THERAPEUTIC MANAGEMENT OF VEXAS SYNDROME: A PRACTICAL REVIEW OF CLINICAL MANIFESTATIONS, COMPLICATIONS AND TREATMENT STRATEGIES
DOI:
https://doi.org/10.31435/ijitss.3(51).2026.6705Keywords:
VEXAS Syndrome, UBA1 Mutation, Autoinflammation, Ruxolitinib, Azacitidine, Hematopoietic Stem Cell Transplantation, Relapsing PolychondritisAbstract
Aim: To summarize current clinical knowledge on the manifestations, organ-specific complications, and medical management of VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic syndrome).
Methods: A review of peer-reviewed clinical cohorts, registry evaluations and consensus reports published between 2020 and 2026 was conducted using PubMed, MEDLINE, and Google Scholar. Studies addressing clinical phenotypes, organ manifestations, and treatment responses were analyzed.
Results: VEXAS syndrome is an adult-onset autoinflammatory disorder caused by somatic mutations in the UBA1 gene within hematopoietic stem cells. It predominantly affects older males and is characterized by systemic inflammation alongside progressive hematologic abnormalities. High-dose oral glucocorticoids reliably achieve rapid flare control - however, steroid dependency is nearly universal and long-term toxicity is substantial. Conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) show minimal efficacy. Janus kinase (JAK) inhibitors have emerged as the most consistent targeted medical therapy for controlling inflammatory symptoms and reducing steroid exposure. Interleukin-1 (IL-1) and interleukin-6 (IL-6) inhibitors provide partial benefit but carry risks of secondary loss of response, severe injection-site reactions, or serious infections. For patients with high-risk myelodysplastic syndrome (MDS) features or severe cytopenias, the hypomethylating agent azacitidine reduces clonal burden and improves blood counts. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative treatment for eligible candidates. Long-term therapeutic anticoagulation is indicated for unprovoked thrombosis, and routine antimicrobial prophylaxis is essential.
Conclusion: Managing VEXAS syndrome requires an integrated strategy: rapid suppression of acute inflammation with corticosteroids, maintenance with targeted therapy (ruxolitinib), clonal suppression (azacitidine or allo-HSCT) for marrow failure and aggressive infection prophylaxis.
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Copyright (c) 2026 Marcin Sękulski, Martyna Mrozek, Igor Zydlewski, Małgorzata Blecharczyk, Martyna Pacanowska-Trawnicka, Paweł Jakubiec
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