LAUSR

Background Digital ulcers (DUs) affect about half of systemic sclerosis (SSc) patients during disease course. In some patients, peripheral vasculopathy can promote critical ischemia and gangrene, severe complications with potential life threatening consequences. Recently the DUO registry suggested a 18% prevalence of gangrene in DU-SSc patients, with smoking and a high number of DUs being predictive factors. However, little is known about gangrene in unselected SSc patients. Objectives To investigate the prevalence, incidence and risk factors for gangrene in the EUSTAR cohort. Methods We included patients from the EUSTAR database satisfying the ACR 1980 or the ACR/EULAR 2013 classification criteria for SSc, with at least one visit recording data on gangrene. We extracted from this database data regarding the reporting of DUs, DUs history and digital gangrene. Centres were asked for supplementary data on traditional cardiovascular (CV) risk factors. We analysed by uni- and multivariable logistic regression the cross-sectional relationship between gangrene and its potential risk factors such as history of DUs, cutaneous subset, disease duration, autoantibodies, traditional CV risk factors. Furthermore, longitudinal data were analysed by Cox proportional hazards regression. Results 1757 patients matched the inclusion criteria (age at inclusion 55.9±14.5 years, disease duration since first non-Raynaud’s symptom 7.9±10.3 years and from onset of Raynaud’s phenomenon (RP) 11.1±11.0 years, male sex 16.7%, 24.6% diffuse cutaneous subset (DcSSc)). At inclusion, 8.9% of patients had either current or previous digital gangrene, 15.7% had current DUs and a further 25.8% had previously had DUs. Among the potential risk factors, older age, a history of DUs and the DcSSc subset were statistically significant risk factors in the cross-sectional multivariable model. For the longitudinal part, during the entire follow-up (median [Q1,Q3] 13.1 [9.6, 19.3] months), 16/771 patients had incident gangrene (2.1%), accounting for an incidence of 1.73/100 patient-years. All 16 patients who developed incident gangrene had previously had DUs and gangrene. Further risk factors for incident gangrene were the DcSSc subset and longer disease duration: hazard ratio [95% confidence interval]: 8.97 [2.90–27.71] and 1.08 [1.04–1.13] respectively, both p<0.001. Conclusions In unselected SSc patients, gangrene still occurs in about 9% of SSc patients. Of the most importance, a history of DUs and, to a lesser extent, the DcSSc subset are strongly and independently associated with gangrene, while traditional CV risk factors were not identified as risk factors. Our results confirm that gangrene is still a concern in SSc. They emphasise the importance of microvascular SSc-associated disease in the pathogenesis of gangrene and suggest that the DcSSc subset should be prioritised for risk-stratification of the patients. Acknowledgements The authors thank all the contributing EUSTAR investigators and patients. Disclosure of Interest C. Mihai Grant/research support from: Actelion Pharmaceuticals Ltd, Abbvie, Speakers bureau: Roche, Geneva Romfarm, O. Distler Grant/research support from: Actelion, Bayer, Boehringer Ingelheim, Mitsubishi Tanabe Pharma, Roche, Consultant for: Actelion, Bayer, BiogenIdec, Boehringer Ingelheim, ChemomAb, espeRare foundation, Genentech/Roche, GSK, Inventiva, Italfarmaco, Lilly, medac, MedImmune, Mitsubishi Tanabe Pharma, Pharmacyclics, Novartis, Pfizer, Sanofi, Sinoxa, A. M. Gheorghiu Grant/research support from: Geneva Romfarm, Abbvie, P. Constantin: None declared, R. Dobrota Grant/research support from: Actelion Pharmaceuticals Ltd, Pfizer, S. Jordan: None declared, V. Smith Grant/research support from: Actelion Pharmaceuticals Ltd, Boehringer-Ingelheim Pharma GmbH, Bayer AG, Roche NV/SA, Fund for Scientific Research Flanders, E. Hachulla: None declared, J. Henes: None declared, E. Siegert: None declared, S. Vettori: None declared, U. Müller-Ladner: None declared, M. Matucci-Cerinic: None declared, Y. Allanore Grant/research support from: BMS, Genentech-Roche, Inventiva, Pfizer, Sanofi, Consultant for: Actelion, Bayer, Biogen, Genentech-Roche, Galapagos, Medac, Pfizer, Sanofi, Servier, UCB