Henoch-Schnlein Purpura (HSP)

anaphylactoid purpura

is a common vasculitis of small vessels with

cutaneous and systemic complications.

It

is the most common cause of

nonthrombocytopenic purpura in children.

EPIDEMIOLOGY
The etiology is unknown
more

frequent in children than adults, with

most cases occurring between 2 and 8 yr of
age,
most frequently in the winter months.
The overall incidence is estimated to be
9/100,000 population.
Males are affected twice as frequently as
females.

PATHOGENESIS
The pathogenesis of HSP is not known,

in specific populations, patients with HSP have a significantly higher

frequency of HLA-DRB1*01 and decreased frequency of the *07 haplotype
than controls.

increased serum concentrations of the cytokines tumor necrosis factor-

(TNF-) and interleukin (IL)-6.

In one study, almost half of the patients had elevated antistreptolysin O (ASO)
anti-bodies, implicating group A streptococcus.

HSP is an IgA-mediated vasculitis of small vessels.

Immunofluorescence techniques show deposition of IgA and C3 in the

small vessels of the skin and the renal glomeruli;

CTLA-4 +49 A/G genotype and HLA-DRB1

polymorphisms in Turkish patients with HenochSchnlein purpura.
Soylemezoglu O, Peru H,

presence of Cytotoxic T lymphocyte-associated

protein 4( CTLA-4) AG genotype and HLA-DRB1*13
could be a risk factor for developing nephrotic-range
proteinuria in these patients.

Pediatr Nephrol. 2008 Aug;23(8):1239-44.

The immunobiology of Henoch-Schnlein

purpura.
Yang YH, Chuang YH, Department of Pediatrics, National Taiwan University Hospital,

group A beta-hemolytic streptococcus (GAS) has widely studied

and found in 2050% of patients with acute HSP by serological tests or bacterial
cultures,

Bartonella henselae (12 of 18 HSP patient sera were positive )

Parvovirus B19 (only one of 29 HSP patients )

Other HSP-associated pathogens have been reported

Staphylococcus aureus,
Helicobacter Pylori,
Hemophilus parainfluenza,
Coxsackie virus,
adenovirus,

hepatitis A virus,

hepatitis B virus

Autoimmun Rev 2008 Jan

CLINICAL MANIFESTATIONS

The disease onset may be acute, or insidious, with

sequential occurrence of symptoms over a period of
weeks or months.

Low-grade fever and fatigue are present in more

than half of affected children.

The typical rash and the clinical symptoms of HSP

are a consequence of the usual location of the acute
small vessel damage primarily in the skin,
gastrointestinal tract, and kidneys.

CLINICAL MANIFESTATIONS

Rash (95-100%), especially involving the legs, may

not be present on initial presentation
Subcutaneous edema (20-50%)
Abdominal pain and vomiting (85%)
Joint pain (60-80%), especially involving the knees
and ankles
Scrotal edema (2-35%)
Bloody stools

Fifteen-year experience of children with

Henoch-Schnlein purpura in southern
Taiwan, 1991-2005

Bao-Ren Nong, Yung-Feng Huang, Chih-Ming Chuang, Chia-Chia Liu, Kai-Sheng Hsieh
Department of Pediatrics, Veterans General Hospital-Kaohsiung, Kaohsiung, Taiwan

No hematuria or proteinuria (n = 77)

Hematuria or proteinur (n = 30)
No. (%)
No. (%)
P
--------------------------------------------------------------------------------------------------------------------Skin rash
GI symptoms
Arthritis

73 (95)
57 (74)
34 (44)

J.Microbiol Immunol Infect. 2007;40:371-376

30 (100)
20 (67)
16 (53)

0.21
0.45
0.40

Fifteen-year experience of children with HenochSchnlein purpura in southern Taiwan, 19912005

Bao-Ren Nong, Yung-Feng Huang, Chih-Ming Chuang, Chia-Chia Liu,
Department of Pediatrics, Taiwan

Variable

Skin rash
Gastrointestinal symptoms Arthritis
No. (%)
No. (%)
No. (%)
-------------------------------------------------------------------------------------------------------Fever group (n = 77)
45 (58)
29 (38)
7 (9)
Non-fever group (n = 30) 15 (50)
9 (30)
6 (20)
P
0.43
0.45
0.12
URI group (n = 64)
Non-URI group (n = 43)
p

33 (52)
27 (63)
0.25

29 (45)
9 (21)
0.01

6 (9)
7 (16)
0.28

Male (n = 63)
Female (n = 44)
P

33 (52)
26 (59)
0.60

25 (40)
13 (30)
0.28

7 (11)
6 (14)
0.69

Rash

beginning as pinkish maculopapules that initially blanch on pressure and progress

to petechiae or purpura,

characterized clinically as palpable purpura that evolve from red to purple to

rusty brown before they eventually fade

last from 3-10 days, and may appear at intervals that vary from a few days to as
long as 3-4 mo.

In <10% of children, recurrences of the rash may not end until as late as a yr,

Damage to cutaneous vessels also results in local angioedema, which may

precede the palpable purpura.

Edema independent of purpura occurs primarily in dependent areas such as

below the waist, over the buttocks (or on the back and posterior scalp in the
infant), or in areas of greater tissue distensibility such as the eyelids, lips, scrotum,
or dorsum of the hands and feet.

Rash

Arthritis

present in more than of children with HSP,

is usually localized to the knees and ankles and

appears to be concomitant with edema.

The effusions are serous, not hemorrhagic,

resolve after a few days without residual deformity or

articular damage.

They may recur during a subsequent reactive phase of

the disease.

Gastrointestinal tract

intermittent abdominal pain that is often colicky in nature.

There may be peritoneal exudate, enlarged mesenteric
lymph nodes, segmental edema, and hemorrhage into
the bowel.
More than half of patients have occult heme-positive
stools,
diarrhea (with or without visible blood), or hematemesis.
Intussusception may occur, which may rarely be followed
by complete obstruction or infarction with bowel
perforation.
If not resolved by hydrostatic reduction during a contrast
study, surgical intervention is necessary.

Significance of bowel wall

abnormalities at ultrasound in HenochSchnlein purpura.
Nchimi
A, Khamis J,
Paquotand
I, Bury
F, Magotteaux

METHODS:
Clinical
ultrasound
dataP.from 43 consecutive
Medical
Imaging
CHC,and
Rue de
Hesbaye,abdominal
75, 4000 Lige,
Belgium
children
withDepartment,
HSP (36 with
7 without
symptoms)

reviewed.

were

Patients with abdominal symptoms were divided into 4 groups (0-III)

The diagnostic value of ultrasound in diagnosing gastrointestinal

involvement of HSP (grades I-III) was calculated using as the
standard of reference the absence or presence of clinical symptoms.

RESULTS: The duration of both symptoms and hospitalization was

significantly higher in group III than in the other groups (P < 0.05).

J Pediatr Gastroenterol Nutr. 2008 Jan;46(1):48-53.

Renal involvement

occurs in 25-50% of children

may manifest with:

hematuria,
proteinuria, or both;
nephritis or nephrosis;
acute renal failure.

Renal involvement at presentation may lead to

chronic hypertension or end-stage renal disease in
the future

Increased serum levels of insulin-like growth

factor (IGF)-1 and IGF-binding protein-3 in
Department
of Pediatric Nephrology and
Rheumatology,, Faculty of Medicine, Turkey
Henoch-Schonlein
purpura.
Yildiz B, Kural N, Aydin B, Colak O.

Serum IGF-1 levels were significantly higher in HSP with proteinuria

than those without proteinuria and controls (p = 0.001 and p =
0.001, respectively).
Also, IGFBP-3 levels were greater in HSP with proteinuria compared
to those without proteinuria and controls (p = 0.005 and p =
0.0001).
Serum immunoglobulin-A/complement-C3 ratio was higher in HSP
than in the controls (p = 0.0001) but this ratio did not change
according to proteinuria, hematuria or positive SOB.
In conclusion, IGF-1 and IGFBP-3 levels could be new markers for
determination of renal involvement in HSP.
Tohoku J Exp Med. 2008 Apr

What is the difference between IgA

nephropathy and Henoch-Schnlein
purpura nephritis?

Davin JC, Ten Berge IJ, Weening JJ.

Department of Pediatrics, Academic Medical Center, University of

Amsterdam, The Netherlands

Kidney Int. 2001 Oct;60(4):1611-2.

What is the difference between IgA

nephropathy
and Henoch-Schnlein
Clinical features
IgAN
HSPN
purpura nephritis
Extra-renal symptoms

Age at onset

<15 y

>15 y

Nephritic/nephrotic syndrome

-/+

+++

Risk of chronic renal failure (CRF)

++

Hypersensitivity

Secondary forms

++

-/+

Endocapillary proliferation

-/+

++

Epithelial crescents

-/+

++

Perivascular glomerular IgA

-/+

++

Subepithelial/subendothelial dense deposits

-/+

++

Fibrin deposits

-/+

++

Relationship between initial clinical

signs and risk of chronic renal failure
in Henoch-Schnlein purpura nephritis

Complications of Henoch-Schnlein Purpura

Hepatosplenomegaly
Myocardial infarction
Pulmonary hemorrhage
Pleural effusion
Unnecessary abdominal surgery
Intussusception
Hemorrhage
Shock
Gastrointestinal bleeding
Bowel infarction
Renal failure
Hematuria
Proteinuria
Seizures
Mononeuropathies
Testicular torsion

Masked severe stenosing ureteritis: a

rare complication of HenochSchnlein purpura.
Siomou E, Serbis A, Salakos C, Papadopoulou F, Stefanidis CJ,
Department of Pediatrics, University Hospital of Ioannina, Stavros Niarchos
Avenue, Ioannina, Greece.

This article reports on a 3.5-year-old boy with HSP

and severe nephritis who developed a unilateral
stenosing ureteritis with atypical
manifestations, resulting in a nonfunctional kidney
and consequent nephrectomy.

Pediatr Nephrol. 2008 May;23(5):821-5

DIAGNOSIS
Diagnostic uncertainty arises when the
symptom complex of edema, rash, arthritis
with abdominal complaints, and renal findings
occurs for a prolonged period.

DIAGNOSIS
Routine laboratory tests are neither specific nor diagnostic.

Affected children often have a moderate thrombocytosis and

leukocytosis.
The erythrocyte sedimentation rate (ESR) may be elevated.
Anemia may result from chronic or acute gastrointestinal blood
loss.
Immune complexes are often present, and 50% of patients have
elevated concentrations of IgA as well as IgM
usually negative for antinuclear antibodies (ANAs), antibodies
to nuclear cytoplasmic antigens (ANCAs), and rheumatoid factor
(even in the presence of rheumatoid nodules).
Anticardiolipin or antiphospholipid antibodies may be
present and contribute to the intravascular coagulopathy.
Intussusception is usually ileoileal in location;
Renal involvement manifests in red blood cells, white blood
cells, casts, or albumin in the urine and azotemia

Endothelin 1 levels in relation to clinical

presentation and outcome of Henoch
Schonlein purpura.
Fessatou S, Nicolaidou P, Gourgiotis D, Georgouli H,

The aim of
the present
study
wasHospital,
to investigate
3rd Department
of Pediatrics
Attikon
University
Greece.

whether ET-1
levels are correlated with the clinical presentation and the
outcome of HSP.

RESULTS:
ET-1 levels in plasma and urine did not differ between patients
and controls at three distinct time points.
urinary ET-1 levels were a significant predictor of the duration
of the acute phase of HSP (HR = 0.98, p = 0.032, CI0.96-0.99).
CONCLUSION: Urinary ET-1 levels are a useful marker for the
duration of the acute phase of HSP but not for the length of
renal involvement.
BMC Pediatr. 2008 Sep 2;8:33.

Definitive diagnosis confirmed by biopsy

cutaneous

site showing leukocytoclastic

angiitis.
Renal

biopsy may show mesangial

deposition of IgA and occasionally IgM, C3,
and fibrin.

H & E stain of skin biopsy showing leukocytoclastic vasculitis with

infiltration of neutrophils.

Henoch-Schnlein purpura.

A: Cutaneous purpura;

B: Urine sediment red blood

cell cast;
C: Acute glomerular
inflammation and crescent
formation;
D: Details of basal membrane
mesangial proliferation
and IgA deposits

Immunofluorescence micrograph of a
glomerulus from a patient with HSP
nephropathy stained for the presence of IgA.

Differential Diagnosis of Henoch-Schnlein

Purpura

Acute abdomen
Meningococcal meningitis or septicemia
Rheumatoid arthritis
Rheumatic fever
Idiopathic thrombocytopenic purpura
Systemic lupus erythematosus
poly-arteritis nodosa,
Child abuse
Drug reactions
Bacterial endocarditis
Rocky Mountain spotted fever
familial Mediterranean fever
inflammatory bowel disease.
Kawasaki disease.

Acute hemorrhagic edema (AHE)

is an acute cutaneous benign leukocytoclastic vasculitis

seen in children 2 yr of age

AHE presents with fever; tender edema of the face, scrotum, hands,
and feet; and ecchymosis (usually larger than the purpura of HSP)
on the face and extremities

petechiae may be seen in mucous membranes.

The patient usually appears well except for the rash.
The platelet count is normal or elevated;
the urinalysis is normal.

The younger age, nature of the lesions, absence of other organ

involvement, and biopsy may help distinguish AHE from HSP.

Acute hemorrhagic edema (AHE)

TREATMENT
Symptomatic treatment

adequate hydration,
bland diet,
pain control with acetaminophen is provided for selflimited complaints of arthritis, edema, fever, and malaise.
Avoidance of competitive activities and avoidance of
maintaining the lower extremities in a dependent position
may decrease local edema.
If edema involves the scrotum, elevation of the scrotum
and local cooling, as tolerated, may decrease discomfort.

TREATMENT

Therapy with oral or intravenous corticosteroids (1-2

mg/kg/day) is often associated with dramatic
improvement of both gastrointestinal and CNS
complications.

the effects of corticosteroids on renal manifestations are

not clear.

intussusception may be life-threatening and managed

with cortico-steroids and, when necessary, hydrostatic
reduction (by air or with contrast) or resection of the
intussusception.

TREATMENT

is the same as for other forms of acute

glomerulonephritis

If anti-cardiolipin or antiphospholipid antibodies are

identified and thrombotic events have occurred,
aspirin (81 mg) given once may decrease the risks
associated with a hypercoagulable state.

Rheumatoid nodules may respond to alternate-day

colchicine (0.6 mg every other day).

Leukocytapheresis for the treatment of

refractory Henoch-Schnlein purpura
resistant to both prednisolone and
intravenous immunoglobulin therapy.

A 5-year-old Japanese girl

. was admitted to a
regional hospital with a generalized purpuric rash
associated with severe abdominal pain
administration of oral PDN at 30 mg daily
additional treatment was initiated with IVIG at the
dose of 1 g kg1 per day. While transient clinical
improvement was noted following
Leukocytapheresis may be attempted as an
effective treatment option in selected patients with
steroid-resistant refractory HSP combined with
severe abdominal symptoms.
Rheumatol Int. 2008 Jun;28(8):

Oki E, Tsugawa K, Suzuki K, Ito E, Tanaka H

Prognosis

HSP is generally a benign disease with an excellent

prognosis.
More than 80% of patients have a single isolated
episode lasting a few weeks.
Approximately 10-20% of patients have recurrences.
Fewer than 5% of patients develop chronic HSP.
Abdominal pain resolves spontaneously within 72
hours in most patients

Clinical outcome in children with HenochSchnlein nephritis

Sevgi Mir1, Onder Yavascan1,

Renal involvement was determined in 58.1%.

Nephrotic and/or nephritic syndrome were found to be

an unfavorable predictor both for short and long-term
outcome (P<0.05).

However, 35% of these patients and 62% of them

showed complete remission after 6 months and longterm course.

Overall prognosis of HSN is relatively good and longterm morbidity is predominantly associated with initial
presentation and renal involvement.

Pediatric Nephrology 21 September 2006

Outcome of Henoch-Schnlein purpura nephritis

treated with long-term immunosuppression
Mohan Shenoy1, Mark G. Bradbury1,

Royal Manchester Children's Hospital

This retrospective study investigated the outcome of 27 children (19 male) with
Henoch-Schnlein purpura nephritis (HSN) of International Study

with long-term immunosuppressive therapy

single centre over a 10-year period.
The treatment protocol comprised daily steroids and cyclophosphamide for
812 weeks followed by azathioprine and a reducing regimen of alternateday steroids for 812 months.
After a mean follow-up period of 7 years following presentation,
37% made a complete recovery
40.7% had persistent proteinuria,
7.4% had persistent proteinuria and were on antihypertensive therapy
14.8% had progressed to end-stage kidney failure (ESKF).
Children with poor outcome were
older at presentation (p 0.005),
had more crescents (p 0.015)
had heavier proteinuria 6 months post initial biopsy (p 0.023).
All of the four children with ESKF had nephrotic range proteinuria and
greater than 50% crescents on initial biopsy.