Henoch Schonlein Purpura A proposed pathway for follow-up

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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 Childrens NHS
  Foundation Trust Hospital Institute of
  Translational Medicine,
• University of Liverpool, UK

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Henoch Schonlein Purpura

• Small vessel vasculitis
• IgA complex, C3 deposition
• Arterioles, Capillaries, Venules
• Inflammatory neutrophils, monocytes
• Typically presents with rash
• Scrotal involvement
• Abdominal pain, bleeding, intussusception
• Non-erosive arthritis, arthralgia
• Renal involvement
• Rarely neurological, lung

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Diagnosis

• More common preschool 90 lt10 years old
• EULAR classification criteria1
• Purpura/petechiae rash
• Plus any one of
• Abdominal involvement,
• Renal involvement,
• Joint involvement (arthritis/arthralgia),
• Histological evidence of IgA deposits.

1. Ozen, 2010
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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 GPs

2. Gardner-Medwin et al, 2002, 3.
http//www.ons.gov.uk
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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

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Screening for HSPN

• Screening varies1
• 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

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HSP diagnosis
Diagnosis EULAR criteria
Screening for nephritis
No renal involvement
Renal involvement
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Evidence-based treatment of HSPN

• Systematic review of RCTs no difference
• Early corticosteroids Vs placebo, total n3791
• Cyclophosphamide Vs supportive, n56
• Cyclosporin Vs methylprednisolone RCT, n242
• Other studies
• Cyclophosphamide methylprednisolone, n123
• Azathioprine steroids, n214
• 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
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HSP diagnosis
Diagnosis EULAR criteria
?
Screening for nephritis
No renal involvement
Renal involvement
?
Diagnosis Renal biopsy ISKDC classification
Resolved renal involvement
HSPN
?
20 ESRF
Persistent/resolve
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HSP screening at Alder Hey

• 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

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Aims

• Primary
• To describe renal involvement in an unselected
  cohort of children with HSP
• Secondary
• To revise our nurse led HSP monitoring pathway

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Primary outcome

• Primary outcome
• Need to exit the nurse led pathway for a medical
  review
• Exit criteria (excluding patients from nurse led
  monitoring)
• Hypertension
• Urine albumincreatinine ratio (UACR) gt
  200mg/mmol
• Serum albumin lt30g/l
• eGFR lt 80 ml/min/1.73m2
• Macroscopic haematuria gt28 days
• 12 months completed monitoring with urine
  abnormalities

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Investigations
Presence of proteinuria
Presence of exit criteria
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HSP coding Identified n176
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Results
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Older patients more likely to develop HSPN

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Outcome

• Primary outcome 9 patients required review
• 2 patients early review (lt3 months)
• 7 patients referred after 12 months monitoring
• All patients who developed proteinuria were lt6m
  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

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Day 7 Urinalysis Predicting outcome

• Proteinuria Poor predictor Confidence
  Interval
• Positive predictive ratio 32 (15 to 55)
• Sensitivity 78 (45 to 94)
• Absence of proteinuria Good predictor of normal
  outcome
• Negative predictive ratio 97 (90 to 99)
• Specificity 84 (75 to 90)

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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

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The Alder Hey HSP pathway
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Exit criteria
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Robust peer review
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Future strategies

• Universal follow up
• Clinical improvements standardise care, equity,
  improved awareness
• Research opportunities describe at risk
  patients, early intervention, facilitate RCTs
• Regional standardisation

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National interest

• Adoption
• NW centres, Scottish region, Evelina Hospital
• UK support to adopt pathway
• 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)

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HSP diagnosis
Diagnosis EULAR criteria
National screening Reliable data
?
Screening for nephritis
Characterise at risk patients
No renal involvement
Renal involvement
Develop renal biopsy indications
?
Diagnosis Renal biopsy ISKDC classification
Resolved renal involvement
HSPN
Evidence based management
?
20 ESRF
Persistent/resolve
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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
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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

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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