VEXAS syndrome: a rare and severe autoinflammatory disease
Authors:
T. Sychrovská; B. Stibůrková; H. Mann
Authors‘ workplace:
Revmatologický ústav, Revmatologická klinika 1. LF UK, Praha
Published in:
Čes. Revmatol., 32, 2024, No. 4, p. 152-161.
Category:
Review Article
Overview
VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic mutation) is a severe disease first described in 2020. It is an X-linked, chronic autoinflammatory condition arising from a somatic mutation in the UBA1 gene within hematopoietic cells. UBA1 encodes the E1 ubiquitin-activating enzyme, a key enzyme for initiating ubiquitination. Due to this mutation, protein degradation is reduced, leading to protein accumulation that triggers a stress response and ultimately results in an uncontrolled inflammatory reaction. Given the nature of the mutation, the disease predominantly affects middle-aged and older men. Multi-organ inflammation presents with systemic symptoms, such as fevers accompanied by elevated inflammatory markers, as well as organ-specific symptoms. The skin is most commonly affected, but nearly any organ can be involved, including the eyes, lungs, joints, cartilage, or blood vessels in the form of vasculitis. Patients are predisposed to thromboembolic events. Hematological manifestations are common, especially changes in the blood count due to bone marrow dysfunction and a predisposition to hematological malignancies, primarily myelodysplastic syndrome.
Diagnosis requires the detection of a pathogenic variant of the UBA1 gene. There is no standardized treatment protocol yet; therapy focuses on managing inflammatory symptoms, targeting the elimination of the mutated clone, and supportive care. For high-risk patients, allogeneic hematopoietic stem cell transplantation may be considered, offering potential curative outcomes.
Keywords:
autoinflammatory disease – VEXAS syndrome – UBA1 mutation
Sources
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Czech Rheumatology
2024 Issue 4
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