Cutaneous and Systemic Manifestations of VEXAS Syndrome

Conclusions

• VEXAS syndrome is an adult-onset somatic UBA1-driven autoinflammatory disease that causes multisystem inflammation, especially in older men and rarely in women with skewed X-inactivation or X monosomy.
• Cutaneous findings are often the presenting clue to VEXAS and can be highly variable over time, including neutrophilic dermatoses, leukocytoclastic vasculitis, urticarial or morbilliform eruptions, and chondritis-associated lesions.
• Common associated systemic features include cytopenias, macrocytic anemia, elevated inflammatory markers, pulmonary infiltrates or pneumonitis, relapsing polychondritis, and thrombotic events.
• Skin biopsy and bone marrow findings may provide important diagnostic clues, with histiocytoid neutrophilic infiltrates and marrow vacuoles supporting the diagnosis.
• Genotype appears to influence phenotype, with some UBA1 variants being more associated with neutrophilic dermatoses and others with vasculitis and cytopenias.
• Early recognition by dermatologists can materially improve outcomes because skin disease frequently appears before other manifestations and can prompt timely UBA1 testing.
• Steroids may temporarily suppress symptoms, but relapses on tapering are common, so longer-term control often requires targeted immunomodulatory therapy such as JAK inhibitors or IL-6 blockade.
• Because VEXAS is multisystem and potentially severe, optimal care depends on multidisciplinary coordination among dermatology, rheumatology, hematology, and pulmonology.