Henoch Schonlein Purpura

A proposed pathway for follow-up

Watson L 1,2 , Richardson A 1 , Holt R.C.L

1 , Jones C.A

1 , Beresford M.W

2 .

Departments of Paediatric Nephrology 1 and Rheumatology 2 , 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 criteria 1 • Purpura/petechiae rash • • • • Plus any one of; 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 population 2 • (SSNS 3 cases per 100,000; IDDM 207 cases per 100,000) Average North West DGH; • Catchment population of 60,000 children 3 • ≈ 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 nephrotic 1 • Up to 20% nephrotic range proteinuria – Cohorts with established HSPN 15-20% ESRF 2,3 – Accounts for 1.7% all UK ESRF 4

1. Mir et al 2007, 2. Shenoy et al, 2007, 3. Butani et al, 2007, 4. UK Renal Registry 2005

Screening for HSPN

• Screening varies 1 – 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 Resolved renal involvement Persistent/r esolve Renal involvement Diagnosis; Renal biopsy ISKDC classification HSPN 20% ESRF

Evidence-based treatment of HSPN

• • Systematic review of RCTs: no difference • • Early corticosteroids V’s placebo, total n=379 1 Cyclophosphamide V’s supportive, n=56 • Cyclosporin V’s methylprednisolone RCT, n=24 2 Other studies • • Cyclophosphamide + methylprednisolone, n=12 3 Azathioprine + steroids, n=21 4 Cochrane: Few RCTs 5 – 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

Diagnosis; EULAR criteria HSP diagnosis

?

Screening for nephritis No renal involvement Resolved renal involvement Persistent/r esolve Renal involvement

?

Diagnosis; Renal biopsy ISKDC classification HSPN

?

20% ESRF

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 outcome

Primary 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/1.73m

2 • • Macroscopic haematuria >28 days 12 months completed monitoring with urine abnormalities

Presence of proteinuria

Investigations

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 Day 7: allocation n=102 DNA n=2 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% – Specificity 84% (90 to 99%) (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

Presentation & diagnosis Day 7 review

Intensive monitoring

Day 14 review 1 month review 1 month review 3 month review 2 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

• Adoption;

National interest

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)

Diagnosis; EULAR criteria National screening Reliable data HSP diagnosis

?

Screening for nephritis No renal involvement Renal involvement Characterise ‘at risk’ patients Develop renal biopsy indications

?

Diagnosis; Renal biopsy ISKDC classification Resolved renal involvement HSPN Persistent/r esolve Evidence based management

?

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