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Effect of different protein diet on the prognosis of children with Henoch-Schönlein Purpura

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Introduction The aim of this study was to explore the association of different protein diet with the recurrence/recurrent rash of Henoch-Schönlein purpura (HSP) and to analyze the potential risk factors for recurrence of HSP. Methods A total of 72 children with HSP treated in Beijing Children's Hospital from January to June 2021 were collected retrospectively. According to the different protein diets, the children were divided into an animal protein group with 32 children and a plant protein group with 40 children. The clinical data of the children were collected, including general data, times of skin rash recurrence, the incidence of HSP recurrence, and the incidence of renal lesions. The daily protein intake of the children was recorded by questionnaire and followed up for 8 weeks after discharge. Results There were no statistical difference between animal protein group and plant protein group in times of skin rash recurrence, the incidence of HSP recurrence, and the incidence of renal lesions of children (p > 0.05). However, the protein intake of animal protein group was significantly higher than that of plant protein group (p < 0.05), which did not affect the recurrence of HSP (p > 0.05). In addition, respiratory infection at the beginning of the disease was potential risk factors for the recurrence of HSP in children (p < 0.05). Conclusions There is no significant association between animal or plant protein diet and the recurrence of HSP or skin rash. Timely avoidance of infection after cure may help to reduce the recurrence rate of HSP in children.
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Effect of different protein diet on the prognosis of
children with Henoch-Schönlein Purpura
HUI LI
Beijing Children's Hospital Capital Medical University
KAI FENG ( 20170941087@bucm.edu.cn )
Beijing Children's Hospital Capital Medical University https://orcid.org/0000-0003-2063-9760
Research Article
Keywords: Henoch-Schönlein Purpura, children, animal protein, plant protein, diet, recurrence
Posted Date: October 28th, 2022
DOI: https://doi.org/10.21203/rs.3.rs-2197720/v1
License: This work is licensed under a Creative Commons Attribution 4.0 International License. 
Read Full License
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Abstract
Introduction
The aim of this study was to explore the association of different protein diet with the recurrence/recurrent
rash of Henoch-Schönlein purpura (HSP) and to analyze the potential risk factors for recurrence of HSP.
Methods
A total of 72 children with HSP treated in Beijing Children's Hospital from January to June 2021 were
collected retrospectively. According to the different protein diets, the children were divided into an animal
protein group with 32 children and a plant protein group with 40 children. The clinical data of the children
were collected, including general data, times of skin rash recurrence, the incidence of HSP recurrence, and
the incidence of renal lesions. The daily protein intake of the children was recorded by questionnaire and
followed up for 8 weeks after discharge.
Results
There were no statistical difference between animal protein group and plant protein group in times of skin
rash recurrence, the incidence of HSP recurrence, and the incidence of renal lesions of children (p > 0.05).
However, the protein intake of animal protein group was signicantly higher than that of plant protein
group (p < 0.05), which did not affect the recurrence of HSP (p > 0.05). In addition, respiratory infection at
the beginning of the disease was potential risk factors for the recurrence of HSP in children (p < 0.05).
Conclusions
There is no signicant association between animal or plant protein diet and the recurrence of HSP or skin
rash. Timely avoidance of infection after cure may help to reduce the recurrence rate of HSP in children.
Background
Henoch-Schönlein purpura (HSP), also known as Anaphylactoid purpura, is a vasculitis syndrome
characterized by systemic vasculitis. Clinical features include non-thrombocytopenic skin rash,
accompanied by joint swelling and pain, abdominal pain, hematochezia, and kidney injury, which are
prone to recurrent attack.1 Recently, with the change of diet structure and environment, the incidence of
HSP in childhood is on the rise.2 Some studies have pointed out that children with HSP need to prohibit
protein diet intake for a long time during their illness to reduce the recurrence.3 However, HSP is mainly
found in school age children, long-term fasting of animal protein will seriously affect children's health,
reduce immunity, increase the chance of infection, and lead to the recurrence of HSP.4 At present, there is
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no unied and standardized diet management for HSP. Therefore, our paper through the retrospective
research method to collect the intake of plant protein and animal protein in children with HSP on
conventional diet restriction scheme, and provides clinical basis for the diet management of children with
HSP.
Methods
Subjects
From January to June 2021, 72 children with HSP hospitalized in the department of Traditional Chinese
Medicine, Beijing Children's Hospital were enrolled. All children were diagnosed according to the HSP
diagnostic criteria formulated by the European anti rheumatism alliance and the European Society of
pediatric rheumatology in 2006.5
These patients were divided into the following two groups by whether take animal protein diet: animal
protein group (32 patients received animal protein diet programs) and plant protein group (40 patients
received plant protein diet programs). Vitamin C were used for intravenous drip injection, and sodium
hydrocortisone succinate (2 mg/kg/day, 2 times/day) were given according to whether the patients had
abdominal pain and the amount was gradually reduced after the symptoms disappeared. The drug was
stopped after 7–10 days, and the symptoms were treated. At the same time, diet was restricted or guide
dietary was followed. Children of the two groups were followed up and dietary survey by telephone every
3 days was performed at 8 weeks after discharge.
Conventional restricted diet programs
All patients in two groups received the following conventional diet restriction scheme in this study:
1. It was forbidden to eat raw, cold, hard and other stimulating food or drinks. Three meals a day included
porridge, noodles, steamed bread, rice and some salt and oil. Patients were advised to drink warm boiled
water.
2. A small amount of one kind of vegetable was added rst after discharge, and no new rash appeared 3
days later, then another vegetable was added. Generally, the vegetables were added in the following
orders, such as green vegetable, cabbage, tomato, potato, cucumber, and reduce the consumption of
vegetables that are dicult to chew, such as broccoli and cauliower.
3. A small amount of fruits can also be added in the following order such as banana, apple, watermelon,
peach, and reduce the consumption of mango, peach and other allergic fruits. The interval between the
two kinds of fruits must be > 3 days.
4. In the process of adding food, when skin rash, abdominal pain and other repeated symptoms occurred,
it was necessary to stop eating the added food and restart after the situation was considered to be stable.
Plant protein group
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1. Bean products were added rst after discharge, such as soy-bean milk, tofu, gluten, etc. And no new
rash appeared 3 days later, another bean product was added.
2. Animal protein is prohibited during follow-up observation, like sh, shrimp, meat, eggs, milk, etc.
Animal protein group
1. The meats were added rst after discharge in the following orders, and no new rash appeared 5 days
later, then another meat was added. Generally, the meats were added in the following orders: lean pork,
chicken, ducks, and reduce the consumption of sh, shrimp, beef and mutton.
2. After adding meats without new rash for 2 weeks, a small amount of eggs could be added. After
adding eggs without repeated rash for 1 week, a small amount of milk could be added in the food. 3.
Bean products rich in plant protein is prohibited during follow-up observation.
Record clinical data
The clinical data of the children were collected, including general data, times of skin rash recurrence, the
incidence of HSP recurrence, and the incidence of renal lesions.6 The daily protein intake of the children
was recorded by questionnaireand followed up for 8 weeks after discharge.
1. Repeated rashes: purpura-like rashes appeared again in batches after the previous rashes were
eliminated and cleared.
2. Recurrence of HSP: the children diagnosed as HSP with purpura-like rashes again at least 1 month
after the disappearance of the rash; hematuria and/or proteinuria occurred during follow-up. 3. No clinical
symptoms of HSP after cure to the end of the follow-up period were determined as non-recurrence.
Statistical analysis
SPSS 26.0 was used for data statistical analysis in this study. The measurement data conforming to
normal distribution were expressed as mean ± SD, the comparison between the two groups adopts two
sample t-test. The measurement data that do not conform to the normal distribution are represented by
the median (interquartile interval) [M (P25, p75)] and Mann Whitney U test is used for the comparison
between the two groups. Counting data were expressed as n (%), and the comparison between the two
groups were examined by χ2 test.
P
value < 0.05 was considered to be statistical signicant.
Results
Comparison of general clinical information of children
There were no signicant differences in age, gender and medical history among the two groups (
p
 > 0.05)
(Table 1).
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Table 1
Comparison of general clinical features of children with HSP
Age
(years)
Gender
(male/female)
Medical history(months)
Plant protein group 8.05 ± 1.77 24/16 3.75 ± 0.87
Animal protein group 8.13 ± 1.91 18/14 3.78 ± 0.79
Different dietary guidance on protein intake level and major clinic features of children.
Eight weeks after admission, times of skin rash recurrence, the incidence of HSP recurrence, and the
incidence of renal lesions of children in the animal protein group were reaching the levels of the plant
protein group with no statistical difference (
p
 > 0.05). Moreover, the protein intake of animal protein group
was signicantly higher than that of plant protein group (
p
 < 0.05) (Table 2).
Table 2
Comparison of dietary guidance on protein intake level and major clinic features of children with HSP
n the number of repeat
[M(
P
25,
P
75)] recurrence
[n(%)] renal
lesions
[n(%)]
protein intake
level(g/d)
Plant protein
group 40 2.0(1.0,3.0) 12(30) 8(20) 12.80 ± 3.28
Animal protein
group 32 2.0(1.3,3.0) 8(25) 8(25) 18.38 ± 3.64
U/χ2/t 605.5 0.222 0.638 6.827
P
0.686 0.257 0.612 < 0.01
The potential risk factors lead to recurrence of HSP.
According to whether the disease recurred, all children were divided into recurrence group and non-
recurrence group. Compared with non-recurrence group, the age, gender, repeated rashes, family history,
glucocorticoid and initial concomitant symptoms included gastrointestinal symptoms, joint swelling and
pain, hematuria or proteinuria and protein intake level (total, animal or plant) were no signicant
differences among two groups (
p
 > 0.05). However, respiratory infection at the beginning of the disease in
the recurrence group was signicantly higher than that of children in another group (
p
 < 0.05). In addition,
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we also found a fascinating phenomenon that the medical history of non-recurrence group was longer
than that of recurrence group (
p
 < 0.05) (Table 3).
Table 3
The potential risk factors lead to recurrence of HSP
recurrence group(n=
20) non-recurrence group(n=
52) t/χ2
P
Age(years)
8 years
 8 years
5
15
19
33
0.865 0.352
Gender
male
female
10
10
32
20
0.791 0.374
Medical history(months)
3 months
 3 months
8
12
38
14
6.850 0.009
Initial concomitant
symptoms
gastrointestinal symptoms
joint swelling and pain
hematuria or proteinuria
respiratory infections
12
4
7
13
34
8
9
8
0.182
0.014
1.692
17.211
0.670
0.906
0.193
< 
0.01
Repeated rashes 3 times 9 18 0.665 0.415
Family history 4 4 1.144 0.285
Glucocorticoid 7 17 0.3035 0.852
Protein intake level
Total protein intake level
Animal protein
Plant protein
8
12
24
28
0.086
-0.332
0.988
0.932
0.742
0.330
Discussion
HSP, now called immunoglobulin A vasculitis, is a systemic, immune complex-mediated, small-vessel
leukocytoclastic vasculitis characterized by nonthrombocytopenic palpable purpura, arthritis, and
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abdominal pain and spontaneously resolves in 94% of children and 89% of adults.7 The exact etiology of
HSP is still largely unknown. At present, the known possible etiologies include infection, genetics,
vaccination, environmental pollution and so on.8 At present, there is no unied and standardized diet
management for HSP. Some studies have pointed out that food allergy, in particular allogeneic protein,
were the main etiological factors.9,10 However, fasting protein for a long time will seriously affect the
health of children, reduce immunity, increase the chance of infection, and lead to the recurrence of HSP.11
Compared with plant protein, animal protein is mainly composed of casein, with a complete range of
essential amino acids and can be better utilized and absorbed by human body.
The HSP children are mainly between the ages of 5 and 15 years and the mean age is 5 to 6 years.10,12 In
our investigation, the children ranged from 4 to 15 years, and the mean age was 8.08 ± 1.82 years, 88.9%
were < 10 years old. Children at this stage were in a critical period of growth and development. If the
protein supply of children with HSP were insucient for a long time, which can lead to anorexia, weight
loss and even malnutrition.13 Moreover, gastrointestinal tract, the largest gathering place of human
immune system, participates in human immune response.14 Fasting protein for a long time may break
the normal immune response of gastrointestinal tract and affect the prognosis of HSP. Our study shows
that the protein intake of animal protein group was signicantly higher than that of plant protein group (p 
< 0.05), but times of skin rash recurrence, the incidence of HSP recurrence, and the incidence of renal
lesions of children between two group with no statistical difference in (p > 0.05). It suggests that there is
no signicant correlation between different protein intake and recurrent rash, recurrence and renal
damage. In addition, we also found that different kinds of protein intake were not associated with disease
recurrence (p > 0.05), but it is contrary to some research results.15,16
Our study also showed that the recurrence rate of HSP in children was 27.8% (20/72), suggesting that the
recurrence rate of HSP in children is high. Therefore, it is necessary to explore the risk factors of HSP
recurrence in children. Through the analysis of potential risk factors, it was found that the proportion of
respiratory infection in the recurrence group were higher than those in the non-recurrence group, which
was consistent with the previous research results.17,18 Other recent study showed that potential infections
occurred in 50.9%, in which streptococcus was the most common infectious agent (17.1%).19 It is
speculated that respiratory infection produce a variety of antigenic stimulus might cause the elevation of
circulating immunoglobulin A and complement activation, leading to inammation of small vessels in
different target-organs and cutaneous leukocytoclastic vasculitis. Symptomatic treatment plus adjunctive
anti-infectious agents could signicantly improve the remission rate of HSP in the infectious cases,
especially help relieve cutaneous rash. HSP is an immune complex-mediated vasculitis and
spontaneously resolves in 94% of children.7 Our research results, the medical history of non-recurrence
group was longer than that of recurrence group, further verify this point. We also found that the repeated
rashes  3 times rate of HSP in recurrence group was 45% (9/20), which is higher than non-recurrence
group [34.7%(18/52) ]. Although the common complications of HSP like repeated rashes, arthritis,
abdominal pain or renal damage effect the prognosis of the disease, but it is not a risk factor for the
recurrence of HSP.
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Conclusions
There was no signicant correlation between long-term fasting animal protein and repeated rash or
disease recurrence in children with HSP. It is suggested that children with HSP should have a balanced
diet, but should not limit their intake of animal protein for a long time. Strengthening the monitoring of
relevant indicators of respiratory infection in children and giving intervention as soon as possible will
reduce the recurrence of HSP. However, the medical community has not yet reached a consensus on the
dietary management of children's HSP, and the number of existing randomized controlled studies is small,
so it needs to be supported by multi center and large sample randomized controlled studies in the future.
List Of Abbreviations
HSP
Henoch-Schönlein purpura
Declarations
Ethics approval and consent to participate
Medical ethics committee of Beijing Children's Hospital [2021]-E-227-R.Written consent was obtained
from the parents of the participant.
Consent for publication
Written informed consent to publish this information was obtained from the patient’s parents.
Availability of data and materials
Data sharing is not applicable to this article as no datasets were generated or analysed during the current
study.
Competing Interest
No conicts of interest have been declared.
Funding
This study was funded by the Key Disciplines of Traditional Chinese Medicine for Children with Spleen
and Stomach Diseases (No: JZZII8).
Author Contributions
LH: Conceptualization and methodology, formal analysis, investigation, writing (original draft, review and
editing), project administration.
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FK: Conceptualization and methodology, investigation, writing (original draft, review and editing),
supervision and project administration. All authors critically revised the manuscript, agree to be fully
accountable for ensuring the integrity and accuracy of the work, and read and approved the nal
manuscript.
Acknowledgments
The study is not applicable.
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Objective: To explore the reasonable and effective enteral nutrition regimen for children with abdominal Henoch-Schönlein purpura (HSP). Methods: A retrospective analysis was performed on the medical data of children with abdominal HSP who were hospitalized from August 2013 to August 2018. According to the starting time of enteral nutrition after abdominal pain relief, the children were divided into three groups: < 24 hours (n=68), 24-48 hours (n=64), and 48-72 hours (n=60). According to the type of enteral nutrition, they were divided into another three groups:amino acid-based formula (n=53), extensively hydrolyzed lactoprotein formula (n=67), and normal diet (n=72). The recurrence rate of clinical symptoms and degree of satisfaction among family members were compared between groups. Based on the retrospective analysis, 166 children with abdominal HSP were enrolled in a prospective study. They were given extensively hydrolyzed lactoprotein formula after abdominal pain relief. According to the feeding time after abdominal pain relief, they were divided into three groups: < 24 hours (n=52), 24-48 hours (n=59), and 48-72 hours (n=55). The three groups were compared in terms of the recurrence rates of abdominal pain, rash, and hematochezia, the rate of use of parenteral nutrition and intravenous steroids, and the incidence rate of weight loss at discharge. Results: The retrospective analysis showed that the children who were given extensively hydrolyzed lactoprotein formula for enteral nutrition at 24-48 hours after abdominal pain relief had a lower recurrence rate of clinical symptoms and the highest degree of satisfaction among their family members (P < 0.0167). The prospective study showed that the children who were given extensively hydrolyzed lactoprotein formula for enteral nutrition at 24-48 hours after abdominal pain relief had lower recurrence rates of rash and abdominal pain, a lower rate of use of parenteral nutrition, and a lower incidence rate of weight loss at discharge (P < 0.05). Conclusions: It is reasonable and effective to start the feeding with extensively hydrolyzed lactoprotein formula at 24-48 hours after abdominal pain relief in children with abdominal HSP.
Article
Henoch-Schönlein purpura, now called immunoglobulin A (IgA) vasculitis, is a systemic, immune complex-mediated, small-vessel leukocytoclastic vasculitis characterized by nonthrombocytopenic palpable purpura, arthritis, and abdominal pain. It is the most common vasculitis in children but can also occur in adults. Diagnostic testing is required only to exclude other etiologies of purpura, to identify renal involvement, and, if indicated, to determine its extent with biopsy. Imaging or endoscopy may be needed to assess organ complications. IgA vasculitis spontaneously resolves in 94% of children and 89% of adults, making supportive treatment the primary management strategy. However, a subset of patients experience renal involvement that can persist and relapse years later. Additional complications can include gastrointestinal bleeding, orchitis, and central nervous system involvement. Systematic reviews have shown that steroids do not prevent complications and should not be used prophylactically. However, randomized trials have demonstrated success with high-dose steroids, cyclosporine, and mycophenolate in treating glomerulonephritis and other complications. Long-term prognosis depends on the extent of renal involvement. Six months of follow-up is prudent to assess for disease relapse or remission.
Article
Objectives: Henoch Schönlein Purpura (HSP) is the most common systemic vasculitis in childhood. We aimed to evaluate the clinical features, seasonal variation, treatment outcomes and the possible predicting factors related to outcome among a large cohort of pediatric HSP patients. Methods: We conducted a medical record review study between July 2016 and January 2019 and evaluated the clinical manifestations and potential risk factors for severe gastrointestinal (GI) involvement, biopsy-proven nephritis and relapses. Results: The study included 420 HSP patients, of which the mean age at diagnosis was 7.68 ± 3.15 years. Clinical manifestations were arthralgia and/or arthritis (n = 244,58.1%), abdominal pain (n = 235,56%), subcutaneous edema (n = 163,38.8%), and renal involvement (n = 125, 29.8%). Disease recurred for at least once, in 69 (16.4%) patients and colchicine treatment yielded a favorable response in 11 of 12 relapsing patients, who did not respond to ibuprofen or steroids. Frequencies of renal involvement and biopsy-proven nephritis were higher in patients with severe GI involvement. Besides, patients with biopsy-proven nephritis had higher rates of abdominal pain, intussusception, severe GI involvement, and systemic steroid administration. Conclusions: We speculate that renal involvement, biopsy-proven nephritis and severe GI involvement can be related to each other. Colchicine may be effective in patients with relapsing disease.
Article
Objective: To study the clinical effect of alanyl-glutamine-enriched nutritional support in the treatment of children with abdominal Henoch-Schönlein purpura. Methods: Children with abdominal Henoch-Schönlein purpura who needed nutritional support were enrolled and stratified according to age, sex and the severity of disease, and were randomly divided into a control group (n=118) and an enriched nutritional support group (n=107). The control group was given nutritional support without using alanyl-glutamine, while the enriched nutritional support group was given alanyl-glutamine-enriched nutritional support. Intravenous steroids were used according to the severity of disease in both groups. Other therapies were the same in the two groups. The two groups were compared in terms of the length of hospital stay, the rate and duration of use of intravenous steroids, the recurrence rate of symptoms during hospitalization, the rate of total parenteral nutrition (TPN), the rate of weight loss and the rate of fasting for more than 5 days. All patients were followed up for 3 months after discharge to monitor the recurrence of symptoms. Results: There were no significant differences in the length of hospital stay, the rate of TPN and the rate of fasting for more than 5 days between the two groups (P>0.05). Compared with the enriched nutritional support group, the control group showed significant increases in the rate and duration of use of intravenous steroids, the recurrence rate of symptoms and the rate of weight loss (P<0.05). After the 3-month follow-up, all the children resumed normal diet, and the recurrence rate of digestive symptoms was less than 20% in each group. Abdominal pain was the most common symptom (83.33%, 30/36), followed by vomiting and abdominal distention. No digestive hemorrhage was observed. All the symptoms were relieved after symptomatic treatment. No significant difference was found between the two groups in the recurrence rate of digestive symptoms (P=0.693). Conclusions: Alanyl-glutamine-enriched nutritional support in the treatment of children with abdominal Henoch-Schönlein purpura can reduce the use of intravenous steroids and weight loss, but without impact on the length of hospital stay and post-discharge recurrence.
Article
Henoch-Schönlein purpura (HSP) is a common autoimmune vasculitis in childhood. The detailed pathogenesis of HSP is still unclear, whereas several types of predisposing factors have been proved to be the initial step. The objectives of present study were to analyze the distribution of predisposing factors, association of the predisposing factors with clinical manifestations and HSP relapse/recurrence. 1200 children with HSP were recruited between January 2015 and December 2017. We reviewed their laboratory tests and medical histories associated with HSP onset. The annual incidence of HSP was 8.13–9.17 per 100 000 in Anhui province. HSP occurred more commonly in spring and winter than in summer with an obvious west-to-east gradient. Cutaneous purpura was the most prevalent manifestation (100%), followed by arthritis/arthralgias (43.67%), abdominal pain (40.17%) and renal involvement (18.17%). On admission, series of potential infections were identified in 611 patients (50.92%). The histories of allergy, injury, surgery, vaccination and tick bite were declared by 231 patients (19.25%), 15 patients (1.25%), 12 patients (1.00%), 4 patients (0.33%) and 3 patients (0.25%), respectively. However, predisposing factors could not be identified in 521 children with HSP (43.42%) yet. 123 cases (10.25%) relapsed or recurred more than one time; the mean number was 2.92, and the mean interval was 11.4 weeks. The infection is the most frequent predisposing factor regardless of clinical phenotypes and relapse/recurrence, whereas the clinical manifestations exhibit an obvious heterogenicity according to different predisposing factors.
Article
Immunoglobulin A vasculitis (IgAV), also referred to as Henoch-Schönlein purpura, is the most common form of childhood vasculitis. The pathogenesis of IgAV is still largely unknown. The disease is characterized by IgA1-immune deposits, complement factors and neutrophil infiltration, which is accompanied with vascular inflammation. Incidence of IgAV is twice as high during fall and winter, suggesting an environmental trigger associated to climate. Symptoms can resolve without intervention, but some patients develop glomerulonephritis with features similar to IgA nephropathy that include hematuria, proteinuria and IgA deposition in the glomerulus. Ultimately, this can lead to end-stage renal disease. In IgA nephropathy immune complexes containing galactose-deficient (Gd-)IgA1 are found and thought to play a role in pathogenesis. Although Gd-IgA1 complexes are also present in patients with IgAV with nephritis, their role in IgAV is disputed. Alternatively, it is has been proposed that in IgAV IgA1 antibodies are generated against endothelial cells. We anticipate that such IgA complexes can activate neutrophils via the IgA Fc receptor FcαRI (CD89), thereby inducing neutrophil migration and activation, which ultimately causes tissue damage in IgAV. In this Review, we discuss the putative role of IgA, IgA receptors, neutrophils and other factors such as infections, genetics and the complement system in the pathogenesis of IgA vasculitis.