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Clinical Note

Journal of International Medical Research


2014, Vol. 42(4) 1043–1049
Henoch–Schönlein purpura ! The Author(s) 2014
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DOI: 10.1177/0300060514530879
clinical features and risk imr.sagepub.com

factors for renal involvement


Youying Mao, Lei Yin, Hua Huang,
Zhengyu Zhou, Tongxin Chen and Wei Zhou

Abstract
Objectives: To analyse the clinical features of Henoch–Schönlein purpura (HSP) with or without
nephritis in Chinese children and to determine the risk factors for renal involvement.
Methods: Patient characteristics, clinical parameters and laboratory data were retrospectively
analysed in patients with HSP with or without nephritis. Logistic regression analysis was used to
identify the risk factors for renal involvement.
Results: A total of 535 patients with HSP were included in the study. HSP nephritis occurred in
267 patients (49.9%), ranging from isolated haematuria in 5.2%, mild proteinuria in 77.5%,
moderate proteinuria in 6.4% and severe proteinuria in 10.9% of cases. In 90% of the
cases, nephritis developed within 1 week of HSP onset; 98.5% of the cases with nephritis
developed the condition within 1 month. Risk factors for the development of nephritis were age
6 years, purpura on sites other than the lower limbs and the presence of occult blood in
the stool.
Conclusion: These results suggest that patients aged 6 years, or who have purpura on the upper
limbs or face, or who have occult blood in the stool should be particularly monitored for signs of
nephritis.

Keywords
Henoch–Schönlein purpura, nephritis, risk factors, children

Date received: 7 February 2014; accepted: 17 March 2014

characterized by nonthrombocytopenic pur-


Introduction pura, arthritis/arthralgia, abdominal pain,
Henoch–Schönlein purpura (HSP) is a
common systemic vasculitis syndrome Corresponding author:
Professor Wei Zhou, Nephrology and Rheumatology
Department, Shanghai Children’s Medical Centre, School
Nephrology and Rheumatology Department, Shanghai of Medicine, Shanghai Jiao Tong University, 1678 Dongfang
Children’s Medical Centre, School of Medicine, Shanghai Road, Shanghai 200127, China.
Jiao Tong University, Shanghai, China Email: scmckidney@163.com

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1044 Journal of International Medical Research 42(4)

gastrointestinal bleeding and glomerulo- Ethics Committee of Shanghai Children’s


nephritis.1 HSP can occur at any age, but Medical Centre.
is more common in children than in adults.2 At the time of diagnosis, standard tests
Extrarenal symptoms typically resolve rap- including full blood count analysis of
idly without complications, and the long- C-reactive protein, serum albumin, cystatin
term prognosis of HSP mainly depends on C, immunoglobulins A, G and M, and
the severity of renal involvement, termed coagulation biomarkers D-dimer and
Henoch–Schönlein purpura nephritis fibrinogen, were performed. In addition,
(HSPN).3,4 Renal manifestations vary from peripheral blood T-cells, B-cells and natural
microhaematuria and minimal proteinuria killer (NK) cells were investigated using flow
to nephrotic syndrome; the proportion of cytometry with CD3/CD4/CD8, CD19 and
patients with renal involvement also varies CD56 antibodies, respectively. After admis-
widely, with incidences ranging between 20 sion, urinary protein and haematuria were
and 56% reported in different studies.5 evaluated every 7 days and stools were tested
Although most patients with HSPN experi- for occult blood to monitor for gastrointes-
ence mild and self-limiting renal disease,6 tinal bleeding every 3 days. For patients
up to 20% of children with HSPN will with severe abdominal pain or arthralgia,
develop chronic kidney disease, with up to 1–2 mg/kg methylprednisolone was given for
2% progressing to end-stage renal pain relief.
disease.4,5,7–9
The present study retrospectively evalu-
ated Chinese children with HSP in order to
HSPN definition and treatment
investigate the clinical features of HSP with Henoch–Schönlein purpura nephritis was
or without nephritis, to examine the rela- defined as the presence of haematuria and/
tionship between clinical features and renal or proteinuria at two different timepoints
manifestations, and to determine the risk within 6 months of HSP onset. Haematuria
factors for developing HSPN. was defined as >5 red blood cells per high-
power microscopic field and proteinuria was
Patients and methods defined as >150 mg protein/24 h, according
to guidelines set out by the Subspecialty
Patients Group of Nephrology of the Chinese Society
Data from all children hospitalized with of Pediatrics.11 HSPN was divided into four
HSP in the Nephrology and Rheumatology subgroups: isolated haematuria; mild pro-
Department, Shanghai Children’s Medical teinuria (25 mg protein/kg per day) plus
Centre, School of Medicine, Shanghai Jiao haematuria; moderate proteinuria (25–
Tong University, Shanghai, China, between 50 mg protein/kg per day) plus haematuria;
January 2006 and June 2012 were retro- severe proteinuria/nephrotic syndrome
spectively analysed. Criteria for inclusion in (50 mg protein/kg per day) plus
the study were: a diagnosis of HSP based on haematuria.
the presence of palpable purpura plus at All patients with proteinuria were treated
least one of abdominal pain, arthralgia, and with angiotensin converting enzyme inhibi-
haematuria/proteinuria (based on the defin- tors. For patients with moderate protein-
itions set out by the European League uria, prednisone was added. If severe
Against Rheumatism10); first onset of HSP; proteinuria was detected, a renal biopsy
follow-up for  6 months. Written informed was performed and a therapy regimen
consent was obtained from patients’ parents based on the histological findings was
and the study protocol was approved by the administered.

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Mao et al. 1045

Table 1. Patient characteristics and clinical fea-


Statistical analyses tures of children with Henoch–Schönlein purpura
Results were reported as mean  SD. (n ¼ 535).
Results were compared using the 2-test
Parameter n (%)
for categorical variables and the independ-
ent samples t-test for continuous variables. Sex
A receiver operating characteristic curve was Male 308 (57.6)
used to detect cut-off values for differentiat- Female 227 (42.4)
ing patients with nephritis from those with- Purpura at sites other than lower 73 (13.6)
out nephritis. A logistic regression model limbs
Arthralgia 308 (57.6)
was used to assess the risk factors for HSPN.
Abdominal pain 266 (49.7)
A P-value < 0.05 was considered to be
Bloody stools 33 (6.2)
statistically significant. All statistical ana- Occult blood in stools 140 (26.2)
lyses were performed using SPSSÕ software Renal involvement 267 (49.9)
version 16.0 (SPSS Inc., Chicago, IL, USA). Isolated haematuria 14 (5.2)
Mild proteinuria 207 (77.5)
Results (25 mg protein/kg
per day) plus haematuria
Patient characteristics Moderate proteinuria 17 (6.4)
A total of 535 patients with HSP were (25–50 mg protein/kg
enrolled in the study: 308 were male; 227 per day) plus haematuria
Severe proteinuria 29 (10.9)
were female. The mean age of onset of HSP
( 50 mg protein/kg
was 6.9  2.7 years (range of 2–16 years) but
per day) plus haematuria
most cases occurred in those aged 4–11
years. Patient characteristics are given in Data presented as n (%) of patients.
Table 1. Of the 267 with renal involvement,
90% developed nephritis within 1 week of without (P ¼ 0.007). In addition, signifi-
HSP onset and 98.5% developed nephritis cantly more patients with nephritis were
within 1 month of HSP onset. positive for occult blood in their stools than
patients without nephritis (P ¼ 0.001).
There were no significant differences in
Risk factors for developing HSPN white blood cell count, platelet count, mean
Clinical features were compared in patients platelet volume or C-reactive protein level
with or without nephritis (Table 2). There between HSP patients with or without neph-
was no sex-related between-group differ- ritis. The percentage of neutrophils was
ence, but patients with nephritis were sig- higher in patients with nephritis than those
nificantly older than those without nephritis without nephritis (P ¼ 0.009). In addition,
(P < 0.001). There were no significant differ- levels of albumin were lower (P ¼ 0.013), and
ences in the incidence of arthralgia and cystatin C (P ¼ 0.016) higher, in patients
abdominal pain between patients with or with nephritis than in patients without neph-
without neprhitis. All patients had purpura ritis. No significant differences were seen in
on the lower limbs, but additional purpura D-dimer or fibrinogen levels (Table 2).
on other sites (e.g. upper limbs, face or neck) There were no significant differences
occurred more frequently in patients with between the two groups in T-cell, B-cell or
nephritis than in those without nephritis NK-cell percentages or ratios, or in levels
(P ¼ 0.002). Bloody stools were seen more of serum immunoglobulin A, M or G
often in patients with nephritis than in those (Table 2).

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1046 Journal of International Medical Research 42(4)

Table 2. Clinical features and laboratory data at disease onset in patients with Henoch–Schönlein purpura
with or without nephritis.

Without nephritis With nephritis Statistical


Parameter n ¼ 268a n ¼ 267a significanceb

Sex NS
Male 148 (55.2) 160 (59.9)
Female 120 (44.8) 107 (40.1)
Age, years 6.38  2.53 7.48  2.79 P < 0.001
Arthralgia 160 (59.7) 148 (55.4) NS
Abdominal pain 124 (46.3) 142 (53.2) NS
Purpura on sites other 24 (9.0) 49 (18.4) P ¼ 0.002
than lower limbs
Bloody stools 9 (3.4) 24 (9.0) P ¼ 0.007
Occult blood in stool 47 (17.5) 93 (34.8) P < 0.001
Systolic pressure, mmHg 100.9  10.1 102.8  10.6 NS
White blood cell count, 109/l 11.8  4.98 12.3  5.12 NS
Neutrophils, % 61.9  15.8 65.4  13.6 P ¼ 0.009
Platelet count, 109/l 334  108 340  118 NS
Mean platelet volume, fl 9.69  1.75 9.55  1.88 NS
C-reactive protein, mg/l 8.26  16.7 9.94  15.1 NS
Albumin, g/l 37.0  4.5 35.8  6.1 P ¼ 0.013
Globulin, g/l 30.0  5.9 29.1  6.9 NS
D-dimer, mg/ml fibrogen 0.87  0.93 (n ¼ 240) 0.88  1.1 (n ¼ 220) NS
equivalent units
Fibrinogen, g/l 3.63  1.05 (n ¼ 240) 3.67  1.17 (n ¼ 220) NS
Cystatin C, mg/l 0.75  0.17 (n ¼ 170) 0.83  0.32 (n ¼ 143) P ¼ 0.016
CD4 þ T-cells, % 31.2  7.8 (n ¼ 198) 32.2  7.6 (n ¼ 219) NS
CD8þ T-cells, % 25.1  6.1 (n ¼ 198) 25.4  6.5 (n ¼ 219) NS
CD4/CD8 ratio 1.32  0.46 (n ¼ 198) 1.35  0.44 (n ¼ 219) NS
CD19þ B-cells, % 24.5  8.0 (n ¼ 115) 23.2  9.7 (n ¼ 112) NS
Natural killer cells, % 11.8  7.4 (n ¼ 115) 10.4  5.6 (n ¼ 112) NS
Immunoglobulin A, g/l 2.11  0.73 (n ¼ 201) 2.16  0.81 (n ¼ 203) NS
Immunoglobulin M, g/l 1.24  0.91 (n ¼ 201) 1.27  1.00 (n ¼ 203) NS
Immunoglobulin G, g/l 11.0  6.0 (n ¼ 201) 10.2  3.4 (n ¼ 203) NS
a
Where data were not available for all study participants, the number of results are shown in parentheses.
b 2
 -test for categorical variables; independent t-test for continuous variables.
Data presented as n (%) of patients or mean  SD.
NS, not statistically significant (P  0.05).

Parameters that showed a significant dif- parameters, receiver operating characteristic


ference between the two groups were ana- curves were used to find the cut-off values for
lysed by logistic regression analysis to differentiating patients with nephritis from
determine the risk factors for nephritis in those without nephritis. Cut-off values for
HSP. As the numbers of patients with occult age, albumin and cystatin C were 6 years,
blood were higher than those with bloody 36 g/l and 0.61 mg/l, respectively. Univariate
stools, the presence of occult blood in the analysis showed that age 6 years, purpura
stool was selected to represent gastrointes- on sites other than the lower limbs, presence
tinal involvement. For continuous of occult blood in the stool and a cystatin C

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Mao et al. 1047

Table 3. Logistic regression analysis of risk factors for the development of nephritis in Henoch–Schönlein
purpura (HSP) in a cohort of 535 Chinese children with HSP.

Univariate analysis Multivariate analysis

Odds 95% confidence Odds 95% confidence


Parameter ratio intervals P-value ratio intervals P-value

Age 6 years 2.25 1.559, 3.260 <0.001 2.16 1.466, 3.176 <0.001
Purpura on sites other 2.29 1.357, 3.849 0.002 2.05 1.165, 3.560 0.013
than lower limbs
Occult blood in stool 2.44 1.628, 3.668 <0.001 2.14 1.350, 3.378 0.001
Cystatin C 0.61 mg/l 2.25 1.099, 4.635 0.024
Albumin <36 g/l 0.89 0.981, 1.135 NS

NS, not statistically significant (P  0.05).

level 0.61 mg/l were associated with HSPN Consistent with previous reports,12–14 in
(Table 3). Multivariate analysis showed that the present study a greater age and the
age 6 years (P < 0.001), purpura on sites presence of occult blood in the stool were
other than the lower limbs (P ¼ 0.013) and positively correlated with the development
the presence of occult blood in the stool of nephritis. Clinically, purpura on the lower
(P ¼ 0.001) were independent risk factors limbs occurred in all patients with HSP, but
for the development of renal involvement a small percentage also had purpura on the
(Table 3). face, neck or upper limbs, and this was an
independent risk factor for nephritis.
Another study reported that persistent pur-
Discussion pura was a risk factor for nephritis in HSP.14
The present study retrospectively analysed To our knowledge, the present study is the
clinical features and renal manifestations in first to focus on the significance of purpura
535 patients with HSP. Of these, 267 distribution in a large cohort analysis.
patients (49.9%) had nephritis, ranging in The pathogenetic mechanisms leading to
severity from isolated haematuria to neph- HSPN have not yet been clearly delineated,
rotic proteinuria. Age 6 years, purpura on but cellular and humoral immune dysfunc-
sites other than the lower limbs and the tion may be involved in the development of
presence of occult blood in the stool were nephritis.15 In the present study, T-cell,
shown to be risk factors for developing B-cell and NK cell percentages and ratios
HSPN. To our knowledge, this is the largest in peripheral blood and serum concentra-
recent survey of this disease in China. tions of immunoglobulins A, M and G were
Studies have reported an incidence of measured, but no significant differences were
nephritis of 20–54% in patients with HSP.4 found between HSP patients with or without
In the present study, 49.9% of patients had nephritis. However, immune function was
renal involvement. Most patients (90%) with only tested at one timepoint; dynamic moni-
renal involvement developed nephritis toring may be required to clarify the roles of
within 1 week of HSP onset, with 98.5% the cellular and humoral immune systems in
developing nephritis within 1 month and HSPN pathogenesis.
only 1.5% developing nephritis between 1 Most patients with HSPN will regain
and 6 months of disease onset. normal renal function; however, a small

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1048 Journal of International Medical Research 42(4)

percentage will progress to chronic kidney 2. Piram M and Mahr A. Epidemiology of


disease, or even to end-stage renal disease immunoglobulin A vasculitis (Henoch–
after 20 years or longer.16 Edström Halling Schönlein): current state of knowledge. Curr
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3. Jauhola O, Ronkainen J, Koskimies O, et al.
nephritic or nephrotic syndrome correlated
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with poor outcomes. In the present study,
years after treatment with a placebo or
17.3% of patients had moderate or severe prednisone at disease onset. Pediatr Nephrol
proteinuria, but the follow-up period was 2012; 27: 933–939.
too short to report on prognosis. 4. Ronkainen J, Nuutinen M and Koskimies O.
The present study has the limitations of The adult kidney 24 years after childhood
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916–920.
In conclusion, the present study showed
6. Coppo R, Andrulli S, Amore A, et al.
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The authors declare that there are no conflicts of
EULAR/PReS endorsed consensus criteria
interest.
for the classification of childhood vasculi-
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11. Subspecialty Group of Nephrology, Society
Funding of Pediatrics and Chinese Medical
Association. Evidence-based guidelines on
This study was supported by the National
diagnosis and treatment of childhood
Natural Science Youth Foundation of China common renal diseases (II): evidence-based
(81100535) and the Doctoral Program Fund of guideline on diagnosis and treatment of
the Education Ministry (20090101120104). Henoch–Schönlein purpura nephritis.
Zhonghua Er Ke Za Zhi 2009; 47: 911–913.
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