BI07 Skin as the clue: cutaneous manifestations of VEXAS syndrome in a tertiary centre cohort

Abstract

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is an adult-onset autoinflammatory disease caused by acquired somatic mutations in the UBA1 gene, leading to systemic inflammation and haematological disease. Cutaneous involvement is common and frequently precedes diagnosis, making dermatological recognition critical. We describe the cutaneous manifestations of 43 patients with confirmed VEXAS syndrome managed through a specialist tertiary clinic. All patients were male, with a mean age of symptom onset of 69 years. Pathogenic variants most commonly affected the p.Met41 codon, with the p.Met41Thr variant present in 35% of cases. Cutaneous disease was a presenting feature in 88% of patients when inflammatory skin disease, chondritis and orbital inflammation were included. Skin findings were heterogeneous and often striking, ranging from painful erythematous dermal nodules and widespread pruritic annular plaques to nonblanching vasculitic eruptions. The limbs were most frequently involved, with facial involvement uncommon. Clinically, 39% of patients were diagnosed with Sweet syndrome, half of whom had biopsy-proven histiocytoid Sweet syndrome. Vasculitic rashes occurred in 21% of patients, encompassing both small- and medium-vessel patterns. Cutaneous disease was commonly accompanied by systemic inflammatory features, including arthralgia (47%), fatigue (33%), weight loss (28%) and recurrent fevers (19%). Haematological abnormalities were prominent: 67% of patients had a diagnosis of myelodysplastic syndrome and 58% had a macrocytic anaemia. This series highlights the breadth and diagnostic importance of cutaneous manifestations in VEXAS syndrome and reinforces skin involvement as a frequent presenting feature. VEXAS should be considered in adult male patients presenting with neutrophilic dermatoses, vasculitic eruptions or chondritis in the context of systemic inflammation and haematological abnormalities. Early dermatological recognition may expedite diagnosis, reduce diagnostic delay and facilitate timely multidisciplinary management.