Case Presentation: A 65-year-old man presented with four months of fever, neutropenia, macrocytic anemia, thrombocytopenia, and recurrent inflammatory manifestations. Between August–December 2023, he experienced multiple hospitalizations for presumed infections (orbital and ankle cellulitis), steroid-responsive gastrointestinal symptoms, petechial rash, pulmonary infiltrates, and bilateral eye pain. Workup revealed weakly positive Francisella tularensis IgG, PET/CT with diffuse marrow and vascular uptake, and bone marrow vacuolization with confirmed UBA1 mutation, establishing VEXAS syndrome. He began prednisone in December 2023, followed by azacitidine and ruxolitinib for disease control. Despite therapy, he continued to experience inflammatory flares requiring readmission. In June 2024, he underwent allogeneic stem cell transplant (alloSCT) with Flu/Cy/rATG and rituximab (CHAMP regimen), using PTCy/Tac/MMF for GVHD prophylaxis. Post-transplant course, he developed prolonged neutropenia requiring G-CSF, parainfluenza infection, progressive hypoxia with multifocal infiltrates, altered mental status, and upper GI bleeding requiring ICU transfer. Management required simultaneous mitigation of infection risk and inflammatory activity, careful adjustment of immunosuppression, and ongoing coordination between the rheumatology, hematology/oncology, and transplant teams.
Discussion: VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome is a rare, late-onset autoinflammatory disorder driven by somatic UBA1 mutations. While diagnostic features are increasingly described, inpatient management remains challenging due to multisystem inflammation, hematologic dysfunction, and the need for high-risk immunosuppressive therapies. Hospitalists serve as the central coordinators of care across multiple specialties. Diagnosing and managing VEXAS syndrome poses unique challenges for hospitalists due to its rarity and overlap between hematologic and rheumatologic manifestations. In this case, diagnosis occurred only when a rheumatologist with prior VEXAS experience happened to be on service, highlighting the need for hospitalists to maintain suspicion for VEXAS in older adults with recurrent inflammatory episodes or fever of unknown origin. Treatment coordination was similarly complex. The diagnosing rheumatologist had limited experience with longitudinal management and ultimately transitioned care to a hematologist familiar with transplant-based therapies. For hospitalists arranging follow up, hematology may be best positioned when stem-cell transplant is anticipated. This case underscores the systems level challenges of VEXAS including therapeutic uncertainty, infection risk, and need for multidisciplinary coordination across inpatient and outpatient settings. Hospitalists play a pivotal role in orchestrating transitions and mitigating complications during prolonged and resource intensive hospitalizations.
Conclusions: Beyond diagnostic hurdles, VEXAS syndrome demands integrated care strategies to navigate treatment escalation, transplant-related complications, and infection risk. Early recognition of these management challenges is critical for safe transitions and optimal outcomes.