VEXAS syndrome: An update

Joint Bone Spine. 2024 Jul;91(4):105700. doi: 10.1016/j.jbspin.2024.105700. Epub 2024 Feb 1.

Abstract

VEXAS (Vacuoles, E1 Enzyme, X-linked, Autoinflammatory, Somatic) syndrome is a recently described autoinflammatory syndrome, mostly affecting men older than 50 years, caused by somatic mutation in the UBA1 gene, a X-linked gene involved in the activation of ubiquitin system. Patients present a broad spectrum of inflammatory manifestations (fever, neutrophilic dermatosis, chondritis, pulmonary infiltrates, ocular inflammation, venous thrombosis) and hematological involvement (macrocytic anemia, thrombocytopenia, vacuoles in myeloid and erythroid precursor cells, dysplastic bone marrow) that are responsible for a significant morbidity and mortality. The therapeutic management is currently poorly codified but is based on two main approaches: controlling inflammatory symptoms (by using corticosteroids, JAK inhibitor or tocilizumab) or targeting the UBA1-mutated hematopoietic population (by using azacitidine or allogeneic hematopoietic stem cell transplantation). Supportive care is also important and includes red blood cell or platelet transfusions, erythropoiesis stimulating agents, thromboprophylaxis and anti-infectious prophylaxis. The aim of this review is to provide a current overview of the VEXAS syndrome, particularly focusing on its pathophysiological, diagnostic and therapeutic aspects.

Keywords: Autoinflammatory diseases; Myelodysplastic syndrome; UBA1; VEXAS syndrome.

Publication types

  • Review

MeSH terms

  • Genetic Diseases, X-Linked / diagnosis
  • Genetic Diseases, X-Linked / genetics
  • Genetic Diseases, X-Linked / therapy
  • Hereditary Autoinflammatory Diseases / diagnosis
  • Hereditary Autoinflammatory Diseases / drug therapy
  • Hereditary Autoinflammatory Diseases / genetics
  • Hereditary Autoinflammatory Diseases / therapy
  • Humans
  • Male
  • Middle Aged
  • Mutation*
  • Syndrome
  • Ubiquitin-Activating Enzymes

Substances

  • UBA1 protein, human
  • Ubiquitin-Activating Enzymes