VEXAS syndrome is caused by a somatic mutation in UBA1 on the X chromosome. This mutation affects hematopoietic progenitor cells, decreasing cell ubiquitylation and increasing activated innate immune pathways in cells of myeloid lineage, with subsequent upregulation of proinflammatory markers that drives systemic inflammation.
Inflammatory manifestations of VEXAS syndrome include chondritis, vasculitis, and neutrophilic dermatosis. Many reported patients carry diagnoses of relapsing polychondritis, giant cell arteritis, Sweet syndrome, and polyarteritis nodosa. Other autoimmune and inflammatory diseases that have been reported include rheumatoid arthritis, systemic lupus erythematosus, antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, and Kikuchi-Fujimoto disease. Hematologic manifestations include thrombocytopenia, macrocytic anemia, thromboembolism, bone marrow failure, and an increased risk of hematologic malignancies, such as myelodysplastic syndrome (MDS) and multiple myeloma. Fever and pulmonary involvement (including neutrophilic alveolitis most commonly and pleural effusions) are further common findings with pulmonary disease developing later in the disease course.
The prognosis is poor, often with severe and progressive clinical presentations.
D89.89 – Other specified disorders involving the immune mechanism, not elsewhere classified
M94.1 – Relapsing polychondritis
724834006 – Neutrophilic dermatosis
782964007 – Genetic disease
Differential diagnosis of vacuoles in bone marrow myeloid / erythroid precursors:
- Alcohol intoxication
- Copper deficiency
- Zinc toxicity
- Myeloid neoplasms