Vacuoles, E1 Enzyme, X-linked, Autoinflammatory, and Somatic (VEXAS) Syndrome: A Diagnostic and Therapeutic Conundrum

Vacuoles, E1 enzyme, X-linked, autoinflammatory, and somatic (VEXAS) syndrome is an adult-onset systemic autoinflammatory condition notable for being simultaneously an autoinflammatory syndrome and a hematologic disease. Here, we present a clinical case of a 67-year-old man referred to the Autoimmune Diseases Outpatient Clinic for a two-year history of maculopapular rash involving the face, trunk, back, and upper limbs. At the time, the patient had already undergone three skin biopsies, with conflicting results. His physical exam was only remarkable for multiple roundly shaped maculopapules involving the trunk, back, and extremities. Laboratory evaluation revealed elevated erythrocyte sedimentation rate and C-reactive protein, increased alpha-2 zone in the serum protein electrophoresis, and positive IgM antibodies against Borrelia burgdorferi. A diagnosis of Lyme disease was assumed, and a trial of doxycycline for two weeks was introduced, as well as hydroxychloroquine at a maximum dosage of 5 mg/kg, without noticeable improvement. A new skin biopsy was performed, suggestive of amyopathic dermatomyositis. Prednisolone at a dosage of 0.5 mg/kg/day was then started, with some improvement. Two years later, the patient developed two episodes of deep vein thrombosis along with a de novo macrocytic anemia and neutropenia. A positron emission computed tomography showed nonspecific medullar activation, whereas bone marrow aspirate and biopsy suggested a diagnosis of myelodysplastic syndrome. The patient became progressively more reliant on regular blood product transfusions, and, three years later, a recrudescence of his skin lesions was also noted under a prednisolone dosage of 5 mg/day. Although an increase in prednisolone to 0.5 mg/kg/day and an association with methotrexate and dapsone were tried, no improvement was noted. Bone marrow aspirate and biopsy were repeated, with aberrant vacuolized bone marrow cells being observed. A genetic analysis revealed a Met41Leu mutation at the ubiquitin-activating enzyme 1 (UBA1) gene, confirming the diagnosis of VEXAS syndrome. The patient was started on tocilizumab 6 mg/kg, but a profound neutropenia required a therapeutical switch to ruxolitinib.