PO:21:028 | A difficult case of VEXAS syndrome: management of myelodysplastic syndrome associated with systemic inflammation and infectious complications

Sandra Lombardi¹, Monica Regis¹, Stefano De Luca¹, Monica Poiani², Rossella Stella², Elisa Lucchini², Francesco Zaja², Fabio Fiammengo¹ | ¹SC Medicina Interna, Azienda Sanitaria Universitaria Giuliano Isontina, Gorizia; ²SC Ematologia, Azienda Sanitaria Universitaria Giuliano Isontina, Trieste, Italy

Background. This work describes a clinical case of VEXAS syndrome associated with myelodysplastic neoplasm, aiming to highlight the clinical and diagnostic features and the importance of a multidisciplinary approach to optimize treatment and improve the patient's prognosis.

Materials and Methods. A 57-year-old male, with a medical history of type 2 diabetes and hypertension, presented between March and June 2024 with marked fatigue, migratory arthralgia in the lower limbs, subcutaneous nodules, an episode of left ear chondritis, and a 20 kg weight loss over 6 months, without fever or apparent infections. Laboratory findings included macrocytic anemia (Hb 6.8 g/dL, MCV 108 fl), without hemolysis, leukocytopenia (WBC 2270/mm³, PMN 1170/mm³), hyperferritinemia (842 µg/L), CRP 111 mg/L, and polyclonal hypergammaglobulinemia. Autoimmune markers (ANA, ENA, ANCA) and HCV/HBV serology were negative. CT scans of the head, chest, and abdomen (August 2024) revealed hepatosplenomegaly. In September, the patient developed a fever with chills, further weight loss, and petechiae at the base of all limbs. PET-CT showed increased lymph node, splenic, and skeletal uptake, while bone marrow biopsy identified myelodysplastic syndrome of the RAEB II subtype, with high IPSS and R-IPSS scores. Microscopic examination noted cytoplasmic vacuoles in granulocytes and blasts. VEXAS syndrome was confirmed by genetic testing identifying a mutation in the UBA1 gene (c.121A>G p.(Met41Val)). The treatment regimen included corticosteroids (methylprednisolone 1 mg/kg/day), with azacitidine as a bridge to transplant.

Results. During follow-up, the patient showed a satisfactory clinical and laboratory response to steroid and antineoplastic drugs, with normalization of inflammatory markers, blood count, and regression of clinical manifestations. In January 2025, he was hospitalized for influenza A pneumonia during neutropenia and treated with antivirals, antibiotics, and corticosteroids. The steroid dose was tapered to 10 mg/day of prednisone, maintaining satisfactory clinical and laboratory control. A follow-up chest CT (3 months later) revealed persistent fibrotic changes and ground-glass opacities, consistent with an inflammatory pattern related to the syndrome. Azacitidine therapy resulted in partial remission, and the option of allogeneic stem cell transplantation was contemplated owing to the patient's youth and the poor prognosis linked to myelodysplasia.

Conclusions. This case underscores the importance of early recognition of VEXAS syndrome, a rare autoinflammatory disorder that combines systemic inflammatory and hematological manifestations. Genetic diagnosis is essential for confirming the diagnosis and guiding treatment. A multidisciplinary approach, involving immunosuppressive therapy and consideration of allogeneic stem cell transplantation, is the most promising strategy to improve patient’s prognosis. Close clinical and radiological monitoring is crucial to manage infectious and inflammatory complications, optimizing the therapeutic choice and the patient's quality of life.