{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T21:17:59Z","timestamp":1780089479239,"version":"3.54.0"},"posted":{"date-parts":[[2025,12,2]]},"group-title":"Rheumatology","reference-count":29,"publisher":"openRxiv","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:\/\/www.medrxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,2,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>Gastrointestinal (GI) complications are common in systemic sclerosis (SSc), yet the value of early symptoms as predictors of progression remains poorly defined. We aimed to determine whether baseline GI symptoms in early SSc predict progression to significant GI outcomes.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We studied 450 participants from the GENISOS cohort with early SSc (\u22645 years from first non-Raynaud\u2019s symptom). Baseline assessments included demographics and clinical variables, including individual GI symptoms (GERD, dysphagia, bloating, constipation, diarrhea, peptic ulcer). Significant GI involvement was defined as Medsger GI severity score \u22652. Cox models evaluated associations between baseline symptoms and progression to significant GI disease and all-cause mortality. Additional models examined total baseline GI symptom burden and outcomes.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Participants were predominantly female (84%) with a mean age of 47.7 \u00b1 13.3 years. Baseline GI symptoms were frequent, most commonly GERD (76%) and dysphagia (41%). 13% of the patients had significant GI involvement, with 4% presenting with significant GI disease at baseline. Baseline GERD (HR 4.15, P=0.019) and diarrhea (HR 2.25, P=0.021) were strong predictors of GI progression. When symptom burden was analyzed, each additional baseline GI symptom increased the hazard of significant GI progression by 53% (P=0.003). On the other hand, peptic ulcer disease (HR 2.21, P=0.007) and diarrhea (HR 1.48, P=0.045) predicted higher mortality, with each additional symptom raising mortality risk by 29% (P&lt;0.001).<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Early GI symptoms and overall symptom burden predict GI progression and mortality in SSc. Symptom-based profiling may offer a practical strategy for clinical risk stratification and trial enrichment.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Key messages<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Key message 1<\/jats:title>\n                    <jats:p>Baseline GERD and diarrhea strongly predict progression to significant gastrointestinal involvement in systemic sclerosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key message 2<\/jats:title>\n                    <jats:p>Greater baseline gastrointestinal symptom burden increases risk of severe GI disease progression and all-cause mortality.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key message 3<\/jats:title>\n                    <jats:p>Simple symptom profiles may guide early risk stratification and patient selection for GI-focused clinical trials.<\/jats:p>\n                  <\/jats:sec>\n                <\/jats:sec>","DOI":"10.64898\/2025.12.01.25341383","type":"posted-content","created":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T11:07:18Z","timestamp":1765278438000},"source":"Crossref","is-referenced-by-count":1,"title":["Early gastrointestinal manifestations predict disease progression and mortality in patients with systemic sclerosis"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2581-7992","authenticated-orcid":false,"given":"Ali Y.","family":"Ayla","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Division of Rheumatology, UTHealth Houston, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6241-926X","authenticated-orcid":false,"given":"Ashish P.","family":"Balar","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Rheumatology, UTHealth Houston, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernesto Calderon","family":"Martinez","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Medical Genetics, UTHealth Houston, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingrui","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The Institute for Clinical Research and Learning Health Care, McGovern Medical School, UTHealth Houston, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4235-1282","authenticated-orcid":false,"given":"Claudia","family":"Pedroza","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The Institute for Clinical Research and Learning Health Care, McGovern Medical School, UTHealth Houston, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Bonomi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Careggi University Hospital, Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Bellando-Randone","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, University of Florence, Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maureen D.","family":"Mayes","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Rheumatology, UTHealth Houston, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Skaug","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Rheumatology, UTHealth Houston, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Hughes","sequence":"additional","affiliation":[{"name":"Division of Musculoskeletal and Dermatological Science, School of Biological Sciences, Faculty of Biological Medicine and Health, Centre for Musculoskeletal Research, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK"},{"name":"Department of Rheumatology, Northern Care Alliance NHS Foundation Trust, Salford Care Organization, Salford, UK"},{"name":"NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8059-9978","authenticated-orcid":false,"given":"Shervin","family":"Assassi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Rheumatology, UTHealth Houston, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6461-8940","authenticated-orcid":false,"given":"Zsuzsanna H.","family":"McMahan","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Rheumatology, UTHealth Houston, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026021209101596000_2025.12.01.25341383v2.1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)30933-9"},{"key":"2026021209101596000_2025.12.01.25341383v2.2","doi-asserted-by":"crossref","unstructured":"Li JX . 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