VEXAS-Syndrom – Eine hämatoinflammatorische Erkrankung

Zusammenfassung

Das VEXAS-Syndrom (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) ist eine erworbene autoinflammatorische Erkrankung, die auf somatischen Mutationen im Gen UBA1 beruht und hauptsächlich Männer älter als 50 Jahre betrifft. Klinisch besteht das Bild einer entzündlichen Systemerkrankung, die sich mit vegetativen Symptomen und vorwiegender Affektion der Haut, der Lunge und des hämatopoetischen Systems präsentiert. Aufgrund der vielfältigen Organmanifestationen kommen zahlreiche Fachdisziplinen für einen Erstkontakt mit den Erkrankten infrage. Zusätzlich muss das VEXAS-Syndrom als Phänokopie verschiedener rheumatologischer Erkrankungen bedacht werden. Die Diagnose des VEXAS-Syndroms beruht gegenwärtig ausschließlich auf dem Nachweis pathogener Varianten im Gen UBA1 im passenden klinischen Kontext. In therapeutischer Hinsicht wird Kontrolle der Hyperinflammation durch Immunsuppression („block the cytokine storm“) und/oder Proliferationshemmung und Eradikation des aberranten Knochenmarkklons („target the clone“) angestrebt. Der Krankheitsverlauf ist durch refraktäre Verläufe und häufige Infektkomplikationen gekennzeichnet. Das 5-Jahresüberleben beträgt aktuell etwa 60%.

Abstract

The VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is a systemic autoinflammatory condition that is caused by an acquired deficiency of the UBA1 gene in haematopoetic progenitor cells and typically affects male older than 50 years. The clinical phenotype is characterised by systemic inflammation, including constitutional symptoms, skin disease, musculoskeletal involvement, lung involvement and haematological manifestations. Specialists from multiple disciplines may encounter VEXAS patients at disease onset, due to the wide spectrum of organ manifestations. In addition, the VEXAS syndrome may mimic various rheumatological diseases. The diagnosis of VEXAS syndrome is currently based on the detection of pathogenic variants in the UBA1 gene in the appropriate clinical context. Therapeutic approaches either target the aberrant mutated clones and/or inflammatory pathways via targeted therapies (“block the cytokine storm”). The course of the disease frequently includes refractory conditions and serious infections. 5-year survival rate is approximately 60%.

Schlüsselwörter

Neutrophile Dermatose - Polychondritis - Makrozytäre Anämie - Myelodysplastisches Syndrom - UBA1

Keywords

Neutrophilic dermatosis - Polychondritis - Macrocytic anemia - Myelodysplastic syndrome - UBA1

Publication History

Received: 29 April 2025

Accepted: 16 June 2025

Article published online:
21 July 2025

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