Immundefekte als Ursache von chronisch-entzündlichen Erkrankungen des Darmes

Zusammenfassung

Chronisch-entzündliche Darmerkrankungen (CED), mit ihren beiden prominentesten Vertretern M. Crohn und Colitis ulcerosa, zeichnen sich durch eine multifaktorielle Ätiologie mit komplexer Regulation zwischen polygenetischer Grundlage und Umwelteinflüssen aus. In den letzten Jahren wurden zahlreiche, jedoch insgesamt seltene, monogenetische Erkrankungen identifiziert, die sich mit einem CED-Phänotyp manifestieren können. Das frühe Erkennen und Anpassen der Therapien dieser heterogenen, immunologischen Erkrankungen sind von hoher Relevanz für den weiteren Verlauf der Erkrankung. In diesem Review diskutieren wir charakteristische Befunde und Umstände, die an das Vorliegen einer monogenetischen Ursache für die intestinale Inflammation denken lassen: Hinweisend können ein früher Krankheitsbeginn, ein Versagen klassischer Therapien, elterliche Konsanguinität, eine auffallende Infektanfälligkeit oder CED-untypische Begleiterkrankungen, Pathologien oder Blutwerte sein. Wir beschreiben ausgewählte Erkrankungen anhand von Fallbeispielen und zeigen auf, wie diese Erkrankungen durch die Kombination von anamnestischen Angaben und klinischen, zellulären sowie genetischen Untersuchungen diagnostiziert werden können. Hierfür schlagen wir eine gestufte, diagnostische Strategie vor, um diesen außergewöhnlichen Erkrankungen als Differenzialdiagnose einer CED nachzugehen.

Summary

Inflammatory bowel diseases (IBD) including Crohn’s disease and ulcerative colitis have a multifactorial pathogenesis with a complex interaction between polygenetic predispositions and environmental factors. Recently, several but alltogether rare monogenetic diseases mimicking an IBD-phenotype have been identified. Early recognition of these conditions and adaption of therapies are highly important for the course of these diseases. In this review we discuss findings that may direct to monogenetic causes of intestinal inflammation such as early onset of disease, failure to respond to standard therapeutic regiments, parental consanguinity, increased susceptibility to infections, or related symptoms, pathology or blood results atypical for CED. We describe selected diseases and discuss in case studies how these conditions can be diagnosed by a combination of patient history, and cellular as well as genetic analyses. Finally, we propose a rational diagnostic pathway to elucidate the underlying cause of these differentials of IBD.

Schlüsselwörter

Immundefekt - chronisch-entzündliche Darmerkrankung (CED) - monogenetische Ursachen von CED

Keywords

Immundeficiency - Inflammatory Bowel Disease (IBD) - monogenetic causes of IBD

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