[VEXAS-like auto inflammatory syndrome: 2 cases].

Area of Science:

• Hematology
• Immunology
• Genetics

Background:

• VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is a recently described condition caused by somatic UBA1 gene mutations, often associated with hemopathy.
• Patients with hemopathy can exhibit inflammatory symptoms similar to VEXAS syndrome but without the characteristic UBA1 mutation.

Purpose of the Study:

• To investigate cases presenting with VEXAS-like symptoms but lacking UBA1 mutations.
• To explore the role of other somatic mutations in the pathophysiology of these inflammatory conditions.

Main Methods:

• Clinical case presentation of two male patients with systemic inflammatory symptoms and hemopathy.
• Diagnostic workup including myelogram, Sanger sequencing, next-generation sequencing (NGS) of a myeloid panel, and whole exome sequencing.
• Assessment of treatment response to corticosteroids, hypomethylating agents, and Janus Kinase inhibitors.

Main Results:

• Two male patients presented with symptoms overlapping with VEXAS syndrome, including arthralgia, chondritis, and venous thrombosis.
• Myelogram revealed vacuoles in myeloid and erythroid precursors, with diagnoses of chronic myelomonocytic leukemia and myelodysplastic syndrome.
• Genetic analysis for UBA1 mutations was negative; however, other somatic mutations indicating clonal hematopoiesis were identified.
• Initial corticosteroid therapy was effective, but dependence necessitated treatment with hypomethylating agents or JAK inhibitors.

Conclusions:

• The study highlights that inflammatory diseases associated with hematologic conditions can occur without UBA1 mutations.
• Somatic mutations play a significant role in the pathophysiology of these complex disorders.
• Further research is needed to better characterize these conditions and develop targeted therapies.