Henoch-Schönlein purpura:can we prevent nephritis and progression? A Oner and J-C Davin: experts Comments :R Bogdanovic ESPN Lyon 2008

Relation between biological IgA abnormalities and mesangial IgA deposits in isolated hematuria in childhood Davin, Foidart, Mahieu Clin Nephrol In HSP, predominant IgA deposits in mesangium and along capillary walls as well as in other organs. High frequence of IgA abnormalities in HSP vs C and NS

No more terminal galactosyl residue No IgA1 hepatic clearance Normal control HSP and IgAN Terminal galactosyl residues binding to hepatocytes

Effecter mechanisms of IgA deposits in HSPN EC activation by IgACC, IL-8:Inflammation vWF:Thrombocyte aggregation MC activation by IgACC EC Podocyte MC Crescents formation Fibrosis

To treat or not to treat? What patient ? dilemma: all kind of initial clinical symptoms can resolve spontaneously or lead to CRF

Risk of CRF in 78 patients with HSPN followed during 23.4 y (mean) Goldstein et al, Lancet 1992 Patients to treat

Long term outcome of HSPN (Goldstein et al, Lancet 1992)

ANY INITIAL RENAL PRESENTATION OR EVEN APPARENT COMPLETE HEALING CAN LEAD TO CHRONIC RENAL INSUFFICIENCY

Major prognostic factors Initial clinical signs Persisting proteinuria Persisting renal insufficiency Frequent relapsing macroscopic hematuria Histology

Therapeutic use of histological findings > 50% Crescents, high activity index High chronicity index, low activity index Add ACE inhibitors, No immunosuppression, Intensify immunosuppression

Interpretation of non prospective randomized studies on HSPN A/ Spontaneous complete recovery Bariety et al (1964), Vernier et al (1975) : the natural history of this disease favors rapid recovery even following the appearance of the nephrotic syndrome, renal insufficiency, or gross haematuria during the first few months of illness B/ Late deterioration by hyperfiltration after apparent complete recovery. C/ Unpredictable evolution according to clinical symptoms D/ No placebo group possible in some categories of patients because of high CRF risk

Effective treatments for HSPN (RCT) Cochrane Renal group 2008 Anti-inflammatory Steroids (no) Plasma exchange (no) Immunosuppressive Steroids (no) CCP,MMF,CsA (no) Rituximab (no) Plasma exchange (no) Anti-coagulation Anti-platelets aggregation (no) Heparin (no) Anti-MC proliferation ACE inhibitors (no but well for IgAN) Anti-hyperfiltration ACE inhibitors (no but well for IgAN)

Methylprednisolone pulse therapy in the treatment of severe forms of Schönlein Henoch purpura nephritis Niaudet and Habib Ped Nephrol 1997 Historical series (no MPNS) NS Patients Number: 29 ESRF:11 (38%) Latest follow-up: ? Relation CRI and > 50% crescents MPNS series NS Patients Number:38 ESRF:4 (10%) Latest follow-up: 1-16 y Relation delayed treatment/ CRI

Treating severe Henoch-Schönlein and IgA nephritis with plasmapheresis alone Shenoy, Ognjanovic, Coulthard HSPN, 2 IgAN -Mean GFR at presentation: 56 ml/min/ 1.73m2 -Nephrotic syndrome -Plasmapheresis only -Mean follow up: 4 years

MPNS followed by prednison MMF Plasmapheresis 3x / w Biopsy 1 Biopsy 2 Proteinuria Case report Presentation: purpura, microhematuria, proteinuria, NS, joints pain, mild renal insufficiency Biopsy 1: diffuse endocapillary proliferation, 25 % crescents Biopsy 2: diffuse endocapillary proliferation, 25 % crescents

MPNS CPP Pred ACE-I Patient history 6 year old girl Palpable purpura 6 months ago Abdominal pain, arthralgia Proteinuria and hypoalbuminemia Delayed treatment Renal biopsy 25% glomeruli with crescents Mesangial proliferation Mesangial and subentothelial IgA deposits Patient History Proteinuria (g/L) Pl. albumin (g/L) Pl.creatinine ( µmol/L Apparent recovery CRF

no renal symptoms, no treatment Isolated hematuria, minimal proteinuria No biopsy no treatment, excepted in repeated macroscopic hematuria. In all other cases: renal biopsy a/ < 50% crescents: MPNS followed by prednisone –Insufficient response: add immunosuppression, »Insufficient response: repeat biopsy: eventually PEs b/ > 50% crescents: ID + immunosuppression –Insufficient response, repeat biopsy »Add PEs c/ residual proteinuria: ACE inhibitors Apparent recovery Look for hyperfiltration and eventually ACE inhibitors What we actually do

Henoch Schonlein purpura in children: an epidemiological study among Dutch paediatricians on incidence and diagnostic criteria. Aalberse J, Dolman K, Ramnath G, Peirera R, Davin JC Ann Rheum Dis 2007 General Data –232 patients/y (1-18y)/16 millions –Incidence 1-18y: 6.1/100, y: 14.9/100,000 IgA in skin biopsy (53%) how many of them have really HSP?

EULAR/PRES Endorsed Consensus Criteria for the Classification of Childhood Vasculatides under review by the ACR (Vienna 2005) Ann.Rheum. Dis. Online Dec 2005 Seza Ozen, Nicolino Ruperto Michael Dillon Arvind Bagga Karryl Barron Jean-Claude Davin Tomisaku Kawasaki Carol Lindsay Ross Petty Anne-Marie Prieur Angello Ravelli Patricia Woo At least one of the following 4 should be present: 1.Diffuse abdominal pain 2.Any biopsy showing predominant IgA deposition 3.Arthritis or arthralgia 4.Renal involvement (any hematuria and/or proteinuria) In the presence of Palpable Purpura (mandatory criterion) EULAR/PRES Classification Criteria for HSP

Message to take home Treat excepted for mild symptoms MPNS and not prednisone only Do not delay treatment Repeat biopsy if treatment failure Adapt treatment according to histology and response Follow at long term even when complete recovery International multicenter RCT are needed