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Syndrome hémolytique et urémique atypique : pour qui l’éculizumab ?

Atypical hemolytic and uremic syndrome: Which patient to treat with eculizumab?

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Réanimation

Résumé

Le syndrome hémolytique et urémique (SHU) est défini par la triade anémie hémolytique mécanique intravasculaire, thrombopénie et insuffisance rénale aiguë. La plupart des SHU non liés à une infection par Escherichia coli produisant une shigatoxine se présentent comme une maladie primitive appelée SHU atypique, en rapport le plus souvent avec une dérégulation du système du complément. Avant l’ère du traitement spécifique, le pronostic était sévère puisque 2 à 10 % des patients décédaient au cours de la première poussée et qu’un tiers évoluait vers l’insuffisance rénale terminale. La compréhension du rôle du complément a ouvert la voie à une nouvelle thérapeutique, l’éculizumab, une immunoglobuline G recombinante monoclonale humanisée anti-C5 qui bloque le clivage du C5. Il a prouvé son efficacité avec 85 % de réponse, que les patients soient plasmarésistants ou plasmadépendants. Il permet un meilleur contrôle de la maladie rénale que la plasmathérapie. L’éculizumab est désormais recommandé en première intention chez l’enfant et dès que les principales causes secondaires de SHU ont été éliminées chez l’adulte. Dans tous les cas, l’utilisation de l’éculizumab est recommandée en cas de résistance à trois à cinq échanges plasmatiques quotidiens. La normalisation du chiffre de plaquettes ne doit pas être le seul critère de jugement de l’efficacité de la plasmathérapie. Elle doit être considérée comme inefficace s’il persiste une thrombopénie, mais aussi si la créatininémie ne diminue pas et/ou si des stigmates d’hémolyse persistent.

Abstract

Hemolytic and uremic syndrome (HUS) is defined by mechanical intravascular hemolytic anemia, thrombocytopenia and acute renal failure. Most HUS, which are not due to shigatoxin-producing Escherichia Coli, present as primary disease called atypical HUS which is due to abnormal control of complement activation. Before the era of specific treatment, prognosis was severe since 2 to 10% of patients died during the first year and one third progressed to end-stage renal disease. Understanding the role of complement lead to a new therapeutic approach based on eculizumab, a recombinant, humanized, monoclonal anti-C5 immunoglobulin G which blocks C5 cleavage. Eculizumab has proven its efficiency with 85% of success in both plasma-resistant and dependent patients, allowing a better control of the disease than plasma therapy when considering renal function. Eculizumab is recommended to date as first-line treatment in children and as soon as the main secondary HUS causes have been ruled out in adults. Eculizumab should be systematically considered in case of resistance to 3–5 daily plasma exchanges, defined by persistent thrombocytopenia but also ongoing hemolysis or lack of improvement in renal function.

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  1. Service de néphrologie et transplantation, hôpital Necker-enfants malades, APHP, Paris Descartes université, 149 rue de Sèvres, F-75015, Paris, France

    A. Servais, A. Hummel & C. Legendre

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  1. A. Servais
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  2. A. Hummel
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  3. C. Legendre
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Correspondence to A. Servais.

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Servais, A., Hummel, A. & Legendre, C. Syndrome hémolytique et urémique atypique : pour qui l’éculizumab ?. Réanimation 23, 645–652 (2014). https://doi.org/10.1007/s13546-014-0928-3

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  • DOI: https://doi.org/10.1007/s13546-014-0928-3

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