Malignancies in Patients with Anti-RNA Polymerase III Antibodies and Systemic Sclerosis: Analysis of the EULAR Scleroderma Trials and Research Cohort and Possible Recommendations for Screening

Maria-Grazia Lazzaroni; Ilaria Cavazzana; Enrico Colombo; Rucsandra Dobrota; Jasmin Hernandez; Roger Hesselstrand; Cecilia Varju; Gabriella Nagy; Vanessa Smith; Paola Caramaschi; Valeria Riccieri; Eric Hachulla; Alexandra Balbir-Gurman; Emmanuel Chatelus; Katarzyna Romanowska-Próchnicka; Ana Carolina Araújo; Oliver Distler; Yannick Allanore; Paolo Airò; EUSTAR co-authors

doi:10.3899/jrheum.160817

Malignancies in Patients with Anti-RNA Polymerase III Antibodies and Systemic Sclerosis: Analysis of the EULAR Scleroderma Trials and Research Cohort and Possible Recommendations for Screening

J Rheumatol. 2017 May;44(5):639-647. doi: 10.3899/jrheum.160817. Epub 2017 Jan 15.

Authors

Maria-Grazia Lazzaroni^{1

2}, Ilaria Cavazzana^{3

4}, Enrico Colombo^{3

4}, Rucsandra Dobrota^{3

4}, Jasmin Hernandez^{3

4}, Roger Hesselstrand^{3

4}, Cecilia Varju^{3

4}, Gabriella Nagy^{3

4}, Vanessa Smith^{3

4}, Paola Caramaschi^{3

4}, Valeria Riccieri^{3

4}, Eric Hachulla^{3

4}, Alexandra Balbir-Gurman^{3

4}, Emmanuel Chatelus^{3

4}, Katarzyna Romanowska-Próchnicka^{3

4}, Ana Carolina Araújo^{3

4}, Oliver Distler^{3

4}, Yannick Allanore^{3

4}, Paolo Airò^{3

4}; EUSTAR co-authors

Affiliations

¹ From the Rheumatology and Clinical Immunology, University of Brescia and Spedali Civili of Brescia, Brescia; Rheumatology Unit, Azienda Ospedaliera Universitaria Integrata, Verona; Department of Internal Medicine and Medical Specialties, University Sapienza, Rome, Italy; Division of Rheumatology, University Hospital Zurich, Zurich, Switzerland; Department of Clinical Sciences, Section of Rheumatology, Lund University, Lund, Sweden; Department of Rheumatology and Immunology, Medical Center, University of Pecs, Pecs, Hungary; Rheumatology, Ghent University Hospital, Ghent University, Ghent, Belgium; Department of Internal Medicine, University Lille Nord-de-France, Lille; Department of Rheumatology, Strasbourg University Hospital, Strasbourg; Department of Rheumatology, University Paris Descartes and Cochin Hospital, Paris, France; B. Shine Rheumatology Unit, Rambam Health Care Campus, Rappaport Faculty of Medicine, Technion - Institute of Technology, Haifa, Israel; Department of Pathophysiology, Medical University of Warsaw and Department of Connective Tissue Diseases, Institute of Rheumatology, Warsaw, Poland; Unidade de Doenças Auto-Imunes, Serviço de Medicina 2, Hospital de Curry Cabral, Centro Hospitalar Lisboa Central, Lisbon, Portugal. mariagrazialazzaroni@gmail.com.
² M.G. Lazzaroni, MD, Rheumatology and Clinical Immunology, University of Brescia and Spedali Civili of Brescia; I. Cavazzana, MD, Rheumatology and Clinical Immunology, Spedali Civili of Brescia; E. Colombo, MD, Rheumatology and Clinical Immunology, University of Brescia and Spedali Civili of Brescia; R. Dobrota, MD, Division of Rheumatology, University Hospital Zurich; J. Hernandez, MD, Division of Rheumatology, University Hospital Zurich; R. Hesselstrand, MD, PhD, Department of Clinical Sciences, Section of Rheumatology, Lund University; C. Varju, MD, Department of Rheumatology and Immunology, Medical Center, University of Pecs; G. Nagy, MD, Department of Rheumatology and Immunology, Medical Center, University of Pecs; V. Smith, MD, PhD, Rheumatology, Ghent University Hospital, Ghent University; P. Caramaschi, MD, Rheumatology Unit, Azienda Ospedaliera Universitaria Integrata; V. Riccieri, MD, Department of Internal Medicine and Medical Specialties, University Sapienza; E. Hachulla, MD, PhD, Department of Internal Medicine, University Lille Nord-de-France; A. Balbir-Gurman, MD, PhD, B. Shine Rheumatology Unit, Rambam Health Care Campus, Rappaport Faculty of Medicine, Technion - Institute of Technology; E. Chatelus, MD, Department of Rheumatology, Strasbourg University Hospital; K. Romanowska-Próchnicka, MD, Department of Pathophysiology, Medical University of Warsaw and Department of Connective Tissue Diseases, Institute of Rheumatology; A.C. Araújo, MD, Unidade de Doenças Auto-Imunes, Serviço de Medicina 2, Hospital de Curry Cabral, Centro Hospitalar Lisboa Central; O. Distler, MD, PhD, Division of Rheumatology, University Hospital Zurich; Y. Allanore, MD, PhD, Department of Rheumatology, University Paris Descartes and Cochin Hospital; P. Airò, MD, Rheumatology and Clinical Immunology, Spedali Civili of Brescia. mariagrazialazzaroni@gmail.com.
³ From the Rheumatology and Clinical Immunology, University of Brescia and Spedali Civili of Brescia, Brescia; Rheumatology Unit, Azienda Ospedaliera Universitaria Integrata, Verona; Department of Internal Medicine and Medical Specialties, University Sapienza, Rome, Italy; Division of Rheumatology, University Hospital Zurich, Zurich, Switzerland; Department of Clinical Sciences, Section of Rheumatology, Lund University, Lund, Sweden; Department of Rheumatology and Immunology, Medical Center, University of Pecs, Pecs, Hungary; Rheumatology, Ghent University Hospital, Ghent University, Ghent, Belgium; Department of Internal Medicine, University Lille Nord-de-France, Lille; Department of Rheumatology, Strasbourg University Hospital, Strasbourg; Department of Rheumatology, University Paris Descartes and Cochin Hospital, Paris, France; B. Shine Rheumatology Unit, Rambam Health Care Campus, Rappaport Faculty of Medicine, Technion - Institute of Technology, Haifa, Israel; Department of Pathophysiology, Medical University of Warsaw and Department of Connective Tissue Diseases, Institute of Rheumatology, Warsaw, Poland; Unidade de Doenças Auto-Imunes, Serviço de Medicina 2, Hospital de Curry Cabral, Centro Hospitalar Lisboa Central, Lisbon, Portugal.
⁴ M.G. Lazzaroni, MD, Rheumatology and Clinical Immunology, University of Brescia and Spedali Civili of Brescia; I. Cavazzana, MD, Rheumatology and Clinical Immunology, Spedali Civili of Brescia; E. Colombo, MD, Rheumatology and Clinical Immunology, University of Brescia and Spedali Civili of Brescia; R. Dobrota, MD, Division of Rheumatology, University Hospital Zurich; J. Hernandez, MD, Division of Rheumatology, University Hospital Zurich; R. Hesselstrand, MD, PhD, Department of Clinical Sciences, Section of Rheumatology, Lund University; C. Varju, MD, Department of Rheumatology and Immunology, Medical Center, University of Pecs; G. Nagy, MD, Department of Rheumatology and Immunology, Medical Center, University of Pecs; V. Smith, MD, PhD, Rheumatology, Ghent University Hospital, Ghent University; P. Caramaschi, MD, Rheumatology Unit, Azienda Ospedaliera Universitaria Integrata; V. Riccieri, MD, Department of Internal Medicine and Medical Specialties, University Sapienza; E. Hachulla, MD, PhD, Department of Internal Medicine, University Lille Nord-de-France; A. Balbir-Gurman, MD, PhD, B. Shine Rheumatology Unit, Rambam Health Care Campus, Rappaport Faculty of Medicine, Technion - Institute of Technology; E. Chatelus, MD, Department of Rheumatology, Strasbourg University Hospital; K. Romanowska-Próchnicka, MD, Department of Pathophysiology, Medical University of Warsaw and Department of Connective Tissue Diseases, Institute of Rheumatology; A.C. Araújo, MD, Unidade de Doenças Auto-Imunes, Serviço de Medicina 2, Hospital de Curry Cabral, Centro Hospitalar Lisboa Central; O. Distler, MD, PhD, Division of Rheumatology, University Hospital Zurich; Y. Allanore, MD, PhD, Department of Rheumatology, University Paris Descartes and Cochin Hospital; P. Airò, MD, Rheumatology and Clinical Immunology, Spedali Civili of Brescia.

PMID: 28089973
DOI: 10.3899/jrheum.160817

Abstract

Objective: To analyze the characteristics of anti-RNA polymerase III antibodies (anti-RNAP3)- positive patients with systemic sclerosis (SSc) in the European League Against Rheumatism Scleroderma Trials and Research group (EUSTAR) registry with a focus on the risk of cancer and the characteristics of malignancies, and the aim to provide guidelines about potential cancer screening in these patients.

Methods: (1) Analysis of the EUSTAR database: 4986 patients with information on their anti-RNAP3 status were included. (2) Case-control study: additional retrospective data, including malignancy history, were queried in 13 participating EUSTAR centers; 158 anti-RNAP3+ cases were compared with 199 local anti-RNAP3- controls, matched for sex, cutaneous subset, disease duration, and age at SSc onset. (3) A Delphi exercise was performed by 82 experts to reach consensus for cancer screening in anti-RNAP3+ patients.

Results: In the EUSTAR registry, anti-RNAP3 were associated in multivariable analysis with renal crisis and diffuse cutaneous involvement. In the case-control study, anti-RNAP3 were associated with gastric antral vascular ectasia, rapid progression of skin involvement, and malignancies concomitant to SSc onset (OR 7.38, 95% CI 1.61-33.8). When compared with other anti-RNAP3+ patients, those with concomitant malignancies had older age (p < 0.001) and more frequent diffuse cutaneous involvement (p = 0.008). The Delphi exercise highlighted the need for malignancy screening at the time of diagnosis for anti-RNAP3+ patients and tight followup in the following years.

Conclusion: Anti-RNAP3+ patients with SSc have a high risk of concomitant malignancy. These results have implications for clinical practice and suggest regular screening for cancer in anti-RNAP3+ patients.

Keywords: AUTOANTIBODIES; NEOPLASMS; SCLERODERMA; SYSTEMIC SCLEROSIS.

MeSH terms

Adult
Autoantibodies / blood*
Case-Control Studies
Female
Humans
Male
Mass Screening
Middle Aged
Neoplasms / blood
Neoplasms / complications*
Neoplasms / immunology
RNA Polymerase III / immunology*
Retrospective Studies
Scleroderma, Systemic / blood
Scleroderma, Systemic / complications*
Scleroderma, Systemic / immunology

Substances

Autoantibodies
RNA Polymerase III