POS1453 OVERLAPPING FEATURES OF RELAPSING POLYCHONDRITIS AND SWEET’S SYNDROME: COULD THIS BE VEXAS (VACUOLES, UBIQUITIN A1E MUTATION, X-LINKED, AUTOINFLAMMATORY, SOMATIC) SYNDROME?
Authors: A. Vivekanantham, M. Kesavan, J. Evans, R. N. Matin, I. Elliott, R. Luqmani
Journal: Annals of the Rheumatic Diseases (2021)

Background: An 83-year-old male presented to the infectious diseases team with intermittent fevers associated with tension headaches, malaise and fatigue for two years, with recent worsening. He had noted a progressive decline in his mobility over the past year following replacement of his right knee for osteoarthritis. His past medical history included atopic eczema, malaria and bilateral cataract extractions. On examination, he had a widespread non-scaly annular urticated rash. He had persistently raised inflammatory markers (CRP 40mg/L, ESR 82mm/hour), normocytic anaemia (Hb 102 g/L, MCV 101.9 fL), lymphopenia (0.70 x10^9/L), fluctuating eosinophilia (0.88-1.25 x10^9/L) and a mildly elevated lactate dehydrogenase (243IU/L). A thorough work up for pyrexia of unknown origin showed no evidence of infection/ vasculitis/ immune pathology. The only positive finding was prior exposure to schistosomiasis, treated with a single dose of praziquantel. An echocardiogram and serial PET-CT scans were normal. Given the deterioration in mobility since the right knee replacement, an MRI knee was performed, and cobalt/ chromium levels to look for allergic responses to the prosthesis, but these tests did not reveal any findings of significance. An initial haematology work-up did not identify an abnormality of concern (screening for a myeloproliferative neoplasm including BCR-ABL studies were negative and mast cell tryptase was not elevated). Due to a worsening skin rash, he was reviewed by dermatology where a skin biopsy showed features of superficial neutrophilic dermatosis which can be observed with Sweet’s syndrome. However, it was felt that this was an unlikely explanation for the persistent systemic symptoms. He proceeded to a bone marrow biopsy which showed reactive features including vacuolation of myeloid precursors with normal cytogenics. During follow up appointments, the patient described new recurrent violaceous patches with episodes of inflammation of the pinna of the ear, suggesting a diagnosis of relapsing polychondritis and so the patient was started on high dose prednisolone (80mg per day [1mg per kg]) and referred for rheumatological assessment. He had an excellent response to prednisolone (fever, ear swelling and rash subsided). The overlapping features of relapsing polychondritis and Sweet’s syndrome in an elderly man suggested a diagnosis of VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory and somatic) syndrome. The prednisolone dose was rapidly reduced to 10mg per day and the patient was commenced on methotrexate, as a steroid-sparing agent. Further blood tests have been sent for genetic analysis for VEXAS syndrome but results are pending. Objectives: N/A Methods: N/A Results: N/A Conclusion: VEXAS syndrome is a newly identified genetically defined syndrome, described by Beck et al in October 2020 consisting of somatic mutations in the UBA1 gene, affecting bone marrow stem cells. In a study of 25 patients with this mutation, diagnostic/ classification criteria for relapsing polychondritis (n=15), Sweet’s syndrome (n=8), polyarteritis nodosa (n=3) or giant cell arteritis (n=1) were met and patients often had severe refractory disease with overlapping systemic inflammatory and haematologic features. Features of VEXAS include the presence of vacuoles in myeloid cells, somatic mutations in the UBA1 (ubiquitin-activating enzyme) gene, X-linkage (therefore only occurring in males), in older people with autoinflammatory syndromes. Although VEXAS syndrome is a relatively rare condition, it was a relevant consideration in this case. References: [1]Beck et al. Somatic Mutations in UBA1 and Severe Adult-Onset Autoinflammatory Disease. N Engl J Med 2020; 383:2628-2638. DOI: 10.1056/NEJMoa2026834 Disclosure of Interests: None declared