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
Service de médecine interne, CHI Poissy-St Germain, 10, rue du Champs Gaillard, 78300 Poissy, France.
Service de medicine interne and inflammation-immunopathology-biotherapy department (DMU i2), Sorbonne Université, AP-HP, Hôpital Saint-Antoine, 75012 Paris, France.
Rev Med Interne. 2025 Mar;46(3):139-145. doi: 10.1016/j.revmed.2024.12.003. Epub 2024 Dec 24.
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.
CASE/DISCUSSION: 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.
VEXAS综合征（空泡、E1酶、X连锁、自身炎症性、体细胞性），最近被描述，由于UBA1基因的体细胞突变，且常与血液病相关，其特征为具有与斯蒂尔病或复发性多软骨炎中描述的症状相似的全身症状。也有血液病患者表现出类似于VEXAS综合征的炎症症状，但UBA1基因无突变。
病例/讨论：两名男性患者因全身症状、皮肤症状、关节痛、软骨炎和静脉血栓前来就诊，类似于法国队列中患有VEXAS综合征的患者。骨髓检查发现髓系和红系前体细胞有空泡，其中一名诊断为慢性粒单核细胞白血病，另一名诊断为骨髓增生异常综合征。通过桑格技术寻找UBA1基因突变、对髓系panel进行二代测序（NGS）分析以及全基因组测序均为阴性，无法确诊为VEXAS综合征。存在其他体细胞突变，表明这种全身炎症状态与克隆性造血有关。初始皮质类固醇治疗有效，但由于皮质类固醇依赖，需要使用低甲基化药物或Janus激酶抑制剂进行减量治疗。
为了更好地对与血液系统疾病相关的自身炎症性疾病进行特征描述并开发靶向治疗方法，必须更好地理解体细胞突变在其病理生理学中的作用。
