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doi:10.1111/jpc.12403
REVIEW ARTICLE
Abstract: HenochSchnlein purpura is the most common systemic vasculitis of childhood. In the majority of children, the outcome of
HenochSchnlein purpura is excellent with spontaneous resolution of symptoms and signs. However, a small subset of patients will develop
long-term sequelae in the form of chronic kidney disease. While the clinical presentation and diagnosis of HenochSchnlein purpura is
straightforward, treatment of HenochSchnlein purpura nephritis and long-term renal outcomes of more severely affected children are less
certain. This review article gives a general overview of HenochSchnlein purpura with emphasis on recently published information, including
the new classication of childhood vasculitis, insights into pathogenesis of HenochSchnlein purpura and a summary of various treatments of
established HenochSchnlein purpura nephritis.
Key words:
History
The first clinical description of HenochSchnlein purpura
(HSP) comes from English physician William Heberden, who
Key Points
1 HenochSchnlein purpura is the most common systemic vasculitis of childhood presenting with a tetrad of purpura, arthritis or arthralgia, abdominal pain and renal disease. While the
presence of purpura is a compulsory criterion for the diagnosis of HenochSchnlein purpura, other signs and symptoms
are more variably present.
2 Abnormal glycosylation of immunoglobulin A1 molecules
predisposes patients with HenochSchnlein purpura to
formation of large immune complexes. Clearance of these
large molecules is impaired, they deposit in small vessel walls
of the affected organs and trigger immune response leading
to inammatory reaction presenting as clinical signs and
symptoms.
3 The long-term morbidity of HenochSchnlein purpura is
related to nephritis. Based on the current evidence, early
immunosuppressive treatment of children with Henoch
Schnlein purpura should be reserved for those presenting
with severe kidney involvement (rapidly progressive glomerulonephritis, nephrotic syndrome). There might be a role for
immunosuppression in patients with ongoing nephritis
(persistent/increasing proteinuria), but this approach will
have to be tested in large prospective studies before it can
be widely accepted in clinical practice.
Correspondence: Dr. Peter Trnka, Queensland Child and Adolescent
Renal Service, Royal Childrens Hospital, Woolworths Building, 5th Floor,
Herston Road, Herston, QLD, 4029, Australia. Fax: (07) 3636 5505; email:
Peter_Trnka@health.qld.gov.au
Conict of interest: None.
Accepted for publication 21 July 2013.
Epidemiology
HSP is the most common childhood vasculitis with a reported
annual incidence that varies between 10 and 30 cases per
100 000 children < 17 years based on hospital and overall population estimates.5,6 These reports are likely to underestimate the
true prevalence of HSP given the voluntary nature of reporting
to these surveys. The mean age of presentation is 6 years with
most cases in children < 10 years of age,7 and recent studies
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HSP in children
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Fig. 1 Glycosylation of IgA1 molecule. (a) The hinge region of the IgA1
molecule is O-glycosylated by the attachment of N-acetylgalactosamine
(GalNAc) to serine residues. (b) The glycan chains may be elongated with
further addition of galactose (Gal) to GalNAc, and a variable degree of
sialylation with N-acetylneuraminic acid (NeuNAc). (with permission from
reference 14).
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Fig. 2 Pathogenesis of IgA glomerulonephritis. In patients with IgA nephropathy (IgAN), galactose-decient IgA1 is recognized by anti-glycan IgG
antibodies. The formed immune complexes cannot enter the space of
Disse due to their size and interact with the asialoglycoprotein receptor
(ASGP-R) on hepatocytes, but are able to pass through the larger fenestrae
in the glomerular capillaries overlying the mesangium. These deposited
complexes induce glomerular injury by activation of the alternative complement pathway and recruiting inammatory cells (with permission from
reference 15).
Clinical Manifestations
HSP is a systemic vasculitis with multiorgan involvement. The
classic tetrad of signs and symptoms includes: 1/ palpable
purpura, 2/ arthritis or arthralgia, 3/ abdominal pain, and 4/
renal disease.
Purpura
Skin involvement is present in all children with HSP.8 Petechiae
and palpable purpura are the most common, but erythematous,
macular, urticarial or even bullous rashes have also been
observed. Purpura is characteristically distributed symmetrically
over the extensor surfaces of the lower limbs, buttocks and
forearms (Fig. 3) with involvement of trunk and face described
occasionally in younger children. Recurrence of purpura, which
might be associated with more severe renal involvement, is
observed in 25% of children with HSP.
HSP in children
Fig. 3
Abdominal pain
Approximately two thirds of children with HSP develop
abdominal pain,17 usually diffuse, increasing after meals, and
sometimes associated with nausea and vomiting. These symptoms are caused by submucosal haemorrhage and oedema of
the bowel wall, predominantly affecting the proximal small
bowel. The most severe gastrointestinal complication is intussusception, affecting 34% patients with HSP. In 60% of these
cases, it is limited to small bowel. Clinical presentation of intussusception is characterised by severe abdominal pain, often
colicky in nature and vomiting. Other significant, though less
common gastrointestinal complications are gangrene of the
bowel, bowel perforation and massive haemorrhage.
Renal disease
Renal involvement is reported in 2055% of children with
HSP.18,19 The most common finding is isolated microscopic haematuria, usually developing within 4 weeks of the onset of the
disease. Proteinuria of variable degree might be present, and
if severe can present as nephrotic syndrome. Hypertension
might develop at the onset or during recovery. Renal function
is usually normal but the occasional patient might present
with a progressive glomerulonephritis with significant renal
impairment.
Other less common clinical manifestations of HSP include
cerebral vasculitis, scrotal or testicular haemorrhage, and interstitial pulmonary haemorrhage.2022 Distal ureteric vasculitis
resulting in ureteric stenosis, presenting as renal colic has also
been described.23 Potential complications of HSP are summarised in Table 2.
Arthritis/arthralgia
Arthritis/arthralgia is present in three quarters of children with
HSP.16 Joint involvement is usually oligoarticular with large
joints of the lower extremities (knee, ankle, hip) most commonly affected. There is usually prominent periarticular swelling, tenderness and pain; erythema and joint effusion are rare.
Arthritis is non-deforming and heals without chronic damage
within a few weeks.
Diagnosis
Diagnosis of HSP is based on the presence of purpura (palpable)
or petechiae (without thrombocytopaenia) with lower limb predominance (mandatory criterion) plus at least one of the flowing
four features: (1) abdominal pain; (2) arthritis or arthralgia; (3)
leukocytoclastic vasculitis or proliferativeglomerulonephritis
with predominant deposition of IgA on histology; (4) renal
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HSP in children
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Urinalysis
Histology
Every child with HSP should have urinalysis performed at diagnosis and during follow-up. Dipstick assessment of urine for
blood and protein is a good screening test for nephritis. Urine
microscopy may reveal dysmorphic red cells and red-cell casts.
Positive dipstick reading for protein requires quantification of
protein excretion either by measuring protein/creatinine ratio
on a first morning urine sample or protein excretion on a timed
urine sample (24-hour collection).
Blood tests
There are no blood tests specific for HSP and measurement of
serum levels of total IgA is not helpful in confirming the diagnosis or providing prognostic information. Galactose-deficient
IgA1 serum levels seem to distinguish patients with HSP nephritis from patients without nephritis, and might become an important commercially available biomarker in the future.14,25
Imaging
Not all patients with HSP require diagnostic imaging, which is
generally reserved for children with abdominal pain in whom
intussusception is suspected. Abdominal ultrasound is the technique of choice with the accuracy in diagnosing intussusception
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Management of HSP
Management of HSP includes supportive care, symptomatic
therapy and, in some cases, immunosuppressive treatment.
HSP in children
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HSP in children
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Prognosis of HSP
In the majority of children, the outcome of HSP is excellent with
spontaneous resolution of symptoms and signs. HSP recurs in
approximately one third of patients, typically within 4 months
of the initial presentation. Recurrent purpura can be occasionally associated with joint complaints and episodes of gross haematuria although each subsequent episode is generally milder
and shorter. The long-term morbidity of HSP is related to the
degree of HSP nephritis.
In unselected cohorts of children, HSP nephritis is a mild
disease, characterised by microscopic haematuria and minimal
proteinuria, with <1% risk of progression to end-stage kidney
disease (ESKD).18 Reports from tertiary centres indicating that
1030% of children will develop ESKD are likely to overestimate the true risk of ESKD due to the selection of cases with
more severe renal impairment seen in these centres.48,49 Children at risk are those with nephrotic or nephritic/nephrotic
syndrome or renal failure at presentation, and those with
impaired kidney function and persistent proteinuria after
several years of follow-up.29 Children with uncomplicated HSP
are usually managed in the primary care setting either by a GP
or a paediatrician. The aim of the initial follow-up is to identify patients with worsening kidney involvement and is based
on serial urinalyses, blood pressure measurement, blood tests
to assess kidney function and exclusion of other causes of glomerulonephritis. A practical pathway for detection and referral
of children with HSP nephritis to a paediatric nephrologist
during the first 612 months after diagnosis has been developed (Fig. 7).50 The involvement of a paediatric rheumatologist
in cases of severe arthritis/arthralgia might also be warranted.
Histological recurrence of HSP nephritis (IgA deposition)
in transplanted kidneys can be as high as 60% but is rarely
associated with clinical recurrence.51 Long-term outcomes of
transplanted kidneys in patients with HSP nephritis are comparable to other primary diseases with 90% survival at 10
years.52
Conclusion
HSP is a common childhood vasculitis with a good outcome in
the majority of affected children. However, there is a small
subgroup of children who will develop significant renal impairment and some of them will eventually progress to ESKD and
require kidney transplantation. To predict which patients are at
risk of long-term renal sequelae, we need better biomarkers
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Acknowledgements
I thank Dr Leo Francis, Pathology Queensland, Royal Brisbane
and Womens Hospital, Brisbane for providing the histological
samples and Dr Steve McTaggart, Queensland Child and Adolescent Renal Service, Brisbane for reviewing this manuscript.
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HSP in children
Fig. 7 Suggested clinical pathway for detection and referral of patients with HSP nephritis. This pathway has been adapted from local guidelines developed
by Dr D Hothi and Bristol Paediatric Nephrologists, and reprinted with permission from reference 50. Abbreviations: EMU early morning urinalysis; UP:PC
urine protein/creatinine ratio.
healthy controls, but this test is not widely available for clinical
purposes. Contrast enema would miss intussusception limited to
the small bowel; abdominal ultrasound is the imaging test of
choice. Kidney biopsy is usually done in patients with uncertain
diagnosis and in those with more severe kidney involvement
(rapidly progressive nephritis, nephrotic syndrome).
Q3. Which one of the following is the correct answer with
regard to management of HenochSchnlein purpura:
a. All children with HSP should be admitted to hospital for
close monitoring and intravenous hydration
b. Treatment with non-steroidal anti-inflammatory drugs is
contraindicated in children with HSP because of the
potential adverse effects on the kidneys
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HSP in children
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References
1 Rook A. William Heberdens cases of anaphylactoid purpura. Arch.
Dis. Child. 1958; 33: 271.
2 Schnlein JL. Allgemeine und Specielle Pathologie und Therapie, Vol.
2, 3rd edn. Wurzburg: Herisau, 1837; 48.
3 Henoch EH. ber eine eigenthmliche Form von Purpura. Berl. Klin.
Wochenschr. 1874; 11: 6413.
4 Ozen S, Ruperto N, Dillon MJ et al. EULAR/PReS endorsed consensus
criteria for the classication of childhood vasculitides. Ann. Rheum.
Dis. 2006; 65: 93641.
5 Dolezalov P, Telekesov P, Nemcov D et al. Incidence of vasculitis in
children in the Czech Republic: 2-year prospective epidemiology
survey. J. Rheumatol. 2004; 31: 22959.
6 Penny K, Fleming M, Kazmierczak D et al. An epidemiological study of
Henoch-Schnlein purpura. Pediatr. Nurs. 2010; 22: 305.
7 Saulsbury ST. Henoch-Schnlein purpura in children: report of 100
children and review of the literature. Medicine 1999; 78: 395409.
8 Gonzlez LM, Janniger CK, Schwartz RA. Pediatric Henoch-Schnlein
purpura. Int. J. Dermatol. 2009; 48: 115765.
9 Weiss PF, Klink AJ, Luan X, Feudtner C. Temporal association of
Streptococcus, Staphylococcus, and parainuanza pediatric
hospitalizations and hospitalized cases of Henoch-Schnlein purpura.
J. Rheumatol. 2010; 37: 258794.
10 Watanabe T. Henoch-Schnlein purpura following inuenza
vaccinations during the pandemic of inuenza A (H1N1). Pediatr.
Nephrol. 2011; 25: 7958.
11 Kiryluk K, Moldoveanu Z, Sanders JT et al. Aberrant glycosylation of
IgA1 is inherited in both pediatric IgA nephropathy and
Henoch-Schnlein purpura nephritis. Kidney Int. 2011; 80: 7987.
12 Sanders JT, Wyatt RJ. IgA nephropathy and Henoch Schnlein purpura
nephritis. Curr. Opin. Pediatr. 2008; 20: 16370.
13 Kerr MA. The structure and function of human IgA. Biochem. J. 1990;
271: 28596.
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8 Ways Aboriginal Perspective, by Ayla Cornall (12) from Operation Art 2012.
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