VEXAS syndrome with eosinophilia and pathologically mimicking histiocytosis: a case report

Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic (VEXAS) syndrome is a recently identified autoinflammatory disorder caused by somatic mutations in the UBA1 gene. This report describes the case of a 54-year-old Japanese man with VEXAS syndrome exhibiting atypical features of eosinophilia and histiocytoid changes that mimic histiocytosis. Initially, the patient presented with recurrent fever, eosinophilia, lymphadenopathy, polyarthritis, and a skin rash. Histopathological examination of the skin and lymph node biopsies revealed the infiltration of CD68-positive histiocytes, raising suspicion of histiocytic disorders. However, immunohistochemistry ruled out Rosai-Dorfman disease and other histiocytoses. Subsequently, the patient developed scleritis and auricular chondritis. Bone marrow analysis revealed dysplastic changes with vacuolated cells. Genetic testing confirmed a somatic UBA1 mutation (p.Met41Leu), thereby establishing a diagnosis of VEXAS syndrome. The patient responded favourably to the oral prednisolone therapy. This case underscores that VEXAS syndrome can manifest with eosinophilia and histiocytoid infiltrates, which are atypical features that may lead to confusion in diagnosis. Eosinophilia has been infrequently reported in patients with VEXAS syndrome and may pose a diagnostic challenge. Histiocytoid changes in skin lesions and lymph nodes may serve as early indicators of VEXAS. Clinicians should be aware of these potential atypical manifestations to prevent delays in the diagnosis and treatment of VEXAS syndrome. Further research is warranted to delineate the full spectrum of clinical and pathological presentations of VEXAS.