Racial differences in systemic sclerosis disease presentation: a European Scleroderma Trials and Research group study

Objectives. Racial factors play a significant role in SSc. We evaluated differences in SSc presentations between white patients (WP), Asian patients (AP) and black patients (BP) and analysed the effects of geographical locations.Methods. SSc characteristics of patients from the EUSTAR cohort were cross-sectionally compared across racial groups using survival and multiple logistic regression analyses.Results. The study included 9162 WP, 341 AP and 181 BP. AP developed the first non-RP feature faster than WP but slower than BP. AP were less frequently anti-centromere (ACA; odds ratio (OR) = 0.4, P < 0.001) and more frequently anti-topoisomerase-I autoantibodies (ATA) positive (OR = 1.2, P = 0.068), while BP were less likely to be ACA and ATA positive than were WP [OR(ACA) = 0.3, P < 0.001; OR(ATA) = 0.5, P = 0.020]. AP had less often (OR = 0.7, P = 0.06) and BP more often (OR = 2.7, P < 0.001) diffuse skin involvement than had WP.AP and BP were more likely to have pulmonary hypertension [OR(AP) = 2.6, P < 0.001; OR(BP) = 2.7, P = 0.03 vs WP] and a reduced forced vital capacity [OR(AP) = 2.5, P < 0.001; OR(BP) = 2.4, P < 0.004] than were WP. AP more often had an impaired diffusing capacity of the lung than had BP and WP [OR(AP vs BP) = 1.9, P = 0.038; OR(AP vs WP) = 2.4, P < 0.001]. After RP onset, AP and BP had a higher hazard to die than had WP [hazard ratio (HR) (AP) = 1.6, P = 0.011; HR(BP) = 2.1, P < 0.001].Conclusion. Compared with WP, and mostly independent of geographical location, AP have a faster and earlier disease onset with high prevalences of ATA, pulmonary hypertension and forced vital capacity impairment and higher mortality. BP had the fastest disease onset, a high prevalence of diffuse skin involvement and nominally the highest mortality

Phenotype of limited cutaneous systemic sclerosis patients with positive anti-topoisomerase I antibodies: data from EUSTAR cohort

Objectives: To characterize patients with positive anti-topoisomerase I (ATA) in the limited cutaneous Systemic Sclerosis (lcSSc). Methods: SSc patients enrolled in the EUSTAR cohort with disease duration ≤3 yrs at database entry were considered. We assessed the risk of major organ involvement in the following groups: 1) ATA-lcSSc vs anticentromere (ACA)-lcSSc and vs antinuclear antibodies without specificity (ANA)-lcSSc; 2) ATA-lcSSc vs ATA-diffuse cutaneous (dc)SSc. Cox regression models with time-dependent covariates were performed with the following outcomes: new-onset interstitial lung disease (ILD), ILD progression (Forced Vital Capacity, FVC decline ≥10% and ≥5% vs values at ILD diagnosis); primary myocardial involvement (PMI); pulmonary hypertension (PH); any organ involvement and all-cause mortality. Results: We included 1252 patients (194 ATA-lcSSc, 15.5%), with 7.7 ± 3.5 yrs follow-up. ILD risk was higher in ATA-lcSSc vs ACA- and ANA-lcSSc, and similar to ATA-dcSSc, although with less frequent restrictive lung disease. Risk of FVC decline ≥ 10% (35% of ATA-lcSSc) was lower in ATA-lcSSc than in ATA-dcSSc, whereas FVC decline ≥5% occurs similarly between ATA-lcSSc (58% of patients) and other SSc subsets, including ATA-dcSSc. The risk of PMI was similar in ATA-lcSSc and ANA-lcSSc, lower than in ACA-lcSSc; no difference in PH and mortality risk was observed among lcSSc subsets. Risk of any organ involvement, PMI, PH was lower and the mortality tended to be lower in ATA-lcSSc vs ATA-dcSSc. Conclusion: ATA-lcSSc patients have a high risk of ILD, albeit with a lower risk of progression compared with ATA-dcSSc, supporting a careful screening for ILD in this subgroup

Phenotype of limited cutaneous systemic sclerosis patients with positive anti-topoisomerase I antibodies: data from EUSTAR cohort

OBJECTIVES To characterize patients with positive anti-topoisomerase I (ATA) in the limited cutaneous Systemic Sclerosis (lcSSc). METHODS SSc patients enrolled in the EUSTAR cohort with disease duration ≤3 yrs at database entry were considered. We assessed the risk of major organ involvement in the following groups: 1) ATA-lcSSc vs anticentromere (ACA)-lcSSc and vs antinuclear antibodies without specificity (ANA)-lcSSc; 2) ATA-lcSSc vs ATA-diffuse cutaneous (dc)SSc. Cox regression models with time-dependent covariates were performed with the following outcomes: new-onset interstitial lung disease (ILD), ILD progression (Forced Vital Capacity, FVC decline ≥10% and ≥5% vs values at ILD diagnosis); primary myocardial involvement (PMI); pulmonary hypertension (PH); any organ involvement and all-cause mortality. RESULTS We included 1252 patients (194 ATA-lcSSc, 15.5%), with 7.7 ± 3.5 yrs follow-up. ILD risk was higher in ATA-lcSSc vs ACA- and ANA-lcSSc, and similar to ATA-dcSSc, although with less frequent restrictive lung disease. Risk of FVC decline ≥ 10% (35% of ATA-lcSSc) was lower in ATA-lcSSc than in ATA-dcSSc, whereas FVC decline ≥5% occurs similarly between ATA-lcSSc (58% of patients) and other SSc subsets, including ATA-dcSSc. The risk of PMI was similar in ATA-lcSSc and ANA-lcSSc, lower than in ACA-lcSSc; no difference in PH and mortality risk was observed among lcSSc subsets. Risk of any organ involvement, PMI, PH was lower and the mortality tended to be lower in ATA-lcSSc vs ATA-dcSSc. CONCLUSION ATA-lcSSc patients have a high risk of ILD, albeit with a lower risk of progression compared with ATA-dcSSc, supporting a careful screening for ILD in this subgroup

Erectile dysfunction is frequent in systemic sclerosis and associated with severe disease: a study of the EULAR Scleroderma Trial and Research group

INTRODUCTION: Erectile dysfunction (ED) is common in men with systemic sclerosis (SSc) but the demographics, risk factors and treatment coverage for ED are not well known. METHOD: This study was carried out prospectively in the multinational EULAR Scleroderma Trial and Research database by amending the electronic data-entry system with the International Index of Erectile Function-5 and items related to ED risk factors and treatment. Centres participating in this EULAR Scleroderma Trial and Research substudy were asked to recruit patients consecutively. RESULTS: Of the 130 men studied, only 23 (17.7%) had a normal International Index of Erectile Function-5 score. Thirty-eight per cent of all participants had severe ED (International Index of Erectile Function-5 score ≤ 7). Men with ED were significantly older than subjects without ED (54.8 years vs. 43.3 years, P < 0.001) and more frequently had simultaneous non-SSc-related risk factors such as alcohol consumption. In 82% of SSc patients, the onset of ED was after the manifestation of the first non-Raynaud's symptom (median delay 4.1 years). ED was associated with severe cutaneous, muscular or renal involvement of SSc, elevated pulmonary pressures and restrictive lung disease. ED was treated in only 27.8% of men. The most common treatment was sildenafil, whose efficacy is not established in ED of SSc patients. CONCLUSIONS: Severe ED is a common and early problem in men with SSc. Physicians should address modifiable risk factors actively. More research into the pathophysiology, longitudinal development, treatment and psychosocial impact of ED is needed

Glucocorticoids prescribing practices in systemic sclerosis: an analysis of the EUSTAR database

To estimate the long-term exposure to glucocorticoids (GC), the factors associated with, and the variations in prescribing practices over time and across recruiting countries

Phenotype of limited cutaneous systemic sclerosis patients with positive anti-topoisomerase I antibodies: data from EUSTAR cohort

OBJECTIVES: To characterize patients with positive anti-topoisomerase I (ATA) in lcSSc. METHODS: SSc patients enrolled in the EUSTAR cohort with a disease duration of ≤3 years at database entry were considered. We assessed the risk of major organ involvement in the following groups: ATA-lcSSc vs ACA-lcSSc and vs ANA without specificity (ANA)-lcSSc, and ATA-lcSSc vs ATA-dcSSc. Cox regression models with time-dependent covariates were performed with the following outcomes: new-onset interstitial lung disease (ILD), ILD progression [forced vital capacity (FVC) decline ≥10% and ≥5% vs values at ILD diagnosis), primary myocardial involvement (PMI), pulmonary hypertension (PH), any organ involvement and all-cause mortality. RESULTS: We included 1252 patients [194 ATA-lcSSc (15.5%)], with 7.7 years (s.d. 3.5) of follow-up. ILD risk was higher in ATA-lcSSc vs ACA- and ANA-lcSSc and similar to ATA-dcSSc, although with less frequent restrictive lung disease. The risk of FVC decline ≥10% (35% of ATA-lcSSc) was lower in ATA-lcSSc than in ATA-dcSSc, whereas FVC decline ≥5% occurs similarly between ATA-lcSSc (58% of patients) and other SSc subsets, including ATA-dcSSc. The risk of PMI was similar in ATA-lcSSc and ANA-lcSSc but lower than in ACA-lcSSc; no difference in PH and mortality risk was observed among lcSSc subsets. The risk of any organ involvement, PMI and PH was lower and the mortality tended to be lower in ATA-lcSSc vs ATA-dcSSc. CONCLUSION: ATA-lcSSc patients have a high risk of ILD, albeit with a lower risk of progression compared with ATA-dcSSc, supporting careful screening for ILD in this subgroup

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

none120noneMihai, Carina*; Landewé, Robert; Van Der Heijde, Désirée; Walker, Ulrich A.; Constantin, Paul I.; Gherghe, Ana Maria; Ionescu, Ruxandra; Rednic, Simona; Allanore, Yannick; Avouac, Jéroˆme; Czirják, László; Hachulla, Eric; Riemekasten, Gabriela; Cozzi, Franco; Airò, Paolo; Cutolo, Maurizio; Mueller-Ladner, Ulf; Matucci-Cerinic, Marco; Launay, David; Dobrota, Rucsandra; Sfrent-Cornateanu, Roxana; Zingarelli, Stefania; Pigatto, Erika; Cuomo, Giovanna; Caramaschi, Paola; Ananieva, Lidia; Ullman, Susanne; Iversen, Line; Gurman, Alexandra Balbir; Braun-Moscovici, Yolanda; Carreira, Patricia E.; Joven, Beatriz E.; Minier, Tünde; Guiducci, Serena; Bellando-Randone, Silvia; Pellerito, Raffaele; Hunzelmann, Nicolas; Tarner, Ingo H.; Radominski, Sebastião Cezar; De Souza Müller, Carolina; Iannone, Florenzo; Henes, Jörg; Bancel, Dominique Farge; Damjanov, Nemanja; Ostojic, Predrag; Pozzi, Maria Rosa; Hesselstrand, Roger; Denton, Christopher; Krasowska, Dorota; Tikly, Mohammed; Riccieri, Valeria; Cantatore, Francesco Paolo; Corrado, Ada; Da Silva, José Antonio Pereira; Salvador, Maria João; Tyndall, Alan; Gabrielli, Armando; Distler, Oliver; Jordan, Suzan; Heitmann, Stefan; Burkhardt, Harald; Himsel, Andrea; Rozman, Blaz; Smith, Vanessa; Keyser, Filip De; Kalitena, Dusanka Martinovic; Radic, Mislav; Filipescu, Ileana; Petcu, Ana; Vlachoyiannopoulos, Panayiotis; Kucharz, Eugene J.; Widuchowska, Malgorzata; Kopec-Medrek, Magdalena; Kotulska, Anna; Szücs, Gabriella; Stankovic, Aleksandra; Stamenkovic, Bojana; Selmi, Carlo Francesco; Santis, Maria De; Marasini, Bianca; Coleiro, Bernard; Santamaria, Vera Ortiz; Westhovens, René; Becvár, Radim; Novak, Srdan; Engelhart, Merete; Meroni, Pierluigi; Ingegnoli, Francesca; Zeni, Silvana; Sulli, Alberto; Distler, Jörg; Yavuz, Sule; Montecucco, Carlomaurizio; Eyerich, Kilian; Krummel-Lorenz, Brigitte; Zenone, Thierry; Midtvedt, Øyvind; Chizzolini, Carlo; Seidel, Matthias; Oleszowsky, Mara; Üprus, Maria; Opriş, Daniela; Groseanu, Laura; Bielecka, Otylia Kowal; Antonio, Zea Mendoza; Szechinski, Jacek; Morovic-Vergles, Jadranka; Scorza, Raffaella; Puppo, Francesco; Mathieu, Alessandro; Anic, Branimir; Stork, Jiri; Stebbings, Simon; Inanc, Murat; Hasler, Paul; Von Mühlen, Carlos Alberto; Aringer, Martin; Popa, Sergei; Li, Mengtao; Rosato, EdoardoMihai, Carina; Landewé, Robert; Van Der Heijde, Désirée; Walker, Ulrich A.; Constantin, Paul I.; Gherghe, Ana Maria; Ionescu, Ruxandra; Rednic, Simona; Allanore, Yannick; Avouac, Jéroˆme; Czirják, László; Hachulla, Eric; Riemekasten, Gabriela; Cozzi, Franco; Airò, Paolo; Cutolo, Maurizio; Mueller-Ladner, Ulf; Matucci-Cerinic, Marco; Launay, David; Dobrota, Rucsandra; Sfrent-Cornateanu, Roxana; Zingarelli, Stefania; Pigatto, Erika; Cuomo, Giovanna; Caramaschi, Paola; Ananieva, Lidia; Ullman, Susanne; Iversen, Line; Gurman, Alexandra Balbir; Braun-Moscovici, Yolanda; Carreira, Patricia E.; Joven, Beatriz E.; Minier, Tünde; Guiducci, Serena; Bellando-Randone, Silvia; Pellerito, Raffaele; Hunzelmann, Nicolas; Tarner, Ingo H.; Radominski, Sebastião Cezar; De Souza Müller, Carolina; Iannone, Florenzo; Henes, Jörg; Bancel, Dominique Farge; Damjanov, Nemanja; Ostojic, Predrag; Pozzi, Maria Rosa; Hesselstrand, Roger; Denton, Christopher; Krasowska, Dorota; Tikly, Mohammed; Riccieri, Valeria; Cantatore, Francesco Paolo; Corrado, Ada; Da Silva, José Antonio Pereira; Salvador, Maria João; Tyndall, Alan; Gabrielli, Armando; Distler, Oliver; Jordan, Suzan; Heitmann, Stefan; Burkhardt, Harald; Himsel, Andrea; Rozman, Blaz; Smith, Vanessa; Keyser, Filip De; Kalitena, Dusanka Martinovic; Radic, Mislav; Filipescu, Ileana; Petcu, Ana; Vlachoyiannopoulos, Panayiotis; Kucharz, Eugene J.; Widuchowska, Malgorzata; Kopec-Medrek, Magdalena; Kotulska, Anna; Szücs, Gabriella; Stankovic, Aleksandra; Stamenkovic, Bojana; Selmi, Carlo Francesco; DE SANTIS, MARIA LINA; Marasini, Bianca; Coleiro, Bernard; Santamaria, Vera Ortiz; Westhovens, René; Becvár, Radim; Novak, Srdan; Engelhart, Merete; Meroni, Pierluigi; Ingegnoli, Francesca; Zeni, Silvana; Sulli, Alberto; Distler, Jörg; Yavuz, Sule; Montecucco, Carlomaurizio; Eyerich, Kilian; Krummel-Lorenz, Brigitte; Zenone, Thierry; Midtvedt, Øyvind; Chizzolini, Carlo; Seidel, Matthias; Oleszowsky, Mara; Üprus, Maria; Opriş, Daniela; Groseanu, Laura; Bielecka, Otylia Kowal; Antonio, Zea Mendoza; Szechinski, Jacek; Morovic-Vergles, Jadranka; Scorza, Raffaella; Puppo, Francesco; Mathieu, Alessandro; Anic, Branimir; Stork, Jiri; Stebbings, Simon; Inanc, Murat; Hasler, Paul; Von Mühlen, Carlos Alberto; Aringer, Martin; Popa, Sergei; Li, Mengtao; Rosato, Edoard

Joint and tendon involvement predict disease progression in systemic sclerosis: A EUSTAR prospective study

OBJECTIVE: To determine whether joint synovitis and tendon friction rubs (TFRs) can predict the progression of systemic sclerosis (SSc) over time. PATIENTS AND METHODS: We performed a prospective cohort study that included 1301 patients with SSc from the EUSTAR database with disease duration 643 years at inclusion and with a follow-up of at least 2 years. Presence or absence at clinical examination of synovitis and TFRs was extracted at baseline. Outcomes were skin, cardiovascular, renal and lung progression. Overall disease progression was defined according to the occurrence of at least one organ progression. RESULTS: Joint synovitis (HR: 1.26, 95% CI 1.01 to 1.59) and TFRs (HR: 1.32, 95% CI 1.03 to 1.70) were independently predictive of overall disease progression, as were also the diffuse cutaneous subset (HR: 1.30, 95% CI 1.05 to 1.61) and positive antitopoisomerase-I antibodies (HR: 1.25, 95% CI 1.02 to 1.53). Regarding skin progression, joint synovitis (HR: 1.67, 95% CI 1.06 to 2.64) and TFRs (HR: 1.69, 95% CI 1.02 to 2.77) were also independently predictive of worsening of the modified Rodnan skin score. For cardiovascular progression, joint synovitis was predictive of the occurrence of new digital ulcer(s) (HR: 1.45, 95% CI 1.08 to 1.96) and decreased left ventricular ejection fraction (HR: 2.20, 95% CI 1.06 to 4.57); TFRs were confirmed to be an independent predictor of scleroderma renal crisis (HR: 2.33, 95% CI 1.03 to 6.19). CONCLUSIONS: Joint synovitis and TFRs are independent predictive factors for disease progression in patients with early SSc. These easily detected clinical markers may be useful for the risk stratification of patients with SSc