Incidence and risk factors for gangrene in patients with systemic sclerosis from the EUSTAR cohort
Authors: Mihai Carina , Distler Oliver , Gheorghiu Ana Maria , Constantin Paul I , Dobrota Rucsandra , Jordan Suzana , Smith Vanessa , Hachulla Eric , Henes Jörg , Siegert Elise , Vettori Serena , Müller-Ladner Ulf , Matucci Cerinic Marco , Allanore Yannick ,   EUSTAR collaborators, Lepri Gemma , Jaeger Veronika K , Walker Ulrich A , Iannone Florenzo , Cacciapaglia Fabio , Tomčík Michal , Becvar Radim , Rednic Simona , Petcu Ana , Szabo Iulia , Codullo Veronica , Caporali Roberto , Montecucco Carlomaurizio , Carreira Patricia , Ioven Beatriz , Minier Tunde , Czirják László , Chizzolini Carlo , Allali Danièle , Zanatta Elisabetta , Doria Andrea , Gabrielli Armando , Airò Paolo , Lazzaroni Maria-Grazia , Radić Mislav , Martinovic Duska , Braun-Moscovici Yolanda , Balbir-Gurman Alexandra , Hunzelmann Nicolas , Caramaschi Paola , Morovic-Vergles Jadranka , Denton Christopher , Santamaria Vera Ortiz , Heitmann Stefan , Krasowska Dorota , Michalska-Jakubus Malgorzata , Seidel Matthias , Foeldvari Ivan , Helmus Nicola , Salvador Maria João , Stamenkovic Bojana , Stankovic Aleksandra , Ananieva Lidia , Herrick Ariane , Engelhart Merete , De La Puente Carlos , Hoffmann-Vold Anna-Maria , Midtvedt Øyvind , Launay David , Sobanski Vincent , Riccieri Valeria , Opris-Belinski Daniela , Groseanu Laura , Ionescu Ruxandra Maria , Bojinca Mihai , Sunderkötter Cord , Distler Jörg , Ingegnoli Francesca , van der Haecke Amber , Ullman Susanne , Pozzi Maria Rosa , Eyerich Kilian , Vanthuyne Marie , Erler Anne , Aringer Martin , De Langhe Ellen , Baresic Marko , Mayer Miroslav , Anic Branimir , Yavuz Sule , Granel Brigitte , Popa Sergei , Agachi Svetlana , Zenone Thierry , Mathieu Alessandro , Vacca Alessandra , Solanki Kamal , Veale Douglas , Loyo Esthela , Tineo Carmen , Gigante Antonetta , Rosato Edoardo , Oksel Fahrettin , Yagurcu Figen , Tănăseanu Cristina-Mihaela , Visalli Elisa , Benenati Alessia , Foti Rosario , Ancuta Codrina , Dan Diana , Adler Sabine , Villiger Peter , Fathi Nihal , de la Peña Lefebvre Paloma García , Martín Jorge Juan González , Chatelus Emmanuel , Sibilia Jean , Litinsky Ira , Del Galdo Francesco , Sakettkoo Lesley Ann , Kerzberg Eduardo , Bianchi Washington A , Bianchi Breno Valdetaro , Castellví Ivan , Limonta Massimiliano , Rimar Doron , Couto Maura , Ribi Camillo , Spertini François , Kahl Sarah , Hsu Vivien , Poindron Vincent , Meghit Kilifa , Martin Thierry , Kolstad Kathleen , Chung Lorinda , Thiele Astrid , Schmeiser Tim , Zdrojewski Zbigniew , Riemekasten Gabriela , Levy Yair , Cardoneanu Anca , Burlui Alexandra , Rezus Elena , Pamuk Omer Nuri , Talotta Rossella , Bongiovanni Sara , Puttini Piercarlo Sarzi 
Published: October 2019

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 classification 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.