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, E. Hachulla, Oliver Distler, Paolo Airo, Patricia Carreira, Alexandra Balbir Gurman, Mohammed Tikly, Serena Vettori, Nemanja Damjanov, U. Müller-Ladner, Jörg H W Distler, Mangtao Li, Ulrich A. Walker, Lidia P. 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 J. Veale, Roger Hesselstrand, Eduardo Mariok, Vanessa Smith, Ingo H. Tarner, Eugene Kucharz, Laszlo Czirjak, Duska Martinovic, Kamal Solanki, Codrina Michaela Ancuta, Jean Sibilia, Caramaschi Paola, Manal Hassanien, Sarah Kahl, Fredrick M. Wigley, M. Vanthuyne, Daniela Opris, Sebastião Cezar Radominski, Andrea Lo Monaco, Ada Corrado, Michaela Koehm, Veronica Codullo, Bevcar Radim, Esthela Loyo, Maria Üprus, Raffaele Pellerito, Thierry Zenone, Armando Gabrielli, O. Kowal-Bielecka, Blaz Rozman, Raffaella Scorza, Lesley Ann Saketkoo, Øyvind Midtvedt, Carlos A. Von Mühlen, Jörg Henes, Ani Branimir, Paul Hasler, Sule Kurhan Yavuz, Sabine Adler, Brigitte Krummel-Lorenz, Magdalena Posa, Merete Engelhart, Christopher Denton, Dorota Krasowska, Paloma García De La Peña Lefebvre, Franco Cozzi, Luc Mouthon, Edoardo Rosato, Carlo Francesco Selmi, Juan José Alegre Sancho, Carmel Mallia, Massimiliano Limonta, Matthias Seidel, Rosario Foti, Lisa Stamp, Susanne Ullman, Simon Stebbings, Vera Ortiz Santamaria, Francesco Del Galdo, Ellen De Langhe, A. Mathieu, Cord Sunderkötter, Kilian Eyerich, Bojana Stamenkovic, Srdan Novak, P. Sampaio-Barros, Cristiane Kayser, Ira Litinsky, Maura Couto

Research output: Contribution to journalArticle

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
Article numbere0163894
JournalPLoS One
Volume11
Issue number10
DOIs
Publication statusPublished - Oct 1 2016

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., ... Couto, M. (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, E.; Distler, Oliver; Airo, Paolo; Carreira, Patricia; Gurman, Alexandra Balbir; Tikly, Mohammed; Vettori, Serena; Damjanov, Nemanja; Müller-Ladner, U.; Distler, Jörg H W; Li, Mangtao; Walker, Ulrich A.; Ananieva, Lidia P.; 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 J.; Hesselstrand, Roger; Mariok, Eduardo; Smith, Vanessa; Tarner, Ingo H.; Kucharz, Eugene; Czirjak, Laszlo; Martinovic, Duska; Solanki, Kamal; Ancuta, Codrina Michaela; Sibilia, Jean; Paola, Caramaschi; Hassanien, Manal; Kahl, Sarah; Wigley, Fredrick M.; Vanthuyne, M.; Opris, Daniela; Radominski, Sebastião Cezar; Monaco, Andrea Lo; Corrado, Ada; Koehm, Michaela; Codullo, Veronica; Radim, Bevcar; Loyo, Esthela; Üprus, Maria; Pellerito, Raffaele; Zenone, Thierry; Gabrielli, Armando; Kowal-Bielecka, O.; Rozman, Blaz; Scorza, Raffaella; Saketkoo, Lesley Ann; Midtvedt, Øyvind; Von Mühlen, Carlos A.; Henes, Jörg; Branimir, Ani; Hasler, Paul; Yavuz, Sule Kurhan; Adler, Sabine; Krummel-Lorenz, Brigitte; Posa, Magdalena; Engelhart, Merete; Denton, Christopher; Krasowska, Dorota; Lefebvre, Paloma García De La Peña; Cozzi, Franco; Mouthon, Luc; Rosato, Edoardo; Selmi, Carlo Francesco; Sancho, Juan José Alegre; Mallia, Carmel; Limonta, Massimiliano; Seidel, Matthias; Foti, Rosario; Stamp, Lisa; Ullman, Susanne; Stebbings, Simon; Santamaria, Vera Ortiz; Del Galdo, Francesco; De Langhe, Ellen; Mathieu, A.; Sunderkötter, Cord; Eyerich, Kilian; Stamenkovic, Bojana; Novak, Srdan; Sampaio-Barros, P.; Kayser, Cristiane; Litinsky, Ira; Couto, Maura.

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, Airo, P, Carreira, P, Gurman, AB, Tikly, M, Vettori, S, Damjanov, N, Müller-Ladner, U, Distler, JHW, Li, M, Walker, UA, Ananieva, LP, 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, DJ, Hesselstrand, R, Mariok, E, Smith, V, Tarner, IH, Kucharz, E, Czirjak, L, Martinovic, D, Solanki, K, Ancuta, CM, Sibilia, J, Paola, C, Hassanien, M, Kahl, S, Wigley, FM, Vanthuyne, M, Opris, D, Radominski, SC, Monaco, AL, Corrado, A, Koehm, M, Codullo, V, Radim, B, Loyo, E, Üprus, M, Pellerito, R, Zenone, T, Gabrielli, A, Kowal-Bielecka, O, Rozman, B, Scorza, R, Saketkoo, LA, Midtvedt, Ø, Von Mühlen, CA, Henes, J, Branimir, A, Hasler, P, Yavuz, SK, Adler, S, Krummel-Lorenz, B, Posa, M, Engelhart, M, Denton, C, Krasowska, D, Lefebvre, PGDLP, Cozzi, F, Mouthon, L, Rosato, E, Selmi, CF, Sancho, JJA, Mallia, C, Limonta, M, Seidel, M, Foti, R, Stamp, L, Ullman, S, Stebbings, S, Santamaria, VO, Del Galdo, F, De Langhe, E, Mathieu, A, Sunderkötter, C, Eyerich, K, Stamenkovic, B, Novak, S, Sampaio-Barros, P, Kayser, C, Litinsky, I & Couto, M 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, E. ; Distler, Oliver ; Airo, Paolo ; Carreira, Patricia ; Gurman, Alexandra Balbir ; Tikly, Mohammed ; Vettori, Serena ; Damjanov, Nemanja ; Müller-Ladner, U. ; Distler, Jörg H W ; Li, Mangtao ; Walker, Ulrich A. ; Ananieva, Lidia P. ; 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 J. ; Hesselstrand, Roger ; Mariok, Eduardo ; Smith, Vanessa ; Tarner, Ingo H. ; Kucharz, Eugene ; Czirjak, Laszlo ; Martinovic, Duska ; Solanki, Kamal ; Ancuta, Codrina Michaela ; Sibilia, Jean ; Paola, Caramaschi ; Hassanien, Manal ; Kahl, Sarah ; Wigley, Fredrick M. ; Vanthuyne, M. ; Opris, Daniela ; Radominski, Sebastião Cezar ; Monaco, Andrea Lo ; Corrado, Ada ; Koehm, Michaela ; Codullo, Veronica ; Radim, Bevcar ; Loyo, Esthela ; Üprus, Maria ; Pellerito, Raffaele ; Zenone, Thierry ; Gabrielli, Armando ; Kowal-Bielecka, O. ; Rozman, Blaz ; Scorza, Raffaella ; Saketkoo, Lesley Ann ; Midtvedt, Øyvind ; Von Mühlen, Carlos A. ; Henes, Jörg ; Branimir, Ani ; Hasler, Paul ; Yavuz, Sule Kurhan ; Adler, Sabine ; Krummel-Lorenz, Brigitte ; Posa, Magdalena ; Engelhart, Merete ; Denton, Christopher ; Krasowska, Dorota ; Lefebvre, Paloma García De La Peña ; Cozzi, Franco ; Mouthon, Luc ; Rosato, Edoardo ; Selmi, Carlo Francesco ; Sancho, Juan José Alegre ; Mallia, Carmel ; Limonta, Massimiliano ; Seidel, Matthias ; Foti, Rosario ; Stamp, Lisa ; Ullman, Susanne ; Stebbings, Simon ; Santamaria, Vera Ortiz ; Del Galdo, Francesco ; De Langhe, Ellen ; Mathieu, A. ; Sunderkötter, Cord ; Eyerich, Kilian ; Stamenkovic, Bojana ; Novak, Srdan ; Sampaio-Barros, P. ; Kayser, Cristiane ; Litinsky, Ira ; Couto, Maura. / 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.",
author = "Jaeger, {Veronika K.} and Wirz, {Elina G.} and Yannick Allanore and Philipp Rossbach and Gabriela Riemekasten and E. Hachulla and Oliver Distler and Paolo Airo and Patricia Carreira and Gurman, {Alexandra Balbir} and Mohammed Tikly and Serena Vettori and Nemanja Damjanov and U. M{\"u}ller-Ladner and Distler, {J{\"o}rg H W} and Mangtao Li and Walker, {Ulrich A.} and Ananieva, {Lidia P.} and Stefan Heitmann and Simona Rednic and Valeria Riccieri and Magdalena Szmyrka-Kaczmarek and Dominique Farge and Giovanni Lapadula and Marco Matucci-Cerinic and Serena Guiducci and Nicolas Hunzelmann and Massimo Ricci and Carina Mihai and Veale, {Douglas J.} and Roger Hesselstrand and Eduardo Mariok and Vanessa Smith and Tarner, {Ingo H.} and Eugene Kucharz and Laszlo Czirjak and Duska Martinovic and Kamal Solanki and Ancuta, {Codrina Michaela} and Jean Sibilia and Caramaschi Paola and Manal Hassanien and Sarah Kahl and Wigley, {Fredrick M.} and M. Vanthuyne and Daniela Opris and Radominski, {Sebasti{\~a}o Cezar} and Monaco, {Andrea Lo} and Ada Corrado and Michaela Koehm and Veronica Codullo and Bevcar Radim and Esthela Loyo and Maria {\"U}prus and Raffaele Pellerito and Thierry Zenone and Armando Gabrielli and O. Kowal-Bielecka and Blaz Rozman and Raffaella Scorza and Saketkoo, {Lesley Ann} and {\O}yvind Midtvedt and {Von M{\"u}hlen}, {Carlos A.} and J{\"o}rg Henes and Ani Branimir and Paul Hasler and Yavuz, {Sule Kurhan} and Sabine Adler and Brigitte Krummel-Lorenz and Magdalena Posa and Merete Engelhart and Christopher Denton and Dorota Krasowska and Lefebvre, {Paloma Garc{\'i}a De La Pe{\~n}a} and Franco Cozzi and Luc Mouthon and Edoardo Rosato and Selmi, {Carlo Francesco} and Sancho, {Juan Jos{\'e} Alegre} and Carmel Mallia and Massimiliano Limonta and Matthias Seidel and Rosario Foti and Lisa Stamp and Susanne Ullman and Simon Stebbings and Santamaria, {Vera Ortiz} and {Del Galdo}, Francesco and {De Langhe}, Ellen and A. Mathieu and Cord Sunderk{\"o}tter and Kilian Eyerich and Bojana Stamenkovic and Srdan Novak and P. Sampaio-Barros and Cristiane Kayser and Ira Litinsky and Maura Couto",
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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, E.

AU - Distler, Oliver

AU - Airo, Paolo

AU - Carreira, Patricia

AU - Gurman, Alexandra Balbir

AU - Tikly, Mohammed

AU - Vettori, Serena

AU - Damjanov, Nemanja

AU - Müller-Ladner, U.

AU - Distler, Jörg H W

AU - Li, Mangtao

AU - Walker, Ulrich A.

AU - Ananieva, Lidia P.

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 J.

AU - Hesselstrand, Roger

AU - Mariok, Eduardo

AU - Smith, Vanessa

AU - Tarner, Ingo H.

AU - Kucharz, Eugene

AU - Czirjak, Laszlo

AU - Martinovic, Duska

AU - Solanki, Kamal

AU - Ancuta, Codrina Michaela

AU - Sibilia, Jean

AU - Paola, Caramaschi

AU - Hassanien, Manal

AU - Kahl, Sarah

AU - Wigley, Fredrick M.

AU - Vanthuyne, M.

AU - Opris, Daniela

AU - Radominski, Sebastião Cezar

AU - Monaco, Andrea Lo

AU - Corrado, Ada

AU - Koehm, Michaela

AU - Codullo, Veronica

AU - Radim, Bevcar

AU - Loyo, Esthela

AU - Üprus, Maria

AU - Pellerito, Raffaele

AU - Zenone, Thierry

AU - Gabrielli, Armando

AU - Kowal-Bielecka, O.

AU - Rozman, Blaz

AU - Scorza, Raffaella

AU - Saketkoo, Lesley Ann

AU - Midtvedt, Øyvind

AU - Von Mühlen, Carlos A.

AU - Henes, Jörg

AU - Branimir, Ani

AU - Hasler, Paul

AU - Yavuz, Sule Kurhan

AU - Adler, Sabine

AU - Krummel-Lorenz, Brigitte

AU - Posa, Magdalena

AU - Engelhart, Merete

AU - Denton, Christopher

AU - Krasowska, Dorota

AU - Lefebvre, Paloma García De La Peña

AU - Cozzi, Franco

AU - Mouthon, Luc

AU - Rosato, Edoardo

AU - Selmi, Carlo Francesco

AU - Sancho, Juan José Alegre

AU - Mallia, Carmel

AU - Limonta, Massimiliano

AU - Seidel, Matthias

AU - Foti, Rosario

AU - Stamp, Lisa

AU - Ullman, Susanne

AU - Stebbings, Simon

AU - Santamaria, Vera Ortiz

AU - Del Galdo, Francesco

AU - De Langhe, Ellen

AU - Mathieu, A.

AU - Sunderkötter, Cord

AU - Eyerich, Kilian

AU - Stamenkovic, Bojana

AU - Novak, Srdan

AU - Sampaio-Barros, P.

AU - Kayser, Cristiane

AU - Litinsky, Ira

AU - Couto, Maura

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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U2 - 10.1371/journal.pone.0163894

DO - 10.1371/journal.pone.0163894

M3 - Article

VL - 11

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 10

M1 - e0163894

ER -