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Systemische Sklerose – klinisches Bild, Diagnostik und Therapie

Systemic sclerosis—clinical picture, diagnosis, and treatment

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Zusammenfassung

Die systemische Sklerose ist eine seltene rheumatische Erkrankung, die durch Haut- und Organfibrose, vaskuläre Veränderungen und das Auftreten spezifischer Autoantikörper charakterisiert ist. Sie zeigt eine hohe Morbidität und Mortalität, weist dabei aber in ihrem Verlauf und den Manifestationen eine beträchtliche Heterogenität auf. Dies macht eine umfassende Diagnostik zur Diagnosestellung und bei den Verlaufsuntersuchungen notwendig, da auch die Therapie den jeweiligen Krankheitsmanifestationen angepasst werden muss. Obwohl spezifische Therapien für gastrointestinale, pulmonale oder auch vaskuläre Komplikationen existieren, sprechen die Patienten meistens nur teilweise an und neue Therapieansätze sind notwendig.

Abstract

Systemic sclerosis is a rare rheumatologic disease that is characterised by skin and organ fibrosis as well as vascular changes and the occurrence of specific autoantibodies. It has a high morbidity and mortality while its manifestations show significant heterogeneity in patients. Thus, diagnosis and follow-up of patients with systemic sclerosis has to be extensive, the more so because treatment must be adapted to organ manifestations. Although specific therapies for gastrointestinal, pulmonary or vascular complications exist, patients respond only partly to these and new therapeutic approaches are still needed.

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Authors and Affiliations

  1. Klinik für Rheumatologie, Universitätsspital Zürich, Gloriastrasse 25, 8091, Zürich, Schweiz

    M. O. Becker, O. Distler & B. Maurer

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  1. M. O. Becker
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Correspondence to M. O. Becker.

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Autoren

M. Becker: finanzielle Interessen: Bayer – Reisekosten | MSD – Referentenhonorar/Reisekosten, | IBSA Institut Biochimique SA – Reisekosten, Roche – Reisekosten – Patente, Geschäftsanteile, Aktien an einer im Medizinbereich aktiven Firma (ausgenommen fondgebundene Beteiligungen): Heidelberg Pharma | Esperion Therapeutics. Nichtfinanzielle Interessen: Angestellter Oberarzt (Rheumatologe), Klinik für Rheumatologie, Universitätsspital Zürich, Schweiz | Mitglied der Deutschen Gesellschaft für Rheumatologie und der Deutschen Gesellschaft für Innere Medizin | Mitglied im Verband Schweizerischer Assistenz- und Oberärztinnen und -ärzte. O. Distler: finanzielle Interessen: Forschungsförderung zur persönlichen Verfügung (finanziell oder als geldwerte Leistungen): Diverse nicht kommerzielle Stiftungen und nationale Wissenschaftsorganisationen (Schweizer Nationalfond (Forschungsförderung) [SNF] etc.) | Actelion, Bayer, Boehringer Ingelheim, Mitsubishi Tanabe – Referentenhonorar: Actelion, Mepha, Pfizer, MSD SHARP & DOHME, Roche, Novartis | Kongress Kostenerstattung: Pfizer (2016, 2015) – bezahlter Berater, interner Schulungsreferent oder Bezug eines Gehalts o. ä.: im Bereich der Sklerodermie und assoziierter Erkrankung: A. Menarini, Amgen, AnaMar, Bayer, Boehringer Ingelheim, Catenion, CSL Behring, ChemomAb, Ergonex, Roche, GSK, Inventiva, Italfarmaco, iQone, iQvia, Lilly, Medac, Medscape, Mitsubishi Tanabe Pharma, MSD SHARP & DOHME, Novartis, Pfizer, Roche, Sanofi, Target Bio Science und UCB. Nichtfinanzielle Interessen: Professor, Klinikdirektor, Klinik für Rheumatologie, UniversitätsSpital Zürich | Direktor Forschung, Zentrum für Experimentelle Rheumatologie, Schlieren | Bereichsleiter Bereich Traumatologie/Dermatologie/Rheumatologie (TDR), UniversitätsSpital Zürich | Mitgliedschaften: Schweizerische Gesellschaft für Rheumatologie Zürich, Board Mitglied European Scleroderma Trials and Research Group (EUSTAR), Walter-Siegenthaler-Gesellschaft, Chefärztegesellschaft des Kantons Zürich, Stiftungsrat, Swiss Clinical Quality Management in Rheumatic Diseases in Zürich, Stiftungsrat Hartmann-Müller-Stiftung, Schweizerische Akademie der Medizinischen Wissenschaften (SAMW), Schweizerische Akademie der Medizinischen Wissenschaften in Bern. B. Maurer: finanzielle Interessen: Forschungsförderung zur persönlichen Verfügung (finanziell oder als geldwerte Leistungen): OPO-Stiftung, Hartmann-Müller-Stiftung, EMDO Stiftung (Forschungsförderung), Vontobel-Stiftung, Herzog-Egli-Stiftung, Olga-Mayenfisch-Stiftung, Lunge Zürich, Zuschuss der Deutschen Gesellschaft für systemische Sklerose, Filling-the-Gap-Zuschuss, Prof.-Max-Cloetta-Stiftung, AbbVie, Protagen, Novartis, Protagen – Kongressunterstützung durch Pfizer, Roche, MSD SHARP & DOHME und Actelion. Nichtfinanzielle Interessen: leitende Ärztin am UniversitätsSpital Zürich (Rheumatologie) | Mitgliedschaften: Zürcher/Schweizer Gesellschaft für Rheumatologie, Foederatio Medicorum Helveticorum (FMH), Verband Schweizerischer Assitenz- und Oberärztinnen und -ärzte (VSAO), Deutschen Gesellschaft für Innere Medizin, EuMyoNet, IMACS, European Scleroderma Trials and Research Group.

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Additional information

Wissenschaftliche Leitung

E. Gaffal, Magdeburg

M. Meurer, Dresden

S. Ständer, Münster

R.-M. Szeimies, Recklinghausen

A. Zink, München

Dieser leicht modifizierte Beitrag erschien ursprünglich in Zeitschrift für Rheumatologie (2019) 78:439–457. Die Teilnahme an der zertifizierten Fortbildung ist nur einmal möglich.

CME-Fragebogen

CME-Fragebogen

Welche Medikamente werden zur Therapie der mit systemischer Sklerose assoziierten pulmonalarteriellen Hypertonie eingesetzt?

Phosphodiesterase(PDE)-5-Hemmer

Kalziumantagonisten

Angiotensininhibitoren

Glukokortikoide

Glyceryl-Nitrate

Welcher der folgenden Befunde ist Teil der neuen Klassifikationskriterien des American College of Rheumatology (ACR)/der European League against Rheumatism (EULAR) für die systemische Sklerose?

Hyper‑/Hypopigmentierung der Haut

Pulmonalarterielle Hypertonie

Kalzinose(n)

Nierenversagen/renale Krise

Kardiomyopathie

Welche Therapieform kann sowohl Haut- als auch Lungenfibrose und die krankheitsbedingten Einschränkungen der Lebensqualität deutlich verbessern, ist aber u. U. mit hohen Nebenwirkungen assoziiert?

Mesenchymale Stammzelltransplantation

Botoxtherapie

Eigenbluttherapie

Autologe Stammzelltransplantation

Langzeitmedikation mit Vasodilatatoren

Ein 48-jähriger Patient wird mit Myalgien, Arthritis (v. a. Handgelenke und oberes Sprunggelenk, aber auch Knie- und Fingergelenke) zu Ihnen überwiesen. Zusätzlich findet sich eine deutliche Hautverdickung an den Unterarmen (nicht den Händen) sowie Unterschenkeln beidseits und „Cellulite“-ähnliche Veränderungen (Orangenhaut). Ein Raynaud-Phänomen hat der Patient nicht. Welche Diagnose ist am wahrscheinlichsten?

Nephrogene systemische Fibrose

Atypische systemische Sklerose

Eosinophile Fasziitis (Shulman-Syndrom)

Skleromyxödem

Mischkollagenose mit Anteilen einer systemischen Sklerose

Welche Therapie hat die beste Evidenz zur Behandlung bzw. Vorbeugung des Raynaud-Phänomens?

Fluoxetin

Riociguat

Kalziumantagonisten

Nitrate

Statine

Welche Autoantikörperspezifität wird typischerweise vor allem bei der systemischen Sklerose gefunden?

Anti-Nukleosomen-Antikörper

Anti-CCP-Antikörper

Anti-Scl70-Antikörper

Anti-U1RNP-Antikörper

Antikörper gegen Doppelstrang-DNA

Welche Untersuchung ist am ehesten sinnvoll zum Screening für pulmonalarterielle Hypertonie als Organmanifestationen der systemischen Sklerose?

CT des Thorax

Lungenfunktion mit Diffusionskapazität

Elektrokardiogramm

Röntgenuntersuchung des Thorax

Rechtsherzkatheter

Eine 35-jährige Patientin wird mit einem Raynaud-Phänomen zu Ihnen in die Praxis überwiesen. Sie machen eine Kapillarmikroskopie, die keine pathologischen Veränderungen ergibt und der Titer der antinukleären Antikörper (ANA) ist mit 1:160 ohne Nachweis von spezifischen Autoantikörpern für eine Kollagenose. Wie hoch ist ungefähr die Wahrscheinlichkeit – gemäß Studien –, dass diese Patientin in den nächsten 5 Jahren eine systemische Sklerose entwickelt?

Etwa 0–5 %

Etwa 5–10 %

Etwa 10–20 %

Etwa 20–35 %

Etwa 35–50 %

Was ist eine typische Krankheitsmanifestation der systemischen Sklerose?

Eine der thrombotisch-thrombozytopenische Purpura (TTP)/dem hämolytisch-urämischen Syndrom (HUS) ähnliche Mikroangiopathie

Mononeuritis multiplex

Glomerulonephritis

Hämorrhagische Alveolitis

Purpura

Eine 58-jährige Patientin mit einer limitiert kutanen systemischen Sklerose (Raynaud-Phänomen, minimale distale Hautbeteiligung) hat eine Erhöhung der alkalischen Phosphatase (>3 ×) und eine leichte Erhöhung der γ‑Glutamyltransferase (GGT; etwa 1–2 ×). Welche Lebererkrankung ist am wahrscheinlichsten?

Primär sklerosierende Cholangitis (PSC)

Autoimmune Hepatitis Typ I/II

Hämochromatose

Nichtalkoholische Steatosis hepatis (NASH)

Primär biliäre Cholangitis (PBC)

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Becker, M.O., Distler, O. & Maurer, B. Systemische Sklerose – klinisches Bild, Diagnostik und Therapie. Hautarzt 70, 723–741 (2019). https://doi.org/10.1007/s00105-019-4454-0

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