{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T19:53:00Z","timestamp":1785268380290,"version":"3.55.0"},"reference-count":45,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Therapeutic Advances in Musculoskeletal"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>The sequence and temporal relationship between Raynaud\u2019s phenomenon (RP) and the first non-Raynaud\u2019s sign\/symptom (NRP) in systemic sclerosis (SSc) have been partially investigated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives:<\/jats:title>\n                    <jats:p>To evaluate whether the mode and ages of clinical onset are associated with disease endotype and survival in SSc.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design:<\/jats:title>\n                    <jats:p>We included SSc patients from the Systemic sclerosis Progression INvestiGation registry of the Italian Society of Rheumatology (SPRING-SIR) registry in a cohort study, with post hoc cross-sectional and longitudinal analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Patients were grouped based on age-RP and age-NRP quartiles. Additionally, categories were defined based on mode of onset: RP group\u2014RP onset at least 1\u2009year before NRP; Simultaneous group\u2014RP onset within the same year of NRP; NRP group\u2014RP onset after at least 1\u2009year after NRP. Comparisons were made using Chi-square and ANOVA tests. Logistic, linear, and multinomial regression models were applied to assess associations, while Kaplan\u2013Meier curves and Cox regression were used to assess mortality.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>A total of 1748 patients were eligible: 682 (39.0%) in the RP group, 1026 (58.8%) in the simultaneous group, and 39 (2.2%) in the NRP group. A higher prevalence of anti-centromere antibodies was found In the RP group, while the simultaneous group had more diffuse cutaneous SSc (dcSSc), anti-topoisomerase-I antibodies, and higher Rodnan\u2019s skin score (mRSS). The NRP group presented higher prevalence of pulmonary arterial hypertension. On logistic regression, the simultaneous group was associated with a higher prevalence of dcSSc compared to the RP group (odds ratio, 1.491, 95% confidence interval (CI): 1.032\u20132.154). Younger age at RP onset was associated with lower systolic pulmonary artery pressure and mRSS. In 943 patients with available follow-up (median 24\u2009months), the simultaneous group had higher mortality compared to the RP group (hazard ratio, 1.975, 95% CI: 1.002\u20133.893).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>The timing of RP and NRP onset may help define SSc endotype and survival. Patients with simultaneous RP-NRP onset have more severe disease features and higher mortality risk, emphasizing the relevance of onset timing in disease stratification.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/1759720x251410243","type":"journal-article","created":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T07:28:05Z","timestamp":1770362885000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":4,"title":["Age and onset timing of Raynaud\u2019s phenomenon and first non-Raynaud symptom as prognostic factors in systemic sclerosis: a retrospective analysis from the Italian national multicenter Systemic Sclerosis Progression INvestiGation registry of the Italian Society for Rheumatology (SPRING-SIR)"],"prefix":"10.1177","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-8159-9754","authenticated-orcid":false,"given":"Silvia","family":"Peretti","sequence":"first","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy"},{"name":"Division of Rheumatology, Department of Medical and Geriatric specialties, Careggi University Hospital, University of Florence, Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2813-2083","authenticated-orcid":false,"given":"Cosimo","family":"Bruni","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, University Hospital Zurich, University of Zurich, Zurich 8091, Switzerland"},{"name":"Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7744-8549","authenticated-orcid":false,"given":"Francesco","family":"Bonomi","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy"},{"name":"Division of Rheumatology, Department of Medical and Geriatric specialties, Careggi University Hospital, University of Florence, Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rossella","family":"De Angelis","sequence":"additional","affiliation":[{"name":"Rheumatology Unit, Department of Clinical and Molecular Sciences, Polytechnic University of Marche, Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluigi","family":"Bajocchi","sequence":"additional","affiliation":[{"name":"Rheumatology Unit, S. Maria Hospital-USL, IRCCS Institute, Reggio Emilia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dilia","family":"Giuggioli","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences for Children and Adults, University Hospital of Modena and Reggio Emilia School of Medicine, Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Orlandi","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences for Children and Adults, University Hospital of Modena and Reggio Emilia School of Medicine, Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5042-1282","authenticated-orcid":false,"given":"Giovanni","family":"Zanframundo","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Therapeutics, Universit\u00e0 di Pavia, Pavia, Italy"},{"name":"Division of Rheumatology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Foti","sequence":"additional","affiliation":[{"name":"Rheumatology Unit, AOU Policlinico San Marco, Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Visalli","sequence":"additional","affiliation":[{"name":"Rheumatology Unit, AOU Policlinico San Marco, Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"Cuomo","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, University of Campania\u2014Luigi Vanvitelli University, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alarico","family":"Ariani","sequence":"additional","affiliation":[{"name":"Department of Medicine, Internal Medicine and Rheumatology, Azienda Ospedaliero\u2014Universitaria di Parma, Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edoardo","family":"Rosato","sequence":"additional","affiliation":[{"name":"Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gemma","family":"Lepri","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy"},{"name":"Division of Rheumatology, Department of Medical and Geriatric specialties, Careggi University Hospital, University of Florence, Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Girelli","sequence":"additional","affiliation":[{"name":"Department of Medicine, Rheumatology Unit, Ospedale GB Morgagni\u2014L Pierantoni, Forl\u00ec, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Riccieri","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Anesthesiology and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabetta","family":"Zanatta","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, University of Padua, Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia Laura","family":"Bosello","sequence":"additional","affiliation":[{"name":"Rheumatology Division, Catholic University of the Sacred Heart, Fondazione Policlinico Universitario A. 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Miulli\u201d General Hospital, Acquaviva delle Fonti, Bari, Italy"},{"name":"Department of Medicine and Surgery, LUM \u201cG. De Gennaro,\u201d Casamassima, Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Murdaca","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Genoa and Allergology, and Clinical Immunology Unit, Ospedale San Bartolomeo, Sarzana, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppina","family":"Abignano","sequence":"additional","affiliation":[{"name":"Rheumatology Unit, Department of Health Science, San Carlo Hospital, University of Basilicata, Potenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgio","family":"Pettiti","sequence":"additional","affiliation":[{"name":"Rheumatology Unit ASO S., Croce e Carle Hospital, Cuneo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Della Rossa","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, University of Pisa, Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Caminiti","sequence":"additional","affiliation":[{"name":"Departmental Rheumatology Unit, Grande Ospedale Metropolitano, Reggio Calabria, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annamaria","family":"Iuliano","sequence":"additional","affiliation":[{"name":"Rheumatology Unit, San Camillo\u2013Forlanini Hospital, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Ciano","sequence":"additional","affiliation":[{"name":"Local Health Department, Hospital of Ariano Irpino, Ariano Irpino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Beretta","sequence":"additional","affiliation":[{"name":"Referral Center for Systemic Autoimmune Diseases, Fondazione IRCCS Ca\u2019 Granda, Ospedale Maggiore Policlinico di Milano, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluca","family":"Bagnato","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ennio","family":"Lubrano","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, University of Molise, Campobasso, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilenia","family":"De Andres","sequence":"additional","affiliation":[{"name":"Rheumatology Unit, Azienda Ospedaliera di Rilievo Nazionale ed Alta Specializzazione Garibaldi, Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7254-4686","authenticated-orcid":false,"given":"Luca","family":"Idolazzi","sequence":"additional","affiliation":[{"name":"Rheumatology Unit, Department of Medicine, University of Verona, Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Saracco","sequence":"additional","affiliation":[{"name":"Rheumatology Unit, Mauriziano-Umberto I Hospital, Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Agnes","sequence":"additional","affiliation":[{"name":"Division of Rehabilitation, Department of Medicine, Torino, ASL TO5, Carmagnola, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corrado","family":"Campochiaro","sequence":"additional","affiliation":[{"name":"IRCCS San Raffaele Scientific Institute, Unit of Immunology, Rheumatology, Allergy and Rare Diseases, &amp; 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Maria Hospital-USL, IRCCS Institute, Reggio Emilia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Codullo","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Therapeutics, Universit\u00e0 di Pavia, Pavia, Italy"},{"name":"Division of Rheumatology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Iandoli","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, University of Campania\u2014Luigi Vanvitelli University, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonietta","family":"Gigante","sequence":"additional","affiliation":[{"name":"Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greta","family":"Pellegrino","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, IRCCS Ospedale Galeazzi\u2014Sant\u2019Ambrogio, Milan, Italy"},{"name":"Dipartimento di Scienze Biomediche e Cliniche, Universit\u00e0 degli Studi di Milano, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika","family":"Pigatto","sequence":"additional","affiliation":[{"name":"Department of Medicine, Villa Salus Hospital, Mestre, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Grazia","family":"Lazzaroni","sequence":"additional","affiliation":[{"name":"Rheumatology and Clinical Immunology, ASST Spedali Civili of Brescia, Brescia, Italy"},{"name":"Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrico","family":"De Lorenzis","sequence":"additional","affiliation":[{"name":"Rheumatology Division, Catholic University of the Sacred Heart, Fondazione Policlinico Universitario A. 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Anna, Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7442-1110","authenticated-orcid":false,"given":"Salvatore","family":"D\u2019Angelo","sequence":"additional","affiliation":[{"name":"Rheumatology Unit, Department of Health Science, San Carlo Hospital, University of Basilicata, Potenza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franco","family":"Cozzi","sequence":"additional","affiliation":[{"name":"Department of Medicine, Villa Salus Hospital, Mestre, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franco","family":"Franceschini","sequence":"additional","affiliation":[{"name":"Rheumatology and Clinical Immunology, ASST Spedali Civili of Brescia, Brescia, Italy"},{"name":"Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"Guiducci","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy"},{"name":"Division of Rheumatology, Department of Medical and Geriatric specialties, Careggi University Hospital, University of Florence, Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Dagna","sequence":"additional","affiliation":[{"name":"IRCCS San Raffaele Scientific Institute, Unit of Immunology, Rheumatology, Allergy and Rare Diseases, &amp; Inflammation, Fibrosis and Ageing initiative, Milan, Italy"},{"name":"Vita-Salute San Raffaele University, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0548-4983","authenticated-orcid":false,"given":"Andrea","family":"Doria","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, University of Padua, Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Salvarani","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences for Children and Adults, University Hospital of Modena and Reggio Emilia School of Medicine, Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Antonietta","family":"D\u2019Agostino","sequence":"additional","affiliation":[{"name":"Rheumatology Division, Catholic University of the Sacred Heart, Fondazione Policlinico Universitario A. 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