VEXAS syndrome – diagnosis at the interface of rheumatology and hematology

Abstract

VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is a rare autoinflammatory late-onset disease caused by UBA1 gene somatic mutation in hematopoietic progenitor cells. In patients, we can observe systemic symptoms (fever and fatigue), inflammatory manifestations on the skin, in the eye area, involvement of the lungs, blood vessels and cartilage with associated hematological symptoms such as macrocytic anemia and thrombocytopenia. Further, vacuoles can be found in myeloid and erythroid precursor cells. In most cases, the patients are refractory to common anti-inflammatory and immunosuppressive treatments and also have a higher risk of developing hematologic malignancies. Subsequently, the inflammation and bone marrow failure often lead to severe morbidity and significant mortality. Currently, there is no effective standardized therapy. Hematopoietic stem cell transplantation may be a suitable treatment for the specific group of the patients. Hypomethylating agents and/or drugs targeting cytokine and inflammatory response pathways appear to be other therapeutic options. Together with an overview of VEXAS syndrome, we present two case reports of the patients with UBA1 mutations detected in our laboratory.