以血小板减少性紫癜为首发表现的儿童系统性红斑狼疮13例诊治分析

目的 总结儿童系统性红斑狼疮的诊治经验.方法 回顾性分析2004年1月至2009年6月我院收治的13例以急性免疫性血小板减少性紫癜为首发症状的小儿系统性红斑狼疮的诊断、治疗及转归情况.结果 13例初诊患儿经临床表现及骨髓检查诊断为急性免疫性血小板减少性紫癜,经用激素及静脉丙种球蛋白治疗效果欠佳,动态随诊免疫指标及其他临床表现,并根据血液系统改变特点和对激素的反应加用其他免疫抑制剂如环孢素A、霉酚酸酯及环磷酰胺等.13例患儿分别于2～24个月确诊为系统性红斑狼疮,加用其他免疫抑制剂后治疗效果满意.结论 对于血小板减少的患儿尤其是青春期女孩要注意动态监测抗核抗体及其他免疫学指标,警惕系统性红斑狼疮的可能.     

儿童系统性红斑狼疮并狼疮性肺炎1例报告

临床资料:患儿,女,9岁11个月。确诊系统性红斑狼疮(SLE)并狼疮性肾炎(弥漫增生型)2个月余,咳嗽、气急7d于2006-04入院。患儿2个月余前纳减、恶心伴眼睑水肿,存在双颊红斑,心包积液、胸腔积液及大量腹水,大量蛋白尿,指趾端血管病变,血象三系减少,脑电图异常,C3减低,抗核抗体1∶100核均质型(+),抗ds-DNA(+),肾穿病理提示弥漫增生型狼疮性肾炎,确诊患有系统性红斑狼疮并狼疮性肾炎(IV型),同时合并存在心功能不全、肾功能不全,予骁悉、强的松龙口服,甲基强的松龙冲击治疗3次,并抗对症治疗后患儿病情平稳,复查SLE活动指标在正常范围,好转出…     

过敏性紫癜合并抗磷脂综合征1例报告并文献复习

目的探讨过敏性紫癜与抗磷脂综合征的关系。方法通过对1例以间断皮疹、血尿、蛋白尿及上肢肿痛为主诉的患儿进行肾组织病理、抗磷脂抗体检查,随访观察治疗反应,并结合文献复习进行综合分析。结果患儿临床表现为过敏性紫癜混合型,肾脏病理为紫癜性肾炎(Ⅳb型);同时有右上肢静脉血栓形成,狼疮抗凝血因子、抗心磷脂抗体IgM及抗β2糖蛋白-I抗体IgM阳性,诊断为过敏性紫癜合并抗磷脂综合征。给予泼尼松口服、环磷酰胺冲击以及抗凝治疗,患儿临床症状好转,尿蛋白和抗磷脂抗体转阴。结论过敏性紫癜可以合并抗磷脂综合征,临床上应引起高度重视。     

儿童系统性红斑狼疮继发抗磷脂综合征及血栓性微血管病1例并文献复习

目的　探讨儿童系统性红斑狼疮（SLE）继发抗磷脂综合征（APS）及血栓性微血管病（TMA）的临床特点。方法　回顾2019-10-29收入重庆医科大学附属儿童医院风湿免疫科的1例SLE继发APS及TMA患儿的临床资料,并结合文献复习对该类疾病临床特征进行分析。结果　患儿女,12岁,病初全身水肿、尿少、皮肤溃疡伴感染,有血小板减少及贫血,肾功能损害,抗核抗体（ANA）及抗心磷脂抗体（aCL）阳性,肾脏病理示弥漫球性增生性狼疮性肾炎Ⅳ-G（A）伴TMA,明确诊断为SLE继发APS及TMA,使用血浆置换、甲基泼尼松龙、环磷酰胺、丙种球蛋白、血液透析滤过及抗凝、抗感染等治疗,患儿放弃治疗后死亡。结合国内外报道13例儿童SLE继发APS患者以及本例患儿资料,14例患儿中,女11例,男3例;14例患儿均发生血栓事件,静脉血栓9例,动脉血栓2例,微血管血栓3例;血小板减少11例,溶血性贫血7例,狼疮性肾炎4例,其中弥漫性增生性狼疮性肾炎Ⅳ2例,膜性肾病2例,1例（本例）抗磷脂综合征肾病,表现为TMA;14例加用激素和（或）免疫抑制剂治疗,10例患儿抗凝治疗,13例患儿病情好转随访无血栓事件复发,仅本例患儿因放弃治疗后死亡,死亡原因肾功能衰竭。结论　SLE合并APS患儿病情重,早期免疫抑制及抗凝治疗可有效缓解病情,血栓事件复发率低,但继发TMA时治疗效果及预后差,病死率高。     

儿童系统性红斑狼疮合并脑后部可逆性脑病综合征4例并文献复习

目的 分析儿童系统性红斑狼疮（SLE）合并脑后部可逆性脑病综合征（PRES）的临床特征,提高对本病的认识。方法 报告北京协和医院诊断的4例儿童SLE合并PRES的临床资料,在PubMed数据库检索相关病例行文献复习,分析儿童SLE合并PRES的临床表现、影像学检查、治疗及预后情况。结果 ①4例SLE患儿均伴有狼疮性肾炎,从确诊SLE至出现PRES的时间1~63个月,出现PRES时1例正在接受甲泼尼龙及环磷酰胺(CTX)冲击治疗。PRES均以惊厥、头痛起病,并伴血压升高。②PubMed数据库检索到11例SLE合并PRES的儿童病例,结合本文报道的4例,15例进入分析。女性14例。年龄最小8岁。从确诊SLE至出现PRES的间隔中位时间为6个月（1个月至8年）。15例出现PRES时均有惊厥发作,10例伴头痛,7例呕吐,9例意识丧失,7例视力障碍。15例均有血压升高。12例有狼疮性肾炎。治疗SLE予甲泼尼龙或CTX冲击治疗分别为4和3例,予羟氯喹2例,予环孢素和利妥昔单抗各1例,PRES分别发生在免疫抑制剂治疗后的2 d至4年。15例行头颅MRI检查示大脑后循环皮质下白质受累为主。12例予降血压治疗,10例予抗惊厥药物短期治疗。9例SLE处于活动期,继予糖皮质激素和免疫抑制剂治疗;6例非活动期的SLE患儿减停糖皮质激素及免疫抑制剂。15例神经系统症状均恢复,随访均未遗留神经系统后遗症。9例复查头颅MRI示颅内病变完全或基本消失。结论 儿童SLE合并PRES主要表现为惊厥、头痛、意识障碍和视觉障碍。对于有狼疮性肾炎的SLE患儿血压升高时,尤其同时予大剂量糖皮质激素或CTX等免疫抑制剂治疗时,应警惕PRES的发生。早期诊断和治疗PRES预后较好。     

儿童狼疮性脑病临床特征

目的探讨儿童狼疮性脑病(NPSLE)的临床特点、辅助检查及治疗。方法对11例NPSLE患儿的临床资料进行分析。结果11例NPSLE患儿均有不同程度的头痛症状,意识障碍及失语各1例,抽搐、记忆力减退和共济失调各3例,出现病理反射及脑膜刺激征各4例。血清学均呈狼疮活动表现。3例脑脊液常规无异常,寡克隆抗体明显升高。其中10例行头颅CT检查,异常9例;10例患儿行脑电图检查,正常1例,且与CT无交叉。经个体化综合治疗,11例患儿神经精神症状均有不同程度的改善。结论系统性红斑狼疮累及神经系统症状最常表现为头痛。目前NPSLE主要根据临床表现作出诊断,血清学、影像学及脑电图检查有助于狼疮性脑病的诊断。对NPSLE的治疗强调个体化的综合治疗。     

儿童系统性红斑狼疮临床不典型病例诊断分析

目的 比较1997 年美国风湿病学会系统性红斑狼疮 （SLE） 诊断标准 （ACR 1997）和 2009 年系统性红斑狼疮国际合作组 （SLICC 2009）制定的 SLE 诊断标准对临床不典型病例的诊断分析。方法 采用回顾性分析方法总结 2011 年 5 月至 2014 年 6 月中国医科大学附属第一医院儿科诊治的 4 例儿童期 SLE不典型病例临床资料, 对比分析ACR 1997标准与SLICC 2009标准在SLE不典型患儿中的使用及诊断差异。结果 4例病例依照ACR 1997诊断标准均证据不足, 不能确诊; 而由于 SLICC 2009标准增加了狼疮皮肤损害类型和狼疮性肾炎的病理诊断依据, 细化了血液系统和免疫学指标的检查项目, 使得4例不典型病例最后得以确诊。结论 SLICC 2009 对SLE不典型病例确诊更佳。积极的免疫学检测和早期肾脏病理检查有助于确诊。     

肉眼血尿,心脏杂音,赘生物

患儿为学龄期女性,因发现肉眼血尿1d入院.入院后迅速完善检查,明确了系统性红斑狼疮诊断.治疗后病情好转,但病程中出现心脏杂音,行心脏彩超提示赘生物.为儿童罕见病例,经过会诊,诊断Libman-Sacks心内膜炎.总结:重视临床体检,注意病情的变化;重视多学科的合作.     

贝利尤单抗治疗以呕吐尿频为首发症状的儿童系统性红斑狼疮一例

系统性红斑狼疮(systemic lupus erythematosus,SLE)是一种以多系统受累为特征的自身免疫性疾病。多数患者以不明原因发热、皮疹或关节肿痛就诊,此外,血液系统、肾脏、神经系统也常受累,但消化道和膀胱的症状通常较轻。故以消化道症状为首发症状,伴有明显的尿频,而其他器官受累不明显的病例,容易被延误诊断及治疗。SLE标准治疗包括诱导期积极应用免疫抑制剂,即大剂量的糖皮质激素与环磷酰胺或霉酚酸酯伍用,但耐药患者的疗效差。贝利尤(belimumab)单抗是目前唯一获批用于治疗SLE生物制剂,国外已有报道该药应用于治疗常规治疗无效的狼疮性肾炎(LN)、皮肤狼疮等案例,但迄今尚无用于治疗以平滑肌受累为主要表现的SLE的报道。由于该药在国内刚刚上市,临床经验甚少。现报道1例以呕吐、尿频等平滑肌受累为主要表现的SLE患儿,其常规治疗效果不佳,使用贝利尤单抗治疗后症状明显改善,疾病活动度显著降低。     

儿童狼疮性肾炎诊治现状及面临的困难

系统性红斑狼疮是一种以多系统损害和血清中出现自身抗体为特征的自身免疫性疾病。狼疮性肾炎是系统性红斑狼疮临床中最常见和最重要的并发症,儿童狼疮性肾炎的发生率更高,预后与早期诊断、积极治疗相关。目前对于狼疮性肾炎的治疗方案主要为激素和免疫抑制剂,但部分患儿不能达到临床缓解或复发,新型的靶向生物制剂有望成为难治性狼疮性肾炎新的治疗方法。     

Systemic lupus erythematosus (SLE) presenting with nephrotic syndrome and membranous glomerulopathy in a 10-year-old girl

The authors report the case of a 10-y-old girl with clinical diagnosis of systemic lupus erythematosus (SLE), made at the age of 6 y, based upon arthritis, serositis, haematological disorder and positive antinuclear antibody. The first manifestation of disease--Raynaud's phenomenon--appeared at the age of 4 y. Seven months after the diagnosis, she developed nephrotic proteinuria with haematuria. Percutaneous renal biopsy showed membranous glomerulonephritis, the least common form of lupus nephritis. CONCLUSION: Intravenous cyclophosphamide therapy associated with oral prednisolone proved effective in inducing complete remission of nephrotic syndrome.     

The favourable effect of cyclophosphamide pulse therapy in the treatment of massive pulmonary haemorrhage in systemic lupus erythematosus

Pulmonary haemorrhage (PH) is a rare but very serious complication of systemic lupus erythematosus (SLE) and the treatment is still controversial. Some authors showed the effectiveness of methylprednisolone pulse therapy for PH, although its effect was often transient. A 12-year-old Japanese girl with lupus nephritis and recurrent massive PH in SLE was treated with methylprednisolone pulse therapy. The effect on PH was transient and she needed three cycles within a month and side-effects developed. Pulse therapy with cyclophosphamide, synchronized with plasmaphaeresis, was tried. Thereafter she did not experience PH for 7 months, whereas lupus nephritis did not improve. Pulse cyclophosphamide would be effective for life threatening massive PH in SLE patients.     

赖氨酸尿性蛋白耐受不良1家系(1例合并系统性红斑狼疮)报告并文献复习

目的总结赖氨酸尿性蛋白耐受不良(LPI)1家系2例患者临床特征及基因突变的特点,提高对该病的认识。方法收集PLI 1家系2例患儿(同胞姐弟)的临床资料,包括病史、肾脏病理、相关实验室检查和家族史等。采用外显子捕获法对患儿及其父母行全外显子测序(WES)并行生物信息学分析,行Sanger验证并在家系其他成员中进行突变分析。结果先证者,女,10岁,断乳后反复呕吐和腹泻,抵触富含蛋白的食物,生长落后,身高低于同年龄、同性别儿童;5岁后鼻自发性出血,外周血"三系"(RBC、WBC、PLT)低于正常值,9.7岁后出现轻度蛋白尿和持续性镜下血尿;免疫系统受累,检出ANA和ds-DNA等多种自身抗体。血清铁蛋白、乳酸脱氢酶和血氨增高,尿乳清酸增高,血清和尿液赖氨酸、精氨酸和瓜氨酸改变不明显。肾活检病理提示狼疮性肾炎。家系调查发现,先证者之弟,男,6.5岁,断乳后反复呕吐,抵触富含蛋白食物,生长落后,身高低于同年龄、同性别儿童,血清铁蛋白、乳酸脱氢酶增高,尿乳清酸增高,血清、尿液赖氨酸、精氨酸和瓜氨酸改变不明显。先证者及其父母WES测序显示SLC7A7基因IVS4+1GA纯合突变,突变来源其父母,先证者之弟也存在该突变。例1诊断为LPI合并SLE,例2诊断为LPI。结论 SLC7A7基因测序是确诊LPI的依据;LPI并发系统性红斑狼疮(SLE)非常罕见,SLC7A7是否为单基因型SLE致病基因需进一步研究。     

Acute pancreatitis in paediatric systemic lupus erythematosus

Acute pancreatitis (AP) rarely complicates the clinical course of systemic lupus erythematosus (SLE). AP as the initial manifestation of SLE is exceptional, but its outcome is often fatal. Corticosteroids have been suspected to play a role in the development of AP, but the therapeutic benefit seems to be far above the risk of exacerbation of pancreatic lesions. We report a 13-y-old girl presenting with arthralgia and malaise, followed by abdominal pain, generalized oedema and haemodynamic instability. Increased CRP (325 ng/ml), serum amylase (14,000 IU/l) and lipase (2500 IU/l) levels suggested AP. Acute anuric renal failure required haemodialysis. Multiorgan involvement suggested SLE, which was confirmed 3 d later by increased anti-ds-DNA levels. Three methylprednisolone pulses were administered promptly, followed by oral prednisone (1.5 mg/kg/d) and six pulses of cyclophosphamide (500 mg/1.73 m2/2 wk). Mycophenolate mofetil was introduced for long-term disease control. Amylase and lipase levels decreased over 4 wk. Renal function was normal after 3 wk and proteinuria negative after 6 wk.This case suggests that steroid pulse therapy should be promptly administered if clinical and biochemical investigations suggest SLE to be responsible for AP. Aggressive treatment may be life saving.     

Recurrent pancreatitis after renal transplantation in a child

Abstract:  A five-yr-old girl, who was a renal transplant recipient, presented with nausea, vomiting, epigastric discomfort, papules, and vesicles on her body. She was diagnosed with acute pancreatitis and varicella zoster infection because her serum amylase and lipase levels were positive. Fourteen months later, she was readmitted with nausea, vomiting, and epigastric pain similar to the previous symptoms and was diagnosed with acute pancreatitis. This case report indicates that acute pancreatitis can be one of a number of complications following pediatric renal transplantation and can recur because of various causes.     

Systemic lupus erythematosus: A case report with unusual manifestations and favourable outcome after plasmapheresis

We report a case of systemic lupus erythematosus (SLE) in a 15-year-old girl with severe neurological disease, platelet function disorder and pulmonary haemorrhage, which remitted after plasmapheresis. The patient developed protein-losing enteropathy shrinking lung, and acute pancreatitis with pseudocyst formation. These infrequent complication of SLE are discussed.     

Modern therapeutic strategies for paediatric systemic lupus erythematosus and lupus nephritis

There is still a significant morbidity and mortality associated with childhood‐onset systemic lupus erythematosus (SLE), despite an increasing armamentarium of immunosuppressive agents. The ideal therapeutic strategy for children and adolescents with SLE should provide the right amount of treatment to allow normal growth, development and fertility while reducing the disease activity and damage that can be accrued over the years. Each patient should have individualized treatments tailored to their organ involvement, disease severity and history of flares together with recent clinical, haematological and immunological parameters to avoid further flares of disease activity and side‐effects of treatment, especially severe infections and future malignancies. The most commonly cited side‐effects of medications include Cushingoid features of corticosteroids, infective complications of cyclophosphamide and gastrointestinal side‐effects of mycophenolate mofetil. There is increasing evidence to support the use of oral mycophenolate mofetil as opposed to cyclophosphamide for both induction and maintenance therapies in many children with SLE with or without lupus nephritis (LN). Recently, case series utilizing B‐lymphocyte depletion therapies with rituximab look promising for patients with severe or refractory disease activity. In this article, we explore current evidence to effectively treat children and adolescents with SLE with or without LN. Conclusion: Modern therapeutic strategies include reduced doses and use of corticosteroids and intravenous cyclophosphamide respectively, with increased use of azathioprine, MMF and rituximab.     

Current topics in childhood lupus nephritis

Lupus nephritis is a major predictor of the prognosis of systemic lupus erythematosus (SLE). The present paper discusses lupus nephritis from clinical and immunopathological points of view. Although recent advances in diagnosis and treatment improve the prognosis of children with SLE, there remain many unsolved clinical problems. One of the current topics in the treatment for SLE is intermittent intravenous cyclophosphamide therapy which is effective even for the steroid-resistant patients with severe lupus nephritis, at least for short-term observation. Immunopathologically, the following issues are discussed: (i) The C5b-9 terminal complement complex plays an important role in the pathogenesis of lupus nephritis. The possible interaction of vitronectin and SP-40,40 is also mentioned; (ii) A semi-quantitative analysis of the charge barrier of the glomerular basement membrane reveals that the charge barrier dysfunction plays an important role in the pathogenesis of proteinuria in lupus nephritis. This study also demonstrates that the charge of immune deposits is important for the initiation of glomerular injury in lupus nephritis; (iii) It is demonstrated that the histopathological diversity of lupus nephritis is based on biological properties of nephritogenic autoantibodies in murine lupus models.     

狼疮抗凝集物检测在系统性红斑狼疮、原发性血小板减少症中的临床应用

目的通过对系统性红斑性狼疮(SLE)310例和原发性血小板减少症(ITP)249例狼疮抗凝集物(LAC)和抗心磷脂抗体亚型(aCL-IgG、IgM、IgA)的测定,研究其与SLE临床表现的关系及LAC在ITP转归中的意义。方法采用脑磷脂-白陶土法(KCCT)及校正试验检测患儿血浆LAC;采用酶联免疫吸附试验(ELISA)测定息儿血清aCL-IgG,IgM、IgA。结果SLE 组中,66.1%显示体内存在高含量LAC,其中45.9%并狼疮肾炎;46.8?L抗体升高,其中90.2%为IgG和(或)IgM,分别有46.9%和11.7%是狼疮并中枢神经系统及血液系统病变。ITP组105例LAC阳性患儿中36.2%经抗核抗体(ANA)检测确诊为SLE,7.6%在2个月-2.4年后发展为SLE。结论LAC和aCL抗体亚型的水平与SLE临床表现密切相关,LAC在狼疮并肾脏病变中为优势病理性自身抗体;aCL抗体亚型的水平则与狼疮性血栓性血管炎性病变有相关关系。对单纯患有ITP的患儿应进行LAC动态观察,可及早确定疾病的转归。