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Vaskulitiden

Vasculitis

  • Leitthema
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Der Nephrologe Aims and scope

Zusammenfassung

Die Einteilung und Nomenklatur der Vaskulitiden wurde in der Chapel-Hill-Konsensuskonferenz 2012 erheblich geändert bzw. aktualisiert. Bei der Pathogenese der ANCA-assoziierten Vaskulitis sind die Modelle komplexer geworden. Genetische Faktoren und infektiöse Trigger spielen neben B- und T-Zell-Response, endothelialen Veränderungen und dem Komplementsystem eine Rolle. Hauptplayer bleiben die Neutrophilen und neu ihre NETs („neutrophil extracellular traps“), die zur Komplementaktivierung und zur Autoantigenpräsentation führen, sowie die B-Zellen mit den ANCA. Bei der Therapie spielen die Aktivitätsstadien eine erhebliche Rolle. Beim lokalisierten oder früh systemischen Stadium kommt bei normaler Nierenfunktion Methotrexat mit Steroiden in Betracht. Im generalisierten Stadium kann Cyclophosphamid i. v. oder Rituximab – beide gemeinsam mit Steroiden – zur Induktionstherapie verwendet werden. Mycophenolat-Mofetil (MMF) ist nicht gleichwertig (weniger Remissionen, mehr Rezidive). Bei schwerer Nierenbeteiligung oder anderem Organversagen sind zusätzlich zu i. v. Steroidpulsen und Cyclophosphamid (wahrscheinlich ist auch Rituximab möglich, Datenlage aber dünn) Plasmapheresen indiziert. Bei der Remissionserhaltung ist Azathioprin besser als MMF, wobei eine längere Therapie zu weniger Rezidiven führt. Besonders Patienten mit PR3-ANCA, Granulomen und kurzer Cyclophosphamid- und Steroidtherapie sind rezidivgefährdet. Rituximab hat sich nach Cyclophosphamid-Induktion bei der Erhaltungstherapie Azathioprin überlegen gezeigt (Cave: „off-label“). Die Frage der Anschlusstherapie nach erfolgreicher Rituximab-Induktion ist noch nicht geklärt. Neben keiner Therapie und Reinduktion bei Rezidiv kommen eine Anschlussbehandlung mit Azathioprin, eine präemptive Rituximab-Gabe (z. B. alle 4–6 Monate für 2 Jahre oder für immer – „off-label“) oder die Gabe von Rituximab bei Rezidivgefahr in Betracht. Hier müssen jedoch erst verlässliche Marker gefunden werden.

Abstract

In 2012 the International ChapeI Hill Consensus Conference led to a substantial revision and much better nomenclature of vasculitides. In the pathogenesis of vasculitis ANCA-associated the models have gained in complexity. Genetic factors, infectious triggers and alterations in B-cell und T-cell responses play a role together with endothelial changes and involvement of the complement system. Major players remain the neutrophils and now recently neutrophil extracellular traps (NETs) leading to complement activation and autoantigen presentation and B-cells together with ANCA. Regarding treatment the stage of activity plays an important role. In a localized or early systemic situation methotrexate can be used together with steroids if renal function is normal. In a generalized stage intravenous (i. v.) cyclophosphamide or rituximab, both in addition to steroids, can be used as induction therapy. Mycophenolate mofetil (MMF) is less effective (lower rate of remission and more relapses). In cases of severe renal disease or other vital organ failure, plasmapheresis should be added to i. v. methylprednisolone pulses and cyclophosphamide (probably rituximab is also possible but there are only sparse data). Regarding remission maintenance treatment azathioprine is superior to MMF and longer treatment periods reduce relapse rates. Patients with PR3-ANCA, granulomas and short-term steroid or cyclophosphamide treatment have a higher risk of relapse. Rituximab has been shown to be superior to azathioprine for maintenance after cyclophosphamide induction (cave: off-label). The question of maintenance treatment after rituximab induction has not yet been clarified. Besides no treatment and re-induction in the case of a relapse, azathioprine may be chosen or preemptive rituximab (e.g. every 4–6 months for 2 years or forever, off-label) or rituximab in the case of increasing biomarkers for a relapse; however, reliable markers still need to be defined.

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Authors and Affiliations

  1. Medizinische Klinik III, Klinikum Fulda gAG, Universitätsmedizin Marburg – Campus Fulda, Pacelliallee 4, 36043, Fulda, Deutschland

    M. Haubitz

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M. Haubitz weist auf folgende Beziehung hin: M. Haubitz hat von Roche für Vorträge und eine Tätigkeit im Advisory Board Reisekosten und Honorare erhalten.

Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.

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J. Floege, Aachen

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Haubitz, M. Vaskulitiden. Nephrologe 11, 124–133 (2016). https://doi.org/10.1007/s11560-015-0024-3

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  • DOI: https://doi.org/10.1007/s11560-015-0024-3

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