Therapie der MuSK-MG und neue Antikörper bei Myasthenia gravis

Zusammenfassung

Bis zu 10 % der Myasthenia gravis (MG)-Patienten haben Antikörper gegen die spezifisch in der Skelettmuskulatur exprimierte Tyrosinkinase MuSK (MuSK-MG). Die MuSK-MG ist gekennzeichnet durch einen spezifischen klinischen Phänotyp und unterscheidet sich in ihrer Behandlung von der AChR-MG. Primärziel der Behandlung ist eine Reduktion der Muskelschwäche, besonders bei oropharyngealer oder ventilatorischer Beteiligung. Nur wenige MuSK-MG-Patienten können die Therapie wieder absetzen, die Mehrheit benötigt eine Langzeitbehandlung. Das Ansprechen auf Azetylcholinesterase-Hemmer (AChE-H) ist normalerweise schlecht und häufig mit cholinergen Nebenwirkungen verbunden. Nichtsdestotrotz ist ein initialer Therapieversuch mit AChE-H sinnvoll. Basierend auf klinischer Evidenz wird eine initiale Kortikosteroidtherapie mit 1,5 – 2 mg/kg/Tag Prednison, gefolgt von einer graduierten und langsamen Reduktion auf eine minimaleffektive Dosis, empfohlen. Steroidsparende Substanzen wie Azathioprin, Methotrexat, Mycophenolat Mofetil oder Cyclosporin werden ergänzend eingesetzt. Cyclophosphamid kann bei ausgewählten Patienten eingesetzt werden. Alternativ zeigt Rituximab vielversprechende Ergebnisse und sollte daher bei schweren refraktären Verläufen erwogen werden. Bei Exazerbationen kann die Plasmapherese oder intravenöse Immunglobuline eingesetzt werden. Auf eine Thymektomie sollte bei MuSK-MG weitgehend verzichtet werden. In den letzten 3 Jahren wurden neue MG-Antikörper nachweisbar. Die Low-density lipoprotein receptor-related protein 4 (LRP4)-MG ist klinisch und therapeutisch vergleichbar der MuSK-MG mit einem okulo-bulbo-zervikalen Phänotyp und einem Beginn um das 40. Lebensjahr. Der Phänotyp der Agrin-MG besteht aus einer fazio-bulbo-zervikalen Schwäche, aber unsere Kenntnis dieser Unterform ist noch limitiert. Von Interesse ist das Auftreten von polyvalenten Antikörpern gegen die neuromuskuläre Endplatte. Diese Patientengruppe kann helfen die Krankheitsausprägung, die Verlaufsvarianz sowie das Therapieansprechen besser in Zukunft zu verstehen.

Abstract

Up to 10 % of myasthenia gravis (MG) patients show antibodies against muscle-specific tyrosine kinase (MuSK) receptors. MuSK-MG has a distinct clinical phenotype and differs for their treatment. Key issue of treatment is to reduce muscular weakness, particular with oropharyngeal or ventilatory involvement. A minority of MuSK-MG patients can halt treatment; however the majority will require long-term treatment. Response to acetylcholinesterase inhibitors (AChE-I) is typically poor with a high incidence of cholinergic side effects. Nevertheless, an initial therapy with AChE-I is rational. Based on clinical evidence initiating corticosteroid treatment starting at a dose of 1.5 – 2 mg/kg/day of prednisone, followed by gradual and slow taper to the minimum effective dose is recommended. Steroid-sparing agents such as azathioprine, methotrexate, mycophenolate mofetil or cyclosporine may be added. Cyclophosphamide may be used in select patients. Rituximab has shown promising results and should be considered in severe and refractory patients. Severe exacerbations may be treated by plasma exchange, which most reports specify superior to immunoglobulins. There is no evidence for a role of thymectomy in MuSK-MG. During the past 3 years, new antibodies are detected in MG. Low-density lipoprotein receptor-related protein 4 (LRP4)-MG seems to be clinically and for treatment responses comparable to the MuSK-MG with an oculo-bulbar-cervical phenotype. The Agrin-MG presents with a facio-bulbar-cervical phenotype, however our current knowledge is limited. Most interestingly, there seems to be several MG patients with a poly-antibody response. This group of patients may help to gain novel insights into modifying elements of the MG spectrum in clinics and therapy.

Schlüsselwörter

Myasthenia gravis - MuSK - LRP4 - Agrin - Diagnostik - Therapie

Keywords

myasthenia gravis - MuSK - LRP4 - Agrin - diagnostics - therapy

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