Henoch Schonlein Purpura
A proposed pathway for follow-up
Watson L1,2, Richardson A1, Holt R.C.L1, Jones C.A1, Beresford M.W2.
Departments of Paediatric Nephrology1 and Rheumatology2, Alder Hey Children’s NHS Foundation
Trust Hospital & Institute of Translational Medicine,
University of Liverpool, UK
Henoch Schonlein Purpura
• Small vessel vasculitis
• IgA complex, C3 deposition
• Arterioles, Capillaries, Venules
• Inflammatory neutrophils, monocytes
• Typically presents with rash
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Scrotal involvement
Abdominal pain, bleeding, intussusception
Non-erosive arthritis, arthralgia
Renal involvement
Rarely neurological, lung
Diagnosis
• More common preschool; 90% <10 years old
• EULAR classification criteria1
• Purpura/petechiae rash
Plus any one of;
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Abdominal involvement,
Renal involvement,
Joint involvement (arthritis/arthralgia),
Histological evidence of IgA deposits.
1. Ozen, 2010
Henoch Schonlein Purpura
• Commonest childhood vasculitis
• Incidence 10-20 cases per 100,000 child
population2
• (SSNS 3 cases per 100,000; IDDM 207 cases per 100,000)
Average North West DGH;
• Catchment population of 60,000 children3
• ≈ 6-12 cases of HSP diagnosed by a DGH/year
Rare for GP population
• Average GP 2000 patients, 18% (274) children; 1 case for
approx. every 36 GP’s
2. Gardner-Medwin et al, 2002, 3. http://www.ons.gov.uk
HSP nephritis (HSPN)
• Seen in up to 40%
– Asymptomatic & only long term consequence
– Requires active screening
• Long term outcome of HSPN
– Unselected cohorts risk of renal impairment 1%
• Risk rises if nephritic or nephrotic1
• Up to 20% nephrotic range proteinuria
– Cohorts with established HSPN 15-20% ESRF2,3
– Accounts for 1.7% all UK ESRF4
1. Mir et al 2007, 2. Shenoy et al, 2007, 3. Butani et al, 2007, 4. UK Renal Registry 2005
Screening for HSPN
1
• Screening varies
– Within a centre, region, national & international
• Centre 1: Paediatrician led follow up
• Centre 2: GP led follow up ‘uncomplicated cases’
• Screening imposes financial burden,
parental anxiety
• Variations also in renal referral process and
biopsy indications
1. Weiss P et al J Ped 2009
HSP diagnosis
Diagnosis; EULAR criteria
Screening for nephritis
No renal
involvement
Renal
involvement
Diagnosis;
Renal biopsy ISKDC classification
Resolved renal
involvement
Persistent/r
esolve
HSPN
20% ESRF
Evidence-based treatment of HSPN
Systematic review of RCTs: no difference
• Early corticosteroids V’s placebo, total n=3791
• Cyclophosphamide V’s supportive, n=56
• Cyclosporin V’s methylprednisolone RCT, n=242
Other studies
• Cyclophosphamide + methylprednisolone, n=123
• Azathioprine + steroids, n=214
• Cochrane: Few RCTs5
–Sparse data, no proven benefit of treatment
• Challenges: self resolving, high risk groups, no
standardised care
1. Tizard et al, unpublished, personal communication; Dudley 2007,
Huber 2004, Mollica 2004, Ronkainen 2006.2. Jauhola et al, 2011 3.
Flynn et al, 2001 4. Bergstein et al, 1998 5. Chartapisak W et al. 2009
HSP diagnosis
?
No renal
involvement
Screening for nephritis
Renal
involvement
?
Resolved renal
involvement
Persistent/r
esolve
Diagnosis; EULAR criteria
Diagnosis;
Renal biopsy ISKDC classification
HSPN
?
20% ESRF
HSP screening at Alder Hey
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Designed in 2004, multi-disciplinary
Paediatric nurse led
Urine dipstick, blood pressure
Parent education
Hand held records
• Triaged according to urinalysis (day 7)
– Intensive (8 visits over 12 months)
– Standard (5 visits)
• Total of 12 months monitoring
Aims
Primary
• To describe renal involvement in an unselected
cohort of children with HSP
Secondary
• To revise our nurse led HSP monitoring pathway
Primary outcome
Primary outcome;
Need to exit the nurse led pathway for a medical
review
Exit criteria (excluding patients from nurse led monitoring)
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•
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Hypertension
Urine albumin:creatinine ratio (UACR) > 200mg/mmol
Serum albumin <30g/l
eGFR < 80 ml/min/1.73m2
Macroscopic haematuria >28 days
12 months completed monitoring with urine abnormalities
Investigations
Presence of proteinuria
Presence of exit criteria
HSP coding: Identified n=176
Excluded: Other diagnosis n=11
No care pathway n=61
HSP & sufficient data n=104
46% renal involvement at diagnosis
DNA n=2
Day 7: allocation n=102
Intensive FU:
Proteinuria n=22
Standard FU:
No proteinuria n=80
Developed proteinuria n=13
Moved area n=2
Standard FU (n=65):
Outcome n=1 renal; n=64 normal
Intensive FU (n=35):
Outcome n=8 renal; n=27 normal
Month 12: outcome n=100
Outcome Discharged n=91; renal n=9
Results
Older patients more likely to
develop HSPN
P<0.01
Outcome
• Primary outcome; 9 patients required review
– 2 patients early review (<3 months)
– 7 patients referred after 12 months monitoring
• All patients who developed proteinuria were <6m
from diagnosis
• Proteinuria triggered medical review prior to other
criteria
• Follow up;
– 2 patients early review; grade 3b HSPN, 1 resolved
– 7 patients late review; monitored+/- ACEi, 4 under FU
Day 7 Urinalysis: Predicting outcome
Proteinuria: Poor predictor
– Positive predictive ratio 32%
– Sensitivity 78%
Confidence Interval
(15 to 55%)
(45 to 94%)
Absence of proteinuria: Good predictor of normal
outcome
– Negative predictive ratio 97% (90 to 99%)
– Specificity 84%
(75 to 90%)
Revised HSP Monitoring Pathway
• Updated our current practice
– ‘The Alder Hey HSP Monitoring Pathway’
• 6 month monitoring period
• Paediatric led
– Availability of BP cuffs, paediatric phlebotomists,
easy referral for paediatric advice, parental anxiety
• Stratified according to day 7 urinalysis
• All urine testing undertaken by trained nurses
• Revised exit criteria
The Alder Hey HSP pathway
Presentation & diagnosis
Day 7 review
Intensive monitoring
Day 14 review
Standard monitoring
1 month review
1 month review
2 month review
3 month review
3 month review
4 month review
6 month review
Discharge
6 month review
Refer for medical review
Exit criteria
Robust peer review
Future strategies
• Universal follow up
– Clinical improvements; standardise care, equity,
improved awareness
– Research opportunities; describe ‘at risk’ patients,
early intervention, facilitate RCTs
• Regional standardisation
National interest
• Adoption;
NW centres, Scottish region, Evelina Hospital
• UK support to adopt pathway
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Welsh Paediatric Society
British Association of General Paediatrics
Scottish Paediatric Network (SPARN)
Paediatric Nephrology CSG (Prof Saleem)
Paediatric Rheumatology CSG (Prof Beresford)
General Paediatric CSG (Dr Powell)
HSP diagnosis
National screening
Reliable data
?
Diagnosis; EULAR criteria
Screening for nephritis
Characterise ‘at risk’ patients
No renal
Renal
involvement
involvement
Develop renal biopsy indications
?
Resolved renal
involvement
Diagnosis;
Renal biopsy ISKDC classification
HSPN
Evidence based management
Persistent/r
esolve
?
20% ESRF
Phased development (3-years)
Phase 1:
Universal screening,
HSP registry
Pathway revalidation
Phase 2:
HSPN Working Group,
HSPN registry
Data biopsy indications & management
Phase 3:
Standardise HSPN management,
Renal biopsy indications & consensus management
Randomised controlled trials
Conclusions
• All HSP patients require 6m renal screening
– Renal involvement common
– Majority will have a normal renal outcome
– High risk groups - proteinuria, older, non-Caucasian
– Evidence based renal monitoring
• Universal monitoring with phased development
Acknowledgements
Patients, families:
• Alder Hey patients and families
Authors:
• Professor Michael Beresford
• Dr. Caroline Jones
• Dr. Richard Holt
• Dr. Amanda Richardson
Original HSP pathway committee:
• Dr. Gavin Cleary
• Dr. Briar Stewart
• Dr. Dave Casson
• Elvina White
• Pauline Stone
Clinicians:
• Dr. Henry Morgan
• Dr. Brian Judd
• Dr. Eileen Baildam
• Dr. Liza McCann
Ward D2 staff