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2. Impact of interstitial lung disease on the survival of systemic sclerosis with pulmonary arterial hypertension

Author

Guillén-Del-Castillo, Alfredo, Meseguer, Manuel López, Fonollosa-Pla, Vicent, Sáez Giménez, Berta, Colunga-Argüelles, Dolores, Revilla-López, Eva, Rubio-Rivas, Manuel, Ropero, Maria José Cristo, Argibay, Ana, Barberá, Joan Albert, Pla Salas, Xavier, Martínez Meñaca, Amaya, Madroñero Vuelta, Ana Belén, Lara Padrón, Antonio, Sáez Comet, Luis, Domingo Morera, Juan Antonio, González-Echávarri, Cristina, Mombiela, Teresa, Ortego-Centeno, Norberto, Marín González, Manuela, Tolosa-Vilella, Carles, Blanco, Isabel, Escribano Subías, Pilar, Simeón-Aznar, Carmen Pilar, Aurtenetxe Pérez, Águeda, Barrios Garrido-Lestache, Elvira, Bedate Díaz, Pedro, Cifrián, José Manuel, Cristo Ropero, Maria Jose, Dos Subirá, Laura, Elías Hernández, Teresa, García Hernández, Francisco José, Carbonell, Juan Gil, Segovia, Ariadna González, Valverde, Tamara Hermida, Baldomero, Idaira Fámara Hernández, Hernández-González, Ignacio, Huertas, Julia Herrero, Palomares, Luis Jara, Arjona, Josefa Jiménez, Padrón, Antonio Lara, Lázaro-Salvador, María, López-Ramón, Marta, López-Reyes, Raquel, González, Manuela Marín, Meñaca, Amaya Martínez, Etxaniz, Francisco Javier Mazo, Velasco, Virginia Naranjo, Candelera, Remedios Otero, González, Isabel Otero, Lozano, Beatriz Rodríguez, Nieto, María Jesús Rodríguez, Soriano, Joaquín Rueda, Giménez, Berta Sáez, Safont, Belén, Llinas, Ernest Sala, Sebastián, Laura, Cubero, Javier Segovia, Domenech, María Teresa Subirana, Masmiquel, Maria Baldà, Moraga, Eduardo Callejas, Chamorro, Antonio-J., Freire, Mayka, Guillén-del-Castillo, Alfredo, Marín, Maria Teresa Herranz, Vuelta, Ana Belén Madroñero, Ballvé, Adela Marín, Fernández, Melany Pestaña, Salas, Xavier Pla, Pintó, Ignasi Rodríguez, Comet, Luis Sáez, Cervelló, Gonzalo Salvador, Parra, José Antonio Todolí, Trapiella, Luis, Hitos, José Antonio Vargas, Marín, Adela (REHAP Consortium), Institut Català de la Salut, [Guillén-Del-Castillo A, Fonollosa-Pla V, Simeón-Aznar CP] Unitat de Malalties Autoimmunes, Servei de Medicina Interna, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Meseguer ML, Revilla-López E] Servei de Pneumologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Sáez Giménez B] Servei de Pneumologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Departament de Fisiologia, Universitat Autònoma de Barcelona, Bellaterra, Spain. [Colunga-Argüelles D] Department of Internal Medicine, Hospital Universitario Central de Asturias, Oviedo, Asturias, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
Respiratory Tract Diseases::Lung Diseases::Lung Diseases, Interstitial [DISEASES], enfermedades respiratorias::enfermedades pulmonares::hipertensión pulmonar [ENFERMEDADES], Hypertension, Pulmonary, Impacte, enfermedades de la piel y tejido conjuntivo::enfermedades del tejido conjuntivo::esclerodermia sistémica [ENFERMEDADES], Pulmonary hypertension, Respiratory Tract Diseases::Lung Diseases::Hypertension, Pulmonary [DISEASES], Anàlisi de supervivència (Biometria), Pulmonary diseases, polycyclic compounds, Survival analysis (Biometry), Humans, Familial Primary Pulmonary Hypertension, skin and connective tissue diseases, Hipertensió pulmonar, Pulmonary Arterial Hypertension, Respiratory tract diseases, Hipotensió arterial, Multidisciplinary, Scleroderma, Systemic, integumentary system, respiratory system, respiratory tract diseases, Malalties dels pulmons, Pulmons - Malalties, Esclerosi sistemàtica progressiva - Tractament, Impact, Scleroderma (Disease), enfermedades respiratorias::enfermedades pulmonares::enfermedades pulmonares intersticiales [ENFERMEDADES], Skin and Connective Tissue Diseases::Connective Tissue Diseases::Scleroderma, Systemic [DISEASES], Càncer de pulmó, Systemic sclerosis, Lung cancer, Esclerodèrmia, Lung Diseases, Interstitial
Abstract

To assess severity markers and outcomes of patients with systemic sclerosis (SSc) with or without pulmonary arterial hypertension (PAH-SSc/non-PAH-SSc), and the impact of interstitial lung disease (ILD) on PAH-SSc. Non-PAH-SSc patients from the Spanish SSc registry and PAH-SSc patients from the Spanish PAH registry were included. A total of 364 PAH-SSc and 1589 non-PAH-SSc patients were included. PAH-SSc patients had worse NYHA-functional class (NYHA-FC), worse forced vital capacity (FVC) (81.2 ± 20.6% vs 93.6 ± 20.6%, P

Published
2022

3. The incidence rate of pulmonary arterial hypertension and scleroderma renal crisis in systemic sclerosis patients with digital ulcers on endothelin antagonist receptors (ERAs) and phosphodiesterase-5 inhibitors (PDE5i).

Author

Pestaña-Fernández, Melani, Rubio-Rivas, Manuel, Tolosa-Vilella, Carles, Guillén-Del-Castillo, Alfredo, Colunga-Argüelles, Dolores, Argibay, Ana, Marí-Alfonso, Begoña, Marín-Ballvé, Adela, Pla-Salas, Xavier, Chamorro, Antonio-J, Castro-Salomó, Antoni, Madroñero-Vuelta, Ana Belén, Sánchez-García, María Esther, Sáez-Comet, Luis, González-Echávarri, Cristina, Ortego-Centeno, Norberto, Vargas-Hitos, José Antonio, Todolí-Parra, José Antonio, Trapiella-Martínez, Luis, and Lledó, Gema María

Subjects
KIDNEY disease diagnosis, CELL receptors, CONFIDENCE intervals, REPORTING of diseases, ENDOTHELINS, FINGERS, KIDNEY diseases, LONGITUDINAL method, MEDICAL records, PULMONARY hypertension, SYSTEMIC scleroderma, TIME, DISEASE incidence, DISEASE prevalence, RETROSPECTIVE studies, PHOSPHODIESTERASE inhibitors, DESCRIPTIVE statistics, ACQUISITION of data methodology, SKIN ulcers, CHEMICAL inhibitors, DISEASE complications
Abstract

Introduction Endothelin antagonist receptors (ERAs) and phosphodiesterase-5 inhibitors (PDE5i) are beneficial in pulmonary arterial hypertension (PAH) and digital ulcers (DU) and prevent from DU recurrences. Our study aimed to determine the difference in the incidence rate of PAH and scleroderma renal crisis (SRC) in patients with SSc and DU (SSc-DU) under ERAs/PDE5i or without treatment. Methods We conducted a retrospective cohort study including SSc-DU patients from the Spanish Scleroderma Registry (RESCLE). The primary outcome was the incidence rate of PAH and SRC in patients under ERAs/PDE5i or not. Results Some 544 patients out of 1817 (29.9%) in the RESCLE database had DU, 221 (40.6%) under ERAs/PDE5i and 323 (59.4%) not. The incidence rate (95% CI) difference between patients under treatment or not under did not reach statistical significance in PAH [−0.1 (−4.8, 4.69), P  = 0.988] or in SRC [0.7 (−2.2, 3.7), P  = 0.620]. However, the time from the first DU to the diagnosis of SRC was delayed in treated patients [mean (s. d.) 7.6 (5.8) years vs 2.9  (5.3); P  = 0.021]. The dcSSc subset was more prevalent in the treatment group (36 vs 26%; P  = 0.018), along with anti-topoisomerase I antibodies (34 vs 18%; P  < 0.001) and tendon friction rubs (12 vs 6%; P  = 0.038), whereas the lcSSc subset was more prevalent in the no-treatment group (57 vs 66%; P  = 0.031) along with ACA (37 vs 46%; P  = 0.031). Conclusion There was no difference in the incidence rate of PAH and SRC between groups. However, treatment with ERAs and/or PDE5i appeared to delay the occurrence of SRC. [ABSTRACT FROM AUTHOR]

Published
2021
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4. Registry of the Spanish network for systemic sclerosis: Survival, prognostic factors, and causes of death

Author

Simeón Aznar, Carmen Pilar, Fonollosa Pla, Vicent, Tolosa Vilella, Carles, Espinosa Garriga, Gerard, Campillo Grau, M., Ramos Casals, Manuel, García Hernández, F.J., Castillo Palma, María Jesús, Sánchez Román, J., Callejas Rubio, José Luis, Ortego Centeno, Norberto, Egurbide Arberas, María Victoria, Trapiella Martínez, Luis, Caminal Montero, L., Sáez Comet, Luis, Velilla Marco, J., Camps García, María Teresa, Ramón Garrido, E . de, Esteban Marcos, E.M., Pallarés Ferreres, Lucio, Navarrete Navarrete, N., Vargas Hitos, José Antonio, Gómez de la Torre, Ricardo, Salvador Cervelló, Gonzalo, Ríos Blanco, Juan José, Vilardell Tarrés, M., Spanish Scleroderma Study Group (SSSG), Autoimmune Diseases Study Group (GEAS), Spanish Society of Internal Medicine (SEMI), Systemic Autoimmune Diseases Group (GEAS), Spanish Scleroderma Study Group (SSSG), Spanish Society of Internal Medicine, Spain, [Simeón-Aznar,CP, Fonollosa-Plá,V, Vilardell-Tarrés,M] Department of Internal Medicine, Hospital Valld’Hebron. [Tolosa-Vilella,C] Department of Internal Medicine, Hospital Parc Taulí, Sabadell. [Espinosa-Garriga,G, Campillo-Grau,M] Department of Autoimmune Diseases, Hospital Clinic. [Campillo-Grau,M] Laboratori of Computacional Medicine, Bioestatistics Unit, Universitat Autònoma de Barcelona, Bellaterra, Barcelona. [García-Hernández,FJ, Castillo-Palma,MJ, Sánchez-Román,J] Unit of Connective Tissue Diseases, Department of Internal Medicine, Hospital Virgen del Rocio, Sevilla. [Callejas-Rubio,JL, Ortego-Centeno,N] Unit of Autoimmune Systemic Diseases, Department of Internal Medicine, Hospital Clínico San Cecilio, Granada. [Egurbide-Arberas,MV] Department of Internal Medicine, Hospital de Cruces, Galdakano, Bilbao. [Trapiellla-Martínez,L] Department of Internal Medicine, Hospital de Cabueñes, Gijón. [Caminal-Montero,L] Department of Internal Medicine, Hospital Universitario Central de Asturias, Oviedo. [Sáez-Comet,L, Velilla-Marco,J] Department of Internal Medicine, Hospital Miguel Servet, Zaragoza. [Camps-García,MT, de Ramón-Garrido,E] Department of Internal Medicine, Hospital Carlos Haya, Málaga. [Esteban-Marcos,EM, Pallarés-Ferreres,L]Department of Internal Medicine, Hospital Son Espases, Palma de Mallorca. [Navarrete-Navarrete,N, Vargas-Hitos,JA] Department of Internal Medicine, Hospital Virgen de las Nieves, Granada. [Gómez de la Torre,R] Department of Internal Medicine, Hospital San Agustín, Avilés. [Salvador-Cervello,G] Department of Internal Medicine, Hospital La Fe, Valencia. [Rios-Blanco,JJ] Department of Internal Medicine, Hospital La Paz, Madrid, and Universitat de Barcelona

Subjects
Male, Multivariate analysis, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Models, Statistical::Proportional Hazards Models [Medical Subject Headings], sistema de registros, Diseases::Respiratory Tract Diseases::Lung Diseases::Hypertension, Pulmonary [Medical Subject Headings], Autoimmune diseases, humanos, Scleroderma Renal Crisis, España, Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Ulcer [Medical Subject Headings], Scleroderma, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [Medical Subject Headings], Diseases::Respiratory Tract Diseases::Lung Diseases::Lung Diseases, Interstitial [Medical Subject Headings], Diseases::Skin and Connective Tissue Diseases::Connective Tissue Diseases::Scleroderma, Systemic [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Úlcera, Risk Factors, Cause of Death, Registries, Masculino, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Vital Statistics::Morbidity::Prevalence [Medical Subject Headings], Diseases::Skin and Connective Tissue Diseases::Connective Tissue Diseases::Scleroderma, Systemic::Scleroderma, Limited [Medical Subject Headings], mediana edad, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Vital Statistics::Mortality::Cause of Death [Medical Subject Headings], Cause of death, Esclerodermia limitada, anciano, Esclerodermia difusa, Malalties autoimmunitàries, Interstitial lung disease, Pronóstico, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Questionnaires [Medical Subject Headings], General Medicine, adulto, Middle Aged, Modelos de riesgos proporcionales, Diseases::Skin and Connective Tissue Diseases::Connective Tissue Diseases::Scleroderma, Systemic::Scleroderma, Limited::CREST Syndrome [Medical Subject Headings], Humanos, Encuestas y cuestionarios, Female, Factores de riesgo, Adult, medicine.medical_specialty, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Analysis of Variance::Multivariate Analysis [Medical Subject Headings], Check Tags::Male [Medical Subject Headings], causas de muerte, Internal medicine, Progresión de la enfermedad, Análisis multivariante, medicine, factores de riesgo, Tasa de supervivencia, Humans, Espanya, Survival rate, Aged, Retrospective Studies, Geographical Locations::Geographic Locations::Europe::Spain [Medical Subject Headings], Diseases::Skin and Connective Tissue Diseases::Connective Tissue Diseases::Scleroderma, Systemic::Scleroderma, Diffuse [Medical Subject Headings], Scleroderma, Systemic, Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Disease Progression [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Vital Statistics::Mortality::Survival Rate [Medical Subject Headings], business.industry, estudios retrospectivos, Retrospective cohort study, medicine.disease, Pulmonary hypertension, Surgery, Causas de muerte, Scleroderma (Disease), Enfermedades pulmonares Intersticiales, Spain, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis [Medical Subject Headings], Esclerodèrmia, business, Síndrome CREST, Prevalencia, Hipertensión pulmonar
Abstract

Systemic sclerosis (SSc) is a rare, multisystem disease showing a large individual variability in disease progression and prognosis. In the present study, we assess survival, causes of death, and risk factors of mortality in a large series of Spanish SSc patients. Consecutive SSc patients fulfilling criteria of the classification by LeRoy were recruited in the survey. Kaplan-Meier and Cox proportional-hazards models were used to analyze survival and to identify predictors of mortality. Among 879 consecutive patients, 138 (15.7%) deaths were registered. Seventy-six out of 138 (55%) deceased patients were due to causes attributed to SSc, and pulmonary hypertension (PH) was the leading cause in 23 (16.6%) patients. Survival rates were 96%, 93%, 83%, and 73% at 5, 10, 20, and 30 years after the first symptom, respectively. Survival rates for diffuse cutaneous SSc (dcSSc) and limited cutaneous SSc were 91%, 86%, 64%, and 39%; and 97%, 95%, 85%, and 81% at 5, 10, 20, and 30 years, respectively (log-rank: 67.63, P

Published
2015

5. Pulmonary hypertension in Spanish patients with systemic sclerosis. Data from the RESCLE registry.

Author

García-Hernández, Francisco J., Castillo-Palma, María J., Tolosa-Vilella, Carles, Guillén-del Castillo, Alfredo, Rubio-Rivas, Manuel, Freire, Mayka, Vargas-Hitos, José A., Todolí-Parra, José A., Rodríguez-Carballeira, Mónica, Espinosa-Garriga, Gerard, Colunga-Argüelles, Dolores, Ortego-Centeno, Norberto, Trapiella-Martínez, Luis, Rodero-Roldán, María M., Pla-Salas, Xavier, Perales-Fraile, Isabel, Pons-Martín del Campo, Isaac, Chamorro, Antonio J., Fernández-de la Puebla Giménez, Rafael A., and Madroñero-Vuelta, Ana B.

Subjects
SYSTEMIC scleroderma, PULMONARY hypertension, INTERSTITIAL lung diseases, PULMONARY artery, HEART diseases
Abstract

Introduction: Our objective was to evaluate the pulmonary hypertension (PH) data for Spanish patients with systemic sclerosis (SSc), define the PH types and determine the associated factors.Method: Descriptive study of PH-related data from the multicentre RESCLE registry. Estimated systolic pulmonary artery pressure (esPAP), measured via echocardiogram was considered elevated if ≥ 35 mmHg. Left heart disease (LHD) and interstitial lung disease (ILD) were identified. When performed, data from right heart catheterisation (RHC) were collected.Results: esPAP was elevated in 350 of 808 patients (43.3%). One hundred and forty-four patients (17.8%) were considered to have PH (88 via RHC and the rest due to elevated esPAP along with evidence of significant LHD or ILD): PAH 3.7%, secondary to ILD 8.3%, secondary to LHD 2.8% and unclassified 3%. Prevalence of elevated esPAP was greater in diffuse SSc (dSSc) than in limited scleroderma (lSSc) (50.5 vs. 42.2%, p 0.046). In the group with elevated esPAP, a lower prevalence of anti-centromere antibodies (41.9% vs. 52.3%, p 0.006) and a greater prevalence of anti-topoisomerase-1 antibodies (ATA) (25.1% vs. 18.6%, p 0.04) were observed compared to the group with normal esPAP. Patients with elevated esPAP had a lower rate of digital ulcers (50.6% vs. 60.2%, p 0.007) and esophageal involvement (83.6% vs. 88.7%, p 0.07) and higher rate of renal crisis (4.6% vs. 1.8%, p 0.066).Conclusions: Prevalence of PAH was lower than expected (3.7%). Probability of having elevated esPAP was higher among patients with dSSc and among those with ATA. [ABSTRACT FROM AUTHOR]

Published
2019
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6. First clinical symptom as a prognostic factor in systemic sclerosis: results of a retrospective nationwide cohort study.

Author

Rubio-Rivas, Manuel, Corbella, Xavier, Pestaña-Fernández, Melany, Tolosa-Vilella, Carles, Guillen-del Castillo, Alfredo, Colunga-Argüelles, Dolores, Trapiella-Martínez, Luis, Iniesta-Arandia, Nerea, Castillo-Palma, María Jesús, Sáez-Comet, Luis, Egurbide-Arberas, María Victoria, Ortego-Centeno, Norberto, Freire, Mayka, Vargas-Hitos, Jose Antonio, Ríos-Blanco, Juan José, Todolí-Parra, Jose Antonio, Rodríguez-Carballeira, Mónica, Marín-Ballvé, Adela, Segovia-Alonso, Pablo, and Pla-Salas, Xavier

Subjects
SYSTEMIC scleroderma, RETROSPECTIVE studies, PULMONARY hypertension, DISEASE risk factors, SYMPTOMS, PROGNOSIS
Abstract

The objective of the study is to determine the importance of the mode of onset as prognostic factor in systemic sclerosis (SSc). Data were collected from the Spanish Scleroderma Registry (RESCLE), a nationwide retrospective multicenter database created in 2006. As first symptom, we included Raynaud’s phenomenon (RP), cutaneous sclerosis, arthralgia/arthritis, puffy hands, interstitial lung disease (ILD), pulmonary arterial hypertension (PAH), and digestive hypomotility. A total of 1625 patients were recruited. One thousand three hundred forty-two patients (83%) presented with RP as first symptom and 283 patients (17%) did not. Survival from first symptom in those patients with RP mode of onset was higher at any time than those with onset as non-Raynaud’s phenomenon: 97 vs. 90% at 5 years, 93 vs. 82% at 10 years, 83 vs. 62% at 20 years, and 71 vs. 50% at 30 years (p < 0.001). In multivariate analysis, factors related to mortality were older age at onset, male gender, dcSSc subset, ILD, PAH, scleroderma renal crisis (SRC), heart involvement, and the mode of onset with non-Raynaud’s phenomenon, especially in the form of puffy hands or pulmonary involvement. The mode of onset should be considered an independent prognostic factor in systemic sclerosis and, in particular, patients who initially present with non-Raynaud’s phenomenon may be considered of poor prognosis. [ABSTRACT FROM AUTHOR]

Published
2018
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7. Early- versus late-onset systemic sclerosis. Differences in clinical presentation and outcome in 1037 patients

Author

Alba Garibay, Marco Antonio, Velasco, César, Simeón Aznar, Carmen Pilar, Fonollosa Pla, Vicent, Trapiellla Martínez, Luis, Egurbide Arberas, María Victoria, Sáez Comet, Luis, Castillo Palma, María Jesús, Callejas Rubio, José Luis, Camps García, María Teresa, Tolosa Vilella, Carles, Ríos Blanco, Juan José, Freire, Mayka, Vargas Hitos, José A., Espinosa Garriga, Gerard, RESCLE Registry, and Universitat de Barcelona

Subjects
education.field_of_study, Pediatrics, medicine.medical_specialty, Malalties autoimmunitàries, business.industry, Mortality rate, Autoimmune diseases, Population, Late onset, General Medicine, medicine.disease, Pulmonary hypertension, Scleroderma, Standardized mortality ratio, Scleroderma (Disease), Spain, Internal medicine, Medicine, Age of onset, Esclerodèrmia, Espanya, business, education, Myositis
Abstract

Peak age at onset of systemic sclerosis (SSc) is between 20 and 50 years, although SSc is also described in both young and elderly patients. We conducted the present study to determine if age at disease onset modulates the clinical characteristics and outcome of SSc patients. The Spanish Scleroderma Study Group recruited 1037 patients with a mean follow-up of 5.2 ± 6.8 years. Based on the mean ± 1 standard deviation (SD) of age at disease onset (45 ± 15 yr) of the whole series, patients were classified into 3 groups: age ≤ 30 years (early onset), age between 31 and 59 years (standard onset), and age ≥ 60 years (late onset). We compared initial and cumulative manifestations, immunologic features, and death rates. The early-onset group included 195 patients; standard-onset group, 651; and late-onset, 191 patients. The early-onset group had a higher prevalence of esophageal involvement (72% in early-onset compared with 67% in standard-onset and 56% in late-onset; p = 0.004), and myositis (11%, 7.2%, and 2.9%, respectively; p = 0.009), but a lower prevalence of centromere antibodies (33%, 46%, and 47%, respectively; p = 0.007). In contrast, late-onset SSc was characterized by a lower prevalence of digital ulcers (54%, 41%, and 34%, respectively; p < 0.001) but higher rates of heart conduction system abnormalities (9%, 13%, and 21%, respectively; p = 0.004). Pulmonary hypertension was found in 25% of elderly patients and in 12% of the youngest patients (p = 0.010). After correction for the population effects of age and sex, standardized mortality ratio was shown to be higher in younger patients. The results of the present study confirm that age at disease onset is associated with differences in clinical presentation and outcome in SSc patients.

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