What is Veseba in medical terms?

VEXAS Syndrome: A Newly Recognized Adult-Onset Autoinflammatory Disease

Definition and Core Pathophysiology

VEXAS syndrome is an acquired monogenic autoinflammatory disease caused by somatic mutations in the UBA1 gene (encoding the E1 ubiquitin-activating enzyme) in hematopoietic progenitor cells, resulting in systemic inflammation and progressive bone marrow failure that predominantly affects adult males. 1, 2

The acronym VEXAS stands for: Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic 1, 3

Key Pathogenic Mechanism

• The disease results from somatic mutations affecting methionine-41 (p.Met41) in the UBA1 gene located on the X chromosome, though rare variants outside this region have been identified 3, 4
• The mutant gene leads to decreased ubiquitination, which activates innate immune pathways and triggers systemic inflammation 4
• Because this is an X-linked somatic mutation in hematopoietic cells, the condition primarily affects adult males and represents myeloid-driven autoinflammation 1, 5

Clinical Presentation

VEXAS syndrome manifests with overlapping rheumatologic and hematologic features that often mimic other systemic inflammatory conditions, making diagnosis challenging and frequently delayed. 2, 3

Inflammatory Manifestations

• Recurrent fevers (treatment-refractory) 2, 4
• Neutrophilic dermatosis (cutaneous inflammation) 2, 4
• Relapsing polychondritis (cartilage inflammation) 2, 4
• Ocular inflammation 2
• Arthritis 4, 5
• Vasculitis 4, 5
• Pulmonary inflammation 4, 5

Hematologic Manifestations

• Cytopenias (single or multi-lineage), particularly macrocytic anemia 3, 5
• Increased risk of myelodysplastic neoplasms 3
• Increased risk of plasma cell neoplasms 3
• Progressive bone marrow failure leading to substantial morbidity and mortality 1

Diagnostic Approach

The diagnosis requires identification of characteristic bone marrow findings combined with genetic confirmation of UBA1 mutation. 3

Bone Marrow Findings

• Characteristic cytoplasmic vacuoles in myeloid precursors (granulocytic and monocytic) and erythroid precursors are present in the vast majority of cases 3
• These vacuoles are a hallmark feature that should prompt consideration of VEXAS syndrome 3

Genetic Testing

• Genetic testing to identify the UBA1 gene mutation is essential for definitive diagnosis 4
• Testing should focus on the p.Met41 mutation, though rare variants exist 3, 4

Clinical Suspicion Triggers

• Strongly consider VEXAS syndrome in any adult patient (especially males) with unexplained systemic inflammatory condition accompanied by cytopenias or myelodysplastic syndrome 2
• Patients often have complex histories and see multiple specialists before diagnosis 3

Treatment Considerations

Currently, there is no cure for VEXAS syndrome, and effective medical treatments are still being identified. 1, 4

Current Management Approach

• Treatment focuses on managing inflammatory symptoms with anti-inflammatory medications and immunosuppressive drugs 4
• Supportive therapies should be tailored to individual patient needs 4
• More studies are needed to determine optimal therapeutic options, which remain limited 3

Clinical Significance

• VEXAS syndrome represents a prototype for a new class of adult-onset monogenic autoinflammatory diseases arising from genetic mosaicism in bone marrow 1, 2
• The condition may not be exceptionally rare and requires multidisciplinary approach involving rheumatology and hematology 2
• International registries (such as the AIDA registry) have been established to better understand long-term outcomes and optimal management 2