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.

过敏性紫癜血清中某些细胞因子和IgA1含量变化的临床意义

目的观察普通过敏性紫癜(GHSP)及紫殿性肾炎(HSPN)患儿血清白细胞介素21(IL-21)、转化生长因子β(TGF-β)、肿瘤坏死因子α(TNF-α)和免疫球蛋白A1(IgA1)含量,进一步探讨过敏性紫癜(HSP)及HSPN的发病机制,为临床诊断和治疗HSP提供新思路。方法抽取2014年1月~2016年1月在河北北方学院附属第一医院儿科住院治疗的65例HSP(38例GHSP,27例HSPN)患儿和30例健康儿童(对照组)外周血,离心后分离血清,采用双抗夹心酶联免疫吸附法(ELISA)检测血清IL-21、TGF-β、TNF-α、IgA1含量,对结果进行统计学分析。结果 HSP患儿IL-21、TGF-β、TNF-α、IgA1水平均高于对照组(P<0.05),且HSPN患儿TGF-β、TNF-α、IgA1水平均明显高于GHSP患儿(P<0.05),而IL-21水平在两组患儿之间差异无统计学意义(P>0.05)。HSPN患儿血清TGF-β与IgA1呈正相关(r=0.346,P<0.05),TNF-α与IgA1呈正相关(r=0.582,P<0.05)。结论 IL-21、TGF-β、TNF-α和IgA1参与GHSP及HSPN的发病及病情进展,血清IgA1含量可作为判断HSPN患儿预后的重要指标之一。

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.

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.