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• 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; • Abdominal involvement, • Renal involvement, • Joint involvement (arthritis/arthralgia), • Histological evidence of IgA deposits.

1. Ozen, 2010

• 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

Henoch Schonlein Purpura

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

• 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

HSP diagnosisHSP diagnosis Diagnosis; EULAR criteria

Screening for nephritis

No renal involvement

No renal involvement

Renal involvement

Renal involvement

Resolved renal involvement

Resolved renal involvement

Persistent/resolve

Persistent/resolve

20% ESRF20% ESRF

HSPNHSPN

Diagnosis; Renal biopsy ISKDC classification

Evidence-based treatment of HSPNSystematic 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 diagnosisHSP diagnosis Diagnosis; EULAR criteria

Screening for nephritis

No renal involvement

No renal involvement

Renal involvement

Renal involvement

Resolved renal involvement

Resolved renal involvement HSPNHSPN

20% ESRF20% ESRFPersistent/resolve

Persistent/resolve

Diagnosis; Renal biopsy ISKDC classification

?

?

?

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

Aims

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

Primary outcomePrimary outcome;

Need to exit the nurse led pathway for a medical review

Exit criteria (excluding patients from nurse led monitoring)• 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

InvestigationsPresence of proteinuria

Presence of exit criteria

HSP coding: Identified n=176

Standard FU: No proteinuria n=80

Intensive FU: Proteinuria n=22

Excluded: Other diagnosis n=11No care pathway n=61

HSP & sufficient data n=10446% renal involvement at diagnosis

DNA n=2Day 7: allocation n=102

Developed proteinuria n=13Moved 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

Outcome Discharged n=91; renal n=9

Month 12: outcome n=100

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 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%)

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

Standard monitoring

1 month review

3 month review

6 month review Discharge

Intensive monitoringDay 14 review

1 month review

2 month review

3 month review

4 month review

6 month review

Refer for medical review

Presentation & diagnosis

Day 7 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 – 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 diagnosisHSP diagnosis Diagnosis; EULAR criteria

Screening for nephritis

No renal involvement

No renal involvement

Renal involvement

Renal involvement

Resolved renal involvement

Resolved renal involvement HSPNHSPN

20% ESRF20% ESRFPersistent/resolve

Persistent/resolve

Diagnosis; Renal biopsy ISKDC classification

?

?

?

National screeningReliable data

Characterise ‘at risk’ patients

Develop renal biopsy indications

Evidence based management

Phased development (3-years)Phase 1:

Universal screening, HSP registry

Pathway revalidationPhase 2:

HSPN Working Group, HSPN registry

Data biopsy indications & managementPhase 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

AcknowledgementsPatients, families:•Alder Hey patients and familiesAuthors:•Professor Michael Beresford•Dr. Caroline Jones•Dr. Richard Holt•Dr. Amanda RichardsonOriginal 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