23/06/2014 1 Cryoglobuline Dominique Chauveau Néphrologie & Immunologie clinique CHU Rangueil – Toulouse Glomérulopathies : Aspects physiopathologiques & thérapeutiques Séminaire national de Néphrologie – Gressy, Juin 2012 Les 2 variétés de cryoprécipité 1. Cryoglobuline (plasma et sérum) 2. Cryofibrinogène (plasma seul)
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Diminue les manifestations « superficielles » :-Ulcère cutané
- Purpura
Effet moindre sur neuropathie (clinique > EMG)
Améliore à court terme, et pas totalement la fonction rénale
Bonne tolérance hépatique
Dammacco F, Blood 2010Petrarca A, Blood 2010
Formes rénales graves des cryo HCV+ :
corticoïdes et immunosuppression
ou rituximab ?
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Formes rénales graves des cryo HCV+ : corticoïdes et immunosuppression
• Pas d’essai contrôlé
• Indications : vascularite sévère ou atteinte rénale grave
• Corticothérapie : - 3 embols méthylprednisolone (0,5-1 gr)- puis 0,5 mg/kg/j x 30 jours- arrêt en 3-6 mois
• Cyclophosphamide : 1-2 mg/kg/j x 60 jours
• Echanges plasmatiques : quelle place ?
Campise, Nephrol Dial Transplant 1999
D’Amico, Kidney Int 1998
Occurrence of severe systemic drug reactions in HCV infected patients with MC vasculitis treated with rituximab infusions
Sene D et al, Arthritis & Rheumatism, 2009
• Occurred in 6 (one-fourth) of 22 individuals
• Major risk factors :
– High baseline levels of cryoglobulin
– The1,000 mg rituximab high-dose infusion,
– And a high level of complement activation
• Should be distinguished of rituximab-associated serum sickness syndromes that typically occurs more than 5 days after rituximab infusion
• In vitro – rituximab formed a complex with the cryoprecipitating IgM that had rheumatoid factor (RF) activity.
– addition of rituximab to serum containing an RF-positive IgM type II mixed cryoglobulin was associated with visibly accelerated cryoprecipitation.
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A. The addition of rituximab (right tube) induced within 30 minutes the appearance of a visible cryoprecipitate in the tube.
In vitro cryoprecipitation experiments after addition of rituximab to serum containing an HCV-positive type II mixed cryoglobulinwith an IgM component.
B, Remaining “pancake-like” deposit (arrow) after a 7-day incubation of an IgM type II mixed cryoglobulin serumwith rituximab at 4°C and after rewarming (right tube).
Occurrence of severe systemic drug reactions in HCV infected patients with MC vasculitis treated with rituximab infusions
Sene D et al, Arthritis & Rheumatism, 2009
• Recommandation for rituximab use in cryoglobulinemic vasculitis,when mixed cryoglobulin serum levels are high (> 1.00 g/l) and C4 serum levels low (< 0.03 g/l) :
�Prior to rituximab administration : perform plasma exchanges to lower mixed cryoglobulin serum levels in patients with high serum levels of mixed cryoglobulin
�Use low-dose rituximab protocol (375 mg/m2 weekly for 4 consecutive weeks) or even lower doses.