 总结儿童侵袭性肺炎链球菌病(IPD)的临床特征及耐药性资料,以提高对该病的诊疗水平.方法 回顾性分析2004年1月-2009年6月55例IPD患儿的临床资料;采集患儿的血液、脑脊液、腹水、纵隔及软组织引流液标本,经实验室培养、分离、鉴定出64株肺炎链球菌(SP),检测其对青霉素等抗生素的敏感性.结果 55例IPD患儿中男32例,女23例,男女比例为1.39:1.年龄47 d～12岁,其中2岁以下占62%.临床诊断败血症38例(69%);化脓性脑膜炎9例(16%);臀部或颈部脓肿7例(13%);化脓性腹膜炎1例.13例(24%)有基础疾病,以白血病最多见(31%).3例(5%)有外科手术史;3例(5%)合并病毒感染,2例(4%)合并支原体感染.发病以冬春季为主(73%),89%系社区获得性感染.临床治愈40例,好转12例,死亡3例(5%);9例(16%)出现神经系统并发症.各年度侵袭性SP检出率间差异有统计学意义(χ~2=33.93,P<0.01);青霉素中介SP和青霉素耐药SP检出率分别为30%和41%;SP对红霉素和氯林可霉素的耐药率高达94%和88%;多重耐药率达89%.结论 IPD好发于5岁以下尤其是2岁以下儿童,24%患儿存在基础疾病.临床疾病以败血症和化脓性脑膜炎最常见.     

Pediatric infections caused by nontuberculous mycobacteria

During the last few years, nontuberculous mycobacteria (NTM) have been isolated with increasing frequency in our environment. However, there are only a few reports of pediatric NTM infections in Spain (13 articles since 1990). This article presents an update of the epidemiology, diagnostic methods, and treatment of these infections in children. The most frequent clinical syndromes caused by NTM include lymphadenitis, pulmonary and disseminated infections in immunocompromised children. NTM cervical adenitis usually causes chronic infection associated with sinus tract formation and scarring. The treatment of choice is surgical excision of the involved node. Incision and drainage of the enlarged node should be avoided because it can lead to chronic drainage or sinus tract formation. Medical treatment with azithromycin or clarithromycin associated with rifabutin, ethambutol or ciprofloxacin should be reserved for cases in which the family refuses surgery, a recurrence occurs or complete excision is impossible. Pulmonary disease caused by NTM is relatively rare in immunocompetent children, but is increasingly reported in children with cystic fibrosis. In these patients, the clinical significance of the presence of NTM in the sputum is unclear. The persistence of positive cultures, especially if bacilloscopy is positive and the patient shows clinical evidence of pulmonary disease exacerbation, is an indication to start treatment. Disseminated infection caused by NTM can appear in patients with severe immunodepression, especially in HIV-infected children with CD4 cell counts of less than 100 cells/mm3. Early antibiotic therapy with at least three drugs including a macrolide, and immune recovery with aggressive antiretroviral therapy are the keys to improving quality of life and survival in these patients.     

Isolated cutaneous response to granulocyte-monocyte colony stimulating factor in fatal idiopathic disseminated Bacillus-Calmette-Guerin infection

Severe disseminated Bacillus-Calmette-Guerin (BCG) infection is very rare and has been regarded as idiopathic when no immunodeficiency is present. This entity seems to be due to several new types of inherited abnormalities in the pathways important in defence against Mycobacteria. Although improvement with interferon-γ (IFN-γ) has been reported in some patients, to our knowledge there are no reports on the effect of other cytokines in the treatment of these patients. We report here the clinical response to IFN-γ and granulocyte-monocyte colony stimulating factor (GM-CSF) treatment in a patient with idiopathic disseminated BCG infection who failed to respond to multiple antimycobacterial agents. The patient showed partial and transitory response to IFN-γ, however, GM-CSF treatment led to rapid improvement of skin lesions within 2 weeks without any effect on the progression of the disease in the other organ systems. Conclusion The response of idiopathic disseminated Bacillus-Calmette-Guerin infection to granulocyte-monocyte colony stimulating factor treatment was limited to cutaneous lesions. Granulocyte-monocyte colony stimulating factor may have acted to promote wound healing or the levels of this factor achieved in other affected organs may have been inadequate. Received: 26 January 1999 / Accepted: 1 July 1999     

儿童多浆膜腔积液38例

目的探讨儿童多浆膜腔积液的临床特点及病因,以提高临床诊治水平。方法回顾性分析2000年1月-2011年6月本院确诊的38例多浆膜腔积液患儿的临床资料,浆膜腔积液标本送检行常规、涂片及细菌培养等检查,采用Light标准判断积液性质。结果本组38例多浆膜腔积液患儿中男24例,女14例;年龄41 d～14岁,其中41 d～3岁8例(21.1%),>3～6岁10例(26.3%),>6～14岁20例(52.6%)。病因以外伤最多见[10例(26.3%)],其次是细菌感染[7例(18.4%)]、肺吸虫病[6例(15.8%)]和心源性疾病[5例(13.2%)]。其中41 d～3岁患儿中外伤最多见,>3～6岁患儿中肺吸虫病多见,>6～14岁患儿以细菌感染为主。多浆膜腔积液以胸腔积液+腹腔积液最多(15例),病因以外伤多见;胸腔积液+心包积液11例,以细菌感染为主;胸腔积液+腹腔积液+心包积液11例,以肺吸虫病多见;心包积液+腹腔积液1例,为高处坠落伤患儿。21例患儿行积液检查,结果显示渗出液16例,其中细菌感染6例,肺吸虫4例,结核病、结缔组织疾病各3例;介于渗出液与漏出液之间5例,渗出液与漏出液为肿瘤及先天性心脏病患儿。肺吸虫病患儿血IgE升高明显,嗜酸性粒细胞均增高。结论儿童多浆膜腔积液好发于6～14岁,以渗出液为主,胸腔积液+腹腔积液最多见;常见病因为外伤、细菌和肺吸虫感染,心源性疾病均为先天性心脏病伴心功能不全;各年龄段的病因构成不同,临床表现无特异性。     

Invasive pneumococcal infections in pediatric cardiac transplant patients

BACKGROUND: Bacterial infections cause significant morbidity and mortality in cardiac transplant patients. Because Streptococcus pneumoniae is the most prominent bacterial pathogen of childhood, the objective of this study was to define the role of S. pneumoniae as a pathogen in the cardiac transplant population. METHODS: Medical records of cardiac transplant patients from March, 1990, through November, 2000, were reviewed to identify invasive pneumococcal infections after transplantation. Demographic, clinical and microbiologic data were reviewed. RESULTS: Nine (11%) of 80 patients had 12 episodes of pneumococcal bacteremia for an incidence rate of 39 cases/1,000 patient years. Patients who were African-American, transplanted before 2 years of age and transplanted because of idiopathic dilated cardiomyopathy were at increased risk of invasive pneumococcal disease (P < 0.05). Six patients were eligible for the 23-valent pneumococcal polysaccharide vaccine before their first invasive infection, but only 1 had received it at the recommended age. Most isolates (82%) were penicillin-susceptible, and no single serotype predominated. There were 2 deaths in the study group, but each was unrelated to infection. Three patients (33%) had recurrent invasive disease with a second serotype an average of 12 months after the first infection. CONCLUSIONS: The incidence of pneumococcal bacteremia in cardiac transplant patients is higher than in the general pediatric population. Risks for infection were being African-American, being younger than 2 years at the time of transplant and being transplanted because of idiopathic cardiomyopathy. It is plausible that pneumococcal vaccine would decrease this risk.     

Serious adverse events associated with bacille Calmette-Guérin vaccine in Canada

BACKGROUND: Targeted Bacille Calmette-Guérin (BCG) vaccination is offered to neonates in some First Nations and Inuit (FNI) communities in Canada. Serious adverse events associated with BCG vaccine prompted a review to assess causality. METHODS: The Immunization Monitoring Program Active (IMPACT), a pediatric hospital-based active surveillance network, reported admissions for BCG-related adverse events between 1993 and April 2002. The Canadian Advisory Committee on Causality Assessment (ACCA) reviewed the reports to assess causality. Data between 1987 and September 2002 from the Vaccine-Associated Adverse Event Surveillance (VAAES) Program, a passive national reporting system, were also reviewed. RESULTS: IMPACT identified 21 pediatric cases; 19 were Canadian-born, and 18 were FNI. Six disseminated BCG cases were identified; 5 were FNI infants who subsequently died. All had immunodeficiencies and concurrent infections. Other adverse events included 2 cases of osteomyelitis, BCG abscesses and lymphadenitis. ACCA reviewed the 21 cases and determined that 14 were very likely associated with the vaccine, including the 6 disseminated BCGs; 5 were probably associated and 1 was possibly associated with the vaccine; 1 was unclassifiable. The VAAES program identified 157 adverse events. No additional serious systemic adverse events (disseminated BCG or osteomyelitis) were identified. CONCLUSIONS: Serious BCG vaccine-associated complications continue to occur in Canada. The numbers of FNI children with disseminated disease was greater than expected from reported rates in the literature.     

不同类型戈谢病患儿感染风险差异分析

背景 戈谢病是一种罕见的免疫功能异常的疾病,患儿易受到不同病原体感染,不同类型戈谢病感染特点值得关注.目的 探讨不同类型的戈谢病与感染相关的临床特征,为预防相关感染提供帮助.设计病例系列报告.方法 采集不同类型的戈谢病患儿反复呼吸道感染、重症肺炎发生情况,减毒活疫苗接种及其发生感染情况,外周血细胞计数,行电话随访预后(...     

Successful treatment of disseminated cryptococcal infection in a pediatric acute lymphoblastic leukemia patient during induction

Disseminated cryptococcal infection is rarely reported in the setting of pediatric acute leukemia, despite the immunocompromised state of these patients. However, when present, disseminated cryptococcal infection poses treatment challenges and is associated with significant morbidity and mortality. Treatment of invasive fungal disease in a child with acute leukemia requires a delicate balance between antifungal and antineoplastic therapy. This balance is particularly important early in the course of leukemia, as both the underlying disease and overwhelming infection can be life threatening. We describe the successful management of life-threatening disseminated cryptococcosis in a child with acute lymphoblastic leukemia during induction therapy.