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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
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