A man in his sixties with chondritis and bone marrow failure.

Background: VEXAS syndrome (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic syndrome) first described in 2020, is caused by a limited repertoire of somatic mutations in UBA1, a gene involved in the initiation of ubiquitination. Ubiquitination, adding an ubiquitin protein to a substrate protein, can have various effects on the substrate. Disruption of UBA1 function results in diverse clinical manifestations, mimicking a variety of disorders.

Case Presentation: A man in his sixties presented with fever, chest pain, fatigue, pulmonary infiltrates and elevated acute phase reactants. Initially he was thought to have extra-cranial giant cell arteritis. When he developed ear and nose chondritis, a revised diagnosis of relapsing polychondritis was made. Subsequently he developed macrocytic anaemia and thrombocytopenia. His condition remained resistant to medical therapy and he died eight years after disease onset. Analysis of stored DNA revealed a somatic mutation in UBA1 confirming the diagnosis of VEXAS syndrome.

Interpretation: VEXAS syndrome is a newly identified inflammatory disorder due to an acquired mutation in haematopoietic bone marrow cells in older men. The syndrome may be misdiagnosed as treatment-refractory relapsing polychondritis, polyarteritis nodosa, Sweet syndrome or giant cell arteritis. We describe the first individual with molecularly confirmed VEXAS syndrome in Norway.