VEXAS Syndrome Complicated by Actinomyces Bacteremia: A Case Report Distinguishing Autoinflammation from Infection

Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is an adult-onset autoinflammatory disorder caused by somatic UBA1 mutations that predominantly affects men older than 50 years, presenting with recurrent fever, neutrophilic dermatoses, chondritis, pulmonary involvement, and macrocytic anemia. Distinguishing autoinflammatory flares from superimposed infection remains a major clinical challenge, particularly in patients receiving chronic immunosuppression. This case report describes a 76-year-old man with genetically confirmed VEXAS syndrome who presented with high-grade fever and a single blood culture positive for Actinomyces species. Despite empiric antibiotics, he defervesced rapidly, repeat blood cultures and imaging were negative, and his overall course was interpreted as more consistent with an autoinflammatory flare than with true infection, although concurrent glucocorticoid escalation and Actinomyces-active antimicrobial therapy limit definitive attribution. Several features supported this interpretation, including a history of recurrent unexplained fever on prednisone tapering and isolation of Actinomyces neuii from only one of two blood culture sets. The absence of leukocytosis and the borderline procalcitonin elevation are difficult to interpret given concurrent JAK inhibition, which can blunt these markers independent of infection. This case illustrates the diagnostic overlap between infection and autoinflammation in VEXAS syndrome and highlights the limitations of current biomarkers, including C-reactive protein (CRP) and procalcitonin, in distinguishing the two. Improved diagnostic tools and validated response criteria are needed to guide antibiotic and immunosuppressive management in this patient population.