VEXAS syndrome: a Spanish national research project to better understand this rare disease.
- Philippe Mertz
- Feb 12
- 2 min read
Article title : VEXAS syndrome through a rheumatologist's lens: insights from a Spanish national cohortservices de rhumatologie espagnols
First author: García-Escudero P
First author: Rheumatology
Lien vers l'article: https://pubmed.ncbi.nlm.nih.gov/39937690/
Auteur du résumé: Philippe Mertz
Introduction
VEXAS syndrome (Vacuoles, E1 enzyme, X‑linked, Autoinflammatory, Somatic) is a recently described, severe autoinflammatory disease associated with somatic variants in the UBA1 gene. It primarily affects men over 50 and combines systemic inflammatory manifestations with hematologic abnormalities. The aim of this study was to describe the clinical and genetic features of VEXAS seen in patients followed in Spanish rheumatology departments and to analyze genotype–phenotype correlations.
Methods
This was a multicenter retrospective study conducted in 126 Spanish hospitals, including 39 patients diagnosed between December 2020 and January 2024. Clinical, laboratory, and genetic data were collected and analyzed.
Key results
All patients were men, with a mean age of 73 years (range 40–92) at diagnosis. Initial working diagnoses included seronegative polyarthritis (9/39), relapsing polychondritis (6/39), Sweet’s syndrome (4/39), polymyalgia rheumatica (4/39), systemic lupus, and medium‑vessel vasculitis (3/39 each). The most frequent clinical features were skin involvement (87%), followed by polyarthritis (82%) and fever (79%). Renal involvement affected 20% of patients, a higher rate than previously reported cohorts, and polyarthritis also appeared more frequent than in earlier series.
Genetically, notable correlations emerged. The UBA1 M41V variant was significantly associated with renal involvement, whereas M41T correlated with thrombocytopenia and an increased rate of thromboembolic events. The study also identified a potentially pathogenic novel UBA1 variant (c.209T>A; p.L70H).
Regarding treatment, all patients received corticosteroids, with better responses observed after diagnostic confirmation and dose adjustments. Interleukin‑6 inhibitors and JAK inhibitors, notably ruxolitinib, showed the highest response rates, reaching 75% and 76% respectively. In contrast, anti‑TNF agents and hypomethylating agents were largely ineffective.
Conclusion
This study confirms that VEXAS remains under‑recognized in rheumatology, particularly among older men presenting with polyarthritis, unexplained cytopenias, or steroid dependence. It also underscores that genotype influences clinical expression, with certain variants associated with more severe disease or specific complications such as renal or thromboembolic involvement. Finally, the results support JAK and IL‑6 inhibitors as key therapeutic strategies in this condition.
In clinical practice, these findings support considering VEXAS promptly in any man over 50 with seronegative polyarthritis and atypical systemic features, cytopenias, or steroid dependence, to avoid diagnostic delay and better tailor therapy.
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