DP04: An elderly man with a relapsing and remitting neutrophilic dermatosis and final unifying diagnosis of VEXAS syndrome

Khimara Naidoo,¹ Sowmya Venkatesan,¹ Andrew McGregor² and Saman Fatah¹

¹The James Cook University Hospital, Middlesbrough, UK; and ²The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK

A 78-year-old man presented with a 1-year history of a relapsing and remitting rash, and skin examination revealed multiple erythematous dermal plaques on his trunk and extremities. Skin biopsy showed marked upper dermal oedema, a perivascular neutrophilic and lymphocytic infiltrate and immature granulocytes and histiocytes, suggestive of histiocytoid Sweet syndrome. He was initiated on dapsone and low-dose prednisolone and his skin remained well controlled. He later complained of weight loss and severe bone pain, and blood tests revealed pancytopenia, macrocytosis and an IgG lambda paraprotein. Bone marrow biopsy showed a monoclonal gammopathy of uncertain significance with dysplastic features. Dapsone was discontinued following a cardiac event, leading to a significant relapse. His symptoms were controlled on a higher dose of prednisolone but relapsed upon attempts to lower the dose, and it remained challenging to identify a steroid-sparing agent in the context of his haematological abnormalities. A unifying diagnosis was suspected following the identification of an association between a range of treatment-recalcitrant autoinflammatory diseases, including neutrophilic dermatosis and myeloid dysplasia, termed VEXAS syndrome. Reassessment of bone marrow samples showed hypercellularity, multilineage marrow dysplasia and vacuolated myeloid and erythroid precursors. Genomic sequencing revealed a somatic mutation in UBA1, confirming the diagnosis of VEXAS syndrome. VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome was first described in 2020 in a cohort of men with late-onset autoinflammatory disease and myeloid changes. It is caused by an acquired somatic mutation in UBA1 (ubiquitin-activating enzyme), resulting in widespread systemic inflammation. The syndrome clinically manifests in a broad range of autoinflammatory symptoms, and features include fever, pulmonary involvement and cutaneous manifestations, including neutrophilic dermatoses and small-to-medium-vessel vasculitis. Haematological abnormalities consist of macrocytic anaemia, myeloid dysplasia and characteristic findings of vacuoles in erythroid and myeloid precursor cells on bone marrow examination. Patients often meet diagnostic criteria for a number of inflammatory syndromes, including Sweet syndrome, relapsing polychondritis and polyarteritis nodosa. VEXAS syndrome is a severe progressive disease associated with poor outcome and is typically refractory to conventional therapies. The mainstay of treatment is high-dose glucocorticoids and further studies are required to evaluate proposed treatment strategies, including biological therapies and haematopoietic stem cell transplantation. A diagnosis of VEXAS syndrome should be considered in treatment-recalcitrant inflammatory disease with suggestive haematological abnormalities. Given that a high proportion of patients have skin findings it is important that dermatologists are aware of this newly described entity and refer suspected cases for further investigation.