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

Mapping and predicting mortality from systemic sclerosis

Objectives To determine the causes of death and risk factors in systemic sclerosis (SSc). Methods Between 2000 and 2011, we examined the death certificates of all French patients with SSc to determine causes of death. Then we examined causes of death and developed a score associated with all-cause mortality from the international European Scleroderma Trials and Research (EUSTAR) database. Candidate prognostic factors were tested by Cox proportional hazards regression model by single variable analysis, followed by a multiple variable model stratified by centres. The bootstrapping technique was used for internal validation. Results We identified 2719 French certificates of deaths related to SSc, mainly from cardiac (31%) and respiratory (18%) causes, and an increase in SSc-specific mortality over time. Over a median follow-up of 2.3 years, 1072 (9.6%) of 11 193 patients from the EUSTAR sample died, from cardiac disease in 27% and respiratory causes in 17%. By multiple variable analysis, a risk score was developed, which accurately predicted the 3-year mortality, with an area under the curve of 0.82. The 3-year survival of patients in the upper quartile was 53%, in contrast with 98% in the first quartile. Conclusion Combining two complementary and detailed databases enabled the collection of an unprecedented 3700 deaths, revealing the major contribution of the cardiopulmonary system to SSc mortality. We also developed a robust score to risk-stratify these patients and estimate their 3-year survival. With the emergence of new therapies, these important observations should help caregivers plan and refine the monitoring and management to prolong these patients' survival

Mapping and predicting mortality from systemic sclerosis

L

Mapping and predicting mortality from systemic sclerosis

To determine the causes of death and risk factors in systemic sclerosis (SSc).status: publishe

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

Health Assessment Questionnaire-Disability Index (HAQ-DI) use in modelling disease progression in diffuse cutaneous systemic sclerosis: an analysis from the EUSTAR database

BACKGROUND: Patients with diffuse cutaneous systemic sclerosis (dcSSc) have a poor prognosis. The importance of monitoring subjective measures of functioning and disability, such as the Health Assessment Questionnaire-Disability Index (HAQ-DI), is important as dcSSc is rated by patients as worse than diabetes or hemodialysis for quality of life impairment. This European Scleroderma Trials and Research (EUSTAR) database analysis was undertaken to examine the importance of impaired functionality in dcSSc prognosis. The primary objectives were to identify predictors of death and HAQ-DI score progression over 1 year. HAQ-DI score, major advanced organ involvement, and death rate were also used to develop a comprehensive model to predict lifetime dcSSc progression. METHODS: This was an observational, longitudinal study in patients with dcSSc registered in EUSTAR. Death and HAQ-DI scores were, respectively, analyzed by Cox regression and linear regression analyses in relation to baseline covariates. A microsimulation Markov model was developed to estimate/predict natural progression of dcSSc over a patient's lifetime. RESULTS: The analysis included dcSSc patients with (N = 690) and without (N = 4132) HAQ-DI score assessments from the EUSTAR database. Baseline HAQ-DI score, corticosteroid treatment, and major advanced organ involvement were predictive of death on multivariable analysis; a 1-point increase in baseline HAQ-DI score multiplied the risk of death by 2.7 (p <  0.001) and multiple advanced major organ involvement multiplied the risk of death by 2.8 (p <  0.05). Multivariable analysis showed that baseline modified Rodnan Skin Score (mRSS) and baseline HAQ-DI score were associated with HAQ-DI score progression at 1 year (p <  0.05), but there was no association between baseline organ involvement and HAQ-DI score progression at 1 year. HAQ-DI score, major advanced organ involvement, and death were successfully used to model long-term disease progression in dcSSc. CONCLUSIONS: HAQ-DI score and major advanced organ involvement were comparable predictors of mortality risk in dcSSc. Baseline mRSS and baseline HAQ-DI score were predictive of HAQ-DI score progression at 1 year, indicating a correlation between these endpoints in monitoring disease progression. It is hoped that this EUSTAR analysis may change physician perception about the importance of the HAQ-DI score in dcSSc

Cutaneous manifestations, clinical characteristics, and prognosis of patients with systemic sclerosis sine scleroderma : data from the International EUSTAR Database

IMPORTANCE Systemic sclerosis (SSc) sine scleroderma (ssSSc) is a subset of SSc defined by the absence of skin fibrosis. Little is known about the natural history and skin manifestations among patients with ssSSc. OBJECTIVE To characterize the clinical phenotype of patients with ssSSc compared with patients with limited cutaneous SSc (lcSSc) and diffuse cutaneous SSc (dcSSc) within the EUSTAR database.DESIGN, SETTING, AND PARTICIPANTS This longitudinal observational cohort study based on the international EUSTAR database included all patients fulfilling the classification criteria for SSc assessed by the modified Rodnan Skin score (mRSS) at inclusion and with at least 1 follow-up visit; ssSSc was defined by the absence of skin fibrosis (mRSS = 0 and no sclerodactyly) at all available visits. Data extraction was performed in November 2020, and data analysis was performed from April 2021 to April 2023.MAIN OUTCOMES AND MEASURES Main outcomes were survival and skin manifestations (onset of skin fibrosis, digital ulcers, telangiectasias, puffy fingers).RESULTS Among the 4263 patients fulfilling the inclusion criteria, 376 (8.8%) were classified as having ssSSc (mean [SD] age, 55.3 [13.9] years; 345 [91.8%] were female). At last available visit, in comparison with 708 patients with lcSSc and 708 patients with dcSSc with the same disease duration, patients with ssSSc had a lower prevalence of previous or current digital ulcers (28.2% vs 53.1% in lcSSc; P 40%) and SSc renal crisis (almost 3%). Patients with ssSSc had a higher survival than other subsets. Dermatologists should be aware that cutaneous findings in this subgroup may be associated with internal organ dysfunction. In particular, skin telangiectasias in ssSSc were associated with diastolic heart dysfunction

Significant weight loss in systemic sclerosis: a study from the EULAR Scleroderma Trials and Research (EUSTAR) database

Gastrointestinal (GI) involvement is almost universal in patients with systemic sclerosis (SSc) and is associated with significant disease-related morbidity and mortality.1 The entire GI tract can be involved and other disease features (eg, low mood, terminal organ failure and functional hand impairment) can result in significant nutritional impairment. Severe GI involvement has been reported to occur in ~10% of patients with SSc and often occurs early in the course of the disease.2 However, identification of patients at high risk of clinically significant weight loss is extremely challenging, including from the high prevalence of GI symptoms in patients with SSc. Therefore, there is a need to understand high-risk patients including potentially modifiable risk factors, with a view to early intervention strategies. Against this background, the aim of this study was to examine potential clinical risk factors of significant weight loss in patients with SSc. We performed an analysis of patients with SSc enrolled in the multinational, longitudinal European League Against Rheumatism (EULAR) Scleroderma Trials and Research (EUSTAR) database. In our study, we defined significant weight loss as 4.5 kg and/or least 5% of their body weight at 5 months onwards.3 Patients with a recorded second visit after 3 months and before 12 months were included in the analysis. We adopted a pragmatic approach (relevant to clinical practice) in

Systemic sclerosis-associated interstitial lung disease in the EUSTAR database: analysis by region

Objectives: The prevalence and characteristics of systemic sclerosis-associated interstitial lung disease (SSc-ILD) vary between geographical regions worldwide. The objectives of this study were to explore the differences in terms of prevalence, phenotype, treatment, and prognosis in patients with SSc-ILD from predetermined geographical regions in the EUSTAR database. Methods: Patients were clustered into seven geographical regions. Clinical characteristics and survival of patients with SSc-ILD were compared among these pre-determined regions. Results: For baseline analyses, 9260 SSc patients were included, with 6732 for survival analyses. The prevalence of SSc-ILD in the overall population was 50.2%, ranging from 44.0% in "Western Europe & Nordic countries" to 67.5% in "Eastern European, Russia & Baltic countries". In all regions, anti-topoisomerase antibodies were associated with SSc-ILD. Management also significantly differed; mycophenolate mofetil was prescribed at baseline in 31.6% of patients with SSc-ILD in "America (North & South)" and 31.7% in "Middle East" but only 4.3% in "Asia & Oceania" (P < 0.0001). Patients from "America (North & South)" and "Middle East" had the highest survival rate at the end of follow-up (85.8% and 85.2%, respectively). Conclusion: Our study highlights key differences among regions in terms of clinical presentation and prognosis of SSc-ILD. This work also demonstrates that the management of SSc-ILD is highly variable among the different regions considered, suggesting that efforts are still needed for the standardisation of medical practice in the treatment of this disease. Keywords: Interstitial lung disease; autoantibodies; lung fibrosis; scleroderma; systemic sclerosis

Systemic sclerosis-associated interstitial lung disease in the EUSTAR database : analysis by region

Objectives The prevalence and characteristics of SSc-associated interstitial lung disease (SSc-ILD) vary between geographical regions worldwide. The objectives of this study were to explore the differences in terms of prevalence, phenotype, treatment and prognosis in patients with SSc-ILD from predetermined geographical regions in the EUSTAR database. Material and methods Patients were clustered into seven geographical regions. Clinical characteristics and survival of patients with SSc-ILD were compared among these pre-determined regions. Results For baseline analyses, 9260 SSc patients were included, with 6732 for survival analyses. The prevalence of SSc-ILD in the overall population was 50.2%, ranging from 44.0% in 'Western Europe and Nordic countries' to 67.5% in 'Eastern European, Russia and Baltic countries'. In all regions, anti-topoisomerase antibodies were associated with SSc-ILD. Management also significantly differed; mycophenolate mofetil was prescribed at baseline in 31.6% of patients with SSc-ILD in 'America (North and South)' and 31.7% in 'Middle East' but only 4.3% in 'Asia and Oceania' (P <0.0001). Patients from 'America (North and South)' and 'Middle East' had the highest survival rate at the end of follow-up (85.8% and 85.2%, respectively). Conclusions Our study highlights key differences among regions in terms of clinical presentation and prognosis of SSc-ILD. This work also demonstrates that the management of SSc-ILD is highly variable among the different regions considered, suggesting that efforts are still needed for the standardization of medical practice in the treatment of this disease