{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T19:25:41Z","timestamp":1791228341061,"version":"4.1.0"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100005788","name":"Medical University of Vienna","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100005788","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Rheumatol Int"],"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>The presence of abnormal nailfold capillaries and antinuclear antibodies (ANA) is associated with increased all-cause mortality in patients presenting with incipient Raynaud\u2019s phenomenon (RP). We conducted a retrospective analysis aiming to assess the association between abnormal nailfold capillaries, ANA, and mortality over a 20-year follow-up period.\u00a0In 2958 patients with incipient RP without previously known connective tissue disease, nailfold capillaroscopies and laboratory tests for ANA and ANA-subsets were obtained. Of these, long-term follow-up data were available for 2922 patients.\u00a0Over a median follow-up period of 23 (IQR 20.2\u201325.2) years, 832 patients died, of which 562 were women (25% of female patients) and 270 were men (41% of male patients). Compared to a demographically matched reference population, mortality was increased in female and male patients with RP (log-rank test\u2009&lt;\u20090.001). In female patients with RP, the presence of ANA, anti-Scl-70 antibodies, and a grouping variable consisting of giant capillaries, reduced capillary density, and avascular fields was associated with an increase in all-cause mortality. The highest mortality was observed in patients presenting both abnormal nailfold capillaries and ANA.\u00a0In the long-term, an excess mortality persists in patients with RP. Our study demonstrates prognostic associations between abnormal nailfold capillaries as well as ANA and mortality.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00296-026-06261-7","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T04:34:54Z","timestamp":1785818094000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Relation of nailfold capillaries and autoantibodies to mortality in patients with Raynaud\u2019s phenomenon: a retrospective analysis"],"prefix":"10.1007","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1350-3742","authenticated-orcid":false,"given":"Markus","family":"M\u00fcller","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael E.","family":"Gschwandtner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5391-1954","authenticated-orcid":false,"given":"Hans","family":"Kiener","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7976-0285","authenticated-orcid":false,"given":"Thomas","family":"Perkmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6863-7997","authenticated-orcid":false,"given":"Sonja","family":"Zehetmayer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7825-1254","authenticated-orcid":false,"given":"Sophie","family":"Brunner-Ziegler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5680-1072","authenticated-orcid":false,"given":"Sabine","family":"Steiner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6934-5355","authenticated-orcid":false,"given":"Oliver","family":"Schlager","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,4]]},"reference":[{"issue":"6","key":"6261_CR1","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1056\/NEJMra1507638","volume":"375","author":"FM Wigley","year":"2016","unstructured":"Wigley FM, Flavahan NA (2016) Raynaud\u2019s phenomenon. N Engl J Med 375(6):556\u2013565","journal-title":"N Engl J Med"},{"issue":"12","key":"6261_CR2","doi-asserted-by":"publisher","first-page":"3317","DOI":"10.1007\/s10067-019-04745-5","volume":"38","author":"JD Pauling","year":"2019","unstructured":"Pauling JD, Hughes M, Pope JE (2019) Raynaud\u2019s phenomenon-an update on diagnosis, classification and management. Clin Rheumatol 38(12):3317\u20133330. https:\/\/doi.org\/10.1007\/s10067-019-04745-5","journal-title":"Clin Rheumatol"},{"issue":"1","key":"6261_CR3","doi-asserted-by":"publisher","first-page":"101474","DOI":"10.1016\/j.berh.2019.101474","volume":"34","author":"AL Herrick","year":"2020","unstructured":"Herrick AL, Wigley FM (2020) Raynaud\u2019s phenomenon. Best Pract Res Clin Rheumatol 34(1):101474. https:\/\/doi.org\/10.1016\/j.berh.2019.101474","journal-title":"Best Pract Res Clin Rheumatol"},{"issue":"5","key":"6261_CR4","first-page":"485","volume":"10","author":"EC LeRoy","year":"1992","unstructured":"LeRoy EC, Medsger TA (1992) Raynaud\u2019s phenomenon: a proposal for classification. Clin Exp Rheumatol 10(5):485\u2013488","journal-title":"Clin Exp Rheumatol"},{"key":"6261_CR5","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1016\/j.jaut.2014.01.020","volume":"48\u201349","author":"E Maverakis","year":"2014","unstructured":"Maverakis E, Patel F, Kronenberg DG, Chung L, Fiorentino D, Allanore Y (2014) International consensus criteria for the diagnosis of Raynaud\u2019s phenomenon. J Autoimmun 48\u201349:60\u201365. https:\/\/doi.org\/10.1016\/j.jaut.2014.01.020","journal-title":"J Autoimmun"},{"issue":"8","key":"6261_CR6","doi-asserted-by":"publisher","first-page":"634","DOI":"10.1136\/ard.47.8","volume":"47","author":"CG Kallenberg","year":"1988","unstructured":"Kallenberg CG, Wouda AA, Hoet MH, van Venrooij WJ (1988) Development of connective tissue disease in patients presenting with Raynaud\u2019s phenomenon: a six year follow up with emphasis on the predictive value of antinuclear antibodies as detected by immunoblotting. Ann Rheum Dis 47(8):634\u2013641. https:\/\/doi.org\/10.1136\/ard.47.8","journal-title":"Ann Rheum Dis"},{"issue":"1","key":"6261_CR7","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/S0889-857X(21)01038-3","volume":"16","author":"CG Kallenberg","year":"1990","unstructured":"Kallenberg CG (1990) Early detection of connective tissue disease in patients with Raynaud\u2019s phenomenon. Rheum Dis Clin North Am 16(1):11\u201330","journal-title":"Rheum Dis Clin North Am"},{"issue":"12","key":"6261_CR8","doi-asserted-by":"publisher","first-page":"3902","DOI":"10.1002\/art.24038","volume":"58","author":"M Koenig","year":"2008","unstructured":"Koenig M, Joyal F, Fritzler MJ, Roussin A, Abrahamowicz M, Boire G (2008) Autoantibodies and microvascular damage are independent predictive factors for the progression of Raynaud\u2019s phenomenon to systemic sclerosis: a twenty-year prospective study of 586 patients, with validation of proposed criteria for early systemic sclerosis. Arthritis Rheum 58(12):3902\u20133912. https:\/\/doi.org\/10.1002\/art.24038","journal-title":"Arthritis Rheum"},{"issue":"3","key":"6261_CR9","doi-asserted-by":"publisher","first-page":"226","DOI":"10.3109\/03009742.2013.847118","volume":"43","author":"O Schlager","year":"2014","unstructured":"Schlager O, Kiener HP, Stein L, Hofkirchner J, Zehetmayer S, Ristl R (2014) Associations of nailfold capillary abnormalities and immunological markers in early Raynaud\u2019s phenomenon. Scand J Rheumatol 43(3):226\u2013233. https:\/\/doi.org\/10.3109\/03009742.2013.847118","journal-title":"Scand J Rheumatol"},{"issue":"5","key":"6261_CR10","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1161\/CIRCULATIONAHA.115.017816","volume":"133","author":"M Mueller","year":"2016","unstructured":"Mueller M, Gschwandtner ME, Gamper J, Giurgea GA, Charwat-Resl S, Kiener HP (2016) Relation of nailfold capillaries and autoantibodies to mortality in patients with Raynaud phenomenon. Circulation 133(5):509\u2013517","journal-title":"Circulation"},{"issue":"3","key":"6261_CR11","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1007\/s00393-010-0618-0","volume":"69","author":"O Sander","year":"2010","unstructured":"Sander O, Sunderk\u00f6tter C, K\u00f6tter I, Wagner I, Becker M, Herrgott I (2010) [Capillaroscopy. Procedure and nomenclature]. Z Rheumatol 69(3):253\u2013262. https:\/\/doi.org\/10.1007\/s00393-010-0618-0","journal-title":"Z Rheumatol"},{"issue":"6","key":"6261_CR12","doi-asserted-by":"publisher","first-page":"885","DOI":"10.1136\/ard.2007.079756","volume":"67","author":"A Sulli","year":"2008","unstructured":"Sulli A, Secchi ME, Pizzorni C, Cutolo M (2008) Scoring the nailfold microvascular changes during the capillaroscopic analysis in systemic sclerosis patients. Ann Rheum Dis 67(6):885\u2013887. https:\/\/doi.org\/10.1136\/ard.2007.079756","journal-title":"Ann Rheum Dis"},{"issue":"4 Pt 1","key":"6261_CR13","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1161\/01.hyp.34.4.655","volume":"34","author":"TF Antonios","year":"1999","unstructured":"Antonios TF, Singer DR, Markandu ND, Mortimer PS, MacGregor GA (1999) Rarefaction of skin capillaries in borderline essential hypertension suggests an early structural abnormality. Hypertension 34(4 Pt 1):655\u2013658. https:\/\/doi.org\/10.1161\/01.hyp.34.4.655","journal-title":"Hypertension"},{"issue":"2","key":"6261_CR14","doi-asserted-by":"publisher","first-page":"e12665","DOI":"10.1111\/micc.12665","volume":"28","author":"M Schoina","year":"2021","unstructured":"Schoina M, Loutradis C, Theodorakopoulou M, Dimitroulas T, Triantafillidou E, Doumas M (2021) The presence of diabetes mellitus further impairs structural and functional capillary density in patients with chronic kidney disease. Microcirculation 28(2):e12665. https:\/\/doi.org\/10.1111\/micc.12665","journal-title":"Microcirculation"},{"issue":"2","key":"6261_CR15","doi-asserted-by":"publisher","first-page":"e12869","DOI":"10.1111\/eci.12869","volume":"48","author":"PP Wadowski","year":"2018","unstructured":"Wadowski PP, H\u00fclsmann M, Sch\u00f6rgenhofer C, Lang IM, Wurm R, Gremmel T (2018) Sublingual functional capillary rarefaction in chronic heart failure. Eur J Clin Invest 48(2):e12869. https:\/\/doi.org\/10.1111\/eci.12869","journal-title":"Eur J Clin Invest"},{"issue":"11","key":"6261_CR16","doi-asserted-by":"publisher","first-page":"1747","DOI":"10.1136\/annrheumdis-2013-204424","volume":"72","author":"F van den Hoogen","year":"2013","unstructured":"van den Hoogen F, Khanna D, Fransen J, Johnson SR, Baron M, Tyndall A (2013) Classification criteria for systemic sclerosis: an American college of rheumatology\/European league against rheumatism collaborative initiative. Ann Rheum Dis 72(11):1747\u20131755. https:\/\/doi.org\/10.1136\/annrheumdis-2013-204424","journal-title":"Ann Rheum Dis"},{"issue":"2","key":"6261_CR17","doi-asserted-by":"publisher","first-page":"e006716","DOI":"10.1136\/rmdopen-2026-006716","volume":"12","author":"A Lescoat","year":"2026","unstructured":"Lescoat A, Allanore Y, Del Galdo F, Kuwana M, Denton CP, Khanna D (2026) Scoping literature review on applied definitions of very early diagnosis of systemic sclerosis (VEDOSS) and pre-systemic sclerosis in original articles. RMD Open 12(2):e006716. https:\/\/doi.org\/10.1136\/rmdopen-2026-006716","journal-title":"RMD Open"},{"issue":"12","key":"6261_CR18","doi-asserted-by":"publisher","first-page":"e834","DOI":"10.1016\/S2665-9913(","volume":"3","author":"S Bellando-Randone","year":"2021","unstructured":"Bellando-Randone S, Del Galdo F, Lepri G, Minier T, Huscher D, Furst DE (2021) Progression of patients with Raynaud\u2019s phenomenon to systemic sclerosis: a five-year analysis of the European scleroderma trial and research group multicentre, longitudinal registry study for very early diagnosis of systemic sclerosis (VEDOSS). Lancet Rheumatol 3(12):e834\u2013e843. https:\/\/doi.org\/10.1016\/S2665-9913(","journal-title":"Lancet Rheumatol"},{"issue":"9","key":"6261_CR19","doi-asserted-by":"publisher","first-page":"1059","DOI":"10.1016\/j.amjmed.2022.04.006","volume":"135","author":"DS Feuer","year":"2022","unstructured":"Feuer DS, Handberg EM, Mehrad B, Wei J, Bairey Merz CN, Pepine CJ (2022) Microvascular dysfunction as a systemic disease: a review of the evidence. Am J Med. 135(9):1059\u20131068.","journal-title":"Am J Med"},{"key":"6261_CR20","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.ijcard.2021.02","volume":"333","author":"L Di Serafino","year":"2021","unstructured":"Di Serafino L, Mangiacapra F, Pyxaras S, Morisco C, Bartunek J, De Bruyne B (2021) Relationship between peripheral arterial reactive hyperemia and the index of myocardial resistance in patients undergoing invasive coronary angiography. Int J Cardiol 333:8\u201313. https:\/\/doi.org\/10.1016\/j.ijcard.2021.02","journal-title":"Int J Cardiol"},{"issue":"11","key":"6261_CR21","doi-asserted-by":"publisher","first-page":"2137","DOI":"10.1016\/j.jacc.2004.08.062","volume":"44","author":"PO Bonetti","year":"2004","unstructured":"Bonetti PO, Pumper GM, Higano ST, Holmes DR, Kuvin JT, Lerman A (2004) Noninvasive identification of patients with early coronary atherosclerosis by assessment of digital reactive hyperemia. J Am Coll Cardiol 44(11):2137\u20132141","journal-title":"J Am Coll Cardiol"},{"issue":"13","key":"6261_CR22","doi-asserted-by":"publisher","first-page":"1352","DOI":"10.1016\/j.jacc.2021.07.042","volume":"78","author":"MG Del Buono","year":"2021","unstructured":"Del Buono MG, Montone RA, Camilli M, Carbone S, Narula J, Lavie CJ (2021) Coronary microvascular dysfunction across the spectrum of cardiovascular diseases: JACC state-of-the-art review. J Am Coll Cardiol 78(13):1352\u20131371","journal-title":"J Am Coll Cardiol"},{"issue":"2","key":"6261_CR23","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1161\/CIRCULATIONAHA.110.953653","volume":"123","author":"TJ Anderson","year":"2011","unstructured":"Anderson TJ, Charbonneau F, Title LM, Buithieu J, Rose MS, Conradson H (2011) Microvascular function predicts cardiovascular events in primary prevention: long-term results from the firefighters and their endothelium (FATE) study. Circulation 123(2):163\u2013169","journal-title":"Circulation"},{"issue":"2","key":"6261_CR24","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1136\/ard.57.2.70","volume":"57","author":"AL Herrick","year":"1998","unstructured":"Herrick AL, Clark S (1998) Quantifying digital vascular disease in patients with primary Raynaud\u2019s phenomenon and systemic sclerosis. Ann Rheum Dis 57(2):70\u201378. https:\/\/doi.org\/10.1136\/ard.57.2.70","journal-title":"Ann Rheum Dis"},{"issue":"2","key":"6261_CR25","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1177\/1358863X231223523","volume":"29","author":"S Brunner-Ziegler","year":"2024","unstructured":"Brunner-Ziegler S, Dassler E, M\u00fcller M, Pratscher M, Forstner NFFM, Koppensteiner R (2024) Capillaroscopic differences between primary Raynaud phenomenon and healthy controls indicate potential microangiopathic involvement in benign vasospasms. Vasc Med 29(2):200\u2013207. https:\/\/doi.org\/10.1177\/1358863X231223523","journal-title":"Vasc Med"},{"issue":"1","key":"6261_CR26","doi-asserted-by":"publisher","first-page":"e003077","DOI":"10.1136\/rmdopen-2023-003077","volume":"9","author":"M Mueller","year":"2023","unstructured":"Mueller M, Gschwandtner ME, Emminger W, Kiener H, Schnaubelt S, Giurgea GA (2023) Associations between nailfold capillary aberrations and autoantibodies in children and adults with Raynaud\u2019s phenomenon. RMD Open 9(1):e003077. https:\/\/doi.org\/10.1136\/rmdopen-2023-003077","journal-title":"RMD Open"},{"issue":"18","key":"6261_CR27","doi-asserted-by":"publisher","DOI":"10.1172\/JCI180076","volume":"134","author":"D Fairweather","year":"2024","unstructured":"Fairweather D, Beetler DJ, McCabe EJ, Lieberman SM (2024) Mechanisms underlying sex differences in autoimmunity. J Clin Invest 134(18):e180076","journal-title":"J Clin Invest"},{"issue":"10","key":"6261_CR28","doi-asserted-by":"publisher","first-page":"626","DOI":"10.1038\/nri.2016.90","volume":"16","author":"SL Klein","year":"2016","unstructured":"Klein SL, Flanagan KL (2016) Sex differences in immune responses. Nat Rev Immunol 16(10):626\u2013638. https:\/\/doi.org\/10.1038\/nri.2016.90","journal-title":"Nat Rev Immunol"}],"container-title":["Rheumatology International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00296-026-06261-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00296-026-06261-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00296-026-06261-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T03:38:00Z","timestamp":1786937880000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00296-026-06261-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,4]]},"references-count":28,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["6261"],"URL":"https:\/\/doi.org\/10.1007\/s00296-026-06261-7","relation":{},"ISSN":["1437-160X"],"issn-type":[{"value":"1437-160X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,4]]},"assertion":[{"value":"17 June 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 July 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 August 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Nothing to disclose.","order":1,"name":"Ethics","label":"Conflict of interest","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"No part of this report is copied, published elsewhere, or generated by AI.","order":2,"name":"Ethics","label":"Disclaimer","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"230"}}