Clinicopathologic characteristic of VEXAS syndrome with UBA1 mutation and skin involvement: Study of 5 cases.

Summary: VEXAS syndrome (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) is a rare, genetically defined autoinflammatory disorder caused by somatic mutations in the UBA1 gene on the X chromosome, primarily affecting men. It presents as an adult-onset systemic inflammatory syndrome with diverse hematological and rheumatic manifestations. Cutaneous involvement is a hallmark of VEXAS, occurring in up to 90% of cases. We present five male patients with confirmed VEXAS syndrome, with an average age of 65 years. All patients presented with erythematous and edematous papules and plaques with four having annular lesions. Two patients had uveitis, polychondritis, or arthritis. Histologically, all cases exhibited neutrophilic dermatoses consistent with Sweet syndrome, with one case diagnosed as histiocytoid Sweet syndrome and three showing histiocytoid cells in the infiltrate. Two cases displayed neutrophilic eccrine hidradenitis-like changes and one case showed small to medium vessel vasculitis. Bone marrow biopsies revealed vacuolization of erythroid precursors in all cases, with at least single-lineage cytopenias. Overt myelodysplasia was observed in three cases. Through this case series, we seek to contribute to a better understanding of VEXAS syndrome and emphasize the importance of early recognition for appropriate management.