Sex-related Differences in Systemic Sclerosis: A Multicenter Cross-sectional Study From the National Registry of the Italian Society for Rheumatology

Rossella De Angelis; Dilia Giuggioli; Gianluigi Bajocchi; Lorenzo Dagna; Giovanni Zanframundo; Rosario Foti; Fabio Cacciapaglia; Giovanna Cuomo; Alarico Ariani; Edoardo Rosato; Serena Guiducci; Francesco Girelli; Valeria Riccieri; Elisabetta Zanatta; Silvia Bosello; Ilaria Cavazzana; Francesca Ingegnoli; Maria De Santis; Giuseppe Murdaca; Giuseppina Abignano; Nicoletta Romeo; Alessandra Della Rossa; Maurizio Caminiti; Annamaria Iuliano; Giovanni Ciano; Lorenzo Beretta; Gianluca Bagnato; Ennio Lubrano; Ilenia De Andres; Alessandro Giollo; Marta Saracco; Cecilia Agnes; Federica Lumetti; Amelia Spinella; Luca Magnani; Corrado Campochiaro; Giacomo De Luca; Veronica Codullo; Elisa Visalli; Francesco Masini; Antonietta Gigante; Silvia Bellando-Randone; Greta Pellegrino; Erika Pigatto; Francesca Dall'Ara; Maria Grazia Lazzaroni; Elena Generali; Gianna Mennillo; Simone Barsotti; Giuseppa Pagano Mariano; Francesca Calabrese; Federica Furini; Licia Vultaggio; Simone Parisi; Clara Lisa Peroni; Anna Maria Risa; Davide Rozza; Anna Zanetti; Greta Carrara; Giampiero Landolfi; Carlo Alberto Scirè; Gerolamo Bianchi; Enrico Fusaro; Gian Domenico Sebastiani; Marcello Govoni; Salvatore D'Angelo; Franco Cozzi; Andrea Doria; Florenzo Iannone; Carlo Salvarani; Marco Matucci-Cerinic; Clodoveo Ferri; Systemic sclerosis PRogression INvestiGation group (SPRING)

doi:10.3899/jrheum.210794

Sex-related Differences in Systemic Sclerosis: A Multicenter Cross-sectional Study From the National Registry of the Italian Society for Rheumatology

J Rheumatol. 2022 Feb;49(2):176-185. doi: 10.3899/jrheum.210794. Epub 2021 Nov 15.

Authors

Rossella De Angelis¹, Dilia Giuggioli², Gianluigi Bajocchi³, Lorenzo Dagna⁴, Giovanni Zanframundo⁵, Rosario Foti⁶, Fabio Cacciapaglia⁷, Giovanna Cuomo⁸, Alarico Ariani⁹, Edoardo Rosato¹⁰, Serena Guiducci¹¹, Francesco Girelli¹², Valeria Riccieri¹³, Elisabetta Zanatta¹⁴, Silvia Bosello¹⁵, Ilaria Cavazzana¹⁶, Francesca Ingegnoli¹⁷, Maria De Santis¹⁸, Giuseppe Murdaca¹⁹, Giuseppina Abignano²⁰, Nicoletta Romeo²¹, Alessandra Della Rossa²², Maurizio Caminiti²³, Annamaria Iuliano²⁴, Giovanni Ciano²⁵, Lorenzo Beretta²⁶, Gianluca Bagnato²⁷, Ennio Lubrano²⁸, Ilenia De Andres²⁹, Alessandro Giollo³⁰, Marta Saracco³¹, Cecilia Agnes³², Federica Lumetti², Amelia Spinella², Luca Magnani³, Corrado Campochiaro⁴, Giacomo De Luca⁴, Veronica Codullo⁵, Elisa Visalli⁶, Francesco Masini⁸, Antonietta Gigante¹⁰, Silvia Bellando-Randone¹¹, Greta Pellegrino¹³, Erika Pigatto³³, Francesca Dall'Ara¹⁶, Maria Grazia Lazzaroni¹⁶, Elena Generali¹⁸, Gianna Mennillo²⁰, Simone Barsotti²², Giuseppa Pagano Mariano²³, Francesca Calabrese²³, Federica Furini³⁴, Licia Vultaggio³⁴, Simone Parisi³⁵, Clara Lisa Peroni³⁵, Anna Maria Risa³⁶, Davide Rozza³⁷, Anna Zanetti³⁷, Greta Carrara³⁷, Giampiero Landolfi³⁷, Carlo Alberto Scirè³⁸, Gerolamo Bianchi³⁹, Enrico Fusaro³⁵, Gian Domenico Sebastiani²⁴, Marcello Govoni³⁴, Salvatore D'Angelo²⁰, Franco Cozzi³³, Andrea Doria¹⁴, Florenzo Iannone⁷, Carlo Salvarani³, Marco Matucci-Cerinic⁴⁰, Clodoveo Ferri²; Systemic sclerosis PRogression INvestiGation group (SPRING)

Collaborators

Systemic sclerosis PRogression INvestiGation group (SPRING):
Clodoveo Ferri, Marco Matucci-Cerinic, Giuseppina Abignano, Cecilia Agnes, Giorgio Amato, Alarico Ariani, Gianluca Bagnato, Gianluigi Bajoicchi, Simone Barsotti, Silvia Bellando-Randone, Alessia Benenati, Lorenzo Beretta, Gerolamo Bianchi, Silvia Bosello, Fabio Cacciapaglia, Francesca Calabrese, Maurizio Caminiti, Corrado Campochiaro, Renato Carignola, Ilaria Cavazzana, Giovanni Ciano, Veronica Codullo, Franco Cozzi, Cuomo Giovanna, Salvatore D'Angelo, Lorenzo Dagna, Dall'Ara Francesca, Ilenia De Andres, Rossella De Angelis, Angelo De Cata, Giacomo De Luca, Maria De Santis, Alessandra Della Rossa, Andrea Doria, Doveri Marica, Rosario Foti, Federica Furini, Enrico Fusaro, Elena Generali, Antonietta Gigante, Alessandro Giollo, Francesco Girelli, Dilia Giuggioli, Marcello Govoni, Serena Guiducci, Florenzo Iannone, Francesca Ingegnoli, Anna Maria Iuliano, Maria Grazia Lazzaroni, Ennio Lubrano, Federica Lumetti, Luca Magnani, Francesco Masini, Gianna Mennillo, Giuseppe Murdaca, Giuseppa Pagano Mariano, Simone Parisi, Greta Pellegrino, Clara Lisa Peroni, Erika Pigatto, Valeria Riccieri, Anna Maria Risa, Nicoletta Romeo, Edoardo Rosato, Gianluca Sambataro, Marta Saracco, Giandomenico Sebastiani, Amelia Spinella, Rossella Talotta, Elisa Visalli, Licia Vultaggio, Elisabetta Zanatta, Giovanni Zanframundo

Affiliations

¹ R. De Angelis, MD, A.M. Risa, MD, Rheumatology Unit, Department of Clinical and Molecular Sciences, Polytechnic University of Marche, Ancona; r.deangelis@staff.univpm.it.
² D. Giuggioli, MD, F. Lumetti, MD, A. Spinella, MD, C. Ferri, MD, Rheumatology Unit, School of Medicine, University of Modena and Reggio Emilia, Modena.
³ G. Bajocchi, MD, L. Magnani, MD, C. Salvarani, MD, Rheumatology Unit, S. Maria Hospital-USL, IRCCS Institute, Reggio Emilia.
⁴ L. Dagna, MD, C. Campochiaro, MD, G. De Luca, MD, Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan.
⁵ G. Zanframundo, MD, V. Codullo, MD, Department of Rheumatology, Policlinico San Matteo, Pavia.
⁶ R. Foti, MD, E. Visalli, MD, AOU Policlinico Vittorio Emanuele, Catania.
⁷ F. Cacciapaglia, MD, F. Iannone, MD, Rheumatology Unit, Department of Emergency Surgery and Organ Transplantations, University of Bari, Bari.
⁸ G. Cuomo, MD, F. Masini, MD, Luigi Vanvitelli University, Naples.
⁹ A. Ariani, MD, Department of Medicine, Internal Medicine and Rheumatology, Azienda Ospedaliero Universitaria di Parma, Parma.
¹⁰ E. Rosato, MD, A. Gigante, MD, Department of Translational and Precision Medicine, Sapienza University of Rome.
¹¹ S. Guiducci, MD, S. Bellando-Randone, MD, Department of Rheumatology, University of Florence, Florence.
¹² F. Girelli, MD, Department of Medicine, Rheumatology Unit, Ospedale GB Morgagni-L Pierantoni, Forlì.
¹³ V. Riccieri, MD, G. Pellegrino, MD, Department of Rheumatology, Sapienza University of Rome, Rome.
¹⁴ E. Zanatta, MD, A. Doria, MD, Department of Rheumatology, University of Padua, Padova.
¹⁵ S. Bosello, MD, Institute of Rheumatology and Affine Sciences, Division of Rheumatology, Catholic University of the Sacred Heart, Rome.
¹⁶ I. Cavazzana, MD, F. Dall'Ara, MD, M.G. Lazzaroni, MD, Department of Rheumatology, Spedali Civili di Brescia, Brescia.
¹⁷ F. Ingegnoli, MD, Division of Clinical Rheumatology, ASST Pini, Dept. of Clinical Sciences & Community Health, Research Center for Adult and Pediatric Rheumatic Diseases, Research Center for Environmental Health, Università degli Studi di Milano, Milan.
¹⁸ M. De Santis, MD, E.Generali, MD, Humanitas Clinical and Research Center IRCCS, Milan.
¹⁹ G. Murdaca, MD, S. Martino Hospital-University of Genoa, Genoa.
²⁰ G. Abignano, MD, G. Mennillo, MD, S. D'Angelo, MD, Department of Translational and Precision Medicine, Sapienza University of Rome.
²¹ N. Romeo, MD, S. Croce e Carle Hospital, Cuneo.
²² A. Della Rossa, MD, S. Barsotti, MD, Department of Rheumatology, University of Pisa, Pisa.
²³ M. Caminiti, MD, G. Pagano Mariano, MD, F. Calabrese, MD, Departmental Rheumatology Unit, Grande Ospedale Metropolitano, Reggio Calabria.
²⁴ A. Iuliano, MD, G.D. Sebastiani, MD, Rheumatology Unit, San Camillo-Forlanini Hospital, Rome.
²⁵ G. Ciano, MD, Local Health Department, Avellino.
²⁶ L. Beretta, MD, Referral Center for Systemic Autoimmune Diseases, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico di Milano, Milan.
²⁷ G. Bagnato, MD, Department of Clinical and Experimental Medicine, University of Messina, Messina.
²⁸ E. Lubrano, MD, Department of Rheumatology, University of Molise, Campobasso.
²⁹ I. De Andres, MD, Rheumatology Unit, Azienda Ospedaliera di Rilievo Nazionale ed Alta Specializzazione Garibaldi, Catania.
³⁰ A. Giollo, MD, Rheumatology Section, Department of Medicine, University of Verona, Verona.
³¹ M. Saracco, MD, Rheumatology Unit, Mauriziano-Umberto I Hospital, Turin.
³² C. Agnes, MD, San Lorenzo Hospital.
³³ E. Pigatto, MD, F. Cozzi, MD, Department of Medicine, Villa Salus Hospital, Venice.
³⁴ F. Furini, MD, L. Vultaggio, MD, M. Govoni, MD, Rheumatology Unit, Department of Medical Sciences, University of Ferrara and Azienda Ospedaliera-Universitaria S. Anna di Ferrara, Ferrara.
³⁵ S. Parisi, MD, C.L. Peroni, MD, E. Fusaro, MD, Rheumatology Unit, Città della Salute e della Scienza, Turin.
³⁶ R. De Angelis, MD, A.M. Risa, MD, Rheumatology Unit, Department of Clinical and Molecular Sciences, Polytechnic University of Marche, Ancona.
³⁷ D.Rozza, MS, A. Zanetti, MS, G. Carrara, MS, G. Landolfi, MS, Epidemiology Unit, Italian Society for Rheumatology, Milan.
³⁸ C.A. Scirè, MD, Epidemiology Unit, Italian Society for Rheumatology, Milan, and Rheumatology Unit, University of Ferrara-S. Anna Hospital, Ferrara.
³⁹ G. Bianchi, MD, Rheumatology Unit, Department of Musculoskeletal Sciences, Local Health Trust 3, La Colletta Hospital, Genoa.
⁴⁰ M. Matucci-Cerinic, MD, Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, and Department of Rheumatology, University of Florence, Florence, Italy.

PMID: 34782448
DOI: 10.3899/jrheum.210794

Abstract

Objective: There is still a great deal to learn about the influence of sex in systemic sclerosis (SSc). In this respect, national registries provide large and homogeneous patient cohorts for analytical studies. We therefore investigated a wide-ranging and well-characterized SSc series with the aim of identifying sex differences in disease expression, with a special focus on demographic, clinical, and serological characteristics.

Methods: A multicenter SSc cohort of 2281 patients, including 247 men, was recruited in the Italian Systemic sclerosis PRogression INvestiGation (SPRING) registry. Demographic data, disease manifestations, serological profile, and internal organ involvement were compared.

Results: The overall female/male ratio was 8.2:1. Female/male ratios for limited cutaneous SSc, diffuse cutaneous SSc, and SSc sine scleroderma subsets were 8.7:1, 4.9:1, and 10.7:1, respectively. A shorter time from onset of Raynaud phenomenon to SSc diagnosis, an increased prevalence of the diffuse cutaneous subset, renal crisis, and digital ulcers were found in males, whereas a significantly higher percentage of sicca syndrome, serum antinuclear antibodies, antiextractable nuclear antigens, anti-La/SSB, and anticentromere protein B was detected in the female group. Males exhibited lower left ventricular ejection fraction, as well as higher prevalence of conduction blocks, arrhythmias, ground glass, and honeycombing. Moreover, forced vital capacity and total lung capacity were medially lower in men than in women. Finally, males were more frequently treated with immunosuppressive drugs.

Conclusion: Our study further supports the presence of several sex-related differences in patients with SSc. These differences were pronounced in the severity of cutaneous, peripheral vascular, and cardiopulmonary involvement for male patients, whereas an increased prevalence of sicca syndrome and a specific autoantibody profile characterized the female sex.

Keywords: scleroderma; sex; systemic sclerosis.

Publication types

Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

Cross-Sectional Studies
Female
Humans
Italy / epidemiology
Male
Registries
Rheumatology*
Scleroderma, Systemic* / diagnosis
Sex Characteristics
Sjogren's Syndrome*
Stroke Volume
Ventricular Function, Left