{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T12:39:40Z","timestamp":1786538380925,"version":"build-2736575974"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:00:00Z","timestamp":1784851200000},"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>Background<\/jats:title>\n                    <jats:p>Systemic lupus erythematosus (SLE) causes substantial premature mortality. Contemporary national data on long-term SLE-related mortality and its demographic and geographic disparities in the United States remain limited, particularly across the transition into the COVID-19 era.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a nationwide observational study using the 1999\u20132023 CDC WONDER Multiple Cause of Death database. SLE-related mortality was defined as any death certificate mention of SLE (ICD-10 M32). An underlying-cause-only sensitivity analysis assessed trend robustness. Annual deaths and age-adjusted mortality rates (AAMRs) were examined overall and by sex, age, race, geography, and urbanization. Temporal trends were evaluated using joinpoint regression to estimate annual percent changes (APCs) and average annual percent changes (AAPCs). Pooled state-level AAMRs were compared between 2016\u20132019 and 2020\u20132023.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>From 1999 to 2023, the national SLE-related AAMR declined from 1.03 to 0.73 per 100,000 (overall AAPC, \u22121.46%), while annual deaths increased slightly from 2,197 to 2,291. Joinpoint analysis identified a significant decline during 1999\u20132014, an increase during 2014\u20132021, and a sharp decline during 2021\u20132023. Women consistently had higher AAMRs than men. Adults aged \u226565 years had the highest mortality burden with little overall improvement. Black individuals maintained the highest AAMRs throughout, despite experiencing the steepest long-term decline. Geographically, the South, HHS Region 6, and Oklahoma remained high-burden areas. Nonmetropolitan areas showed smaller overall declines and steeper late-period increases. The underlying-cause-only sensitivity analysis also showed an AAMR decline from 0.59 to 0.29 per 100,000 (AAPC, \u22123.23%).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>U.S. SLE-related mortality declined overall from 1999 to 2023, but the absolute burden remained substantial and unequally distributed across demographic and geographic strata. Persistent excess mortality among women, older adults, Black individuals, and residents of high-burden areas highlights the need for more equitable translation of advances in lupus care into real-world survival gains.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1850485","type":"journal-article","created":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T05:36:18Z","timestamp":1784871378000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Systemic lupus erythematosus-related mortality declined but disparities persisted in the United States: a nationwide multiple-cause-of-death analysis, 1999\u20132023"],"prefix":"10.3389","volume":"17","author":[{"given":"Yuhuan","family":"Song","sequence":"first","affiliation":[{"name":"Department of Nephrology, Aerospace Center Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Public Health, Guizhou Medical University","place":["Guiyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The Second People\u2019s Hospital of Guiyang","place":["Guiyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuju","family":"Yang","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Genetic Diagnostics, Guiyang Maternal and Child Health Care Hospital, Guiyang Children\u2019s Hospital","place":["Guiyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaide","family":"Xia","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Genetic Diagnostics, Guiyang Maternal and Child Health Care Hospital, Guiyang Children\u2019s Hospital","place":["Guiyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2024.2315","article-title":"Systemic lupus erythematosus: a review","volume":"331","author":"Siegel","year":"2024","journal-title":"JAMA"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(24)00398-2","article-title":"Systemic lupus erythematosus","volume":"403","author":"Hoi","year":"2024","journal-title":"Lancet"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1100359","article-title":"Systemic lupus erythematosus","volume":"365","author":"Tsokos","year":"2011","journal-title":"N Engl J Med"},{"key":"B4","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.ejim.2023.02.004","article-title":"Mortality and causes of death in systemic lupus erythematosus over the last decade: data from a large population-based study","volume":"112","author":"Zen","year":"2023","journal-title":"Eur J Intern Med"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.589474","article-title":"COVID-19 and systemic lupus erythematosus: focus on immune response and therapeutics","volume":"11","author":"Spihlman","year":"2020","journal-title":"Front Immunol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2017-211663","article-title":"Survival in adults and children with systemic lupus erythematosus: a systematic review and Bayesian meta-analysis of studies from 1950 to 2016","volume":"76","author":"Tektonidou","year":"2017","journal-title":"Ann Rheum Dis"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1136\/ard-2022-223035","article-title":"Global epidemiology of systemic lupus erythematosus: a comprehensive systematic analysis and modelling study","volume":"82","author":"Tian","year":"2023","journal-title":"Ann Rheum Dis"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-021-00668-1","article-title":"Global epidemiology of systemic lupus erythematosus","volume":"17","author":"Barber","year":"2021","journal-title":"Nat Rev Rheumatol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.mm6818a4","article-title":"Racial disparities in mortality associated with systemic lupus erythematosus - Fulton and DeKalb Counties, Georgia, 2002-2016","volume":"68","author":"Lim","year":"2019","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1136\/lupus-2024-001383","article-title":"Association of race and ethnicity with mortality in adults with SLE: a systematic literature review and meta-analysis","volume":"12","author":"Patel","year":"2025","journal-title":"Lupus Sci Med"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.7326\/M17-0102","article-title":"46-year trends in systemic lupus erythematosus mortality in the United States, 1968 to 2013: a nationwide population-based study","volume":"167","author":"Yen","year":"2017","journal-title":"Ann Intern Med"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-022-06268-y","article-title":"Health disparities in systemic lupus erythematosus-a narrative review","volume":"41","author":"Hasan","year":"2022","journal-title":"Clin Rheumatol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2025.103887","article-title":"Social determinants of health and disparities across the patient pathway in systemic lupus erythematosus: a narrative review","volume":"24","author":"Guimar\u00e3es de Oliveira","year":"2025","journal-title":"Autoimmun Rev"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.rdc.2020.07.010","article-title":"Health disparities in systemic lupus erythematosus","volume":"46","author":"Peschken","year":"2020","journal-title":"Rheum Dis Clin North Am"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1136\/lupus-2022-000750","article-title":"Risks of mortality and severe coronavirus disease 19 (COVID-19) outcomes in patients with or without systemic lupus erythematosus","volume":"10","author":"Bruera","year":"2023","journal-title":"Lupus Sci Med"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1002\/acr2.70057","article-title":"Trends in systemic lupus erythematous mortality in the United States, 1999-2022","volume":"7","author":"Patel","year":"2025","journal-title":"ACR Open Rheumatol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.2105\/ajph.83.9.1289","article-title":"CDC WONDER: a comprehensive on-line public health information system of the Centers for Disease Control and Prevention","volume":"83","author":"Friede","year":"1993","journal-title":"Am J Public Health"},{"key":"B18","unstructured":"Multiple Cause of Death 1999\u20132023 on CDC WONDER Online Database\n          \n          \n          \n          2024"},{"key":"B19","unstructured":"Census Regions and Divisions of the United States\n          \n          \n          \n          2012"},{"key":"B20","unstructured":"HHS Regional Offices\n          \n          \n          \n          2023"},{"key":"B21","first-page":"1","article-title":"2013 NCHS urban-rural classification scheme for counties","volume":"166","author":"Ingram","year":"2014","journal-title":"Vital Health Stat 2"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1002\/(sici)1097-0258(20000215)19:3<335::aid-sim336>3.0.co;2-z","article-title":"Permutation tests for joinpoint regression with applications to cancer rates","volume":"19","author":"Kim","year":"2000","journal-title":"Stat Med"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1136\/lupus-2023-001124","article-title":"Disease-modifying therapies in systemic lupus erythematosus for extrarenal manifestations","volume":"11","author":"Askanase","year":"2024","journal-title":"Lupus Sci Med"},{"key":"B24","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1136\/ard-2023-224762","article-title":"EULAR recommendations for the management of systemic lupus erythematosus: 2023 update","volume":"83","author":"Fanouriakis","year":"2024","journal-title":"Ann Rheum Dis"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa043731","article-title":"Mycophenolate mofetil or intravenous cyclophosphamide for lupus nephritis","volume":"353","author":"Ginzler","year":"2005","journal-title":"N Engl J Med"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2008101028","article-title":"Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis","volume":"20","author":"Appel","year":"2009","journal-title":"J Am Soc Nephrol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1014460","article-title":"Mycophenolate versus azathioprine as maintenance therapy for lupus nephritis","volume":"365","author":"Dooley","year":"2011","journal-title":"N Engl J Med"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2019.10.017","article-title":"Update on lupus nephritis: core curriculum 2020","volume":"76","author":"Parikh","year":"2020","journal-title":"Am J Kidney Dis"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)61354-2","article-title":"Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomised, placebo-controlled, phase 3 trial","volume":"377","author":"Navarra","year":"2011","journal-title":"Lancet"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1002\/art.30613","article-title":"A phase III, randomized, placebo-controlled study of belimumab, a monoclonal antibody that inhibits B lymphocyte stimulator, in patients with systemic lupus erythematosus","volume":"63","author":"Furie","year":"2011","journal-title":"Arthritis Rheum"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3436","article-title":"Belimumab","volume":"10","author":"Sanz","year":"2011","journal-title":"Nat Rev Drug Discov"},{"key":"B32","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1007\/s00296-025-05910-7","article-title":"Sex- and gender-related differences in systemic lupus erythematosus: a scoping review","volume":"45","author":"Albrecht","year":"2025","journal-title":"Rheumatol Int"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1089\/jwh.2017.6334","article-title":"Impact of sex on systemic lupus erythematosus-related causes of premature mortality in the United States","volume":"26","author":"Falasinnu","year":"2017","journal-title":"J Women\u2019s Health"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2019-031850","article-title":"Association between organ damage and mortality in systemic lupus erythematosus: a systematic review and meta-analysis","volume":"10","author":"Murimi-Worstell","year":"2020","journal-title":"BMJ Open"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2023.103374","article-title":"Organ damage in systemic lupus erythematosus patients: a multifactorial phenomenon","volume":"22","author":"Ceccarelli","year":"2023","journal-title":"Autoimmun Rev"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1097\/BOR.0000000000000527","article-title":"Glucocorticoids and antimalarials in systemic lupus erythematosus: an update and future directions","volume":"30","author":"Ugarte","year":"2018","journal-title":"Curr Opin Rheumatol"},{"key":"B37","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1038\/s41392-025-02168-0","article-title":"Systemic lupus erythematosus: updated insights on the pathogenesis, diagnosis, prevention and therapeutics","volume":"10","author":"Dai","year":"2025","journal-title":"Signal Transduct Target Ther"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-024-07173-2","article-title":"Frailty in older adults with systemic lupus erythematosus and emergency department utilization: an administrative claims data analysis of Medicare beneficiaries","volume":"44","author":"Lieber","year":"2025","journal-title":"Clin Rheumatol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.semarthrit.2025.152709","article-title":"Prevalence of frailty and prefrailty in systemic lupus erythematosus: a systematic review and meta-analysis","volume":"72","author":"Sang","year":"2025","journal-title":"Semin Arthritis Rheum"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.3390\/healthcare13182285","article-title":"Integrating multimorbidity assessment into rheumatology care: prognostic role of the Charlson comorbidity index in systemic lupus erythematosus","volume":"13","author":"Ohta","year":"2025","journal-title":"Healthcare (Basel)"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kead427","article-title":"Mortality and causes of death in systemic lupus erythematosus in New Zealand: a population-based study","volume":"63","author":"Lao","year":"2024","journal-title":"Rheumatol (Oxford)"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-205139","article-title":"Treat-to-target in systemic lupus erythematosus: recommendations from an international task force","volume":"73","author":"van Vollenhoven","year":"2014","journal-title":"Ann Rheum Dis"},{"key":"B43","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.trsl.2020.12.007","article-title":"COVID-19 in patients with systemic lupus erythematosus: lessons learned from the inflammatory disease","volume":"232","author":"Fernandez-Ruiz","year":"2021","journal-title":"Transl Res"},{"key":"B44","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1097\/01.md.0000091181.93122.55","article-title":"Morbidity and mortality in systemic lupus erythematosus during a 10-year period: a comparison of early and late manifestations in a cohort of 1,000 patients","volume":"82","author":"Cervera","year":"2003","journal-title":"Med (Baltimore)"}],"updated-by":[{"DOI":"10.3389\/fimmu.2026.1955024","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000}}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1850485\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T12:10:55Z","timestamp":1786536655000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1850485\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,24]]},"references-count":44,"alternative-id":["10.3389\/fimmu.2026.1850485"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1850485","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,24]]},"article-number":"1850485"}}