Original article Incidence and risk factors for gangrene in patients with systemic sclerosis from the EUSTAR cohort Carina Mihai 1,2 , Oliver Distler 1 , Ana Maria Gheorghiu 2 , Paul I. Constantin 2 , Rucsandra Dobrota 1,2 , Suzana Jordan 1 , Vanessa Smith 3 , Eric Hachulla 4 , Jo ¨ rg Henes 5 , Elise Siegert 6 , Serena Vettori 7 , Ulf Mu ¨ ller-Ladner 8 , Marco Matucci Cerinic 9 , Yannick Allanore 10 and EUSTAR collaborators Abstract Objective. In patients with SSc, peripheral vasculopathy can promote critical ischaemia and gangrene. The aim of this study was to investigate the prevalence, incidence and risk factors for gangrene in the EUSTAR cohort. Methods. We included patients from the EUSTAR database fulfilling the ACR 1980 or the ACR/EULAR 2013 classi- fication criteria for SSc, with at least one visit recording data on gangrene. Centres were asked for supplementary data on traditional cardiovascular risk factors. We analysed the cross-sectional relationship between gangrene and its potential risk factors by univariable and multivariable logistic regression. Longitudinal data were analysed by Cox proportional hazards regression. Results. 1757 patients were analysed (age 55.9 [14.5] years, disease duration 7.9 [10.3] years, male sex 16.7%, 24.6% diffuse cutaneous subset [dcSSc]). At inclusion, 8.9% of patients had current or previous digital gangrene, 16.1% had current digital ulcers (DUs) and 42.7% had ever had DUs (current or previous). Older age, DUs ever and dcSSc were statistically significant risk factors for gangrene in the cross-sectional multivariable model. During a median follow-up of 13.1 months, 16/771 (0.9%) patients developed gangrene. All 16 patients who developed gangrene had previously had DUs and gangrene. Further risk factors for incident gangrene were the dcSSc subset and longer disease duration. Conclusion. In unselected SSc patients, gangrene occurs in about 9% of SSc patients. DUs ever and, to a lesser extent, the dcSSc subset are strongly and independently associated with gangrene, while traditional cardiovascular risk factors could not be identified as risk factors. Key words: systemic sclerosis, vasculopathy, digital ulcers, gangrene Rheumatology key messages . In patients with SSc, digital gangrene tends to have a recurring course. . Patients with diffuse cutaneous SSc and digital ulcers are at higher risk for gangrene. . In patients with SSc, traditional cardiovascular risk factors are not strongly associated with gangrene. 1 Department of Rheumatology, University Hospital Zurich, Zurich, Switzerland, 2 Internal Medicine and Rheumatology, Cantacuzino Hospital, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania, 3 Department of Rheumatology, Ghent University Hospital, and Department of Internal Medicine, Ghent University, Ghent, Belgium, 4 Department of Internal Medicine and Clinical Immunology, Huriez Hospital, University of Lille, Lille, France, 5 Medizinische Universita ¨ tsklinik, University of Tu ¨ bingen, Tu ¨ bingen, Germany, 6 Department of Rheumatology and Clinical Immunology, Charite ´ – Universita ¨ tsmedizin Berlin Charite ´ and Berlin Institute of Health (BIH), Germany, Berlin, 7 Department of Precision Medicine, University of Campania ‘Luigi Vanvitelli’, Naples, Italy, 8 Department of Rheumatology and Clinical Immunology, Justus Liebig University Giessen, Campus Kerckhoff, Bad Nauheim, Germany, 9 Department of Experimental and Clinical Medicine, Division of Rheumatology AOUC, University of Florence, Florence, Italy and 10 Cochin Hospital, Rheumatology A Department, Paris Descartes University, Paris, France Submitted 13 January 2019; accepted 14 October 2019 Correspondence to: Carina Mihai, Department of Rheumatology, University Hospital Zurich, Gloriastrasse 25, 8091 Zurich, Switzerland. E-mail: Carmen-Marina.Mihai@usz.ch *See Acknowledgements section for a list of the EUSTAR collaborators. CLINICAL SCIENCE V C The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com Rheumatology Rheumatology 2020;59:2016–2023 doi:10.1093/rheumatology/kez558 Advance Access publication 2 December 2019 Downloaded from https://academic.oup.com/rheumatology/article/59/8/2016/5650399 by guest on 11 July 2022