Case report: VEXAS syndrome: first documented cases in Latin America

Frontiers in Hematology, Journal Year: 2025, Volume and Issue: 3

Published: Jan. 16, 2025

Introduction VEXAS syndrome (Vacuoles, E1 Enzyme, X-linked, Autoinflammatory, Somatic) is a recently identified disorder associated with somatic mutations in the UBA1 gene. Predominantly affecting adult males, it characterized by wide range of autoinflammatory symptoms and hematologic abnormalities. Methods We present three cases from Latin America, marking first reported occurrences this region, to illustrate clinical variability diagnostic challenges syndrome. Results Each patient exhibited unique presentations, including refractory symptoms, myelodysplastic syndrome, bone marrow vacuolization. All were confirmed via genetic testing, revealing pathogenic alongside other variants commonly linked myeloid neoplasms. Discussion These findings underscore importance considering patients unexplained inflammatory symptoms. The coexistence suggests potential overlap clonal hematopoiesis, complicating picture. contribute understanding highlight need for increased awareness testing diverse populations ensure early accurate diagnosis.

Language: Английский

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VEXAS, Chediak–Higashi syndrome and Danon disease: myeloid cell endo-lysosomal pathway dysfunction as a common denominator?

Cellular & Molecular Biology Letters, Journal Year: 2025, Volume and Issue: 30(1)

Published: Jan. 26, 2025

Abstract Vacuolization of hematopoietic precursors cells is a common future several otherwise non-related clinical settings such as VEXAS, Chediak–Higashi syndrome and Danon disease. Although these disorders have priori nothing to do with one other from point view, all share abnormal vacuolization in different cell types including the erythroid/myeloid lineage that likely consequence moderate drastic dysfunctions ubiquitin proteasome system and/or endo-lysosomal pathway. Indeed, genes affected three diseases UBA1, LYST or LAMP2 are known be direct indirect regulators lysosome trafficking function modes autophagy. Furthermore, highly expressed more mature myeloid pointing out their important cells. deficiency for instance associated alterations architecture function. It thus well established disease patients harbor invalidating mutations exhibit giant lysosomes containing undigested materials characteristic defects fusion autophagosomes, feature also found VEXAS CHS. Other similarities regarding include granulocyte monocyte recurrent inflammatory climate. In present review we discuss possibility some manifestations diseases, notably ones consecutive dysfunction pathway myeloid/erythroid progenitors neutrophiles, monocytes macrophages. Finally, propose reacidification way reinducing functionalities autophagy potential approach better management diseases.

Language: Английский

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Efficacy and safety of conventional disease-modifying antirheumatic drugs in VEXAS syndrome: real-world data from the international AIDA network

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: March 7, 2025

Background VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is an adult-onset autoinflammatory condition resulting in severe, often treatment-refractory inflammation. Currently, there are no established treatment guidelines for syndrome. Objectives To assess the efficacy and safety of conventional disease-modifying antirheumatic drugs (cDMARDs) a cohort patients. Methods Data from patients were obtained International AIDA Network registry. Results 36 evaluated, with 28 (77.8%) treated cDMARDs as monotherapy - concomitant glucocorticoids (GC) 8 (22.2%) receiving combination different plus GC. Complete response (CR), partial (PR), failure to reported 4/22 (18.2%), 11/22 (50%), 7/22 (31.8%) courses, respectively. All GCs at start cDMARD monotherapy, GC discontinuation was observed later. No significant differences dosage 3-month ( p = 0.43), 6-month 0.31), 12-month 0.21) visits. Conversely, sparing resulted be statistically when using methotrexate 0.02). As combinations, cases achieved CR, while PR 5/9 (55.6%). Seventeen adverse events reported, seven which led discontinuation. Conclusion Many report benefit cDMARDs, smaller yet not negligible number exhibit CR; remain viable option this disorder, especially initial low need steroid-sparing effect immediately urgent.

Language: Английский

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How Protein Ubiquitination Can Influence Cytokine Expression—Updated Review on Autoinflammatory VEXAS Syndrome

Immuno, Journal Year: 2024, Volume and Issue: 4(3), P. 286 - 300

Published: Sept. 23, 2024

VEXAS syndrome is a new disease entity with symptoms that can mimic hematological, rheumatic and dermatological diseases. It important to take multidisciplinary approach patient care, taking into account genetic testing, in which the presence of mutations UBA1 gene confirm diagnosis. mutation has been shown be involved induction inflammatory response through many different mechanisms. NF-κB TNF-α pathways appear most syndrome. There are result outcomes, suggesting it possible prognostic factor. Furthermore, differ how they impair function. Cytokines have significantly altered patients; however, their exact expression importance were not clearly defined. Interleukins, such as interleukin (IL)-6, IL-1, IL-2R others, reported expressed at an level, similarly other cytokines, IFN-γ or TNF-α. worth noting certain cytokines vary between patients, poses therapeutic difficulties selecting right drug. Therefore, aim this review was describe associate mutation.

Language: Английский

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VEXAS in a Patient with Hypereosinophilia and Sweet’s-like Lesions

JAAD Case Reports, Journal Year: 2024, Volume and Issue: 53, P. 71 - 74

Published: Sept. 7, 2024

Language: Английский

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VEXAS syndrome: an adult-onset autoinflammatory disorder with underlying somatic mutation

Current Opinion in Rheumatology, Journal Year: 2024, Volume and Issue: 37(1), P. 21 - 31

Published: Oct. 25, 2024

VEXAS syndrome (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) was first described in 2020, where a cohort of adults with unexplained fever or inflammation, systematic genetic testing performed and 25 men median age 64 years somatic mutations the UBA1 gene were identified. In current review, we aim to discuss relevant literature from January 2023 until July 2024 give new insights into pathophysiology, epidemiology, diagnosis treatment VEXAS.

Language: Английский

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