VEXAS Syndrome

Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic (VEXAS) syndrome was described in 2020 as an autoinflammatory disease caused by postzygotic variants in the UBA1 gene. VEXAS syndrome mostly occurs in adult males with a constellation of inflammatory manifestations, among which stand out recurrent fever, musculoskeletal complaints, auricular/nasal chondritis, neutrophilic dermatoses skin lesions, lung inflammatory infiltrates, venous thrombosis and different-sized vessel vasculitis. Laboratory tests are characterized by increased levels of acute-phase reactants and macrocytic anemia. At the bone marrow examination, myelodysplastic changes are frequent, and cytoplasmic vacuoles in myeloid and erythroid precursors in bone marrow are highly characteristic. Glucocorticoids at moderate-to-high doses are effective, but the remaining immunosuppressive (conventional or biological) drugs tend to show limited or absent efficacy. Azacitidine has been associated with a good response, particularly in patients with accompanying myelodysplastic syndrome. Allogeneic hematopoietic stem cell transplantation currently appears to be the only curative therapy for VEXAS syndrome. The wide spectrum of clinical presentations with a common difficult-to-treat disease characteristic of VEXAS syndrome is leading to a paradigm shift in certain hematologic conditions and systemic diseases, such as relapsing polychondritis, neutrophilic dermatoses and several types of vasculitis, which now have become part of VEXAS syndrome.