How I diagnose and manage VEXAS syndrome

Area of Science:

• Hematology
• Immunology
• Genetics

Background:

• VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a recently identified adult-onset autoinflammatory disorder.
• It presents with overlapping rheumatologic and hematologic manifestations, posing diagnostic challenges.

Purpose of the Study:

• To provide a comprehensive overview of VEXAS syndrome.
• To discuss its clinical and pathological features, diagnostic difficulties, and current treatment strategies.

Main Methods:

• A case-based approach was employed.
• A review of relevant medical literature was conducted.

Main Results:

• VEXAS syndrome is linked to somatic mutations in the UBA1 gene, affecting ubiquitylation.
• Key features include systemic inflammation, cytopenias (especially macrocytic anemia), and characteristic cytoplasmic vacuoles in myeloid and erythroid precursors.
• Patients often experience diagnostic delays due to complex presentations and multi-specialty involvement.

Conclusions:

• Diagnosis can be suspected by clinicians or pathologists based on clinical and bone marrow findings.
• Optimal therapeutic options for VEXAS syndrome require further investigation, as current treatments are limited.