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Morbus Still – Ähnlichkeiten und Differenzen zwischen juveniler und adulter Form

Still’s syndrome—similarities and differences between the juvenile and adult forms

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Zusammenfassung

Die systemische juvenile idiopathische Arthritis (sJIA) und die adulte Form des Morbus Still („adult-onset Still’s disease“, AOSD) gehören zum Still-Syndrom. Bis auf das Lebensalter finden sich viele Gemeinsamkeiten zwischen sJIA und AOSD. Heutzutage wird ein biphasisches Krankheitsmodell angenommen. Initial steht dabei die Autoinflammation im Vordergrund, die v. a. durch die Dysregulation des angeborenen Immunsystem bedingt ist. Im späteren Verlauf kann die Erkrankung zu einer chronisch-artikulären Verlaufsform wechseln, die vorwiegend durch das adaptive Immunsystem und somit durch Autoimmunität hervorgerufen wird. Die Hypothese des „Window of Opportunity“ beruht auf diesem biphasischen Modell und besagt, dass durch eine frühe zielgerichtete Therapie ein Wechsel der Verlaufsformen verhindert werden kann. Eine schwere Komplikation des „Zytokinsturms“ der systemischen Krankheitsphase stellt das Makrophagenaktivierungssyndrom dar. Klinisch bestehen viele Gemeinsamkeiten zwischen sJIA und AOSD. So gehören u. a. rezidivierende Fieberschübe, ein flüchtiges lachsfarbenes Exanthem und Arthralgien bzw. Arthritis zu häufigen Beschwerden in allen Altersgruppen. Die wenigen Unterschiede betreffen v. a. die Therapien und Nebenwirkungsspektren bei Kindern gegenüber Erwachsenen. Die genetischen Komponenten sind beim AOSD etwas weniger stark ausgeprägt als bei der sJIA, aber auch diesbezüglich gibt es fließende Übergänge. Ferner sind beide Erkrankungen durch exogene Faktoren wie mikrobielle Trigger stark beeinflusst. Zukünftige Forschungsaspekte könnten die tiefer gehende Untersuchung dieser Auslöser wie Viren, Bakterien oder eines dysbiotischen humanen Mikrobioms beinhalten.

Abstract

Still’s syndrome includes systemic juvenile idiopathic arthritis (sJIA) and the adult form of Still’s disease (adult-onset Still’s disease, AOSD). Except for age, there are many similarities between sJIA and AOSD. A biphasic disease model is currently put forth. At disease onset, autoinflammation predominates, which is caused by dysregulation of the innate immune system. Later on, the disease can progress to a chronic-articular form, which is predominantly mediated by the adaptive immune system and is consequently due to autoimmunity. The “window-of-opportunity” hypothesis is based on this biphasic model and supports the assumption that an early, targeted therapy with cytokine blockade can prevent disease progression to chronic destructive arthritis. Macrophage activation syndrome (MAS) is a serious complication of the so-called cytokine storm during the systemic phase of the disease. Clinically, there are many similarities between sJIA and AOSD. Recurrent fever, a fleeting, salmon-colored rash, and arthralgia/arthritis are common signs and symptoms of both sJIA and AOSD. The few differences are mainly related to the therapies and their side effects in children versus adults. In addition, the contribution of genetics to pathogenesis is more pronounced in sJIA compared to AOSD, but there are also smooth transitions in this respect and both diseases are heavily influenced by exogenous factors such as microbial triggers. Future research aspects could include additional investigation of these triggers such as viruses, bacteria, or dysbiosis of the human microbiome.

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Authors and Affiliations

  1. Sektion für Rheumatologie und Klinische Immunologie, Medizinische Klinik D, Universitätsklinikum Münster, 48149, Münster, Deutschland

    Andrea Regel &  Martin A. Kriegel

  2. Klinik für Pädiatrische Rheumatologie und Immunologie, Universitätsklinikum Münster, 48149, Münster, Deutschland

    Dirk Föll

  3. Abteilung für Translationale Rheumatologie und Immunologie, Institut für Muskuloskelettale Medizin, Universitätsklinikum Münster, 48149, Münster, Deutschland

    Martin A. Kriegel

  4. Department of Immunobiology, Yale University School of Medicine, 06511, New Haven, CT, USA

    Martin A. Kriegel

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  1. Andrea Regel
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Correspondence to Martin A. Kriegel.

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Interessenkonflikt

A. Regel gibt an, dass kein Interessenkonflikt besteht. M. Kriegel gibt die folgenden potenziellen Interessenskonflikte an: Beratertätigkeiten für die Firmen Novartis, Glaxo-Smith Kline, Bristol-Meyers Squibb, Merck Sharp & Dohme, Eligo Biosciences, und vorige Forschungsunterstützung von AbbVie und Anstellung bei Roche. D. Föll gibt die folgenden potenziellen Interessenskonflikte an: Beratertätigkeiten für die Firmen Novartis, Sobi und Boehringer. Forschungsunterstützung durch die Firmen Novartis, Sobi und Pfizer.

Für diesen Beitrag wurden von den Autoren keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

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Hans-Iko Huppertz, Bremen

Hanns-Martin Lorenz, Heidelberg

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Regel, A., Föll, D. & Kriegel, M.A. Morbus Still – Ähnlichkeiten und Differenzen zwischen juveniler und adulter Form. Z Rheumatol 81, 22–27 (2022). https://doi.org/10.1007/s00393-021-01117-w

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