{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T09:12:58Z","timestamp":1780391578827,"version":"3.54.1"},"reference-count":19,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T00:00:00Z","timestamp":1764633600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      VEXAS syndrome (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) is a late-onset autoinflammatory disorder caused by somatic mutations in the\n                      <jats:italic>UBA1<\/jats:italic>\n                      gene. It is characterized by systemic inflammation, a wide spectrum of rheumatologic features, including chondritis and inflammatory arthritis, dermatologic manifestations (e.g. neutrophilic dermatosis or vasculitis-like lesions), and hematologic abnormalities like macrocytic anemia and myelodysplastic syndrome. Due to its heterogeneity, diagnosis is frequently delayed. Early recognition of hallmark inflammatory symptoms, particularly by rheumatologists, is critical for timely diagnosis and management.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a retrospective analysis of 37 patients over the age of 50. Next-Generation Sequencing (Illumina HiSeq2500) was employed to assess mutations. Clinical, genetic, and demographic data were extracted from electronic medical records.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Twenty patients [100% male; median age 73 years (IQR 67\u201377)] were confirmed to carry somatic\n                      <jats:italic>UBA1<\/jats:italic>\n                      mutations. All patients exhibited constitutional symptoms (100%) and at least one rheumatologic manifestation, including chondritis (75%), arthralgia or arthromyalgia (50%), arthritis (30%), osteopenia or osteoporosis (15%), myalgia or myositis (10%), and tenosynovitis (5%). Dermatologic and hematologic abnormalities frequently co-occurred. Infectious complications were observed in 80% of patients and were a major contributor to overall morbidity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study underscores the need for a phenotype-driven diagnostic approach to facilitate earlier identification of VEXAS syndrome. Our findings suggest that current estimates of prevalence in rheumatology settings may significantly underestimate the true disease burden. Improved awareness and interdisciplinary collaboration, particularly among rheumatologists, hematologists, and dermatologists, are essential to enhance recognition, diagnosis, and comprehensive care for individuals affected by this complex syndrome.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1700737","type":"journal-article","created":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T05:14:37Z","timestamp":1764652477000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["VEXAS syndrome in rheumatology practice: features from a multicenter cohort in north-east Italy"],"prefix":"10.3389","volume":"16","author":[{"given":"Sara","family":"Bindoli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greta","family":"Morello-Pasin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Guidea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Padoan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Iorio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Bixio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Orsolini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Maiolini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Lombardi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Lombardi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Favero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Bernardi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd","family":"Raffeiner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Doria","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Ramonda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Sfriso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,12,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2026834","article-title":"Somatic mutations in UBA1 and severe adult-onset autoinflammatory disease","volume":"383","author":"Beck","year":"2020","journal-title":"N Engl J Med"},{"key":"B2","doi-asserted-by":"crossref","DOI":"10.1182\/blood.2022016985","article-title":"Translation of cytoplasmic UBA1 contributes to VEXAS syndrome pathogenesis","volume":"140","author":"Ferrada","year":"2022","journal-title":"Blood"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keaf293\/8164134","article-title":"Clinical features in VEXAS syndrome: a systematic review","volume":"64","author":"Al-Hakim","year":"2025","journal-title":"Rheumatology"},{"key":"B4","unstructured":"Comunicato-territoriale\/il-censimento-permanente-della-popolazione-in-veneto-anno-2021"},{"key":"B5","doi-asserted-by":"crossref","DOI":"10.1016\/j.ard.2025.05.767","article-title":"Development of A disease activity index for the assessment of vexas syndrome (Vexas-dai)","volume":"84","author":"Byram","year":"2025","journal-title":"Ann Rheum Dis"},{"key":"B6","doi-asserted-by":"crossref","DOI":"10.1111\/bjd.20805","article-title":"Further characterization of clinical and laboratory features in VEXAS syndrome: large-scale analysis of a multicentre case series of 116 French patients","volume":"186","author":"Georgin-Lavialle","year":"2022","journal-title":"Br J Dermatol"},{"key":"B7","doi-asserted-by":"crossref","first-page":"3879","DOI":"10.57187\/s.3879","article-title":"VEXAS syndrome: a Swiss national retrospective cohort study","volume":"155","author":"Wolff","year":"2024","journal-title":"Swiss Med Wkly"},{"key":"B8","doi-asserted-by":"crossref","DOI":"10.1093\/rheumatology\/keaf094","article-title":"VEXAS syndrome through a rheumatologist\u2019s lens: insights from a Spanish national cohort","volume":"64","author":"Garc\u00eda-Escudero","year":"2025","journal-title":"Rheumatology"},{"key":"B9","doi-asserted-by":"crossref","DOI":"10.1016\/j.jaad.2022.10.052","article-title":"Clinical and pathological features of cutaneous manifestations in VEXAS syndrome: A multicenter retrospective study of 59 cases","volume":"88","author":"Zakine","year":"2023","journal-title":"J Am Acad Dermatol"},{"key":"B10","doi-asserted-by":"crossref","DOI":"10.1093\/rheumatology\/keae550","article-title":"Vasculitis associated with VEXAS syndrome","volume":"64","author":"Sullivan","year":"2025","journal-title":"Rheumatology"},{"key":"B11","doi-asserted-by":"crossref","DOI":"10.1016\/j.chest.2022.10.011","article-title":"Pleuropulmonary manifestations of vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome","volume":"163","author":"Borie","year":"2023","journal-title":"Chest"},{"key":"B12","doi-asserted-by":"crossref","first-page":"152430","DOI":"10.1016\/j.semarthrit.2024.152430","article-title":"Orbital\/ocular inflammatory involvement in VEXAS syndrome: Data from the international AIDA network VEXAS registry","volume":"66","author":"Vitale","year":"2024","journal-title":"Semin Arthritis Rheum"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1002\/art.41992","article-title":"VEXAS syndrome: A case series from a single-center cohort of italian patients with vasculitis","volume":"74","author":"Muratore","year":"2022","journal-title":"Arthritis Rheum"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keae530","article-title":"Low remission rates and high incidence of adverse events in a prospective VEXAS syndrome registry","volume":"64","author":"Kirino","year":"2025","journal-title":"Rheumatology"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2025.1462254","article-title":"Efficacy and safety profile of biotechnological agents and Janus kinase inhibitors in VEXAS syndrome: data from the international AIDA Network VEXAS registry","volume":"16","author":"Vitale","year":"2025","journal-title":"Front Pharmacol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1136\/ard-2023-224819","article-title":"French VEXAS Group. Serious infections in patients with VEXAS syndrome: data from the French VEXAS registry","volume":"83","author":"De Valence","year":"2024","journal-title":"Ann Rheum Dis"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.27169","article-title":"Diagnostic capabilities, clinical features, and longitudinal UBA1 clonal dynamics of a nationwide VEXAS cohort","volume":"99","author":"Gurnari","year":"2024","journal-title":"Am J Hematol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2022.24836","article-title":"Estimated prevalence and clinical manifestations of UBA1 variants associated with VEXAS syndrome in a clinical population","volume":"24","author":"Beck","year":"2023","journal-title":"JAMA J Am Med Assoc"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2022.926500","article-title":"Development and implementation of the AIDA international registry for patients with VEXAS syndrome","volume":"9","author":"Vitale","year":"2022","journal-title":"Front Med (Lausanne)"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1700737\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T05:14:39Z","timestamp":1764652479000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1700737\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,2]]},"references-count":19,"alternative-id":["10.3389\/fimmu.2025.1700737"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1700737","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,2]]},"article-number":"1700737"}}