VEXAS Syndrome in a Patient with Myeloproliferative Neoplasia

Abstract

VEXAS syndrome stands for vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic syndrome. The syndrome is a combined hematological and rheumatological condition caused by a somatic mutation in the UBA1. There is an association between VEXAS and hematological conditions such as myelodysplastic syndrome (MDS), monoclonal gammopathies of uncertain conditions (MGUS), multiple myeloma (MM), and monoclonal B-cell lymphoproliferative conditions. There are not many descriptions of patients having VEXAS in combination with myeloproliferative neoplasm (MPN). With this article, we want to present a case history of a man in his sixties with a JAK2V617F mutated essential thrombocythemia (ET) developing VEXAS syndrome. The inflammatory symptoms occurred three and a half years after the ET diagnosis. He started to experience symptoms of autoinflammation and an overall worsening of his health, and blood work showed high inflammatory markers, leading to repeated hospitalizations. His major complaint was stiffness and pain, and high dosages of prednisolone were necessary to obtain pain relief. He subsequently developed anemia and significantly variable levels of thrombocytes, which previously were at a steady level. To evaluate his ET, we made a bone marrow smear demonstrating vacuolated myeloid and erythroid cells. Having VEXAS syndrome in mind, genetic testing identifying the UBA1 gene mutation was performed, thus confirming our suspicion. The work-up with myeloid panel on his bone marrow identified genetic mutation in the DNMT3 too. After developing VEXAS syndrome, he experienced thromboembolic events with both cerebral infarction and pulmonary embolism. Thromboembolic events are also common in JAK2 mutated patients, but in his case, they presented first after VEXAS had developed. Throughout the course of his condition, several attempts with prednisolone tapering and steroid sparing drugs were tried. He could not get pain relief unless the combination of medications included a relatively high dose of prednisolone. Currently, the patient uses prednisolone, anagrelide, and ruxolitinib, with partial remission and fewer hospitalizations and more stabilized hemoglobin and thrombocytes.

VEXAS syndrome: A review of cutaneous findings and treatments in an emerging autoinflammatory disease

“…One case reported stabilization of VEXAS clinical course with a combination of prednisolone, anagrelide and ruxolitinib. The patient experienced partial remission, fewer hospitalizations and more stabilized haemoglobin and thrombocytes 38 . Loschi et al.…”

“…The patient experienced partial remission, fewer hospitalizations and more stabilized haemoglobin and thrombocytes. 38 Loschi et al reported a 60-year-old male with VEXAS with worsening inflammation flares with ruxolitinib tapering prior to allogeneic stem cell transplantation. Eighty-one days posttransplantation, the patient was able to taper corticosteroids and ruxolitinib.…”

“…In the case of VEXAS syndrome, over 80% of cases have reported using corticosteroids as the first‐prescribed treatment (particularly prednisone and prednisolone at varying dosages). Patients started on oral steroids often saw relief of symptoms within 2 weeks; however, in several cases, patients were unable to taper off the steroid without symptomatic relapse 10,23,26,30–50 . Most patients required long‐term oral steroid use for management of VEXAS, and when there was no response to oral steroids, steroid‐sparing agents—most commonly methotrexate—were prescribed as alternatives but were not always able to control symptoms.…”

VEXAS and Myelodysplastic Syndrome: An Interdisciplinary Challenge

“…Limited but promising results have been achieved with the JAK1/2 inhibitor ruxolitinib or the hypomethylating agent 5-azacytidine [8][9][10]18,24]. Due to this fact and the absence of evidence-based recommendations, we treated our patients with these two substances.…”

“…Common clinical features observed in VEXAS syndrome patients include skin lesions (83%), non-infectious fever (64%), weight loss (62%), lung involvement (50%), ocular symptoms (39%), relapsing chondritis (36%), venous thrombosis (35%), lymphadenopathy (34%), and arthralgia (27%) [3]. Additionally, patients with VEXAS syndrome experience progressive hematologic abnormalities such as macrocytic anemia, thrombocytopenia, and myeloid dyspoiesis [8][9][10]. In a substantial number of cases, the disease may progress to an overt hematologic malignant condition [11][12][13].…”