Henoch-Schönlein Purpura Nephritis Research Articles

Efficacy and safety of mycophenolate mofetil versus cyclophosphamide therapy for Henoch schonlein purpura nephritis in children: A meta-analysis.

The objective of this meta-analysis was to compare the efficacy and safety between glucocorticoids combined with mycophenolate mofetil (MMF) versus glucocorticoids combined with cyclophosphamide (CTX) for henoch schonlein purpura nephritis (HSPN) in children. Databases including PubMed, EMbase, the Cochrane Library, China National Knowledge Infrastructure, and Wanfang database were searched from the inception to April 5th, 2024. Eligible studies comparing glucocorticoids combined with MMF versus glucocorticoids combined with CTX for HSPN in children were included. Data were analyzed using Review Manager Version 5.3. Ten studies were included in the meta-analysis. Six randomized controlled trials (RCTs) and 4 non-randomized studies involving 675 patients were identified. Compared with CTX therapeutic schedule, MMF therapeutic schedule had a higher complete remission (CR) within the 6 months (OR 1.61, 95%CI 1.16-2.22, P = .004) and CR within the 12 months (OR 1.73, 95%CI 1.00-2.97, P = .05). However, there was no significant difference between MMF and CTX therapeutic schedule concerning total remission (TR) within the 6 months (OR 1.54, 95%CI 0.82-2.92, P = .18) and TR within the 12 months (OR 2.08, 95%CI 0.86-5.01, P = .10). In addition, incidences of gastrointestinal discomfort (OR 0.33, 95%CI 0.19-0.56, P < .0001), liver function injury (OR 0.28, 95%CI 0.09-0.87, P = .03), myelosuppression (OR 0.15, 95%CI 0.06-0.41, P = .0001), alopecia (OR 0.25, 95%CI 0.07-0.91, P = .03) in MMF therapeutic schedule were all lower than CTX therapeutic schedule. There was no statistically significant difference between the 2 therapeutic schedules concerning infection (OR 0.90, 95%CI 0.50-1.61, P = .72), rash (OR 0.38, 95%CI 0.07-2.04, P = .26). Glucocorticoids combined with MMF had a higher CR and lower incidence of adverse effects compared with glucocorticoids combined with CTX in the treatment of HSPN in children.

Changes in the spectrum of biopsy-proven renal diseases over 11 years: a single-center study in China

Background There have been some shifts in the frequency and distribution of biopsy-proven renal diseases in China over recent years. The aim of the study was to investigate the changing spectrum of renal diseases from the view of kidney biopsy data in a single center of China. Methods and results A total of 10,996 cases of native renal biopsies from patients aged ≥15 years old in Huashan Hospital, Fudan University, between 2008 and 2018 were analyzed retrospectively. The results showed that primary glomerular nephropathy (PGN) remained the most common biopsy-proven renal disease (69.42% of total), with IgA nephropathy (IgAN) accounting for 44.40% of PGN, membranous nephropathy (MN) for 28.55%, minimal change disease (MCD) for 13.26% and focal segmental glomerulosclerosis (FSGS) for 8.00%. During the study period, the proportion of MN in PGN appeared an increasing tendency, while that of IgAN and MCD remained stable and that of FSGS showed a decline. Secondary glomerular nephropathy (SGN) constituted 21.54% of total cases, among which the leading two diseases were lupus nephritis (LN) and Henoch-Schonlein purpura nephritis (HSN) which accounted for 41.08% and 19.11% respectively. Conclusions The 11-year retrospective study revealed that PGN was the predominant histologic diagnosis among patients undergoing renal biopsy and the most frequent type of PGN remained to be IgAN, followed by MN which increased dramatically.

Effectiveness and safety of tripterygium wilfordii poly-glycosides on glomerulonephritis: a systematic review and meta-analysis.

Treatment of glomerulonephritis presents several challenges, including limited therapeutic options, high costs, and potential adverse reactions. As a recognized Chinese patent medicine, Tripterygium wilfordii poly-glycosides (TWP) have shown promising benefits in managing autoimmune diseases. To evaluate clinical effectiveness and safety of TWP in treating glomerulonephritis, we systematically searched PubMed, Cochrane Library, Web of Science, and Embase databases for controlled studies published up to 12 July 2023. We employed weighted mean difference and relative risk to analyze continuous and dichotomous outcomes. This meta-analysis included 16 studies that included primary membranous nephropathy (PMN), type 2 diabetic kidney disease (DKD), and Henoch-Schönlein purpura nephritis (HSPN). Analysis revealed that additional TWP administration improved patients' outcomes and total remission rates, reduced 24-h urine protein (24hUP) and decreased relapse events. The pooled results demonstrated the non-inferiority of TWP to glucocorticoids in achieving total remission, reducing 24hUP, and converting the phospholipase A2 receptor (PLA2R) status to negative. For DKD patients, TWP effectively reduced 24hUP levels, although it did not significantly improve the estimated glomerular filtration rate (eGFR). Compared to valsartan, TWP showed comparable improvements in 24hUP and eGFR levels. In severe cases of HSPN in children, significant clinical remission and a reduction in 24hUP levels were observed with the addition of TWP treatment. TWP did not significantly increase the incidence of adverse reactions. Therefore, TWP could offer therapeutic benefits to patients with PMN, DKD, and severe HSPN, with a minimal increase in the risk of side effects.

Exploring potential predictors of Henoch-Schönlein purpura nephritis: a pilot investigation on urinary metabolites.

Henoch-Schönlein purpura nephritis (HSPN) is the most severe manifestation of Henoch-Schönlein purpura (HSP). This study aimed to determine the role of urine metabolomics in predicting HSPN and explore the potential mechanisms of HSP. A liquid chromatography-tandem mass spectrometry-based untargeted metabolomics analysis was performed to investigate the urinary metabolic profiles of 90 participants, comprising 30 healthy children (group CON) and 60 patients with HSP, including 30 HSP patients without renal involvement (group H) and 30 HSPN patients (group HSPN). The differentially expressed metabolites (DEMs) were identified using orthogonal partial least squares discriminant analysis (OPLS-DA), and subsequent bioinformatics analysis was conducted to elucidate the perturbed metabolic pathways. A total of 43 DEMs between H and HSPN groups were analyzed by the Kyoto Encyclopedia of Gene and Genome (KEGG) database, and the result indicates that glycine, serine and threonine metabolism, and cysteine and methionine metabolism were significantly disturbed. A composite model incorporating propionylcarnitine and indophenol sulfate was developed to assess the risk of renal involvement in pediatric patients with HSP. Conclusion: This study reveals the metabolic alterations in healthy children, HSPN patients, and HSP patients without renal involvement. Furthermore, propionylcarnitine and indophenol sulfate may be potential predictive biomarkers of the occurrence of HSPN. What is Known: • HSP is the predominant type of vasculitis observed in children. The long-term prognosis of HSP is contingent upon the extent of renal impairment. In severe nephritis, a delay in appropriate treatment may lead to fibrosis progression and subsequent development of chronic kidney disease (CKD), even leading to renal failure. • The application of metabolomics in investigating diverse renal disorders has been documented. Urine is a robust and sensitive medium for metabolomics detection. What is New: • The metabolic profiles were identified in urine samples of healthy children and those with HSP at the early stage of the disease. Different metabolites were identified between HSP patients without nephritis and those who developed HSPN. • These different metabolites may affect oxidative stress in the progression of HSPN.

Molecular Targets and Mechanisms of Poria cocos-Licorice Drug Pair for the Treatment of Henoch–Schönlein Purpura Nephritis Based on Network Pharmacology

Background: The herbal Poria cocos-Liquorice drug pair (PLDP) possesses the ability to be a diuretic, stimulating the spleen and benefiting the kidney, which plays an important role in the treatment of Henoch–Schönlein purpura nephritis (HSPN). However, the mechanism of action is unknown. Objectives: Through the method of network pharmacology, this research sought to determine the mechanism of PLDP against HSPN. Materials and Methods: The screening of active ingredients in PLDP was conducted by Traditional Chinese Medicine Systems Pharmacology (TCMSP) databases, while their targets were obtained from the TCMSP and Swiss Target Prediction (STP) databases. The genes of HSPN were searched by OMIM, DisGeNET, and GeneCards databases. Then, the common targets of active ingredients in PLDP and HSPN were mapped by Venn analysis. To get the main targets, the researchers utilized the STRING database to construct the protein–protein interaction (PPI) network of the common targets. Then, the function of gene ontology (GO) and the enrichment of the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway of the main targets were examined on the Metascape database to identify the molecular mechanism of PLDP against HSPN. The most relevant signaling pathways with HSPN screened from the top 20 pathways were defined as the key pathways. Finally, the “active ingredient-main target-key pathway” network was built in order to identify the core targets and key active ingredients of PLDP against HSPN. Results: There were 101 active ingredients and 360 targets for PLDP. One hundred and fifty-seven genes for HSPN and 35 common targets between PLDP and HSPN were identified. Through the “active ingredient-main target-key pathway” network, quercetin, kaempferol, polyporenic acid C, dehydrotumulosic acid, poricoic acid A, and naringenin were identified as key active ingredients; TNF, NOS3, RELA, AKT1, ICAM1, and IFNG were identified as core targets; and the key pathways include TNF signaling pathways, HIF-1 signaling pathways, and IL-17 signaling pathways. Conclusion: The research initially investigated the pathways, active ingredients, and targets involved in PLDP against HSPN. The mechanism appears to be linked to its immunomodulatory and anti-inflammatory properties, thus establishing a scientific foundation for further investigation.

Demographic distribution analysis of different glomerular diseases in Southwest China from 2008 to 2022.

Environmental and lifestyle factors play an etiological role in the pathogenesis of different glomerular diseases. Thus, exploring the epidemic characteristics of renal disease in different nationalities and regions is important. Patients who underwent renal biopsy from October 2008 to October 2022 were included. The proportion and change tendency of glomerular diseases and the differences between the sexes and different ages and races were analyzed. There were 15,146 cases of glomerular diseases (98.5%), involving 7538 males (49.8%) and 7608 females (50.2%). The mean age was 37.0years (range 0-80years). The proportion of membranous nephropathy (MN) and diabetic nephropathy (DN) showed an increased trend. The most common primary glomerulonephritis (PGN) was IgA nephropathy (IgAN, 44.6%), followed by minimal-change disease (MCD, 24.3%) and MN (15.4%). Lupus nephritis (LN, 30%) accounted for the largest proportion of SGNs, followed by Henoch-Schonlein purpura nephritis (HSPN, 20.9%) and DN (19.8%). Compared with adults aged 18-60years old, MCD and HSPN were more common in children and MN and DN in elderly individuals, statistically significant differences. Additionally, the sex and age distribution of PGN and SGN between the Tibetan and Han populations differed significantly, whereby LN was higher in the Han population and HSPN in the Tibetan population. The distribution of glomerular diseases showed age, sex and race differences. This research will be beneficial for providing epidemiological evidence for clinical diagnosis, disease prevention and public health decision-making.

Therapeutic effect of mycophenolate mofetil or cyclophosphamide in children with Henoch-Schönlein purpura nephritis of different age groups

To investigate the difference in the therapeutic effect of mycophenolate mofetil (MMF) or cyclophosphamide (CTX) in children with Henoch-Schönlein purpura nephritis (HSPN) of different age groups. A retrospective analysis was conducted on the clinical data of 135 children with HSPN who were treated with MMF or CTX in the Department of Nephrology, Children's Hospital Affiliated to Capital Institute of Pediatrics, from October 2018 to October 2020. According to the immunosuppressant used, they were divided into two groups: MMF group and CTX group, and according to the age, each group was further divided into two subgroups: ≤12 years and >12 years, producing four groups, i.e, the ≤12 years MMF subgroup (n=30), the >12 years MMF subgroup (n=15), the ≤12 years CTX subgroup (n=71), and the >12 years CTX subgroup (n=19). All children were followed up for at least 12 months, and the above groups were compared in terms of clinical outcomes and the incidence rate of adverse reactions. There was no significant difference in the complete response rate between the MMF group and the CTX group after 3, 6, and 12 months of treatment (P>0.05). There were no significant difference in the complete response rate and the incidence rate of adverse reactions between the >12 years MMF subgroup and the ≤12 years MMF subgroup at 3, 6, and 12 months of treatment (P>0.05). The >12 years CTX subgroup had a significantly lower complete response rate than the ≤12 years CTX subgroup at 6 and 12 months of treatment (P<0.05). The >12 years CTX subgroup had a significantly higher incidence rate of adverse reactions than the >12 years MMF subgroup (P<0.05). The efficacy and adverse reactions of MMF are not associated with age, but the efficacy of CTX is affected by age, with a higher incidence rate of adverse reactions. CTX should be selected with caution for children with HSPN aged >12 years.

Diagnostic performance of renal cortical elasticity by supersonic shear wave imaging in pediatric glomerular disease

PurposeTo explore the diagnostic performance of renal cortical elasticity expressed by Young’s modulus (YM) using the supersonic shear wave imaging (SSI) technique in pediatric glomerular disease. Materials and methodsSeventy-one children with glomerular disease confirmed by renal biopsy and sixty healthy volunteers were enrolled in this study. Conventional and SSI ultrasound examinations were performed in all individuals for both kidneys. We measured renal length, renal width, renal thickness, parenchyma thickness, interlobar arterial resistive index (RI) and the YM of the middle and lower pole. ResultsRegardless of which pole and which side of the kidney, the YM in the disease group was significantly higher than that in the control group (P < 0.001). The YM of the middle pole in the left kidney demonstrated the largest AUC (0.936, P < 0.001), and the corresponding cut-off value was 15.48 kPa with a sensitivity of 87.3% and a specificity of 86.7%. There was no significant difference in the YM among different pathological types of pediatric glomerular disease in the disease group, and the same in different grades of patients with Immunoglobulin A (IgA) nephropathy by Lee classification and the Oxford Classification as well as Henoch-Schonlein purpura nephritis (HSPN) by International Study of Kidney Disease in Children (ISKDC) classification (P > 0.05). We found positive but weak correlations between the YM and renal length (r = 0.299, P = 0.001), renal width (r = 0.408, P < 0.001), renal thickness (r = 0.299, P = 0.001), and parenchyma thickness (r = 0.212, P = 0.015), whereas the YM had no significant correlations with age, sex, BMI, interlobar arterial RI, and laboratory findings (P > 0.05). ConclusionsSSI technology is a non-invasive and feasible method for the diagnosis of pediatric glomerular disease. However, SSI did not show good performance in distinguishing different pathological types and disease grades in our study.

Association of Interleukin-2 Gene Polymorphism with Henoch-schönlein Purpura Nephritis.

Henoch-Schönlein purpura nephritis (HSPN) is a common vasculitis that mostly affects children, and previous studies have indicated that genetic factors may influence disease susceptibility. The aim of this study was to evaluate a possible association of three interleukin-2(IL-2) gene polymorphisms (rs3136534, rs2069776, and rs2069762) with HSPN in the Chinese population. A total of 81 patients with HSPN and 200 healthy children were enrolled. The distribution of genotypes, allelic frequencies, and haplotype frequencies among the three IL-2 polymorphisms were analyzed using the Sequenom MassARRAY system by means of matrix-assisted laser desorption ionization-time of flight mass spectrometry method. Compared to the healthy controls, genotyping analysis demonstrated rs3136534 was associated with a decreased HSPN risk in the dominant inheritance model (G/T+T/T vs. G/G; OR, 0.54; 95% CI, 0.31-0.93). However, the frequency of the T allele and haplotypes of rs3136534 showed no statistical significance. For the frequency of genotype, allele, and haplotype of the rs2069776 and rs20697622 polymorphisms, no significant differences were observed between HSPN patients and controls. Our results suggest that the rs3136534 polymorphism of the IL-2 gene is associated with susceptibility to HSPN in Chinese children.

Value of the modified semiquantitative classification in predicting outcomes in children with Henoch–Schönlein purpura nephritis

AbstractBackgroundThe modified semiquantitative classification (SQC) is a new pathological classification for Henoch–Schönlein purpura nephritis (HSPN), and its prognostic value with regard to the outcomes of HSPN is unclear.MethodsWe performed a retrospective review of 249 patients with biopsy‐proven HSPN admitted to the Children's Hospital of Chongqing Medical University. In addition to the International Study of Kidney Disease in Children (ISKDC) classification, renal biopsy specimens were also reevaluated according to the SQC.ResultsDuring the follow‐up period of 2.9 (1.0–6.9) years, 14 (5.6%) patients reached the poor outcome at the end of follow‐up. The SQC activity and chronicity indexes were positively correlated with the clinical manifestations, conventional pathology grades, and 24‐h urinary protein (24hUP). The difference in the areas under the curve between the total biopsy SQC scores and ISKDC classification was 0.12 (p = .001, 95% CI: 0.0485–0.192). In the receiver operating characteristic (ROC) curve analysis of 1‐year, 3‐year, and 5‐year poor outcomes and total biopsy SQC scores, a total biopsy score ≥10 was associated with a higher risk of an adverse outcome.ConclusionOur study suggests that the SQC indexes are clearly correlated with the clinical and pathological findings of HSPN. The SQC is more sensitive than ISKDC classification for the prediction of the long‐term outcomes of HSPN in children.

#2777 RISK FACTORS ASSOCIATED WITH OUTCOMES IN PATIENTS WITH HENOCH - SCHӧNLEIN PURPURA NEPHRITIS

Abstract Background and Aims Henoch - Schӧnlein purpura (HSP) is an immuno-mediated small-vessel vasculitis that manifests as non—thrombocytopenic purpura, arthritis or arthralgia, abdominal pain and/or kidney involvement. HSP nephritis can presented is micro- or macroscopic hematuria, proteinuria, nephrotic or nephritic syndrome, as well as acute renal failure. The aim of the study is to identify risk factors associated with unfavorable outcomes in patients with HSP nephritis. Method This retrospective study enrolled 68 patients with HSP nephritis. Renal and extra-renal symptoms were analyzed. A diagnosis of HSP nephritis was made when hematuria and/or proteinuria, and/or renal failure was associated with a palpable purpuric eruption or abdominal or joint pains (at least two of these three clinical signs) and predominant mesangial IgA immune deposits, confirmed by renal biopsy. The patients were subdivided into five classes according to the renal manifestation at onset of disease: 1) micro- or macroscopic hematuria; 2) mild proteinuria (&amp;lt;1 g/L) ± hematuria; 3) acute nephritic syndrome, defined as moderate proteinuria, hematuria, increased serum creatinine and/or hypertension; 4) nephrotic syndrome; 5) mixed nephritic-nephrotic syndrome. Results Of 68 patients with HSP nephritis, diagnosed by kidney biopsy, 41 (60,29%) were male and 27 (39,71%) - female. Age of onset was between 18 and 66 years (mean 37,28 ± 9,34). Duration of follow-up was between 2 and 28 years. 29 patients had histories of infection preceding presentation. At onset all patients had palpable purpura and urinary abnormalities (only hematuria - in 16,18%; mild proteinuria ± hematuria – in 44,12%; moderate or severe proteinuria and hematuria – in 39,70%). Arthralgias were present in 49 patients (72,06%), gastrointestinal involvement – in 32 patients (47,05%). Renal function was impaired in 26,47% of patients, and 51,47% were hypertensive. Mesangial hypercellularity lesions were found in most patients (97,06%), endocapillary proliferation – in 20,58%, segmental sclerosis – in 32,35%, tubular atrophy/interstitial fibrosis – in 38,23%. Corticosteroids and cyclophosphamide were prescribed in patients who presented with severe clinical and histological features and/or rapidly progressing renal disease. During follow-up classical extra-renal organ diseases were seen in 55,88% of patients, and hematuria and/or proteinuria – in 77,94%. At final review 26,47% had progression of renal failure. Risk factors for renal failure were moderate or severe proteinuria during follow-up (p&amp;lt;0,001), renal impairment at presentation (p&amp;lt;0,001), hypertension at presentation and during follow up (p&amp;lt;0,05), crescents, interstitial fibrosis and tubular atrophy (p&amp;lt;0,001). No significant difference in renal outcome was observed between patients who had relapses in extra-renal organs versus in those who did not. Conclusion Our results indicated that lower GFR, nephrotic syndrome, nephritic-nephrotic syndrome and crescentic nephritis were risk factors for unfavorable outcomes.

Steroid- and immunosuppressant-based protocol of Henoch-Schönlein purpura nephritis without angiotensin inhibitors in the acute phase.

The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines suggest initially using angiotensin-converting-enzyme inhibitors (ACE-Is) and/or angiotensin receptor blockers (ARBs) to treat Henoch-Schönlein purpura nephritis (HSPN). However, these guidelines might overlook the potential benefits of aggressive therapy. Therefore, we evaluated the efficacy of an HSPN protocol that primarily uses steroids and immunosuppressants, without ACE-Is or ARBs. We determine treatment intensity based on International Study of Kidney Diseases in Children (ISKDC) grading. Fifty-one patients were treated with our protocol that primarily uses steroids and immunosuppressants. ACE-Is and ARBs were not used in the acute phase, including before renal biopsy. We evaluated the proteinuria disappearance rate, duration to proteinuria disappearance, and estimated glomerular filtration rate (eGFR) at the time of last observation and compared them to those in previous reports. Proteinuria disappeared in 49 patients (96%) within a median of 5 months. The median eGFR was 116.0 mL/min/1.73 m2 at the time of last observation. Six of 51 patients had acute kidney injury (eGFR<90 mL/min/1.73 m2) before treatment, but all recovered during the observation period (median 52 months). Our steroid- and immunosuppressant-based protocol without ACE-Is or ARBs in the acute phase of HSPN had almost equivalent efficacy to that in previous studies that used ACE-Is and/or ARBs with steroids and immunosuppressants.

Efficacy and Safety of Plasma Exchange as an Adjunctive Therapy for Rapidly Progressive IgA Nephropathy and Henoch-Schönlein Purpura Nephritis: A Systematic Review.

Patients with IgA nephropathy (IgAN), including Henoch-Schönlein purpura nephritis (HSP), who present with rapidly progressive glomerulonephritis (RPGN) have a poor prognosis despite aggressive immunosuppressive therapy. The utility of plasmapheresis/plasma exchange (PLEX) for IgAN/HSP is not well established. This systematic review aims to assess the efficacy of PLEX for IgAN and HSP patients with RPGN. A literature search was conducted using MEDLINE, EMBASE, and through Cochrane Database from inception through September 2022. Studies that reported outcomes of PLEX in IgAN or HSP patients with RPGN were enrolled. The protocol for this systematic review is registered with PROSPERO (no. CRD42022356411). The researchers systematically reviewed 38 articles (29 case reports and 9 case series articles) with a total of 102 RPGN patients (64 (62.8%) had IgAN and 38 (37.2%) had HSP). The mean age was 25 years and 69% were males. There was no specific PLEX regimen utilized in these studies, but most patients received at least 3 PLEX sessions that were titrated based on the patient's response/kidney recovery. The number of PLEX sessions ranged from 3 to 18, and patients additionally received steroids and immunosuppressive treatment (61.6% of patients received cyclophosphamide). Follow-up time ranged from 1 to 120 months, with the majority being followed for at least 2 months after PLEX. Among IgAN patients treated with PLEX, 42.1% (n = 27/64) achieved remission; 20.3% (n = 13/64) achieved complete remission (CR) and 18.7% (n = 12/64) partial remission (PR). 60.9% (n = 39/64) progressed to end-stage kidney disease (ESKD). Among HSP patients treated with PLEX, 76.3% (n = 29/38) achieved remission; of these, 68.4% (n = 26/38) achieved CR and 7.8% achieved (n = 3/38) PR. 23.6% (n = 9/38) progressed to ESKD. Among kidney transplant patients, 20% (n = 1/5) achieved remission and 80% (n = 4/5) progressed to ESKD. Adjunctive plasmapheresis/plasma exchange with immunosuppressive therapy showed benefits in some HSP patients with RPGN and possible benefits in IgAN patients with RPGN. Future prospective, multi-center, randomized clinical studies are needed to corroborate this systematic review's findings.

Angiotensin-converting enzyme insertion/deletion gene polymorphism and Henoch-Schonlein purpura nephritis risk in children: ameta-analysis.

It has been demonstrated in many studies that angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism is related to Henoch-Schonlein purpura nephritis (HSPN) risk in children. However, this conclusion remains controversial. In this study, we systemically retrieved relevant studies in electronic databases such as PUBMED, CNKI, and EMBASE followed by calculation ofodds ratios (OR) with 95% confidence intervals (CI). In addition, meta-package in STATA version 12.0 was used. Angiotensin-converting enzyme I/D polymorphism was related to HSPN susceptibility in children (D vs. I: OR 1.47, 95% CI: 1.13-1.93; DD vs. II: OR 2.29, 95% CI: 1.29-4.07; DI vs. II: OR 1.10, 95% CI: 0.82-1.48; dominant model: OR 1.44, 95% CI: 1.09-1.89; recessive model: OR 2.26, 95% CI: 1.67-3.06). In addition, subgroup analysis stratified according to ethnicity indicated asignificant relationship between this polymorphism and HSPN susceptibility among Asians and Caucasians. Thedata extracted from HaploReg indicated that ACE I/D polymorphism was not in linkage disequilibrium with other variants in theACE gene. Theresearch shows that ACE I/D polymorphism is related to HSPN susceptibility in children.

A chronic EBV infection causing persistent facial erythema multiforme and a retrospective literature review: A case report

Epstein-Barr virus (EBV) infection is associated with a variety of diseases and can involve multiple organs and systems, with complex and nonspecific clinical manifestations that are easily misdiagnosed. Chronic EBV infection with persistent erythema multiforme (EM) on the cheek as the main manifestation is very rare and has been reported rarely. This article reports a case of an adolescent female with chronic EBV infection who presented with chronic symmetrical erythema lesions on the face for 4 years, exacerbated with photophobia, lacrimation, Henoch-Schonlein purpura (HSP)-like rash, decline in granulocyte and erythrocyte lineages, hematuria, and proteinuria for 1 week. The disease was initially misdiagnosed as systemic lupus erythematosus (SLE) and later confirmed as chronic EBV infection by skin biopsy. In the case, EBV infection not only caused chronic facial EM, but also induced acute HSP and purpura nephritis (hematuria and proteinuria type). The child was treated with 1 week of glucocorticosteroids in adequate doses combined with acyclovir antiviral therapy and 3 sessions of hemoperfusion. After discharge, she took prednisone acetate (15 mg twice a day) orally for 1 month and then discontinued. She was discharged with her rash relieved and normal blood routine test and urine routine test. After 13 months of long-term follow-up, her facial erythema and hyperpigmentation became lighter, and there was no new rash on the whole body, and no abnormality in continuous monitoring of complete blood count and urine test. This case suggests the need to be alert for chronic EBV infection in adolescent females with chronic facial EM rash and multiple organs and systems injury, in addition to connective tissue diseases such as SLE.

Hemoperfusion and intravenous immunoglobulins for refractory gastrointestinal involvement in pediatric Henoch-Schönlein purpura: a single-center retrospective cohort study

BackgroundHenoch-Schönlein purpura (HSP) with refractory gastrointestinal (GI) symptoms is always difficult to handle because of its resistance to supportive therapies and glucocorticoid. This study aimed to evaluate the efficacy of hemoperfusion (HP) and intravenous immunoglobulins (IVIG) therapies in this population.MethodsSixty-four HSP patients with refractory GI involvement (R-GI group) and 64 cases with mild GI symptoms (control group) were retrospectively analyzed in our center from March 2016 to October 2019. In R-GI group, 42 cases (subgroup A) were treated with IVIG and steroid, 13 cases (subgroup B) used HP and steroid, 9 cases (subgroup C) executed a combination of IVIG, HP and steroid. Demographic characteristics, clinical features, laboratory indexes and treatment outcomes were recorded. t-test, One-way ANOVA, Mann-Whitney U test, and multivariate logistic regression were used in comparing differences among subgroups and predicting independent risk factors.ResultsCompared with the control group, R-GI cases experienced higher risk of renal involvement (P = 0.000), more steroid exposure (P = 0.000), six times expenses (P = 0.000) and 2.3 times length of hospitalization (P = 0.000). The independent risk factors of R-GI group were elevated neutrophils (OR 1.250 [95% CI 1.130-1.383]) and the percentage of B lymphocytes (OR 1.100 [95% CI 1.026-1.179]) as well as decreased IgG (OR 0.847 [95% CI 0.732-0.98]). In R-GI group, increased age (OR 1.039 [95% CI 1.016-1.062]) and IgM (OR 5.994 [95% CI 1.403-27.611]) were verified to be risk factors of HSP nephritis. All three subgroups could alleviate the symptoms effectively. Compared with those in subgroup A, patients in subgroup B were elder (P = 0.004), had less relapse (P = 0.002), steroid exposure (P = 0.033) and expenses (P = 0.031), more significant decrease of WBC (P = 0.026) after treatment.ConclusionThe HSP with refractory GI involvement had much higher risk of medical burden and renal involvement. Both IVIG and HP therapies could ameliorate refractory GI symptoms efficiently. HP therapy tended to reduce the relapse, costs and steroid exposure in its audiences who were cooperated and with stable hemodynamics, while IVIG had better use in younger children.

Effects of Shengjiangsan, white silkworm and Periostracum cicadae on cytokines in Henoch-Schönlein purpura nephritis

Henoch-Schönlein purpura (HSP, also named IgA vasculitis) is a common childhood vascular disease, which is characterized by immunoglobulin A (IgA deposition) in small blood vessels; HSP causes kidney involvement to develop Henoch-Schönlein purpura nephritis (HSPN). However, the exact pathogenesis of HSPN is not fully understood, and it is still necessary to explorer new drugs for the treatment of HSPN. In this study, bovine serum albumin (BSA), lipopolysaccharide (LPS) and carbon tetrachloride (ClC4) were used to induce IgAN in rat, and the blood stasis and heat syndrome model was established concurrently, and was combined to establish the HSPN model. The therapeutic effects of different doses of Shengjiangsan (5, 10, 20 g/kg), white silkworm (1, 2, 4 g/kg), and Periostracum cicadae (0.5, 1, 2 g/kg) on HSPN model rats were studied, then 24 h urine was collected and blood from the abdominal aorta was taken to detect the protein changes in urine and blood. Immunofluorescence staining was used assess to IgA deposition in glomeruli. Tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin 6 (IL-6), and immunoglobulin A (IgA) levels were measured in serum by enzyme-linked immunosorbent assay. Hematoxylin and eosin (H&amp;E) and periodic acid Schiff (PAS), immunohistochemical staining was performed to observe the histopathological changes in kidney tissues. In addition, Western blotting was used to detect the changes in the expression levels of IgA, TNF-α, and toll-like receptor 4 (TLR4). In the results, Shengjiangsan, white silkworm, and Periostracum cicadae could significantly reduce the levels of urine protein, blood urea nitrogen (BUN) and serum creatinine (CREA) in HSPN rats. Serum levels of IgA, TNF-α, IL-1β, and IL-6 were significantly reduced in the treatment groups. The treatment group can effectively improve renal tissue inflammation and mesangial hyperplasia. The accumulation of IgA protein in renal tissue was significantly reduced in the treatment group. The expression of monocyte chemoattractant protein (MCP)-1, TLR4, and IgA were significantly reduced and responded in a dose-dependent manner. Moreover, levels of transforming growth factor beta 1 (TGF-β1) decreased in kidney tissues in the treatment groups. In conclusion, Shengjiangsan, white silkworm, and Periostracum cicadae could improve HSPN in rats by reducing renal inflammation and fibrosis, and the therapeutic effects of white silkworm and Periostracum cicadae were slightly better than Shengjiangsan.

A disease-targeted picture book for children with Henoch-Schonlein purpura nephritis: A quasi-experimental study.

Children with Henoch-Schonlein purpura nephritis are frequently burdened with psychological problems besides disease treatment and adherence. Currently, there is a shortage of appropriate and effective educational materials to facilitate physical and psychological recovery. To examine a picture book for the effectiveness of disease-related knowledge, coping strategies, resilience, quality of lifeand depressive symptoms in children with Henoch-Schonlein purpura nephritis in China. A quasi-experimental design with repeated measures was adopted. The control group received standard care. The intervention group received the standard care plus a free picture book. This disease-specific picture book narrated the story of two rabbits diagnosed with Henoch-Schonlein purpura nephritis who underwent a series of examinations, faced difficulties taking medication, and eventually recovered. The study recruited 60 children diagnosed with Henoch-Schonlein purpura nephritis. Disease-related knowledge, resilience, coping strategies, depressionand paediatric quality of life were measured at baseline, the third day, the first monthand the third month after recruitment. The acceptability of the picture book was evaluated at the last data-collection point. The data showed that children in the intervention group demonstrated higher levels of knowledge (p < 0.001), less usage of emotional coping strategies (p = 0.003), reduced depressive symptoms (p = 0.003), improved psychological resilience (p < 0.001), and better quality of life (p < 0.046) than those in the control group in the third month. Most children (83.3%) in the intervention group were satisfied with the picture book. The targeted picture book is an effective educational tool for improving clinical outcomes and was highly accepted by children.

A retrospective study on the characteristics of renal pathological grades in HSPN children with mild to moderate proteinuria.

To investigate the characteristics of renal pathological grades in Henoch-Schönlein purpura nephritis (HSPN) children with mild to moderate proteinuria and the correlation between pathological grade and severity of proteinuria among this population. HSPN children who were presented with mild (150 mg <24 h urinary protein <25 mg/kg) to moderate (25 mg/kg ≤24 h urinary protein <50 mg/kg) proteinuria and performed renal biopsy without steroid ± immunosuppressant treatment in the Second Xiangya Hospital between January 2010 and March 2021 were involved. We retrospectively analyzed the correlation between age, disease course, degree of proteinuria, type of immunoglobulin deposits, C3 deposits in glomeruli and renal pathological grade. (1) 72 HSPN children including 46 boys and 26 girls were included, with a mean age of onset of 9.01 ± 2.65 years old. The majority of these patients (62.5%) had a disease course between 1 week to 1 month. 51 patients presented with mild proteinuria and 21 patients with moderate proteinuria. (2) Renal biopsy results showed that ISKDC Grade IIIa were both predominant in mild proteinuria group (25, 49%) and moderate proteinuria group (11, 52.4%). 32 patients had grade II (44.4%), 2 had grade IIIb (2.8%), 1 had grade IV (1.4%), and 1 had grade VI (1.4%). There was no correlation between age, disease course and renal pathological grade (p > 0.05). (3) In patients with mild proteinuria (n = 51), 27 (52.9%) HSPN children had a pathological grade ≥ grade III. In patients with moderate proteinuria (n = 21), 13 (61.9%) HSPN children had grade ≥ III. There was no significant difference in the proportion of renal pathological grade between the 2 groups (p > 0.05). (4) There was no significant correlation between glomerular C3 deposits or immunoglobulin deposit types and renal pathological grade (p = 0.776 and p = 0.056 respectively). In HSPN children with mild to moderate proteinuria, longer disease course or heavier urinary protein level is not completely parallel with higher renal pathological grade. ISKDC grade IIIa is the most common pathological grade. Clinicians should pay great attention to the renal injury in patients with mild to moderate proteinuria.

Network Pharmacology and Molecular Docking Analysis to Explore the Mechanism of Huaiqihuang-Mediated Alleviation of Henoch-Schönlein Purpura Nephritis.

Henoch-Schönlein purpura nephritis (HSPN) is considered a major cause of chronic renal failure and is the most common secondary glomerular disease in children. Huaiqihuang (HQH), a traditional Chinese herbal formula, exhibits therapeutic effects against HSPN in clinical practice. However, the potential molecular targets and mechanisms underlying HSPN treatment remain unclear. By constructing a protein-protein interaction (PPI) network, core targets related to HQH and HSPN were identified. Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathways were analyzed to identify the main pathways related to HSPN based on the core targets. To screen the main active ingredients of HQH against HSPN, an ingredient-target-pathway network was constructed using the top 10 main pathways associated with HSPN. Then, molecular docking was performed to explore the interactions and binding patterns between molecules and proteins. Clinical data showed that HQH combined with conventional medicine significantly reduced 24-hour urine protein excretion, urine microalbumin levels, and erythrocyte counts in the urine sediment of HSPN patients. By constructing PPI models, 15 potential core targets were identified. The top 10 main pathways showed higher enrichment ratios, including the cytokine-cytokine receptor interaction and signaling pathways related to NOD-like receptor, IL-17, etc. Through the ingredient-target-pathway network and molecular docking, we revealed that five active ingredients of HQH had good affinities with three core targets, AKT1, MMP9, and SERPINE1, which may be vital in treating HSPN. The study preliminarily explored the active ingredients, targets, and pathways involved in HQH therapy for HSPN. The mechanism of HQH therapy may be attributed to the modulation of inflammatory response, immune response, and oxidative stress. Combined with clinical data, our results indicate that HQH is highly effective in treating HSPN.