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 diagnosis Diagnosis; EULAR criteria

Screening for nephritis

No renal involvement

Renal involvement

Resolved renal involvement

Persistent/resolve

20% ESRF

HSPN

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 diagnosis Diagnosis; EULAR criteria

Screening for nephritis

No renal involvement

Renal involvement

Resolved renal involvement HSPN

20% ESRFPersistent/resolve

Diagnosis; Renal biopsy ISKDC classification

?

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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

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 & diagnosisDay 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 diagnosis Diagnosis; EULAR criteria

Screening for nephritis

No renal involvement

Renal involvement

Resolved renal involvement HSPN

20% ESRFPersistent/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