Case Presentation: 67 year old man with a history of psoriasiform dermatitis refractory to dapsone and hydroxychloroquine, thrombotic thrombocytopenic purpura status post plasma exchange and rituximab, and a history of multiple venous thromboemboli, and a fever of unknown origin presented with progressive worsening of his skin lesions. On exam, the patient was febrile (temperature 39.3C), tachycardic (heart rate 141), blood pressure 153/77, respiratory rate was 22, and O2 saturation was 94% on room air. He had a diffuse poikilodermatous, erythematous patches and plaques ranging from pink to violaceous involving about 75% of his body; retiform purpura on his bilateral lower extremities; and the left side of his face had vegetative, yellow, scaly plaques with overlying hemorrhagic crusting. The remainder of the exam was normal. White blood cell count was 20.6 x 103/mcL (normal range 4.2-9.1 x103/mcl), hemoglobin was 6.3 gm/dl (normal range 12.9-16.1 gm/dl), and an MCV 96.3 fl (normal range 70.0-92.2 fl). Biopsies of the scaly poikilodermatous plaques showed psoriasiform dermatitis, however, a peripheral blood flow cytometry did not identify any abnormal hematolymphoid cell populations and a bone marrow biopsy did not show evidence of an atypical hematolymphoid population. Biopsy of the retiform purpura on his lower extremities showed a thrombotic vasculopathy. A biopsy of his vegetative, yellow, scaly plaques on the left side of his face showed a medium-size vessel vasculitis. He was initially treated with Cyclosporine 50mg PO Q12h, Methotrexate 5mg PO Qweekly (with folic acid 2mg PO daily), Prednisone (started on 40mg PO daily and tapered down to 15mg PO daily, Acitretin 25mg PO daily, and triamcinolone 0.1% ointment BID with only a mild improvement of his skin lesions so he was also started on Ustekinumab 45mg SC Q4weeks x 2 then q3months. The patient’s combination of an adult onset systemic inflammatory condition of unknown etiology, a cutaneous vasculitis, fever of unknown origin, thrombocytopenia, anemia, and multiple venous thromboemboli that is refractory or poorly responsive to multiple types of immunosuppressant therapies is consistent with VEXAS syndrome.
Discussion: VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a severe, progressive disease with primarily rheumatologic and hematologic features caused by a mutation UBA1 gene (X chromosome) and was first reported in 2020. It is characterized by systemic inflammation of the skin, lungs, blood vessels, most commonly manifesting as a vasculitis, polychondritis, or neutrophilic dermatoses, among others. The hematologic manifestations often include a macrocytic anemia, thrombocytopenia, thromboembolic disease, and in some cases, progressive bone marrow failure. Currently, there are no established treatment guidelines so outcomes tend to be poor.
Conclusions: VEXAS syndrome is a newly discovered disease entity that requires additional study to better understand its epidemiology, etiology, pathology, prognosis, and in order to develop more effective treatments. VEXAS syndrome should be included in the differential diagnosis in hospitalized patients who present with treatment-refractory systemic inflammatory conditions, such as a vasculitis, polychondritis, or neutrophilic dermatoses who also have hematologic abnormalities, most commonly a macrocytic anemia, thrombocytopenia, and thromboembolic disease to help guide management.