Clinical Challenges of Emerging Acquired Autoinflammatory Diseases, Including VEXAS Syndrome

Abstract

Vacuoles, E1-ubiquitin-activating enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome, caused by an acquired mutation in the ubiquitin-activating enzyme ubiquitin-like modifier activating enzyme 1 (UBA1), was discovered in 2020. Since then, many cases have been reported worldwide. Recently, we performed UBA1 genetic testing in suspected cases of VEXAS throughout Japan and investigated the clinical features of these cases. Most cases were elderly patients in their 70s with clinical features consistent with VEXAS syndrome, such as myelodysplastic syndrome, high-grade fever, skin rash, chondritis, and pulmonary infiltration. However, approximately half of the analyzed patients were negative for the UBA1 variant. As the concept of "acquired autoinflammatory diseases", including VEXAS syndrome, has gained popularity, the number of suspected cases is expected to increase. Currently, there are no established diagnostic or treatment guidelines for these conditions, and they need to be urgently developed. This review summarizes the clinical problems faced by patients with acquired autoinflammatory diseases, including VEXAS.