自身免疫性溶血性贫血和Evans综合征复发后再治疗探讨

自身免疫性溶血性贫血(AIHA)和Evans综合征复发率高,长期缓解率只有13%～16%[1,2].复发后如何再治疗是临床上一大难题.我们对我院收治的AIHA/Evans综合征复发患者30例进行再治疗观察,了解再治疗疗效,并分析不同治疗方案对再治疗疗效的影响.现将结果报告如下.     

雷帕霉素治疗难治性Evans综合征六例临床观察

Evans综合征是一种自身免疫性溶血性贫血伴血小板减少综合征.其发病机制与自身免疫功能紊乱有关,糖皮质激素、环孢素A等治疗有效,但一部分患者治疗效果差,且副反应大,难以耐受.为进一步探讨Evans综合征的治疗,我们应用雷帕霉素治疗难治性Evans综合征患者6例,进行疗效分析.     

环孢菌素A治疗难治性Evans综合征12例临床观察

Evans综合征是一种自身免疫性溶血性贫血和血小板减少性紫癜同时或相继发生的综合征.其发病机制与自身免疫功能紊乱有关,用激素治疗有效,但有相当一部分患者用激素治疗效果差,且副反应大,难以耐受.为进一步探讨对Evans综合征的治疗,我们应用环孢菌素A(CsA)治疗难治性Evans 综合征患者12例.现报告如下.     

系统性红斑狼疮合并Evans综合征临床特点

目的总结系统性红斑狼疮(systemic lupus erythematosus,SLE)合并Evans综合征患者的临床特点。方法回顾性分析北京协和医院2004年1月至2012年7月SLE合并Evans患者的临床表现及实验室特点及治疗和预后。结果 SLE并发Evans综合征患者22例,占同期SLE住院患者3400例的0.65%。其中男3例,女19例,平均35.1岁(16~53岁)。22例患者中以血液系统受累[特发性血小板减少性紫癜(idiopathic thrombocytopenic purpura,ITP)或自身免疫性溶血性贫血(autoimmune hemolytic anemia,AIHA)]为首发表现的11例(50%),确诊SLE后诊断Evans综合征者6例,二者同时诊断的5例。SLE并发Evans综合征时,患者往往有多系统受累,表现为肾脏受累13例(59.1%),皮肤黏膜受累、关节炎各9例(40.9%),神经系统受累4例(18.2%),胃肠道、肺部受累各2例等。Evans综合征多发生于SLE活动期,患者平均狼疮活动指数评分(11.45±7.6)分(3~30分)。伴发其他结缔组织病5例(22.7%)。经激素联合免疫抑制剂治疗后,20例好转,2例无效者应用利妥昔单抗后好转。结论 SLE合并Evans综合征罕见,发生于SLE多系统受累及活动期。部分患者以ITP或AIHA为SLE首发表现,应及时筛查多种自身抗体,并定期随访密切观察,以期早期诊治。     

合并脑静脉窦血栓形成的Evans综合征一例并文献复习

作者回顾性分析1例合并脑静脉窦血栓形成(CVST)的Evans综合征患者的临床资料。患者中年女性,因突发头痛、呕吐入诊首都医科大学宣武医院神经内科,既往Evans综合征病史9个月。患者入院即存在溶血和血小板减少,MR静脉血管成像和DSA示上矢状窦、直窦及右侧乙状窦静脉血栓形成。脑脊液压力增高,眼底示双侧视乳头水肿,确诊为Evans综合征合并CVST。给予抗凝、激素及降颅压等治疗,症状好转。Evans综合征是自身免疫性溶血性贫血和免疫性血小板减少症并发的综合征,可增加发生血栓的风险。当患者出现头痛、呕吐及视乳头水肿等症状时,需警惕合并CVST的可能。Evans综合征合并CVST的患者,需长期抗凝治疗,同时在激素治疗的减量过程中,应警惕Evans综合征的复发。     

部分脾栓塞术治疗自身免疫性溶血性贫血和Evans综合征疗效观察

1991～2004年,我们采用部分脾栓塞术治疗自身免疫性溶血性贫血（AIHA）和Evans综合征18例。并与单独采用糖皮质激素治疗的26例进行了对比观察。现报告如下。临床资料：AIHA及Evans综合征患者共44例,男15例,女29例;中位年龄39（13～63）岁。其中AIHA36例,Evans综合征8例;原发40例,继发于类风湿性关节炎2例、系统性红斑狼疮2例。随机分为部分脾栓塞组18例与传统方案组26例。     

切脾治疗难治和复发自身免疫性溶血性贫血和Evans综合征的临床疗效

自身免疫性溶血性贫血(AIHA)是一类体内存在针对自身成熟红细胞抗体的溶血性疾病,若并发免疫性血小板减少性紫癜(ITP),称为Evans综合征.糖皮质激素(以下简称激素)治疗成人AIHA的持续缓解率仅为20%～35%[1],若出现激素耐药或严重并发症时可行脾切除等二线治疗,现就我院7例脾切除AIHA和Evans综合征患者疗效总结如下.     

苄胺唑啉丹参及大黄预防重症肝炎肝肾综合症

早期应用苄胺唑啉、丹参及大黄治疗急重肝4例,亚重肝14例,慢活肝重型18例.通过对比研究及患者24小时尿量、血尿素氮、血尿肌酐、钠和水负荷试验的观察,发现肝肾综合征发生率:治疗组36.1%(13/36),对照组62%(18/29),(P<0.05);病死率:治疗组38.9%(14/36),对照组65.5%(19/29),(P<0.05),即两组疗效具有显著性差异.该结果提示三种药物早期联合应用,能明显阻止肝肾综合征的发生和发展,能降低病死率.     

~(131)I治疗儿童及青少年Graves病甲亢疗效评价

目的分析~(131)I治疗儿童及青少年甲亢的临床效果,探讨应用~(131)I治疗儿童及青少年甲亢的可行性。方法从确诊为甲亢并进行~(131)I治疗的468例儿童、青少年患者的临床资料中,抽取临床资料完整(包括随访资料、甲功、肝功、外周血常规等复查结果)的253例患者的病例资料进行分析。结果 253例患者中,1次治愈229例(90.51%)、好转21例(8.30%)、无效3例(1.19%),治疗总有效率为98.81%。2次治疗后,治愈14例(5.53%)。出现甲减37例(14.62%),综合甲减率为11.85%,复发9例(3.55%)。结论~(131)I治疗儿童青少年甲亢疗效肯定、相对安全,无明显近期和远期副作用,~(131)I可作为治疗儿童青少年甲亢的首选方案。     

儿童及青少年2型糖尿病的诊断和治疗

儿童及青少年糖尿病一直是威胁儿童及青少年健康成长的重要危险因素,目前儿童及青少年糖尿病中2型糖尿病占很大一部分.对儿童及青少年2型糖尿病的诊断主要是与1型糖尿病的鉴别.儿童及青少年2型糖尿病多伴有肥胖、多囊卵巢综合征（PCOS）、黑棘皮病等,可以通过临床症状、空腹血糖、口服葡萄糖耐量试验（OGTT）、胰岛素自身抗体和C肽水平来诊断儿童及青少年2型糖尿病.儿童及青少年2型糖尿病与1型糖尿病相比,更早、更易出现糖尿病微血管并发症.目前的治疗方案主要有糖尿病健康教育、饮食控制、运动疗法、口服药物和胰岛素治疗.     

Evans syndrome in adults - incidence,prevalence, and survival in a nationwide cohort

Patients with Evans syndrome have both immune thrombocytopenia and autoimmune hemolytic anemia, but little is known about the epidemiology of this rare syndrome. Evans syndrome can be primary or secondary. This nationwide retrospective study linked health registries to identify 242 patients with Evans syndrome in Denmark in 1977-2017. For comparison, we identified three age-matched and sex-matched cohorts of patients with only immune thrombocytopenia or only autoimmune hemolytic anemia, and a general population cohort. The Evans syndrome cohort had a mean age of 58.5 years at diagnosis, 51.2% were women, and 27.3% were classified as secondary Evans syndrome. The annual Evans syndrome incidence and prevalence rose significantly during the study period, to 1.8 per million person-years and 21.3 per million persons, respectively, in 2016. The median survival with Evans syndrome was 7.2 years (primary Evans syndrome: 10.9 years; secondary Evans syndrome: 1.7 years). Secondary Evans syndrome was associated with higher mortality rates than any of the other cohorts, with a 5-year survival of 38%. Among patients with Evans syndrome, the prevailing causes of death were bleeding, infections, and hematological cancer. In conclusion, we found that both primary and secondary Evans syndrome conferred a poor prognosis. Lethal complications probably derive primarily from manifestations of underlying autoimmune hemolytic anemia and immune thrombocytopenia. Our findings suggested that suspicion of Evans syndrome should prompt vigilant clinical follow-up. International collaborations are warranted to advance our knowledge of optimal management of this rare disease.     

Evans syndrome: a study of six cases with review of literature

Abstract

Evans syndrome is an uncommon condition characterised by simultaneous or sequential development of immune thrombocytopenia (ITP) and autoimmune haemolytic anaemia (AIHA) with a positive direct antiglobulin test (DAT) in the absence of a known underlying aetiology. The great majority of patients with Evans syndrome have a chronic relapsing course despite treatment, which is associated with significant morbidity and mortality. We reviewed the clinical and laboratory features of six patients with Evans syndrome. All patients had thrombocytopenia, bleeding symptoms and haemolytic anaemia with positive direct Coombs test at presentation. We discuss the aetiopathogenic, clinical, therapeutic and natural history of Evans syndrome.     

von Willebrand factor cleaving protease and ADAMTS13 mutations in childhood TTP

Thrombotic thrombocytopenic purpura (TTP) is caused by the persistence of the highly reactive high-molecular-weight multimers of von Willebrand factor (VWF) due to deficiency of the specific VWF-cleaving protease (VWF-CP) ADAMTS13, resulting in microangiopathic disease. The acquired form is caused by autoantibodies against VWF-CP, whereas homozygous or compound heterozygous mutations of ADAMTS13 are responsible for recessively inherited TTP. We investigated 83 children with hemolytic or thrombocytopenic episodes with or without additional neurologic symptoms or renal failure. The presumed diagnosis was chronic idiopathic thrombocytopenic purpura (ITP; n = 50), TTP (n = 8), hemolytic uremic syndrome (HUS; n = 24), and Evans syndrome (n = 1). A severe deficiency of VWF-CP (< or = 5%) was found in all investigated patients with TTP and in none of those with HUS. Additionally, 2 of 50 patients with a prior diagnosis of ITP were deficient for VWF-CP. Antibodies against VWF-CP were found in 4 children. Mutation analysis of the ADAMTS13 gene in the patients deficient in VWF-CP by direct sequencing of all 29 exons identified 8 different mutations, suggesting the hereditary form of TTP in 1 patient with ITP, in the patient with Evans syndrome, and in 5 of the 8 patients with TTP. The phenotype of TTP in childhood can be rather variable. Besides the classical clinical picture, oligosymptomatic forms may occur that can delay the identification of patients at risk.     

Felty's syndrome in a child

The occurrence of the triad of leukopenia, splenomegaly and rheumatoid arthritis (RA) (Felty's syndrome) during childhood has not been reported previously. We describe an adolescent with onset during childhood of seropositive, nodular, erosive, polyarticular RA in whom both leukopenia and splenomegaly were accompanying features. Neither nonsteroidal antiinflammatory agents nor plasmapheresis were therapeutically beneficial, but low dose oral prednisone therapy resulted in both clinical and hematological improvement.     

Clinical review: Identifying children at risk for polycystic ovary syndrome

CONTEXT: Polycystic ovary syndrome (PCOS) appears to arise as a complex trait with contributions from both heritable and nonheritable factors. Polygenic influences appear to account for about 70% of the variance in pathogenesis. In view of this evidence for congenital contributions to the syndrome, childhood manifestations may be expected. OBJECTIVE: The objective has been to review the evidence that risk factors for PCOS can be recognized in childhood. DESIGN: This study consisted of screening of the PCOS literature for articles pertaining to potential childhood and adolescent antecedents. RESULTS: Congenital virilizing disorders; above average or low birth weight for gestational age; premature adrenarche, particularly exaggerated adrenarche; atypical sexual precocity; or intractable obesity with acanthosis nigricans, metabolic syndrome, and pseudo-Cushing syndrome or pseudo-acromegaly in early childhood have been identified as independent prepubertal risk factors for the development of PCOS. During adolescence, PCOS may masquerade as physiological adolescent anovulation. Asymptomatic adolescents with a polycystic ovary occasionally (8%) have subclinical PCOS but often (42%) have a subclinical PCOS type of ovarian dysfunction, the prognosis for which is unclear. CONCLUSION: Identifying children at risk for PCOS offers the prospect of eventually preventing some of the long-term complications associated with this syndrome once our understanding of the basis of the disorder improves.     

儿童肾上腺皮质肿瘤的临床特征

目的 分析儿童肾上腺皮质肿瘤的临床特征,提高对本病诊断的认识以及判别能力.方法 回顾分析广州中山大学附属第一医院31例儿童肾上腺皮质肿瘤患儿的症状、实验室检查、影像学检查等.结果 腺瘤16例,腺癌15例.诊断时平均年龄(4.49±3.51)岁,男女比例为1:1.4.12例呈单纯外周性性早熟表现,4例单纯库欣综合征表现,10例兼有二者表现,5例无内分泌异常症状.92.3%患儿睾酮升高.B超和CT诊断分别仅12.5%、20.8%与病理符合.结论 儿童肾上腺皮质肿瘤以外周性性早熟及雄激素升高表现多见.影像学检查无法准确定性,最后诊断须综合临床表现、实验室检查、影像学和病理结果.     

Childhood Sleep Problems,Response Inhibition,and Alcohol and Drug Outcomes in Adolescence and Young Adulthood

Background: To our knowledge, no prospective studies examine the relationships among childhood sleep problems, adolescent executive functioning, and substance outcomes (i.e., substance use and substance‐related problems). In this study, we examined whether childhood sleep problems predicted adolescent sleep problems and response inhibition. We also tested whether adolescent sleep problems and poor response inhibition mediated the relationship between childhood sleep problems and substance (alcohol and drug) outcomes in young adulthood. Methods: Study participants were 292 boys and 94 girls (M = 4.85, SD = 1.47) from a community sample of high‐risk families and controls. Results: When compared to their counterparts, those with trouble sleeping in childhood were twice as likely to have the same problem in adolescence. Childhood overtiredness predicted poor response inhibition in adolescence. Persistent trouble sleeping from childhood to adolescence and response inhibition in adolescence mediated the relationship between childhood sleep problems and drug outcomes in young adulthood, whereas overtiredness in childhood directly predicted alcohol use outcomes and alcohol‐related problems in young adulthood. Conclusions: This is the first study showing a long‐term relationship between childhood sleep measures and subsequent alcohol and drug outcomes. The developmental and clinical implications of these findings were discussed. Prevention and intervention programs may want to consider the role of sleep problems and response inhibition on substance use and abuse.     

Impact of neoadjuvant therapy on gut microbiome in patients with resectable/borderline resectable pancreatic ductal adenocarcinoma

Background/Objectives: Effects of chemotherapy on gut microbiota have been reported in various carcinomas. The current study aimed to evaluate the changes in the gut microbiota before and after neoadjuvant chemotherapy (NAC) in patients with resectable (R) and borderline resectable (BR) pancreatic ductal adenocarcinoma (PDAC) and understand their clinical implications.MethodsTwenty patients diagnosed with R/BR-PDAC were included in this study. Stool samples were collected at two points, before and after NAC, for microbiota analysis using 16S ribosomal RNA (16S rRNA) gene sequences.ResultsOf the 20 patients, 18 (90%) were treated with gemcitabine plus S-1 as NAC, and the remaining patients received gemcitabine plus nab-paclitaxel and a fluorouracil, leucovorin, irinotecan, and oxaliplatin combination. No significant differences were observed in the α- and β-diversity before and after NAC. Bacterial diversity was not associated with Evans classification (histological grade of tumor destruction by NAC) or postoperative complications. The relative abundance of Actinobacteria phylum after NAC was significantly lower than that before NAC (P = 0.02). At the genus level, the relative abundance of Bifidobacterium before NAC in patients with Evans grade 2 disease was significantly higher than that in patients with Evans grade 1 disease (P = 0.03). Patients with Evans grade 2 lost significantly more Bifidobacterium than patients with Evans grade 1 (P = 0.01).ConclusionsThe diversity of gut microbiota was neither decreased by NAC for R/BR-PDAC nor associated with postoperative complications. Lower incidence of Bifidobacterium genus before NAC may be associated with a lower pathological response to NAC.