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1. Characterization and Outcomes of SARS-CoV-2 Infection in Patients with Sarcoidosis

Author

Brito-Zerón, P., Gracia-Tello, B., Robles, A., Alguacil, A., Bonet, M., De-Escalante, B., Noblejas-Mosso, A., Gómez-de-la-Torre, R., Akasbi, M., Pérez-de-Lis, M., Pérez-Alvarez, R., Ramos-Casals, M., and Registry, on behalf of the SarcoGEAS-SEMI

Subjects
Adult, Male, medicine.medical_specialty, SARS-Cov-2, Comorbidity, comorbidities, Microbiology, survival, Article, law.invention, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, law, Virology, Internal medicine, Diabetes mellitus, medicine, Humans, 030212 general & internal medicine, Registries, sarcoidosis, Cardiopulmonary disease, Aged, 030203 arthritis & rheumatology, Aged, 80 and over, business.industry, COVID-19, Odds ratio, Middle Aged, medicine.disease, Intensive care unit, QR1-502, Hospitalization, hospital admission, Infectious Diseases, Treatment Outcome, Cohort, Female, Sarcoidosis, France, business, Cohort study
Abstract

To analyze the clinical characteristics and outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with sarcoidosis from a large multicenter cohort from Southern Europe and to identify the risk factors associated with a more complicated infection. We searched for patients with sarcoidosis presenting with SARS-CoV-2 infection (defined according to the European Centre for Disease Prevention and Control guidelines) among those included in the SarcoGEAS Registry, a nationwide, multicenter registry of patients fulfilling the American Thoracic Society/European Respiratory Society/World Association of Sarcoidosis and Other Granulomatous Disorders 1999 classification criteria for sarcoidosis. A 2:1 age-sex-matched subset of patients with sarcoidosis without SARS-CoV-2 infection was selected as control population. Forty-five patients with SARS-CoV-2 infection were identified (28 women, mean age 55 years). Thirty-six patients presented a symptomatic SARS-CoV-2 infection and 14 were hospitalized (12 required supplemental oxygen, 2 intensive care unit admission and 1 mechanical ventilation). Four patients died due to progressive respiratory failure. Patients who required hospital admission had an older mean age (64.9 vs. 51.0 years, p = 0.006), a higher frequency of baseline comorbidities including cardiovascular disease (64% vs. 23%, p = 0.016), diabetes mellitus (43% vs. 13%, p = 0.049) and chronic liver/kidney diseases (36% vs. 0%, p = 0.002) and presented more frequently fever (79% vs. 35%, p = 0.011) and dyspnea (50% vs. 3%, p = 0.001) in comparison with patients managed at home. Age- and sex-adjusted multivariate analysis identified the age at diagnosis of SARS-Cov-2 infection as the only independent variable associated with hospitalization (adjusted odds ratio 1.18, 95% conficence interval 1.04–1.35). A baseline moderate/severe pulmonary impairment in function tests was associated with a higher rate of hospitalization but the difference was not statistically significant (50% vs. 23%, p = 0.219). A close monitoring of SARS-CoV-2 infection in elderly patients with sarcoidosis, especially in those with baseline cardiopulmonary diseases and chronic liver or renal failure, is recommended. The low frequency of severe pulmonary involvement in patients with sarcoidosis from Southern Europe may explain the weak prognostic role of baseline lung impairment in our study, in contrast to studies from other geographical areas.

Published
2021
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2. Behcet's disease and genetic interactions between HLA-B*51 and variants in genes of autoinflammatory syndromes

Author

Burillo-Sanz, Sergio, Montes-Cano, M. A., García-Lozano, J. R., Olivas-Martínez, I., Ortego-Centeno, Norberto, García-Hernández, Francisco-José, Espinosa, G., Graña-Gil, G., Sánchez-Bursón, J., Juliá, M. R., Solans, Rosa, Blanco, R., Barnosi-Marín, A. C., Gómez de la Torre, R., Fanlo, P., Rodríguez-Carballeira, M., Rodriguez-Rodriguez, Luis, Camps i Miró, Teresa, Castañeda, Santos, Alegre-Sancho, Juan José, Martín, J., González-Escribano, M. F., Universitat Autònoma de Barcelona, Instituto de Salud Carlos III, Junta de Andalucía, European Commission, Burillo Sanz, Sergio, Blanco, Ricardo, Martín, J., Burillo Sanz, Sergio [0000-0002-6895-7875], Blanco, Ricardo [0000-0003-2344-2285], and Martín, J. [0000-0002-2202-0622]

Subjects
Male, 0301 basic medicine, humanos, lcsh:Medicine, ComputingMilieux_LEGALASPECTSOFCOMPUTING, Disease, Behcet's disease, Cohort Studies, 0302 clinical medicine, Polymorphism (computer science), mediadores de la inflamación, Genotype, lcsh:Science, estudios de cohortes, Genetics, péptidos y proteínas de señalización intracelular, Multidisciplinary, Behcet Syndrome, Intracellular Signaling Peptides and Proteins, antígenos HLA-B, adulto, MEFV, proteínas citoesqueléticas, Receptors, Tumor Necrosis Factor, Type I, Female, Inflammation Mediators, Adult, Human leukocyte antigen, Biology, Article, 03 medical and health sciences, NLR Family, Pyrin Domain-Containing 3 Protein, medicine, Humans, Genetic Predisposition to Disease, síndrome de Behçet, Adaptor Proteins, Signal Transducing, enfermedades autoinflamatorias hereditarias, Polymorphism, Genetic, lcsh:R, Hereditary Autoinflammatory Diseases, predisposición genética a la enfermedad, Epistasis, Genetic, Pyrin, medicine.disease, Minor allele frequency, Cytoskeletal Proteins, 030104 developmental biology, HLA-B Antigens, Epistasis, lcsh:Q, genotipo, 030217 neurology & neurosurgery
Abstract

Supplementary information:Rights and permissions.Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/., Behcet's disease (BD) is an immune-mediated systemic disorder with a well-established genetic base. In a previous study, using a next generation sequencing approach, we found many rare variants and some functional polymorphisms in genes related to autoinflammatory syndromes (AID): CECR1, MEFV, MVK, NLRP3, NOD2, PSTPIP1 and TNFRSF1A in our BD cohort. Our strategy did not allow us to establish either number of patients with variants, proportion of individuals accumulating them or relationship with other genetic factors. With the goal to answer these questions, the individual samples were sequenced. Additionally, three functional polymorphisms: NLRP3 p.Gln703Lys, NOD2 p.Arg702Trp and p. Val955Ile were genotyped using TaqMan assays. A total of 98 patients (27.6%) carried at least one rare variant and 13 of them (3.7%) accumulated two or three. Functional regression model analysis suggests epistatic interaction between B51 and MEFV (P=0.003). A suggestive protective association of the minor allele of NOD2 p.Arg702Trp (P=0.01) was found in both, B51 positive and negative individuals. Therefore, a high percentage of patients with BD have rare variants in AID genes. Our results suggest that the association of MEFV with BD could be modulated by the HLA molecules; whereas the protective effect of NOD2 p.Arg702Trp would be independent of HLA., This work was supported by Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III (PI16/01373), Fondos FEDER and Plan Andaluz de Investigacion (CTS-0197).

Published
2019

3. Genetic Analysis with the Immunochip Platform in Behcet Disease. Identification of Residues Associated in the HLA Class I Region and New Susceptibility Loci

Author

Ortiz-Fernández, Lourdes, Carmona, F. David, Montes-Cano, Marco-Antonio, García-Lozano, José-Raúl, Conde-Jaldón, Marta, Ortego-Centeno, Norberto, Castillo, María Jesús, Espinosa, Gerard, Graña, Jenaro, Sánchez-Bursón, Juan, Juliá, María Rosa, Solans, Roser, Blanco, Ricardo, Barnosi-Marín, Ana-Celia, Gómez de la Torre, Ricardo, Fanlo, Patricia, Rodríguez-Carballeira, Mónica, Rodriguez-Rodriguez, Luis, Camps i Miró, Teresa, Castañeda, Santos, Alegre-Sancho, Juan José, Martín, Javier, González-Escribano, María Francisca, Universitat Autònoma de Barcelona, [Ortiz-Fernandez, Lourdes] Hosp Univ Virgen Rocio IBiS CSIC US, Dept Immunol, Seville 41013, Spain, [Montes-Cano, Marco-Antonio] Hosp Univ Virgen Rocio IBiS CSIC US, Dept Immunol, Seville 41013, Spain, [Garcia-Lozano, Jose-Raul] Hosp Univ Virgen Rocio IBiS CSIC US, Dept Immunol, Seville 41013, Spain, [Conde-Jaldon, Marta] Hosp Univ Virgen Rocio IBiS CSIC US, Dept Immunol, Seville 41013, Spain, [Francisca Gonzalez-Escribano, Maria] Hosp Univ Virgen Rocio IBiS CSIC US, Dept Immunol, Seville 41013, Spain, [Carmona, Francisco-David] PTS Granada, CSIC, Inst Parasitol & Biomed Lopez Neyra, Granada 18016, Spain, [Martin, Javier] PTS Granada, CSIC, Inst Parasitol & Biomed Lopez Neyra, Granada 18016, Spain, [Ortego-Centeno, Norberto] Hosp Clin San Cecilio, Dept Internal Med, Granada 18003, Spain, [Jesus Castillo, Maria] Hosp Univ Virgen Rocio, Dept Internal Med, Seville 41003, Spain, [Espinosa, Gerard] Hosp Univ Clin, Dept Autoimmune Dis, Barcelona 08036, Spain, [Grana-Gil, Genaro] Dept Rheumatol, Complejo Hosp Univ A Coruna, La Coruna 15006, Spain, [Sanchez-Burson, Juan] Hosp Univ Valme, Dept Rheumatol, Seville 41014, Spain, [Rosa Julia, Maria] Hosp Univ Son Espases, Dept Immunol, Palma de Mallorca 07120, Spain, [Solans, Roser] Univ Autonoma Barcelona, Hosp Vall Hebron, Autoimmune Syst Dis Unit, Dept Internal Med, Barcelona 08035, Spain, [Blanco, Ricardo] Hosp Univ Marques Valdecilla, Dept Rheumatol, Santander 39008, Spain, [Barnosi-Marin, Ana-Celia] Dept Internal Med, Complejo Hosp Torrecardenas, Almeria 04009, Spain, [Gomez de la Torre, Ricardo] Hosp Univ Cent Asturias, Dept Internal Med, Asturias 33011, Spain, [Fanlo, Patricia] Hosp Virgen Camino, Dept Internal Med, Pamplona 31008, Spain, [Rodriguez-Carballeira, Monica] Hosp Univ Mutua Terrassa, Dept Internal Med, Terrassa 08221, Spain, [Rodriguez-Rodriguez, Luis] Hosp Clin San Carlos, Dept Rheumatol, Madrid 28040, Spain, [Camps, Teresa] Hosp Reg Univ Malaga, Dept Internal Med, Malaga 29010, Spain, [Castaneda, Santos] IIS Princesa, Hosp Princesa, Dept Rheumatol, Madrid 28006, Spain, [Alegre-Sancho, Juan-Jose] Hosp Univ Doctor Peset, Dept Rheumatol, Valencia 46017, Spain, Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III (ISCIII), Fondos FEDER, Plan Andaluz de Investigacion, ISCIII, RETICS Program (RIER, ISCIII), Instituto de Salud Carlos III, Junta de Andalucía, Red de Investigación en Inflamación y Enfermedades Reumáticas (España), [Ortiz-Fernández,L, Montes-Cano,MA, García-Lozano,JR, Conde-Jaldón,M, González-Escribano,MF] Department of Immunology, Hospital Universitario Virgen del Rocío (IBiS, CSIC, US), Sevilla, Spain. [Carmona,FD, Martín,J] Instituto de Parasitología y Biomedicina 'López-Neyra', CSIC, Granada, Spain. [Ortego-Centeno,N] Department of Internal Medicine, Hospital Clínico San Cecilio, Granada, Spain. [Castillo,MJ] Department of Internal Medicine, Hospital Universitario Virgen del Rocío, Sevilla, Spain. [Espinosa,G] Department Autoimmune Diseases, Hospital Universitari Clínic, Barcelona, Spain. [Graña-Gil,G] Department of Rheumatology, Complejo Hospitalario Universitario A Coruña, A Coruña, Spain. [Sánchez-Bursón,J] Department of Rheumatology, Hospital Universitario de Valme, Sevilla, Spain. [Juliá,MR] Department of Immunology, Hospital Universitari Son Espases, Palma de Mallorca, Spain. [Solans,R] Department of Internal Medicine, Autoimmune Systemic Diseases Unit, Hospital Vall d’Hebron, Universidad Autonoma de Barcelona, Barcelona, Spain. [Blanco,R] Department of Rheumatology, Hospital Universitario Marqués de Valdecilla, Santander, Spain. [Barnosi-Marín,AC] Department of Internal Medicine, Complejo Hospitalario Torrecárdenas, Almería, Spain. [Gómez de la Torre,R] Department of Internal Medicine, Hospital Universitario Central de Asturias, Asturias, Spain. [Fanlo,P] Department of Internal Medicine, Hospital Virgen del Camino, Pamplona, Spain. [Rodríguez-Carballeira,M] Deparment of Internal Medicine, Hospital Universitari Mútua Terrassa, Terrassa, Spain. [Rodríguez-Rodríguez,L] Department of Rheumatology, Hospital Clínico San Carlos, Madrid, Spain. [Camps,T] Department of Internal Medicine, Hospital Regional Universitario de Málaga, Málaga, Spain. [Castañeda,S] Department of Rheumatology, Hospital de la Princesa, IIS-Princesa, Madrid, Spain. [Alegre-Sancho,JJ] Department of Rheumatology, Hospital Universitario Doctor Peset, Valencia, Spain., and This work was supported by Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III (ISCIII, 13/01118), Fondos FEDER and Plan Andaluz de Investigación (CTS-0197). LOF is the recipient of a fellowship (ISCIII, FI11/00547) and FDC was funded by the RETICS Program (RIER, ISCIII, RD12/0009/0013).

Subjects
alelos, modelos logísticos, Genes clase I del complejo de histocompatibilidad (MHC), España, frecuencia génica, sitios genéticos, lcsh:Science, Diseases::Stomatognathic Diseases::Mouth Diseases::Behcet Syndrome [Medical Subject Headings], Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Glycoproteins::Membrane Glycoproteins::Histocompatibility Antigens Class I::HLA-B Antigens [Medical Subject Headings], Geographicals::Geographic Locations::Europe::Spain [Medical Subject Headings], Immunoassay, education.field_of_study, Behcet Syndrome, Genomics, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Models, Statistical::Logistic Models [Medical Subject Headings], Phenomena and Processes::Genetic Phenomena::Genotype [Medical Subject Headings], Mhc class-i, Genotyping, estudios de casos y controles, Locus (genetics), Human leukocyte antigen, subunidad p35 de la interleucina-12, 03 medical and health sciences, Contactins, Rheumatoid-arthritis, Genetics, Genome-Wide Association Studies, Genetic predisposition, Humans, Molecular Biology Techniques, education, Molecular Biology, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Amino Acids [Medical Subject Headings], síndrome de Behçet, Alleles, Molecular Biology Assays and Analysis Techniques, Sclerosis, lcsh:R, Biology and Life Sciences, Computational Biology, Receptors, Interleukin, 030104 developmental biology, Logistic Models, Genetic Loci, HLA-B Antigens, Case-Control Studies, lcsh:Q, Síndrome de Behçet, Genotipo, Models, Molecular, 0301 basic medicine, humanos, lcsh:Medicine, HLA-A3 Antigen, Genetic analysis, Geographical Locations, Gene Frequency, antígeno HLA-A3, Il23r-il12rb2, Aminoácidos, Multidisciplinary, antígeno HLA-B51, Genome-wide association, Antígenos HLA-B, antígenos HLA-B, Modelos logísticos, Europe, Peptide, Amino Acid Analysis, HLA-B51 Antigen, Alelos, Research Article, Risk, Population, Biology, Research and Analysis Methods, Genetic Predisposition, inmunoanálisis, Interleukin-12 Subunit p35, Genetic Predisposition to Disease, Allele, Allele frequency, Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::Alleles [Medical Subject Headings], Imputation, contactinas, Human Genetics, predisposición genética a la enfermedad, Binding, Genome Analysis, Microarray Analysis, Spain, Genetics of Disease, People and Places, análisis por micromatrices, Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::Major Histocompatibility Complex::Genes, MHC Class I [Medical Subject Headings]
Abstract

Behcet's disease (BD) is an immuno-mediated vasculitis in which knowledge of its etiology and genetic basis is limited. To improve the current knowledge, a genetic analysis performed with the Immunochip platform was carried out in a population from Spain. A discovery cohort comprising 278 BD cases and 1,517 unaffected controls were genotyped using the Immunochip platform. The validation step was performed on an independent replication cohort composed of 130 BD cases and 600 additional controls. The strongest association signals were observed in the HLA class I region, being HLA-B*51 the highest peak (overall P = 6.82E-32, OR = 3.82). A step-wise conditional logistic regression with classical alleles identified HLA-B*57 and HLA-A*03 as additional independent markers. The amino acid model that best explained the association, includes the position 97 of the HLA-B molecule and the position 66 of the HLA-A. Among the non-HLA loci, the most significant in the discovery analysis were: IL23R (rs10889664: P = 3.81E-12, OR = 2.00), the JRKL/CNTN5 region (rs2848479: P = 5.00E-08, OR = 1.68) and IL12A (rs1874886: P = 6.67E-08, OR = 1.72), which were confirmed in the validation phase (JRKL/CNTN5 rs2848479: P = 3.29E-10, OR = 1.66; IL12A rs1874886: P = 1.62E-08, OR = 1.61). Our results confirm HLA-B*51 as a primary-association marker in predisposition to BD and suggest additional independent signals within the class I region, specifically in the genes HLA-A and HLA-B. Regarding the non-HLA genes, in addition to IL-23R, previously reported in our population; IL12A, described in other populations, was found to be a BD susceptibility factor also in Spaniards; finally, a new associated locus was found in the JRKL/CNTN5 region., This work was supported by Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III (ISCIII, 13/01118), Fondos FEDER and Plan Andaluz de Investigación (CTS-0197). LOF is the recipient of a fellowship (ISCIII, FI11/00547) and FDC was funded by the RETICS Program (RIER, ISCIII, RD12/0009/0013). Instituto de Salud Carlos III Junta de Andalucía Red de Investigación en Inflamación y Enfermedades Reumáticas (España) RIER

Published
2016

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

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