VEXAS syndrome mimicking lupus-like disease.

Dear Editor, We report on an 81-year-old male Caucasian patient, who initially presented with oral ulcerations and disseminated erythematous papules on the upper back, chest, arms and legs with histopathological evidence of lymphocytic infiltration and small vessel vasculitis matching subacute lupus erythematous (Fig. 1A and B). His skin manifestations improved with topical CS and HCQ at standard dosages. However, a complete remission of the lesions could not be achieved. Therefore, repeated skin biopsies were performed, showing features of subacute eczema or Sweet Syndrome. Fourteen months later, the patient developed recurrent episodes of oral ulcerations, painful auricular and nasal erythematous swelling and arthritis in hands and feet (Fig. 1C and D). A hand MRI showed a moderate to severe wrist joint synovitis. Another 6 months later, he presented with clinical symptoms and laboratory findings of anaemia with increased, corpuscular volume (102.9 fl; normal range 81–98 fl), leukopoenia, lymphopenia, thrombocytopenia, increased levels of CRP, serum amyloid A and IL-6 as well as anti-mutated citrullinated vimentin (MCV) antibodies (Fig. 1G). Treatment with MTX was started at 15 mg/week and was well tolerated, leading to improvement of skin and joint symptoms. The patient experienced one episode of epilepsy with generalized convulsions. Cerebral MRI scan showed unspecific cerebral microangiopathy but no specific lesion. To rule out further foci of inflammation, an 18-fluorodeoxyglucose (18FDG)-PET/CT was performed, showing an enhanced FDG uptake typical for bone marrow activation (Fig. 1E and F), in accordance with a previous description [1]. Over the last 6 months, his skin and joints were well controlled by MTX. However, haematological and inflammatory parameters did not improve. As the patient fulfilled the major diagnostic traits of VEXAS [2], including male sex, increased corpuscular volume >100 fl and low platelets G/l, genetic testing was done. This patient was identified to carry the pathogenic variant c.121A>C, p. (Met41Leu) in exon 2 of UBA1 (NM_003334) (ACMG class 5) in mosaic state (68% of 93 reads), confirming the diagnosis of VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome.