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1. Digital ulcers predict a worse disease course in patients with systemic sclerosis

Author

Mihai, Carina, Landewé, Robert, van der Heijde, Désirée, Walker, Ulrich A, Constantin, Paul I, Gherghe, Ana Maria, Ionescu, Ruxandra, Rednic, Simona, Allanore, Yannick, Avouac, Jérôme, Czirják, László, Hachulla, Eric, Riemekasten, Gabriela, Cozzi, Franco, Airò, Paolo, Cutolo, Maurizio, Mueller-Ladner, Ulf, Matucci-Cerinic, Marco, Launay, David, Dobrotă, Rucsandra, Sfrenţ-Cornăţeanu, Roxana, Zingarelli, Stefania, Pigatto, Erika, Cuomo, Giovanna, Caramaschi, Paola, Ananieva, Lidia, Ullman, Susanne, Iversen, Line, Gurman, Alexandra Balbir, Braun-Moscovici, Yolanda, Carreira, Patricia E., Joven, Beatriz E, Minier, Tünde, Guiducci, Serena, Bellando-Randone, Silvia, Pellerito, Raffaele, Hunzelmann, Nicolas, Tarner, Ingo H., Radominski, Sebastião Cezar, de Souza Müller, Carolina, Iannone, Florenzo, Henes, Jörg, Bancel, Dominique Farge, Damjanov, Nemanja, Ostojić, Predrag, Pozzi, Maria Rosa, Hesselstrand, Roger, Denton, Christopher, Krasowska, Dorota, Tikly, Mohammed, Riccieri, Valeria, Cantatore, Francesco Paolo, Corrado, Ada, Da Silva, José Antonio Pereira, Salvador, Maria João, Tyndall, Alan, Gabrielli, Armando, Distler, Oliver, Jordan, Suzan, Heitmann, Stefan, Burkhardt, Harald, Himsel, Andrea, Rozman, Blaz, Smith, Vanessa, De Keyser, Filip, Kalitena, Dusanka Martinovic, Radic, Mislav, Filipescu, Ileana, Petcu, Ana, Vlachoyiannopoulos, Panayiotis, Kucharz, Eugene J., Widuchowska, Malgorzata, Kopec-Medrek, Magdalena, Kotulska, Anna, Szücs, Gabriella, Stankovic, Aleksandra, Stamenkovic, Bojana, Selmi, Carlo Francesco, De Santis, Maria, Marasini, Bianca, Coleiro, Bernard, Santamaria, Vera Ortiz, Westhovens, René, Bečvář, Radim, Novak, Srdan, Engelhart, Merete, Meroni, Pierluigi, Ingegnoli, Francesca, Zeni, Silvana, Sulli, Alberto, Distler, Jörg, Yavuz, Sule, Montecucco, Carlomaurizio, Eyerich, Kilian, Krummel-Lorenz, Brigitte, Zenone, Thierry, Midtvedt, Øyvind, Chizzolini, Carlo, Seidel, Matthias, Oleszowsky, Mara, Üprus, Maria, Opriş, Daniela, Groşeanu, Laura, Bielecka, Otylia Kowal, Antonio, Zea Mendoza, Szechinski, Jacek, Morović-Vergles, Jadranka, Scorza, Raffaella, Puppo, Francesco, Mathieu, Alessandro, Anic, Branimir, Stork, Jiri, Stebbings, Simon, Inanc, Murat, Hasler, Paul, von Mühlen, Carlos Alberto, Aringer, Martin, Popa, Sergei, Li, Mengtao, and Rosato, Edoardo

Published
2016
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2. Incidence and risk factors for gangrene in patients with systemic sclerosis from the EUSTAR cohort

Author

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, Lepri, G, Jaeger, Vk, Walker, Ua, Iannone, F, Cacciapaglia, F, Tomčík, M, Becvar, R, Rednic, S, Petcu, A, Szabo, I, Codullo, V, Caporali, R, Montecucco, C, Carreira, P, Ioven, B, Minier, T, Czirják, L, Chizzolini, C, Allali, D, Zanatta, E, Doria, A, Gabrielli, A, Airò, P, Lazzaroni, Mg, Radić, M, Martinovic, D, Braun-Moscovici, Y, Balbir-Gurman, A, Hunzelmann, N, Caramaschi, P, Morovic-Vergles, J, Denton, C, Santamaria, V, Heitmann, S, Krasowska, D, Michalska-Jakubus, M, Seidel, M, Foeldvari, I, Helmus, N, Salvador, M, Stamenkovic, B, Stankovic, A, Ananieva, L, Herrick, A, Engelhart, M, De La Puente, C, Hoffmann-Vold, Am, Midtvedt, Ø, Launay, D, Sobanski, V, Riccieri, V, Opris-Belinski, D, Groseanu, L, Ionescu, R, Bojinca, M, Sunderkötter, C, Distler, J, Ingegnoli, F, van der Haecke, A, Ullman, S, Pozzi, Mr, Eyerich, K, Vanthuyne, M, Erler, A, Aringer, M, De Langhe, E, Baresic, M, Mayer, M, Anic, B, Yavuz, S, Granel, B, Popa, S, Agachi, S, Zenone, T, Mathieu, A, Vacca, A, Solanki, K, Veale, D, Loyo, E, Tineo, C, Gigante, A, Rosato, E, Oksel, F, Yagurcu, F, Tănăseanu, Cm, Visalli, E, Benenati, A, Foti, R, Ancuta, C, Dan, D, Adler, S, Villiger, P, Fathi, N, de la Peña Lefebvre PG, González Martín, J, Chatelus, E, Sibilia, J, Litinsky, I, Del Galdo, F, Ann Sakettkoo, L, Kerzberg, E, Bianchi, Wa, Bianchi, Bv, Castellví, I, Limonta, M, Rimar, D, Couto, M, Ribi, C, Spertini, F, Kahl, S, Hsu, V, Poindron, V, Meghit, K, Martin, T, Kolstad, K, Chung, L, Thiele, A, Schmeiser, T, Zdrojewski, Z, Riemekasten, G, Levy, Y, Cardoneanu, A, Burlui, A, Rezus, E, Pamuk, On, Talotta, R, Bongiovanni, S, Puttini, Ps., 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, Giovanna, Cuomo, Chizzolini, Carlo, Allali, Danièle, and University of Zurich

Subjects
Adult, Male, medicine.medical_specialty, Databases, Factual, systemic sclerosis, digital ulcer, 610 Medicine & health, Disease, ddc:616.07, Logistic regression, Systemic scleroderma, Cohort Studies, Rheumatology, Risk Factors, Internal medicine, Cox proportional hazards regression, medicine, Humans, Pharmacology (medical), In patient, digital ulcers, gangrene, vasculopathy, Aged, Gangrene, Scleroderma, Systemic, business.industry, Incidence (epidemiology), Incidence, 10051 Rheumatology Clinic and Institute of Physical Medicine, food and beverages, Middle Aged, medicine.disease, Cross-Sectional Studies, Cohort, Female, business, systemic sclerosi
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.

Published
2019

3. Digital ulcers predict a worse disease course in patients with systemic sclerosis

Author

Mihai, Carina, Landewé, Robert, Van Der Heijde, Désirée, Walker, Ulrich A., Constantin, Paul I., Gherghe, Ana Maria, Ionescu, Ruxandra, Rednic, Simona, Allanore, Yannick, Avouac, Jéroˆme, Czirják, László, Hachulla, Eric, Riemekasten, Gabriela, Cozzi, Franco, Airò, Paolo, Cutolo, Maurizio, Mueller Ladner, Ulf, Matucci Cerinic, Marco, Launay, David, Dobrota, Rucsandra, Sfrent Cornateanu, Roxana, Zingarelli, Stefania, Pigatto, Erika, Cuomo, Giovanna, Caramaschi, Paola, Ananieva, Lidia, Ullman, Susanne, Iversen, Line, Gurman, Alexandra Balbir, Braun Moscovici, Yolanda, Carreira, Patricia E., Joven, Beatriz E., Minier, Tünde, Guiducci, Serena, Bellando Randone, Silvia, Pellerito, Raffaele, Hunzelmann, Nicolas, Tarner, Ingo H., Radominski, Sebastião Cezar, De Souza Müller, Carolina, Iannone, Florenzo, Henes, Jörg, Bancel, Dominique Farge, Damjanov, Nemanja, Ostojic, Predrag, Pozzi, Maria Rosa, Hesselstrand, Roger, Denton, Christopher, Krasowska, Dorota, Tikly, Mohammed, Riccieri, Valeria, Cantatore, Francesco Paolo, Corrado, Ada, Da Silva, José Antonio Pereira, Salvador, Maria João, Tyndall, Alan, Gabrielli, Armando, Distler, Oliver, Jordan, Suzan, Heitmann, Stefan, Burkhardt, Harald, Himsel, Andrea, Rozman, Blaz, Smith, Vanessa, Keyser, Filip De, Kalitena, Dusanka Martinovic, Radic, Mislav, Filipescu, Ileana, Petcu, Ana, Vlachoyiannopoulos, Panayiotis, Kucharz, Eugene J., Widuchowska, Malgorzata, Kopec Medrek, Magdalena, Kotulska, Anna, Szücs, Gabriella, Stankovic, Aleksandra, Stamenkovic, Bojana, Selmi, Carlo Francesco, Santis, Maria De, Marasini, Bianca, Coleiro, Bernard, Santamaria, Vera Ortiz, Westhovens, René, Becvár, Radim, Novak, Srdan, Engelhart, Merete, Meroni, Pierluigi, Ingegnoli, Francesca, Zeni, Silvana, Sulli, Alberto, Distler, Jörg, Yavuz, Sule, Montecucco, Carlomaurizio, Eyerich, Kilian, Krummel Lorenz, Brigitte, Zenone, Thierry, Midtvedt, Øyvind, Chizzolini, Carlo, Seidel, Matthias, Oleszowsky, Mara, Üprus, Maria, Opriş, Daniela, Groseanu, Laura, Bielecka, Otylia Kowal, Antonio, Zea Mendoza, Szechinski, Jacek, Morovic Vergles, Jadranka, Scorza, Raffaella, Puppo, Francesco, Mathieu, Alessandro, Anic, Branimir, Stork, Jiri, Stebbings, Simon, Inanc, Murat, Hasler, Paul, Von Mühlen, Carlos Alberto, Aringer, Martin, Popa, Sergei, Mengtao, Li, Rosato, Edoardo, University of Zurich, and Mihai, Carina

Subjects
Genetics and Molecular Biology (all), Lung Diseases, Male, 0301 basic medicine, Databases, Factual, Epidemiology, 2745 Rheumatology, Vital Capacity, Disease, Biochemistry, Scleroderma, Systemic autoimmune disease, High morbidity, 0302 clinical medicine, Cardiovascular Disease, Immunology and Allergy, Medicine (all), 10051 Rheumatology Clinic and Institute of Physical Medicine, Systemic Sclerosis, Adult, Aged, Cardiovascular Diseases, Disease Progression, Female, Hand Dermatoses, Humans, Hypertension, Pulmonary, Kidney Diseases, Middle Aged, Multivariate Analysis, Prognosis, Proportional Hazards Models, Pulmonary Diffusing Capacity, Retrospective Studies, Scleroderma, Systemic, Skin Ulcer, Stroke Volume, Fingers, Rheumatology, Immunology, Biochemistry, Genetics and Molecular Biology (all), Orvostudományok, Pulmonary, Hypertension, 2723 Immunology and Allergy, medicine.medical_specialty, 610 Medicine & health, Klinikai orvostudományok, General Biochemistry, Genetics and Molecular Biology, Disease course, Databases, 03 medical and health sciences, 1300 General Biochemistry, Genetics and Molecular Biology, Internal medicine, Cox proportional hazards regression, medicine, In patient, Factual, 030203 arthritis & rheumatology, 2403 Immunology, business.industry, Systemic, medicine.disease, 030104 developmental biology, Physical therapy, business
Abstract

ObjectiveSystemic sclerosis (SSc) is a systemic autoimmune disease with high morbidity and significant mortality. There is a great need of predictors that would allow risk stratification of patients with SSc and ultimately initiation of treatment early enough to ensure optimal clinical results. In this study, we evaluated whether a history of digital ulcers (HDU) at presentation may be a predictor of vascular outcomes and of overall clinical worsening and death in patients with SSc.MethodsPatients from the EULAR Scleroderma Trials and Research (EUSTAR) database, satisfying at inclusion the 1980 American College of Rheumatology classification criteria for SSc, who had a follow-up of at least 3 years since baseline or who have died, were included in the analysis. HDU at presentation as a predictor of disease worsening or death was evaluated by Cox proportional hazards regression analysis.Results3196 patients matched the inclusion criteria (male sex 13.2%, 33.4% diffuse subset). At presentation, 1092/3196 patients had an HDU (34.1%). In multivariable analysis adjusting for age, gender and all parameters considered potentially significant, HDU was predictive for the presence of active digital ulcers (DUs) at prospective visits (HR (95% CI)): 2.41 (1.91 to 3.03), pConclusionsIn patients with SSc, HDU at presentation predicts the occurrence of DUs at follow-up and is associated with cardiovascular worsening and decreased survival.

Published
2015
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4. Incidence and risk factors for gangrene in patients with systemic sclerosis from the EUSTAR cohort.

Author

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, Cerinic, Marco Matucci, Allanore, Yannick, and collaborators, EUSTAR

Subjects
AGE distribution, FOOT ulcers, GANGRENE, PERIPHERAL vascular diseases, RISK assessment, SYSTEMIC scleroderma, TOES, MULTIPLE regression analysis, CROSS-sectional method, PROPORTIONAL hazards models, DISEASE duration, DESCRIPTIVE statistics, DISEASE complications, DISEASE risk factors
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. [ABSTRACT FROM AUTHOR]

Published
2020
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