Journal of Infection and Public Health 13 (2020) 110–117

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Journal of Infection and Public Health

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Association of the infectious triggers with childhood

Henoch–Schonlein purpura in Anhui province, China
Jing Jing Wang, Yao Xu, Fei Fei Liu, Yue Wu, Sama Samadli, Yang Fang Wu,
Huang Huang Luo, Dong Dong Zhang, Peng Hu ∗
Department of Pediatrics, The First Affiliated Hospital of Anhui Medical University, Hefei, China

a r t i c l e i n f o a b s t r a c t

Article history: Background: Although the specific etiology of Henoch–Schonlein purpura (HSP) is still unknown, several
Received 19 September 2018 kinds of infectious triggers have been proved to participate in its pathogenesis. The objectives of present
Received in revised form 4 June 2019 study were to analyze the association of the infectious triggers with childhood HSP in Anhui province,
Accepted 4 July 2019
China.
Methods: 1200 HSP children were recruited from January 2015 to December 2017. Serum antistreptolysin
Keywords:
O titer, TORCH, Epstein-Barr virus, helicobacter pylori (HP), Mycoplasma antibodies (MP-Ab), tubercle
Children
bacillus antibody (TB-Ab), respiratory pathogens (legionella pneumophila, chlamydia pneumoniae, ade-
Henoch–Schonlein
Purpura
novirus, respiratory syncytial virus, influenza A virus, influenza B virus, rickettsia, parainfluenza virus)
Infection were determined. Patients’ histories were obtained by interviews and questionnaires.
Prednisone Results: The annual incidence of HSP was 8.13–9.17 per 100,000. HSP occurred more commonly in spring
Streptococcus and winter than in summer with an obvious west-to-east gradient. On admission, several potential
infections were identified in 611 cases (50.92%). The infectious agents including streptococcus, HP, MP,
parainfluenza, respiratory syncytial virus, TB and toxoplasma gondii were identified in 205 cases (17.08%),
71 cases (5.92%), 58 cases (4.83%), 6 cases (0.5%), 1 case (0.08%), 1 case (0.08%) and 1 case (0.08%) respec-
tively. 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 was the most frequent trigger regardless of clinical phe-
notypes and relapse/recurrence. Symptomatic treatment plus adjunctive anti-infectious agents could
significantly improve the remission rate of purpura in the infectious cases (x2 = 24.60, p < 0.01).
Conclusions: Streptococcus is the most frequent infectious agent in HSP children regardless of clinical phe-
notype or relapse/recurrence. The complete elimination of infectious triggers may help relieve cutaneous
purpura.
© 2019 The Authors. Published by Elsevier Limited on behalf of King Saud Bin Abdulaziz University
for Health Sciences. This is an open access article under the CC BY-NC-ND license (http://
creativecommons.org/licenses/by-nc-nd/4.0/).

Introduction occasionally be involved. Trapani et al. [5] retrospectively reviewed

Henoch–Schonlein purpura (HSP) is the most frequent autoim-
mune vasculitis in children under 17 years old [1], with an annual
incidence of 17.55 per 100,000 children in southern Sweden [2],
18.60 per 100,000 children in France [3] and 55.90 per 100,000
children in Korea [4] respectively. The main clinical manifesta-
tions include nonthrombocytopenic purpura, arthritis/arthralgia,
abdominal pain, gastrointestinal bleeding and glomerulonephritis.
Other organs, such as brain, lungs, heart, liver and scrotum, may
∗ Corresponding author at: The First Affiliated Hospital of Anhui Medical Univer-
sity, No. 218 Ji-Xi Road, Hefei 230022, China.
E-mail address: hupeng28@aliyun.com (P. Hu).
the clinical records of 150 HSP children from 1998 to 2002, and
encountered 4 cases suffered from nervous system involvement
characterized by headache, mental status change and seizures.
In 2017, a 9-year-old girl was admitted to our department with
a 10-day history of low-grade fever, cough, and purpuric rash
on her eyelids, buttocks, and lower limbs; computed tomogra-
phy of her thorax revealed massive left-sided hemothorax with
mediastinal shift to the right side [6]. Although HSP is usually
considered as a self-limiting disease, sometimes it may also be life-
threatening if multiple internal organs are involved. The detailed
pathogenesis of HSP is still unclear up to date. Several studies
have documented that the genetic variation play an important
role in HSP onset. He et al. [7] systematically reviewed 45 stud-
ies on the susceptibility loci in 39 genes for HSP, and identified

https://doi.org/10.1016/j.jiph.2019.07.004
1876-0341/© 2019 The Authors. Published by Elsevier Limited on behalf of King Saud Bin Abdulaziz University for Health Sciences. This is an open access article under the
CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
 J.J. Wang et al. / Journal of Infection and Public Health 13 (2020) 110–117
Table 1
Treatment principles for HSP.
Symptom severity
Minimal
Mild (mild arthralgias or abdominal pain)
Moderate (signifcant arthritis, abdominal pain, or early
renal involvement)
Severe (progressive renal disease, pulmonary hemorrhage)
that HLA-DRB1*01 and 11 increased the total risks for predisposi-
tion to HSP (OR = 1.805, p < 0.01; OR = 2.001, p < 0.01, respectively),
while HLA-DRB1*07 conferred a protective effect against HSP onset
(OR = 0.671, p < 0.05). López-Mejías et al. [8] recruited 349 Spanish
HSP patients and 335 sex ethnically matched controls and observed
that a statistically significant increase of HLA-B*41:02 allele in HSP
patients was found when compared with controls (8.3% versus 1.5%
respectively; P = 0.0001; OR (odds ratio) = 5.76 [2.15–19.3]).
Numerous epidemiological surveys have noted several kinds of
triggers participating in HSP onset, such as infection, food, drug,
vaccination, insect bite, and so on [9,10]. Among them, infection
serves as the most conspicuous one. According to the published
data at home and abroad, respiratory tract infection is a major factor
to induce HSP (42%–53.5%), followed by gastrointestinal infection
(2.2%–5%) cellulitis (0.9%), and urinary tract infection (0.6%) [5,11].
In a clinical investigation from Jordan, Albaramki [12] analyzed
the potential triggers of 55 HSP children and found that 49.1% of
patients had a history of antecedent respiratory tract infection;
more specifically, 36.8% of cases were infected with group A or B
hemolytic streptococuss by antistreptolysin O (ASO) titer test and
grew culture. In addition, the morbidity of HSP has a prominent sea-
sonal variation, paralleling to some specific infectious agents. Weiss
et al. [13] retrospectively reviewed 3132 admissions from January
2002 to December 2008, and found that the rate of HSP admissions
in a given month increased significantly as the standardized rates
of group A hemolytic streptococcus, staphylococcus aureus and
parainfluenza admissions increased. However, few studies have
elucidated the association between infection and HSP in detail. On
this background, the aim of the present study is mainly to bridge
this gap in Anhui province, China.
Methods
Patient selection
1200 HSP children, younger than 17 years old, were recruited
in the present study between January 2015 and December 2017.
The diagnosis of HSP was dependent on European League against
Rheumatism (EULAR) endorsed consensus criteria for HSP clas-
sification [14]. All cases exhibited skin purpura, simultaneously
accompanied with at least one of the 4 following clinical man-
ifestations: (1) abdominal pain: diffuse abdominal colicky pain
with acute onset assessed by history and physical examina-
tion, also including intussusception and gastrointestinal bleeding.
(2) Histopathology: typically leucocytoclastic vasculitis with pre-
dominant IgA deposit or proliferative glomerulonephritis with
predominant IgA deposit. (3) Arthritis or arthralgias: arthritis of
acute onset defined as joint swelling or joint pain with limitation
on motion. Arthralgia of acute onset defined as joint pain without
joint swelling or limitation on motion. (4) Renal involvement: pro-
teinuria: >0.3 g/24 h or >30 mmol/mg of urine albumin/creatinine
ratio on a spot morning sample. Haematuria 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 exclusion criteria were:
(1) patients with incomplete information. (2) Patients unable to
comply with the treatment. (3) Patients with severe heart, liver,
111
Treatment
Supportive care
Acetaminophen or nonsteroidal anti-inflammatory drug
Corticosteroids
Consider subspecialty consultation
Corticosteroids plus adjunctive immunosuppressant or plasmapheresis
Arrange subspecialty consultation
lung, kidney or other organ system diseases. Treatment principles
for HSP were adopted in the present study according to the report
of Reamy et al. [15] (Table 1). Anti-infectious agents were recom-
mended for those who suffered from an infection. Approval for
this study was acquired from the Medical Ethic Committee of the
First Affiliated Hospital of Anhui Medical University (Code number;
LLSC/20150009) and obtained consent from all parents.
Data collection
Patients underwent laboratory tests such as white blood cells
counts (WBC), platelet counts (PLT), C-reaction protein (CRP), ery-
throcyte sedimentation rate (ESR), urine tests, fecal occult blood,
ASO, TORCH (toxoplasma gondii, others, rubella virus, cytomegalo
virus, herpes virus), Epstein-Barr virus (EBV), helicobacter pylori
(HP), mycoplasma antibodies (MP-Ab), tubercle bacillus antibody
(TB-Ab), respiratory pathogens (legionella pneumophila, chlamy-
dia pneumoniae, adenovirus, respiratory syncytial virus, influenza
A virus, influenza B virus, rickettsia, parainfluenza virus), aspartate
aminotransferase (AST), alanine aminotransferase (ALT), creatine
kinase (CK), CK-MB, complement (C) 3, C4, and immunoglobulin A
(IgA). Patients’ histories associated with HSP onset (foods, drugs,
vaccinations, insect bites) were obtained by interviews and ques-
tionnaires.
Statistical analysis
Normally distributed continuous data were expressed as
mean ± standard deviation. Comparisons of the frequencies among
groups were analyzed using Chi-square tests. Comparison of mean
values between groups was carried out using the independent sam-
ple t-test. Comparison of mean values among groups was carried
out using one-way ANOVA, and post hoc analysis was calculated
using the Student–Newman–Keuls test. All P values were 2 sided
and P < 0.05 were considered significant. Statistical analyses were
performed on Statistical Package for the Social Sciences (SPSS), ver-
sion 16.0 (SPSS Inc., Chicago, IL, USA).
Results
Demographic features and laboratory tests
A total of 1200 children suffered from HSP, younger than 17
years old, including 672 (56%) boys and 528 (44%) girls from January
2015 to December 2017 (male: female = 1.27:1). The average age
was 9.05 ± 2.82 years old and median age was 9 years old (95% CI
8.99–9.11). Interquartile range (IQR) for the onset age fell in the
interval between 7 and 9 years old. The annual incidence of HSP
was 8.13–9.17 per 100,000, which was calculated according to the
demographic data from Anhui Health and Family Planning Commis-
sion. The monthly distribution of HSP children is presented in Fig. 1.
A bimodal distribution for HSP onset emerged annually that were
January and December in 2015, January and November in 2016,
January and December in 2017 respectively. In contrast, the lowest
onset of HSP appeared in July, August or September throughout the
observational period. In the present study, all 3 years displayed an
112 J.J. Wang et al. / Journal of Infection and Public Health 13 (2020) 110–117
Fig. 1. Monthly distribution of 1200 children with HSP from 2015 to 2017.
Table 2
The laboratory results of WBC, PLT, CRP, ESR, IgA, C3 and C4.
Non-infectious group (n = 589)
WBC (×10 /l) 9
10.01 ± 3.02
PLT (×109 /l) 336.37 ± 96.49
CRP (mg/l)* 11.08 ± 6.98
ESR (mm/h)* 17.72 ± 11.32
IgA (g/l)* 2.08 ± 0.78
C3 (g/l) 1.23 ± 0.18
C4 (g/l) 0.27 ± 0.07
*
P < 0.05.
identical seasonal variation, and HSP occurred more commonly in
spring and winter than in summer. The geographical distribution of
HSP children is shown in Fig. 2. The cities with the highest propor-
tion were clustered together in the central region of Anhui province.
More specifically, Hefei had the highest proportion (37.17%), fol-
lowed by Fuyang (14.58%) and Luan (13.33%), whereas Huangshan
and Huaibei occupied the lowest proportion at 0.08%. The mor-
bidity of HSP exhibited an evident west-to-east gradient in Anhui
province, and it experienced almost a 10-fold increase in the west-
ern compared with the eastern. However, no marked difference was
found from south to north. The laboratory results of WBC, PLT, CRP,
ESR, IgA, C3 and C4 are shown in Table 2. CRP, ESR and IgA were sig-
nificantly increased in the infectious group when compared with
the non-infectious group (P < 0.01).
Clinical manifestations
The major clinical manifestations of HSP are displayed in Table 3.
Purpura consisted of the characteristic skin lesions 2–10 mm in
diameter, mainly over the buttocks and lower extremities but not
restricted to those areas. Since cutaneous purpura is a necessary
element in the diagnosis of HSP, all cases in the present study had
skin involvement. Arthritis/arthralgia, the second most prevalent
characteristic of HSP, occurred in 43.67% of patients and affected the
knees and/or ankles most commonly (35.33%), resulting in severe
pain and even walking restriction. The joints of the lower extrem-
ities were involved in 5.83% of patients with arthritis/arthralgia.
Abdominal pain was observed in 40.17% of patients who dominantly
developed gastrointestinal bleeding, intussusceptions, appendici-
tis or ileus. Gastrointestinal bleeding was usually occult (3.50%),
but 2.17% of patients had grossly bloody or melanotic stools. This
Infectious group (n = 611) T value P value
10.55 ± 4.27 1.59 0.11
348.42 ± 95.22 1.42 0.15
19.99 ± 13.21 8.37 0.00
29.88 ± 13.69 7.47 0.00
2.40 ± 0.97 3.78 0.00
1.20 ± 0.26 1.4 0.16
0.27 ± 0.21 0.48 0.63
study also encountered 3 cases (0.25%) with intussusceptions, 2
cases (0.17%) with appendicitis, 2 cases (0.17%) with ileus and
2 cases (0.17%) with pancreatitis. Renal involvement in HSP was
diverse and manifested as proteinuria and/or haematuria. In the
present study, 218 cases (18.17%) suffered from kidney injury;
among them, 69 cases (5.75%) had proteinuria, 55 cases (4.58%) had
haematuria and 94 cases (7.83%) had haematuria and proteinuria
simultaneously. Besides, other clinical manifestations including car-
diac damage (5.00%), and liver dysfunction (1.33%) were also found
in the present study.
Possible triggers
The possible triggers of HSP are presented in Table 3. On admis-
sion, series of potential infections were identified in 50.92% of 1200
HSP children. Based on the site of infection, 569 cases (47.42%) had
a respiratory tract infection, 75 cases (6.25%) had a gastrointesti-
nal infection and 16 cases (1.33%) had a urinary tract infection;
according to the laboratory results, there were 205 cases (17.08%)
with streptococcal infection, 71 cases (5.92%) with HP infection,
58 cases (4.83%) with MP infection, 6 cases (0.5%) with parain-
fluenza infection, 1 case (0.08%) with respiratory syncytial virus
(RSV) infection, 1 case (0.08%) with TB infection and 1 case (0.08%)
with toxoplasma gondii infection. The allergic histories obtained by
questionnaires indicated 231 patients (19.25%) with positive dec-
larations, including 196 cases (16.33%) with food allergy, 21 cases
(1.75%) with drugs, 10 cases (0.83%) with house dust mite and 4
cases (0.33%) with grass pollen. In the present study, 15 (1.25%)
and 12 (1.00%) cases suffered from injury and surgery respectively.
Moreover, 4 cases reported a cutaneous rash after being immunized
with rabies vaccine or meningitis vaccine within one week, and 3
 J.J. Wang et al. / Journal of Infection and Public Health 13 (2020) 110–117 113

Fig. 2. A. Region distribution of 1200 children with HSP from 2015 to 2017. B. Region distribution of 1200 children with HSP from 2015 to 2017.

cases complained a recent history of tick bites. However, triggers
could not be identified in 521 HSP children (43.42%) yet.
Association of infectious agents with clinical manifestations
The association of infectious agents with clinical manifesta-
tions in HSP patients is shown in Fig. 3. Streptococcus was the
most frequent infectious agent in HSP children regardless of
clinical phenotype, and detected in 20.61% of cases with arthri-
tis/arthralgia, 18.35% of cases with renal involvement, 17.08%
of cases with purpura and 15.98% of cases with abdominal
pain. In addition, HP served as the second commonest infec-
tious agent contributing to HSP onset, and detected in 9.34% of
cases with abdominal pain, 7.34% of cases with renal involve-
ment, 6.68% of cases with arthritis/arthralgia and 5.92% of cases
with purpura. No significant variations in the distribution of
infectious agents were observed among HSP children with dif-
ferent clinical manifestations (x2 = 10.13, P = 0.34) (Fig. 3A). On
114 J.J. Wang et al. / Journal of Infection and Public Health 13 (2020) 110–117

Table 3
Clinical manifestations and possible triggers in HSP on admission.

Clinical manifestations Number of cases (%) Possible triggers Number of cases (%)

Purpura 1200 (100%) Infection 611 (50.92%)

Arthritis/arthralgia 524 (43.67%) Respiratory tract infection 569 (47.42%)
Upper extremities 70 (5.83%) Gastrointestinal infection 75 (6.25%)
Lower extremities 424 (35.33%) Urinary tract infection 16 (1.33%)
Both upper and lower extremities 30 (2.50%) Streptococcal infection 205 (17.08%)
Abdominal pain 482 (40.17%) HP infection 71 (5.92%)
Isolated abdominal pain 405 (33.75%) MP infection 58 (4.83%)
Gastrointestinal bleeding not associated with the following situations 68 (5.67%) Parainfluenza infection 6 (0.5%)
Intussusception 3 (0.25%) RSV infection 1 (0.08%)
Appendicitis 2 (0.17%) TB infection 1 (0.08%)
Ileus 2 (0.17%) Toxoplasma gondii infection 1 (0.08%)
Pancreatitis 2 (0.17%) Allergy 231 (19.25%)
Renal involvement 218 (18.17%) Food allergy 196 (16.33%)
Proteinuria 69 (5.75%) Drug allergy 21 (1.75%)
Heamaturia 55 (4.58%) House dust mite allergy 10 (0.83%)
Hematuria plus albuminuria 94 (7.83%) Grass pollen allergy 4 (0.33%)
Injury 15 (1.25%)
Surgery 12 (1.00%)
Vaccination 4 (0.33%)
Tick bite 3 (0.25%)
Unknown 521 (43.42%)

Fig. 3. A. Association of infectious agents with clinical manifestations. B. Association of infectious agents with clinical manifestations.

the other hand, arthritis/arthralgia (52.68%) was the most preva-
lent phenotype among these cases infected by streptococcus, as
compared with abdominal pain (37.56%) and renal involvement
(19.51%); HP-triggered HSP exhibited abdominal pain (63.38%)
most frequently, followed by arthritis/arthralgia (49.30%) and renal
involvement (22.54%) respectively; MP-triggered HSP exhibited
arthritis/arthralgia (46.55%) most frequently, followed by abdom-
inal pain (34.48%) and renal involvement (13.79%) respectively.
However, the clinical manifestations presented no significant het-
erogenicity among different infectious agents (x2 = 11.05, P = 0.27)
(Fig. 3B).
Therapeutic response
The therapeutic response between non-infectious cases and
infectious cases is presented in Table 4. In the non-infectious group,
there were 589 cases with purpura, 244 cases with abdominal
pain, 228 cases with arthritis/arthralgia and 112 cases with renal
involvement. During hospitalization, abdominal pain and arthri-
tis/arthralgia persisted for 2.73 ± 1.55 days and 2.47 ± 1.65 days
respectively, and resolved completely in all cases; purpura and
renal involvement persisted for 4.49 ± 2.25 days and 4.67 ± 1.66
days respectively, and resolved in 479 cases and 49 cases respec-
 J.J. Wang et al. / Journal of Infection and Public Health 13 (2020) 110–117
Table 4
Therapeutic response between non-infectious cases and infectious cases.
Non-infectious group (n = 589)
Clinical manifestations Total cases Relieved cases (%) Duration time (day)
Purpura 589 479 (81.32%) 4.49 ± 2.25
Arthritis/arthralgia 228 228 (100%) 2.47 ± 1.65
Abdominal pain 244 244 (100%) 2.73 ± 1.55
Renal involvement 112 49 (43.75%) 4.67 ± 1.66
tively. In the infectious group, there were 611 cases with purpura,
296 cases with arthritis/arthralgia, 238 cases with abdominal pain
and 106 cases with renal involvement. During hospitalization,
arthritis/arthralgia and abdominal pain persisted for 2.54 ± 2.17
days and 2.85 ± 1.97 days respectively, and resolved completely in
all cases; purpura and renal involvement persisted for 4.63 ± 2.07
days and 4.10 ± 2.59 days respectively, and resolved in 557 cases
and 51 cases respectively. Although no significant differences were
observed in the duration time of main symptoms between the two
groups, it was notable that symptomatic treatment plus adjunctive
anti-infectious agents could significantly improve the remission
rate of purpura in the infectious group (x2 = 24.60, P < 0.01).
Influence of infectious agents to relapse/recurrence
123 of 1200 HSP children (10.25%) were hospitalized more than
one time from January 2015 to December 2017. Relapse/recurrence
was defined when a patient previously diagnosed with HSP and
asymptomatic for at least 2 weeks, presented again a new flare
of cutaneous lesions or other systemic manifestations of the vas-
culitis [16]. The number of relapse/recurrence ranged from 2 to
10 with a mean of 2.92 during the observational period. The
relapse/recurrence occurred over a time span ranged from 2 weeks
to 139 weeks, with a mean of 11.4 weeks after initial resolu-
tion of symptoms. In 123 cases with relapse/recurrence, 65 cases
had potential infections and streptococcus was the commonest
infectious agent (16.26%), followed by HP (7.32%) and MP (5.69%)
respectively. In the other 1077 cases without relapse/recurrence,
546 cases had potential infections and streptococcus was also the
commonest infectious agent (33.88%), followed by HP (11.36%) and
MP (9.34%) respectively. No significant differences in the infectious
agents were observed between the above two groups (x2 = 0.59,
P = 0.75).
Discussion
HSP is the most common childhood vasculitis in the world-
wide. The present study retrospectively reviewed the records of
1200 hospitalized patients with HSP in the recent 3 years and the
annual incidence ranged from 8.13 to 9.17 per 100,000 based on
our local demographic data. An epidemiological survey in Taiwan,
China from 1999 to 2002 demonstrated that a total of 2759 chil-
dren with HSP were recruited with an annual incidence of 12.9 per
100,000 children [17]. We speculated the lower annual incidence
in our region may be attributed to the following two reasons. First,
HSP is usually considered benign and self-limited so hospitaliza-
tion is not always indicated. Second, the registration and follow-up
system of chronic disease are incomplete in mainland China so
the clinical records of some patients may be lost. In general, the
main clinical manifestations of HSP include cutaneous purpura,
arthritis/arthralgia, abdominal pain and renal involvement. Calvo-
Río et al. [18] reviewed the data of 417 HSP children in Northern
Spain and revealed that cutaneous purpura were observed in all the
patients, abdominal pain was presented in 64.5% of patients, arthri-
tis/arthralgia occurred in 63.1% of patients, and renal involvement
was observed in 41.2% of patients. Similarly, all the patients in our
115
Infectious group (n = 611)
Clinical manifestations Total cases Relieved cases (%) Duration time (day)
Purpura 611 557 (91.16%) 4.63 ± 2.07
Arthritis/arthralgia 296 296 (100%) 2.54 ± 2.17
Abdominal pain 238 238 (100%) 2.85 ± 1.97
Renal involvement 106 51 (48.11%) 4.10 ± 2.59
study also had cutaneous purpura, whereas the second most preva-
lent symptom was arthritis/arthralgia, followed by abdominal pain
and renal involvement respectively. The variable distribution of
HSP symptoms appears due to different ethnic origin and/or hav-
ing different environmental factors, and different ascertainment of
case.
Currently, the etiology of HSP remains unclear. Several triggers
have been documented to participate in its pathogenesis [5,18]. In
the present study, infection was one of the most prevalent triggers
(47.42%); HSP onset was subject to a dramatic seasonal variation
with more cases in spring and winter than in summer, which
coincided with infection. In Finland, a prospective study encom-
passing 223 HSP children indicated that HSP was preceded by an
upper respiratory tract infection in 72% of patients and occurred
more commonly in the coldest time of the year (78% diagnosed
between September and March) [19]. In Saudi Arabia, Lardhi [20]
reviewed the medical records of 78 HSP children from January 1996
to December 2010, and found that half of them experienced a his-
tory of upper respiratory tract infection and approximately 60% of
them were presented during autumn and winter. However, the cli-
mate is really diverse in the whole world, thus the association of
HSP onset with seasons may be slightly variable.
Streptococcus is capable of causing a broad spectrum of postin-
fectious autoimmune diseases, such as rheumatic fever, movement
disorders (chorea, tics, Parkinsonism) [21], Behçet’s disease [22]
and poly-arteritis nodosa [23]. The immunopathogenesis of these
diseases is incompletely defined but may be due to molecular
mimicry, superantigen production and endothelial injury. Similar
mechanisms may also work in HSP onset. In the present study,
streptococcus was the most frequent infectious agent and iden-
tified in 205 cases (33.55%) from 611 infectious cases according to
the findings of ASO titer test and throat swab culture; moreover,
39 cases triggered by streptococcus had renal involvement. Almost
identically, another clinical study from northwestern Spain demon-
strated that a streptococcal infection was confirmed by throat swab
culture in 8 (36.36%) of 22 HSP patients [24]. Several previous stud-
ies have supported the direct evidence of HSP nephritis (HSPN)
caused by streptococcus. Masuda et al. [25] observed the biopsy
specimens from 33 patients with HSPN, and showed that a strepto-
coccal antigen significantly overexpressed in renal mesangium of
10 cases with higher ASO titer. More directly, Schmitt et al. [26] car-
ried out renal and skin biopsies from HSP patients, and noted that
the deposits of IgA-binding streptococcal M proteins were detected
in 54% of kidneys and 80% of skin biopsies respectively.
The other infectious agents, such as HP and MP, have also been
proved to trigger HSP onset. In the present study, HP and MP infec-
tion were identified in 71 cases (11.62%) and 58 cases (9.49%) from
611 infectious cases respectively. A meta-analysis involving 749
Chinese children with HSP showed that 369 cases (49.27%) had
the evidence of HP infection; however, the majority of patients
in the report of Xiong et al. [27] suffered from gastrointestinal
involvement, which may cause a significant higher prevalence of
HP infection in comparison with our findings. HSP is an unusual
extrapulmonary manifestation of MP infection. Timitilli et al. [28]
investigated extrapulmonary manifestations among 92 children
with MP infection, and found that only one 5-year-old girl had HSP.
116 J.J. Wang et al. / Journal of Infection and Public Health 13 (2020) 110–117
In our previous report, we also encountered a 19-month-old female
infant who had HSP and MP infection simultaneously [29]. The eti-
ology of HP/MP-associated HSP is mainly attributed to the host
response to antigens on HP/MP, such as immune-complexmediated
injury, cytotoxic T-cell-mediated immune responses, and autoim-
mune reactions [29,30]. In addition, a recent study by Kurata et al.
[31] indicated that interleukin-10 and interleukin-17A may also be
involved in the extrapulmonary complications of MP infection. Very
interestingly, in the present study, we encountered an unusual case
of HSP in combination with pulmonary tuberculosis in a 13-year-
old girl. After treatment with isoniazid (10 mg/kg/day), rifampicin
(20 mg/kg/day) and pyrazinamide (20 mg/kg/day) for 2 weeks, her
cutaneous purpura disappeared, abdominal pain resolved, and
cough stopped. However, further studies will be warranted to probe
the potential mechanisms in the future.
Symptomatic treatment plays a fundamental role in HSP man-
agement. Although nonsteroidal anti-inammatory drugs alleviate
arthritis/arthralgia and cutaneous purpura, it should be used
cautiously in patients with renal insufficiency and intestinal hem-
orrhage. Early steroid treatment is most appropriate for children
with renal involvement or severe extrarenal symptoms; gener-
ally, oral prednisone at 1–2 mg kg daily for two weeks has been
used to treat moderate to severe abdominal and joint symp-
toms, and to hasten the resolution of HSP in children [32]. The
most unique objective of the present study was to explore the
therapeutic response between non-infectious cases and infec-
tious cases through analyzing the remission rate and duration
time of main clinical manifestations. In comparison with the
non-infectious group, symptomatic treatment plus adjunctive anti-
infectious agents could significantly improve the remission rate of
purpura in the infectious group. In this circumstance, we consid-
ered that the complete elimination of infectious triggers may help
relieve the skin lesion of HSP. Furthermore, in the present study,
10.25% of HSP relapsed or recurred more than one time within a 3-
year observational period; the mean number of relapse/recurrence
was 2.92 and the mean interval was 11.4 weeks; the infection
was the most common trigger of HSP onset whether or not the
relapse/recurrence existed. Therefore, the infectious triggers have
no influences on the relapse/recurrence of HSP. Prais et al. [33]
reviewed the clinical data of 260 HSP children in Israel from 1969
to 2004, and discovered that only 7 cases (2.7%) were hospital-
ized more than once within 2–3 months of the primary episode
whereas no clinical or laboratory characteristics predicted to HSP
recurrence. Calvo-Río et al. [34] established a multivariable logis-
tic regression model and screened the potential predictors of HSP
relapse in 417 Spanish patients; almost one-third HSP patients
experienced at least 1 relapse and a prodromic infection could
significantly decrease the risk of HSP relapse after a 12-year follow-
up (OR = 0.57, P = 0.025), which may be attributed to the targeted
clearance of infectious triggers.
Conclusions
Although the etiology of HSP remains unknown, several
infectious agents have been documented to participate in its patho-
genesis. Based on the findings of the present study, streptococcus
is the most frequent infectious agent in HSP children regardless
of clinical phenotype or relapse/recurrence. In addition, the com-
plete elimination of infectious triggers may help relieve cutaneous
purpura.
Funding
This study was supported by the National Natural Science Foun-
dation of China (No. 81570637, 81000306) and the New Technology
Project of the First Affiliated Hospital, Anhui Medical University
(2014-01).
Conflicts of interest
None declared.
Acknowledgments
At the point of finishing this paper, I’d like to express my sin-
cere thanks to all those who have lent me hands in the course of
my writing this paper. We greatly appreciate PhD. Xun Xia, Dr. Bo
Hu and Dr. Wei Wei for their helpful comments, Department of
Pediatrics, the First Affiliated Hospital of Anhui Medical University,
Hefei, China.
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