Clinical Manifestations, Diagnosis, and Case Reports of VEXAS Syndrome

Conclusions

• VEXAS syndrome is a somatic UBA1-driven autoinflammatory disease that causes multisystem inflammation through defective ubiquitination and downstream cytokine activation.
• Although it is classically seen in older men, VEXAS can also occur rarely in women through skewed X-inactivation, mosaicism, or X-chromosome loss.
• Cutaneous disease is often an early and common clue, and dermatologists can play a key role in recognizing VEXAS before the diagnosis is delayed.
• The skin findings are diverse and can include neutrophilic dermatoses, leukocytoclastic vasculitis, urticarial or morbilliform eruptions, periorbital edema, and chondritis.
• Histopathology may show histiocytoid neutrophilic dermatosis or vasculitic patterns, which can provide important diagnostic clues.
• The syndrome is strongly associated with hematologic and systemic abnormalities such as macrocytic anemia, cytopenias, elevated inflammatory markers, pulmonary disease, vasculitis, and relapsing polychondritis.
• Different UBA1 mutations appear to correlate with different phenotypes, with leucine variants tending toward neutrophilic dermatosis and milder disease, and valine variants toward vasculitis, cytopenias, and worse outcomes.
• Early UBA1 testing is essential when the clinical pattern fits, because confirming the mutation can prevent prolonged misdiagnosis and guide treatment.
• Steroids may produce temporary improvement, but flares on taper are common, so steroid-sparing therapy is often needed.
• JAK inhibitors and IL-6 blockade can lead to meaningful clinical improvement in selected patients, though fatigue and other residual symptoms may persist.
• Because VEXAS is multisystemic, optimal care requires a multidisciplinary approach involving dermatology, rheumatology, hematology, and pulmonology.