BG07 VEXAS syndrome without the V: a New Zealand case report

Abstract

Abstract VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is an autoinflammatory condition first described in 2020, often with cutaneous features. Effective treatments are yet to be established. We describe the case of a 60-year-old man who presented with rapidly enlarging cutaneous lesions to the face and neck, polychondritis, myalgia, arthralgia and fevers over a 2-month period. Skin biopsy showed a neutrophilic dermatosis with a differential diagnosis of seronegative rheumatoid neutrophilic dermatosis and atypical Sweet syndrome. His cutaneous complaints improved following treatment with prednisone 30 mg. His cutaneous symptoms relapsed on attempts to wean prednisone to < 20 mg. He then developed macrocytic anaemia and transient thrombocytopenia. He was then hospitalized and treated for community-acquired pneumonia. Bone marrow biopsy was normal and without evidence of vacuoles. The patient developed progressive fatigue and shortness of breath, with transient stenosing tenosynovitis and Raynaud symptoms over 3 years. He was most burdened by soft tissue and joint swelling, with muscular stiffness and pain particularly affecting his hands and feet. Methotrexate was partially effective in managing myalgia. Dapsone, hydroxy­chloroquine, mycophenolate, cyclophosphamide and colchicine were tried without benefit. Following a regional dermatology multidisciplinary team meeting, the patient was screened for VEXAS syndrome. Blood and bone marrow genetic testing found a UBA1 mutation load which is 50% of total DNA, confirming a diagnosis of VEXAS syndrome and the highest found in a New Zealand laboratory to date. Bone marrow images were re-examined, with no vacuolization noted. Our patient had a heterozygous UBA1C (Met41Leu) variant present in 50% of his blood and bone marrow DNA—to our knowledge the highest VEXAS genetic mutation seen in a New Zealand laboratory so far. Our case illustrates that, in patients with clinical evidence of VEXAS syndrome, the absence of vacuolization on bone marrow biopsy should not be a criterion for exclusion.