A new disorder to keep in mind: VEXAS syndrome

The VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic), which has recently been described, is a monogenic autoinflammatory syndrome that primarily affects males and has its onset in adulthood. The disease is caused by somatic mutations in the UBA1 gene (ubiquitin-like modifier activating enzyme 1), which is responsible for cellular processes, particularly in maintaining protein homeostasis. It presents with severe and progressive systemic inflammation that is resistant to therapy. Common symptoms include fever and constitutional syndrome, along with hematological manifestations such as macrocytic anemia, other cytopenias, myelodysplastic syndrome, and characteristic vacuolization of myeloid and erythroid cells. Additional symptoms may involve the skin (neutrophilic dermatosis), lungs, chondritis, and vasculitis. Thus, in a case where a male patient presents with recurrent neutrophilic dermatosis unresponsive to treatment, macrocytic anemia, and systemic autoinflammatory manifestations, it is important to suspect this newly identified condition and proceed with a confirmatory genetic test.