CPC01 Diagnostic challenge of chronic urticarial vasculitis: unmasking VEXAS syndrome in an older man

Abstract

Urticarial vasculitis is an uncommon small-vessel vasculitis, either idiopathic or secondary to systemic disease. VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a recently described adult-onset autoinflammatory disorder caused by somatic UBA1 mutations. It typically affects older men, presenting with systemic inflammation, cytopenias and vasculitic skin lesions. Cutaneous vasculitis is recognized in VEXAS, but presentations dominated by chronic urticarial vasculitis have rarely been reported. In early 2024, an 84-year-old man developed a 6-month history of nonpruritic erythematous patches on the legs, later spreading to the trunk and arms, beginning several weeks after COVID-19 and shingles vaccinations. Initial biopsy showed nonspecific inflammation. He was empirically treated for discoid eczema or prebullous pemphigoid with topical corticosteroids and fexofenadine, achieving partial benefit. Over the following year, the eruption became more purpuric and pruritic. He developed arthralgia, malaise, night sweats and progressive macrocytic anaemia. Inflammatory markers were raised, but vasculitic, autoimmune and infection screens, as well as imaging for malignancy, were unremarkable. A further skin biopsy in late 2024 demonstrated leucocytoclastic vasculitis consistent with urticarial vasculitis. In 2025, bone marrow biopsy for worsening macrocytic anaemia showed dysplastic changes with vacuolization of myeloid precursors. Next-generation sequencing identified a somatic UBA1 mutation, confirming VEXAS syndrome. Systemic prednisolone led to rapid improvement of the rash, and subsequent treatment with erythropoietin, low-dose prednisolone and colchicine achieved sustained control of rash, resolution of systemic inflammation and normalization of haemoglobin. This case illustrates the evolving diagnosis from presumed eczema to urticarial vasculitis and ultimately VEXAS syndrome. VEXAS should be considered in older men with chronic or refractory urticarial vasculitis, systemic inflammation and unexplained macrocytic anaemia. Early haematology assessment with bone marrow examination and UBA1 testing may reduce diagnostic delay.