Risk factors for intussusception in children with Henoch-Schönlein purpura:A case-control study

BACKGROUND The etiology of Henoch-Schönlein purpura(HSP)with intussusception remains undefined.AIM To investigate the risk factors for intussusception in children with HSP and gastrointestinal(GI)involvement.METHODS Sixty children with HSP and concomitant intussusception admitted to the Beijing Children’s Hospital of Capital Medical University between January 2006 and December 2018 were enrolled in this study.One hundred pediatric patients with HSP and GI involvement but without intussusception,admitted to the same hospital during the same period,were randomly selected as a control group.The baseline clinical characteristics of all patients,including sex,age of onset,duration of disease,clinical manifestations,laboratory test results,and treatments provided,were assessed.Univariate and multiple logistic regression analyses were performed to identify possible risk factors.RESULTS The 60 children in the intussusception group comprised 27 girls(45%)and 33 boys(55%)and the 100 children in the non-intussusception group comprised 62 girls(62%)and 38 boys(38%).The median age of all patients were 6 years and 5 mo.Univariate and multiple regression analyses revealed age at onset,not receiving glucocorticoid therapy within 72 h of emergence of GI symptoms,hematochezia,and D-dimer levels as independent risk factors for intussusception in children with HSP(P<0.05).CONCLUSION The four independent risk factors for intussusception in pediatric HSP with GI involvement would be a reference for early prevention and treatment of this potentially fatal disease.

Severe Henoch-Schonlein purpura with infliximab forulcerative colitis

Infliximab （IFX） is an anti-tumor necrosis factorchimeric antibody that is effective for treatment ofautoimmune disorders such as Crohn＇s disease andulcerative colitis （UC）. IFX is well tolerated with alow incidence of adverse effects such as infections,skin reactions, autoimmunity, and malignancy.Dermatological manifestations can appear as infusionreaction, vasculitis, cutaneous infections, psoriasis,eczema, and skin cancer. Here, we present anunusual case of extensive and sporadic subcutaneousecchymosis in a 69-year-old woman with severe UC,partial colectomy and cecostomy, following her initialdose of IFX. The reaction occurred during infliximabinfusion, and withdrawal of IFX led to gradual alleviationof her symptoms. We concluded that Henoch-Sch？nleinpurpura, a kind of leukocytoclastic vasculitis, mighthave contributed to the development of the bruising.Although the precise mechanisms of the vasculitis arestill controversial, such a case highlights the importanceof subcutaneous adverse effects in the management ofUC with IFX.

Henoch-Schnlein purpura complicating adalimumab therapy for Crohn's disease

Anti-tumour necrosis factor-α(TNF) therapy has revolutionised the management of chronic inflammatory conditions.With ever increasing numbers of patients being treated with these agents,uncommon adverse reactions will inevitably occur more frequently.Cutaneous manifestations are associated with many of these chronic conditions and can complicate anti-TNF therapy in about 20% of cases.Vasculitic complications are rarely associated with anti-TNF therapy.Henoch-Schnlein purpura(HSP),a small vessel vasculitis,has been described following infliximab and etanercept therapy but never with adalimumab,a fully humanized TNF antibody.The risk of such immune-mediated reactions is theoretically less with adalimumab compared to infliximab but can still occur.Here we report the f irst case in the literature of HSP that can be attributed to the use of adalimumab in a 19-year-old male with recalcitrant Crohn's disease.

Effect of intestinal flora from children with Henoch-Sch?nlein purpura on visceral sensitivity, gastrointestinal hormones and cytokines secretion in pseudo-sterile rats

Objective:To investigate the effect of intestinal flora from Henoch-Schönlein purpura(HSP)on visceral sensitivity,gastrointestinal hormones and cytokines in pseudo-sterile rats.Methods:The pseudo-sterile rat model was established.The rats were was given fecal microbiota solutions of children with abdominal HSP and healthy children,respectively.The visceral sensitivity was determined by abdominal withdrawal reflex(AWR)which was induced by rectal balloon distention in all the rats.And serum gastrin(Gas),motilin(MTL),cholecystokinin(CCK),substance P(SP),tumor necrosis factor(TNF)-αand interleukin(IL)-6 levels in rats were measured with ELISA method.Results:The volume of rectum water injection under the score 3 of AWR in the rats administrated with fecal microbiota solution from HSP children(HSP group)was significantly decreased compared with that in the rats administrated with fecal microbiota solution from healthy children(HC group),and there was significant difference between these two groups(P<0.05).The serum Gas,MTL,CCK and SP levels were higher in HSP group than those in HC group.And serum MTL,CCK and SP levels in HSP group were significantly different from those in the HC group.The serum TNF-αandIL-6 levels were higher in HSP group than those in HC group,there was significant difference between these two groups(P<0.05).Conclusion:Intestinal flora from HSP can induce the production of visceral sensitivity,inhibit gastrointestinal hormone secretion and prompt cytokine production.

Effect of Activation of the Ca2+-Permeable Acid-Sensing Ion Channel 1a on Acid-Induced Vascular Endothelial Cell Injury of Henoch-Schönlein Purpura Children

Acidosis in local environment plays a critical role in cell injury. One key mediator of acidosis-induced cell injury is the acid-sensing ion channels (ASICs), particularly ASIC1a. Herein, we investigated the role of ASIC1a in acid-induced vascular endothelial cell injury of Henoch-Schonlein purpura (HSP) children. Acid-induced ASIC1a, Calpain and Calcineurin expression in vascular endothelial cells pretreated with IgA1 isolated from HSP were detected by real time quantitative polymerase chain reaction and western blot methods, respectively. Cell cytotoxicity was measured by interleukin-8 and nitric oxide production with ELISA. The results showed acid-induced ASIC1a, Calpain and Calcineurin expression in cells increased, especially at PH6.5. The cytotoxicity of vascular endothelial cells was increased by extracellular acidosis. Moreover non-specific or specific blockers of ASIC1a, Amiloride and PcTX-1 could remarkably decrease these parameters. These findings show that increased [Ca2+]i, mediated via ASIC1a, might contribute to acid-induced vascular endothelial cell injury of HSP.

Henoch-Schönlein purpura nephritis in children:incidence,pathogenesis and management

Background:Henoch-Schönlein purpura(HSP)is one of the most common vasculitides in children.It is manifested by skin purpura,arthritis,abdominal pain,renal involvement,etc.Typically,HSP is considered to be self-limiting,although renal involvement(HSP purpura nephritis,HSPN)is the principal cause of morbidity from this disease.For this reason,it is important to clarify the mechanism of onset and clinical manifestations of HSPN and to ascertain the most appropriate treatment for HSPN.In this article,we review the updated pathophysiology and treatment strategies for HSPN.Data sources:We searched databases including PubMed,Elsevier and Wanfang for the folowing key words:Henoch-Schönlein purpura,nephritis,mechanism and treatment,and we selected those publications written in English that we judged to be relevant to the topic of this review.Results:Based on the data present in the literature,we reviewed the following topics:1)the possible pathogenesis of HSPN:several studies suggest that immunoglobulin A immune complexes deposit in the mesangium and induce renal injury;2)multiple-drug treatment for HSPN:although there have been few evidence-based treatment strategies for HSPN,several studies have suggested that immunosuppressive drugs and multiple drug combination therapy were effective in ameliorating proteinuria and histological severity.Conclusions:HSPN is a severe disease of childhood.To better understand this disease,detailed investigations into the pathogenesis of HSPN and prospective randomized controlled treatment studies on children with severe HSPN are needed.

Clinicopathological features and prognosis of membranoproliferative-like Henoch-Schönlein purpura nephritis in children

Background: The aim of this retrospective study was to defi ne the clinical manifestations, pathological features and prognosis of children with membranoproliferative-like Henoch-Schönlein purpura nephritis (HSPN), representing International Study of Kidney Disease in Children (ISKDC) grade VI. Methods: Among 245 patients with HSPN treated in our hospital between 2008 and 2010, nine patients (3.7%) were diagnosed with HSPN of ISKDC grade VI (males=5, females=4, age: 9.5±2.03 years, mean±SD). The clinical features, laboratory and pathologicalfi ndings, treatment and outcome of the 9 patients were retrospectively analyzed. Results: Of the 9 patients, 7 (78%) presented with hematuria and nephrotic syndrome, and were treated with steroids (oral prednisone or intravenous methylprednisolone pulse therapy) and immunosuppressants (oral tripterygium glycosides or intravenous cyclophosphamide pulse therapy). One (11%) patient had hematuria and nephrotic range proteinuria (>50 mg/kg per 24 hours) and was treated with oral prednisone and tripterygium glycosides. Another (11%) patient presented with hematuria and moderate proteinuria (25-50 mg/kg per 24 hours) and was treated with oral tripterygium glycoside only. Histopathological examination showed diffuse glomerular mesangial and endocapillary proliferation, mesangial interposition, double-contour formation, podocyte hypertrophy, shedding, and cytoplasmic absorption droplets. The percentages of glomeruli with small cellular crescents varied from 4%-25% in 6 of 9 patients. Follow-up for 2 to 4 years showed excellent recovery in all patients. Conclusions: The main clinical feature of ISKDC grade VI HSPN in children is a nephrotic syndrome with hematuria. The excellent prognosis of the disease was probably related to early diagnosis and treatment with steroids and/or immunosuppressants, and mild degree of glomerulosclerosis and tubulointerstitial damage.

Heat shock protein 70-2 and tumor necrosis factor-α gene polymorphisms in Chinese children with Henoch- Schönlein purpura

Background:Henoch-Schönlein purpura(HSP)or IgAassociated vasculitis is related to immune disturbances.Polymorphisms of the heat shock protein 70-2 gene(HSP70-2)and the tumor necrosis factor-αgene(TNF-α)are known to be associated with immune diseases.The purpose of this study was to investigate the likely association of HSP70-2(+1267A/G)and TNF-α(+308A/G)gene polymorphisms with HSP in children.Methods:The polymerase chain reaction restriction fragment length polymorphism method was used to detect the HSP70-2 and TNF-αpolymorphisms in 205 cases of children with HSP and 53 controls;and the association of these polymorphisms with HSP and HSP nephritis(HSPN)was analyzed.Results:The G/G genotypic frequencies at the+1267A/G position of HSP70-2 in the HSP group(22.9%)were signifi cantly higher than those in the healthy control group(9.4%)(χ^(2)=4.764,P<0.05).The frequencies of the A/A,A/G and G/G genotypes of HSP70-2 in patients in the nephritis-free group and the HSPN group showed no statistically significant difference.The A/A genotype frequency at the+308G/A position of TNF-αin the HSP group was 8.3%,which was higher than that in the control group(χ^(2)=6.447,P<0.05).The A allele frequency of TNF-αin the HSP group was higher than that in the control group,with a statistically significant difference(χ^(2)=7.241,P<0.05).Conclusions:The HSP70-2(+1267A/G)and TNF-α(+308G/A)gene polymorphisms were associated with HSP in children.The G/G homozygosity of HSP70-2 and the A/A homozygosity of TNF-αmay be genetic predisposing factors for HSP.

过敏性紫癜患儿肾损害的早期实验室检查及干预(附45例分析)

目的 探讨过敏性紫癜 (HSP)患儿肾损害早期诊断的实验室指标及早期干预的临床疗效。方法 对 50例多次尿常规检查正常的 HSP患儿通过检测尿微量蛋白 (Ig G,MA,TRF,α1 - m G,β2 - m G)及尿酶 (NAG,γ- GT)的含量。采用对比研究方法 ,将 45例异常的 HSP患儿随机分成两组。两组均在甲氰咪胍 ,维生素 C,克敏能 ,钙剂等综合治疗的基础上。A组 (干预组 ) 2 2例加用肝素钠皮下注射 ,甘利欣口服治疗。B组 (对照组 ) 2 3例 ,未加任何处理。结果 多次尿常规正常的 HSP患儿肾损害占 90 %。干预组治疗后 2个月、 4个月尿微量蛋白 ,尿酶各指标均较治疗前降低 ,差异有显著性 (P<0 .0 5或 P<0 .0 1 )。对照组治疗 4个月尿 Ig G,MA,β2 - m G,NAG,γ- GT等较治疗前降低 ,差异有显著性 (P<0 .0 1 )。但干预组治疗 2个月 ,4个月尿微量蛋白 ,尿酶各指标均较对照组低 ,差异有显著性 (P<0 .0 5或 P<0 .0 1 )。尿 Ig G、MA、TRF、NAG恢复较快 ,干预组治疗 4个月时已基本接近正常。而尿 α1 - m G、β2 - m G、γ- GT恢复较慢 ,干预组治疗 4个月时 ,仍有轻重不一的异常。两组治疗 4个月时 ,出现尿常规异常者 ,对照组较干预组高 ,差异有显著性 (P<0 .0 5)。结论 尿微量蛋白 ,尿酶是早期诊断 HSP肾损害的良好指标。

Three-Month-Induction Therapy with Prednisone and Mycophenolate Followed by Maintenance Therapy with Mycophenolate Alone for 2 Years: An Effective and Safe Autoimmune Treatment for Triggering Factors Adults with Acute Non-Crescentic Nephritis Associated with Henoch-Schönlein Purpura

Background: Henoch-Schönlein purpura (HSP) is an acute systemic disorder characterized by IgA associated vasculitis. The available data indicate an inherited predisposition to disease with triggering autoimmune phenomena. Hence, we evaluated prospectively the role of a new autoimmune regimen in treatment of its severe nephrotic/nephritic flares associated with non-crescentic nephritis in adult patients. Patients and methods: The regimen consisted of an initial induction phase of 3-month Prednisone and Mycophenolate followed by a maintenance phase of Mycophenolate alone for 2 years. Results: They were satisfactory with complete remission in 5 of 7 patients and partial in 2. Creatinine clearance was normalized in patients with complete remission and remained stable in the partially-responsive ones. Conclusion: Our study has shown the short- and long-term safety and efficacy of such autoimmune regimen directed towards the autoimmune triggering factors in severe forms of non-crescentic HSP.

Acute hemorrhagic edema of infancy: the experience of a large tertiary pediatric center in Israel

Background:Acute hemorrhagic edema of infancy (AHEI) is a rare leukocytoclastic vasculitis of the small vessels occurring at a young age and considered as a benign self-limited disease.Due to its low prevalence,there are limited data on the presentation and complications of this disease.Methods:All computerized files of children who were hospitalized at a tertiary pediatric center due to AHEI over a 10 year period were reviewed.Clinical,laboratory and histopathological data were collected.Results:Twenty-six patients were included in our study,accounting for 0.7 cases per 1000 admissions of children aged 2 years or less.Mean age was 12.9 months.More than two thirds of the children had preceding symptoms compatible with a viral infection.Upon admission,all patients presented with typical findings of a rash and edema.Edema was most profound over the lower extremities (73%).Concomitant viral or bacterial infections were found in six children.Skin biopsy was performed in six patients revealing leukocytoclastic vasculitis.Thirteen children (50%) had systemic involvement including joint involvement (n=9),gastrointestinal hemorrhage (n=4),microscopic hematuria (n=1) and compartment syndrome of the limb (n=1).The latter was diagnosed in a patient with familial Mediterranean fever.Conclusions:Our largest data series highlighted what is known regarding clinical and histological findings in children with AHEI.However,contrary to what was previously reported,we found a higher rate of systemic involvement.Although AHEI is a rare entity,pediatricians should be familiar with its presentation,management and our reported complications.

过敏性紫癜患者外周血Th17/Treg细胞平衡性检测

目的 探讨Th17细胞/Treg细胞（CD4＋CD25＋Foxp3＋T细胞）失衡在过敏性紫癜（HSP）发病机制中的作用.方法 采用流式细胞仪检测59例HSP患儿外周血Th17细胞和Treg细胞的比例、实时定量RT-PCR检测Th17细胞与Treg细胞转录因子RORγt、Foxp3 mRNA的表达.同时以38例性别、年龄匹配的健康儿童做对照.结果 HSP组外周血Th17细胞比例（CD4＋IL-17＋/CD4＋T细胞,1.87%±0.56%）及RORγt mRNA表达量（7.71±1.95）,均显著高于正常人对照组（CD4＋IL-17＋/CD4＋T细胞：0.39%±0.15%,P＜0.01;RORγt mRNA：1.49±0.57,P＜0.01）;HSP组外周血Treg细胞比例（CD4＋CD25＋Foxp3＋/CD4＋T细胞,1.63%±0.44%）及Foxp3 mRNA的表达量（0.34±0.11）,均明显低于正常人对照组（CD4＋CD25＋Foxp3＋/CD4＋T细胞：5.04%±1.44%,P＜0.01;Foxp3 mRNA：1.71±0.69,P＜0.01）.HSP各组间Th17细胞、Treg细胞比例及RORγt、Foxp3 mRNA的表达量差异无统计学意义（P＞0.05）.结论 过敏性紫癜患者外周血Th17、Treg细胞水平及其转录因子表达量发生变化,其比例的失平衡可能参与过敏性紫癜的发病.

链球菌感染与过敏性紫癜及紫癜性肾炎的相关性研究进展

人体链球菌感染中以A族链球菌（group A streptococcus ，GAS）感染最为常见，诸多研究发现GAS感染是导致过敏性紫癜（Henoch-Sch？nlein purpura，HSP）发病的重要因素之一，并可以促进和加重紫癜性肾炎（Henoch-Sch？nlein purpura nephritis，HSPN）的发生和发展。GAS可通过溶血素、蛋白酶及超抗原等参与致病。该文对GAS感染与HSP及HSPN之间相关性研究进展进行综述。

β-1,3半乳糖基转移酶基因多态性与儿童过敏性紫癜的相关性研究进展

过敏性紫癜是儿童时期最常见的小血管炎.基因多态性与过敏性紫癜关系的研究对于从基因水平上揭示过敏性紫癜的发病机制和病人临床表现多样性的物质基础具有重要意义.有研究在认为,β-1,3半乳糖基转移酶（C1 GALT1）基因多态性与过敏性紫癜存在关联.目前C1 GALT1基因多态性与过敏性紫癜相关性的研究报道较少,因此就C1 GALT1基因多态性在过敏性紫癜的研究进展及对其他疾病的影响进行系统回顾和总结很有必要.

过敏性紫癜患儿心肌酶谱改变及其临床意义

目的 研究过敏性紫癜（HSP）患儿心肌酶谱变化,了解HSP对心肌的损害及其临床意义,指导临床营养心肌药物的应用.方法 选择158例HSP患儿与50例健康儿童（对照组）.将HSP患儿根据入院时临床受累部位分为单纯组（仅皮肤受累,63例）和混合组（皮肤受累伴有关节、胃肠道、肾脏及其他症状,95例）.采集空腹静脉血,采用日立7600-020全自动生化分析仪检测血清心肌肌钙蛋白Ⅰ （cTnⅠ）、α-羟基丁酸脱氢酶（HBDH）、天冬氨酸氨基转移酶（AST）、乳酸脱氢酶（LDH）、肌酸激酶同工酶MB（CK-MB）、肌酸激酶（CK）.HSP患儿cTnⅠ、心肌酶异常者行心电图检查.结果 单纯组和混合组cTnⅠ、CK-MB、α-HBDH、AST、LDH水平均显著高于对照组[（1.41±0.61）、（1.86±0.92） μgL比（0.66±0.39） μg/L,（19.60±11.28）、（28.12±6.00） U/L比（14.64±4.41） U/L,（258.00±52.73）、（327.90±65.60） U/L比（158.40±45.11） U/L,（35.7±7.2）、（39.6±12.0） U/L比（27.2±7.3） U/L,（300.5±80.0）、（320.5±65.0） U/L比（260.0±30.0） U/L],差异有统计学意义（P＜0.05）;且混合组cTnⅠ、CK-MB、α-HBDH水平与单纯组比较差异亦有统计学意义（P＜0.05）.单纯组16例有1项或多项检测指标升高,混合组39例有1项或多项检测指标升高,混合组各项指标异常率均高于单纯组,且两组cTnⅠ、CK-MB、α-HBDH异常率比较差异有统计学意义[15.87％（10/63）比30.53％（29/95）、7.94％（5/63）比21.05％（20/95）、11.11％（7/63）比24.21％（23/95）]（P＜0.05）.cTnⅠ、心肌酶谱异常的HSP患儿心电图表现：心动过速15例,其中单纯组4例,混合组11例;心动过缓2例,均为混合组;窦性心律不齐10例,其中单纯组4例,混合组6例;无其他心律失常表现.结论 HSP可致患儿cTnⅠ、心肌酶谱异常改变,且混合型较单纯型致cTnⅠ、心肌酶谱异常改变更加明显.HSP患儿合并心肌损害时,心电图无特征性改变.