P01 Severe adult-onset inflammatory disorder with associated UBA1 somatic mutation

Abstract

Abstract A 70-year-old man was admitted to the hospital with a 2-week history of fatigue, florid erythematous maculopapular rash, elevated inflammatory markers and thrombocytopenia. A skin biopsy was performed that showed features in keeping with Sweet syndrome, which was initially thought to relate to concurrent gastrointestinal sepsis. The patient was commenced on oral prednisolone 30 mg daily. His rash and inflammatory markers improved, but his ferritin levels remained elevated. Within 1 month, he presented again with a widespread rash comprising tender and erythematous nodules. Serial computed tomography did not reveal an underlying malignancy. The patient was referred to haematology for consideration of a bone marrow biopsy, which showed hypercellular marrow with active trilineage haematopoiesis, and dysplastic changes in granulocytes and megakaryocytes. Molecular analysis showed a characteristic UBA1 p.(Met41Leu) mutation, which confirmed a diagnosis of VEXAS syndrome. He was considered for treatment with tocilizumab, but his skin symptoms responded well initially to oral steroids and, later, dapsone. He remains asymptomatic on dapsone. VEXAS syndrome is an autoinflammatory condition, first described in 2020, that results in a constellation of inflammatory and haematological manifestations due to a somatic mutation in UBA1 on the X chromosome. It can affect the skin, cartilaginous structures, lungs, joints and vasculature, as well as the haematopoietic cells. Patients with this condition have only been partially responsive to treatment, with high doses of corticosteroids showing the most consistent benefit of all the modalities tried thus far. The prognosis is poor and diagnosis is usually delayed. To date, relatively little is known about the dermatological manifestations of VEXAS syndrome. These are usually characterized by neutrophilic dermatoses or vasculitis. More recent studies have shown that skin involvement is associated with clonal infiltration of the skin rather than a general proinflammatory activation. This suggests that therapies that target the pathological clone, as well as the proinflammatory milieu, such as steroids and Janus kinase inhibitors, may be useful. However, further studies and trials are required to understand how to best cure the disease.