Challenging the paradigm: a case of early-onset VEXAS syndrome

Dear Editor, VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a recently characterized autoinflammatory disease that primarily affects elderly male patients [1]. VEXAS syndrome is recognized as a prototypical example of hematoinflammatory diseases, which represent a novel category of conditions wherein somatic mutations in blood cells give rise to systemic inflammation that can potentially evolve into myeloproliferative, myelodysplastic or lymphoproliferative disorders [2]. Herein, we describe a male patient who presented in June 2020 at the age of 23 with fever, myalgias and episcleritis. He was treated with systemic and topical non-steroidal anti-inflammatory drugs. Subsequently, he developed painful chondritis in the right ear, initially managed with antibiotics and betamethasone, followed by episodes affecting both ears (Fig. 1A). In August 2020, the patient sought the care of a rheumatologist, who diagnosed relapsing polychondritis and prescribed prednisone and azathioprine. Throughout 2021, the patient experienced ankle and midfoot arthritis, heel pain, costochondritis, left testicular pain, vertigo and tinnitus. These episodes were accompanied by fever and occurred when prednisone was tapered below 20 mg per day, responding to the increase of doses of prednisone. The patient also presented with superficial thrombophlebitis at sites of venipunctures, suggestive of pathergy phenomenon. Laboratory tests revealed mild macrocytic anaemia [haemoglobin: 11.7 g/dl; mean corpuscular volume (MCV): 103 fL], leukopenia (3400/µL), neutropenia (920/µL), and platelet count in 156 000/µL, elevated erythrocyte sedimentation rate (103 mm/h), C-reactive protein (403 mg/l), and ferritin levels (869 ng/ml). In early January 2022, the patient experienced another episode of fever and chondritis accompanied with oxygen desaturation, tachycardia and chest pain. A left lobar pneumonia was identified on a computed tomography scan and treated with antibiotics, resulting in a two-day hospital stay.