{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T05:19:03Z","timestamp":1764307143984,"version":"3.46.0"},"reference-count":27,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T00:00:00Z","timestamp":1764288000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>VEXAS syndrome is a rare and severe systemic inflammatory disorder caused by somatic mutations in the X-linked UBA1 gene, primarily affecting men. Since its initial description in 2020, it has been recognized for its complex clinical phenotype and tendency to be misdiagnosed. We report a case of a 77-year-old Chinese man diagnosed with VEXAS syndrome. The patient presented with recurrent fever, elevated inflammatory markers, anemia (decreased hemoglobin), multifocal interstitial pneumonia, and cardiac arrhythmia. On the day of admission, the patient developed rapidly progressive respiratory distress with a marked worsening of inflammatory markers. While providing supportive symptomatic treatment, we performed next-generation sequencing (NGS), 18F-fluorodeoxyglucose positron emission tomograph\u2013computed tomography (18FDG PET-CT), and whole-exome sequencing. Based on a presumed clinical diagnosis of small-vessel vasculitis, the patient was empirically treated with glucocorticoids combined with intravenous immunoglobulin (IVIG). Once the patient\u2019s condition improved, whole-exome sequencing revealed a UBA1 splice-site mutation (c.118-1G&amp;gt;C), consistent with VEXAS syndrome. After reviewing related reports, we subsequently performed a bone marrow aspiration, which showed characteristic cytoplasmic vacuolization in myeloid precursor cells. Retrospective history review revealed that the patient had developed skin lesions one year before the onset of fever. The clinical presentation of VEXAS syndrome is heterogeneous and associated with high mortality. It can be difficult to distinguish VEXAS from other autoimmune diseases, hematologic malignancies, and infectious diseases. In this case, given the patient\u2019s rapidly progressive interstitial pneumonia, we used NGS and 18FDG PET-CT to exclude infection and hematologic malignancy, and focused on empirical treatment for presumed small-vessel vasculitis, which quickly halted disease progression. Meanwhile, whole-exome sequencing ultimately identified the underlying cause.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1724045","type":"journal-article","created":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T05:14:47Z","timestamp":1764306887000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: VEXAS syndrome with extensive pulmonary, cardiac, and skeletal involvement"],"prefix":"10.3389","volume":"16","author":[{"given":"Zhongbiao","family":"Fang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tingwei","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chaonan","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anwen","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yudan","family":"Gu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chuhan","family":"Lan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zongming","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lingling","family":"Tang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,11,28]]},"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","article-title":"VEXAS Syndrome","volume-title":"GeneReviews","author":"Hadjadj","year":"1993"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2023012478","article-title":"Allogeneic hematopoietic cell transplantation for VEXAS syndrome: results of a multicenter study of the EBMT","volume":"8","author":"Gurnari","year":"2024","journal-title":"Blood Adv"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1136\/ard-2024-225640","article-title":"Efficacy and safety of targeted therapies in VEXAS syndrome: retrospective study from the FRENVEX","volume":"83","author":"Hadjadj","year":"2024","journal-title":"Ann Rheum Dis"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1136\/ard-2023-224819","article-title":"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":"B6","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.901063\/full","article-title":"Case Report: Tocilizumab Treatment for VEXAS Syndrome With Relapsing Polychondritis: A Single-Center, 1-Year Longitudinal Observational Study In Japan","volume":"13","author":"Kunishita","year":"2022","journal-title":"Front Immunol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1002\/art.41743","article-title":"Somatic Mutations in UBA1 Define a Distinct Subset of Relapsing Polychondritis Patients With VEXAS","volume":"73","author":"Ferrada","year":"2021","journal-title":"Arthritis Rheumatol Hoboken NJ"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(20)30113-7","article-title":"Human ubiquitin-activating enzyme, E1. 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