VEXAS-like auto inflammatory syndrome: 2 cases

• Published in: La revue de medecine interne Vol. 46; no. 3; p. 139
• Main Authors: Devaux, Mathilde, Jachiet, Vincent, Hirsch, Pierre, Georgin-Lavialle, Sophie, Mekinian, Arsene, Salmeron, Geraldine, Sep-Hieng, Sonnthida, Flandrin-Gresta, Pascale, Chretiennot, Andrea, Ghit, Lilia, Masson, Helene, Le Lostec, Zoe, Veyssier-Belot, Catherine
• Format: Journal Article
• Language: French
• Published: France 01.03.2025
• Subjects: Hereditary Autoinflammatory Diseases - diagnosis; Hereditary Autoinflammatory Diseases - genetics; Humans; Male; Mutation; Myelodysplastic Syndromes; Skin Diseases, Genetic; Ubiquitin-Activating Enzymes - genetics; Syndrome auto-inflammatoire; Clonal hematopoïesis; VEXAS syndrome; Syndrome VEXAS; Corticosteroid dependence; Hematopoïèse clonale; Auto inflammatory syndrome; Corticodépendance
• ISSN: 1768-3122; 1768-3122
• DOI: 10.1016/j.revmed.2024.12.003

VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic), recently described, due to a somatic mutation of the UBA1 gene and often associated with hemopathy, is characterized by systemic symptoms close to those described in Still's disease or relapsing polychondritis. There are also patients with hemopathy, presenting inflammatory symptoms reminiscent of those of VEXAS syndrome but without mutation of the UBA1 gene. Two male patients consulted for general signs, dermatological symptoms, arthralgia, chondritis and venous thrombosis, like patients in the French cohort suffering from VEXAS syndrome. The myelogram found vacuoles in the myeloid and erythroid precursors, with a diagnosis of chronic myelomonocytic leukemia for one and myelodysplastic syndrome for the other. The search for a mutation of the UBA1 gene by the sanger technique, the next-generation sequencing (NGS) analysis of a myeloid panel and the complete sequencing was negative, not allowing the diagnosis of VEXAS syndrome to be retained. There were other somatic mutations, indicating clonal hematopoiesis associated with this systemic inflammatory state. Initial corticosteroid therapy was effective but corticosteroid dependence required sparing treatment with hypomethylating agents or Janus Kinase inhibitors. The role of somatic mutations in the pathophysiology of autoinflammatory diseases associated with hematologic diseases must be better understood in order to better characterize them and develop targeted treatments.