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 1987.

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:InflammationvWF: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 2007

-14 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 reportPresentation: purpura, microhematuria, proteinuria, NS, joints pain, mild renal insufficiency

Biopsy 1: diffuse endocapillary proliferation, 25 % crescents

Biopsy 2: diffuse endocapillary proliferation, 25 % crescents

MPNSCPP

Pred ACE-IPatient 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

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: 6.1/100,000• 3-6 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 pain2. Any biopsy showing

predominant IgA deposition3. Arthritis or arthralgia4. 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