2025+中国指南：儿童IgA血管炎的诊断和管理（英文）

Abstract

Background Immunoglobulin A vasculitis (IgAV) is the most common cause of systemic vasculitis in childhood. Due to the continued use of the disease name "anaphylactoid purpura" in China, several misunderstandings have arisen in clinical prac-tice and treatment regimens differ widely. In addition, new research and evidence-based data have grown. The Subspecialty Group of Immunology, Society of Pediatrics, Chinese Medical Association and the Chinese Alliance of Pediatric Haeomatic and Immunologic Diseases initiated an update of guidelines for the diagnosis and management of childhood IgAV. The aim therefore was to provide agreed consensus recommendations for diagnosis and treatment for children with IgAV.

Methods This study utilized the Delphi technique to develop an evidence-based expert consensus for childhood IgAV. We conducted a systematic literature review to retrieve evidence, which was graded using GRADE(Grading of Recommenda-tions Assessment, Development, and Evaluation) criteria. Two rounds of Delphi voting and a consensus meeting involving 23 experts were conducted. Recommendations were accepted when $\ge 75\%$ of experts agreed.

 Hong-Mei Song songhm1021@hotmail.com

Ⅺ Xiao-Chuan Wu xiaochuanwu@csu.edu.cn

1 Department of Pediatrics, The Second Xiangya Hospital,Central South University, Changsha 410011, China

2 Department of Pediatric Nephrology, Rheumatology and Immunology, The Affiliated Hospital of Qingdao University, Qingdao 266000, China

3 Department of Nephrology and Immunology, Children's Hospital of Soochow University, Suzhou 215000, China

4 Department of Pediatrics, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, China

5 Department of Pediatrics, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China

${ }^{6}$ Department of Pediatrics, Fujian Provincial Hospital,Puzzy350001,China

$\boxed{7}$ Department of Pediatrics Medical, General Hospital of Ningxia Medical University, Yinchuan 750000, China

${ }^{8}$ Department of Pediatrics, Renji Hospital Affiliated to Shanghai JiaoTong University School of Medicine, Shanghai 201112, China

9 Department of Rheumatology and Immunology, Children's Hospital of Urnmqi City 830000, China

10 Department of Rheumatology and Immunology, Xi'an Children's Hospital, Xi'an 710002, China

11 Department of Rheumatology and Immunology,Children's Hospital of Chongqing Medical University,Chongqing 40014, China

12 Department of Rheumatology, School of Medicine UESTC,The Affiliated Women's and Children's Hospital, Chengdu Women and Children's Central Hospital, Chengdu 611731,China

13 Department of Pediatricology and Allergy, The First Hospital, Jilin University, Changchun 130021, China

14 Department of Pediatrics, Nanfang Physics, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China

15 Department of Rheumatology and Immunology, Children's Hospital of Nanjing Medical University, Nanjing 210008,China

<EndOfPara>16 Department of Nephrology, Shanghai Children's Medical Center, Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200127, China

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Results In total, five recommendations for diagnosis, six for treatment, one for prognosis, and two for health education for pediatric IgAV were accepted. Diagnostic recommendations included the use of the European Alliance of Associations for Rheumatology/Pediatricology International Trials Organization/Pediatric Rheumatology European Society-endorsed Ankara 2008 classification criteria for IgAV diagnosis. In addition, appropriate use of imaging, gastrointestinal endoscopy, skin biopsy, and kidney biopsy are recommended. Kidney biopsy is recommended for children with IgAV pre-senting with nephrotic syndrome/nephrotic-range proteinuria, reduced estimated glomerular filtration rate, acute nephritis syndrome, or persistent moderated/mild proteinuria. Treatment recommendations involved indications for glucocorticoid use, immunosuppressant use, and intravenous immunoglobulin use. It also addressed the inappropriate use of prophylactic glucocorticoid treatment and recommended against routine employment of plasmapheresis. Health education placed emphasis on the inappropriate use of anti-anaphylactic treatment and proffers dietary suggestions.

Conclusions This guideline provides evidence-based recommendations for the diagnosis and management of IgAV in chil-dren. This will facilitate improved and standardized care.

Graphical abstract

Guidelines for the diagnosis and management of childhood immunoglobulin A vasculitis

 Keywords Children·Diagnosis·Immunoglobulin A vasculitis· Management· Recommendation

17 Department of Nephrology and Rheumatology, Shanghai Children's Hospital, Children's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,Shanghai 200062, China

18 Department of Rheumatology and Immunology, Shenzhen Children's Hospital, Shenzhen 518038, China

${}^{19}$ Department of Immunology, National Center for Children's Health, Beijing Children's Hospital, Capital Medical University, Beijing 100045, China

20 Department of Pediatrics, The First Affiliated Hospital of Xiamen University, Xiamen 361000, China

21 Department of Rheumatology and Immunology, The First People's Hospital of Yunnan Province, Kunming 650032,China

${}^{22}$ Department of Pediatrics, First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China

${}^{23}$ Institute of Health Data Science, Lanzhou University,Lanzhou 730000, China

24 Evidence Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China

25 School of Public Health, Lanzhou University,Lanzhou 730000, China

26 Department of Pediatrics, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China

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Introduction

Immunoglobulin A vasculitis (IgAV), previously known as Henoch-Schönlein purpura (HSP), is a common systemic vasculitis in childhood. The annual incidence in children is 6.1-55.9 per 100,000, with the highest incidence (70.3 per 100,000) in 4 to 6 year-olds[1-4]. Incidence varies among different ethnic groups, being higher in Asians and lower in Blacks[1, 3]. It mainly occurs in autumn, winter, and spring,with a male-to-female incidence ratio of (1.1-1.5):1[1,2,4]. While the prognosis is generally good for most children with IgAV, severe kidney or gastrointestinal involvement can lead to adverse outcomes. Hence, accurate diagnosis and standardized management are essential cornerstones of care.

In the 2012 Chapel Hill Consensus Conference on the Clas-sification of Vasculitides, it was proposed to rename HSP as IgAV, highlighting the crucial role of the IgA-mediated immune response in its pathogenesis [5]. In 2013, the Subspecially Group of Immunology, the Society of Pediatrics, Chinese Medical Association, formulated "Evidence-based recom-mendations for the diagnosis and management in children with Henoch-Schönlein Purpura", which has been instrumental in standardizing the clinical diagnosis and management of HSP in this group [6]. However, due to the continued use in China of the previous disease name "anaphylactoid purpura", several misunderstandings have arisen in clinical practice and treatment regimens differ widely. In addition, new research and evidence-based data have grown. Therefore, we organized experts nation-wide who majored in pediatric rheumatology, pediatric immu-nology, pediatric nephrology, and epidemiology to develop and update Chinese guidelines for the diagnosis and management of childhood IgAV. Our overall aim was to facilitate pediatricians to provide improved and standardized care.

Guideline development

This guideline was developed by the Subspecialty Group of Immunology, Society of Pediatrics, Chinese Medical Asso-ciation and the Chinese Alliance of Pediatric Rheumatic and Immunologic Diseases. It was revised in accordance with the methods and procedures specified in the "Guidelines for the development and revision of clinical diagnosis and treatment guidelines in China (2022 edition)" issued by the Chinese Medi-cal Association [7]. Figure 1 outlines process methodology.Recommendations in this guideline apply to pediatric patients(defined as $\leq 18$ years old) with suspected or confirmed IgAV.

Guideline formulation working group

<BeginOfPara>The guideline formulation working group consists of a steering committee, a secretariat group, an expert group,

 Fig. 1 Process flow for guideline development. PREPARE practice guideline registration for transparency, PICO population, interven-tion, comparison, outcome; GRADE Grading of Recommendations Assessment, Development, and Evaluation

<EndOfPara>an evidence evaluation group, and an external review expert group. The expert group consisted of 23 members who were pediatric rheumatologists, pediatric immun-ogists, and pediatric nephrologists from major hospitals nationwide. They were primarily responsible for selecting clinical issues, revising consensus opinions, and achieving consensus through four rounds of online Delphi voting and a face-to-face consensus meeting. Seven(30.43%) of them were female. Fifteen(65.22%) held a doctorate degree,five(21.74%) a master's degree, and three(13.04%) a bachelor's degree. The specific composition and respon-sibilities of the remaining groups are described in Sup-plement Table 1.

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Table 1 Grading of quality of evidence and strength of recommendation

|Grading|Description| |---|---| |Quality of evidence|| |High(A)|Further research is very unlikely to change confidence in the estimated effect| |Moderate(B)|Further research is likely to impact confidence in estimate and may change the effect estimate| |Low(C)|Further research is very likely to impact confidence in the estimate and may change the estimate| |Very Low(D)|Any estimate of effect is highly uncertain| |Strength of recommendation|| |Strong(1)|Clearly demonstrates that the benefits of the intervention outweigh the harms(or the harms| |Weak/conditional(2)|The balance of benefits and harms of the intervention is uncertain, or it requires individualized decision-making that incorporates patient preferences, resource constraints and other contex- total factors|

Guideline registration

This guideline has been registered on the international prac-tice guideline registration for transparency(PREPARE) plat-form(http://www.guidelines-registry.org), with a registra-tion number PREPARE-2022CN587.

Selection of clinical issues

The secretariat group proposed four main clinical topics(diagnosis, treatment, prognosis, and health education for IgAV in children) with 16 clinical questions based on literature reviews and experts' opinions from the steering committee. Expert panel members were invited to rate these topics and questions online regarding their impor-tance and operability using a seven-point Likert scale(https://www.wjx.cn/). Expert panel participants were encouraged to give comments on each question and pro-pose new questions. The clinical question was retained when the mean score of importance was not less than 6 or more than 75% of the experts chose scores of 6-7. The question(s) were modified, added, or deleted according to comments from the experts. Consequently, the secretariat group deleted four and added two clinical questions to the second-round questionnaire. After two rounds of Delphi voting, a consensus of four main clinical topics and 14 key clinical questions was ultimately reached.

Evidence retrieval and quality rating

The Evidence Evaluation Group utilized the PICO(popu-lation, intervention, comparison, outcome) framework to deconstruct and formulate the final clinical questions.Comprehensive literature searches were then carried out across multiple databases, including PubMed, the Cochrane Library, Web of Science, China Biology Medicine disc,Wanfang Data Knowledge Service Platform, and China

National Knowledge Infrastructure. The primary types of evidence sought encompassed systematic reviews, meta-analyses, randomized controlled trials, cohort studies,case-control studies and case series. The search scope cov-ered the period from the inception of each database up to September 14, 2022 and was restricted to publications in Chinese and English languages. The literature search was also updated with relevant articles as they became available during manuscript preparation up to May 1, 2025.

The Evidence Evaluation Group employed the Risk of Bias in Systematic Reviews tool to assess the risk of bias in the systematic reviews and meta-analyses included[8]. For primary studies, methodological quality was appraised using the Cochrane Risk of Bias Tool for randomized controlled trials and the Newcastle-Ottawa Scale for observational studies[9, 10]. The evaluation procedure was independently performed by two members. In case of any discrepancies,they were resolved through discussion or by consulting a third party.

The Grading of Recommendations Assessment, Develop-ment, and Evaluation(GRADE) framework was applied to rate the evidence and recommendations, as shown in Table 1[11]. For clinical questions lacking adequate evidence to allow generation of a recommendation, Good Practice Statements(GPS) are developed. These statements cannot be evaluated using GRADE but may still be regarded as equiva-lent to a strong recommendation when consensus is achieved through a Delphi survey conducted by the expert panel.

Consensus formulation

Drawing on the evidence summary table provided by the Evidence Evaluation Group, and taking into account the values of Chinese children and their parents, as well as the costs, benefits and disadvantages of the interventions, the recommendation proposals were crafted. The third round of online Delphi surveys(conducted via https://www.wjx.cn)

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Table 2 Summary of recommendations and good practice statements for the diagnosis, treatment, and management of childhood immunoglobu-lin A vasculitis

||Type of statement|Certainty in the evidence| |---|---|---| |Diagnosis|Diagnosis|Diagnosis| |Classification criteria||| |The EULAR/PRINTO/PRSe-Sendorsed Ankara 2008 criteria is recommended for diagnosis of IgAV in GPS||| |children|children|children| |Diagnostic work-up|Diagnostic work-up|Diagnostic work-up| |Imaging||| |Abdominal ultrasound or X-ray should be performed in cases with suspected intestinal intussception or intestinal perforation. CT may be considered if unclear|Strong recommendation|Low| |Endoscopy of the digestive tract||| |Routine endoscopy is not recommended|GPS|NA| |It may be considered in patients with severe GI involvement who need further differential diagnosis|Conditional recommendation|Low| |Skin biopsy||| |Skin biopsy is recommended in patients with atypical rash or uncertain diagnosis|GPS|NA| |Kidney biopsy||| |Kidney biopsy is recommended for children with IgAV presenting with nephrotic syndrome/nephrotic- range proteinuria,eGFR<90 mL/min/1.73 m2, acute nephrotic syndrome(hypertension,hematuria, and/or proteinuria with acute kidney injury), or persistent moderate/mild proteinuria|GPS|NA| |Treatment|Treatment|Treatment| |Glucocorticoids||| |Treatment with glucocorticoids||| |Severe GI involvement|Strong recommendation|Moderate| |Joint involvement|Conditional recommendation|Moderate| |IgAVN|GPS|NA| |Severe skin involvement,angioedema,orchitis,cerebral vasculitis, pulmonary hemorrhage, and other severe organ or life-threatening vasculitis|Strong recommendation|Low| |Prophylactic glucocorticoid treatment for recurrent rash of IgAV||| |Glucocorticoids are not recommended for routine prevention of skin relapse|Strong recommendation|Low| |Prophylactic glucocorticoid treatment for the prevention of IgAVN development||| |Prophylactic use of glucocorticoid to prevent IgAVN is not recommended|Strong recommendation|Moderate| |Other immunosuppressants||| |MMF may be considered for steroid-resistant or steroid-dependent severe GI involvement|Conditional recommendation|Very low| |CTX may be considered for patients with severe organ involvement such as pulmonary hemorrhage, severe|Conditional recommendation|Very low| |GI involvement or CNS vasculitis||| |Hemorrhagic bullous rash|Conditional recommendation|Very low| |CNS vasculitis|Conditional recommendation|Very low| |Plasmapheresis||| |Routine application of plasmapheresis is not recommended in severe IgAV|Strong recommendation|Low| |Prognosis||| |Risk factors||| |Short-term prognosis is mainly related to GI and vital organ involvement|GPS|NA| |Long-term prognosis is primarily determined by the severity of kidney involvement|Strong recommendation|Low| |Health education||| |Food allergy and anti-allergic therapy||| |No causal link between IgAV and food allergy has been confirmed; routine anti-allergic therapy is not recommended|GPS|NA| |Dietary notes||| |In GI-involved patients, short-term fasting and rehydration may be required|GPS|NA| |Long-term restriction of animal protein is not recommended|Strong recommendation|Very low|

IgAV Immunoglobulin A vasculitis, EULAR European Alliance of Associations for Rheumatology, PRINTO Pediatric Technology International Tri-als Organization, PReS Pediatric Rheumatology European Society, GPS good practice statement, CT computed tomography, GI gastrointestinal, CNS central nervous system, IgAVN IgA vasculitis nephritis, MMF mycophenolate mofetil, CT cyclophosphamide, IVIG intravenous immunoglobulin

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were carried out among the 23-member expert group. Three response options were provided: agree, disagree, and unsure.Expert panel participants were encouraged to provide revi-sion suggestions. Subsequently, the recommendations were revised based on responses received and discussed at a face-to-face consensus meeting. After the fourth-round of online Delphi surveys(again via https://www.wjx.cn), the final recommendations were only accepted when at least 75% of experts reached an agreement.

Recommendations and good practice statement

In total, 14 items comprising recommendations and GPS for pediatric IgAV, categorized into four sections(5 for diagnosis, 6 for treatment, 1 for prognosis, and 2 for health education), were officially accepted. A detailed breakdown is presented in Table 2.

Diagnosis

Classification criteria for pediatric IgAV

Good practice statement

The European Alliance of Associations for Rheumatology(EULAR)/Pediatric Rheumatology International Trials Organization(PRINTO)/Pediatric Rheumatology European Society(PReS)-endorsed Ankara 2008 classification criteria is recommended for diagnosis of IgAV in children. Differen-tial diagnosis should be noted for atypical IgAV.

Summary of the evidence

In the absence of a definitive diagnostic test, the diagnosis of pediatric IgAV primarily hinges on clinical criteria and laboratory findings. There remains a lack of internationally recognized evidence-based recommendations. The EULAR/

PRINTO/PReS-endorsed Ankara 2008 classification criteria were developed based on large-scale international patient registry studies and specifically validated for pediatric patients[12]. These criteria exhibit a sensitivity of 100%and a specificity of 87%. In comparison, the 2006 EULAR/PReS classification proposal had a sensitivity of 100% but a specificity of only 69%, and the 1990 American College of Rheumatology classification criteria for HSP showed a sensitivity of 100% with a mere 2% specificity[13, 14].

Diagnostic recommendations of IgAV are summarized in Table 3. However, it should be noted that classification criteria should not be used as diagnostic criteria[15]. Clini-cally, diagnosing IgAV when it presents with typical mani-festations is not challenging. However, for atypical cases,specific laboratory examinations are necessary. Moreover,differential diagnosis from other diseases is required. These diseases include idiopathic thrombocytopenic purpura, sur-gical acute abdomen, infectious diseases, necrotizing entero-colitis, rheumatic arthritis, juvenile idiopathic arthritis, acute infantile hemorrhagic edema, Wilson's disease, other rheu-matic diseases such as anti-neutrophil cytoplasmic antibody-associated vasculitis, polyarteritis nodosa, systemic lupus erythematosus, Sjogren's syndrome, mixed connective tissue disease, dermatomyositis, and autoinflammatory diseases.Furthermore, in the case of children who have isolated skin manifestations, when the rash is characteristic and other rheumatic diseases have been ruled out, IgAV can be con-sidered as a diagnosis. If deemed necessary, a skin biopsy can be performed to help confirm the diagnosis.

Diagnostic workup for pediatric IgAV

Imaging(abdominal ultrasound,abdominal X-ray,and abdominal computed tomography)

Recommendation Abdominal ultrasound and abdominal X-ray are recommended for the diagnosis of severe gas-trointestinal complications(intussusception and intestinal perforation) in IgAV. A computed tomography(CT) scan

Table 3 Diagnostic recommendations for childhood immunoglobulin A vasculitis

Diagnostic recommendations

Purpura or petechiae(mandatory) with lower limb predominance and at least one of the four following criteria:

Abdominal pain

Histopathology(typically leucocytoclastic vasculitis with predominant IgA deposit or proliferative glomerulonephritis with predominant IgA deposit)

Arthritis or arthralglas

Kidney involvement(proteinuria> 0.3 g/24 h or> 30 mg/mmol of urine albumin/creatinine ratio in a spot morning sample; hematuria or red blood cell casts: 5 red blood cells/high power field or red blood cells casts in the urinary sediment or≥2+on dipstick)

The Ankara 2008 classification criteria, endorsed by the European Alliance of Associations for Rheumatology, the Pediatric Rheumatology International Trials Organization, and the Pediatric Rheumatology European Society are recommended for the diagnosis of immunoglobulin A vasculitis(IgAV) in children

 Springer

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is recommended when there are doubts regarding X-ray or ultrasound examination results(1C).

Summary of the evidence The incidence of gastrointes-tinal involvement in IgAV ranges from 50% to 75%, with clinical manifestations mainly including abdominal pain and gastrointestinal bleeding[16, 17]. In cases of IgAV,abdominal ultrasound can disclose significant thicken-ing of the intestinal wall, intestinal dilation, widening of the intestinal loops, and diminished intestinal motility. A small amount of ascites may be evident in some patients[18]. Abdominal X-ray may demonstrate thickened mucosal folds, thumb printing, increased spacing between intestinal loops, and small bowel distension featuring air-fluid levels.CT scans typically reveal multifocal segmental bowel dam-age. The affected bowel wall appears edematous and thick-ened, bowel stenosis may be present, and a small amount of ascites is frequently observable around the affected section of bowel[19]. Imaging findings provide limited assistance in the diagnosis of IgAV. Therefore, routine implementa-tion of the aforementioned imaging examinations for chil-dren with IgAV is not recommended. However, IgAV may be complicated by severe gastrointestinal complications,such as intussusception and intestinal perforation, which are manifested as persistent or severe abdominal pain and/or Hematochezia. The overall incidence of intussusception in IgAV is 0.4%-10.2%[20-22]. Unlike idiopathic intus-susception(ileocolic intussusception), 50%-60% of intus-susception cases in IgAV are ileo-ileal[16, 17]. For children with IgAV suspected of having intussusception, abdominal ultrasound is recommended as the examination of choice.Performing X-ray barium enema or air enema may exc-rebate the inflammation and potentially lead to intestinal perforation. The incidence of intestinal perforation in IgAV generally does not exceed 1%. A single-center retrospective analysis conducted in China revealed that the incidence of gastrointestinal perforation in IgAV is approximately 0.1%(11 out of 10,791)[23]. In these cases, ultrasound detected three, while CT scan diagnosed eight. Among these, five had negative ultrasound findings and were finally diagnosed using CT scanning[23]. Therefore, in children with IgAV who exhibit persistent or severe gastrointestinal symptoms such as abdominal pain and/or hematochezia, it is recom-mended to perform abdominal ultrasound or abdominal X-ray to exclude intussusception or intestinal perforation.When the results of X-ray or ultrasound examinations are inconclusive, CT scans are generally the preferred option.

Endoscopy of the digestive tract

Recommendation and good practice statement Gastroin-testinal endoscopy is not recommended as a routine proce-dure for children with IgAV(GPS). Nevertheless, for chil-

dren with IgAV or suspected IgAV who experience severe abdominal pain or gastrointestinal bleeding(either acute massive gastrointestinal bleeding or recurrent gastrointes-tinal bleeding), gastrointestinal endoscopy is suggested for further differential diagnosis(2C).

Summary of the evidence Under endoscopy, the gastro-intestinal mucosa in patients with IgAV exhibits purpuric alterations, erosions, and ulcers. Lesions are predominantly segmental, chiefly involving the stomach, duodenum, small intestine, and colon. Among these, the small intestine is most commonly and severely affected; the esophagus is scarcely involved. The duodenal mucosa exhibits the most promi-nent changes. In addition, irregular ulcers in the descending part of the duodenum are also regarded as a characteristic manifestation of IgAV in the gastrointestinal tract[24-26].Although endoscopy can assist in the early detection of IgAV and also evaluation of disease condition to guide treatment[24, 25, 27, 28], the majority of endoscopy-related stud-ies are retrospective and observational with a small sample size and low-quality evidence. In children presenting with only gastrointestinal symptoms but without skin purpura,gastrointestinal endoscopy can directly observe the typical lesions in the gastrointestinal mucosa, but histopathology of typically leucocytoclastic vasculitis with predominant IgA deposit is rarely revealed by biopsy. Moreover, since it does not meet the IgAV classification criteria, diagnos-ing IgAV based solely on endoscopic findings should also be carried out with caution[29]. Therefore, this guideline does not advocate for routine gastrointestinal endoscopy in children with IgAV. In cases of children with IgAV or those suspected of having IgAV who experience severe abdominal pain or severe gastrointestinal bleeding and need further dif-ferential diagnosis, gastrointestinal endoscopy can be con-sidered as appropriate.

Skin biopsy

Good practice statement It is recommended to perform a skin biopsy in children with suspected IgAV or atypical rashes to aid in diagnosis or exclude other pathologies.

Summary of the evidence Indications for skin biopsy in IgAV are primarily based on expert consensus recommen-dations[30]. Skin biopsy is generally not required for typi-cal presentations. For suspected cases or those with atypi-cal rashs, biopsies should target new skin lesions within 24 hours of onset. Older lesions may exhibit vascular dam-age leading to nonspecific leakage of all immunoglobulin isotypes which can compromise the accuracy of immuno-fluorescence staining. However, it is important to note that negative IgA immunofluorescence staining in biopsy speci-mens does not definitively exclude a diagnosis of IgAV. A

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10-year single-center retrospective-controlled study enrolled 62 patients with skin biopsy-confirmed leukocytoclastic vasculitis and demonstrated that direct immunofluorescence(DIF) detection of IgA positivity was positively correlated with IgAV[31]. In the DIF-positive group, 84% (26/31)met the EULAR classification criteria for IgAV, while 19%(6/31) in the DIF-negative group also fulfilled these criteria(P=0.0001); sensitivity and specificity were 81% and 83%,respectively[31].

Kidney biopsy

Good practice statement Kidney biopsy is recommended for children with IgAV presenting with nephrotic syndrome/nephrotic-range proteinuria, estimated glomerular filtration rate(eGFR)<90 mL/min/1.73 m2, acute nephrotic syndrome(hypertension, hematuria, and/or proteinuria with acute kid-ney injury), or persistent moderate/mild proteinuria.

Persistent moderate proteinuria is defined as: urine pro-tein-to-creatinine ratio (UPCR) in a morning urine sample:1-2 mg/mg or 100-250 mg/mmol, or 24-hour urine protein excretion: 25-50 mg/kg/24 hours, sustained for 2-4 weeks[30, 32, 33].

Persistent mild proteinuria is defined as: UPCR in a morning urine sample: 0.2-0.5 mg/mg or 20-50 mg/mmol,or 24-hour urine protein excretion:>150 mg/24 hours and<25 mg/kg/24 hours, sustained for 12 weeks[30, 32,33].

Summary of the evidence The incidence of kidney involve-ment in IgAV ranges from 20% to 80%. It typically manifests as hematuria and/or proteinuria. Some cases may present as acute nephritic or nephrotic syndrome; severe cases can lead to acute renal failure. Kidney involvement in IgAV is mostly mild or self-limiting, with a risk of developing end-stage kid-ney disease(ESKD) of approximately 2%[34]. A systematic review revealed that only 1.6% of children presenting with iso-lated Hematuria or proteinuria as initial manifestations devel-oped long-term kidney impairment, whereas 19.5% of those with nephrotic or nephrotic syndrome as early-onset features

progressed to long-term kidney damage[35]. Furthermore, chil-dren presenting with early stage nephritic/nephrotic syndrome have a 45%-50% risk of developing long-term kidney dam-age[36]. In addition, among patients presenting with nephritic,nephrotic, or nephrotic/nephrotic syndrome at disease onset,5%-20% progress to ESKD[37, 38]. A meta-analysis demon-strated that reduced eGFR, nephrotic syndrome or nephritic/nephrotic syndrome at disease onset and kidney biopsy and end to $k$ 69%, and other 5%-40% progress to ESKD[37, 38]. A meta-analysis demon-strated that reduced eGFR, nephrotic syndrome or nephritic/nephrotic syndrome at disease onset and kidney biopsy and end to $k$ 69%, and other 5%-40% progress to ESKD[37, 38]. A meta-analysis demon-indicating crescentic glomerulonephritis[grades III-V accord-ing to the International Study of Kidney Disease in Children(ISKDC) classification] are significant risk factors for poor prognosis in IgAV nephritis(IgVAN)[39]. A multicenter clini-cal study in China revealed that children with IgAVN presenting with clinical phenotypes of isolated proteinuria, hematuria and proteinuria, acute nephritis, or nephrotic syndrome predomi-nantly exhibited kidney biopsy findings of ISKDC grade III or higher[40]. Multiple studies have also shown that nephrotic syndrome or nephrotic-range proteinuria at initial diagnosis in children with IgAV is associated with histological severity and poor prognosis[41-43]. Furthermore, reduced eGFR at onset,hypertension, and histological features of tubular atrophy and segmental sclerosis are predictors of poor outcome[44]. Early kidney biopsy may help improve long-term kidney outcomes[45]. Therefore, combining data from the Chinese multicenter survey and in line with the SHARE guidelines and IPNA 2024 guidelines, we established the GPS for kidney biopsy in child-hood IgAV(Table 4)[30, 33, 40]. Of note, while the use of ISKDC is currently recommended, MEST-C scores also appear to be of value, and both ISKDC and MEST-C should be consid-ered for inclusion in the biopsy report[46].

Treatment

Glucocorticoids

Treatment with glucocorticoids

Recommendation and good practice statement Glucocor-ticoids are indicated for IgAV with severe abdominal pain

Table 4 Indications for kidney biopsy in childhood immunoglobulin A vasculitis

Clinical or laboratory evidence(meet any one)

Nephrotic syndrome/nephrotic-range proteinuria

eGFR:<90 mL/min/1.73 mL ${}^{2}$

Acute nephritic syndrome(hypertension, hematuria, and/or proteinuria with acute kidney injury)

Persistent moderate/mild proteinuria

Moderate proteinuria for 2-4 wk: UPC R 1-2 mg/mg or 100-250 mg/mmol or 24-h urine protein excretion is 25-50 mg/kg/24 h [30, 32, 33]Mild proteinuria for 12 wk: UPCR 0.2-0.5 mg/mg or 20-50 mg/mmol or 24-h urine protein excretion> 150 mg/24 h and< 25 mg/kg/24 h [30,32,33]

eGFR estimated glomerular filtration rate,UPCR urine protein-to-creatinine ratio(usually morning urine sample)

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and/or gastrointestinal bleeding(1B), arthritis(2B), IgAVN(GPS), and severe rash(rapidly progressing, hemorrhagic bullous, ulcerative, or necrotic rash), as well as angioedema,orchitis, cerebral vasculitis, pulmonary hemorrhage, and other severe organ involvement or life-threatening vasculitis(1C).

Summary of the evidence Glucocorticoids are effective for gastrointestinal and joint involvement in IgAV. A Finnish multicenter, prospective, randomized, double-blind, pla-cebo-controlled study demonstrated that prednisone(1 mg/kg/day for 2 weeks followed by a 2-week taper) significantly reduced abdominal pain intensity(pain score: 2.5 vs. 4.8,P=0.029) and joint pain severity(pain score: 4.6 vs. 7.3,P=0.030) compared to placebo; it shortened the duration of abdominal pain(1.5 vs. 2.7 days, P=0.028)[47]. Another randomized placebo-controlled study suggested that gluco-corticoids did not reduce the duration of abdominal or joint pain(P=0.8, 0.1), but reported a lower risk of intusscep-tion(0/21 vs. 2/19)[48]. Weiss et al.[49] conducted a sys-tematic review indicating that early glucocorticoid treatment in children with IgAV increases the probability of abdomi-nal pain relief within 24 hours, reduces the risk of intus-sorption and gastrointestinal bleeding, and may decrease the need for surgical intervention. A subsequent large multi-center retrospective case-control study confirmed that early glucocorticoid use significantly lowers the hazard ratio(HR) for abdominal surgery[HR=0.39, 95% confidence interval(CI)=0.17-0.91][50]. In addition, Jauhola et al.[51] confirmed that prednisone treatment in children with IgAV results in a shorter duration of abdominal and joint pain, along with correspondingly lower pain intensity.

For patients presenting with abdominal pain, oral pred-nisone is recommended as the first-line treatment at 1-2 mg/kg/day with a maximum of 60 mg/day for 1-2 weeks, fol-lowed by a 1-2 week tapering period[30, 47]. In pediat-ric patients with severe gastrointestinal symptoms (e.g.,persistent abdominal pain, intestinal bleeding, mesenteric vasculitis, and pancreatitis) who cannot tolerate oral gluco-corticoids, intravenous glucocorticoids should be adminis-tered. Options include methylprednisolone at 5-10 mg/kg/day, dexamethasone at 0.3 mg/kg/day, or hydrocortisone at 5-10 mg/kg per dose, repeatable every 4-8 hours based on clinical need. For critical cases, pulsed intravenous methyl-prednisolone 10-30 mg/kg/day to a maximum of 1000 mg/day for 3 consecutive days is recommended. This regimen may be repeated after 1-2 weeks if necessary[30]. After controlling severe symptoms, patients should transition to oral glucocorticoids with gradual dose reduction. The total treatment course should not be prolonged unnecessarily,with a recommended duration of 2-4 weeks.

Severe rash, angioedema, orchitis, cerebral vasculitis,pulmonary hemorrhage, and other severe organ involvement

or life-threatening vasculitis are also recommended to be treated with standard-dose or pulse-dose glucocorticoid therapy[30,52,53]. For IgAVN, refer to the“IPNA clinical practice recommendations for the diagnosis and manage-ment of children with IgA nephropathy and IgA vasculitis nephritis"[33].

Prophylactic glucocorticoid treatment for recurrent rash in IgAV

Recommendation Prophylactic glucocorticoid treatment to prevent recurrent rash in IgAV is not recommended(1C).

Summary of the evidence Glucocorticoids are ineffective in preventing recurrence of the rash associated with IgAV.A randomized, placebo-controlled 1-year study conducted in Canada in 2004 demonstrated no statistically significant difference in the recurrence of rash between the prednisone prophylaxis and placebo groups(2/21 vs. 4/19, P=0.4)[48]. Subsequently, a multicenter, prospective, randomized,double-blind, placebo-controlled study carried out in Fin-land demonstrated that, 7-10 days after enrollment, the inci-dence of purpura in the prednisone prophylaxis group was lower than that in the placebo group[36%(27/75) vs. 56%(41/73), P=0.021]. Nevertheless, there were no statistically significant differences in cutaneous symptoms at 1 month or in the recurrence rates of purpura after 1 month between the two groups[47].

Prophylactic glucocorticoid treatment to prevent IgAVN development

Recommendation Prophylactic glucocorticoid treatment to prevent the development of IgAVN is not recommended(1B).

Summary of the evidence Before 2004, a number of rel-evant studies demonstrated an inclination toward advocating-ing the utilization of glucocorticoids for the prevention of IgAVN. However, due to the lack of placebo-controlled design, proper blinding procedures and unclear randomiza-tion and allocation concealment methods, all of these studies presented a high risk of bias[54, 55]. Subsequently, several randomized controlled trials have shown that patients who received glucocorticoids at the early stage of the disease developed kidney involvement as frequently as those who did not[47, 48, 56, 57]. A Chinese meta-analysis of these studies showed that the incidence of kidney injury within 6 months after diagnosis of IgAV was 22.2%(42/189) in the glucocorticoid-prophylaxis group and 26.3%(50/190) in the control group[relative risk(RR)=0.67,95% CI=0.17-2.62,P=0.57][58]. The incidence of kidney injury more than 6 months after the diagnosis of IgAV was 10.9%(41/373) in

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the glucocorticoid-prophylaxis group and 12.6%(46/364) in the control group(RR=0.85,95% CI=0.44-1.64,P=0.65)[58]. A Cochrane meta-analysis showed that there was no statistically significant difference in the risk of kidney injury in newly diagnosed children with IgAV between prednisone treatment and placebo or supportive treatment(5 studies,746 children, RR=0.73,95% CI=0.43-1.24, I^2=44\%)[59]. There were also no statistically significant differ-ences in the risk of progression or persistence of kidney injury at 1 month(4 studies, 655 children, RR=0.80, 95%CI=0.34-1.84,I^2=72\%),3 months(4 studies,655 chil-dren, RR=0.83,95% CI=0.46-1.52,I^2=44\%),6 months(3 studies, 379 children, RR=0.51, 95% CI=0.24-1.11,I^2=0), and 12 months(3 studies, 455 children, RR=1.06,95% CI=0.38-2.91,I^2=32\%) thereafter[59]. Based on the available evidence, the use of glucocorticoids for the pre-vention of IgAVN is not recommended in this guideline.

Other immunosuppressants

Recommendation and good practice statement

Mycophenolate mofetil(MMF) is suggested for the treat-ment of severe gastrointestinal involvement in IgAV patients who do not respond to high-dose glucocorticoids or are glucocorticoid dependent(2D). Cyclophosphamide is indicated for pulmonary hemorrhage, severe gastrointes-tinal bleeding that is unresponsive to high-dose glucocortici-coid treatment, cerebrovascular vasculitis, and other severe organ vasculitis in IgAV(2D). For the use of immuno-suppressants in IgAVN, it is recommended to refer to the"IPNA clinical practice recommendations for the diagnosis and management of children with IgA nephropathy and IgA vasculitis nephritis"[33](GPS).

Summary of the evidence

A retrospective observational study reported 18 pediat-ric cases of IgAV featuring refractory gastrointestinal involvement[60]. Among these cases, three had severe gastrointestinal complications, including intussuscep-tion and/or intestinal perforation, and one case presented with massive gastrointestinal bleeding. All patients were administered glucocorticoid therapy at a dose of≥2 mg/kg/day for 3 days. For patients with persistent gastrointes-tinal symptoms or glucocorticoid dependence, defined as experiencing relapse twice during the glucocorticoid dose-reduction process, MMF was added at a dose of 20-30 mg/kg/day orally in two divided doses. In all cases, gastro-intestinal symptoms resolved within a median of 3 days(range: 1-14 days) following treatment. The MMF dose was gradually tapered after 1 month and discontinued

after 3 months. In addition, some case series and case reports have clearly recorded the successful application of MMF in treating gastrointestinal involvement in chil-dren with IgAV[61-63]. Chen et al. conducted a review of 17 reported cases of IgAV complicated by pulmonary hemorrhage[64]. Among the eight children who devel-oped respiratory failure necessitating intubation, all three treated with cyclophosphamide pulse therapy survived.In contrast, two out of the five patients treated solely with glucocorticoids died. Subsequently, Di Pietro et al.expanded the review by incorporating additional cases and likewise discovered that cyclophosphamide therapy might be beneficial for children with IgAV-associated pulmo-nary hemorrhage[65]. Consequently, cyclophosphamide pulse therapy should be considered for IgAV patients with pulmonary hemorrhage, particularly in cases involving respiratory failure. In addition, there are some reports of successful cases in which cyclophosphamide was used to treat IgAV-associated cerebral vasculitis, intracranial hem-orrhage, severe gastrointestinal hemorrhage refractory to corticosteroid therapy, peripheral neuropathy, and cardiac involvement[66-71]. There is also a case report of the effective treatment of IgAV complicated by alveolar hem-orrhage with intravenous cyclosporine A[72]. However,owing to the limited quantity of evidence and its remark-ably low-quality grade, this guideline currently refrains from making recommendations regarding the indications for calcineurin inhibitors in IgAV patients, excluding those with kidney involvement.

Intravenous immunoglobulin

Recommendation

Intravenous immunoglobulin(IVIG) is suggested for the treatment of: severe gastrointestinal involvement in IgAV patients who are either refractory to glucocorticoid ther-apy or have contraindications to their use(2B); hemor-rhagic bullous rash(2D); and cerebral vasculitis(2D).

Summary of the evidence

A meta-analysis shows that, in comparison to the sole use of glucocorticoids, the combination of glucocorticoids and IVIG can reduce the intensity of abdominal pain in pediatric patients[mean differences(MD)=-1.74,95% CI=-2.74 to-0.74,P<0.05],lieve hematochezia(MD=-1.81,95% CI=-2.95 to-0.67,P<0.05), and shorten hospital stay and disease duration(MD=-5.12, 95% CI=-7.42 to-2.82,P<0.05) and the recurrence rate at 6 months is lower than that of using glucocorticoids alone[odds ratio(OR)=0.15,95% CI=0.03-0.73,P<0.05][73]. There are

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also multicenter non-controlled retrospective observational studies and case reports on the successful treatment of severe gastrointestinal involvement in IgAV patients with IVIG who are refractory to glucocorticoid therapy or have con-traindications to their use[74-78]. In addition, a case report has detailed the successful treatment of hemorrhagic bullous rash in IgAV patients with IVIG that was unresponsive to glucocorticoid therapy[79]. Furthermore, case series reports have demonstrated the effective treatment of IgAV-associ-ated cerebral vasculitis including intracranial hemorrhage with a combination of IVIG and glucocorticoids[80, 81].The recommended dose of IVIG is 1 g/kg/day for two con-secutive days, or 2 g/kg/day for 1 day or 400 mg/kg/day for five consecutive days. However, the quality of the evidence supporting the use of IVIG in IgAV treatment, as described above, remains low. Given the potential kidney injury asso-ciated with IVIG[82] and the high cost of treatment, this guideline does not currently issue a strong recommendation for the application of IVIG in the management of IgAV.

Plasmapheresis

Recommendation

The effectiveness of plasmapheresis in treating severe IgAV remains undetermined. Consequently, the routine application of plasmapheresis in the management of severe IgAV is not recommended(1C).

Summary of the evidence

In 1999, Hattori et al. initiated a study involving nine pediatric patients with severe IgAVN[83]. The average age was 8.3±2.9 years at presentation with nephrotic-range proteinuria of 4.9±2.5 g/m2/day and an estimated GFR of 46.5±9.5 mL/min/1.73 m2. These patients under-went a single plasmapheresis treatment protocol: 3 ses-sions per week for 2 weeks, followed by 1 session per week for 6 weeks, amounting to a total of 12 treatments.Following treatment, all patients demonstrated improve-ments in kidney function, a reduction in proteinuria, and the disappearance of rashes and abdominal pain. By the end of the study, four patients achieved complete recov-ery, while two had only microscopic hematuria during the final follow-up(with a follow-up period of 9.6±4.3 years). However, the remaining three patients experi-enced a rebound increase in proteinuria post-treatment.Notably, two of these three patients progressed to ESKD 14.1 and 1.8 years after disease onset, respectively. A systemic review showed 76.3%(29/38) of plasmaphere-sis-treated IgAV patients achieved remission, including 68.4%(26/38) with complete remission and 7.8%(3/38)

with partial remission; 23.6%(9/38) progressed to ESKD[84]. In addition, case reports and case series have docu-mented successful treatment with plasmapheresis for IgAV-associated gastrointestinal involvement, pulmonary hemorrhage, necrotizing purpura, and central nervous system involvement in children[64, 85-87]. A single-center randomized controlled study in China enrolled 60 children with severe IgAVN presenting a nephrotic syn-drome phenotype and an ISKDC grade of IIb or higher at kidney biopsy[88]. Participants were randomly assigned to either a control group(n=30, treated with methyl-prednisolone in combination with cyclophosphamide) or a treatment group(n=30, receiving double-plasma exchange along with methylprednisolone and cyclo-phosphamide). The treatment group achieved complete remission significantly earlier than the control group,with a time to remission of 4.6±0.7 months compared to 5.0±0.5 months(P=0.028). However, when comparing remission further, no statistically significant differences were observed between the two groups after three treat-ment courses[80%(24/30) in the treatment group vs. 63%(19/30) in the control group, P>0.05] or after 6 months[87%(26/30) in the treatment group vs. 77%(23/30) in the control group, P=0.307]. These findings indicate that children with severe IgAVN may benefit from plasma-pheresis during the acute phase, but there is no long-term advantage. It is important to note that this study has limi-tations such as unclear allocation concealment, lack of blinding, and a relatively small sample size; these pose a high risk of bias. High-quality evidence substantiating the efficacy of plasmapheresis in treating severe IgAV in children remains scarce. Plasmapheresis, being an inva-sive medical procedure, exposes patients to significant risks. These include hemodynamic instability, bleeding due to the use of anticoagulants during the process, poten-tial infections from transfusion-transmitted diseases, and exorbitant treatment costs. In light of these multiple risk factors and the absence of strong evidence for efficacy,this guideline does not recommend the routine utilization of plasmapheresis in the management of severe IgAV.

Prognosis

Risk factors affecting the prognosis of IgAV

Recommendation and good practice statement

Short-term prognosis of IgAV is predominantly deter-mined by the degree of gastrointestinal and vital organ involvement(GPS); long-term prognosis is principally influenced by the severity of kidney involvement(1B).

World Journal of Pediatrics

Summary of the evidence

Most patients with IgAV experience a favorable prognosis.This prognosis depends mainly on the severity of gastro-intestinal and kidney involvement. Short-term prognosis is related to the severity of gastrointestinal involvement.For instance, complications such as intussception, intes-tinal perforation, or refractory gastrointestinal bleeding can be life threatening. As for long-term prognosis, this is principally linked to the severity of kidney involvement.A meta-analysis incorporating nine case-control stud-ies, which altogether included 969 children with IgAVN,showed that older age at onset[weighted mean difference(WMD)=1.77,95% CI=0.35-3.18,P=0.014], lower GFR(WMD=-23.93, 95% CI=-33.78 to-14.09,P<0.0001), initial kidney manifestations with nephrotic syndrome(OR=1.74,95% CI=1.12-2.7,P=0.013)or nephrotic-nephrotic syndrome(OR= 4.55, 95% CI=2.89-7.15,P<0.0001) and crescentic nephritis shown by kidney biopsy(ISKDC grade III-V)(OR=3.85, 95%CI=2.37-6.28,P<0.0001) were significant risk factors associated with poor outcomes of IgAVN[39]. In addition,although involvement of organs such as the heart, lungs,brain, eyes, and testes is infrequent, these remains closely correlated with the prognosis of IgAV.

Health education

Food allergy and anti-allergic therapy

Good practice statement

There is no evidence indicating that food allergy is a cause of IgAV and routine application of antihistamines or anti-allergic therapy is not recommended.

Summary of the evidence

Currently, it is believed that IgAV is an immune-mediated vasculitis caused by the deposition of IgA dominant immune complexes[89]. Accumulating evidence from multiple research studies has demonstrated that in children diagnosed with IgAV and IgAVN, there exists a distinct aberration in IgA1 O-linked glycosylation within the circulatory system and various tissues. This abnormality is predominantly mani-fested as a significant elevation in the levels of galactose-deficient IgA1(GD-IgA1)[90,91]. IgA1-IgG antibodies are generated in response to this abnormal IgA1. IgA1 combines with IgA1-IgG to form circulating immune complexes which deposit on the blood vessel walls and within the kidneys;these trigger immune-mediated inflammation[92]. Vascu-litis induced by the deposition of these immune complexes

is classified as a type III hypersensitivity reaction. In con-trast, food allergy encompasses a spectrum of immunological responses, including IgE-mediated type I hypersensitivity,non-IgE-mediated non-type I hypersensitivity, and those with a mixed mechanism. Clinically, food allergy typically pre-sents with a range of manifestations, including but not limited to urticaria, angioemeda, rhinoconjunctivitis, asthma, gastro-intestinal symptoms, and atopic dermatitis[93]. Although a small number of domestic studies in China have focused on the presence of food-specific IgG antibodies in children with IgAV[94], there remains a lack of direct evidence establish-ing a causal link between these IgG antibodies and the devel-opment of IgAV. Furthermore, detection of food-specific IgG antibodies cannot serve as a reliable diagnostic criterion for food allergy[93]. Taking into account this pathogenesis and the absence of high-quality evidence-based data demonstrat-ing efficacy of antihistamines or anti-anaphylactic treatments in IgAV, this guideline does not recommend the routine administration of antihistamines or anti-allergic therapy in pediatric patients with IgAV.

Dietary notes

Recommendation and good practice statement

It is recommended that children with IgAV involving the gastrointestinal tract implement dietary modifications. For those with mild abdominal pain, a bland, low-residue and easily digestible diet is advised. Patients experiencing severe abdominal pain, vomiting, or gastrointestinal bleeding should be temporarily fasted and provided with parenteral nutritional support(GPS). However, prolonged restriction of animal protein dietary intake is not recommended(1D).

Summary of the evidence

There is currently no evidence to suggest that dietary factors are the primary cause of the development or progression of IgAV. Therefore, it is recommended that dietary modifica-tions for pediatric IgAV patients should only be implemented when gastrointestinal involvement is present, to avoid exac-erbating gastrointestinal damage. A non-randomized con-trolled study revealed that, during the 6-month follow-up period, there were no statistically significant differences in the frequency of rash recurrence, relapse rates of IgAV or the incidence of kidney injury between IgAV patients with normal animal protein intake and those on restricted ani-mal protein diets(P>0.05)[95]. In addition, there was no significant difference in daily animal protein consumption between relapsed and non-relapsed IgAV cases(P>0.05)[95]. Therefore, there is a lack of correlation between animal protein dietary intake and the recurrence of IgAV or the exacerbation of rash.

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Conclusions

This expert consensus provides evidence-based recom-mendations for the diagnosis and management of childhood IgAV in China. These guidelines aim to optimize clinical practice and promote greater consistency of care.

Nonetheless, significant controversies remain, particu-larly regarding treatment strategies and drug selection. Glu-cocorticoids, though commonly used as first-line therapy, are associated with notable side effects when used long-term.There is ongoing debate over appropriate dosage and dura-tion based on disease severity. Similarly, the use of immu-nosuppressive agents-such as mycophenolate of mofetil,tacrolimus, and cyclosporine A as steroid-sparing options,lacks robust evidence, resulting in variability across clinical practice. The efficacy of biologics like rituximab needs to be established. Emerging treatments such as targeted-release budesonide(TRF-budesonide) and sodium-glucose cotrans-porter-2 inhibitors(SGLT2i) show promise, but their effec-tiveness and safety require further clinical validation[96].

Given the overall limitations in evidence quality and the scarcity of region-specific data, some recommendations carry lower evidence grades. Clinicians are encouraged to integrate these guidelines into individual patient contexts to formulate personalized treatment plans. Future research should focus on early identification and prevention of kidney involvement, the development of new therapies for severe or refractory IgAV, and high-quality randomized controlled tri-als to evaluate both existing and emerging treatment options.These efforts are essential to improve patient outcomes and refine future clinical practice guidelines for childhood IgAV.

Supplementary Information The online version contains supplemen-tary material available at https://doi.org/10.1007/s12519-025-00974-8.

Acknowledgements The Chinese version of this guideline was pub-lished in the Zhonghua Er Ke Za Zhi in 2023. The authors sincerely appreciate the help provided by the external review experts(Professor Zhu-Wen Yi from the Second Xiangya Hospital of Central South Uni-versity,China and Professor Jian Hu from Tianjin Children's Hospital,China) during formulation of this guideline.

Author contributions SLJ contributed to conceptualization, investiga-tion, methodology, visualization, writing of the original draft, review,and editing.ZQY,LXZ,RZH,NGM,WT,MJH,LYM,ZDM,and LXQ all contributed to writing of the original draft, with contribution from and approval of all co-authors. The steering committee was composed of SHM, WXC, TXM, ZQY, LXZ, RZH, and NGM. The secretariat group consisted of SLJ,ST, and LYZ. SLJ,WY,ST, SYJ and LH per-formed the systematic literature review and quality rating, supervised by CYL. The expert group consisted of TXM, ZW, WT, NGM, RZH,YSR,SLY,HMG,MJZ,YQZ,WLY,HM,ZY,MH,WL,XZ,LXQ,XH,ZDM,WYJ,ZJJ,SHM,and WXC; they completed the online surveys and participated in the subsequent consensus meetings. WXC and SHM contributed to conceptualization, investigation, methodology,project administration, resources, supervision, visualization, writing of the original draft, review, and editing. All authors approved the final version.

Funding This work was supported by the National Key Research and Development Program of China(2021YFC2702004).

Data availability Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.

Declarations

Ethical approval Not required.

Conflict of interest No financial or non-financial benefits have been re-ceived or will be received from any party related directly or indirectly to the subject of this article. Author Hong-Mei Song is a member of the Editorial Board for World Journal of Pediatrics. The paper was handled by the other Editor and has undergone rigorous peer review process. Author Hong-Mei Song was not involved in the journal re-view of, or decisions related to, this manuscript. The authors have no conflict of interest to declare.

References

1. Watts RA, Hatemi G, Burns JC, Mohammad AJ. Global epidemi-ology of vasculitis. Nat Rev Rheumatol. 2022;18:22-34.

2.Piram M, Maldini C, Biscardi S, Suremain ND, Orzechowski C,Georget E,et al.Incidence of IgA vasculitis in children estimated by four-source capture-recapture analysis: a population-based study. Rheumatology(Oxford).2017;56:1358-66.

3.Shim JO, Han K, Park S, Kim GH, Ko JS, Chung JY. Ten-year nationwide population-based survey on the characteristics of children with Henoc, Schonlein purpura in Korea. J Korean Med Sci.2018;33:e174.

4.Yang YH,Hung CF,Hsu CR,Wang LC,Chuang YH,Lin YT,et al. A nationwide survey on epidemiological characteristics of childhood Henoch-Schonlein purpura in Taiwan Province of China. Rheumatology(Oxford).2005;44:618-22.

5.Jennette JC, Falk RJ, Bacon PA, Basu N, Cid MC, Ferrario F,et al.2012 revised international chapel hill consensus conference nomenclature of vasculitides. Arthritis Rheum.2013;65:1-11.

6. The Subspecially Group of Immunology, the Society of Pediatrics,Chinese Medical Association, the Editorial Board of Chinese Journal of Pediatrics. Evidence-based recommendations for the diagnosis and management in the children with Henoch-Schönlein Purpura. Zhonghua Er Ke Za Zhi. 2013;51:502-7(in Chinese).

7.Chen Y,Yang K,Wang X,Kang D,Zhan S,Wang J,et al.Guide-lines for the development and revision of clinical diagnosis and treatment guidelines in China(2022 edition). Zhonghua Yi Xue Za Zhi.2022;102:697-703(in Chinese).

8.Shea BJ, Reeves BC, Wells G, Thuku M, Hamel C, Moran J,et al. AMSTAR 2: a critical appraisal tool for systematic reviews that include randomised or non-randomised studies of healthcare interventions, or both. BMJ.2017;358:j4008.

9.Sterne JAC,Savovic J, Page MJ, Elbers RG, Blencowe NS,Boutron I,et al.RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ.2019;366:14898.

10.Wells GA, Shea BJ, O'Connell D, Robertson J, Peterson J, Welch V, et al. The Newcastle-Ottawa Scale(NOS) for assessing the quality of nonrandomized studies in meta-analyses. Ottawa Hos-pital Research Institute. https://www.ohri.ca/programs/clinical_epidemiology/oxford.asp.

11.Guyatt G, Oxman AD, Akl EA, Kunz R, Vist G, Brozek J, et al.GRADE guidelines: 1. introduction-grade evidence profiles and summary of findings tables. J Clin Epidemiol. 2011;64:383-94.

World Journal of Pediatrics

12. Ozen S, Pistorio A, Iusan SM, Bakkaloglu A, Herlin T, Brik R,et al. EULAR/PRINTO/PRES criteria for Henoch-Schonlein pur-pura, childhood polyarteritis nodata, childhood Wegener granu-lomatosis and childhood Takayas arteritis: Ankara 2008. Part II final classification criteria. Ann Rheum Dis. 2010;69:798-806.

13.Ozen S, Ruperto N, Dillon MJ, Bagga A, Barron K, Davin JC,et al. EULAR/PRReS endorsed consensus criteria for the classifica-tion of childhood vasculitis. Ann Rheum Dis. 2006;65:936-41.

14. Mills JA, Michel BA, Bloch DA, Calabrese LH, Hunder GG,Arend WP,et al.The American college of rheumatology 1990 cri-teria for the classification of Henoch-Schönlein purpura. Arthritis Rheum.1990;33:1114-21.

15. Hunder GG. The use and misuse of classification and diagnostic criteria for complex diseases. Ann Intern Med. 1998;129:417-8.

16. Leung A, Barankin B, Leong KF. Henoch-schönlein purpura in children: an updated review. Curr Pediatr Rev.2020;16:265-76.

17. Saglam MK, Yildrmim S, Ergiven M, Sungur MA. Gastroin-testinal features of pediatric ia vasculitis and their association with renal complications: an observational study. Eur J Pediatr.2025;184:320.

18. Schimi K, Ahamis J, Paoupiot, I Bury F, Magotteaux P. Significance of bowel wall abnormalities at ultrasound in Henoch-Schonlein purpura. J Pediatr Gastroenterol Nutr. 2008;46:48-53.

19. Jeong YK,Ha HK,Yon Chong,G Kim PN, Lee MG,et al.Gastrointestinal involvement in Henoch-Schonlein syndrome: CT findings.AJR JAm Roentgenol. 1997;168:965-8.

20. Chang WL,Yang YH,Lin YT,Chiang BL. Gastrointestinal mani-festations in Henoch-Schonlein purita: a review of 261 patients.Acta Paediatr.2004;93:1427-31.

21. Karadag$G,Tanatar A,Sonmez HE,Cakmak F,Kiyak A,Yavuz S,et al.The clinical spectrum of Henoch-Schonlein purpura in children: a single-center study. Clin Rheumatol. 2019;38:1707-14.

22. Rubino C, Monacelli C, Marrani E, Paci M, Indolfi G, Simonini G,et al. Gastrointestinal involvement in IgA vasculitis: a single-center 11-year study on a cohort of 118 children. Clin Rheumatol.2021;40:5041-6.

23. Guo Q,Hu X,Song C,Ren X,Zhai W,Ding Y,et al.Clinical char-acteristics and associating risk factors of gastrointestinal perfora-tion in children with IgA vasculitis. Ann Med.2021;53:2315-20.

24. Nishiyama R, Nakajima N, Ogihara A, Oota S, Kobayashi S,Yokoyama K, et al. Endoscope images of Schonlein-henoch pura. Purid. Science.2008;77:236-41.

25. Zhang Y, Huang X. Gastrointestinal involvement in Henoch-Schonlein purpura. Scand J Gastroenterol. 2008;43:1038-43.

26. Wang L. Endoscopic features and treatment of Henoch-Schönlein purpura in children. Lin Chuang Er Ke Za Zhi.2017;35:946-8(in Chinese).

27.Han Y,Jin SY,Kim DW,Jeen YM,Kim YH,Choi IH. Endoscopic and microscopic findings of gastrointestinal tract in Henoch-Schönlein purpura: single institute experience with review of literature. Medicine(Baltimore), 2019:98:e15643.

28.Fang Y,Peng K,Zhao H,Chen J.The characteristics of video cap subleos endography in pediatric Hench-Schonlein purpura with gas-trointestinal symptoms. Pediatr Rheumatol Online J.2020;18:84.

29.Louie CY,Gomez AJ,Sibley RK,Bass D,Longacre TA.Histo-logic features of gastrointestinal tract biopsies in IgA vasculitis(Henoch-Schönlein purpura). Am J Surg Pathol. 2018;42:529-33.

30.Ozen S, Marks SD, Brogan P, Groot N, Graeff N, Avcin T, et al.European consensus-based recommendations for diagnosis and treatment of immunoglobulin A vasculitis- the SHARE initiative.Rheumatology(Oxford).2019;58:1607-16.

31.Linskey KR,Kroshinsky D, Mihm MC Jr.,Hoang MP. Immuno-globulin-A-associated small-vessel vasculitis: a 10-year experi-ence at the Massachusetts General Hospital. J Am Acad Dermatol.2012;66:813-22.

32. Yi.Z. Interpretation of the evidence-based guidelines for the diag-nosis and treatment of Henoch-Schönlein purpura nephritis in children. Zhongguo Zhong Xi Yi Jiie He Er Ke Xue. 2010;2:289-91(in Chinese).

35. Vivarelli M, Samuel S, Coppo R, Barratt J, Bonilla-Felix M,Haffner D,et al.IPNA clinical practice recommendations for the diagnosis and management of children with IgA nephropathy and IgA vasculitis nephritis. Pediatr Nephrol. 2025;40:533-69.

34.Goldstein AR, White RH, Akuse R, Chantler C. Long-term follow-up of childhood Henoch-Schönlein nephritis. Lancet.1992;339:280-2.

35. Narchi H. Risk of long term impairment and duration of fol-low up recommended for Henoch-Schonlein purpura with normal or minimal urinary findings: a systematic review. Arch Dis Child.2005;90:916-20.

36. Bogdanovic R. Henoch-Schönlein purpura nephritis in chil-dren: risk factors, prevention and treatment. Acta Paediatr.2009;98:1882-9.

47. Ronkainen J, Nuutinen M, Kosimies O. The adult kidney 24 years after childhood Henoch-Schonlein purpura: a retrospective cohort study.Lancet.2002;360:666-70.

38. Butani L, Morgenstern BZ. Long-term outcome in children after Henoch-Schönlein purpura nephritis. Clin Pediatr(Phila).2007;46:505-11.

39. Shi D, Chan H, Yang X, Zhang G, Yang H, Wang M, et al. Risk factors associated with IgA vasculitis with nephritis(Henoch-Schönne purpura nephritis) progressing to unfavorable out-comes: a meta-analysis. PLoS One. 2019;14:e0223218.

40. Working Group for National Survey on Status and Treatment of Children Renal Disease. Multicenter investigation of diagnosis and treatment of Henoch-Schonlein purpura nephritis in child-hood.Zhonghua Er Za Zhi.2013;51:881-7(in Chinese).

41.Mizerska-Wasiak M, Turczyn A, Cichoi-Kawa K, Maldyk J,Miklaszewska M, Drozd Z, et al. IgA vasculitis nephritis clini-cal course and kidney biopsy- national study in children. Pediatr Rheumatol Online J. 2021;19:150.

42. Clavé S, Sordet M, Tsimaratos M, Decramer S, Fila M, Guigonis V, et al. Association of kidney biopsy findings with short- and medium-term outcomes in children with moderate-to-severe IgA vasculitis nephritis. Eur J Pediatr. 2021;180:3209-18.

43.Xi L, Sun Y, Chen Y, Yang X, Su H, Ren X. Clinicopathological features and prognosis of IgA vasculitis nephritis with nephrotic-range proteinuria in children. Pediatr Nephrol. 2024;39:3241-50.

44.Rohner K, Marlais M, Ahn YH, Ali A, Alsharief A, Novak AB, et al. Outcome of immunosuppression in children with IgA vasculitis-related nephritis. Nephrol Dial Transplant.2024;39:1299-309.

45.Avramescu M, Lahoche A, Hogan J, Salomon R, Rousse G,Bacchetta J, et al. To biopsy or not to biopsy: Henoch-Schönlein nephritis in children, a 5-year follow-up study. Pediatr Nephrol.2022;37:147-52.

46. Barbour SJ, Coppo R, Er L, Pillebout E, Russo ML, Alpers CE,et al.Histologic and clinical factors associated with kidney outcomes in IgA vasculitis nephritis. Clin J Am Soc Nephrol.2024;19:438-51.

47. Ronkainen J, Kosimies O, Ala-Houhala M, Antikainen M, Mer-enies J, Rajantie J, et al. Early prednisone therapy in Henoch-Schönlein purpura: a randomized, double-blind, placebo-con-trolled trial.J Pediatr.2006;149:241-7.

48. Huber AM, King J, McLaine P, Klassen T, Pothos M. A rand-onized, placebo-controlled trial of prednisone in early Henoch Schonnol IP. ReshCTN85109383]. BMC Med. 2004;2:7.

49. Weiss PF, Feinstein JA, Luan X, Burnham JM, Feudtner C. Effects of corticosteroid on Henoch- Henoch-Schönlein purpura: a systematic review. Pediatrics.2007;120:1079-87.

World Journal of Pediatrics

50. Weiss PF, Klink AJ, Localio R, Hall M, Hexem K, Burnham JM, et al. Corticosteroids may improve and clinical outcomes dur-ing hospitalization for Henoch-schönlein purpera. Pediatrics.2010;126:674-81.

51. Jauhola O, Ronkainen J, Koskimies O, Ala-Houhala M, Ariko-ski P,Holtta T,et al. Clinical course of extrarenal symptoms in Henoch-Schonlein purpura: a 6-month prospective study. Arch Dis Child.2010;95:871-6.

52. Gulati G, Siv J, Ware AE. Bullus skin lesions in an adult male:a diagnostic dilemma. Am J Case Rep. 2015;16:215-9.

53. Nothhaft M. Klepper J, Kneiz H, Meyer T, Hamm H, Morbach H. Hemorrhagic bullous Henoch-Schönlein purpura: case report and review of the literature. Front Pediatr. 2019;6:413.

54. Molica F, Li Volti S, Garozzo R, Russo G. Effectiveness of early prednisone treatment in preventing the development of nephropa-tively in anaphylactoid purpura. Eur J Pediatr. 1992;151:140-4.

55. Huang WY, Chen RH, Wu W, Ding GX, Huang SM. Study and prednisone on preventing renal involvement of Hench-Schönlein purpura in children. Nanjing Yi Ke Da Xue Xue Bao Zi Ran Ke Xue Ban.2002;22:214-6(in Chinese).

56.Jauola O, Ronkainen J, Koskimies O, Ala-Houala M, Arikoski P, Holtta T, et al. Outcome of Henoch-Schönlein purpura 8 years after treatment with a placebo or prednisone at disease onset.Pediatn Nephrol. 2012;27:933-9.

57. Dudley J, Smith G, Llewelyn-Edwards A, Bayliss K, Pike K,Tizard J, Randomised, double-blind, placebo-controlled trial to determine whether steroids reduce the incidence and severity of nephropathy in Henoch-Schonlein purpura(HSP). Arch Dis Child.2013;98:756-63.

58. Zhang Y,Xia ZK,Gao YF,Fan ZM,Gao CL,He X,et al.Effect of corticosteroid on preventing renal impairment in children with Hench-Schönlein purpura: a meta-analysis of randomized con-trolled trials. Zhongguo Xun Zheng Er Ke Za Zhi. 2012;7:349-53(in Chinese).

59. Hahn D,Hodson EM,Craig JC.Interventions for preventing and treating kidney disease in IgA vasculitis. Cochrane Database Syst Rev.2023;2:CD005128.

60. Wang H,Zhang B,Li S,Ou R,Liu Y,Tan W.Clinical out-come in pediatric refractory gastrointestinal Henoch-schönlein purpura treated with mycophenolate mofetil. Eur J Pediatr.2020;179:1361-6.

61.Nikibakhsh AA, Mahmoodzadeh H, Karamyyar M, Hejazi S, Noroozi M, Macooie AA, et al. Treatment of com-plicated henoch-schonlein purpura by mycophenolate mofetil: a retrospective case series report. Int J Rheumatol.2010;2010:254316.

62. Gicchino MF, Iafusco D, Marrapodi MM, Melone R, Cuomo G,Zanfardino A,et al. Gastrointestinal Henoch-Schönlein purpura successfully treated with Mycophenolate Mefotii: description of 2 case reports. Medicine(Baltimore).2021;100:e24093.

63. Chou T.,Louissant RS.A.,Gurkan S, Chefitz D, Weller AS,et al. Successful treatment of Henoch-Schonlein purpura with recurrent gastrointestinal involvement with mycophenolate mofetil: a brief report. Clin Pediatr(Phila). 2015;54:900-3.

64.Chen SY,Chang KC,Yu MC,Asueh S,Ou LS. Pulmonary hemorrhage associated with Henoch-Schönlein purpura in pedi-atric patients: case report and review of the literature. Semin Arthritis Rheum.2011;41:305-12.

Di Pietro GM, Castellazzi ML, Mastrangelo o, Montini G,Marchisio P, Tagliabue C. Henoch-Schonlein purpura in chil-dren: not only kidney but also lung. Pediatr Rheumatol Online J.2019;17:75.

6.CAkaboy M,Fidan K,Kandur Y,Lsiyel E,Buyikkaragoz B,Bakkaloglu Ezgü SA. Cerebral vasculitis in Henoch-Schönlein purpura: a case report. Arch Rheumatol. 2017;32:264-7.

67. Karamadoukis L, Ludeman L, Williams AJ. Henoch-schönlein purpura with intracerebral haemorrhage in an adult patient: a case report.J Med Case Rep.2008;2:200.

68. Ulcau U,Ece A,Sen V,Yel S,Tan L,Karabel D. Management of intestinal bleeding with single-dose cyclophosphamide in Henoch-Schönlein purpura. Pediatr Int. 2015;57:498-500.

9. Aydn F, Kurt T, Unliü E, Tekin ZE, Cikelel E, Acar B C. Ster-oid-resistant peripheral neuropathy in a child: a rare finding in immunoglobulin A vasculitis. Turk J Pediatr. 2022;64:576-9.

70. Yulmaz N, Yuksel S, Becerir T, Girisgen L, Ufuk F, Gürses D.Myocarditis and intracardiac thrombus due to Henoch-Schön-lin der purpina: case report and literature review. Clin Rheumatol.2021;40:1635-44.

11. Lutz HH, Ackermann T, Krombach GA, Grone HJ, Rauen T,Flogee J, et al. Henoc-Schönlein purpura complicated by car-diac involvement: case report and review of the literature. Am J Kidney Dis.2009;54:e9-15.

72. Matsubayashi R, Matsubayashi T, Fujita N, Yokota T, Ohro Y, Enoki H. Pulmonary hemorrhage associated with Henoch-Schonlein purpura in a child. Clin Rheumatol. 2008;27:803-5.

73.Zheng Q,Zhang M,Gao X,Wan C,Huang Y. Meta-analysis on efficacy of gammaculbulin combined with glucocorticoid and glucocorticoid alone in the treatment of children with abdominal Henchol-Schönlein purpura. Er Ke Yao Xue Za Zhi.2022;28:34-8(in Chinese).

74. Cheraqoui B, Chausset A, Stephan JL, Merlin E. Intravenous immunoglobulins for severe gastrointestinal involvement in pediatric Henoch-Schönlein purpura: a French retrospective study. Arch Pediatr. 2016;23:584-90.

75. Morotti F, Bracciolini G, Caorsi R, Cattaneo L, Gattorno M,Ravelli A, et al. Intravenous immunoglobulin for corticosteroid-8id-resistant intestinal Henoch-Schönlein purpura: worth a con-trolled trial against corticosteroids? Rheumatology(Oxford).2021;60:3868-71.

76. Naifa G, Totidis G, Alexiadou S, Kolona C, Mantadakis E.Intravenous y globulin for intractable abdominal pain due to IgA Vasculitis. Case Rep Pediatr. 2020;2020:8867621.

77. Fagbemi AA, Torrente F, Hilson AJ, Thomason MA, Heu-schkel RB, Murch SH. Massive gastrointestinal haemorrhage in isolated intestinal Henoch-Schönlein purpura with response to intravenous immunoglobulin infusion. Eur J Pediatr.2007;166:915-9.

78. Oner N, Celikel E, Tekin ZE, Gungörer V, Kurt T, Tekgoz PN,et al. Intravenous immunoglobulin therapy in immunoglobulin A vasculitis with gastrointestinal tract involvement. Clin Exp Med.2023;23:1773-82.

79.Mauro A, Mauro S, Rega R, Martemucci L, Sottile R. Successful treatment of hemorrhagic bullous Henoch-Schönlein purpura with intravenous immunoglobulins. Pediatr Dermatol.2019;36:e34-6.

80.De Maddi F, Dinardo R, Buonocore MC, Dinardo M, Bartolomei B, Donato R. Intravenous immunoglobulin in Henoch-Schönlein purpura complicated by cerebral hemorrhage. Rheumatol Int.2013;33:2451-3.

81. He SW, Chen F, Hu Y,Zhen XF. Henoch-Schönlein purpura with central nervous system dysfunction in 18 children. Zhonghua Shi Yong Er Ke Lin Chuang Za Zhi. 2013;28:1821-4(in Chinese).

82. Orbach H,Tishler M, Shoenfeld Y. Intravenous immunoglobu-lin and the kidney-a two-edged sword. Semin Arthritis Rheum.2004;34:593-601.

World Journal of Pediatrics

83. Hattori M, Ito K, Konomoto T, Yoshioka T, Khono M. Plas-mapheresis as the sole therapy for rapidly progressive Henoch-Schönlein purpura nephritis in children. Am J Kidney Dis.1999;33:427-33.

84. Nguyen B, Acharya C, Tangpanithandee S, Miao J, Krisanapan P, Thongprayon C, et al. Efficacy and safety of plasma exchange as an adjunctive therapy for rapidly progressive IgA nephropathy and Henoch-Schönlein purpura nephritis: a systematic review. Int J Mol Sci. 2023;24:3977.

85. Basaran O, Cakar N, Uncu N, Cikelel BA, Kara A, Cayci FS.Plasma exchange therapy for severe gastrointestinal involvement of Henoch Schonlein purpura in children. Clin Exp Rheumatol.2015;33(2 Suppl 89):S176-80.

86.Acar B,Arikan FI,Alioglu B,Oner N,Darral Y. Successful treat-ment of gastrointestinal involvement in Henoch-Schönlein purpura with plasmapheresis. Pediatr Nephrol. 2008;23:2103.

87. Eun SH, Kim SJ, Cho DS, Chung GH, Lee DY, Hwang PH.Cerebral vasculitis in Henoch-Schönlein purpura: MRI and MRA findings, treated with plasmapheresis alone. Pediatr Int.2003;45:484-7.

88. Liu N, Ma ZZ, Yan HF, Li Q, Lyu XQ, Kang WL, et al. Clinical effect of double filtration plasmapheresis combined with gluco-corticoid and immunosuppressant in treatment of children with severe Henoch-Schönlein purpura nephritis. Zhongguo Dang Dai Er Ke Za Zhi.2019;21:955-9(in Chinese).

89. Xu L, Li Y, Wu X. IgA vasculitis update: epidemiology, patho-genesis, and biomarkers. Front Immunol. 2022;13:921864.

90.Saulsbury FT. Alterations in the O-linked glycosylation of IgA1 in children with Henoch-Schönlein purpura. J Rheumatol.1997;24:2246-9.

91. Allen AC, Willis FR, Beattie TJ, Feehally J. Abnormal IgA glyco-sylation in Henoch-Schonlein purpura restricted to patients with clinical nephritis. Nephrol Dial Transplant. 1998;13:930-4.

92.Kiryluk K, Moldoveanu Z, Sanders JT, Eison TM, Suzuki H,Julian BA, et al. Aberrant glycosylation of IgA1 is inherited in both pediatric IgA nephropathy and Henoch-Schönlein purpura nephritis. Kidney Int. 2011;80:79-87.

9. Zhou W, Zhao J, Chen H, Hong J, Hong L, Li H, et al. Evidence-based guidelines for food allergy of children in China. Zhonghua Shi Yong Er Ke Lin Chuang Za Zhi. 2022;37:572-83(in Chinese).

94.Zhang JJ, Shi PP, Zhang LG, Lu FX, Zhao LL. Correlation between food intolerance and Henoch-Schonlein purpura in children. Zhon-ghua Shen Zang Bing Za Zhi. 2011;27:337-40(in Chinese).

Yin DH,Guo YL,Cao TT, Pan CL,Zhao GJ,Hu Y,et al.Effect of animal protein diet on the prognosis of children with Henoch-Schönlein purpura. Zhongguo Dang Dai Er Ke Za Zhi.2021;23:927-32(in Chinese).

96. Castaneda S, Quiroga-Colina P,Floranes P, Uriarte-Ecenarro M,Valero-Martinez C, Vicente-Rabaneda EF,et al.IgA vasculitis(Henoch-schonlein purpura): an update on treatment. J Clin Med.2024;13:6621.

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