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1. ACE inhibitors in SSc patients display a risk factor for scleroderma renal crisis—a EUSTAR analysis

Author

Bütikofer L, Varisco PA, Distler O, Kowal-Bielecka O, Allanore Y, Riemekasten G, Villiger PM, Adler S, Avouac J, Walker UA, Guiducci S, Airò P, Hachulla E, Valentini G, Carreira PE, Cozzi F, Gurman AB, Braun-Moscovici Y, Damjanov N, Ananieva LP, Scorza R, Jimenez S, Busquets J, Li M, Müller-Ladner U, Maurer B, Tyndall A, Lapadula G, Iannone F, Becvar R, Sierakowsky S, Bielecka OK, Cutolo M, Sulli A, Cuomo G, Vettori S, Rednic S, Nicoara I, Vlachoyiannopoulos P, Montecucco C, Caporali R, Novak S, Czirják L, Varju C, Chizzolini C, Kucharz EJ, Kotulska A, Kopec-Medrek M, Widuchowska M, Rozman B, Mallia C, Coleiro B, Gabrielli A, Farge D, Hij A, Hesselstrand R, Scheja A, Wollheim F, Martinovic D, Govoni M, Monaco AL, Hunzelmann N, Pellerito R, Bambara LM, Caramaschi P, Black C, Denton C, Henes J, Santamaria VO, Heitmann S, Krasowska D, Seidel M, Oleszowsky M, Burkhardt H, Himsel A, Salvador MJ, Stamenkovic B, Stankovic A, Tikly M, Starovoytova MN, Engelhart M, Strauss G, Nielsen H, Damgaard K, Szücs G, Mendoza AZ, de la Puente Buijdos C, Sifuentes Giraldo WA, Midtvedt Ø, Garen T, Launay D, Valesini G, Riccieri V, Ionescu RM, Opris D, Groseanu L, Wigley FM, Mihai CM, Cornateanu RS, Ionitescu R, Gherghe AM, Gorga M, Dobrota R, Bojinca M, Schett G, Distler JHW, Meroni P, Zeni S, Mouthon L, De Keyser F, Smith V, Cantatore FP, Corrado A, Ullman S, Iversen L, Pozzi MR, Eyerich K, Hein R, Knott E, Szechinski J, Wiland P, Szmyrka-Kaczmarek M, Sokolik R, Morgiel E, Krummel-Lorenz B, Saar P, Aringer M, Günther C, Anic B, Baresic M, Mayer M, Radominski SC, de Souza Müller C, Azevedo VF, Agachi S, Groppa L, Chiaburu L, Russu E, Zenone T, Stebbings S, Highton J, Stamp L, Chapman P, Baron M, O'Donnell J, Solanki K, Doube A, Veale D, O'Rourke M, Loyo E, Rosato E, Pisarri S, Tanaseanu CM, Popescu M, Dumitrascu A, Tiglea I, Chirieac R, Ancuta C, Furst DE, Kafaja S, de la Peña Lefebvre PG, Rubio SR, Exposito MV, Sibilia J, Chatelus E, Gottenberg JE, Chifflot H, Litinsky I, Venalis A, Butrimiene I, Venalis P, Rugiene R, Karpec D, Kerzberg E, Montoya F, Cosentino V, Castellvi I., Publica, Bütikofer, L, Varisco, Pa, Distler, O, Kowal-Bielecka, O, Allanore, Y, Riemekasten, G, Villiger, Pm, Adler, S, Avouac, J, Walker, Ua, Guiducci, S, Airò, P, Hachulla, E, Valentini, G, Carreira, Pe, Cozzi, F, Gurman, Ab, Braun-Moscovici, Y, Damjanov, N, Ananieva, Lp, Scorza, R, Jimenez, S, Busquets, J, Li, M, Müller-Ladner, U, Maurer, B, Tyndall, A, Lapadula, G, Iannone, F, Becvar, R, Sierakowsky, S, Bielecka, Ok, Cutolo, M, Sulli, A, Cuomo, G, Vettori, S, Rednic, S, Nicoara, I, Vlachoyiannopoulos, P, Montecucco, C, Caporali, R, Novak, S, Czirják, L, Varju, C, Chizzolini, C, Kucharz, Ej, Kotulska, A, Kopec-Medrek, M, Widuchowska, M, Rozman, B, Mallia, C, Coleiro, B, Gabrielli, A, Farge, D, Hij, A, Hesselstrand, R, Scheja, A, Wollheim, F, Martinovic, D, Govoni, M, Monaco, Al, Hunzelmann, N, Pellerito, R, Bambara, Lm, Caramaschi, P, Black, C, Denton, C, Henes, J, Santamaria, Vo, Heitmann, S, Krasowska, D, Seidel, M, Oleszowsky, M, Burkhardt, H, Himsel, A, Salvador, Mj, Stamenkovic, B, Stankovic, A, Tikly, M, Starovoytova, Mn, Engelhart, M, Strauss, G, Nielsen, H, Damgaard, K, Szücs, G, Mendoza, Az, de la Puente Buijdos, C, Sifuentes Giraldo, Wa, Midtvedt, Ø, Garen, T, Launay, D, Valesini, G, Riccieri, V, Ionescu, Rm, Opris, D, Groseanu, L, Wigley, Fm, Mihai, Cm, Cornateanu, R, Ionitescu, R, Gherghe, Am, Gorga, M, Dobrota, R, Bojinca, M, Schett, G, Distler, Jhw, Meroni, P, Zeni, S, Mouthon, L, De Keyser, F, Smith, V, Cantatore, Fp, Corrado, A, Ullman, S, Iversen, L, Pozzi, Mr, Eyerich, K, Hein, R, Knott, E, Szechinski, J, Wiland, P, Szmyrka-Kaczmarek, M, Sokolik, R, Morgiel, E, Krummel-Lorenz, B, Saar, P, Aringer, M, Günther, C, Anic, B, Baresic, M, Mayer, M, Radominski, Sc, de Souza Müller, C, Azevedo, Vf, Agachi, S, Groppa, L, Chiaburu, L, Russu, E, Zenone, T, Stebbings, S, Highton, J, Stamp, L, Chapman, P, Baron, M, O'Donnell, J, Solanki, K, Doube, A, Veale, D, O'Rourke, M, Loyo, E, Rosato, E, Pisarri, S, Tanaseanu, Cm, Popescu, M, Dumitrascu, A, Tiglea, I, Chirieac, R, Ancuta, C, Furst, De, Kafaja, S, de la Peña Lefebvre, Pg, Rubio, Sr, Exposito, Mv, Sibilia, J, Chatelus, E, Gottenberg, Je, Chifflot, H, Litinsky, I, Venalis, A, Butrimiene, I, Venalis, P, Rugiene, R, Karpec, D, Kerzberg, E, Montoya, F, Cosentino, V, and Castellvi, I.

Subjects
INVOLVEMENT, Male, Hypertension, Renal, ACE inhibitors, lcsh:Diseases of the musculoskeletal system, Scleroderma Renal Crisis, MULTICENTER, Angiotensin-Converting Enzyme Inhibitors, Scleroderma, Scleroderma renal crisis, 0302 clinical medicine, Risk Factors, Medicine and Health Sciences, Medicine, 030212 general & internal medicine, Prospective Studies, 610 Medicine & health, Renal, Antihypertensive drugs, Outcome, antihypertensive drugs, arterial hypertension, outcome, scleroderma renal crisis, Incidence (epidemiology), Incidence, Hazard ratio, Acute Kidney Injury, Middle Aged, Europe, Treatment Outcome, Population Surveillance, Cohort, Hypertension, Female, 360 Social problems & social services, Proto-oncogene tyrosine-protein kinase Src, Research Article, Arterial hypertension, medicine.medical_specialty, 03 medical and health sciences, ENDOTHELIN-1, Internal medicine, Humans, Risk factor, Aged, 030203 arthritis & rheumatology, Scleroderma, Systemic, business.industry, SYSTEMIC-SCLEROSIS, Systemic, medicine.disease, Concomitant, lcsh:RC925-935, business
Abstract

Objectives To investigate the effect of ACE inhibitors (ACEi) on the incidence of scleroderma renal crisis (SRC) when given prior to SRC in the prospectively collected cohort from the European Scleroderma Trial and Research Group (EUSTAR). Methods SSc patients without prior SRC and at least one follow-up visit were included and analyzed regarding SRC, arterial hypertension, and medication focusing on antihypertensive medication and glucocorticoids (GC). Results Out of 14,524 patients in the database, we identified 7648 patients with at least one follow-up. In 27,450 person-years (py), 102 patients developed SRC representing an incidence of 3.72 (3.06–4.51) per 1000 py. In a multivariable time-to-event analysis adjusted for age, sex, disease severity, and onset, 88 of 6521 patients developed SRC. The use of ACEi displayed an increased risk for the development of SRC with a hazard ratio (HR) of 2.55 (95% confidence interval (CI) 1.65–3.95). Adjusting for arterial hypertension resulted in a HR of 2.04 (95%CI 1.29–3.24). There was no evidence for an interaction of ACEi and arterial hypertension (HR 0.83, 95%CI 0.32–2.13, p = 0.69). Calcium channel blockers (CCB), angiotensin receptor blockers (ARB), endothelin receptor antagonists, and GC—mostly in daily dosages below 15 mg of prednisolone—did not influence the hazard for SRC. Conclusions ACEi in SSc patients with concomitant arterial hypertension display an independent risk factor for the development of SRC but are still first choice in SRC treatment. ARBs might be a safe alternative, yet the overall safety of alternative antihypertensive drugs in SSc patients needs to be further studied.

Published
2020

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. Outcomes of patients with systemic sclerosis treated with rituximab in contemporary practice: a prospective cohort study

Author

Elhai, M, Boubaya, M, Distler, O, Smith, V, Matucci-Cerinic, M, Sancho, JJ, Truchetet, ME, Braun-Moscovici, Y, Iannone, F, Novikov, PI, Lescoat, A, Siegert, E, Castellvi, I, Airo, P, Vettori, S, Langhe, E, Hachulla, E, Erler, A, Ananieva, L, Krusche, M, Lopez-Longo, FJ, Distler, JHW, Hunzelmann, N, Hoffmann-Vold, AM, Riccieri, V, Hsu, VM, Pozzi, MR, Ancuta, C, Rosato, E, Mihai, C, Kuwana, M, Saketkoo, LA, Chizzolini, C, Hesselstrand, R, Ullman, S, Yavuz, S, Rednic, S, Caimmi, C, Bloch-Queyrat, C, Allanore, Y, Guiducci, S, Walker, UA, Kyburz, D, Lapadula, G, Maurer, B, Jordan, S, Dobrota, R, Becvar, R, Sierakowsky, S, Bielecka, OK, Sulli, A, Cutolo, M, Cuomo, G, Nicoara, I, Kahan, A, Vlachoyiannopoulos, PG, Montecucco, CM, Caporali, R, Stork, J, Inanc, M, Carreira, PE, Novak, S, Czirjak, L, Varju, C, Kucharz, EJ, Kotulska, A, Kopec-Medrek, M, Widuchowska, M, Cozzi, F, Rozman, B, Mallia, C, Coleiro, B, Gabrielli, A, Farge, D, Wu, C, Marjanovic, Z, Faivre, H, Hij, D, Dhamadi, R, Wollheim, F, Scheja, A, Wuttge, DM, Andreasson, K, Martinovic, D, Balbir-Gurman, A, Trotta, F, Lo Monaco, A, Pellerito, R, Mauriziano, O, Caramaschi, P, Morovic-Vergles, J, Black, C, Denton, C, Damjanov, N, Henes, J, Santamaria, VO, Heitmann, S, Krasowska, D, Matthias, Hasler, P, Burkhardt, H, Himsel, A, Bajocchi, G, Da Silva, JAP, Salvador, MJ, Stamenkovic, B, Stankovic, A, Selmi, CF, De Santis, M, Tikly, M, Denisov, LN, Herrick, A, Muller-Ladner, U, Frerix, M, Tarner, I, Scorza, R, Puppo, F, Engelhart, M, Strauss, G, Nielsen, H, Damgaard, K, Szucs, G, Mendoza, AZ, de la Puente, C, Giraldo, WAS, Midtvedt, O, Reiseter, S, Garen, T, Launay, D, Valesini, G, Ionescu, RM, Groseanu, L, Opris, D, Cornateanu, RS, Ionitescu, R, Gherghe, AM, Soare, A, Gorga, M, Bojinca, M, Milicescu, M, Sunderkotter, C, Kuhn, A, Sandorfi, N, Schett, G, Beyer, C, Meroni, P, Ingegnoli, F, Mouthon, L, De Keyser, F, Melsens, K, Cantatore, FP, Corrado, A, Iversen, L, von Muhlen, CA, Bohn, JM, Lonzetti, LS, Eyerich, K, Hein, R, Knott, E, Wiland, P, Szmyrka-Kaczmarek, M, Sokolik, R, Morgiel, E, Madej, M, Houssiau, FA, Krummel-Lorenz, B, Saar, P, Aringer, M, Gunther, C, Westhovens, R, Lenaerts, J, Anic, B, Baresic, M, Mayer, M, Uprus, M, Otsa, K, Granel, B, Muller, CD, Radominski, SC, Azevedo, VF, Jimenez, S, Busquets, J, Agachi, S, Groppa, L, Chiaburu, L, Russu, E, Popa, S, Zenone, T, Pileckyte, M, Mathieu, A, Vacca, A, Sampaio-Barros, PD, Yoshinari, NH, Marangoni, RG, Martin, P, Fuocco, L, Stebbings, S, Highton, J, Chapman, P, O'Donnell, J, Stamp, L, Doube, A, Solanki, K, Veale, D, O'Rourke, M, Loyo, E, Li, MT, Mohamed, WAAA, Amoroso, A, Gigante, A, Oksel, F, Yargucu, F, Tanaseanu, CM, Popescu, M, Dumitrascu, A, Tiglea, I, Foti, R, Chirieac, R, Furst, D, Villiger, P, Adler, S, van Laar, J, Kayser, C, Fathi, N, Hassanien, M, Lefebvre, PGD, Rubio, SR, Exposito, MV, Chatelus, E, Sibilia, J, Gottenberg, JE, Chifflot, H, Litinsky, I, Emery, P, Buch, M, Del Galdo, F, Venalis, A, Butrimiene, I, Venalis, P, Rugiene, R, Karpec, D, Lasky, JA, Cosentino, V, Kerzberg, E, Montoya, F, Bianchi, W, Carneiro, S, Maretti, GB, Bianchi, DV, Limonta, M, Lupi, ALBE, Lupi, E, Rosner, I, Rozenbaum, M, Slobodin, G, Boulman, N, Rimar, D, Couto, M, Kahl, S, Chen, F, McCloskey, D, Malveaux, H, Spertini, F, Ribi, C, Buss, G, Martin, T, Guffroy, A, Poindron, V, Chotchaeva, F, Mukhin, NA, Moiseev, S, EUSTAR Network, Elhai, Muriel, Boubaya, Marouane, Distler, Oliver, Smith, Vanessa, Matucci-Cerinic, Marco, Alegre Sancho, Juan José, Truchetet, Marie-Elise, Braun-Moscovici, Yolanda, Iannone, Florenzo, Novikov, Pavel I, Lescoat, Alain, Siegert, Elise, Castellví, Ivan, Airó, Paolo, Vettori, Serena, De Langhe, Ellen, Hachulla, Eric, Erler, Anne, Ananieva, Lidia, Krusche, Martin, López-Longo, F. J., Distler, Jörg H W, Hunzelmann, Nicola, Hoffmann-Vold, Anna-Maria, Riccieri, Valeria, Hsu, Vivien M, Pozzi, Maria R, Ancuta, Codrina, Rosato, Edoardo, Mihai, Carina, Kuwana, Masataka, Saketkoo, Lesley Ann, Chizzolini, Carlo, Hesselstrand, Roger, Ullman, Susanne, Yavuz, Sule, Rednic, Simona, Caimmi, Cristian, Bloch-Queyrat, Coralie, Allanore, Yannick, and Cuomo, Giovanna

Subjects
Male, Vital capacity, systemic sclerosis, Pulmonary Fibrosis, Vital Capacity, Scleroderma, lung fibrosis, rituximab, skin fibrosis, immune system diseases, DLCO, hemic and lymphatic diseases, Immunology and Allergy, Medicine, Prospective Studies, Registries, skin and connective tissue diseases, Prospective cohort study, Lung, skin fibrosi, Skin, ddc:616, integumentary system, Orvostudományok, Middle Aged, Respiratory Function Tests, lung fibrosis, rituximab, skin fibrosis, systemic sclerosis, Treatment Outcome, lung fibrosi, Antirheumatic Agents, Systemic sclerosis, Rituximab, Female, systemic sclerosi, medicine.drug, Adult, medicine.medical_specialty, Immunology, Klinikai orvostudományok, General Biochemistry, Genetics and Molecular Biology, FEV1/FVC ratio, Rheumatology, Internal medicine, Humans, Adverse effect, Propensity Score, Aged, Biochemistry, Genetics and Molecular Biology (all), Scleroderma, Systemic, Skin fibrosis, business.industry, medicine.disease, Fibrosis, Lung fibrosis, business
Abstract

ObjectiveTo assess the safety and efficacy of rituximab in systemic sclerosis (SSc) in clinical practice.MethodsWe performed a prospective study including patients with SSc from the European Scleroderma Trials and Research (EUSTAR) network treated with rituximab and matched with untreated patients with SSc. The main outcomes measures were adverse events, skin fibrosis improvement, lung fibrosis worsening and steroids use among propensity score-matched patients treated or not with rituximab.Results254 patients were treated with rituximab, in 58% for lung and in 32% for skin involvement. After a median follow-up of 2 years, about 70% of the patients had no side effect. Comparison of treated patients with 9575 propensity-score matched patients showed that patients treated with rituximab were more likely to have skin fibrosis improvement (22.7 vs 14.03 events per 100 person-years; OR: 2.79 [1.47–5.32]; p=0.002). Treated patients did not have significantly different rates of decrease in forced vital capacity (FVC)>10% (OR: 1.03 [0.55–1.94]; p=0.93) nor in carbon monoxide diffusing capacity (DLCO) decrease. Patients having received rituximab were more prone to stop or decrease steroids (OR: 2.34 [1.56–3.53], pConclusionRituximab use was associated with a good safety profile in this large SSc-cohort. Significant change was observed on skin fibrosis, but not on lung. However, the limitation is the observational design. The potential stabilisation of lung fibrosis by rituximab has to be addressed by a randomised trial.

Published
2019

4. A candidate gene study identifies a haplotype of CD2 as novel susceptibility factor for systemic sclerosis

Author

Koumakis, E., Bouaziz, M., Dieude, P., Cauvet, A., Ruiz, B., Airo, P., Cusi, D., Matucci-Cerinic, M., Salvi, E., Cuome, G., Hachulla, E., Diot, E., Caramaschi, P., Valeria RICCIERI, Avouac, J., Allanore, Y., Université Sorbonne Paris Cité (USPC), Departement A de Rhumatologie, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Statistique et Génome (SG), Institut National de la Recherche Agronomique (INRA)-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Mathématiques et Modélisation d'Evry, Université d'Evry Val d'Essonne, Departement de Rhumatologie, Hôpital Bichat - Claude Bernard, Assistance Publique - Hôpitaux de Paris (AP-HP), Université Paris Diderot - Paris 7 (UPD7), UMR 699 Service de Rhumatologie, Institut National de la Santé et de la Recherche Médicale (INSERM), Reumatologia e Immunologia, Spedali Civil Brescia, Biomedical Laboratory Techniques, Università degli Studi di Milano [Milano] (UNIMI), Department of Experimental and Clinical Medicine, Università degli Studi 'Magna Graecia' di Catanzaro [Catanzaro, Italie] (UMG), Department of Health Science, Università del Molise, Department of Internal Medicine, Huntsman Cancer Institute, Hôpital Claude Huriez [Lille], CHU Lille, IFR 618 Service de Pneumologie, Hôpital Bretonneau, Assistance Publique - Hôpitaux de Paris (AP-HP), Unità di Reumatologia, Azienda Ospedaliera, University of Verona (UNIVR), Dipartimento di Medicina Interna e Specialitá Mediche, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Koumakis, Eugenie, Bouaziz, Matthieu, Dieudé, Philippe, Cauvet, Anne, Ruiz, Barbara, Airò, Paolo, Cusi, Daniele, Matucci Cerinic, Marco, Salvi, Erika, Cuomo, Giovanna, Hachulla, Eric, Diot, Elisabeth, Caramaschi, Paola, Riccieri, Valeria, Avouac, Jerome, Allanore, Yannick, Université Sorbonne Paris Cité ( USPC ), CHU Cochin [AP-HP], Université Paris Descartes - Paris 5 ( UPD5 ), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire Statistique et Génome ( SG ), Institut National de la Recherche Agronomique ( INRA ) -Université d'Évry-Val-d'Essonne ( UEVE ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Mathématiques et Modélisation d'Evry ( LaMME ), Institut National de la Recherche Agronomique ( INRA ) -Université d'Évry-Val-d'Essonne ( UEVE ) -ENSIIE-Centre National de la Recherche Scientifique ( CNRS ), Hôpital Bichat - Claude Bernard, Assistance Publique - Hôpitaux de Paris ( AP-HP ), Université Paris Diderot (Paris 7), Institut National de la Santé et de la Recherche Médicale ( INSERM ), Universita degli Studi di Milano ( UNIMI ), University 'Magna Græcia', Hôpital Claude Huriez, Hôpital Bretonneau, Assistance Publique - Hôpitaux de Paris ( AP-HP ), Università degli Studi di Verona, Università degli Studi di Roma 'La Sapienza', Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Mathématiques et Modélisation d'Evry (LaMME), Institut National de la Recherche Agronomique (INRA)-Université d'Évry-Val-d'Essonne (UEVE)-ENSIIE-Centre National de la Recherche Scientifique (CNRS), Università degli studi di Milano [Milano], Università degli Studi di Roma 'La Sapienza' [Rome], Université d'Évry-Val-d'Essonne (UEVE), Università degli Studi di Milano = University of Milan (UNIMI), Università degli Studi 'Magna Graecia' di Catanzaro = University of Catanzaro (UMG), Università degli Studi del Molise = University of Molise (UNIMOL), Università degli studi di Verona = University of Verona (UNIVR), and Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA)

Subjects
Adult, Genetic Markers, Male, systemic sclerosis, [SDV]Life Sciences [q-bio], CD2 Antigens, Polymorphism, Single Nucleotide, White People, polymorphism, sclérose, polymorphisme génétique, Gene Frequency, Risk Factors, sclerosis, autoimmunité, Odds Ratio, Humans, genetic polymorphism, Genetic Predisposition to Disease, genetics, skin and connective tissue diseases, Genetic Association Studies, Aged, Scleroderma, Systemic, [ SDV ] Life Sciences [q-bio], integumentary system, autoimmunity, Middle Aged, CD2, Phenotype, Haplotypes, Italy, Case-Control Studies, Female, France
Abstract

Systemic sclerosis (SSc) is a rare autoimmune disease (AID) with a complex genetic etiology. Evidence for a shared pathogenesis across AIDs is given by the well-known pleiotropism of autoimmune genes. Recently, several unbiased approaches have identified an association between polymorphisms of the CD2 gene, and rheumatoid arthritis (RA) susceptibility. The objective of this study was to investigate whether CD2 polymorphisms are associated with SSc. Objective. Systemic sclerosis (SSc) is a rare autoimmune disease (AID) with a complex genetic aetiology. Evidence for a shared pathogenesis across AIDs is given by the well-known pleiotropism of autoimmune genes. Recently, several unbiased approaches have identified an association between polymorphisms of the CD2 gene, and rheumatoid arthritis (RA) susceptibility. The objective of this study was to investigate whether CD2 polymorphisms are associated with SSc.Methods. Two SNPs of CD2, rs624988 and rs798036, were genotyped in a total of 1,786 SSc patients and 2,360 healthy individuals from two European populations (France and Italy). Meta analyses were performed to assess whether an association exists between CD2 polymorphisms or haplotypes and SSc or its main subtypes.Results. The combined analyses revealed an association between the rs624988 A allele and SSc susceptibility: p(adj)=0.023, OR=1.14 (95%CI 1.04-1.25). Single marker analysis did not reveal any association between rs798036 and SSc. Haplotype analysis identified that the A-T haplotype, previously described in RA, was associated with higher susceptibility for SSc (p(adj)=0.029, OR=1.14, 95%CI 1.04-1.25) and with the positive anticentromere antibody sub-group of SSc patients (p(adj)=0.009, OR=1 95%CI 1.07-1.32). Genotype-mRNA expression correlations revealed that the CD2 risk haplotype was associated with decreased CD2 mRNA expression in SSc patients.Conclusion. Our study establishes CD2 as a new susceptibility factor for SSc, in a European Caucasian population, confirming the sharing of autoimmune risk factors by SSc and RA.

Published
2016

5. A regulatory variant in CCR6 is associated with susceptibility to antitopoisomerase-positive systemic sclerosis

Author

Koumakis, E., Bouaziz, M., Dieude, P., Ruiz, B., Riemekasten, G., Airo, P., Muller Nurasyid, M., Cusi, D., Matucci Cerinic, M., Melchers, I., Salvi, E., Strauch, K., Peters, A., Cuomo, G., Hachulla, E., Diot, E., Hunzelmann, N., Caramaschi, P., Riccieri, Valeria, Distler, J. H., Tarner, I., Avouac, J., Letenneur, L., Amouyel, P., Lambert, J. C., Chiocchia, G., Boileau, C., Allanore, Y., Institut Cochin (IC UM3 (UMR 8104 / U1016)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), UMR 1152 Statistique et Génome, Institut National de la Recherche Agronomique (INRA), U699, Institut National de la Santé et de la Recherche Médicale (INSERM), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Leibniz Association, Civil Hospital, Ludwig Maximilians University of Munich, Helmholtz Zentrum für Umweltforschung = Helmholtz Centre for Environmental Research (UFZ), University Hospital, Università degli Studi di Milano [Milano] (UNIMI), Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), University of Freiburg [Freiburg], Munich Heart Alliance, Munich, Germany, Partenaires INRAE, Helmholtz-Zentrum München (HZM), Università degli studi di Napoli Federico II, Université de Lille, Droit et Santé, University of Cologne, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Justus-Liebig-Universität Gießen (JLU), Kerckhoff clinic, U 897, Epidémiologie des maladies chroniques : impact des interactions gène environnement sur la santé des populations, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Université Paris Descartes - Paris 5 (UPD5), Hôpital Ambroise Paré [AP-HP], Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Actelion, Bayer, GlaxoSmithKline, Bristol-Myers Squibb, UCB, Celgene, JB Therapeutics, Boehringer Ingelheim, Novartis, RuiYi, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Statistique et Génome (SG), Institut National de la Recherche Agronomique (INRA)-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), Ludwig-Maximilians University [Munich] (LMU), Università degli Studi di Milano = University of Milan (UNIMI), Università degli Studi di Firenze = University of Florence (UniFI), Helmholtz Zentrum München = German Research Center for Environmental Health, University of Naples Federico II = Università degli studi di Napoli Federico II, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Justus-Liebig-Universität Gießen = Justus Liebig University (JLU), Koumakis, E, Bouaziz, M, Dieudé, P, Ruiz, B, Riemekasten, G, Airo, P, Müller Nurasyid, M, Cusi, D, Matucci Cerinic, M, Melchers, I, Salvi, E, Strauch, K, Peters, A, Cuomo, Giovanna, Hachulla, E, Diot, E, Hunzelmann, N, Caramaschi, P, Riccieri, V, Distler, Jh, Tarner, I, Avouac, J, Letenneur, L, Amouyel, P, Lambert, Jc, Chiocchia, G, Boileau, C, and Allanore, Y.

Subjects
Adult, Male, Receptors, CCR6, Scleroderma, Systemic, antitopoisomerase, Genotype, [SDV]Life Sciences [q-bio], Polymorphism, Single Nucleotide, autoantibodies, genetic regulatory variant, systemic sclerosis, White People, Systemic sclerosi, Humans, Female, Genetic Predisposition to Disease, Alleles, DNA Topoisomerases, Genetic Association Studies, Autoantibodies
Abstract

International audience; Objective: Recognition of the well-known pleiotropism of autoimmune genes supports the concept of a shared pathogenesis across autoimmune diseases such as rheumatoid arthritis (RA) and systemic sclerosis (SSc). Studies have reproducibly demonstrated an association between susceptibility to RA and polymorphisms of the CCR6 gene, a surface marker for Th17 cells, and the causal variant was recently identified. The present study was thus undertaken to investigate whether CCR6 polymorphisms could also be associated with susceptibility to SSc. Methods: Twelve tag single-nucleotide polymorphisms (SNPs) of CCR6, including the known RA-associated SNP rs3093023, were genotyped in a total of 2,411 SSc patients and 7,084 healthy individuals from 3 European populations (France, Italy, and Germany). Meta-analyses of the data were performed to assess whether an association exists between CCR6 polymorphisms and susceptibility to SSc or its main subtypes. Direct sequencing of DNA was performed to ascertain whether the functional dinucleotide polymorphism of CCR6 previously identified in RA (CCR6DNP) was also present in SSc. Results: Combined analyses revealed an association between the rs10946216 SNP and SSc susceptibility (odds ratio [OR] 1.13, 95% confidence interval [95% CI] 1.05-1.21, adjusted P [P-adj] = 0.026). The rs3093023 A allele and rs10946216 T allele were in high linkage disequilibrium, and both were found to confer disease susceptibility in the antitopoisomerase-positive subset of SSc patients (OR 1.27, 95% CI 1.13-1.42, P-adj = 1.5 x 10(-3) and OR 1.32, 95% CI 1.17-1.48, P-adj = 9.0 x 10(-5), respectively, relative to healthy controls). Direct sequencing of the DNA of 78 individuals supported the hypothesis that the regulatory dinucleotide CCR6DNP could be the causal variant in SSc. Conclusion: The results of this study establish CCR6 as a new susceptibility factor for antitopoisomerase-positive SSc, as demonstrated in 3 European Caucasian populations, confirming the notion that SSc and RA could conceivably share autoimmune risk alleles. The results also suggest a potential role of the interleukin-17 pathway in SSc.

Published
2013

6. Preliminary analysis of the Very Early Diagnosis of Systemic Sclerosis (VEDOSS) EUSTAR multicentre study: evidence for puffy fingers as a pivotal sign for suspicion of systemic sclerosis

Author

Minier, T., Guiducci, S., Bellando-Randone, S., Bruni, C., Lepri, G., Czirjak, L., Distler, O., Walker, U. A., Fransen, J., Allanore, Y., Denton, C., Cutolo, M., Tyndall, A., Muller-Ladner, U., Matucci-Cerinic, M., Airo, P., Zingarelli, S., Ananieva, L., Desinova, O., Ancuta, C. M., Belibou, C. I., Avouac, J., Becvar, R., Skacelova, S., Beretta, L., Vigone, B., Caramaschi, P., Sabbagh, D., Carpentier, P., Damjanov, N., Simic-Pasalic, K., Distler, J. H. W., Farge-Bancel, D., Hadj-Khelifa, S., Foti, R., Di Gangi, M., De La Pena Lefebvre, P. G., Hachulla, E., Salvador, M. J., Kayser, C., Camargo, C. Z., Kumanovics, G., Li, M., Xu, D., Marasini, B., Belloli, L., Maurer, B., Mayer, M., Mihai, C., Gherghe, A. M., Riccieri, V., Stefanantoni, K., Salsano, F., Rosato, E., Senecal, J. -L., Koenig, M., Senet, P., Frances, C., Sipek, A., Stankovic, A., Stamenkovic, B., Smith, V., Tarner, I. H., Wiland, P., University of Zurich, and Matucci-Cerinic, Marco

Subjects
Male, Anti-nuclear antibody, Pulmonary Fibrosis, 2745 Rheumatology, Scleroderma, Microscopic Angioscopy, Cohort Studies, Antinuclear, Immunology and Allergy, skin and connective tissue diseases, integumentary system, 10051 Rheumatology Clinic and Institute of Physical Medicine, Middle Aged, Connective tissue disease, Autoantibodies, Disease Activity, Outcomes research, Systemic Sclerosis, Adult, Antibodies, Antinuclear, Early Diagnosis, Female, Fingers, Humans, Raynaud Disease, Scleroderma, Systemic, Skin Ulcer, Telangiectasis, Cohort, 2723 Immunology and Allergy, musculoskeletal diseases, medicine.medical_specialty, Immunology, 610 Medicine & health, General Biochemistry, Genetics and Molecular Biology, Antibodies, Rheumatology, 1300 General Biochemistry, Genetics and Molecular Biology, Internal medicine, medicine, 2403 Immunology, business.industry, Systemic, Autoantibody, medicine.disease, Surgery, stomatognathic diseases, Inflammatory diseases Radboud Institute for Health Sciences [Radboudumc 5], Observational study, business, Rheumatism
Abstract

Item does not contain fulltext OBJECTIVES: The EULAR (European League Against Rheumatism) Scleroderma Trials and Research Group (EUSTAR) has identified preliminary criteria for very early diagnosis of systemic sclerosis (SSc). Our aim was to assess the prevalence of each proposed diagnostic item in a large observational patient cohort with Raynaud's phenomenon (RP). METHODS: Baseline data of 469 RP patients enrolled into the Very Early Diagnosis of Systemic Sclerosis (VEDOSS) cohort are presented. RESULTS: 68% of all RP patients were antinuclear antibody (ANA) positive. ANA+ RP patients more frequently had previous or current puffy fingers (PuFi) (38.5% and 23.3%, p

Published
2014

7. Causes and risk factors for death in systemic sclerosis: a study from the EULAR Scleroderma Trials and Research (EUSTAR) database

Author

Tyndall, A. J., Bannert, B., Vonk, M., Airo, P., Cozzi, F., Carreira, P. E., Bancel, D. F., Allanore, Y., Muller Ladner, U., Distler, O., Iannone, F., Pellerito, R., Pileckyte, M., Miniati, I., Ananieva, L., Gurman, A. B., Damjanov, N., Mueller, A., Valentini, G., Riemekasten, G., Tikly, M., Hummers, L., Henriques, M. J. S., Caramaschi, P., Scheja, A., Rozman, B., Ton, E., Kumanovics, G., Coleiro, B., Feierl, E., Szucs, G., Von Muhlen, C. A., Riccieri, Valeria, Novak, S., Chizzolini, C., Kotulska, A., Denton, C., Coelho, P. C., Kotter, I., Simsek, I., La Pena, D. E., Lefebvre, P. G. D. L. P., Hachulla, E., Seibold, J. R., Rednic, S., Stork, J., Morovic Vergles, J., Walker, U. A., Tyndall, Aj, Bannert, B, Vonk, M, Airò, P, Cozzi, F, Carreira, Pe, Bancel, Df, Allanore, Y, MÜLLER LADNER, U, Distler, O, Iannone, F, Pellerito, R, Pileckyte, M, Miniati, I, Ananieva, L, Gurman, Ab, Damjanov, N, Mueller, A, Valentini, Gabriele, Riemekasten, G, Tikly, M, Hummers, L, Henriques, Mj, Caramaschi, P, Scheja, A, Rozman, B, Ton, E, Kumánovics, G, Coleiro, B, Feierl, E, Szucs, G, VON MÜHLEN, Ca, Riccieri, V, Novak, S, Chizzolini, C, Kotulska, A, Denton, C, Coelho, Pc, Kötter, I, Simsek, I, DE LA PENA LEFEBVRE, Pg, Hachulla, E, Seibold, Jr, Rednic, S, Stork, J, MOROVIC VERGLES, J, and Walker, Ua

Subjects
Lung Diseases, systemic sclreosis, risk factors, Male, Lung Diseases/mortality, Comorbidity, 030204 cardiovascular system & hematology, 0302 clinical medicine, Neoplasms, Epidemiology, Pulmonary fibrosis, Immunology and Allergy, skin and connective tissue diseases, Cause of death, ddc:616, integumentary system, Interstitial lung disease, Sepsis/mortality, Middle Aged, Prognosis, 3. Good health, Pneumonia/mortality, Cohort, Female, Neoplasms/mortality, Gastrointestinal Hemorrhage, Scleroderma, Systemic/*mortality, Adult, medicine.medical_specialty, Heart Diseases, Immunology, Auto-immunity, transplantation and immunotherapy [N4i 4], General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Rheumatology, Sepsis, Internal medicine, medicine, Humans, Gastrointestinal Hemorrhage/mortality, Risk factor, Health care ethics [NCEBP 5], Aged, 030203 arthritis & rheumatology, Scleroderma, Systemic, business.industry, Proportional hazards model, Heart Diseases/mortality, Pneumonia, medicine.disease, Surgery, Evaluation of complex medical interventions [NCEBP 2], Heart failure, business, Epidemiologic Methods
Abstract

Item does not contain fulltext OBJECTIVES: To determine the causes and predictors of mortality in systemic sclerosis (SSc). METHODS: Patients with SSc (n=5860) fulfilling the American College of Rheumatology criteria and prospectively followed in the EULAR Scleroderma Trials and Research (EUSTAR) cohort were analysed. EUSTAR centres completed a structured questionnaire on cause of death and comorbidities. Kaplan-Meier and Cox proportional hazards models were used to analyse survival in SSc subgroups and to identify predictors of mortality. RESULTS: Questionnaires were obtained on 234 of 284 fatalities. 55% of deaths were attributed directly to SSc and 41% to non-SSc causes; in 4% the cause of death was not assigned. Of the SSc-related deaths, 35% were attributed to pulmonary fibrosis, 26% to pulmonary arterial hypertension (PAH) and 26% to cardiac causes (mainly heart failure and arrhythmias). Among the non-SSc-related causes, infections (33%) and malignancies (31%) were followed by cardiovascular causes (29%). Of the non-SSc-related fatalities, 25% died of causes in which SSc-related complications may have participated (pneumonia, sepsis and gastrointestinal haemorrhage). Independent risk factors for mortality and their HR were: proteinuria (HR 3.34), the presence of PAH based on echocardiography (HR 2.02), pulmonary restriction (forced vital capacity below 80% of normal, HR 1.64), dyspnoea above New York Heart Association class II (HR 1.61), diffusing capacity of the lung (HR 1.20 per 10% decrease), patient age at onset of Raynaud's phenomenon (HR 1.30 per 10 years) and the modified Rodnan skin score (HR 1.20 per 10 score points). CONCLUSION: Disease-related causes, in particular pulmonary fibrosis, PAH and cardiac causes, accounted for the majority of deaths in SSc. 01 oktober 2010

Published
2010

8. Prediction of worsening of skin fibrosis in patients with diffuse cutaneous systemic sclerosis using the EUSTAR database

Author

Maurer, B., Graf, N., Michel, B. A., Muller Ladner, U., Czirjak, L., Denton, C. P., Tyndall, A., Metzig, C., Lanius, V., Khanna, D., Distler, O., Arner, I. H., Cerinic, M. M., Guiducci, S., Walker, U., Lapadula, G., Iannone, F., Becvar, R., Sierakowsky, S., Bielecka, O. K., Cutolo, M., Sulli, A., Valentini, G., Cuomo, G., Vettori, S., Riemekasten, G., Rednic, S., Nicoara, I., Kahan, A., Allanore, Y., Vlachoyiannopoulos, P., Montecucco, C., Caporali, R., Carreira, P. E., Novak, S., Varju, C., Chizzolini, C., Kucharz, E. J., Kotulska, A., Kopec Medrek, M., Widuchowska, M., Cozzi, F., Rozman, B., Mallia, C., Coleiro, B., Gabrielli, A., Farge, D., Hij, A., Airo, P., Hesselstrand, R., Scheja, A., Wollheim, F., Martinovic, D., Gurman, A. B., Braun Moscovici, Y., Govoni, Marcello, LO MONACO, Andrea, Hunzelmann, N., Pellerito, R., Bambara, L. M., Caramaschi, P., Black, C., Damjanov, N., Santamaria, V. O., Heitmann, S., Krasowska, D., Seidel, M., Oleszowsky, M., Burkhardt, H., Himsel, A., Salvador, M. J., Stamenkovic, B., Stankovic, A., Tikly, M., Starovoytova, M. N., Ananieva, L. P., Scorza, R., Engelhart, M., Strauss, G., Nielsen, H., Damgaard, K., Szucs, G., Mendoza, A. Z., Buijdos, C. d. l. P., Sifuentes Giraldo, W. A., Midtvedt, O., Garen, T., Hachulla, E., Launay, D., Valesini, G., Riccieri, V., Ionescu, R. M., Opris, D., Groseanu, L., Wigley, F. M., Mihai, C. M., Cornateanu, R. S., Ionitescu, R., Gherghe, A. M., Gorga, M., Dobrota, R., Bojinca, M., Schett, G., Distler, J. H., Meroni, P., Zeni, P., Mouthon, L., Keyser, F. D., Cantatore, F. P., Corrado, A., Ullman, S., Iversen, L., Pozzi, M. R., Eyerich, K., Hein, R., Knott, E., Szechinski, J., Wiland, P., Szmyrka Kaczmarek, M., Sokolik, R., Morgiel, E., Krummel Lorenz, B., Saar, P., Aringer, M., Gunther, C., Anic, B., Baresic, M., Mayer, M., Radominski, S. C., Muller, C. d. S., Azevedo, V. F., Agachi, S., Groppa, L., Chiaburu, L., Russu, E., Zenone, T., Highton, J., Stamp, L., Chapman, P., O'Donnell, J., Solanki, K., Doube, A., Veale, D., O'Rourke, M., Loyo, E., Li, M., Rosato, E., Pisarri, S., Tanaseanu, C. M., Popescu, M., Dumitrascu, A., Tiglea, I., Chirieac, R., Ancuta, C., Furst, D. E., Kafaja, S., Lefebvre, P. G. d. l. P., Rubio, S. R., Exposito, M. V., Sibilia, J., Chatelus, E., Gottenberg, J. E., Chifflot, H., Litinsky, I., Venalis, A., Butrimiene, I., Venalis, P., Rugiene, R., Karpec, D., Kerzberg, E., Montoya, F., Cosentino, V., Chizzolini, Carlo, Maurer, Britta, Graf, Nicole, Michel, Beat A, Müller Ladner, Ulf, Czirják, László, Denton, Christopher P, Tyndall, Alan, Metzig, Carola, Lanius, Vivian, Khanna, Dinesh, Distler, Oliver, Tarner, Ingo H, Cerinic, Marco Matucci, Guiducci, Serena, Walker, Ulrich, Lapadula, Giovanni, Iannone, Florenzo, Becvar, Radim, Sierakowsky, Stanislaw, Bielecka, Otylia Kowal, Cutolo, Maurizio, Sulli, Alberto, Valentini, Gabriele, Cuomo, Giovanna, Vettori, Serena, Riemekasten, Gabriele, Rednic, Simona, Nicoara, Ileana, Kahan, André, Allanore, Yannick, Vlachoyiannopoulos, P, Montecucco, Carlomaurizio, Caporali, Roberto, Carreira, Patricia E, Novak, Srdan, Varju, Cecilia, Kucharz, Eugene J, Kotulska, Anna, Kopec Medrek, Magdalena, Widuchowska, Malgorzata, Cozzi, Franco, Rozman, Blaz, Mallia, Carmel, Coleiro, Bernard, Gabrielli, Armando, Farge, Dominique, Hij, Adrian, Airò, Paolo, Hesselstrand, Roger, Scheja, Agneta, Wollheim, Frank, Martinovic, Duska, Gurman, Alexandra Balbir, Braun Moscovici, Yolanda, Govoni, M, Monaco, Andrea Lo, Hunzelmann, Nicola, Pellerito, Raffaele, Bambara, Lisa Maria, Caramaschi, Paola, Black, Carol, Damjanov, Nemanja, Santamaria, Vera Ortiz, Heitmann, Stefan, Krasowska, Dorota, Seidel, Matthia, Oleszowsky, Mara, Burkhardt, Harald, Himsel, Andrea, Salvador, Maria J, Stamenkovic, Bojana, Stankovic, Aleksandra, Tikly, Mohammed, Starovoytova, Maya N, Ananieva, Lidia P, Scorza, Raffaella, Engelhart, Merete, Strauss, Gitte, Nielsen, Henrik, Damgaard, Kirsten, Szücs, Gabriella, Mendoza, Antonio Zea, Buijdos, Carlos de la Puente, Giraldo, Walter A. Sifuente, Midtvedt, Øyvind, Garen, Torhild, Hachulla, Eric, Launay, David, Valesini, Guido, Riccieri, Valeria, Ionescu, Ruxandra Maria, Opris, Daniela, Groseanu, Laura, Wigley, Fredrick M, Mihai, Carmen M, Cornateanu, Roxana Sfrent, Ionitescu, Razvan, Gherghe, Ana Maria, Gorga, Marilena, Dobrota, Rucsandra, Bojinca, Mihai, Schett, Georg, Distler, Jörg HW, Meroni, Pierluigi, Zeni, Silvana, Mouthon, Luc, Keyser, Filip De, Cantatore, Francesco P, Corrado, Ada, Ullman, Susanne, Iversen, Line, Pozzi, Maria R, Eyerich, Kilian, Hein, Rüdiger, Knott, Elisabeth, Szechinski, Jacek, Wiland, Piotr, Szmyrka Kaczmarek, Magdalena, Sokolik, Renata, Morgiel, Ewa, Krummel Lorenz, Brigitte, Saar, Petra, Aringer, Martin, Günther, Claudia, Anic, Branimir, Baresic, Marko, Mayer, Miroslav, Radominski, Sebastião C, Müller, Carolina de Souza, Azevedo, Valderílio F, Agachi, Svetlana, Groppa, Liliana, Chiaburu, Lealea, Russu, Eugen, Zenone, Thierry, Highton, John, Stamp, Lisa, Chapman, Peter, O'Donnell, John, Solanki, Kamal, Doube, Alan, Veale, Dougla, O’Rourke, Marie, Loyo, Esthela, Li, Mengtao, Rosato, Edoardo, Pisarri, Simonetta, Tanaseanu, Cristina Mihaela, Popescu, Monica, and University of Zurich

Subjects
Genetics and Molecular Biology (all), Male, Time Factors, Databases, Factual, systemic sclerosis, 2745 Rheumatology, computer.software_genre, Biochemistry, Severity of Illness Index, Outcomes Research, Qualitative Research, Systemic Sclerosis, Adult, Cohort Studies, Creatine Kinase, Decision Support Techniques, Deglutition Disorders, Dyspnea, Female, Fibrosis, Humans, Logistic Models, Middle Aged, Multivariate Analysis, Scleroderma, Diffuse, Sex Factors, Skin, Synovitis, Disease Progression, Rheumatology, Immunology, Biochemistry, Genetics and Molecular Biology (all), Immunology and Allergy, Medicine (all), Scleroderma, skin fibrosis, skin and connective tissue diseases, ddc:616, EUSTAR, Univariate analysis, Database, integumentary system, 10051 Rheumatology Clinic and Institute of Physical Medicine, Orvostudományok, Diffuse, Connective tissue disease, Cohort, 2723 Immunology and Allergy, Cohort study, medicine.medical_specialty, 610 Medicine & health, Klinikai orvostudományok, General Biochemistry, Genetics and Molecular Biology, NO, outcomes research, qualitative research, Databases, 1300 General Biochemistry, Genetics and Molecular Biology, Internal medicine, Severity of illness, medicine, Factual, 2403 Immunology, business.industry, medicine.disease, business, computer
Abstract

ObjectivesTo identify predictive parameters for the progression of skin fibrosis within 1 year in patients with diffuse cutaneous SSc (dcSSc).MethodsAn observational study using the EUSTAR database was performed. Inclusion criteria were dcSSc, American College of Rheumatology (ACR) criteria fulfilled, modified Rodnan skin score (MRSS) ≥7 at baseline visit, valid data for MRSS at 2nd visit, and available follow-up of 12±2 months. Worsening of skin fibrosis was defined as increase in MRSS >5 points and ≥25% from baseline to 2nd visit. In the univariate analysis, patients with progressive fibrosis were compared with non-progressors, and predictive markers with pResultsA total of 637 dcSSc patients were eligible. Univariate analyses identified joint synovitis, short disease duration (≤15 months), short disease duration in females/patients without creatine kinase (CK) elevation, low baseline MRSS (≤22/51), and absence of oesophageal symptoms as potential predictors for progressive skin fibrosis. In the multivariate analysis, by employing combinations of the predictors, 17 models with varying prediction success were generated, allowing cohort enrichment from 9.7% progressive patients in the whole cohort to 44.4% in the optimised enrichment cohort. Using a second validation cohort of 188 dcSSc patients, short disease duration, low baseline MRSS and joint synovitis were confirmed as independent predictors of progressive skin fibrosis within 1 year resulting in a 4.5-fold increased prediction success rate.ConclusionsOur study provides novel, evidence-based criteria for the enrichment of dcSSc cohorts with patients who experience worsening of skin fibrosis which allows improved clinical trial design.

Published
2014

9. Clinical risk assessment of organ manifestations in systemic sclerosis: a report from the EULAR Scleroderma Trials And Research group database

Author

Walker U. A., Tyndall A., Czirják L, Denton C. ., Farge Bancel D., Kowal Bielecka O., Müller Ladner U., Bocelli Tyndall C., Matucci Cerinic M., Riemekasten G. ., Brückner C. ., Airó P. ., Scarsi M. ., Scorza R. ., Beretta L. ., Cozzi F. ., Tiso F., Vonk Mc M. C., Hoogen Van Den, Fhj F. H. J., Wigley Fm F. M., Hummers L. ., Nevskaya T. ., Ananieva L. ., Miniati I. ., Tartaglia N. ., Lomater C. ., Balbir Gurman A. ., Braun Moscovici Y. ., Bambara Lm L. M., Caramaschi P. ., Ruocco L. ., Krieg T. ., Hunzelmann N. ., Varjú C. ., Carriera Pe P. E., Joven B. ., Iannone F. ., Lapadula G. ., Kahan A. ., Allanore Y. ., Gabrielli A. ., Imperatore M. ., Scheja A. ., Wollheim F. ., Damjanov N. ., Ostojic P. ., Saar P. ., Tarner Ih I. H., Kötter I. ., Bombardieri S. ., Bazzichi L. ., Papa Del N. ., Comina Dp D. P., Monaco Lo A. ., Corte La R. ., Hachulla E. ., Launay D. ., Distler O. ., Ciurea A. ., Sierakowski S. ., Mitchell H. ., Silver Rm R. M., Krasowska D. ., Michalska Jakubus M. ., Tikly M. ., Aboo N. ., Worm M. ., Klaus P. ., Rovenský J. ., Lukáčová O. ., Rozman B. ., Sipek A. ., Clemente Coelho P. ., Shoenfeld Y. ., Langewitch P. ., José Da Silva Ap A. P., Salvador Mj M. J., Kuhn A. ., Erdmann G. ., Bečvář R. ., Friedl E. ., Graninger W. ., Riccieri V. ., Caporali R. ., Montecucco C. ., Vlachoyiannopoulos P. ., Distler M. ., Reich K. ., Majdan M. ., Wielosz E. ., Rednic S. ., Laar Van Jm J. M., Heitmann S. ., Bruckner A. ., Himsel A. ., Riemann J. ., Meyringer R. ., Müller A. ., Martinovic D. ., Radic M. ., Sticherling M. ., Szekanecz Z. ., Szücs G. ., Giacomelli R. ., Marrelli A. ., Stamenkovic B. ., Stankovic A. ., Aringer M. ., Smolen Js J. S., Kucharz Ej E. J., Kotulska At A. T., Jablonska S. ., Blasczik M. ., Jun J. B. J. B., Mallia C. ., Coleiro B. ., Santamaria Vo V. O., Hinrichs R. ., Nielsen H. ., Cossutta R. ., Ionescu R. ., Opris D. ., Steinbrink K. ., Grundt B. ., Bajocchi G. ., Jiří Š. ., Lefebvre Pgdlp P. G. D. L. P., Mendoza ZeaAc A. C., Ribi C. ., Chizzolini C. ., Wisłowska M. ., Novak S. ., Indiveri F. ., Jacobsen S. ., Frandsen Pb P. B., Gorska Iz I. Z., Gran Tore J. ., Midtvedt Ø. ., Ramos Fo F. O., Rajcevska Ld L. D., Bozinovski G. ., Schöffel D. ., Sunderkötter C. ., Böhm M. ., Morović Vergles J. ., Čulo M. I. M. I., Cutolo M. ., Sulli A. ., Derk Ct C. T., Jimenez Sa S. A., Siakka P. ., Søndergaard K. ., Stengaard Pedersen K. ., Cabane J. ., Tiev Kp K. P., Mihai C. ., Sfrent Cornateanu R. ., Jendro M. ., Tuvik P. ., Antivalle M. ., Randisi G. ., Seidel M. ., Clarenbach R. ., Simsek I. ., Dinc A. ., Inanc M. ., Capraru Ms M. S., Capraru D. ., Bañegil I. ., Richter J. ., Alhasani S. ., Földvari I. ., Pinto S. ., Brandão F. ., VALENTINI, Gabriele, Walker, U. A., Tyndall, A., Czirják, L, Denton, C. ., Farge Bancel, D., Kowal Bielecka, O., Müller Ladner, U., Bocelli Tyndall, C., Matucci Cerinic, M., Riemekasten, G. ., Brückner, C. ., Airó, P. ., Scarsi, M. ., Scorza, R. ., Beretta, L. ., Cozzi, F. ., Tiso, F., Vonk Mc, M. C., Hoogen Van, Den, Fhj, F. H. J., Wigley Fm, F. M., Hummers, L. ., Nevskaya, T. ., Ananieva, L. ., Miniati, I. ., Tartaglia, N. ., Lomater, C. ., Balbir Gurman, A. ., Braun Moscovici, Y. ., Bambara Lm, L. M., Caramaschi, P. ., Valentini, Gabriele, Ruocco, L. ., Krieg, T. ., Hunzelmann, N. ., Varjú, C. ., Carriera Pe, P. E., Joven, B. ., Iannone, F. ., Lapadula, G. ., Kahan, A. ., Allanore, Y. ., Gabrielli, A. ., Imperatore, M. ., Scheja, A. ., Wollheim, F. ., Damjanov, N. ., Ostojic, P. ., Saar, P. ., Tarner Ih, I. H., Kötter, I. ., Bombardieri, S. ., Bazzichi, L. ., Papa Del, N. ., Comina Dp, D. P., Monaco Lo, A. ., Corte La, R. ., Hachulla, E. ., Launay, D. ., Distler, O. ., Ciurea, A. ., Sierakowski, S. ., Mitchell, H. ., Silver Rm, R. M., Krasowska, D. ., Michalska Jakubus, M. ., Tikly, M. ., Aboo, N. ., Worm, M. ., Klaus, P. ., Rovenský, J. ., Lukáčová, O. ., Rozman, B. ., Sipek, A. ., Clemente Coelho, P. ., Shoenfeld, Y. ., Langewitch, P. ., José Da Silva Ap, A. P., Salvador Mj, M. J., Kuhn, A. ., Erdmann, G. ., Bečvář, R. ., Friedl, E. ., Graninger, W. ., Riccieri, V. ., Caporali, R. ., Montecucco, C. ., Vlachoyiannopoulos, P. ., Distler, M. ., Reich, K. ., Majdan, M. ., Wielosz, E. ., Rednic, S. ., Laar Van Jm, J. M., Heitmann, S. ., Bruckner, A. ., Himsel, A. ., Riemann, J. ., Meyringer, R. ., Müller, A. ., Martinovic, D. ., Radic, M. ., Sticherling, M. ., Szekanecz, Z. ., Szücs, G. ., Giacomelli, R. ., Marrelli, A. ., Stamenkovic, B. ., Stankovic, A. ., Aringer, M. ., Smolen Js, J. S., Kucharz Ej, E. J., Kotulska At, A. T., Jablonska, S. ., Blasczik, M. ., Jun, J. B. J. B., Mallia, C. ., Coleiro, B. ., Santamaria Vo, V. O., Hinrichs, R. ., Nielsen, H. ., Cossutta, R. ., Ionescu, R. ., Opris, D. ., Steinbrink, K. ., Grundt, B. ., Bajocchi, G. ., Jiří, Š. ., Lefebvre Pgdlp, P. G. D. L. P., Mendoza ZeaAc, A. C., Ribi, C. ., Chizzolini, C. ., Wisłowska, M. ., Novak, S. ., Indiveri, F. ., Jacobsen, S. ., Frandsen Pb, P. B., Gorska Iz, I. Z., Gran Tore, J. ., Midtvedt, Ø. ., Ramos Fo, F. O., Rajcevska Ld, L. D., Bozinovski, G. ., Schöffel, D. ., Sunderkötter, C. ., Böhm, M. ., Morović Vergles, J. ., Čulo, M. I. M. I., Cutolo, M. ., Sulli, A. ., Derk Ct, C. T., Jimenez Sa, S. A., Siakka, P. ., Søndergaard, K. ., Stengaard Pedersen, K. ., Cabane, J. ., Tiev Kp, K. P., Mihai, C. ., Sfrent Cornateanu, R. ., Jendro, M. ., Tuvik, P. ., Antivalle, M. ., Randisi, G. ., Seidel, M. ., Clarenbach, R. ., Simsek, I. ., Dinc, A. ., Inanc, M. ., Capraru Ms, M. S., Capraru, D. ., Bañegil, I. ., Richter, J. ., Alhasani, S. ., Földvari, I. ., Pinto, S. ., Brandão, F. ., Ribi, Camillo, and Chizzolini, Carlo

Subjects
Male, Systemic disease, Databases, Factual, Cross-sectional study, Scleroderma, Immunopathology, Immunology and Allergy, Age of Onset, skin and connective tissue diseases, ddc:616, integumentary system, Nuclear Proteins, Orvostudományok, Middle Aged, Connective tissue disease, Extended Report, Raynaud Disease/etiology/immunology, DNA Topoisomerases, Type I, Nuclear Proteins/immunology, Female, Adult, medicine.medical_specialty, Scleroderma, Diffuse/complications/immunology, Immunology, Klinikai orvostudományok, Scleroderma, Systemic/complications/immunology, Risk Assessment, General Biochemistry, Genetics and Molecular Biology, systemic sclerosis, EULAR, risk assessment, Age Distribution, Sex Factors, Rheumatology, Scleroderma, Limited, medicine, Humans, Risk factor, Aged, Autoantibodies, Scleroderma, Systemic, business.industry, Autoantibody, Raynaud Disease, medicine.disease, Dermatology, Cross-Sectional Studies, Scleroderma, Diffuse, Scleroderma, Limited/complications/immunology, Age of onset, business, Autoantibodies/blood
Abstract

Background: Systemic sclerosis (SSc) is a multisystem autoimmune disease which is classified into a diffuse cutaneous (dcSSc) and a limited cutaneous (lcSSc) subset according to the skin involvement. In order to better understand the vascular, immunological and fibrotic processes of SSc and to guide its treatment the EULAR Scleroderma Trials And Research (EUSTAR) group was formed in June 2004. Aims and Methods: EUSTAR collects prospectively the Minimal Essential Data Set (MEDS) on all sequential patients fulfilling the ACR diagnostic criteria in participating centres. We aimed to characterize demographic, clinical and laboratory characteristics of disease presentation in SSc and analysed EUSTAR baseline visits. Results: In April 2006, a total of 3656 patients (1349 with dcSSc and 2101 with lcSSc) were enrolled in 102 centres and 30 countries. 1330 individuals had autoantibodies against Scl70 and 1106 against anticentromere antibodies. 87% of patients were female. On multivariate analysis, scleroderma subsets (dcSSc vs. lcSSc), antibody status and age at onset of Raynaud’s phenomenon, but not gender were independently associated with the prevalence of organ manifestations. Autoantibody status in this analysis appeared more closely associated with clinical manifestations than were SSc subsets. Conclusion: dcSSc and lcSSc subsets are associated with particular organ manifestations, but in this analysis the clinical distinction appeared superseded by an antibody based classification in predicting some scleroderma complications. The EUSTAR MEDS data base facilitates the analysis of clinical patterns in SSc and contributes to the standardised assessment and monitoring of SSc internationally.

Published
2007

10. Homocysteine plasma concentration is related to severity of lung impairment in scleroderma

Author

Caramaschi, P., Nicola Martinelli, Biasi, D., Carletto, A., Faccini, G., Volpe, A., Ferrari, M., Scambi, C., and Bambara, L. M.

Subjects
Adult, Aged, 80 and over, Lung Diseases, Male, Scleroderma, Systemic, Systemic, Hyperhomocysteinemia, blood/complications/diagnosis, Middle Aged, Severity of Illness Index, Scleroderma, Adult, Aged, Aged, 80 and over, Female, Homocysteine, blood, Humans, Hyperhomocysteinemia, blood/complications/diagnosis, Lung Diseases, blood/diagnosis/etiology, Male, Middle Aged, Scleroderma, blood/complications/diagnosis, Severity of Illness Index, blood/diagnosis/etiology, blood, 80 and over, Humans, Female, Homocysteine, Aged
Abstract

To investigate the correlation between plasma concentration of total homocysteine and pulmonary involvement in patients with limited or diffuse scleroderma (systemic sclerosis, SSc).Seventy-one patients with scleroderma were divided into 3 groups based on pulmonary involvement: Group A comprised patients without lung involvement (9 cases); Group B patients with lung involvement of mild and moderate stages (44 cases); and Group C patients with lung involvement of severe stage and endstage (18 cases). At the time of evaluation of lung involvement all patients underwent determination of plasma homocysteine concentration. Homocysteine concentration was also measured in 30 healthy controls homogeneous for sex and age.In patients with scleroderma the homocysteine concentration was significantly higher than in controls (11.1 and 6.9 micromol/l, respectively; p0.001). We found a significant association between plasma homocysteine concentration and severity of lung involvement that was not modified by correction for age, time from the diagnosis, type of scleroderma pattern, and serum creatinine and folate levels. Homocysteine concentration progressively increases in scleroderma patients with more severe pulmonary involvement. Subjects with high homocysteine concentration (i.e.,or = 75th percentile of homocysteine concentration in patients with scleroderma without lung involvement) were mostly present in the group with the greatest lung involvement.High level of homocysteinemia is associated with an increased risk of pulmonary disease in patients with scleroderma. We hypothesize that hyperhomocysteinemia may worsen injury of the endothelium, a key lesion in scleroderma disease, favoring the development of lung involvement. Our data support the hypothesis that homocysteine could be involved in the pathogenetic process of scleroderma pulmonary involvement.

Published
2003

11. [High prevalence of hepatitis C virus infection in patients with non-Hodgkin's lymphoma at the onset. Preliminary results of an Italian multicenter study]

Author

Catassi, C., Fabiani, E., Coppa, G. V., Gabrielli, A., Centurioni, R., Leoni, P., Barbato, M., Viola, F., Martelli, M., Renzo, A., Rotoli, B., Bertolani, P., Federico, M., antonio carroccio, Iannitto, E., Baldassarre, M., Guarini, A., Guariso, G., Favaretto, G., Caramaschi, P., and Ambrosetti, A.

Subjects
Adult, Aged, 80 and over, Male, Time Factors, Adolescent, Lymphoma, Non-Hodgkin, Enzyme-Linked Immunosorbent Assay, Hepacivirus, Hepatitis C Antibodies, Middle Aged, Hepatitis C, Polymerase Chain Reaction, Cross-Sectional Studies, Italy, Risk Factors, Case-Control Studies, Humans, RNA, Viral, Female, Aged
Abstract

143 patients with non-Hodgkin lymphoma (NHL) at the onset entered this perspective study on NHL-associated risk factors. They were 87 males and 56 females with a mean age of 52.3 years (range 14.6-82.3). An associated hepatitis C virus (HCV) infection was found in 16 of the 143 NHL cases (11.2%; 95% CI 6.5-17.5). They were 11 males and 5 females [mean age 59.9] year with disseminated (13/16) or localized NHL disease (3/16)]. The NHL histological subgroup was low grade (6/16), intermediate grade (2/16) or high grade (8/16). The cell origin was B in 15/16 cases and B cell-T cell rich in 1/16. The discovery of HCV infection was contemporary to lymphoma diagnosis in 6/16 cases but preceded the NHL onset in the other 10 patients. In these 10 patients the median time between HCV infection diagnosis and NHL onset was 3.6 years (range 1-14.5). These data confirm that in Italy the prevalence of HCV infection in patients with NHL (11.2%) is significantly higher than expected in the general population (1.3-3.2%). The finding that, in most cases, HCV infection was definitely antecedent to NHL onset, usually by years, adds evidence to the possible causative role of the HCV in lymphomagenesis.

Published
1998

12. Neutrophil functions, spondylarthropathies and HLA-B27: a study of 43 patients

Author

Biasi, Domenico, Carletto, A., Caramaschi, P., Bellavite, Paolo, Andrioli, G., Caraffi, M., Pacor, Maria Luisa, and Bambara, Lisa Maria

Subjects
Adult, Male, HLA-B27, Neutrophils, Middle Aged, Arthritis, Reactive, Cell Movement, Superoxides, Cell Adhesion, Humans, Female, Spondylitis, Ankylosing, spondylarthropathies, Neutrophil functions, HLA-B27 Antigen, Retrospective Studies
Abstract

Several hypotheses have been proposed regarding the role of HLA-B27 antigen in the pathogenesis of the spondylarthropathies.We studied some neutrophil functions in vivo in patients affected by ankylosing spondylitis or by reactive arthritis, with or without HLA-B27, and in healthy control subjects. In vivo neutrophil migration was investigated by Senn's skin window technique. An adhesion assay was also conducted and superoxide production was measured in circulating and migrating neutrophils after different stimuli.Neutrophil migration in vivo was higher in the HLA-B27 positive patients than in the controls, while no difference was found between the HLA-B27 negative patients and controls. Our data showed an increased response to formyl-methionyl-leucyl-phenylalanine by circulating neutrophils in the patients with ankylosing spondylitis, both HLA-B27 positive and negative, in comparison with all the other subjects.Our results revive the question of the role of HLA-B27 in the regulation of neutrophil migration; the reported in vivo priming of circulating neutrophils seems to be related to ankylosing spondylitis rather than to HLA-B27.

Published
1995

13. An observational cohort study of patients with newly diagnosed digital ulcer disease secondary to systemic sclerosis registered in the EUSTAR database

Author

Brand, M., Hollaender, R., Rosenberg, D., Scott, M., Hunsche, E., Tyndall, A., Denaro, V., Patricia E Carreira, Varju, C., Gabrielli, B., Zingarelli, S., Caramaschi, P., Simic-Pasalic, K., Müller-Ladner, U., Vasile, M., Mihai, C., Rosato, E., Vacca, A., Zenone, T., Mohamed, W. A., Ancuta, C., Zampogna, G., Rednic, S., Jabaar, N., Belloli, L., Pozzi, M. R., Foti, R., and Walker, U. A.

Subjects
Adult, Male, Scleroderma, Systemic, Time Factors, Databases, Factual, Hypertension, Pulmonary, Incidence, Middle Aged, Prognosis, Activities of Daily Living, Cost of Illness, Europe, Female, Fingers, Hospitalization, Humans, Logistic Models, Odds Ratio, Prospective Studies, Quality of Life, Recurrence, Risk Factors, Skin Ulcer
Abstract

This study describes clinical characteristics, prognostic factors, and quality of life in patients with newly diagnosed (incident) digital ulcers (DU).Observational cohort study of 189 consecutive SSc patients with incident DU diagnosis identified from the EUSTAR database (22 centres in 10 countries). Data were collected from medical charts and during one prospective visit between 01/2004 and 09/2010.Median age at DU diagnosis was 51 years, majority of patients were female (88%), and limited cutaneous SSc was the most common subtype (61%). At incident DU diagnosis, 41% of patients had one DU and 59% had ≥2 DU; at the prospective visit 52% had DU. Pulmonary arterial hypertension (PAH) and multiple DU at diagnosis were associated with presence of any DU at the prospective visit (odds ratios: 4.34 and 1.32). During the observation period (median follow-up was 2 years) 127 patients had ≥1 hospitalisation. The event rate of new DU per person-year was 0.66, of DU-associated complications was 0.10, and of surgical or diagnostic procedures was 0.12. At the prospective visit, patients with ≥1 DU reported impairment in daily activities by 57%, those with 0 DU by 37%. The mean difference between patients with or without DU in the SF-36 physical component was 2.2, and in the mental component 1.4. DU patients were not routinely prescribed endothelin receptor antagonists or prostanoids.This real world cohort demonstrates that DU require hospital admission, and impair daily activity. PAH and multiple DU at diagnosis were associated with future occurrence of DU.

14. Surfactant protein D and KL-6 serum levels in systemic sclerosis: Correlation with lung and systemic involvement

Author

Francesco Bonella, Volpe, A., Caramaschi, P., Nava, C., Ferrari, P., Schenk, K., Ohshimo, S., Costabel, U., and Ferrari, M.

Subjects
Male, Scleroderma, Systemic, Pulmonary Fibrosis, Mucin-1, Medizin, Enzyme-Linked Immunosorbent Assay, Middle Aged, Prognosis, Pulmonary Surfactant-Associated Protein D, Severity of Illness Index, Respiratory Function Tests, lung, pneumoproteins, Humans, Systemic sclerosis, Female, Biomarkers, Autoantibodies, Follow-Up Studies
Abstract

The aim of this study was to investigate the relationship between SP-D and KL-6 serum concentrations and the extent of interstitial lung involvement, as measured by a quantitative HRCT score and the functional impairment, in patients with systemic sclerosis (SSc). Moreover we analysed the association between these lung-specific biomarkers and skin involvement, anti-Scl-70 antibody titres and an index of disease activity.Serum SP-D, KL-6 and anti-Scl-70 concentrations were determined by ELISA in 25 SSc patients. Disease activity and lung function parameters were assessed, and the extent of ILD was measured by a HRCT score.SP-D and KL-6 concentrations were higher in patients with SSc and lung fibrosis than in healthy controls. KL-6 correlated positively with the HRCT-fibrosis score (r=0.68, p0.001), SP-D showed a weaker correlation (r=0.44, p=0.025). Increased KL-6 concentrations were associated with decreased DLCO and decreased FVC in SSc patients, SP-D showed no association. Furthermore KL-6, but not SP-D, showed a strong association with skin involvement as expressed by the modified Rodnan skin score (r=0.71, p0.0001) and a disease activity index (r=0.73, p0.0001).KL-6 is more strongly associated than SP-D with the HRCT-fibrosis score, and, different from SP-D, it correlates with skin involvement and disease activity. We suggest that KL-6 may be a useful biomarker in the assessment of scleroderma patients.

15. Clinical determinants of elevated systolic pulmonary artery pressure measured by transthoracic Doppler echocardiography in early systemic sclerosis

Author

Patricia E Carreira, Carmona, L., Joven, B. E., Loza, E., Andreu, J. L., Riemekasten, G., Vettori, S., Allanore, Y., Balbir-Gurman, A., Airò, P., Walker, U. A., Damjanov, N., Ananieva, L. P., Rednic, S., Czirják, L., Distler, O., Farge, D., Hesselstrand, R., Corrado, A., Caramaschi, P., Tikly, M., Matucci-Cerinic, M., Carreira, Patricia E., Carmona, Loreto, Joven, Beatriz E., Loza, Estibaliz, Andreu, Josã© Lui, Riemekasten, Gabriela, Vettori, Serena, Allanore, Yannick, Balbir gurman, Alexandra, Airã², Paolo, Walker, Ulrich A., Damjanov, Nemanja, Ananieva, Lidia P., Rednic, Simona, Czirjã¡k, Lã¡szlã³, Distler, Oliver, Farge, Dominique, Hesselstrand, Roger, Corrado, Ada, Caramaschi, Paola, Tikly, Mohammed, and Matucci cerinic, Marco

Subjects
Adult, Male, Scleroderma, Systemic, Systole, Immunology, Middle Aged, Pulmonary Artery, Pulmonary arterial hypertension, Echocardiography, Doppler, Systemic sclerosi, Cross-Sectional Studies, Logistic Models, Rheumatology, Right heart catheterisation, Echocardiography, Immunology and Allergy, Humans, Female, Aged
Abstract

Objective. To explore the prevalence and clinical associations of elevated systolic pulmonary artery pressure (sPAP), measured by Transthoracic Dopplerechocardiography (TTE) in patients with early systemic sclerosis (SSc). Methods. A cross-sectional analysis of the prospective EULAR Scleroderma Trial and Research (EUSTAR) database was performed. SSc patients with < 3 years from the first non-Raynaud's phenomenon (RP) symptom at baseline EUSTAR visit, were selected. Elevated sPAP was defined as sPAP > 40 mmHg on baseline TTE. First visit SSc related variables, including disease subsets, antibodies and visceral involvement, were examined. Results. From 1,188 patients, 81% were women. Mean (SD) age at first non-RP symptom was 50 (14) years, 55% had limited cutaneous SSc (lcSSc) and 42% active disease. Elevated sPAP was found in 17% of patients, both lcSSc and diffuse cutaneous SSc (dc- SSc). In lcSSc, older age at first non- RP symptom, ACA positivity, joint contractures, restrictive defect and lower DLCO, were independently associated with elevated sPAP. In dcSSc, older age at first non-RP symptom, longer time between RP onset and first non-RP symptom, digital ulcers, cardiac blocks, and proteinuria were associated with elevated sPAP. Conclusion. The prevalence of elevated sPAP on TTE in early SSc patients is considerable. Association with cardiac, lung and renal involvement suggests that, although some patients might have pulmonary arterial hypertension, others may present pulmonary hypertension secondary to lung or heart involvement. Our findings emphasise the need to consider right heart catheterisation in selected early SSc patients with PH suspicion, to clearly determine the cause of PH.

16. Risk of Non-Hodgkin Lymphoma in Celiac Disease

Author

Umberto Volta, Pietro Leoni, Amalia De Renzo, Graziella Guariso, Gino Roberto Corazza, E Fabiani, Antonio Carroccio, Mariella Baldassarre, Armando Gabrielli, Paola Caramaschi, Carlo Catassi, P. Bertolani, Maria Barbato, Angelo Michele Carella, Giovanni Corrao, Michele Sozzi, Catassi, C, Fabiani, E, Corrao, G, Barbato, M, De Renzo, A, Carella, A, Gabrielli, A, Leoni, P, Carroccio, A, Baldassarre, M, Bertolani, P, Caramaschi, P, Sozzi, M, Guariso, G, Volta, U, Corazza, G, Catassi, C., Fabiani, E., Corrao, G., Barbato, M., De Renzo, A., Carella, A., Gabrielli, A., Leoni, P., Carroccio, A., Baldassarre, M., Bertolani, P., Caramaschi, P., Sozzi, M., Guariso, G., Volta, U., and Corazza, G.

Subjects
Adult, Male, medicine.medical_specialty, Pathology, Lymphoma, B-Cell, Settore MED/09 - Medicina Interna, Population, Lymphoma, T-Cell, Non-Hodgkin lymphoma, celiac disease, Gastroenterology, Coeliac disease, Risk Factors, immune system diseases, hemic and lymphatic diseases, Internal medicine, Immunopathology, medicine, Humans, T-cell lymphoma, Non-hodgkin disease, education, Mass screening, Aged, Aged, 80 and over, education.field_of_study, business.industry, Lymphoma, Non-Hodgkin, Case-control study, General Medicine, Odds ratio, Middle Aged, medicine.disease, Lymphoma, Case-Control Studies, Female, business
Abstract

CONTEXT: Celiac disease is one of the most common lifelong disorders. Non-Hodgkin lymphoma is a possible complication of celiac disease and may lead to a large portion of lymphoma cases. OBJECTIVE: To quantify the risk for developing non-Hodgkin lymphoma of any primary site associated with celiac disease. DESIGN AND SETTING: Multicenter, case-control study conducted between January 1996 and December 1999 throughout Italy. PATIENTS: Cases were older than 20 years (median, 57; range, 20-92 years) with non-Hodgkin lymphoma of any primary site and histological type and were recruited at the time of the diagnosis. Controls were healthy adults (2739 men and 2981 women) from the general population. MAIN OUTCOME MEASURE: Positive test result for class A serum antiendomysial antibody. RESULTS: Celiac disease was diagnosed in 6 (0.92%) of 653 patients with lymphoma. Of the 6 cases, 3 were of B-cell and 3 were of T-cell origin. Four of 6 cases had lymphoma primarily located in the gut. In the control group, 24 (0.42%) had celiac disease. The odds ratio (adjusted for age and sex) for non-Hodgkin lymphoma of any primary site associated with celiac disease was 3.1 (95% confidence interval [CI], 1.3-7.6), 16.9 (95% CI, 7.4-38.7) for gut lymphoma, and 19.2 (95% CI, 7.9-46.6) for T-cell lymphoma, respectively. The risk for non-Hodgkin lymphoma for the overall population, which was adjusted for age and sex, was 0.63% (95% CI, - 0.12% to 1.37%). CONCLUSION: Celiac disease is associated with an increased risk for non-Hodgkin lymphoma, especially of T-cell type and primarily localized in the gut. However, the association does not represent a great enough risk to justify early mass screening for celiac disease

Published
2002

17. Revised European Scleroderma Trials and Research Group Activity Index is the best predictor of short-term severity accrual

Author

Elisabetta Zanatta, Gabriele Valentini, Jérôme Avouac, Ulrich A. Walker, Valeria Riccieri, Florenzo Iannone, Ellen De Langhe, Paola Caramaschi, Carina Mihai, Valentina Messiniti, Otylia Kowal-Bielecka, Edoardo Rosato, Jörg H W Distler, Alessandra Vacca, Yannick Allanore, Serena Fasano, Vanessa Smith, Antonella Riccardi, Britta Maurer, Oliver Distler, Elise Siegert, Paolo Airò, Paloma García de la Peña Lefebvre, Fasano, S., Riccardi, A., Messiniti, V., Caramaschi, P., Rosato, E., Maurer, B., Smith, V., Siegert, E., De Langhe, E., Riccieri, V., Airo, P., Mihai, C., Avouac, J., Zanatta, E., Walker, U. A., Iannone, F., De La Pena Lefebvre, P. G., Distler, J. H. W., Vacca, A., Distler, O., Kowal-Bielecka, O., Allanore, Y., Valentini, G., University of Zurich, and Kowal-Bielecka, Otylia

Subjects
Male, medicine.medical_specialty, Index (economics), Multivariate analysis, Time Factors, Accrual, systemic sclerosis, 2745 Rheumatology, Immunology, 610 Medicine & health, autoimmune disease, Logistic regression, Severity of Illness Index, General Biochemistry, Genetics and Molecular Biology, Scleroderma, outcomes research, Rheumatology, 1300 General Biochemistry, Genetics and Molecular Biology, Predictive Value of Tests, Internal medicine, Immunology and Allergy, Medicine, Humans, autoimmune diseases, Prospective Studies, 2403 Immunology, Clinical Trials as Topic, Scleroderma, Systemic, business.industry, Vascular disease, 10051 Rheumatology Clinic and Institute of Physical Medicine, Middle Aged, medicine.disease, Prognosis, Europe, 2723 Immunology and Allergy, Disease Progression, Female, Outcomes research, Group activity, business, Follow-Up Studies
Abstract

BackgroundThe European Scleroderma Trials and Research Group (EUSTAR) recently developed a preliminarily revised activity index (AI) that performed better than the European Scleroderma Study Group Activity Index (EScSG-AI) in systemic sclerosis (SSc).ObjectiveTo assess the predictive value for short-term disease severity accrual of the EUSTAR-AI, as compared with those of the EScSG-AI and of known adverse prognostic factors.MethodsPatients with SSc from the EUSTAR database with a disease duration from the onset of the first non-Raynaud sign/symptom ≤5 years and a baseline visit between 2003 and 2014 were first extracted. To capture the disease activity variations over time, EUSTAR-AI and EScSG-AI adjusted means were calculated. The primary outcome was disease progression defined as a Δ≥1 in the Medsger’s severity score and in distinct items at the 2-year follow-up visit. Logistic regression analysis was carried out to identify predictive factors.Results549 patients were enrolled. At multivariate analysis, the EUSTAR-AI adjusted mean was the only predictor of any severity accrual and of that of lung and heart, skin and peripheral vascular disease over 2 years.ConclusionThe adjusted mean EUSTAR-AI has the best predictive value for disease progression and development of severe organ involvement over time in SSc.

Published
2019

18. Progressive skin fibrosis is associated with a decline in lung function and worse survival in patients with diffuse cutaneous systemic sclerosis in the european scleroderma trials and research (eustar) cohort

Author

Wu, Wanlong, Jordan, Suzana, Graf, Nicole, Pena, Janethe de Oliveira, Curram, John, Allanore, Yannick, Matucci-Cerinic, Marco, Pope, Janet E., Denton, Christopher P., Khanna, Dinesh, Distler, Oliver, Guiducci, Serena, Walker, Ulrich, Jaeger, Veronika, Bannert, Bettina, Lapadula, Giovanni, Becvarare, Radim, Cutolo, Maurizio, Valentini, Gabriele, Siegert, Elise, Rednic, Simona, Montecucco, C., Carreira, Patricia E., Novak, Srdan, Czirjak, Laszlo, Varju, Cecilia, Chizzolini, Carlo, Allai, Daniela, Kucharz, Eugene J., Cozzi, Franco, Rozman, Blaz, Mallia, Carmel, Gabrielli, Armando, Bancel, Dominique Farge, Airo, Paolo, Hesselstrand, Roger, Martinovic, Duska, Balbir-Gurman, Alexandra, Braun-Moscovici, Yolanda, Hunzelmann, Nicolas, Pellerito, Raffaele, Caramaschi, Paola, Black, Carol, Damjanov, Nemanja, Henes, Joerg, Ortiz Santamaria, Vera, Heitmann, Stefan, Seidel, Matthias, Pereira Da Silva, Jose Antonio, Stamenkovic, Bojana, Selmi, Carlo Francesco, Tikly, Mohammed, Denisov, Lev N., Mueller-Ladner, Ulf, Engelhart, Merete, Hachulla, Eric, Riccieri, Valeria, Ionescu, Ruxandra Maria, Mihai, Carina, Sunderkoetter, Cord, Kuhn, Annegret, Schett, Georg, Distler, Joerg, Meroni, Pierluigi, Ingegnoli, Francesca, Mouthon, Luc, De Keyser, Filip, Smith, Vanessa, Cantatore, Francesco Paolo, Corrado, Ada, Ullman, Susanne, Iversen, Line, Pozzi, Maria Rosa, Eyerich, Kilian, Hein, Ruediger, Knott, Elisabeth, Wiland, Piotr, Szmyrka-Kaczmarek, Magdalena, Sokolik, Renata, Morgiel, Ewa, Madej, Marta, Jose Alegre-Sancho, Juan, Krummel-Lorenz, Brigitte, Saar, Petra, Aringer, Martin, Guenther, Claudia, Anne, Erler, Westhovens, Rene, De Langhe, Ellen, Lenaerts, Jan, Anic, Branimir, Baresic, Marko, Mayer, Miroslav, Uprus, Maria, Otsa, Kati, Yavuz, Sule, Radominski, Sebastiao Cezar, Mueller, Carolina de Souza, Azevedo, Valderilio Feijo, Popa, Sergei, Zenone, Thierry, Stebbings, Simon, Highton, John, Mathieu, Alessandro, Vacca, Alessandra, Stamp, Lisa, Chapman, Peter, O'Donnell, John, Solanki, Kamal, Doube, Alan, Veale, Douglas, O'Rourke, Marie, Loyo, Esthela, Li, Mengtao, Rosato, Edoardo, Amoroso, Antonio, Gigante, Antonietta, Oksel, Fahrettin, Yargucu, Figen, Tanaseanu, Cristina-Mihaela, Popescu, Monica, Dumitrascu, Alina, Tiglea, Isabela, Foti, Rosario, Visalli, Elisa, Benenati, Alessia, Amato, Giorgio, Ancuta, Codrina, Chirieac, Rodica, Villiger, Peter, Adler, Sabine, Dan, Diana, de la Pena Lefebvre, Paloma Garcia, Rodriguez Rubio, Silvia, Valero Exposito, Marta, Sibilia, Jean, Chatelus, Emmanuel, Gottenberg, Jacques Eric, Chifflot, Helene, Litinsky, Ira, Del Galdo, Francesco, Venalis, Algirdas, Saketkoo, Lesley Ann, Lasky, Joseph A., Kerzberg, Eduardo, Montoya, Fabiana, Cosentino, Vanesa, Limonta, Massimiliano, Brucato, Antonio Luca, Lupi, Elide, Spertini, Francois, Ribi, Camillo, Buss, Guillaume, Martin, Thierry, Guffroy, Aurelien, Poindron, Vincent, Chung, Lori, Schmeiser, Tim, Zebryk, Pawel, Riso, Nuno, Riemekasten, Gabriela, Rezus, Elena, Puttini, Piercarlo Sarzi, Wu, W., Jordan, S., Graf, N., de Oliveira Pena, J., Curram, J., Allanore, Y., Matucci-Cerinic, M., Pope, J. E., Denton, C. P., Khanna, D., Distler, O., Guiducci, S., Walker, U., Jaeger, V., Bannert, B., Lapadula, G., Becvarare, R., Cutolo, M., Valentini, G., Siegert, E., Rednic, S., Montecucco, C., Carreira, P. E., Novak, S., Czirjak, L., Varju, C., Chizzolini, C., Allai, D., Kucharz, E. J., Cozzi, F., Rozman, B., Mallia, C., Gabrielli, A., Bancel, D. F., Airo, P., Hesselstrand, R., Martinovic, D., Balbir-Gurman, A., Braun-Moscovici, Y., Hunzelmann, N., Pellerito, R., Caramaschi, P., Black, C., Damjanov, N., Henes, J., Santamaria, V. O., Heitmann, S., Seidel, M., Pereira Da Silva, J. A., Stamenkovic, B., Selmi, C. F., Tikly, M., Denisov, L. N., Muller-Ladner, U., Engelhart, M., Hachulla, E., Riccieri, V., Ionescu, R. M., Mihai, C., Sunderkotter, C., Kuhn, A., Schett, G., Distler, J., Meroni, P., Ingegnoli, F., Mouthon, L., De Keyser, F., Smith, V., Cantatore, F. P., Corrado, A., Ullman, S., Iversen, L., Pozzi, M. R., Eyerich, K., Hein, R., Knott, E., Wiland, P., Szmyrka-Kaczmarek, M., Sokolik, R., Morgiel, E., Madej, M., Alegre-Sancho, J. J., Krummel-Lorenz, B., Saar, P., Aringer, M., Gunther, C., Anne, E., Westhovens, R., De Langhe, E., Lenaerts, J., Anic, B., Baresic, M., Mayer, M., Uprus, M., Otsa, K., Yavuz, S., Radominski, S. C., de Souza Muller, C., Azevedo, V. F., Popa, S., Zenone, T., Stebbings, S., Highton, J., Mathieu, A., Vacca, A., Stamp, L., Chapman, P., O'Donnell, J., Solanki, K., Doube, A., Veale, D., O'Rourke, M., Loyo, E., Li, M., Rosato, E., Amoroso, A., Gigante, A., Oksel, F., Yargucu, F., Tanaseanu, C. -M., Popescu, M., Dumitrascu, A., Tiglea, I., Foti, R., Visalli, E., Benenati, A., Amato, G., Ancuta, C., Chirieac, R., Villiger, P., Adler, S., Dan, D., de la Pena Lefebvre, P. G., Rubio, S. R., Exposito, M. V., Sibilia, J., Chatelus, E., Gottenberg, J. E., Chifflot, H., Litinsky, I., Del Galdo, F., Venalis, A., Saketkoo, L. A., Lasky, J. A., Kerzberg, E., Montoya, F., Cosentino, V., Limonta, M., Brucato, A. L., Lupi, E., Spertini, F., Ribi, C., Buss, G., Martin, T., Guffroy, A., Poindron, V., Chung, L., Schmeiser, T., Zebryk, P., Riso, N., Riemekasten, G., Rezus, E., Sarzi Puttini, P., Ege Üniversitesi, Chizzolini, Carlo, Allali, Danièle, University of Zurich, and Distler, Oliver

Subjects
INVOLVEMENT, Male, BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences, diffuse, Time Factors, Databases, Factual, Skin Diseases/etiology/mortality/physiopathology, PREDICTION, Fibrosi, 2745 Rheumatology, Diffuse/complications/mortality/pathology, Immunology, General Biochemistry, Genetics and Molecular Biology, Immunology and Allergy, Rheumatology, Kaplan-Meier Estimate, ddc:616.07, Severity of Illness Index, Scleroderma, Cohort Studies, PROGNOSTIC-FACTORS, Fibrosis, Medicine and Health Sciences, scleroderma, Lung, Skin, integumentary system, progressive skin fibrosis, Lung function decline, BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti, 10051 Rheumatology Clinic and Institute of Physical Medicine, DEATH, Middle Aged, ddc, Europe, VARIABILITY, factual, Cohort, Visceral organ progression, 2723 Immunology and Allergy, Disease Progression, Female, Survival Analysi, Life Sciences & Biomedicine, Cohort study, Human, Adult, Skin/pathology, medicine.medical_specialty, databases, All-cause death, risk analysis, diffuse cutaneous systemic sclerosis, 610 Medicine & health, IMPROVEMENT, Systemic Sclerosis, Skin Diseases, THICKNESS SCORE, VALIDATION, Databases, FEV1/FVC ratio, 1300 General Biochemistry, Genetics and Molecular Biology, Internal medicine, medicine, Humans, Factual, Survival analysis, 2403 Immunology, Science & Technology, Proportional hazards model, business.industry, Surrogate endpoint, MORTALITY, Skin Disease, fibrosis, Progressive skin fibrosi, Lung/physiopathology, biomarkers, Diffuse cutaneous systemic sclerosi, medicine.disease, Survival Analysis, all-cause death, lung function decline, visceral organ progression, adult, cohort studies, databases, factual, disease progression, female, humans, Scleroderma, Diffuse, Cohort Studie, business
Abstract

PubMed: 30852552, Objectives To determine whether progressive skin fibrosis is associated with visceral organ progression and mortality during follow-up in patients with diffuse cutaneous systemic sclerosis (dcSSc). Methods We evaluated patients from the European Scleroderma Trials and Research database with dcSSc, baseline modified Rodnan skin score (mRSS) ?7, valid mRSS at 12±3 months after baseline and ?1 annual follow-up visit. Progressive skin fibrosis was defined as an increase in mRSS >5 and ?25% from baseline to 12±3 months. Outcomes were pulmonary, cardiovascular and renal progression, and all-cause death. Associations between skin progression and outcomes were evaluated by Kaplan-Meier survival analysis and multivariable Cox regression. Results Of 1021 included patients, 78 (7.6%) had progressive skin fibrosis (skin progressors). Median follow-up was 3.4 years. Survival analyses indicated that skin progressors had a significantly higher probability of FVC decline ?10% (53.6% vs 34.4%; p, Bayer Bayer, 1Department of Rheumatology, University Hospital Zurich, Zurich, switzerland 2Graf Biostatistics, Winterthur, switzerland 3Clinical Development Pulmonology, Bayer Us llC, Whippany, new Jersey, Usa 4Data science and analytics, Bayer plc, Reading, UK 5Rheumatology a Department, Paris Descartes University, inseRM U1016, sorbonne, Paris Cité, Cochin Hospital, Paris, France 6Division of Rheumatology, University of Florence, Florence, italy 7Department of Medicine, Division of Rheumatology, University of Western Ontario, st. Joseph’s Health Care, london, Western Ontario, Canada 8Department of Rheumatology, Royal Free Hospital, University College london, london, UK 9scleroderma Program, Department of internal Medicine, Division of Rheumatology, University of Michigan, ann arbor, Michigan, Usa Acknowledgements The authors thank nicole schneider for excellent administration and data entry into the eUsTaR cohort. Medical writing assistance was provided by adelphi Communications ltd (Bollington, UK), funded by Bayer aG (Berlin, Germany)., This study was supported by a grant from Bayer aG.

Published
2019

19. Phenotypes determined by cluster analysis and their survival in the prospective European Scleroderma Trials and Research cohort of patients with systemic sclerosis

Author

Sobanski, Vincent, Giovannelli, Jonathan, Allanore, Yannick, Riemekasten, Gabriela, Airo, Paolo, Vettori, Serena, Cozzi, Franco, Distler, Oliver, Matucci-Cerinic, Marco, Denton, Christopher, Launay, David, Hachulla, Eric, Cerinic, Marco Matucci, Guiducci, Serena, Walker, Ulrich, Kyburz, Diego, Lapadula, Giovanni, Iannone, Florenzo, Maurer, Britta, Jordan, Suzana, Becvar, Radim, Sierakowsky, Stanislaw, Bielecka, Otylia Kowal, Cutolo, Maurizio, Sulli, Alberto, Valentini, Gabriele, Cuomo, Giovanna, Siegert, Elise, Rednic, Simona, Nicoara, Ileana, Kahan, Andre, Vlachoyiannopoulos, Panayiotis, Montecucco, Carlo, Caporali, Roberto, Stork, Jiri, Inanc, Murat, Carreira, Patricia E, Novak, Srdan, Czirjak, Laszlo, Varju, Cecilia, Chizzolini, Carlo, Kucharz, Eugene J, Kotulska, Anna, Kopec-Medrek, Magdalena, Widuchowska, Malgorzata, Rozman, Blaz, Mallia, Carmel, Coleiro, Bernard, Gabrielli, Armando, Farge, Dominique, Wu, Chen, Marjanovic, Zora, Faivre, Helene, Hij, Darin, Dhamadi, Roza, Hesselstrand, Roger, Wollheim, Frank, Wuttge, Dirk M, Andreasson, Kristofer, Martinovic, Duska, Balbir-Gurman, Alexandra, Braun-Moscovici, Yolanda, Trotta, Francesco, Lo Monaco, Andrea, Hunzelmann, Nicolas, Pellerito, Raffaele, Bambara, Lisa Maria, Caramaschi, Paola, Morovic-Vergles, Jadranka, Black, Carol, Damjanov, Nemanja, Henes, Joerg, Ortiz Santamaria, Vera, Heitmann, Stefan, Krasowska, Dorota, Seidel, Matthias, Hasler, Paul, Burkhardt, Harald, Himsel, Andrea, Bajocchi, Gianluigi, Nuova, Arcispedale Santa Maria, Salvador, Maria Joao, Pereira Da Silva, Jose Antonio, Stamenkovic, Bojana, Stankovic, Aleksandra, Selmi, Carlo Francesco, De Santis, Maria, Marasini, Bianca, Tikly, Mohammed, Ananieva, Lidia P, Denisov, Lev N, Mueller-Ladner, Ulf, Frerix, Marc, Tarner, Ingo, Scorza, Raffaella, Puppo, Francesco, Engelhart, Merete, Strauss, Gitte, Nielsen, Henrik, Damgaard, Kirsten, Szucs, Gabriella, Szamosi, Szilvia, Zea Mendoza, Antonio, de la Puente, Carlos, Sifuentes Giraldo, Walter Alberto, Midtvedt, Oyvind, Reiseter, Silje, Garen, Torhild, Valesini, Guido, Riccieri, Valeria, Ionescu, Ruxandra Maria, Opris, Daniela, Groseanu, Laura, Wigley, Fredrick M, Cornateanu, Roxana Sfrent, Ionitescu, Razvan, Gherghe, Ana Maria, Soare, Alina, Gorga, Marilena, Bojinca, Mihai, Mihai, Carina, Milicescu, Mihaela, Sunderkoetter, Cord, Kuhn, Annegret, Sandorfi, Nora, Schett, Georg, Distler, Joerg HW, Beyer, Christian, Meroni, Pierluigi, Ingegnoli, Francesca, Mouthon, Luc, De Keyser, Filip, Smith, Vanessa, Cantatore, Francesco Paolo, Corrado, Ada, Ullman, Susanne, Iversen, Line, von Muehlen, Carlos Alberto, Bohn, Jussara Marilu, Lonzetti, Lilian Scussel, Pozzi, Maria Rosa, Eyerich, Kilian, Hein, Ruediger, Knott, Elisabeth, Wiland, Piotr, Szmyrka-Kaczmarek, Magdalena, Sokolik, Renata, Morgiel, Ewa, Madej, Marta, Houssiau, Frederic A, Jose Alegre-Sancho, Juan, Krummel-Lorenz, Brigitte, Saar, Petra, Aringer, Martin, Guenther, Claudia, Westhovens, Rene, de Langhe, Ellen, Lenaerts, Jan, Anic, Branimir, Baresic, Marko, Mayer, Miroslav, Uprus, Maria, Otsa, Kati, Yavuz, Sule, Granel, Brigitte, Radominski, Sebastiao Cezar, Mueller, Carolina de Souza, Azevedo, Valderilio Feijo, Jimenez, Sergio, Busquets, Joanna, Agachi, Svetlana, Groppa, Liliana, Chiaburu, Lealea, Russu, Eugen, Popa, Sergei, Zenone, Thierry, Pileckyte, Margarita, Stebbings, Simon, Highton, John, Mathieu, Alessandro, Vacca, Alessandra, Sampaio-Barros, Percival D, Yoshinari, Natalino H, Marangoni, Roberta G, Martin, Patricia, Fuocco, Luiza, Stamp, Lisa, Chapman, Peter, O'Donnell, John, Solanki, Kamal, Doube, Alan, Veale, Douglas, O'Rourke, Marie, Loyo, Esthela, Li, Mengtao, Mohamed, Walid Ahmed Abdel Atty, Rosato, Edoardo, Amoroso, Antonio, Gigante, Antonietta, Oksel, Fahrettin, Yargucu, Figen, Tanaseanu, Cristina-Mihaela, Popescu, Monica, Dumitrascu, Alina, Tiglea, Isabela, Foti, Rosario, Chirieac, Rodica, Ancuta, Codrina, Furst, Daniel E, Villiger, Peter, Adler, Sabine, van Laar, Jacob, Kayser, Cristiane, Eduardo, Andrade Luis C, Fathi, Nihal, Hassanien, Manal, de la Pena Lefebvre, Paloma Garcia, Rodriguez Rubio, Silvia, Valero Exposito, Marta, Sibilia, Jean, Chatelus, Emmanuel, Gottenberg, Jacques Eric, Chifflot, Helene, Litinsky, Ira, Emery, Paul, Buch, Maya, Del Galdo, Francesco, Venalis, Algirdas, Butrimiene, Irena, Venalis, Paulius, Rugiene, Rita, Karpec, Diana, Saketkoo, Lesley Ann, Lasky, Joseph A, Kerzberg, Eduardo, Montoya, Fabiana, Cosentino, Vanesa, Limonta, Massimiliano, Brucato, Antonio Luca, Lupi, Elide, Rosner, Itzhak, Rozenbaum, Michael, Slobodin, Gleb, Boulman, Nina, Rimar, Doron, Couto, Maura, Spertini, Francois, Ribi, Camillo, Buss, Guillaume, Kahl, Sarah, Hsu, Vivien M, Chen, Fei, McCloskey, Deborah, Malveaux, Halina, Pasquali, Jean Louis, Martin, Thierry, Gorse, Audrey, Guffroy, Aurelien, Poindron, Vincent, EUSTAR Collaborators, Guiducci, S., Walker, U., Kyburz, D., Lapadula, G., Iannone, F., Maurer, B., Jordan, S., Becvar, R., Sierakowsky, S., Kowal Bielecka, O., Cutolo, M., Sulli, A., Valentini, G., Cuomo, G., Siegert, E., Rednic, S., Nicoara, I., Kahan, A., Vlachoyiannopoulos, P., Montecucco, C., Caporali, R., Stork, J., Inanc, M., Carreira, P.E., Novak, S., Czirják, L., Varju, C., Chizzolini, C., Kucharz, E.J., Kotulska, A., Kopec-Medrek, M., Widuchowska, M., Rozman, B., Mallia, C., Coleiro, B., Gabrielli, A., Farge, D., Wu, C., Marjanovic, Z., Faivre, H., Hij, D., Dhamadi, R., Airò, P., Hesselstrand, R., Wollheim, F., Wuttge, D.M., Andréasson, K., Martinovic, D., Balbir-Gurman, A., Braun-Moscovici, Y., Trotta, F., Lo Monaco, A., Hunzelmann, N., Pellerito, R., Mauriziano, O., Maria Bambara, L., Caramaschi, P., Morovic-Vergles, J., Black, C., Damjanov, N., Henes, J., Ortiz Santamaria, V., Heitmann, S., Krasowska, D., Seidel, M., Hasler, P., Burkhardt, H., Himsel, A., Bajocchi, G., Maria Nuova, A.S., João Salvador, M., Pereira Da Silva, J.A., Stamenkovic, B., Stankovic, A., Francesco Selmi, C., De Santis, M., Marasini, B., Tikly, M., Ananieva, L.P., Denisov, L.N., Müller-Ladner, U., Frerix, M., Tarner, I., Scorza, R., Puppo, F., Engelhart, M., Strauss, G., Nielsen, H., Damgaard, K., Szücs, G., Szamosi, S., Zea Mendoza, A., de la Puente, C., Sifuentes Giraldo, W.A., Midtvedt, Ø., Reiseter, S., Garen, T., Valesini, G., Riccieri, V., Maria Ionescu, R., Opris, D., Groseanu, L., Wigley, F.M., Sfrent Cornateanu, R., Ionitescu, R., Maria Gherghe, A., Soare, A., Gorga, M., Bojinca, M., Mihai, C., Milicescu, M., Sunderkötter, C., Kuhn, A., Sandorfi, N., Schett, G., Distler, J.H., Beyer, C., Meroni, P., Ingegnoli, F., Mouthon, L., De Keyser, F., Smith, V., Paolo Cantatore, F., Corrado, A., Ullman, S., Iversen, L., Alberto von Mühlen, C., Marilu Bohn, J., Scussel Lonzetti, L., Rosa Pozzi, M., Eyerich, K., Hein, R., Knott, E., Wiland, P., Szmyrka-Kaczmarek, M., Sokolik, R., Morgiel, E., Madej, M., Houssiau, F.A., Jose Alegre-Sancho, J., Krummel-Lorenz, B., Saar, P., Aringer, M., Günther, C., Westhovens, R., de Langhe, E., Lenaerts, J., Anic, B., Baresic, M., Mayer, M., Üprus, M., Otsa, K., Yavuz, S., Granel, B., Cezar Radominski, S., de Souza Müller, C., Azevedo, V.F., Jimenez, S., Busquets, J., Agachi, S., Groppa, L., Chiaburu, L., Russu, E., Popa, S., Zenone, T., Pileckyte, M., Stebbings, S., Highton, J., Mathieu, A., Vacca, A., Sampaio-Barros, P.D., Yoshinari, N.H., Marangoni, R.G., Martin, P., Fuocco, L., Stamp, L., Chapman, P., O'Donnell, J., Solanki, K., Doube, A., Veale, D., O'Rourke, M., Loyo, E., Li, M., Abdel Atty Mohamed, W.A., Rosato, E., Amoroso, A., Gigante, A., Oksel, F., Yargucu, F., Tanaseanu, C.M., Popescu, M., Dumitrascu, A., Tiglea, I., Foti, R., Chirieac, R., Ancuta, C., Furst, D.E., Villiger, P., Adler, S., van Laar, J., Kayser, C., Eduardo C, A.L., Fathi, N., Hassanien, M., de la Peña Lefebvre, P.G., Rodriguez Rubio, S., Valero Exposito, M., Sibilia, J., Chatelus, E., Gottenberg, J.E., Chifflot, H., Litinsky, I., Emery, P., Buch, M., Del Galdo, F., Venalis, A., Butrimiene, I., Venalis, P., Rugiene, R., Karpec, D., Ann Saketkoo, L., Lasky, J.A., Kerzberg, E., Montoya, F., Cosentino, V., Limonta, M., Luca Brucato, A., Lupi, E., Rosner, I., Rozenbaum, M., Slobodin, G., Boulman, N., Rimar, D., Couto, M., Spertini, F., Ribi, C., Buss, G., Kahl, S., Hsu, V.M., Chen, F., McCloskey, D., Malveaux, H., Louis Pasquali, J., Martin, T., Gorse, A., Guffroy, A., Poindron, V., and Chizzolini, Carlo

Subjects
0301 basic medicine, Male, BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences, Databases, Factual, systemic sclerosis, SUBSETS, Disease, Severity of Illness Index, Scleroderma, DISEASE, 0302 clinical medicine, Medicine and Health Sciences, Immunology and Allergy, Cluster Analysis, CRITERIA, Prospective Studies, Prospective cohort study, skin and connective tissue diseases, integumentary system, BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti, Adult, Aged, Autoantibodies/blood, Europe/epidemiology, Female, Humans, Middle Aged, Phenotype, Prognosis, Scleroderma, Diffuse/blood, Scleroderma, Diffuse/epidemiology, Scleroderma, Diffuse/pathology, Scleroderma, Limited/blood, Scleroderma, Limited/epidemiology, Scleroderma, Limited/pathology, Scleroderma, Systemic/blood, Scleroderma, Systemic/epidemiology, Scleroderma, Systemic/pathology, Connective tissue disease, ddc, Europe, MANIFESTATIONS, Cohort, Life Sciences & Biomedicine, medicine.medical_specialty, Immunology, PROFILE, CLASSIFICATION, 03 medical and health sciences, Rheumatology, Scleroderma, Limited, Internal medicine, Severity of illness, medicine, Autoantibodies, 030203 arthritis & rheumatology, Science & Technology, Scleroderma, Systemic, business.industry, Autoantibody, Systemic sclerosis (SSc), medicine.disease, 030104 developmental biology, Scleroderma, Diffuse, business
Abstract

OBJECTIVE: Systemic sclerosis (SSc) is a heterogeneous connective tissue disease that is typically subdivided into limited cutaneous SSc (lcSSc) and diffuse cutaneous SSc (dcSSc) depending on the extent of skin involvement. This subclassification may not capture the entire variability of clinical phenotypes. The European Scleroderma Trials and Research (EUSTAR) database includes data on a prospective cohort of SSc patients from 122 European referral centers. This study was undertaken to perform a cluster analysis of EUSTAR data to distinguish and characterize homogeneous phenotypes without any a priori assumptions, and to examine survival among the clusters obtained. METHODS: A total of 11,318 patients were registered in the EUSTAR database, and 6,927 were included in the study. Twenty-four clinical and serologic variables were used for clustering. RESULTS: Clustering analyses provided a first delineation of 2 clusters showing moderate stability. In an exploratory attempt, we further characterized 6 homogeneous groups that differed with regard to their clinical features, autoantibody profile, and mortality. Some groups resembled usual dcSSc or lcSSc prototypes, but others exhibited unique features, such as a majority of lcSSc patients with a high rate of visceral damage and antitopoisomerase antibodies. Prognosis varied among groups and the presence of organ damage markedly impacted survival regardless of cutaneous involvement. CONCLUSION: Our findings suggest that restricting subsets of SSc patients to only those based on cutaneous involvement may not capture the complete heterogeneity of the disease. Organ damage and antibody profile should be taken into consideration when individuating homogeneous groups of patients with a distinct prognosis. ispartof: ARTHRITIS & RHEUMATOLOGY vol:71 issue:9 pages:1553-1570 ispartof: location:United States status: published

Published
2019

20. Predictors of disease worsening defined by progression of organ damage in diffuse systemic sclerosis: A European Scleroderma Trials and Research (EUSTAR) analysis

Author

Becker, Mike, Graf, Nicole, Sauter, Rafael, Allanore, Yannick, Curram, John, Denton, Christopher P., Khanna, Dinesh, Matucci-Cerinic, Marco, Pena, Janethe de Oliveira, Pope, Janet E., Distler, Oliver, Guiducci, Serena, Walker, Ulrich, Jaeger, Veronika, Bannert, Bettina, Lapadula, Giovanni, Becvarare, Radim, Cutolo, Maurizio, Valentini, Gabriele, Siegert, Elise, Rednic, Simona, Montecucco, C., Carreira, Patricia E., Novak, Srdan, Czirjak, Laszlo, Varju, Cecilia, Chizzolini, Carlo, Allai, Daniela, Kucharz, Eugene J., Cozzi, Franco, Rozman, Blaz, Mallia, Carmel, Gabrielli, Armando, Bancel, Dominique Farge, Airo, Paolo, Hesselstrand, Roger, Martinovic, Duska, Balbir-Gurman, Alexandra, Braun-Moscovici, Yolanda, Hunzelmann, Nicolas, Pellerito, Raffaele, Caramaschi, Paola, Black, Carol, Damjanov, Nemanja, Henes, Joerg, Ortiz Santamaria, Vera, Heitmann, Stefan, Seidel, Matthias, Pereira Da Silva, Jose Antonio, Stamenkovic, Bojana, Selmi, Carlo Francesco, Tikly, Mohammed, Denisov, Lev N., Mueller-Ladner, Ulf, Engelhart, Merete, Hachulla, Eric, Riccieri, Valeria, Ionescu, Ruxandra Maria, Mihai, Carina, Sunderkoetter, Cord, Kuhn, Annegret, Schett, Georg, Distler, Joerg, Meroni, Pierluigi, Ingegnoli, Francesca, Mouthon, Luc, De Keyser, Filip, Smith, Vanessa, Cantatore, Francesco Paolo, Corrado, Ada, Ullman, Susanne, Iversen, Line, Pozzi, Maria Rosa, Eyerich, Kilian, Hein, Ruediger, Knott, Elisabeth, Wiland, Piotr, Szmyrka-Kaczmarek, Magdalena, Sokolik, Renata, Morgiel, Ewa, Madej, Marta, Jose Alegre-Sancho, Juan, Krummel-Lorenz, Brigitte, Saar, Petra, Aringer, Martin, Guenther, Claudia, Anne, Erler, Westhovens, Rene, De langhe, Ellen, Lenaerts, Jan, Anic, Branimir, Baresic, Marko, Mayer, Miroslav, Uprus, Maria, Otsa, Kati, Yavuz, Sule, Radominski, Sebastiao Cezar, Mueller, Carolina de Souza, Azevedo, Valderilio Feijo, Popa, Sergei, Zenone, Thierry, Stebbings, Simon, Highton, John, Mathieu, Alessandro, Vacca, Alessandra, Stamp, Lisa, Chapman, Peter, O'Donnell, John, Solanki, Kamal, Doube, Alan, Veale, Douglas, O'Rourke, Marie, Loyo, Esthela, Li, Mengtao, Rosato, Edoardo, Amoroso, Antonio, Gigante, Antonietta, Oksel, Fahrettin, Yargucu, Figen, Tanaseanu, Cristina-Mihaela, Popescu, Monica, Dumitrascu, Alina, Tiglea, Isabela, Foti, Rosario, Visalli, Elisa, Benenati, Alessia, Amato, Giorgio, Ancuta, Codrina, Chirieac, Rodica, Villiger, Peter, Adler, Sabine, Dan, Diana, de la Pena Lefebvre, Paloma Garcia, Rodriguez Rubio, Silvia, Valero Exposito, Marta, Sibilia, Jean, Chatelus, Emmanuel, Gottenberg, Jacques Eric, Chifflot, Helene, Litinsky, Ira, Del Galdo, Francesco, Venalis, Algirdas, Saketkoo, Lesley Ann, Lasky, Joseph A., Kerzberg, Eduardo, Montoya, Fabiana, Cosentino, Vanesa, Limonta, Massimiliano, Brucato, Antonio Luca, Lupi, Elide, Spertini, Francois, Ribi, Camillo, Buss, Guillaume, Martin, Thierry, Guffroy, Aurelien, Poindron, Vincent, Chung, Lori, Schmeiser, Tim, Zebryk, Pawel, Riso, Nuno, Riemekasten, Gabriela, Rezus, Elena, Puttini, Piercarlo Sarzi, Ege Üniversitesi, University of Zurich, Distler, Oliver, Chizzolini, Carlo, Allai, Daniela, Becker, M., Graf, N., Sauter, R., Allanore, Y., Curram, J., Denton, C. P., Khanna, D., Matucci-Cerinic, M., de Oliveira Pena, J., Pope, J. E., Distler, O., Guiducci, S., Walker, U., Jaeger, V., Bannert, B., Lapadula, G., Becvarare, R., Cutolo, M., Valentini, G., Siegert, E., Rednic, S., Montecucco, C., Carreira, P. E., Novak, S., Czirjak, L., Varju, C., Chizzolini, C., Allai, D., Kucharz, E. J., Cozzi, F., Rozman, B., Mallia, C., Gabrielli, A., Bancel, D. F., Airo, P., Hesselstrand, R., Martinovic, D., Balbir-Gurman, A., Braun-Moscovici, Y., Hunzelmann, N., Pellerito, R., Caramaschi, P., Black, C., Damjanov, N., Henes, J., Santamaria, V. O., Heitmann, S., Seidel, M., Pereira Da Silva, J. A., Stamenkovic, B., Selmi, C. F., Tikly, M., Denisov, L. N., Muller-Ladner, U., Engelhart, M., Hachulla, E., Riccieri, V., Ionescu, R. M., Mihai, C., Sunderkotter, C., Kuhn, A., Schett, G., Distler, J., Meroni, P., Ingegnoli, F., Mouthon, L., De Keyser, F., Smith, V., Cantatore, F. P., Corrado, A., Ullman, S., Iversen, L., Pozzi, M. R., Eyerich, K., Hein, R., Knott, E., Wiland, P., Szmyrka-Kaczmarek, M., Sokolik, R., Morgiel, E., Madej, M., Alegre-Sancho, J. J., Krummel-Lorenz, B., Saar, P., Aringer, M., Gunther, C., Anne, E., Westhovens, R., De Langhe, E., Lenaerts, J., Anic, B., Baresic, M., Mayer, M., Uprus, M., Otsa, K., Yavuz, S., Radominski, S. C., de Souza Muller, C., Azevedo, V. F., Popa, S., Zenone, T., Stebbings, S., Highton, J., Mathieu, A., Vacca, A., Stamp, L., Chapman, P., O'Donnell, J., Solanki, K., Doube, A., Veale, D., O'Rourke, M., Loyo, E., Li, M., Rosato, E., Amoroso, A., Gigante, A., Oksel, F., Yargucu, F., Tanaseanu, C. -M., Popescu, M., Dumitrascu, A., Tiglea, I., Foti, R., Visalli, E., Benenati, A., Amato, G., Ancuta, C., Chirieac, R., Villiger, P., Adler, S., Dan, D., de la Pena Lefebvre, P. G., Rubio, S. R., Exposito, M. V., Sibilia, J., Chatelus, E., Gottenberg, J. E., Chifflot, H., Litinsky, I., Del Galdo, F., Venalis, A., Saketkoo, L. A., Lasky, J. A., Kerzberg, E., Montoya, F., Cosentino, V., Limonta, M., Brucato, A. L., Lupi, E., Spertini, F., Ribi, C., Buss, G., Martin, T., Guffroy, A., Poindron, V., Chung, L., Schmeiser, T., Zebryk, P., Riso, N., Riemekasten, G., Rezus, E., and Sarzi Puttini, P.

Subjects
INVOLVEMENT, SELECTION, BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences, diffuse, predictive factors, systemic sclerosis, 2745 Rheumatology, epidemiologic methods, morbidity, Disease, Immunology, General Biochemistry, Genetics and Molecular Biology, Immunology and Allergy, Rheumatology, INTERSTITIAL LUNG-DISEASE, disease worsening, mortality, predictive factors, systemic sclerosis, predictive factor, disease worsening, DESIGN, middle aged, Medicine and Health Sciences, FIBROSIS, scleroderma, SKIN THICKNESS SCORE, mortality, skin and connective tissue diseases, Prospective cohort study, humans, lung diseases, ddc:616, education.field_of_study, heart diseases, integumentary system, clinical trials as topic, BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti, 10051 Rheumatology Clinic and Institute of Physical Medicine, Interstitial lung disease, follow-up studies, ddc, female, Cohort, 2723 Immunology and Allergy, europe, Life Sciences & Biomedicine, CLINICAL-TRIALS, survival rate, medicine.medical_specialty, Population, 610 Medicine & health, disease progression, male, 1300 General Biochemistry, Genetics and Molecular Biology, Internal medicine, Severity of illness, REGRESSION, medicine, severity of illness index, education, Survival rate, METAANALYSIS, 2403 Immunology, Science & Technology, Scleroderma, Systemic, business.industry, MORTALITY, systemic, medicine.disease, prospective studies, Clinical trial, prognosis, scleroderma, diffuse, scleroderma, systemic, Scleroderma, Diffuse, business
Abstract

PubMed: 31227488, Objectives Mortality and worsening of organ function are desirable endpoints for clinical trials in systemic sclerosis (SSc). The aim of this study was to identify factors that allow enrichment of patients with these endpoints, in a population of patients from the European Scleroderma Trials and Research group database. Methods Inclusion criteria were diagnosis of diffuse SSc and follow-up over 12±3 months. Disease worsening/organ progression was fulfilled if any of the following events occurred: new renal crisis; decrease of lung or heart function; new echocardiography-suspected pulmonary hypertension or death. In total, 42 clinical parameters were chosen as predictors for the analysis by using (1) imputation of missing data on the basis of multivariate imputation and (2) least absolute shrinkage and selection operator regression. Results Of 1451 patients meeting the inclusion criteria, 706 had complete data on outcome parameters and were included in the analysis. Of the 42 outcome predictors, eight remained in the final regression model. There was substantial evidence for a strong association between disease progression and age, active digital ulcer (DU), lung fibrosis, muscle weakness and elevated C-reactive protein (CRP) level. Active DU, CRP elevation, lung fibrosis and muscle weakness were also associated with a significantly shorter time to disease progression. A bootstrap validation step with 10 000 repetitions successfully validated the model. Conclusions The use of the predictive factors presented here could enable cohort enrichment with patients at risk for overall disease worsening in SSc clinical trials. © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ., Bayer Bayer, United Kingdom Université Paris Descartes Li Ka Shing Foundation, LKSF University of Michigan, U-M, 1Department of Rheumatology and the Centre of experimental Rheumatology, University Hospital Zurich, Zurich, switzerland 2Graf Biostatistics, Winterthur, switzerland 3Big Data institute, li Ka shing Centre for Health information and Discovery, nuffield Department of Medicine, University of Oxford, Oxford, UK 4Rheumatology a Department, Paris Descartes University, sorbonne Paris Cité, Cochin Hospital, Paris, France 5Data science and analytics, Bayer plc, Reading, UK 6UCl Division of Medicine, Royal Free Campus, london, UK 7Division of Rheumatology, Department of internal Medicine, University of Michigan scleroderma Program, University of Michigan, ann arbor, Michigan, Usa 8Department of experimental and Clinical Medicine, University of Florence, Florence, italy 9Bayer Us llC, Whippany, new Jersey, Usa 10Department of Medicine, Division of Rheumatology, University of Western Ontario, st. Joseph’s Health Care, london, Ontario, Canada Acknowledgements The R-code for the linear Mi-lassO was received from Qixuan Chen.21 Medical writing assistance was provided by adelphi Communications ltd (Bollington, UK), funded by Bayer aG (Berlin, Germany)., Contributors study conception and design, acquisition of data, analysis and interpretation of data and drafting and revising the article: OD and MB; analysis and interpretation of data: OD, MB, Rs and nG. all authors have critically reviewed and approved the final submitted version to be published. Funding This study was supported by a grant from Bayer aG. Bayer employees are coauthors of this paper and supported the study design and interpretation of the data, but otherwise Bayer had no influence on the study., Competing interests MOB declares no conflict of interest. OD has had consultancy relationships with actelion, Bayer, Biogen idec, Boehringer ingelheim, Chemomab, espeRare foundation, Genentech/Roche, GsK, inventiva, italfarmaco, lilly, medac, Medimmune, Mitsubishi Tanabe Pharma, Pharmacyclics, novartis, Pfizer, sanofi, sinoxa and UCB in the area of potential treatments of scleroderma and its complications. OD has received research funding from actelion, Bayer, Boehringer ingelheim, Mitsubishi Tanabe Pharma and Roche in the area of potential treatments of scleroderma and its complications. OD has a patent for mir-29 licensed for the treatment of systemic sclerosis. DK has consultancy relationships and/or has received grant/research support from Bayer, Bristol-Myers squibb, Boehringer ingelheim, Genentech/Roche, niH, Pfizer, sanofi-aventis Pharmaceuticals, actelion Pharmaceuticals Us, Chemomab, Corbus, Covis, Cytori, eicos, eMD serono, Gilead, GlaxosmithKline, and UCB Pharma. He is a shareholder of eicos. CPD has consultancy relationships with and/or has received speakers’ bureau fees from actelion Pharmaceuticals Us, Bayer aG, GlaxosmithKline, Csl Behring, Merck serono, Roche Pharmaceuticals, Genentech and Biogen iDeC inc., inventiva, sanofi-aventis Pharmaceuticals and Boehringer ingelheim. JeP has consultancy relationships with and/or has received grant/research support from actelion, Bayer aG, Bristol-Myers squibb, Merck, Pfizer inc. and Roche. MM-C has consultancy relationships and/ or has received grant/research support from Pfizer, Bristol-Myers squibb, actelion, UCB Pharma, Bayer, Chemomab, Genentech/Roche, inventiva and lilly. Ya has consultancy relationships with and/or has received grant/research support from actelion, Pharmaceuticals Us, Bayer aG, Bristol-Myers squibb, inventiva, Medac, Pfizer inc., Roche Pharmaceuticals, Genentech and Biogen iDeC inc., sanofi-aventis Pharmaceuticals and servier. JdOP and JC are employees of Bayer. nTG has nothing to disclose.

Published
2019

21. Differences associated with age at onset in early systemic sclerosis patients: a report from the EULAR Scleroderma Trials and Research Group (EUSTAR) database

Author

José Luis Andreu, Alexandra Balbir-Gurman, Roger Hesselstrand, Simona Rednic, Mohammed Tikly, G. Riemekasten, Paola Caramaschi, Serena Vettori, Marco Matucci-Cerinic, Dominique Farge, Yannick Allanore, Nemanja Damjanov, L. Czirják, Ada Corrado, Beatriz Joven, Loreto Carmona, Estíbaliz Loza, Paolo Airò, Ulrich A. Walker, Oliver Distler, Patricia Carreira, Lidiya P. Ananieva, Carreira, Pe, Carmona, L, Joven, Be, Loza, E, Andréu, Jl, Riemekasten, G, Vettori, S, Balbir-Gurman, A, Airò, P, Walker, U, Damjanov, N, Matucci-Cerinic, M, Ananieva, Lp, Rednic, S, Czirják, L, Distler, O, Farge, D, Hesselstrand, R, Corrado, A, Caramaschi, P, Tikly, M, and Allanore, Y

Subjects
Adult, Male, medicine.medical_specialty, Databases, Factual, Cross-sectional study, Immunology, Disease, Scleroderma, 03 medical and health sciences, Age Distribution, 0302 clinical medicine, Rheumatology, Internal medicine, Cardiac conduction, Prevalence, medicine, Humans, Immunology and Allergy, Registries, 030212 general & internal medicine, Age of Onset, Sex Distribution, skin and connective tissue diseases, Retrospective Studies, 030203 arthritis & rheumatology, Scleroderma, Systemic, integumentary system, business.industry, Incidence, Incidence (epidemiology), Age Factors, Retrospective cohort study, General Medicine, Middle Aged, medicine.disease, 3. Good health, Europe, Cross-Sectional Studies, Female, Age of onset, business
Abstract

Objective: The aim of this study was to analyse differences in clinical presentation in patients with early (< 3 years’ duration) systemic sclerosis (SSc), comparing three age groups according to disease subsets. Method: Cross-sectional analysis of the prospective EULAR Scleroderma Trials and Research database (EUSTAR) was performed. Patients fulfilling preliminary American College of Rheumatology 1980 classification criteria for SSc, with < 3 years from the first non-Raynaud’s SSc symptom at first entry, were selected. Patients with < 3 years from the first SSc symptom, including Raynaud’s phenomenon, were also analysed. SSc-related variables, including antibodies, SSc subsets, and organ involvement, were examined. Age was categorized into ≤ 30, 31–59, and ≥ 60 years. We performed descriptive and bivariate analyses. Results: The study included 1027 patients: 90% Caucasian, 80% women, and 40% with diffuse disease. In early stages of SSc, younger patients had significantly more anti-Scl-70 antibodies and diffuse disease. With increasing age, we observed more elevation of estimated pulmonary systolic pressure on echocardiography (5%, 13%, and 30%, respectively, in the three age groups), cardiac conduction blocks (6%, 6%, and 15%), and left ventricular diastolic dysfunction (4%, 12%, and 27%). The results were similar for 650 patients with < 3 years from first SSc symptom, including Raynaud’s. Conclusion: In early stages of SSc, older patients showed data indicating more severe disease with greater cardiac involvement. The diffuse subset was more frequent in the younger subgroup. The identification of such differences may help in selecting appropriate management for individual patients in clinical practice. (Less)

Published
2018

22. Value of systolic pulmonary arterial pressure as a prognostic factor of death in the systemic sclerosis EUSTAR population

Author

Hachulla, Eric, Clerson, Pierre, Airò, Paolo, Cuomo, Giovanna, Allanore, Yannick, Caramaschi, Paola, Rosato, Edoardo, Carreira, Patricia E., Riccieri, Valeria, Sarraco, Marta, Denton, Christopher P., Riemekasten, Gabriela, Pozzi, Maria Rosa, Zeni, Silvana, Mihai, Carmen Marina, Ullman, Susanne, Distler, Oliver, Rednic, Simona, Smith, Vanessa, Walker, Ulrich A., Matucci-Cerinic, Marco, Müller-Ladner, Ulf, Launay, David, Bellando Randone, S, Guiducci, S, University of Zurich, Hachulla, Eric, Hachulla, E, Clerson, P, Airò, P, Cuomo, Giovanna, Allanore, Y, Caramaschi, P, Rosato, E, Carreira, Pe, Riccieri, V, Sarraco, M, Denton, Cp, Riemekasten, G, Pozzi, Mr, Zeni, S, Mihai, Cm, Ullman, S, Distler, O2, Rednic, S2, Smith, V2, Walker, Ua, Matucci Cerinic, M, Müller Ladner, U, Launay, D1, and on behalf of the EUSTAR co, Workers

Subjects
Male, European League Against Rheumatism Scleroderma Trial and Research, systemic sclerosis, 2745 Rheumatology, MULTICENTER, systolic pulmonary artery pressure, Blood Pressure, Systemic scleroderma, Scleroderma, Cohort Studies, Systemic sclerosi, DLCO, Risk Factors, Diffusing capacity, pulmonary hypertension, survival, systolic pulmonary arterial pressure, tricuspid regurgitant jet velocity, Medicine and Health Sciences, Medicine, 2736 Pharmacology (medical), Pharmacology (medical), education.field_of_study, 10051 Rheumatology Clinic and Institute of Physical Medicine, Pulmonary, Orvostudományok, Clinical Science, Middle Aged, Prognosis, Europe, Survival Rate, Echocardiography, Hypertension, Cardiology, SURVIVAL, Female, Adult, medicine.medical_specialty, DATABASE, Systole, Hypertension, Pulmonary, Population, Pulmonary hypertension, Survival, Systemic sclerosis, Systolic pulmonary arterial pressure, Tricuspid regurgitant jet velocity, Aged, Follow-Up Studies, Humans, Multivariate Analysis, Pulmonary Artery, Retrospective Studies, Scleroderma, Systemic, Rheumatology, 610 Medicine & health, Klinikai orvostudományok, DIAGNOSIS, Internal medicine, Risk factor, education, Survival rate, HYPERTENSION, business.industry, Systemic, medicine.disease, stomatognathic diseases, Blood pressure, EULAR SCLERODERMA TRIALS, business
Abstract

Objective. The aim of this study was to assess the prognostic value of systolic pulmonary artery pressure (sPAP) estimated by echocardiography in the multinational European League Against Rheumatism Scleroderma Trial and Research (EUSTAR) cohort. Methods. Data for patients with echocardiography documented between 1 January 2005 and 31 December 2011 were extracted from the EUSTAR database. Stepwise forward multivariable statistical Cox pulmonary hypertension analysis was used to examine the independent effect on survival of selected variables. Results. Based on our selection criteria, 1476 patients were included in the analysis; 87% of patients were female, with a mean age of 56.3 years (S.D. 13.5) and 31% had diffuse SSc. The mean duration of follow-up was 2.0 years (S.D. 1.2, median 1.9). Taking index sPAP of 50 mmHg. In a multivariable Cox model, sPAP and the diffusing capacity for carbon monoxide (DLCO) were independently associated with the risk of death [HR 1.833 (95% CI 1.035, 3.247) and HR 0.973 (95% CI 0.955, 0.991), respectively]. sPAP was an independent risk factor for death with a HR of 3.02 (95% CI 1.91, 4.78) for sPAP >= 36 mmHg. Conclusion. An estimated sPAP >36mmHg at baseline echocardiography was significantly and independently associated with reduced survival, regardless of the presence of pulmonary hypertension based on right heart catheterization.

Published
2015

23. Quantitative chest computed tomography is associated with two prediction models of mortality in interstitial lung disease related to systemic sclerosis

Author

Veronica Alfieri, Simone Parisi, G. Lucchini, Carlo Alberto Scirè, Alarico Ariani, Paola Caramaschi, Greta Carrara, M. Saracco, Nicola Sverzellati, G. Delsante, Marina Aiello, Eugenio Arrigoni, Alfredo Chetta, Raffaele Pellerito, E. Bravi, Federica Lumetti, Fabio De Gennaro, Elisa Bonati, Emanuele Michieletti, Mario Silva, F. Mozzani, Luca Idolazzi, Flavio Cesare Bodini, C. Benini, Daniele Santilli, D. Imberti, Valeria Seletti, Enrico Fusaro, Ariani, A, Silva, M, Seletti, V, Bravi, E, Saracco, M, Parisi, S, Gennaro, F, Idolazzi, L, Caramaschi, P, Benini, C, Bodini, F, Scire, C, Carrara, G, Lumetti, F, Alfieri, V, Bonati, E, Lucchini, G, Aiello, M, Santilli, D, Mozzani, F, Imberti, D, Michieletti, E, Arrigoni, E, Delsante, G, Pellerito, R, Fusaro, E, Chetta, A, and Sverzellati, N

Subjects
Lung Diseases, Male, systemic sclerosis, Mortality risk model, Systemic scleroderma, Pulmonary function testing, Scleroderma, Correlation, Systemic sclerosi, 0302 clinical medicine, Models, Pulmonary fibrosis, Medicine, Horo, Pharmacology (medical), Tomography, interstitial lung disease, mortality risk mode, Interstitial lung disease, Middle Aged, Statistical, X-Ray Computed, Italy, Horos, OsiriX, mortality risk model, pulmonary fibrosis, quantitative chest CT, Female, Humans, Lung Diseases, Interstitial, Models, Statistical, Retrospective Studies, Risk Assessment, Scleroderma, Systemic, Tomography, X-Ray Computed, Radiology, Pulmonary fibrosi, Risk assessment, medicine.medical_specialty, NO, 03 medical and health sciences, Rheumatology, 030203 arthritis & rheumatology, Receiver operating characteristic, business.industry, Systemic, Retrospective cohort study, medicine.disease, body regions, 030228 respiratory system, interstitial lung disease, pulmonary fibrosis, systemic sclerosis, Horos, OsiriX, quantitative chest CT, mortality risk mode, business, Interstitial
Abstract

Objective. In this multicentre study, we aimed to evaluate the capacity of a computer-assisted automated QCT method to identify patients with SSc-associated interstitial lung disease (SSc-ILD) with high mortality risk according to validated composite clinical indexes (ILD-Gender, Age, Physiology index and du Bois index). Methods. Chest CT, anamnestic data and pulmonary function tests of 146 patients with SSc were retrospectively collected, and the ILD-Gender, Age, Physiology score and DuBois index were calculated. Each chest CT underwent an operator-independent quantitative assessment performed with a free medical image viewer (Horos). The correlation between clinical prediction models and QCT parameters was tested. A value of P

Published
2017

24. A comparison between nailfold capillaroscopy patterns in adulthood in juvenile and adult-onset systemic sclerosis: A EUSTAR exploratory study

Author

F. Lauffer, Kati Otsa, Oliver Distler, S. Zeni, Marco Matucci Cerinic, Maria Rosa Pozzi, Margarita Pileckyte, John Highton, Paola Caramaschi, Jacek Szechiński, Maria João Salvador, Diana Karpec, Maurizio Cutolo, Codrina Ancuta, Patrizia Boracchi, Simonetta Pisarri, Fabiana Montoya, Vanessa Smith, Mengtao Li, Carolina de Souza Müller, Patricia Carreira, C. Mihai, Henrik Nielsen, Luc Mouthon, L. Denisov, Marc Frerix, Pier Luigi Meroni, Øyvind Midtvedt, Francesco Paolo Cantatore, Ada Corrado, Sebastião Cezar Radominski, Serena Guiducci, Francesco Puppo, Simon Stebbings, Armando Gabrielli, Giovanna Cuomo, Irena Butrimiene, Piotr Wiland, Ira Litinsky, Maria Uprus, Merete Engelhart, Roger Hesselstrand, Ulrich A Walker, Rodica Chirieac, Ulf Müller-Ladner, David Launay, Kirsten Damgaard, Kamal Solanki, Cristina Mihaela Tanaseanu, Torhild Garen, Isabela Tiglea, Aleksandra Stanković, L. Ananieva, Francesca Ingegnoli, Magdalena Szmyrka-Kaczmarek, Jörg Henes, Alan Tyndall, Roberta Gualtierotti, Rüdiger Hein, Ewa Morgiel, Edoardo Rosato, Ivan Foeldvari, Valderílio Feijó Azevedo, Gitte Strauss, Valeria Riccieri, Anna Kotulska, Marta Valero Exposito, R. Becvar, José António Pereira da Silva, Blaz Rozman, Vera Ortiz-Santamaria, Paloma García de la Peña Lefebvre, Szilvia Szamosi, Małgorzata Widuchowska, Gabriella Szücs, Martin Aringer, Paulius Venalis, Roberto Caporali, Kilian Eyerich, Florenzo Iannone, Alina Dumitrascu, Eugene J. Kucharz, Laura Groseanu, Alessandra Vacca, Monica Popescu, Cristiane Kayser, Yannick Allanore, Brigitte Krummel-Lorenz, P. Saar, Mihai Bojinca, Magdalena Kopec-Medrek, Eduardo Kerzberg, Cecília Varjú, Nemanja Damjanov, Luis Eduardo Coelho Andrade, Rita Rugiene, Paolo Airò, Filip De Keyser, Nicola Ughi, Bojana Stamenkovic, Claudia Günther, Ruxandra Ionescu, László Czirják, Matthias Seidel, Silvia Rodriguez Rubio, Paola Gottschalk, Dirk M. Wuttge, Alan Doube, Vanesa Cosentino, Thierry Zenone, Dominique Farge-Bancel, Esthela Loyo, Algirdas Venalis, Renata Sokolik, Alberto Sulli, Rosario Foti, Stefan Heitmann, Eric Hachulla, Juan José Alegre-Sancho, Carlomaurizio Montecucco, Daniela Opris, Ingegnoli, F, Boracchi, P, Gualtierotti, R, Smith, V, Cutolo, M, Foeldvari, I, Airò, P, Alegre-Sancho, Jj, Allanore, Y, Ananieva, Lp, Ancuta, C, Andrade, Le, Aringer, M, Becvar, R, Bojinca, M, Butrimiene, I, Cantatore, Fp, Caporali, R, Caramaschi, P, Carreira, Pe, Chirieac, R, Corrado, A, Cosentino, V, Cuomo, G, Czirjak, L, Da Silva, Ja, la Peña Lefebvre, Pg, De Keyser, F, de Souza Müller, C, Damgaard, K, Damjanov, N, Denisov, Ln, Distler, O, Doube, A, Dumitrascu, A, Engelhart, M, Exposito, Mv, Eyerich, K, Farge-Bancel, D, Azevedo, Vf, Foti, R, Frerix, M, Gabrielli, A, Garen, T, Gottschalk, P, Groseanu, L, Guiducci, S, Günther, C, Hachulla, Hein, R, Heitmann, S, Henes, J, Hesselstrand, R, Highton, J, Iannone, F, Ionescu, Rm, Kayser, C, Karpec, D, Kerzberg, E, Kotulska, A, Kopec-Medrek, M, Kucharz, E, Krummel-Lorenz, B, Lauffer, F, Launay, D, Li, M, Litinsky, I, Loyo, E, Cerinic, Mm, Meroni, P, Midtvedt, Ø, Mihai, Cm, Montecucco, C, Montoya, F, Morgiel, E, Mouthon, L, Müller-Ladner, U, Nielsen, H, Opris, D, Ortiz-Santamaria, V, Otsa, K, Pileckyte, M, Pisarri, S, Popescu, M, Pozzi, Mr, Puppo, F, Radominski, Sc, Riccieri, V, Rosato, E, Rozman, B, Rubio, Sr, Rugiene, R, Saar, P, Salvador, Mj, Seidel, M, Sokolik, R, Solanki, K, Stamenkovic, B, Stankovic, A, Stebbings, S, Strauss, G, Sulli, A, Szamosi, S, Szechinski, J, Szmyrka-Kaczmarek, M, Szücs, G, Tanaseanu, Cm, Tiglea, I, Tyndall, A, Ughi, N, Uprus, M, Vacca, A, Varju, C, Venalis, A, Venalis, P, Walker, Ua, Widuchowska, M, Wiland, P, Wuttge, Dm, Zeni, S, and Zenone, T.

Subjects
Adult, Male, medicine.medical_specialty, Pathology, Adolescent, Klinikai orvostudományok, Biochemistry, Juvenile systemic sclerosi, Scleroderma, Microscopic Angioscopy, Systemic sclerosi, Scleroderma, Localized, Young Adult, Medicine, Juvenile, Humans, Young adult, Age of Onset, skin and connective tissue diseases, Child, Nailfold Capillaroscopy, Videocapillaroscopy, Aged, Retrospective Studies, EUSTAR, Scleroderma, Systemic, integumentary system, Capillaroscopy, business.industry, Similar distribution, Microcirculation, Autoantibody, Retrospective cohort study, Orvostudományok, Cell Biology, Middle Aged, medicine.disease, Dermatology, Capillaries, Nailfold capillaroscopy, Female, Age of onset, Cardiology and Cardiovascular Medicine, business, Juvenile systemic sclerosis, Systemic sclerosis
Abstract

Objective: Qualitative capillaroscopy patterns in juvenile- and adult-onset systemic sclerosis (SSc) were studied in adulthood using data from the EULAR Scleroderma Trials and Research (EUSTAR) database. Methods: Data collected between June 2004 and April 2013 were examined with focus on capillaroscopy. In this retrospective exploratory study, series of patients with juvenile-onset SSc were matched with series of adult-onset SSc having the same gender and autoantibody profile. Results: 30 of 123 patients with juvenile-onset and 2108 of 7133 with adult-onset SSc had data on capillaroscopy. Juvenile-onset SSc showed scleroderma pattern more frequently than adult-onset SSc (93.3% and 88%). The OR was 2.44 and 95% Cl 0.57-10.41. An active scleroderma pattern was present in 58% of juvenile- and 61% of adult-onset SSc. The OR was 0.91 and 95% Cl 0.28-2.93. The late scleroderma pattern was present in 61% of juvenile- and 55.5% of adult-onset SSc. The OR was 1.06 and 95% Cl 0.34-3.56. Conclusion: This is the first exploratory study on the comparison of capillaroscopy between juvenile- and adult-onset SSc in adulthood. Juvenile-onset SSc had an increase prevalence of sderoderma pattern, but a similar distribution of the three patterns was suggested. Further studies are needed to define this issue. (C) 2015 Elsevier Inc. All rights reserved.

Published
2015

25. Operator-independent quantitative chest computed tomography versus standard assessment of interstitial lung disease related to systemic sclerosis: A multi-centric study

Author

D. Imberti, Paola Caramaschi, Valeria Seletti, G. Lucchini, Daniele Santilli, Fabio De Gennaro, Raffaele Pellerito, Carlo Alberto Scirè, Alarico Ariani, G. Delsante, Flavio Cesare Bodini, E. Bravi, C. Benini, Federica Lumetti, M. Saracco, Simone Parisi, Eugenio Arrigoni, F. Mozzani, Luca Idolazzi, Nicola Sverzellati, Mario Silva, Enrico Fusaro, Ariani, A, Silva, M, Bravi, E, Saracco, M, Parisi, S, De Gennaro, F, Lumetti, F, Idolazzi, L, Seletti, V, Caramaschi, P, Benini, C, Bodini, F, Scire, C, Lucchini, G, Santilli, D, Mozzani, F, Imberti, D, Arrigoni, E, Delsante, G, Pellerito, R, Fusaro, E, and Sverzellati, N

Subjects
Lung Diseases, Male, medicine.medical_specialty, CT quantitative assessment, Chest ct, CT indexe, Computed tomography, Interstitial lung disease, NO, Scleroderma, Diagnosis, Differential, Rheumatology, Diagnosis, Medicine, Humans, Tomography, Scleroderma, Systemic, medicine.diagnostic_test, business.industry, Systemic, OsiriX, respiratory system, Middle Aged, medicine.disease, Prognosis, Respiratory Function Tests, X-Ray Computed, Tomography x ray computed, ROC Curve, Radiological weapon, Differential, CT indexes, Systemic sclerosis, Female, Lung Diseases, Interstitial, Tomography, X-Ray Computed, Radiology, Differential diagnosis, business, Interstitial
Abstract

Purpose. Interstitial lung disease (ILD) related to systemic sclerosis (SSc) is assessed with pulmonary functional tests (PFTs) and semi-quantitative scores based on extent of ILD detectable on chest computed tomography (CT). CT quantitative indexes (QCTIs) are promising tools to assess extent of ILD. This study's aim is to evaluate the validity of QCTI compared with that of chest CT standard evaluation and PFTs. Moreover, QCTI differences between patients subgroups according to prognostic stratifications were investigated. Methods. ILD-SSc of patients from six rheumatological clinics was routinely assessed with chest CT and PFTs. Patients were clustered according to prognosis based on functional and/or radiological examinations. Finally, chest CTs were processed with OsiriX in order to obtain QCTI. Results. Two hundred fifty-seven SSc patients were enrolled. QCTI correlation between extent of ILD and PFTs range from - 0.60 to 0.58 and from - 0.54 to 0.52, respectively. The majority of QCTI have a different distribution in patients subgroups based on prognosis. Most of QCTI discriminate patients with an ILD severity leading to a poor prognosis. Conclusions. QCTI assessment of ILD-SSc is comparable to the evaluation based on chest CT and/or PFTs. QCTI values corresponding to severe ILD were identified. QCTIs are excellent candidates for a new and more reliable SSc-ILD assessment.

Published
2015

26. TGFβ receptor gene variants in systemic sclerosis-related pulmonary arterial hypertension: results from a multicentre EUSTAR study of European Caucasian patients

Author

Gilles Chiocchia, Marco Matucci-Cerinic, Otylia Kowal-Bielecka, Jean-Luc Cracowski, Ulrich A. Walker, Julien Wipff, Jörg H W Distler, Matthieu Bouaziz, László Czirják, Inga Melchers, Nicolas Hunzelmann, Elisabeth Diot, Daniele Cusi, Catherine Boileau, Sara Lupoli, Philippe Dieudé, Marc Humbert, Yannick Allanore, Giovanna Cuomo, H.-Erich Wichmann, G. Riemekasten, Ulf Müller-Ladner, Eric Hachulla, P. G. Vlachoyiannopoulos, Paola Caramaschi, Costanza Conti, Paolo Airò, Martina Müller-Nurasyid, Barbara Ruiz, Mickaël Guedj, Valeria Riccieri, Lucile Revillod, Franco Cozzi, Nemanja Damjanov, Vasiliki Kalliopi Bournia, Eugénie Koumakis, Kiet Tiev, Université Paris Descartes - Paris 5 (UPD5), Université Paris Diderot - Paris 7 (UPD7), Université d'Évry-Val-d'Essonne (UEVE), Laboratoire Statistique et Génome (SG), Institut National de la Recherche Agronomique (INRA)-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Université Paris-Sud - Paris 11 (UP11), Hôpital Antoine Béclère, Assistance Publique - Hôpitaux de Paris (AP-HP), Centre Chirurgical Marie Lannelongue (CCML), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Leibniz Association, Spedali Civil Brescia, University of Freiburg [Freiburg], Université de Lille, Droit et Santé, Università degli Studi di Milano [Milano] (UNIMI), Fdn Filarete, Partenaires INRAE, European League Against Rheumatism Scleroderma Trials and Research group (EUSTAR), Association des Sclerodermiques de France, INSERM, Agence Nationale pour la Recherche [R07094KS], Pfizer, Koumakis, E, Wipff, J, Dieudé, P, Ruiz, B, Bouaziz, M, Revillod, L, Guedj, M, Distler, Jh, Matucci Cerinic, M, Humbert, M, Riemekasten, G, Airo, P, Melchers, I, Hachulla, E, Cusi, D, Wichmann, He, Hunzelmann, N, Tiev, K, Caramaschi, P, Diot, E, Kowal Bielecka, O, Cuomo, Giovanna, Walker, U, Czirják, L, Damjanov, N, Lupoli, S, Conti, C, Müller Nurasyid, M, Müller Ladner, U, Riccieri, V, Cracowski, Jl, Cozzi, F, Bournia, Vk, Vlachoyiannopoulos, P, Chiocchia, G, Boileau, C, Allanore, Y., Università degli Studi di Firenze = University of Florence (UniFI), and Università degli Studi di Milano = University of Milan (UNIMI)

Subjects
Genetics and Molecular Biology (all), Male, Systemic disease, Candidate gene, DNA Mutational Analysis, Biochemistry, DISEASE, Scleroderma, 0302 clinical medicine, Medizinische Fakultät, Transforming Growth Factor beta, Receptors, Immunology and Allergy, Familial Primary Pulmonary Hypertension, [MATH]Mathematics [math], skin and connective tissue diseases, 0303 health sciences, biology, integumentary system, arterial pulmonary hypertension, Pulmonary, Single Nucleotide, ASSOCIATION, Connective tissue disease, 3. Good health, Hypertension, Female, systemic sclerosi, Genotype, Hypertension, Pulmonary, European Continental Ancestry Group, Immunology, Polymorphism, Single Nucleotide, General Biochemistry, Genetics and Molecular Biology, White People, 03 medical and health sciences, Rheumatology, medicine, SNP, Humans, [INFO]Computer Science [cs], Genetic Predisposition to Disease, ddc:610, Polymorphism, HEREDITARY HEMORRHAGIC TELANGIECTASIA, Genotyping, ALK-1, 030304 developmental biology, 030203 arthritis & rheumatology, Scleroderma, Systemic, business.industry, MUTATIONS, Systemic, Receptors, Transforming Growth Factor beta, Biochemistry, Genetics and Molecular Biology (all), Transforming growth factor beta, medicine.disease, Pulmonary hypertension, BMPR2, biology.protein, business
Abstract

IntroductionSystemic sclerosis (SSc)-related pulmonary arterial hypertension (PAH) has emerged as a major mortality prognostic factor. Mutations of transforming growth factor beta (TGFβ) receptor genes strongly contribute to idiopathic and familial PAH.ObjectiveTo explore the genetic bases of SSc–PAH, we combined direct sequencing and genotyping of candidate genes encoding TGFβ receptor family members.Materials and methodsTGFβ receptor genes, BMPR2, ALK1, TGFR2 and ENG, were sequenced in 10 SSc–PAH patients, nine SSc and seven controls. In addition, 22 single-nucleotide polymorphisms (SNP) of these four candidate genes were tested for association in a first set of 824 French Caucasian SSc patients (including 54 SSc–PAH) and 939 controls. The replication set consisted of 1516 European SSc (including 219 SSc–PAH) and 3129 controls from the European League Against Rheumatism Scleroderma Trials and Research group network.ResultsNo mutation was identified by direct sequencing. However, two repertoried SNP, ENG rs35400405 and ALK1 rs2277382, were found in SSc–PAH patients only. The genotyping of 22 SNP including the latter showed that only rs2277382 was associated with SSc–PAH (p=0.0066, OR 2.13, 95% CI 1.24 to 3.65). Nevertheless, this was not replicated with the following result in combined analysis: p=0.123, OR 0.79, 95% CI 0.59 to 1.07.ConclusionsThis study demonstrates the lack of association between these TGFβ receptor gene polymorphisms and SSc–PAH using both sequencing and genotyping methods.

Published
2012

27. Brief report: candidate gene study in systemic sclerosis identifies a rare and functional variant of the TNFAIP3 locus as a risk factor for polyautoimmunity

Author

Eugénie Koumakis, Paola Caramaschi, Yannick Allanore, E. Diot, Patrick H. Carpentier, Jean Sibilia, André Kahan, Matthieu Giraud, Jean-Luc Cracowski, Vanessa Cohignac, Mirko Manetti, Philippe Dieudé, Olivier Meyer, Anne Cosnes, Gabriele Valentini, Luc Mouthon, Serena Guiducci, Kiet Tiev, Camille Francès, Paolo Airò, Gilles Chiocchia, Marco Matucci-Cerinic, Zahir Amoura, Catherine Boileau, Valeria Riccieri, Giovanna Cuomo, Eric Hachulla, Koumakis, E, Giraud, M, Dieudé, P, Cohignac, V, Cuomo, Giovanna, Airo, P, Hachulla, E, Cerinic, Mm, Diot, E, Caramaschi, P, Mouthon, L, Riccieri, V, Cracowski, Jl, Tiev, Kp, Frances, C, Amoura, Z, Sibilia, J, Cosnes, A, Carpentier, P, Valentini, Gabriele, Manetti, M, Guiducci, S, Meyer, O, Kahan, A, Boileau, C, Chiocchia, G, and Allanore, Y.

Subjects
Adult, Male, Candidate gene, Linkage disequilibrium, Genotype, systemic sclerosis, Immunology, Single-nucleotide polymorphism, Locus (genetics), Autoimmunity, Biology, TNFAIP3, Polymorphism, Single Nucleotide, Linkage Disequilibrium, Rheumatology, Risk Factors, Immunology and Allergy, Humans, Pharmacology (medical), genetics, Genetic Predisposition to Disease, skin and connective tissue diseases, Tumor Necrosis Factor alpha-Induced Protein 3, Aged, Genetics, TNFAIP3 locus, Scleroderma, Systemic, Case-control study, Intracellular Signaling Peptides and Proteins, Nuclear Proteins, Odds ratio, Middle Aged, Phosphoproteins, DNA-Binding Proteins, Exodeoxyribonucleases, Phenotype, Case-Control Studies, Female
Abstract

Objective Systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) share some pathophysiologic bases as evidenced by individual and familial polyautoimmunity and common susceptibility genetic factors. With regard to the latter, there has been a recent shift from the “common variant” to the “rare variant” paradigm, since rare variants of TNFAIP3 and TREX1 with large effect sizes have recently been discovered in SLE. The present study was undertaken to investigate whether rare variants of TNFAIP3 and TREX1 are also associated with SSc. Methods TREX1 single-nucleotide polymorphisms (SNPs) rs3135946, rs7626978, rs3135943, and rs11797 and TNFAIP3 SNPs rs9494883, rs72063345, rs5029939, rs2230926, rs117480515, and rs7749323 were genotyped in a discovery set (985 SSc patients and 1,011 controls), and replication analysis of the most relevant results was performed in a second set (622 SSc patients and 493 controls). Results No association between TREX1 variants and SSc was observed. For TNFAIP3, we first demonstrated that a low-frequency variant, rs117480515, tagged the recently identified TT>A SLE dinucleotide. In the discovery sample, we observed that all tested TNFAIP3 variants were in linkage disequilibrium and were associated with SSc and various SSc subsets, including the polyautoimmune phenotype. We subsequently genotyped rs117480515 in the replication sample and found it to be associated solely with the SSc polyautoimmune subset (odds ratio 3.51 [95% confidence interval 2.28–5.41], P = 8.58 × 10−9) in the combined populations. Genotype–messenger RNA (mRNA) expression correlation analysis revealed that the TNFAIP3 rs117480515 risk allele was associated with decreased mRNA expression. Conclusion The present findings establish the TNFAIP3 locus as a susceptibility factor for the subset of SSc with a polyautoimmune phenotype. Our results support the implication of rare/low-frequency functional variants and the critical role of A20 in autoimmunity.

Published
2012

28. Genome-wide scan identifies TNIP1, PSORS1C1, and RHOB as novel risk loci for systemic sclerosis

Author

Valeria Riccieri, László Czirják, Yannick Allanore, Jean-Luc Cracowski, Catherine Boileau, Inga Melchers, H.-Erich Wichmann, Jean-Charles Lambert, Oliver Meyer, Julien Wipff, Mohamad Saad, Jörg H W Distler, Luc Mouthon, Anne Marie Dupuy, Costanza Conti, Martina Müller, Nicolas Hunzelmann, Maria Martinez, Marco Matucci-Cerinic, Elisabeth Diot, Ulf Müller-Ladner, Paola Caramaschi, Otylia Kowal-Bielecka, André Kahan, Erika Salvi, G. Riemekasten, Arnold Munnich, Paolo Airò, Luc Letenneur, Eric Hachulla, Kiet Tiev, Barbara Ruiz, Daniele Cusi, Jérôme Avouac, Nemanja Damjanov, Philippe Dieudé, Gabriele Valentini, Philippe Amouyel, Service de rhumatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement (Inserm U781), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Rhumatologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-PRES Sorbonne Paris Cité, Immunopathologie rénale, récepteurs et inflammation, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Internal Medicine 3, Institute for Clinical Immunology Erlangen-Nuremberg, Epidémiologie des maladies chroniques : impact des interactions gène environnement sur la santé des populations, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Departments of Medicine, Biomedicine & Rheumatology, Università degli Studi di Firenze = University of Florence (UniFI)-Division of Rheumatology AOUC - Denothe Centre, Department of Rheumatology and Clinical Immunology, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Rheumatology and Clinical Immunology, Spedali Civili, Clinical Research Unit for Rheumatology, Universitäts Klinikum Freiburg = University Medical Center Freiburg (Uniklinik), Service de médecine interne, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Department of Medicine, Surgery, and Dentistry, University of Milano, Genomics and Bioinformatics Platform, Fondazione Filarete, Institute of Medical Informatics, Biometry, and Epidemiology, Ludwig-Maximilians-Universität München (LMU)-Chair of Epidemiology, Institute of Epidemiology I, Helmholtz Zentrum München = German Research Center for Environmental Health, Department of Dermatology, University of Cologne, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Rheumatology Unit, Università degli studi di Verona = University of Verona (UNIVR), Pathologies Respiratoires : Protéolyse et Aérosolthérapie, Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Rheumatology and Internal Medicine, Medical University of Białystok (MUB), Department of Clinical and Experimental Medicine, University of Naples Federico II = Università degli studi di Napoli Federico II, Service de médecine interne et centre de référence des maladies rares [CHU Cochin], Department of Immunology and Rheumatology, University of Pecs, Institute of Rheumatology, University of Belgrade [Belgrade], Kos Genetic SRL, Institute of Genetic Epidemiology, Justus-Liebig-Universität Gießen = Justus Liebig University (JLU), Division of Rheumatology, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Centre d'Investigation Clinique [Grenoble] (CIC Grenoble), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Hôpital Michallon-Institut National de la Santé et de la Recherche Médicale (INSERM), Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Service de biochimie, d'hormonologie et de génétique moléculaire [CHU Amrboise Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], This project was funded by Agence Nationale pour la Recherche (Project ANR-08-GENO-016-1) and supported by research grants from SERVIER research group, SANOFI-AVENTIS, Association des Sclérodermies de France, and Groupe Français de Recherche sur la Sclérodermie. The KORA (Cooperative health research in the Region of Augsburg) studies were financed by the Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany, and supported by grants from the German Federal Ministry of Education and Research (BMBF) and by the State of Bavaria. Part of this work was financed by the German National Genome Research Network (NGFN). This research was supported within the Munich Center of Health Sciences (MC Health) as part of LMUinnovativ. HYPERGENES (European Network for Genetic-Epidemiological Studies) is funded by EU within the FP7: HEALTH-F4-2007-201550., European Project: 201550,EC:FP7:HEALTH,FP7-HEALTH-2007-A,HYPERGENES(2008), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-PRES Sorbonne Paris Cité, Division of Rheumatology AOUC - Denothe Centre-Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Freiburg University Medical Center, German Research Center for Environmental Health-Helmholtz-Zentrum München (HZM), Service de médecine interne [Saint-Antoine], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), University of Verona (UNIVR), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), Medical University of Bialystok, University of Naples Federico II, German Research Center for Environmental Health, Justus-Liebig-Universität Gießen (JLU), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI)-Division of Rheumatology AOUC - Denothe Centre, Allanore, Y, Saad, M, Dieudé, P, Avouac, J, Distler, Jh, Amouyel, P, MATUCCI CERINIC, M, Riemekasten, G, Airo, P, Melchers, I, Hachulla, E, Cusi, D, Wichmann, He, Wipff, J, Lambert, Jc, Hunzelmann, N, Tiev, K, Caramaschi, P, Diot, E, KOWAL BIELECKA, O, Valentini, Gabriele, Mouthon, L, Czirják, L, Damjanov, N, Salvi, E, Conti, C, Müller, M, MÜLLER LADNER, U, Riccieri, V, Ruiz, B, Cracowski, Jl, Letenneur, L, Dupuy, Am, Meyer, O, Kahan, A, Munnich, A, Boileau, C, Martinez, M., Autard, Delphine, European Network for Genetic-Epidemiological Studies: building a method to dissect complex genetic traits, using essential hypertension as a disease model - HYPERGENES - - EC:FP7:HEALTH2008-01-01 - 2011-12-31 - 201550 - VALID, and Service de médecine interne [CHU Saint-Antoine]

Subjects
Male, Cancer Research, Linkage disequilibrium, Epidemiology, systemic sclerosis, RHOB, Genome-wide association study, [SDV.GEN] Life Sciences [q-bio]/Genetics, Linkage Disequilibrium, MESH: Scleroderma, Systemic, Scleroderma, Major Histocompatibility Complex, Disease Mapping, TNIP1 locus, 0302 clinical medicine, Germany, Genetics of the Immune System, HLA-DQ beta-Chains, MESH: Proteins, Connective Tissue Diseases, rhoB GTP-Binding Protein, Genetics (clinical), Genetics, 0303 health sciences, MESH: Polymorphism, Single Nucleotide, MESH: Genetic Predisposition to Disease, MESH: Case-Control Studies, 3. Good health, DNA-Binding Proteins, Europe, Italy, MESH: Linkage Disequilibrium, Genetic Epidemiology, Medicine, Cytokines, Female, Inflammatory and Psoriatic Arthritis, France, Research Article, Adult, lcsh:QH426-470, Medizinische Fakultät -ohne weitere Spezifikation, Rheumatoid Arthritis, Single-nucleotide polymorphism, Locus (genetics), Biology, Systemic Lupus Erythematosus, Polymorphism, Single Nucleotide, Autoimmune Diseases, 03 medical and health sciences, MESH: Major Histocompatibility Complex, Rheumatology, RhoB GTP-Binding Protein, functional polymorphism, extracellular-matrix, association, scleroderma, population, disease, susceptibility, fibrosis, receptor, stat4, Psoriasis, Humans, SNP, Genetic Predisposition to Disease, genome-wide scan, ddc:610, Molecular Biology, MESH: Germany, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, Genetic association, MESH: rhoB GTP-Binding Protein, 030203 arthritis & rheumatology, [SDV.GEN]Life Sciences [q-bio]/Genetics, Scleroderma, Systemic, MESH: Humans, Proteins, MESH: Italy, MESH: Adult, MESH: HLA-DQ beta-Chains, MESH: Male, MESH: France, lcsh:Genetics, Immune System, Case-Control Studies, Immunology, MESH: Genome-Wide Association Study, Clinical Immunology, MESH: Europe, MESH: Female, MESH: DNA-Binding Proteins, Genome-Wide Association Study
Abstract

Systemic sclerosis (SSc) is an orphan, complex, inflammatory disease affecting the immune system and connective tissue. SSc stands out as a severely incapacitating and life-threatening inflammatory rheumatic disease, with a largely unknown pathogenesis. We have designed a two-stage genome-wide association study of SSc using case-control samples from France, Italy, Germany, and Northern Europe. The initial genome-wide scan was conducted in a French post quality-control sample of 564 cases and 1,776 controls, using almost 500 K SNPs. Two SNPs from the MHC region, together with the 6 loci outside MHC having at least one SNP with a P, Author Summary Systemic sclerosis (SSc) is a connective tissue disease characterized by generalized microangiopathy, severe immunologic alterations, and massive deposits of matrix components in the connective tissue. Epidemiological investigations indicate that SSc follows a pattern of multifactorial inheritance; however, only a few loci have been replicated in multiple studies. We undertook a two-stage genome-wide association study of SSc involving over 8,800 individuals of European ancestry. Combined analyses showed independent association at the known HLA-DQB1 region and revealed associations at PSORS1C1, TNIP1, and RHOB loci, in agreement with a strong immune genetic component. Because of its biological relevance, and previous reports of genetic association at this locus with other connective tissue disorders, we investigated TNIP1 expression. We observed a markedly reduced expression of the gene and its protein product in SSc, as well as its potential implication in control of extra-cellular matrix synthesis, providing a new clue for a link between inflammation/immunity and fibrosis.

Published
2011

29. Risk factors for a first thrombotic event in antiphospholipid antibody carriers: a prospective multicentre follow-up study

Author

Amelia, Ruffatti, Teresa, Del Ross, Manuela, Ciprian, Maria T, Bertero, Savino, Sciascia, Sciascia, Salvatore, Salvatore, Scarpato, Carlomaurizio, Montecucco, Silvia, Rossi, Paola, Caramaschi, Domenico, Biasi, Andrea, Doria, Mariaelisa, Rampudda, Nuzzo, Monica, Fabio, Fischetti, Ugo, Picillo, Antonio, Brucato, Elisa, Salvan, Pengo, Vittorio, Pierluigi, Meroni, Angela, Tincani, A, T, Ruffatti, A, Del Ross, T, Ciprian, M, Bertero, Mt, Sciascia, S, Scarpato, S, Montecucco, C, Rossi, S, Caramaschi, P, Biasi, D, Doria, A, Rampudda, M, Monica, N, Fischetti, Fabio, Picillo, U, Brucato, A, Salvan, E, Vittorio, P, Meroni, P, and Tincani, A.

Subjects
Adult, Male, medicine.medical_specialty, Antibodies, Antiphospholipid, Antiphospholipid Syndrome, Autoantibodies, Epidemiologic Methods, Female, Humans, Hypertension, Lupus Coagulation Inhibitor, Middle Aged, Thrombosis, Young Adult, Immunology, Antiphospholipid, Antibodies, General Biochemistry, Genetics and Molecular Biology, connective diseases, Rheumatology, Antiphospholipid syndrome, Internal medicine, Epidemiology, medicine, Immunology and Allergy, thrombosi, Risk factor, Young adult, phospholipids, phospholipid, Lupus anticoagulant, business.industry, Vascular disease, medicine.disease, autoantibodie, Surgery, autoantibodies, thrombosis, business
Abstract

ObjectivesTo assess risk factors for a first thrombotic event in confirmed antiphospholipid (aPL) antibody carriers and to evaluate the efficacy of prophylactic treatments.MethodsInclusion criteria were age 18–65 years, no history of thrombosis and two consecutive positive aPL results. Demographic, laboratory and clinical parameters were collected at enrolment, once a year during the follow-up and at the time of the thrombotic event, whenever that occurred.Results258 subjects were prospectively observed between October 2004 and October 2008. The mean±SD follow-up was 35.0±11.9 months (range 1–48). A first thrombotic event (9 venous, 4 arterial and 1 transient ischaemic attack) occurred in 14 subjects (5.4%, annual incidence rate 1.86%). Hypertension and lupus anticoagulant (LA) were significantly predictive of thrombosis (both at pConclusionsHypertension and LA are independent risk factors for thrombosis in aPL carriers. Thromboprophylaxis in these subjects should probably be limited to high-risk situations.

Published
2011

30. Association of a KCNA5 gene polymorphism with systemic sclerosis-associated pulmonary arterial hypertension in the European Caucasian population

Author

J.L. Cracowski, Julien Wipff, Eric Hachulla, Philippe Dieudé, Paolo Airò, Patrick H. Carpentier, Kiet Tiev, E. Diot, Yannick Allanore, Gabriele Valentini, Barbara Ruiz, Catherine Boileau, Paola Caramaschi, Barbara Girerd, Bruno Degano, Marc Humbert, Marco Matucci-Cerinic, Olivier Meyer, Jérôme Avouac, G. Riemekasten, Inga Melchers, Jean Sibilia, Zahir Amoura, J. H. W. Distler, Valeria Riccieri, Mickaël Guedj, André Kahan, Luc Mouthon, Nicolas Hunzelmann, Ingo H. Tarner, Wipff, J, Dieudé, P, Guedj, M, Ruiz, B, Riemekasten, G, Cracowski, Jl, MATUCCI CERINIC, M, Melchers, I, Humbert, M, Hachulla, E, Airo, P, Diot, E, Hunzelmann, N, Caramaschi, P, Sibilia, J, Valentini, Gabriele, Tiev, K, Girerd, B, Mouthon, L, Riccieri, V, Carpentier, Ph, Distler, J, Amoura, Z, Tarner, I, Degano, B, Avouac, J, Meyer, O, Kahan, A, Boileau, C, Allanore, Y., Association des Sclerodermiques de France, INSERM, Agence Nationale pour la Recherche [R07094KS], Societe Francaise de Rhumatologie, Groupe Francais de Recherche sur la Sclerodermie, and German Federal Ministry for Education and Research [01 GM 0310, 01 GM 0634]

Subjects
Adult, Male, Pathology, medicine.medical_specialty, Candidate gene, STRATEGIES, SMOOTH-MUSCLE-CELLS, [SDV]Life Sciences [q-bio], Hypertension, Pulmonary, Immunology, Population, Single-nucleotide polymorphism, SUSCEPTIBILITY, Gastroenterology, Polymorphism, Single Nucleotide, CLASSIFICATION, White People, CAPACITY, Kv1.5 Potassium Channel, Rheumatology, RISK-FACTOR, IRF5, SCLERODERMA, Internal medicine, medicine, Odds Ratio, Immunology and Allergy, Humans, Pharmacology (medical), Genetic Predisposition to Disease, PREDICTORS, skin and connective tissue diseases, education, Allele frequency, Associated Pulmonary Arterial Hypertension, Aged, education.field_of_study, Scleroderma, Systemic, integumentary system, MUTATIONS, business.industry, Case-control study, Odds ratio, Middle Aged, Europe, Case-Control Studies, Female, Gene polymorphism, business
Abstract

Objective Pulmonary arterial hypertension (PAH) has emerged as a leading cause of death in systemic sclerosis (SSc). The genetic basis of PAH has been unraveled in recent years, with a major role played by transforming growth factor β receptors; however, some other candidate genes have also been advocated, including potassium voltage-gated channel, shaker-related subfamily, member 5 (KCNA5). We undertook this study to determine whether KCNA5 polymorphisms confer susceptibility to SSc and its vascular phenotype, including PAH. Methods Four KCNA5 single-nucleotide polymorphisms (SNPs), rs10744676, rs1860420, rs3741930, and rs2284136, were genotyped in a discovery set of 638 SSc patients and 469 controls. In addition, rs10744676 was genotyped in an independent replication sample (938 SSc patients and 564 controls) and in a cohort of 168 patients with different PAH subtypes. Results The KCNA5 rs10744676 variant was found to be associated with SSc in the discovery sample, with an odds ratio (OR) of 0.62 (95% confidence interval [95% CI] 0.48–0.79, adjusted P = 0.0003) in comparison with controls (C allele frequency 11.4% versus 17.2%). When subphenotypes were investigated, an association was found solely for PAH associated with SSc (OR 0.31 [95% CI 0.13–0.71], adjusted P = 0.04). The other KCNA5 SNPs tested were not associated with any SSc subset. The above association with PAH associated with SSc was replicated in the second set. In the combined population, rs10744676 was strongly associated with PAH associated with SSc in comparison with controls (OR 0.36 [95% CI 0.21–0.63], P = 0.0002). In the independent cohort of patients with PAH, after investigating PAH subtypes, only rs10744676 showed an association with PAH associated with SSc. Conclusion Our results provide the first evidence for an association between the KCNA5 rs10744676 variant and PAH associated with SSc.

Published
2010

31. A case-control study of occupational exposures and systemic sclerosis

Author

Federica Edith Pisa, Luciano Romeo, Alberto Betta, Paola Caramaschi, Domenico Biasi, Fabio Barbone, Massimo Bovenzi, A. Tonello, Bovenzi, Massimo, Barbone, F, Pisa, Fe, Betta, A, Romeo, L, Tonello, A, Biasi, D, and Caramaschi, P.

Subjects
Adult, Male, medicine.medical_specialty, Multivariate analysis, chemical, systemic sclerosis, chemicals, occupational exposures, solvent, Vibration, Occupational medicine, hand-arm vibration, organic solvents, Risk Factors, Environmental health, Occupational Exposure, occupation, Medicine, Humans, solvents, silica, Occupations, Sex Distribution, Scleroderma, Systemic, business.industry, Incidence (epidemiology), Incidence, Public Health, Environmental and Occupational Health, Case-control study, Odds ratio, Middle Aged, Silicon Dioxide, Confidence interval, Surgery, Logistic Models, Italy, Case-Control Studies, Multivariate Analysis, Etiology, Solvents, Female, Occupational exposure, business, systemic sclerosi
Abstract

Objectives: A case–control study was conducted in Verona, Italy, to assess the relationship between occupation, occupational exposures and systemic sclerosis (SSc). Methods: Fifty-five cases (46 female and nine male) and 171 controls were recruited. Interviews provided work histories, including job titles, industry and likelihood of occupational exposure to silica, hand– arm vibration, organic solvents, and other chemicals. Odds ratios (ORs) and 95% confidence intervals (95% CI) were estimated. Results: Female teachers (OR 3.4, 95% CI 1.2–10.1) and textile workers (OR 2.1, 95% CI 1.0–4.6) were at an increased risk of SSc. Compared with those never exposed, age-adjusted and gender-adjusted ORs were 2.3 (95% CI 1.0–5.4) among subjects exposed to organic solvents, 2.5 (95% CI 0.8–8.0) for exposure to selected chemicals, 1.7 (95% CI 0.4–7.6) for exposure to silica, and 1.5 (95% CI 0.5–4.8) for usage of vibrating tools. When data analysis was stratified according to gender, only men showed a significant increase in risk for exposure to solvents and selected chemicals. Conclusions: The findings of this study tend to support the role of organic solvents and certain chemicals in SSc causation. The association with teaching and working in the textile industry suggests that other exposures are involved in the aetiology of SSc among women. However, because of the small number of subjects, particularly in stratified analyses, chance cannot be ruled out as an explanation of some findings of this study.

Published
2003

32. Gender differences in early systemic sclerosis patients: A report from the EULAR scleroderma trials and research group (EUSTAR) database

Author

Carreira, Patricia E, Carmona, Loreto, Joven, Beatriz E, Loza, Estíbaliz, Andreu, Jose Luis, Riemekasten, Gabriela, Vettori, Serena, Balbir-Gurman, Alexandra, Airò, Paolo, Walker, Ulrich A, Damjanov, Nemanja, Matucci-Cerinic, Marco, Ananieva, Lidia P, Rednic, Simona, Czirják, László, Distler, Oliver, Farge, Dominique, Hesselstrand, Roger, Corrado, Ada, Caramaschi, Paola, Tikly, Mohammed, Allanore, Yannick, Eustar, Coauthors, Sulli, Alberto, Carreira, Pe, Carmona, L, Joven, Be, Loza, E, Andreu, Jl, Riemekasten, G, Vettori, S, Balbir-Gurman, A, Airò, P, Walker, Ua, Damjanov, N, Matucci-Cerinic, M, Ananieva, Lp, Rednic, S, Czirják, L, Distler, O, Farge, D, Hesselstrand, R, Corrado, A, Caramaschi, P, Tikly, M, Allanore, Y, University of Zurich, Carreira, Patricia E, and Chizzolini, Carlo

Subjects
Lung Diseases, Male, 0301 basic medicine, Databases, Factual, 2745 Rheumatology, Acute-Phase Proteins/analysis, 610 Medicine & health, Severity of Illness Index, Scleroderma, Databases, 03 medical and health sciences, Sex Factors, 0302 clinical medicine, Scleroderma, Limited, Risk Factors, Humans, Limited, skin and connective tissue diseases, Lung Diseases/diagnosis/etiology, Factual, Diffuse/blood/complications/diagnosis/immunology, Autoantibodies, ddc:616, 030203 arthritis & rheumatology, 2403 Immunology, integumentary system, Raynaud Disease/diagnosis/etiology, 10051 Rheumatology Clinic and Institute of Physical Medicine, Nuclear Proteins, Raynaud Disease, Health Status Disparities, Acute-Phase Proteins, Biomarkers, Cross-Sectional Studies, Disease Progression, Female, Prognosis, Scleroderma, Diffuse, Diffuse, 030104 developmental biology, DNA Topoisomerases, Type I, 2723 Immunology and Allergy, Nuclear Proteins/immunology, Autoantibodies/blood, Limited/blood/complications/diagnosis/immunology, Biomarkers/blood
Abstract

OBJECTIVES: To describe differences in clinical presentation between men and women in a large group of patients with early (

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