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 Rednic & 31 others Valeria 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, Andrea Lo Monaco, Ada Corrado, Carlo Selmi, Eustar Co-Authors

Research output: Contribution to journalArticle

27 Citations (Scopus)

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 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 (US)
Article numbere0163894
JournalPLoS One
Volume11
Issue number10
DOIs
StatePublished - Oct 1 2016
Externally publishedYes

Fingerprint

Systemic Scleroderma
sclerosis
longitudinal studies
Longitudinal Studies
risk factors
Raynaud Disease
incidence
Skin
Incidence
skin (animal)
RNA Polymerase III
Kidney
kidneys
Regression analysis
Autoantibodies
pericardial effusion
Pericardial Effusion
Sclerosis
autoantibodies
DNA-directed RNA polymerase

ASJC Scopus subject areas

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

Cite this

Jaeger, V. K., Wirz, E. G., Allanore, Y., Rossbach, P., Riemekasten, G., Hachulla, E., ... Eustar Co-Authors (2016). Incidences and risk factors of organ manifestations in the early course of systemic sclerosis: A longitudinal EUSTAR study. PLoS One, 11(10), [e0163894]. https://doi.org/10.1371/journal.pone.0163894

Incidences and risk factors of organ manifestations in the early course of systemic sclerosis : A longitudinal EUSTAR study. / Jaeger, Veronika K.; Wirz, Elina G.; Allanore, Yannick; Rossbach, Philipp; Riemekasten, Gabriela; Hachulla, Eric; Distler, Oliver; Airò, Paolo; Carreira, Patricia E.; Gurman, Alexandra Balbir; Tikly, Mohammed; Vettori, Serena; Damjanov, Nemanja; Müller-Ladner, Ulf; Distler, Jörg H W; Li, Mangtao; Walker, Ulrich A.; Ananieva, Lidia; Heitmann, Stefan; Rednic, Simona; Riccieri, Valeria; Szmyrka-Kaczmarek, Magdalena; Farge, Dominique; Lapadula, Giovanni; Matucci-Cerinic, Marco; Guiducci, Serena; Hunzelmann, Nicolas; Ricci, Massimo; Mihai, Carina; Veale, Douglas; Hesselstrand, Roger; Mariok, Eduardo; Smith, Vanessa; Tarner, Ingo H.; Kucharz, Eugene J.; Czirják, László; Martinovic, Duska; Solanki, Kamal; Ancuta, Codrina Mihaela; Sibilia, Jean; Paola, Caramaschi; Hassanien, Manal; Kahl, Sarah; Wigley, Frederick; Vanthuyne, Marie; Opris, Daniela; Radominski, Sebastião C.; Monaco, Andrea Lo; Corrado, Ada; Selmi, Carlo; Eustar Co-Authors.

In: PLoS One, Vol. 11, No. 10, e0163894, 01.10.2016.

Research output: Contribution to journalArticle

Jaeger, VK, Wirz, EG, Allanore, Y, Rossbach, P, Riemekasten, G, Hachulla, E, Distler, O, Airò, P, Carreira, PE, Gurman, AB, Tikly, M, Vettori, S, Damjanov, N, Müller-Ladner, U, Distler, JHW, Li, M, Walker, UA, Ananieva, L, Heitmann, S, Rednic, S, Riccieri, V, Szmyrka-Kaczmarek, M, Farge, D, Lapadula, G, Matucci-Cerinic, M, Guiducci, S, Hunzelmann, N, Ricci, M, Mihai, C, Veale, D, Hesselstrand, R, Mariok, E, Smith, V, Tarner, IH, Kucharz, EJ, Czirják, L, Martinovic, D, Solanki, K, Ancuta, CM, Sibilia, J, Paola, C, Hassanien, M, Kahl, S, Wigley, F, Vanthuyne, M, Opris, D, Radominski, SC, Monaco, AL, Corrado, A, Selmi, C & Eustar Co-Authors 2016, 'Incidences and risk factors of organ manifestations in the early course of systemic sclerosis: A longitudinal EUSTAR study', PLoS One, vol. 11, no. 10, e0163894. https://doi.org/10.1371/journal.pone.0163894
Jaeger, Veronika K. ; Wirz, Elina G. ; Allanore, Yannick ; Rossbach, Philipp ; Riemekasten, Gabriela ; Hachulla, Eric ; Distler, Oliver ; Airò, Paolo ; Carreira, Patricia E. ; Gurman, Alexandra Balbir ; Tikly, Mohammed ; Vettori, Serena ; Damjanov, Nemanja ; Müller-Ladner, Ulf ; Distler, Jörg H W ; Li, Mangtao ; Walker, Ulrich A. ; Ananieva, Lidia ; Heitmann, Stefan ; Rednic, Simona ; Riccieri, Valeria ; Szmyrka-Kaczmarek, Magdalena ; Farge, Dominique ; Lapadula, Giovanni ; Matucci-Cerinic, Marco ; Guiducci, Serena ; Hunzelmann, Nicolas ; Ricci, Massimo ; Mihai, Carina ; Veale, Douglas ; Hesselstrand, Roger ; Mariok, Eduardo ; Smith, Vanessa ; Tarner, Ingo H. ; Kucharz, Eugene J. ; Czirják, László ; Martinovic, Duska ; Solanki, Kamal ; Ancuta, Codrina Mihaela ; Sibilia, Jean ; Paola, Caramaschi ; Hassanien, Manal ; Kahl, Sarah ; Wigley, Frederick ; Vanthuyne, Marie ; Opris, Daniela ; Radominski, Sebastião C. ; Monaco, Andrea Lo ; Corrado, Ada ; Selmi, Carlo ; Eustar Co-Authors. / Incidences and risk factors of organ manifestations in the early course of systemic sclerosis : A longitudinal EUSTAR study. In: PLoS One. 2016 ; Vol. 11, No. 10.
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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 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.",
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TY - JOUR

T1 - Incidences and risk factors of organ manifestations in the early course of systemic sclerosis

T2 - A longitudinal EUSTAR study

AU - Jaeger, Veronika K.

AU - Wirz, Elina G.

AU - Allanore, Yannick

AU - Rossbach, Philipp

AU - Riemekasten, Gabriela

AU - Hachulla, Eric

AU - Distler, Oliver

AU - Airò, Paolo

AU - Carreira, Patricia E.

AU - Gurman, Alexandra Balbir

AU - Tikly, Mohammed

AU - Vettori, Serena

AU - Damjanov, Nemanja

AU - Müller-Ladner, Ulf

AU - Distler, Jörg H W

AU - Li, Mangtao

AU - Walker, Ulrich A.

AU - Ananieva, Lidia

AU - Heitmann, Stefan

AU - Rednic, Simona

AU - Riccieri, Valeria

AU - Szmyrka-Kaczmarek, Magdalena

AU - Farge, Dominique

AU - Lapadula, Giovanni

AU - Matucci-Cerinic, Marco

AU - Guiducci, Serena

AU - Hunzelmann, Nicolas

AU - Ricci, Massimo

AU - Mihai, Carina

AU - Veale, Douglas

AU - Hesselstrand, Roger

AU - Mariok, Eduardo

AU - Smith, Vanessa

AU - Tarner, Ingo H.

AU - Kucharz, Eugene J.

AU - Czirják, László

AU - Martinovic, Duska

AU - Solanki, Kamal

AU - Ancuta, Codrina Mihaela

AU - Sibilia, Jean

AU - Paola, Caramaschi

AU - Hassanien, Manal

AU - Kahl, Sarah

AU - Wigley, Frederick

AU - Vanthuyne, Marie

AU - Opris, Daniela

AU - Radominski, Sebastião C.

AU - Monaco, Andrea Lo

AU - Corrado, Ada

AU - Selmi, Carlo

AU - Eustar Co-Authors

PY - 2016/10/1

Y1 - 2016/10/1

N2 - 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.

AB - 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.

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