Early-onset VEXAS syndrome mimicking orbital cellulitis and successfully treated with allogeneic hematopoietic stem cell transplantation.

backgroundVEXAS syndrome is a somatic autoinflammatory disorder caused by UBA1 mutations in hematopoietic progenitor cells, typically affecting older men and characterized by systemic inflammation and hematologic abnormalities. Early-onset cases are extremely rare. CASE PRESENTATION: We report a 25-year-old male patient presenting with recurrent fever, weight loss, arthralgia, and inflammation mimicking orbital cellulitis. Imaging demonstrated orbital soft tissue inflammation. Laboratory investigations revealed macrocytic anemia, leukopenia, thrombocytopenia, and elevated inflammatory markers; FDG-PET/CT showed splenomegaly and hypermetabolic lymphadenopathy. Bone marrow examination revealed hypercellularity, multilineage morphological abnormalities, and vacuolated blasts. Following exclusion of infectious and classical autoinflammatory diseases, the somatic UBA1 c.121A > G (p.Met41Val) mutation confirmed VEXAS syndrome. The patient initially responded to corticosteroids but subsequently developed refractory disease and progressive pancytopenia despite tocilizumab therapy. He underwent allogeneic hematopoietic stem cell transplantation from a 10/10 HLA-matched sibling donor using a myeloablative conditioning regimen. At 3 months post-transplantation, 99% donor chimerism and hematologic remission were achieved.

conclusionVEXAS syndrome should be considered in young adults presenting with unexplained systemic inflammation and cytopenias, even with atypical manifestations such as orbital cellulitis. Early genetic evaluation is crucial for diagnosis, and allogeneic stem cell transplantation may provide effective disease control in refractory cases.