2. • Synonyms include anaphylactoid purpura,
allergic vasculitis, leukocytoclastic vasculitis,
and rheumatoid purpura.
3. • First description was by
Heberden in 1806
• Schӧnlein first described
the association of
arthralgias and purpura,
and he termed it ‘peliosis
rheumatica’ in 1837.
• Henoch (Schӧnlein’s
student) described GI and
renal manifestations
in 1874 and 1899
respectively.
4. HSP in Children
• Self limited
• 20% long standing renal involvement. Of that
20%, 7% need HD
• Children with renal involvement have a 35-
44% higher incidence of CKD in 24 year follow
up.
(Ronkainen J: The adult kidney 24 years after childhood HSP: retrospective
cohort. Lancet 360: 666-670, 2002)
5. HSP in Adults
• NO comparable incidence in adults
• Overall 26% mortality in adults
• Knowledge of natural history in adults is limited due to small
series with short follow up.
• More serious skin and joint involvement.
• Renal disease is more frequent and more severe in adults, and
more likely to progress.
• Recurrence 10-40%, within 4 months.
• Recurrence does not worsen prognosis.
6. Pathogenesis
• Remains unknown; however, it is generally considered
• Immune complex-mediated disease characterized by
the presence of polymeric IgA1 (pIgA1)-containing
immune complexes predominantly in dermal,
gastrointestinal, and glomerular capillaries .
• The pathognomonic granular IgA and C3 deposits in
the mesangium are indistinguishable from those seen
in IgA nephropathy
7. • C1GALT1 polymorphisms are associated with
Henoch–Schönlein purpura nephritis
• the G allele and GG genotype of 1365A/G
were significantly increased in HSPN patients
8. Clinical feature
• Rieu and Noel reported renal involvement in 33% of children and
63% of adults with HSP
• A characteristic feature is hematuria- often is macroscopic but may
be microscopic and either transient, persistent, or recurrent
• Hematuria may accompany relapses of purpura or recur long after
the extrarenal manifestations have resolved, often in association
with upper respiratory infections
• Usually, there is associated proteinuria of variable intensity, and the
frequency of the nephrotic syndrome is also extremely variable.
• Deterioration of GFR may occur, and azotemia or end-stage renal
failure may ensue
9. Renal Involvement- Children
• Only 1-5% progress to ESRD.
• 10-50% of children get microscopic hematuria,
mild GN, and proteinuria that resolves
spontaneously.
• Up to 33% recurrence in children, but
symptoms are milder and shorter duration
10. Renal Involvement-Adults
• 11% on HD
• 10-30% ESRD at 15 years
• 27% CrCl <50%
• 50% persistent hematuria
• 47% moderate proteinuria
• 8% nephrotic range
• 20% remission
Evangeline, P: HSP in adults, Outcome and Prognosis factors, J Am Soc Nephrology 13:1271: 2002
11. Children versus Adults
• 95 adults and 57 children, 5 year follow up
• Crescents and nephrotic range proteinuria equal incidence
• Residual CKD 31% in adults versus 24% children.
• Adults 2x more likely to progress to HD/ESRD. (16 versus 7%)
• Poor prognosis: >50% crescents, renal impairment at
presentation, UP/C> 1.5 g/day, HTN
Coppo R: Long term Prognosis of HSP nephritis in adults and children. Nephrol Dial
Transplant 12: 2277-2283, 1997
13. Diagnostic criteria
Palpable purpura (mandatory) in the presence of
at least one of the following four features:
– Diffuse abdominal pain
– Arthritis (acute) or arthralgia
– Renal involvement (any haematuria and/or proteinuria)
– Any biopsy showing predominant IgA deposition
Ozen S et al Ann Rheu Dis 65:936-41, 2006 ,EULAR/PReS consensus criteria
14.
15. What constitutes renal involvement?
• Isolated Haematuria
• Isolated Proteinuria
• Nephrotic syndrome
• Nephritic syndrome
– Renal impairment
– Hypertension
Risk of long term renal impairment and duration of follow up recommended for Henoch-Schönlein purpura with
normal or minimal urinary findings: a systematic review. Narchi H. Arch Dis Child 2005
16. What investigations if renal involvement?
Primary Investigations
U&E, HCO3, creatinine
Albumin
urine Protein:Creatinine
urine dipstix and microscopy
FBC
Clotting screen
Secondary Investigations
Anti-streptococcal titre (ASOT)
Antinuclear antibody (ANA) + dsDNA
Antinuclear cytoplasmic antibody (ANCA)
Complement – C3, C4
ESR
CRP
Renal ultrasound
17. HSP – Onset of nephritis
Time of onset of urinary abnormalities after the
diagnosis of HSP
Weeks after HSP diagnosis
1 2 4 6 8 24
% 37 54 84 90 91 97
Narchi H Arch Dis Child 90:916-20, 2005
18. Indications for renal biopsy
• Acute renal impairment/nephritic syndrome at presentation
• Nephrotic syndrome with normal renal function persisting at
4 weeks
• Nephrotic range proteinuria (urine protein/creatinine ratio,
>250 mg/mmol) at 4–6 weeks (if not improving
spontaneously)
• Persistent proteinuria
• urine protein/creatinine ratio >100 mg/mmol at >3 months
particularly if diagnosis is not clear.
Clinical practice: Diagnosis and management of Henoch–Schönlein purpura.
McCarthy H & Tizard EJ. Eur J Pediatr (2010)
19. Henoch- Schönlein Nephritis histological classification
– ISKDC
Class Mesangial change Crescents Frequency %
(n = 355) *
I Minimal changes 8
II Pure mesangial
proliferation
29
III a
b
focal
diffuse
mesangial proliferation
mesangial proliferation
<50% 43
IV a
b
focal
diffuse
mesangial proliferation
mesangial proliferation
50 – 75% 12
V a
b
focal
diffuse
mesangial proliferation
mesangial proliferation
>75% 6
VI Membranoproliferative
like glomerulonephritis
3
* Pooled data from Pathology of the Kidney, 6th Edition, Jennette et al. Philadelphia,
Lippincott Williams & Wilkins, 2007.
21. Normal glomerulus
Moderate mesangial expansion –
class 2 – ‘mild’.
Mesangial proliferation and
crescent formation
Focal and segmental mesangial
hypercellularity with associated
capillary luminal leukocytes
22. • Immunofluorescence microscopy. There is granular staining for IgA
in mesangial regions and segmentally along capillary walls.
• which is often accompanied by C3, fibrinogen, and both light
chains, and less frequently by IgG and/or IgM
23. • Electron microscopy. There are electron-dense
deposits in the mesangium, and segmentally
in subendothelial locations.
24. What treatments can be used for HSP
Nephritis?
• Immunosuppressants
– Steroids
• IV MP
• po Prednisolone
– Cyclophosphamide (CyP)
– Ciclosporin
– Plasma exchange
– Rituximab?
• ACEi
25. • No adequate evidence
• No RCTs for treatment of HSP nephritis
• The treatment of HSP nephritis is
controversial, and recommendations are
based on small, often uncontrolled series.
26. Current RHSC(G) guideline
HSP Class Management
I & II No immunosuppressant treatment routinely
ACEi if persistent proteinuria
III Pulse IV methylprednisolone 600mg/m2 for 3 days
Oral prednisolone 60mg/m2 (max 60mg) for 1 month and taper
Consider Cyclophosphamide 2.5mg/kg/day for 56 days
ACEi if persistent proteinuria
IV & V (VI) Pulse IV methylprednisolone 600mg/m2 for 3 days
Oral prednisolone 60mg/m2 (max 60mg) for 1 month and taper
Cyclophosphamide 2.5mg/kg/day for 56 days
Consider Plasma exchange
ACEi if persistent proteinuria
27. Will steroids prevent renal disease in HSP?
• No!
ChartapisakW, Opastirakul S, Willis NS, Craig JC, Hodson EM. ADC, 2008
and Cochrane review updated, 2010.
28. Will steroids improve outcome for acute mild
renal symptoms?
• RCT early steroid in HSP
• Sub group analysis
• 71 with renal symptoms
in first month
• More rapid resolution
with steroids at 6 months
– Ronkainen et al. J Ped 2006.
29. Recommended follow-up
• BP & urine dipstix for
– week 1-6 weekly
– Week 7-24 monthly
Narchi H Arch Dis Child 90:916-20, 2005
30. The adult kidney 24 years after childhood HSP: a
retrospective cohort study.
Clinical presentation at onset of Henoch -
Schönlein purpura
I no renal symptoms
II proteinuria + haematuria, and
no biopsy specimen or ISKDC
biopsy grade I - II
III renal symptoms > 1 month,
nephritis or nephrosis, and
ISKDC biopsy grade III or more
Nephritis:
haematuria and 2/3 symptoms: increase in
serum creatinine, oliguria, hypertension.
Nephrosis:
proteinuria > 40 mg/m2/hr.
Clinical outcome
A healthy
B minor urinary abnormalities
(intermittent hypertension,
proteinuria, haematuria)
C active renal disease
(hypertension, constant
proteinuria)
D end-stage renal disease (dialysis
treatment or renal
transplantation)
Ronkainen et al. Lancet, 2002
31. The adult kidney 24 years after childhood HSP: a
retrospective cohort study.
Onset Grade Number of patients Good outcome
A + B
Poor Outcome
C + D
I 9 9 (100%) 0
II 18 16 (89%) 2 (11%)
III 20 13 (65%) 7 (35%)
• Clinical outcome after mean follow-up of 24·1 years, by symptoms at
onset
• Ronkainen et al. Lancet, 2002
32. Discuss with Nephrologist
• Hypertension
• Abnormal renal function
• Macroscopic haematuria > 5 days
• Persisting proteinuria
33. Summary
• HSP is the commonest vasculitis of childhood
• Renal involvement is frequent
• Significant renal disease is less common but can develop up to 3 months
from presentation
• Early steroid therapy in HSP does not prevent nephritis
• Treatment interventions for HSP nephritis are not well evidence based
• Variations in long term outcomes may reflect changes in clinical practice
over time
• Prompt intervention in more severe nephritis with immunosuppression is
still used
• ACEi for persistent ‘chronic’ proteinuric nephropathy is recommended
