To report the case of a patient diagnosed with Acute Myeloid Leukemia (AML) with Myelodysplastic Syndrome (MDS) related changes, whose hematological precursors'morphology and clinical picture were consistent with VEXAS Syndrome (VS). Material and methods: Assessment of patient's information kept on HSPE computer-based patient records.

75-year-old female, diagnosed with AML on 04/2022 and treated with the AZAVIT-ABCDEF protocol (Azacytidine, Filgrastim, Erythropoietin, associated with high doses of vitamins B1, C and D), after signing the consent form, (protocol registered in Plataforma Brasil under CAAE 53015421000005463). Complete Blood Count (CBC) at diagnosis: Hb 6.0 g/dL, WBC 5380/mm3, ANC 2690/mm3, Ly 1506/mm3, blasts 107/mm3 and Platelets 28000/mm3; Bone marrow aspirate (BMA):26% blasts; Flow Cytometry (FC):blasts positive for CD13, CD33, CD34, CD38, CD56, CD117, CD123, HLA-DR and MPO; FISH: RUNX1 on chromosome 21 and Del 5q. Complex karyotype. During the first 3 months of treatment, the average transfusion need (TN) was 3 packed Red Blood Cells (pRBC)/month. From month 4th to 10th of treatment, TN dropped to an average value of 0.8 pRBC/month. In the last month of survival (11th), TN ramped up to 3 pRBC/month again. At that time, her CBC showed Hb 8.8 g/dL, WBC 29240/mm3, ANC 13158/mm3, Ly 2339/mm3, Blasts 1169/mm3, monocytes 8479/mm3, Platelets 40000/mm3; BMA: Hypercellular with 12% blasts and increased macrophage activity. FC like that at diagnosis; Complex karyotype with X-chromosome monosomy. Vacuoles in the erythroid and granulocytic precursors as well as multisystemic inflammation were seen (neutrophilic aseptic arthritis in the right knee, deep venous thrombosis, and pulmonary inflammatory infiltrate). The patient ended up dying from progression of systemic inflammatory reaction, affecting mainly the lungs.

VS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is an entity that typically manifests auto-inflammation and hematological disease, due to the presence of ubiquitin-activating enzyme E1 (UBA-1) gene mutation, which encodes the E1 enzyme. Unlike the majority of systemic autoinflammatory diseases, it seems to be caused by acquired somatic X-linked mutation, such chromosome X monosomy in females. E1 enzyme is involved in the normal activation of the Ubiquitin system and in protein degradation and cellular homeostasis. Impaired UBA-1 activity likely leads to overexpression of pro-inflammatory cytokines, triggering disease manifestations. Morphologically, VS causes hematological precursors to present with vacuoles, which should raise suspicion when in association with MDS. Progressive inflammatory conditions, such as arthritis, chondritis, Sweet's Syndrome, fever, uveitis, scleritis and thrombosis are characteristic. Currently, there is still no standard therapy for VS, but some anti-inflammatory drugs like steroids, Ruxolitinib and Canakinumab have been tested, as well as Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) for eligible patients.

This newly described entity imposes diagnostic challenge, especially considering that many of its manifestations are indistinguishable from other inflammatory conditions. In addition, it's not clear what would be the best therapy, with HSCT being an option for high-risk eligible patients. Therefore, further studies are needed.