Peritoneal hemorrhage due to a ruptured ovarian cyst in ITP

Immune thrombocytopenic purpura in children rarely causes severe bleeding. The incidence of intracranial hemorrhage is approximately 0.2% to 1.0%, and severe bleeding (defined as persistent epistaxis, melena, menorrhagia, gastrointestinal bleeding, etc, requiring hospitalization or transfusion) occurs in only 5% of patients. Epstein-Barr virus (EBV) associated idiopathic thrombocytopenic purpura (ITP) tends to behave similarly to non-EBV - associated ITP with no increase in hemorrhagic complications and only a small increase in time to remission. Immune thrombocytopenic purpura diagnosed in adolescence is more likely to be chronic then in childhood ITP, but has a higher rate of spontaneous resolution than in adults. However, females in this age group are in their early childbearing years and present a unique set of possible hemorrhagic complications not seen in younger patients. We present the case of an 18-year-old female with EBV-associated ITP, who developed a severe intra-abdominal bleed secondary to a hemorrhagic ovarian cyst.     

Epstein-Barr virus-associated infectious mononucleosis in Chinese children

BACKGROUND: According to seroprevalence studies the majority of children in Hong Kong are infected by Epstein-Barr virus (EBV) before 10 years of age, but the characteristics of EBV-associated infectious mononucleosis (IM) in Chinese children are largely unreported. This study aims at defining the clinical presentation and complications of Chinese childhood IM in relation to age of the children. METHODS: A retrospective study was performed on 77 consecutive Chinese childhood IM patients who fulfilled the serologic criteria for the diagnosis of primary EBV infection (viral capsid antigen IgM+ viral capsid antigen IgG+ Epstein-Barr nuclear antigen-). The clinical, hematologic and biochemical findings were evaluated among four age groups of <2 years, 2 to 4 years, 5 to 9 years and 10 to 15 years. RESULTS AND CONCLUSIONS: EBV-associated IM occurred at all age groups with a peak incidence at 2 to 4 years, corresponding to the rapid rise in the seroprevalence of EBV in early childhood in the Hong Kong Chinese. The majority of children presented with fever, tonsillopharyngitis, lymphadenopathy and hepatosplenomegaly, similar to the adult IM patients, and recovered without major complications. Marked lymphocytosis with the presence of atypical lymphocytes was a consistent hematologic finding in all age groups. The occurrence of hepatitis showed a clear association with advancing age (P = 0.003). The age-related increase in IM-associated hepatitis may reflect difference in the host immune response against EBV between the infants and older children.     

Virus-associated immune thrombocytopenic purpura in childhood

Idiopathic thrombocytopenic purpura (ITP) in children is usually a self-limiting disorder. It may follow a viral infection or immunization and is caused by an inappropriate response of the immune system. Many viruses, such as human immunodeficiency virus, cytomegalovirus (CMV), Epstein-Barr virus (EBV), varicella, rubeola, mumps, and parvovirus, have been implicated in childhood ITP. This study is a retrospective chart review of pediatric patients diagnosed with virus-associated ITP at the Hacettepe University, Ihsan Dogramaci Children's Hospital from 1997 to end of 2000. In viral serological studies, the EBV, CMV, and rubella antibodies were investigated for all patients at diagnosis (ELlSA). The proportion of children whose ITP was associated with documented acute viral infection was 13.3% in this group. In the present study, clinical manifestations and laboratory data of virus-associated or not associated groups are similar except age. Median age of the virus-associated group is younger than that of the other, but it is not statistically significant.     

VIRUS-ASSOCIATED IMMUNE THROMBOCYTOPENIC PURPURA IN CHILDHOOD

Idiopathic thrombocytopenic purpura (ITP) in children is usually a self-limiting disorder. It may follow a viral infection or immunization and is caused by an inappropriate response of the immune system. Many viruses, such as human immuno deficiency virus, cytomegalovirus (CMV), Epstein-Barr virus (EBV), varicella, rubeola, mumps, and parvovirus, have been implicated in childhood ITP. This study is a retrospective chart review of pediatric patients diagnosed with virus-associated ITP at the Hacettepe University, &#71 hsan Do &#60 ramaci Children's Hospital from 1997 to end of 2000. In viral serological studies, the EBV, CMV, and rubella antibodies were investigated for all patients at diagnosis (ELISA). The proportion of children whose ITP was associated with documented acute viral infection was 13.3% in this group. In the present study, clinical manifestations and laboratory data of virus-associated or not associated groups are similar except age. Median age of the virus-associated group is younger than that of the other, but it is not statistically significant.     

EBV diseases

Epstein-Barr virus (EBV) infection in early childhood is usually asymptomatic or associated with symptoms common to many other viral infections, such as pharyngitis, bronchitis or enteritis. Typical infectious mononucleosis, as seen in young adult patients, is rare in early childhood. There is also a lower rate of heterophil antibody responses in young children. Many complications of the infection are known, and many atypical manifestations can be identified as EBV-associated using modern EBV-specific serological methods. The problems of EBV infection during gestation and the neonatal period are described and the chronic and persistent infections, as well as the lymphoproliferative syndromes associated with EBV infection, are particularly taken into consideration.     

91例EB病毒相关疾病儿童血浆EB病毒DNA的检测

目的:了解EB病毒（EBV）感染患儿外周血血浆中游离EBV DNA的拷贝数,确定EBV原发感染后外周血血浆中EBV游离DNA的拷贝数与发病天数及病情轻重的关系。方法:应用荧光定量PCR方法,测定73例EBV原发感染和18例EBV相关重症疾病患儿外周血血浆中EBV游离DNA。结果:①原发EBV感染患儿外周血血浆中EBV游离DNA随发病天数呈下降趋势,发病2周后很难检测到。②EBV相关重症疾病组患儿外周血血浆中EBV游离DNA阳性率明显高于原发EBV感染组,差异有显著性(89% vs 16%, P＜0.05）。结论: 原发EBV感染后随病程天数的增加,病毒复制水平逐渐下降。血浆中EBV游离DNA检测对评价EBV相关疾病的严重程度有一定参考价值。［中国当代儿科杂志,2009,11（11）：897-900］     

Acute thrombocytopenic purpura associated with primary Epstein-Barr virus infection

Acute idiopathic thrombocytopenic purpura (ITP) often appears to be related to the sensitization by some viral infections. However, the causative viral agents are not identified in most cases. Although the primary infection with Epstein-Barr virus (EBV) occurs during early childhood in Japan, the majority of cases are usually asymptomatic. A minority are associated with acute infectious mononucleosis (IM), which is characterized by fever, tonsillitis, lymphadenopathy, splenomegaly and liver dysfunction. In this report, three cases are described of children with EBV-induced ITP who clinically had atypical findings of IM. Their primary EBV infections were confirmed by serological test and, in addition, were verified by the enhanced expression of activation antigens (HLA-DR and CD45RO) on T cells as well as the inverted ratio of CD4⁺ to CD8⁺ subsets. These observations imply that ITP can occur as one of the host responses during primary EBV infections, irrespective of clinical manifestations. Evaluation of lymphocyte subpopulations may be useful for the assessment of primary EBV infection in ITP.     

91例EB病毒相关疾病儿童血浆EB病毒DNA的检测

目的了解EB病毒(EBV)感染患儿外周血血浆中游离EBVDNA的拷贝数,确定EBV原发感染后外周血血浆中EBV游离DNA的拷贝数与发病天数及病情轻重的关系。方法应用荧光定量PCR方法,测定73例EBV原发感染和18例EBV相关重症疾病患儿外周血血浆中EBV游离DNA。结果①原发EBV感染患儿外周血血浆中EBV游离DNA随发病天数呈下降趋势,发病2周后很难检测到。②EBV相关重症疾病组患儿外周血血浆中EBV游离DNA阳性率明显高于原发EBV感染组,差异有显著性(89%vs16%,P<0.05)。结论原发EBV感染后随病程天数的增加,病毒复制水平逐渐下降。血浆中EBV游离DNA检测对评价EBV相关疾病的严重程度有一定参考价值。     

Clinical significance of peripheral blood Epstein-Barr viral load monitoring using polymerase chain reaction in renal transplant recipients

PTLD is a complication of EBV infection. We examined the efficacy of EBV-PCR monitoring to detect early replication in an attempt to prevent EBV-associated PTLD. Blood EBV levels in 156 renal transplant recipients (58 children) from three institutions over nine yr were retrospectively analyzed. Patients who were asymptomatic and at high risk for PTLD were monitored for EBV infection by PCR or serology followed by PCR at the time of EBV seropositivity. More children than adults had positive EBV-PCR (12/58 vs. 2/98, p < 0.001). Adults remained asymptomatic and viremia resolved post-therapy. 3/12 EBV-PCR positive children developed PTLD (3/12 children vs. 0/2 adults, p = NS). Two out of three with PTLD were initially monitored by serology, and later by PCR. PTLD resolved post-therapy in all three patients. The remaining 9/12 EBV-PCR positive children stayed asymptomatic. None of the children and adults with negative EBV-PCR developed PTLD. EBV-PCR monitoring in high-risk renal transplant recipients, especially in children, may allow early diagnosis and intervention, and therefore may help in preventing EBV-associated PTLD.     

Persistent Low Level Epstein-Barr Virus DNAemia in Childhood Cancer Survivors

Background: Clinical observation of Epstein-Barr virus (EBV) status has not documented in childhood cancer survivors (CCSs) sustaining long-term remission of malignant diseases. Thus, the aim of this study was to evaluate the EBV status in children with various malignant diseases after they completed their treatments. Patients and Methods: Thirty consecutive children with various malignant diseases previously received treatment at the University of Tsukuba Hospital. Nine cases had acute lymphoblastic leukemia (ALL), 10 had solid tumors, 4 had lymphoma, 4 had CNS tumors, and 3 had acute myeloid leukemia (AML). EBV DNA in 328 whole blood samples were monitored by real-time QPCR for all cases after treatment. Clinical records and laboratory data were also reviewed. Results: There were 6/30 (20%) cases with continuous detection of EBV DNA while there were 24/30 (80%) cases without continuous EBV DNA. EBV DNAemia was persistently observed in 4/9 (44.4%) cases with ALL and in 2/4 (50%) cases with lymphoma. Persistent EBV DNAemia can be observed for >5 years without any EBV associated symptoms or diseases. Conclusions: Childhood cancer survivors have persistent EBV DNAemia more frequently, which is thought to be observed in cases with ALL and lymphoma with higher tendency for >5 years after treatment. Persistent EBV DNAemia is frequent in CCSs aged 5–10 years. Any immunological alteration is speculative in a pathophysiology of persistent EBV DNAemia.     

Prevalence of Epstein-Barr Viral DNA among children at a single hospital in Suzhou,China

ObjectiveThis study aimed to describe the prevalence of Epstein-Barr virus (EBV)-DNA among children in Suzhou, and to explore the association between plasma EBV load and disease diagnosis.MethodsAll children admitted to the Children's Hospital of Soochow University between January 2018 and September 2020 and subjected to the plasma EBV-DNA assay were included. The authors retrospectively collected demographic and discharge diagnostic information of the participants, and ascribed the disease distribution characteristics of children with positive plasma EBV-DNA by age and viral load.ResultsA total of 38,175 patients underwent plasma EBV-DNA PCR assay, of which 2786 (7.3%) had EBV-DNA in their plasma. Children aged 3–4 years had a high prevalence of EBV infection. Plasma EBV positivity was common with infectious mononucleosis (IM, 40.0%), respiratory infection (20.1%), atypical EBV infection (14.2%), acute leukemia (6.4%), hemophagocytic lymphohistiocytosis (HLH, 4.8%), and idiopathic thrombocytopenic purpura (ITP, 2.9%). With increasing age, plasma EBV positivity was more common in children with IM and atypical EBV infection. However, an inverse correlation was observed in children with respiratory infections and ITP. High levels of EBV loads were more likely to occur in HLH, IM, and atypical EBV infection, especially in HLH. However, lower viral loads were found in respiratory infection and acute leukemia.ConclusionsThis is a large sample study that revealed the prevalence of plasma EBV-DNA levels in children of various ages and presenting illnesses.     

急性淋巴细胞白血病并EB病毒感染的临床分析

目的 探讨EB病毒(EBV)在急性淋巴细胞白血病(ALL)儿童中的感染及其临床意义.方法采用荧光定量聚合酶链反应(FQ-PCR)技术检测EBV DNA,ELISA法检测EB病毒衣壳抗原IgM抗体(EBV-CA-IgM),共检测47例.其中新发45例,复发2例;年龄0～14岁[(8.06±3.71)岁].另取14例健康儿童作为健康对照组.男9例,女5例;年龄2～10岁[(7.24±2.54)岁].结合临床表现、诱导治疗骨髓完全缓解(CR)率、形态学CR状态下的微小残留病(MRD)、复发率及无事件生存(EFS)率等分析ALL患儿中EBV感染情况及其临床意义.结果 47例ALL患儿中检出EBV感染15例(31.9%),其中11例(23.40%)检出EBV DNA,EBV DNA水平为(3.28±5.95)×108copy·L-1;14例健康对照组外周血未检测到EBV DNA及EBV-CA-IgM.ALL中EBV感染组与非EBV感染组白细胞数分别为(78.00±58.38)×109 L-1、(27.46±60.10)×109 L-1(t=2.70,P=0.01),诱导治疗CR率分别为 46.7%、87.5%(P<0.01),MRD>10-3分别为90.0%、26.1%(P<0.01),复发率分别为53.8%、13.8%(P<0.01),EFS率分别为 23.1%、82.8%(P<0.01).结论 ALL并EBV感染具有高白细胞数、低诱导治疗CR率、高复发率、低EFS率,提示EBV感染可能参与儿童ALL的发生发展过程,亟待改善EBV感染ALL的治疗方法.     

Atypische Epstein-Barr-Virus(EBV)-Infektionen im Kindes- und Jugendalter

The clinical syndrome of acute infectious mononucleosis is predominantly a disease of older children and adolescents. Primary EBV infection in younger infants is often subclinical. Complications may affect any organ system and are usually mild. In the majority of cases acute infectious mononucleosis has an excellent prognosis. Severly immuncompromised children and adolescents (i. e. under immunosuppressive therapy, after stem cell transplantation) may develop EBV⁺ B-cell lymphoproliferative disorders and malignant B-cell lymphoma. In this review, mainly the following forms of atypical EBV infections are described in detail: Fulminant, mostly fatal acute infectious mononucleosis following primary EBV infection may occur 1) sporadically (approx. 1 per 3000 cases of acute infectious mononucleosis), 2) in aprox. 60% of boys with X-linked lymphoproliferative disease (XLP), and 3) in very rare cases of a fulminant EBV+ T-cell lymphoproliferative disorder. No efficient therapy exists so far. Early allogeneic stem cell transplantation in boys with XLP may prevent fatal acute infectious mononucleosis and other complications. Chronic active EBV (CAEBV) infection is characterized by recurrent clinical episodes of severe infectious mononucleosis over months or years and additional unusual clinical signs and complications such as coronary artery aneurisms, hypersensitivity to mosquito bites and hydroa vacciniforme, as well as an markedly increased risk for malignant lymphoma, mostly of a T-cell type. In general, prognosis of CAEBV infection is poor. Allogeneic stem cell transplantation may lead to clinical remission. EBV-associated hemophagocytic syndrome may occur as an independent disorder [EBV-related hemophagocytic lymphhistiocytosis (EBV-HLH)] or as a serious complication of fatal infectious mononucleosis or CAEBV infection. Early treatment with etoposide, cyclosporine A and corticosteroids may improve the otherwise poor prognosis. The pathogenesis of atypical EBV infections is not known in most cases. Further molecular and immunologic studies may help to characterize these severe disorders and to develop more specific and more efficient therapies.     

Platelet-associated immunoglobulin G in childhood idiopathic thrombocytopenic purpura

Childhood ITP is an acquired hemorrhagic disorder with a heterogeneous clinical course. We measured PAIgG levels in 20 children with ITP (7 acute, 13 chronic). Both groups had significantly greater PAIgG values than age-matched normal subjects and thrombocytopenic controls (P less than 0.001). In addition, PAIgG values in chronic ITP were significantly lower than those in acute ITP (P less than 0.003). Serial PAIgG values were obtained in some patients; most returned to normal in association with clinical recovery. The measurement of PAIgG is useful in the diagnosis and follow-up of childhood ITP. PAIgG values may assist in differentiating acute and chronic disease in children.     

儿童特发性血小板减少性紫癜病毒感染的临床分析

目的探讨儿童ITP病毒感染情况及其治疗与病情转归。方法(1)统计患儿发病的诱因,部分患儿检测EB病毒、巨细胞病毒、微小病毒B19、单纯疱疹病毒、支原体、自身抗体。分析病毒感染与ITP预后关系。(2)分析难治性与慢性TIP预后与治疗的关系。结果(1)病情严重程度与预后无关。(2)有特殊病毒感染诱因者共22例,其中12例(54.5%)为难治性或转为慢性;无特殊病毒感染诱因者共77例,其中19例(24.7%)为难治性或慢性,差异有显著性(P<0.05)。(3)难治性ITP转慢性的12例治疗效果均欠佳。(4)慢性ITP有特殊病毒感染者6例,其中好转的4例均多次短期大剂量应用丙种球蛋白,此4例中的3例同时或之前应用抗病毒药物,2例应用肾上腺皮质激素冲击。无特殊病毒感染史者13例,治疗好转6例,无效6例,均未应用大剂量丙种球蛋白。结论由特殊病毒感染引起的儿童ITP预后欠佳,加强联合大剂量丙种球蛋白、抗病毒的力度可改善预后。     

Intended management of children with acute idiopathic thrombocytopenic purpura: a national survey

OBJECTIVE: In Australia acute idiopathic thrombocytopenic purpura (ITP) is mainly treated by paediatricians (either general paediatricians or paediatric haematologists/oncologists). A survey was conducted to gauge the current practice of treating children with acute ITP in Australia. METHODS: All practising Australian paediatricians registered by the Royal Australasian College of Physicians were surveyed regarding their intended management of children with acute ITP. The questionnaire, adapted from a study of paediatric haematologists/oncologists in North America, presented four clinical scenarios of children with acute ITP with a platelet count of 3000 x 10(9)/L, with and without mucosal bleeding (wet and dry purpura, respectively). Questionnaires were returned by mail or filled in online at a dedicated webpage. RESULTS: Five hundred and sixty-three of 1097 (51%) paediatricians responded to the survey. Data from 140 who had treated at least one child with ITP in the previous 12 months were analysed. Respondents indicated that children with acute ITP are usually or always hospitalised (58-92%) and that 48% would be given active treatment, even with dry purpura. Various regimens of i.v. immunoglobulin or corticosteroids are used when treatment is administered. In comparing Australian and North American management of acute ITP there were many similarities, although Australian paediatricians were less likely to arrange a bone marrow aspirate if corticosteroids were prescribed. CONCLUSIONS: There is great variation in the intended management of children with acute ITP in Australia. Previously published management recommendations regarding investigation and treatment have had little impact on intended practice. Prospective studies are required to evaluate hypotheses so as to produce evidence-based recommendations for treatment of patients with acute ITP.     

儿童新诊断免疫性血小板减少症与幽门螺杆菌感染的相关性研究

目的明确幽门螺杆菌(H.pylori)感染对儿童新诊断免疫性血小板减少症(ITP)的影响。方法选取2011年1月至2013年12月间首次住院并新诊断为ITP的495例患儿为病例组;随机选取无血小板减少及其他血液系统疾病的普通呼吸道感染住院患儿123例作为对照组。依据年龄将两组患儿分为1岁组(n=219)、1岁~组(n=161)、3岁~组(n=76)和7~14岁组(n=39)。回顾性分析各年龄段患儿H.pylori感染率,以及H.pylori感染阳性及阴性ITP患儿经过相同治疗后的预后情况。结果病例组中H.pylori感染率随着ITP患儿年龄的增长而增加,与对照组各年龄段H.pylori感染率比较差异均无统计学意义(均P0.05)。H.pylori感染阳性ITP患儿均未接受针对H.pylori的相关治疗,而针对血小板减少经丙种球蛋白和/或激素治疗后缓解率随着年龄的增长而呈现逐渐下降趋势,与各年龄段H.pylori阴性的ITP患儿治疗后缓解率比较差异均无统计学意义(均P0.05)。结论 H.pylori感染可能不是ITP患儿发病的一个主要致病因素;是否治疗H.pylori并不影响儿童急性ITP的治疗效果。     

Idiopathic thrombocytopenic purpura diagnosed during the second decade of life

OBJECTIVE: To retrospectively review our institutional experience of adolescents with idiopathic thrombocytopenic purpura (ITP). STUDY DESIGN: Medical record review of all patients diagnosed with ITP between the ages of 10 and 18 years seen at our center from January 1976 to March 2000. RESULTS: Data were collected from 126 patients. Of the evaluable 110 cases, 63 (57%) satisfied the criteria for chronic ITP, 30 (27%) for acute ITP, and 17 (15%) were uncertain. Sex distribution and mean ages were similar in all 3 groups. Platelet count at presentation was higher in patients with chronic ITP. Splenectomy was performed in 24 patients, with 17 (77%) of 22 having normal platelet counts at last follow-up. Outcome for the nonsplenectomized patients with chronic ITP included normalization of platelet count (n = 4), minimal or no bleeding without treatment (n = 29), treatment for ongoing symptoms (n = 5), and unknown (n = 1). Two patients died, 1 from intracranial hemorrhage and 1 from Escherichia coli sepsis and pulmonary hemorrhage. CONCLUSIONS: Patients 10 to 18 years of age with ITP are more likely than younger children to have chronic disease. Many patients with ITP recover without drug therapy or need for splenectomy. ITP in adolescents shares features of both childhood and adult ITP.     

Is bone marrow examination justified in idiopathic thrombocytopenic purpura?

Bone marrow examination is widely accepted among pediatric hematologists as a mandatory investigation in childhood idiopathic thrombocytopenic purpura (ITP). The aim of this procedure is to confirm the presence of megakaryocytes and to exclude other conditions, such as leukemia and aplastic anemia. To assess the need for bone marrow examination, we reviewed the charts of 127 children with presumed ITP and found that bone marrow examination led to a different diagnosis in five (3.9%) of them. All five patients had presented with clinical and/or laboratory features atypical of acute ITP; none had leukemia. The initial clinical and laboratory findings of 50 patients with aplastic anemia also were reviewed; all had features atypical of acute ITP. Proper history and physical examination as well as a complete blood cell count are reliable means of recognizing patients with typical vs atypical features of ITP. Bone marrow aspiration could be limited safely to those patients with atypical features of ITP or to patients being treated with corticosteroids.     

特发性血小板减少性紫癜患儿血清微小病毒B_(19)检测及意义

目的探讨人微小病毒B19(HPVB19)感染与儿童特发性血小板减少性紫癜(ITP)发病的关系。方法采用酶联免疫法(ELISA)对46例ITP患儿利30例健康儿童的血清标本进行HPVB19-IgM、IgG及血小板相关抗体检测。结果46例ITP患儿血清中HPVB19抗体总刚性率43.48%(20/46),30例健康儿童HPVB19-IgM、IgG均为阴性,2组间差异有统计学意义(P<0.01);ITP组中急性型与慢性型之间HPVB19抗体总阳性率差异有统计学意义(P<0.05);病毒感染刚性患儿的血小板相关抗体明显高于病毒感染阴性患儿,差异有统计学意义(P<0.01)。结论ITP患儿血清中HPVB19抗体总刚性率高,尤其是急性型;HPVB19感染后可导致血小板相关抗体升高而致血小板减少。