Incidences and risk factors of organ manifestations in the early course of systemic sclerosis: A longitudinal EUSTAR study

Veronika K. Jaeger, Elina G. Wirz, Yannick Allanore, Philipp Rossbach, Gabriela Riemekasten, Eric Hachulla, Oliver Distler, Paolo Airò, Patricia E. Carreira, Alexandra Balbir Gurman, Mohammed Tikly, Serena Vettori, Nemanja Damjanov, Ulf Müller-Ladner, Jörg H W Distler, Mangtao Li, Ulrich A. Walker, Lidia Ananieva, Stefan Heitmann, Simona RednicValeria Riccieri, Magdalena Szmyrka-Kaczmarek, Dominique Farge, Giovanni Lapadula, Marco Matucci-Cerinic, Serena Guiducci, Nicolas Hunzelmann, Massimo Ricci, Carina Mihai, Douglas Veale, Roger Hesselstrand, Eduardo Mariok, Vanessa Smith, Ingo H. Tarner, Eugene J. Kucharz, László Czirják, Duska Martinovic, Kamal Solanki, Codrina Mihaela Ancuta, Jean Sibilia, Caramaschi Paola, Manal Hassanien, Sarah Kahl, Frederick Wigley, Marie Vanthuyne, Daniela Opris, Sebastião C. Radominski, Veronica Codullo, Raffaella Scorza, Carlo Selmi, Eustar Co-Authors

Research output: Contribution to journalArticlepeer-review


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 antitopoisomerase autoantibody positivity and older age. Male sex, anti-RNA-polymerase-III positivity, and older age were risk factors associated with incident renal crisis. Conclusion 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.

Original languageEnglish
Article numbere0163894
JournalPLoS One
Issue number10
Publication statusPublished - Oct 1 2016

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)


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