title: Incidences and Risk Factors of Organ Manifestations in the Early Course of Systemic Sclerosis: A Longitudinal EUSTAR Study.
abstract: OBJECTIVE
  Systemic sclerosis (SSc) is a rare and clinically heterogeneous autoimmune disorder characterised by fibrosis and microvascular obliteration of the skin and internal organs. Organ involvement mostly manifests after a variable period of the onset of Raynaud's phenomenon (RP). We aimed to map the incidence and predictors of pulmonary, cardiac, gastrointestinal (GI) and renal involvement in the early course of SSc.
  
  
  METHODS
  In the EUSTAR cohort, patients with early SSc were identified as those who had a visit within the first year after RP onset. Incident SSc organ manifestations and their risk factors were assessed using Kaplan-Meier methods and Cox regression analysis.
  
  
  RESULTS
  Of the 695 SSc patients who had a baseline visit within 1 year after RP onset, the incident non-RP manifestations (in order of frequency) were: skin sclerosis (75%) GI symptoms (71%), impaired diffusing capacity for monoxide<80% predicted (65%), DU (34%), cardiac involvement (32%), FVC<80% predicted (31%), increased PAPsys>40mmHg (14%), and renal crisis (3%). In the heart, incidence rates were highest for diastolic dysfunction, followed by conduction blocks and pericardial effusion. While the main baseline risk factor for a short timespan to develop FVC impairment was diffuse skin involvement, for PAPsys>40mmHg it was higher patient age. The main risk factors for incident cardiac manifestations were anti-topoisomerase autoantibody positivity and older age. Male sex, anti-RNA-polymerase-III positivity, and older age were risk factors associated with incident renal crisis.
  
  
  CONCLUSIONS
  In SSc patients presenting early after RP onset, approximately half of all incident organ manifestations occur within 2 years and have a simultaneous rather than a sequential onset. These findings have implications for the design of new diagnostic and therapeutic strategies aimed to 'widen' the still very narrow 'window of opportunity'. They may also enable physicians to counsel and manage patients presenting early in the course of SSc more accurately.
authors.affiliation: Department of Rheumatology, University Hospital Basel, Basel, Switzerland.
authors.forename: Veronika K
authors.initials: VK
authors.lastname: Jaeger
authors.affiliation: Department of Rheumatology, University Hospital Basel, Basel, Switzerland.|Department of Dermatology, University Hospital Basel, Basel, Switzerland.
authors.forename: Elina G
authors.identifier: http://orcid.org/0000-0002-7201-2188
authors.initials: EG
authors.lastname: Wirz
authors.affiliation: Department of Rheumatology A, Cochin Hospital, Paris Descartes University, Paris, France.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Allanore
authors.affiliation: Department of Rheumatology, University Hospital Basel, Basel, Switzerland.
authors.forename: Philipp
authors.initials: P
authors.lastname: Rossbach
authors.affiliation: Department of Rheumatology, University Clinic Schleswig-Holstein, Lübeck, Germany.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Riemekasten
authors.affiliation: Service de Médecine Interne, Hôpital Huriez, Université de Lille, Lille, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Hachulla
authors.affiliation: Department of Rheumatology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Oliver
authors.initials: O
authors.lastname: Distler
authors.affiliation: UO Reumatologia ed Immunologia Clinica, Spedali Civili, Brescia, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Airò
authors.affiliation: Servicio de Reumatologia, Hospital Universitario 12 de Octubre, Madrid, Spain.
authors.forename: Patricia E
authors.initials: PE
authors.lastname: Carreira
authors.affiliation: B. Shine Rheumatology Unit, Rambam Health Care Campus, Rappaport Faculty of Medicine, Technion-Institute of Technology, Haifa, Israel.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Balbir Gurman
authors.affiliation: Division of Rheumatology, Chris Hani Baragwanath Academic Hospital, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Mohammed
authors.identifier: http://orcid.org/0000-0001-7850-3538
authors.initials: M
authors.lastname: Tikly
authors.affiliation: Rheumatology Department, Second University of Naples, Naples, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Vettori
authors.affiliation: Institute of Rheumatology, University of Belgrade Medical School, Belgrade, Serbia.
authors.forename: Nemanja
authors.initials: N
authors.lastname: Damjanov
authors.affiliation: Department of Rheumatology and Clinical Immunology, Kerckhoff Clinic, Justus-Liebig University Giessen, Bad Nauheim, Germany.
authors.forename: Ulf
authors.initials: U
authors.lastname: Müller-Ladner
authors.affiliation: Department of Internal Medicine 3, University of Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Jörg H W
authors.initials: JH
authors.lastname: Distler
authors.affiliation: Department of Rheumatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Mangtao
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Rheumatology, University Hospital Basel, Basel, Switzerland.
authors.forename: Ulrich A
authors.initials: UA
authors.lastname: Walker
mesh_terms: D000328:Adult; D000368:Aged; D001323:Autoantibodies; D005260:Female; D005767:Gastrointestinal Diseases / Q000453:epidemiology*; D006331:Heart Diseases / Q000453:epidemiology*; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D007674:Kidney Diseases / Q000453:epidemiology*; D008137:Longitudinal Studies; D008171:Lung Diseases / Q000453:epidemiology* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011928:Raynaud Disease / Q000150:complications* / Q000503:physiopathology; D012044:Regression Analysis; D012189:Retrospective Studies; D012307:Risk Factors; D012595:Scleroderma, Systemic / Q000150:complications* / Q000503:physiopathology; D012871:Skin Diseases / Q000453:epidemiology*
chemical_list: D001323:Autoantibodies