Sjögren's syndrome-associated interstitial lung disease: A multicenter study

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"identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:7 [ 0 => array:3 [ "entidad" => "Servicio de Reumatología, Hospital Sant Joan Despí Moisès Broggi, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Reumatología, Hospital de Sant Pau, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Servicio de Reumatología, Hospital Parc Taulí, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Servicio de Reumatología, Hospital de Bellvitge, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Servicio de Reumatología, Hospital de Granollers, Spain" "etiqueta" => "e" "identificador" => "aff0025" ] 5 => array:3 [ "entidad" => "Servicio de Neumología, Hospital Sant Joan Despí Moisès Broggi, Spain" "etiqueta" => "f" "identificador" => "aff0030" ] 6 => array:3 [ "entidad" => "Clinical Epidemiology Department, Consorci Sanitari Integral, Spain" "etiqueta" => "g" "identificador" => "aff0035" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Enfermedad pulmonar instersticial asociada a síndrome de Sjögren: estudio multicéntrico" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 873 "Ancho" => 995 "Tamanyo" => 152638 ] ] "descripcion" => array:1 [ "en" => "HRCT. Peribronchial ground glass compatible with OP." ] ] ] "textoCompleto" => "IntroductionPrimary Sjögren syndrome (PSS) is a chronic inflammatory autoimmune disease characterized typically by lymphocytic infiltration of the exocrine glands resulting in the sicca syndrome. Although sicca features are the central clinical manifestations of the disease, PSS can cause systemic extraglandular manifestations.<a class="elsevierStyleCrossRef" href="#bib0090">1</a>Pulmonary manifestations can be an extraglandular complication, with reported prevalence varying widely (9–75%), depending on the methods of detection and patient selection. Lung involvement (symptoms and either pulmonary function testing or radiographic abnormalities) can occur in 10–20% of patients.<a class="elsevierStyleCrossRef" href="#bib0095">2</a> Image techniques, such as chest radiographs and high resolution computerized tomography (HRCT), are the most useful tools to detect lung involvement. A plain chest X-ray has a low sensitivity to detect early lung involvement. Studies that systematically perform HRCTs, even in asymptomatic patients, report higher rates of pulmonary abnormalities compared with studies based on clinical symptoms.<a class="elsevierStyleCrossRef" href="#bib0100">3</a> HRCT may identify ground-glass attenuation, thin-walled cysts, honeycombing, reticular pattern, small nodules and enlarged mediastinal lymph nodes. Several histopathologic patterns have been described in PSS, including nonspecific interstitial pneumonia (NSIP), usual interstitial pneumonia (UIP), organizing pneumonia (OP) and lymphocytic interstitial pneumonia (LIP). Most of these patterns are known as diffuse interstitial lung disease (ILD). LIP has a typical radiographic appearance in ground glass opacities with thin-walled cysts, and the presence of these cysts on HRCT scan should raise clinical suspicion for PSS with ILD.<a class="elsevierStyleCrossRefs" href="#bib0105">4,5</a>NSIP is the most commonly observed histopathological pattern in connective tissue diseases with ILD, including PSS. In patients with PSS and ILD, HRCT and histopathological findings are well correlated<a class="elsevierStyleCrossRef" href="#bib0115">6</a> and a lung biopsy is usually not recommended. However, radiographic features suggestive of lymphoma (consolidation, large nodules or pleural effusions) require thorough investigation<a class="elsevierStyleCrossRef" href="#bib0120">7</a> (<a class="elsevierStyleCrossRefs" href="#fig0005">Figs. 1–3</a>).<elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia>Bronchiolitis and bronchiectasis are the most common airway manifestations (occasionally secondary to the fibrosis of the ILD). Patients with PSS are also at an increased risk of lymphoma. Other lung abnormalities have been described: amyloidosis, granulomatosis lung disease, pseudolymphoma, pulmonary hypertension and pleural disease.<a class="elsevierStyleCrossRef" href="#bib0095">2</a>Patients with ILD also show a restrictive functional defect that limits respiratory functionality in a variable range of severity. Diffuse ILD is the most serious form of lung involvement due to its potentially progressive nature and simultaneously its risk of respiratory failure.<a class="elsevierStyleCrossRef" href="#bib0125">8</a>Pulmonary function test (PFT) are also necessary to demonstrate functional respiratory disability, even in asymptomatic patients. PFT might also be done very early after disease onset, and the most reliable variable to detect functional defect related to an ILD is DLCO. The presence of lower DLCO has been associated to higher mortality rates.Recently, an estimated prevalence of 22% of diffuse ILD in PSS in a population-based hospital patient cohort has been described. Pulmonary involvement is related to an increased mortality in PSS patients.<a class="elsevierStyleCrossRef" href="#bib0130">9</a>ObjectivesConsidering the low prevalence of the lung involvement in PSS, the heterogeneous pattern that can be found in the lung and the severity of the ILD, the aim of this study was to evaluate the clinical characteristics of patients diagnosed with PSS with ILD at 5 Rheumatology clinics in the Barcelona area.Materials and methodsWe performed a multicenter cohort in various Hospitals in Barcelona including 25 patients with PSS and ILD. From a total of 743 patients with PSS, 25 (3.4%) developed ILD. The average of follow up of those patients with PSS was 15 years (range 5–35).An identical database was used in the 5 clinics to collect the information. The information of the study, included in the database, was collected retrospectively during 2013 from the 5 different clinics participating in the study.The PSS was diagnosed according to the American-European Consensus Group (AECG) criteria for PSS from 2002. Registry data included: age at evaluation, gender, date of diagnosis of PSS, the type of criteria fulfilled for PSS, immunology data (anti-Ro 60, anti-Ro 52, anti-La, RF, ANA). We also included the poor outcome prognostic factors of the illness, such as hypergammaglobulinemia or b2-microglobulin and acute phase reactants.Lung involvement disease variables included: date of diagnosis of ILD, results of bronchoalveolar lavage (BAL), HRCT, pulmonary biopsy if needed, PFTs with DLCO. We recorded complementary tests that suggest poor further prognosis of the outcome of the disease: echocardiography to measure pulmonary hypertension and a walking test to determine the functional respiratory capacity. We also collected clinical information: arthritis, Raynaud phenomenon, polyneuropathy, parotid gland disease, periodontal disease and purpura or cryoglobulinemia. Treatment received before and during the process of the disease were collected, such as the complications or associated processes.Eular Sjögren's syndrome disease activity index (ESSDAI) was calculated.<a class="elsevierStyleCrossRef" href="#bib0135">10</a> The ESSDAI is a clinical index designed to measure disease activity in patients with PSS. There are 12 domains associated with disease activity (scoring goes from 0 to 3).The data were analyzed descriptively.ResultsIn our cohort (n=25), the mean age at evaluation was 70 years old (±8 years). The majority were females. In 15/25 of the patients the diagnosis of ILD was done before the diagnosis of PSS. The mean disease duration at evaluation was 7±10 years. The wide variety of histopathological patterns from our cohort was: 12 NSIP, 5 UIP, 4 OP, 2 LIP. Apart from those, one patient was diagnosed of bronchoalveolitis and another one of lung fibrosis. The majority of patients (20/25) referred keratoconjunctivitis sicca, and 20/25 had xerosis. The Schirmer test was pathological in 20 patients. We did 15 salivary scintigraphies, 11 were pathological, and 15 lip biopsies were performed, 10 with the specific focal lymphocytic sialoadenitis, characterized by one or more tightly aggregated lymphocytes (over 50) adjacent to normal gland tissue. These aggregates of lymphocytes are called foci and their total density is called a “focus score”, highly specific of PSS pattern. Anti-Ro 60 was positive in 16/25 patients, anti-Ro 52 was determined positive in 4/9 patients. Anti-La was positive in 10/25 patients, RF in 17/25 and ANA in 22/25 (most of these determinations had a spotted pattern and a title ≥320). Ten patients had hypergammaglobulinemia and the determination of b2microglobulin was normal almost in every patient. The mean ESR when data was collected was 35mm/h and the PCR was 2.3mg/dL. BAL was performed in 11 patients, 5 of them with >10% of lymphocytes (5–70%). In 2 patients a lung biopsy was needed to confirm the diagnosis.The PFRs results are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>, the majority had a clear restrictive pattern.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Analytical findings and ESSDAI results, as well as titers and patterns of ANA in the different pulmonary patterns are shown in <a class="elsevierStyleCrossRefs" href="#tbl0010">Tables 2 and 3</a>.<elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia>Four patients had pulmonary hypertension and the walking test was performed in 20 patients, showing pathological findings in half of them. We collected 6 patients with arthritis, 5 with Raynaud phenomenon, 3 with polyneuropathy and 6 with parotid gland disease, 1 with periodontal disease, 4 with purpura or cryoglobulinemia. As with other associated processes we collected: 4 osteoporosis, 2 respiratory infections, 1 plaquetopenia, 1 pernicious anemia, 1 corneal ulcer and 1 primary biliary cirrhosis. The majority of the patients received glucocorticoid therapy (12 at a low dose and 16 at a high dose), 7 needed antimalarial treatment and 10 immunosupressive treatment. One patient needed a pulmonary transplant.Mean ESSDAI was 4.2 (2–9).DiscussionAbove the glandular manifestations, present in almost all PSS patient, a wide range of extraglandular clinical syndromes may appear in longstanding diseases with a heavy autoimmune background. PSS can affect peripheral and central nervous system, kidney, skin, musculoskeletal and the lungs. Lung disease in the PSS patients can affect their superior and lower respiratory tract, the diaphragm, and the pulmonary vessels. Furthermore, lung lymphoproliferative disease can also be found.Palm and collegues found a high population-based prevalence of clinical pulmonary involvement (22%) among patients with PSS. They also affirmed that patients with lung involvement had reduced quality of life and increased mortality.<a class="elsevierStyleCrossRef" href="#bib0130">9</a>Patients with extraglandular manifestations frequently can have ILD. Gardiner and collegues wrote that the prevalence of ILD in PSS patients is approximately 8%.<a class="elsevierStyleCrossRef" href="#bib0140">11</a>Recently, Kreider wrote that 10–20% of patients with PSS have lung involvement, and subclinical lung disease is even more frequent and can include evidence of small airway disease and inflammation.<a class="elsevierStyleCrossRef" href="#bib0095">2</a>ILD can be found in various connective tissue diseases. In the PSS, ILD is an extraglandular severe manifestation and it is particularly associated with patients that are positive with anti-Ro and anti-Ro52. In a study done by Ito and collegues<a class="elsevierStyleCrossRef" href="#bib0115">6</a> they found that 61% of 33 patients who had PSS had NSIP in the lung biopsy, 4 had diffuse bronchiolitis, 4 had non-Hodgkin's lymphomas of mucosal associated lymphoid tissue (MALT) and 5 patients had evidence of amyloidosis, but none of these patients had evidence of LIP. LIP was considered one of the most common pulmonary manifestations in PSS, but recent studies have demonstrated a much lower prevalence (0.9–17%)<a class="elsevierStyleCrossRef" href="#bib0105">4</a>. The findings from our study show different results from the study done by Ito, although we did not conduct biopsies in all the patients for the diagnosis. We based our diagnosis basically on the HRCT due to findings in the HCRT are used to be well correlated to histopathologic finding.In patients with active extra-glandular manifestations and in those that are immunologically active it is mandatory to discard the presence of ILD by doing a HRCT and PFTs. The symptoms of ILD are cough, dyspnea, bilateral infiltrates on radiograph and various patters of abnormalities on HRCT scan.<a class="elsevierStyleCrossRef" href="#bib0125">8</a> These exams must be done in the primary stages due to the possible severity of the ILD.The lung disease can occur before the other more usual manifestations of the syndrome<a class="elsevierStyleCrossRefs" href="#bib0145">12,13</a> and also approximately 15% to 20% of patients presenting with chronic ILD can have an occult connective tissue disease.<a class="elsevierStyleCrossRef" href="#bib0155">14</a> In our cohort, in 60% of the patients, the ILD diagnosis was made before the PSS diagnosis.Although, some factors have been proposed to be associated with a poor outcome in PSS, specifically with a higher risk of lymphoma, high levels of beta2-microglobulin, presence of skin vasculitis, decreased levels of C3, C4 factors, lower level of CD4 lymphocytes and a CD4/CD8 beyond 0.8,<a class="elsevierStyleCrossRef" href="#bib0160">15</a> the levels of b2microglobulin are not associated with the ILD.The pulmonary manifestation often shows a restrictive pattern and a low DLCO, associated with a high morbidity and a high mortality. In some patients the course of the illness could be benign with a stabilization in the lung disease. Keeping in mind that the PSS with ILD associated to other connective tissue diseases can develop into a pulmonary fibrosis.It is mandatory a cross and a multi-disciplinary collaboration in the management of any of the connective tissue diseases with lung disease between rheumatologists and pulmonologists. Rheumatologists help to detect an occult connective tissue disease in patients with “idiopathic ILD” by requiring careful attention to the historical clues, the physical examination findings, specific autoantibodies, radiological and histopathological features.<a class="elsevierStyleCrossRef" href="#bib0165">16</a> For pulmonologists it is important to recognize that PSS with ILD can result in severe disease and they can help in the lung disease management. For a multidisciplinary approach pulmonologists need to learn clues to distinguish between idiopathic interstitial pneumonia from connective tissue disease associated with ILD.<a class="elsevierStyleCrossRef" href="#bib0170">17</a>Our study has an important limitation: the information was collected retrospectively.ConclusionTo summarize, we shall consider that lung involvement can occur in patients with PSS. ILD is one of the extraglandulars manifestations in those patients. In our cohort we observed the following histopathological patterns: NSIP, UIP, OP and LIP (in this order).Higher rates of mortality and morbidity in PSS are related to the ILD, therefore, patients affected with PSS must be screened to catch a precocious diagnosis doing all the complementary tests needed. It is important to discard a connective tissue disease in patients with ILD. In our cohort the majority of the patients were diagnosed of ILD before being diagnosed of PSS.Due to the low prevalence of the ILD in PSS, multicentre cohorts are increasingly demanded to give information about the characteristics, the management and treatment not only of the disease, but also of the single organ complications. A multidisciplinary management is needed.Ethical disclosuresProtection of human and animal subjectsThe authors declare that no patient data appear in this article.Confidentiality of dataThe authors declare that they have followed the protocols of the workplace on the publication of patient data.Right to privacy and informed consentThe authors declare that no patient data appear in this article.Conflict of interestThe authors declare no conflict of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:12 [ 0 => array:3 [ "identificador" => "xres824570" "titulo" => "Abstract" "secciones" => array:5 [ 0 => array:1 [ "identificador" => "abst0005" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Objective" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Methods" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Results" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec821049" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres824569" "titulo" => "Resumen" "secciones" => array:5 [ 0 => array:1 [ "identificador" => "abst0030" ] 1 => array:2 [ "identificador" => "abst0035" "titulo" => "Objetivo" ] 2 => array:2 [ "identificador" => "abst0040" "titulo" => "Métodos" ] 3 => array:2 [ "identificador" => "abst0045" "titulo" => "Resultados" ] 4 => array:2 [ "identificador" => "abst0050" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec821048" "titulo" => "Palabras clave" ] 4 => array:3 [ "identificador" => "sec0005" "titulo" => "Introduction" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0010" "titulo" => "Objectives" ] ] ] 5 => array:2 [ "identificador" => "sec0015" "titulo" => "Materials and methods" ] 6 => array:2 [ "identificador" => "sec0020" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0025" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0030" "titulo" => "Conclusion" ] 9 => array:3 [ "identificador" => "sec0040" "titulo" => "Ethical disclosures" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0045" "titulo" => "Protection of human and animal subjects" ] 1 => array:2 [ "identificador" => "sec0050" "titulo" => "Confidentiality of data" ] 2 => array:2 [ "identificador" => "sec0055" "titulo" => "Right to privacy and informed consent" ] ] ] 10 => array:2 [ "identificador" => "sec0035" "titulo" => "Conflict of interest" ] 11 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2015-07-31" "fechaAceptado" => "2015-09-24" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec821049" "palabras" => array:2 [ 0 => "Interstitial lung disease" 1 => "Sjögren syndrome" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec821048" "palabras" => array:2 [ 0 => "Enfermedad pulmonar intersticial" 1 => "Síndrome de Sjögren" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "Primary Sjögren syndrome (PSS) is a chronic inflammatory autoimmune disease. Interstitial lung disease (ILD) can be an extraglandular complication. ObjectiveTo evaluate the clinical characteristics of patients diagnosed with PSS with ILD. MethodsMulticentre cohort study with 25 patients diagnosed with PSS and ILD. Data of PSS, prognostic factors, pulmonary involvement variables, complementary tests that suggest a worse diagnosis and treatment given were collected. EULAR index was measured for Sjögren's syndrome. ResultsWe identified 25 patients. In 15/25 the diagnosis of ILD was done before the diagnosis of PSS. The histopathological patterns found were: 12 NSIP, 5 UIP, 4 OP, 2 LIP. PFRs showed restrictive pattern. The majority of the patients received glucocorticoid therapy, antimalarial or immunosuppressive treatment. ConclusionsPatients affected with PSS must be screened to catch a precocious diagnosis of ILD. The majority of the patients were diagnosed of ILD before being diagnosed of PSS. Multicenter cohorts are increasingly demanded and a multidisciplinary management is needed." "secciones" => array:5 [ 0 => array:1 [ "identificador" => "abst0005" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Objective" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Methods" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Results" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "El síndrome de Sjögren primario (SSP) es una enfermedad inflamatoria autoinmune. La enfermedad pulmonar intersticial (EPI) puede ser una complicación extraglandular. ObjetivoEvaluar las características clínicas de los pacientes diagnosticados de SSP con EPI. MétodosEstudio de cohortes multicéntrico con 25 pacientes diagnosticados de SSP y EPI. Se recopilaron datos propios del SSP, factores pronóstico, variables de medida de la afectación pulmonar, pruebas complementarias que sugieren un peor pronóstico, así como el tratamiento recibido. Se calculó el índice EULAR para el síndrome de Sjögren. ResultadosSe identificaron 25 pacientes. Quince de ellos fueron diagnosticados de EPI antes que de SSP. Los patrones histopatológicos encontrados fueron 12 con neumonía intersticial inespecífica, 5 con neumonía intersticial común, 4 con neumonía organizada, 2 con neumonía intersticial linfocítica. Las pruebas de función respiratoria mostraron un patrón restrictivo. La mayoría de los pacientes recibió un tratamiento con glucocorticoides, antipalúdicos o inmunodepresores. ConclusionesLos pacientes afectados por SSP deben ser sometidos a pruebas para detectar un diagnóstico precoz de EPI. La mayoría de los pacientes fueron diagnosticados de EPI antes que de SSP. Los estudios de cohortes multicéntricos son cada vez más demandados y se precisa una gestión multidisciplinar." "secciones" => array:5 [ 0 => array:1 [ "identificador" => "abst0030" ] 1 => array:2 [ "identificador" => "abst0035" "titulo" => "Objetivo" ] 2 => array:2 [ "identificador" => "abst0040" "titulo" => "Métodos" ] 3 => array:2 [ "identificador" => "abst0045" "titulo" => "Resultados" ] 4 => array:2 [ "identificador" => "abst0050" "titulo" => "Conclusiones" ] ] ] ] "multimedia" => array:6 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 706 "Ancho" => 995 "Tamanyo" => 140210 ] ] "descripcion" => array:1 [ "en" => "HRCT. Patchy involvement in ground glass opacity in right lung tending to fibrosis due to NSIP." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 873 "Ancho" => 995 "Tamanyo" => 152638 ] ] "descripcion" => array:1 [ "en" => "HRCT. Peribronchial ground glass compatible with OP." ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 891 "Ancho" => 995 "Tamanyo" => 220379 ] ] "descripcion" => array:1 [ "en" => "HRCT. Bilateral interstitial involvement with ground glass areas and established fibrosis with traction bronchiectasis, without honey combing, compatible with fibrosing NSIP." ] ] 3 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "TLC: total lung capacity; FEV1: Force dexpiratory volume in 1s; FVC: forced vital capacity; DLCO: carbonmonoxide diffusing capacity; KCO: CO transfer coefficient." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">FEV1/FVC (%) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">TLC (%) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">%FVC \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">KCO (%) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">DLCO (%) \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">89 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">56 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">52 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">35 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">21 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">80 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">129 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">103 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">86 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">70 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" 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align="char" valign="top">81 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">41 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">56 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">62 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">60 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">42 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">80 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">59 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">46 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">71 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">35 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">77 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">58 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">58 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">71 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">35 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">79 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">76 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">86 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">58 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">45 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">104 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">86 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">86 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">80 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">56 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">75 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">66 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">85 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">57 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">84 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">84 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">79 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">65 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" 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valign="top">103 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">71 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">92 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">77 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">49 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">89 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">52 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">103 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">112 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">101 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">73 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">130 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">61 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">56 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">62 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">37 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">89 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">94 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">89 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">80 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">58 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">78 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">56 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">40 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">79 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">76 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">59 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">80 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">123 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">107 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">54 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">57 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">68 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">112 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">81 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">64 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">45 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">56 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">108 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">64 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">37 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">21 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1386289.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Results of the PFRs." ] ] 4 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "ESSDAI: Eular Sjögren's syndrome disease index; RF: rheumatoid factor; NSIP: nonspecific interstitial pneumonia; UIP: usual interstitial pneumonia; OP: organizing pneumonia; LIP: lymphocytic interstitial pneumonia." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">NSIP \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">UIP \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">OP \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">LIP \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ESSDAI \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 (2–8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 (2–3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 (2–3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6 (5–7) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hypergammaglobulinemia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">45% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">20% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">25% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">100% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Cryoglobulinemia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">25% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">50% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Positive Anti-Ro \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">50% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">60% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">75% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">100% \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Positive RF \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">75% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">40% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">67% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">100% \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1386290.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Analytical findings and ESSDAI results in the different pulmonary patterns." ] ] 5 => array:7 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "NSIP: nonspecific interstitial pneumonia; UIP: usual interstitial pneumonia; OP: organizing pneumonia; LIP: lymphocytic interstitial pneumonia." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">NSIP (%) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">UIP (%) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">OP (%) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">LIP (%) \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ANA titer ≥1/40 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">92 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">80 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">75 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">100 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ANA titer ≥1/320 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">64 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">100 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">67 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">100 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Homogeneous pattern \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">25 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">67 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Spotted pattern \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">82 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">50 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">33 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">100 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Nucleolar pattern \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">25 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1386288.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Titers and patterns of ANA in the different pulmonary patterns." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:17 [ 0 => array:3 [ "identificador" => "bib0090" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "New concepts in the pathogenesis of Sjögren's syndrome: many questions, fewer answers" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "A. 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Sjögren's syndrome-associated interstitial lung disease: A multicenter study

Enfermedad pulmonar instersticial asociada a síndrome de Sjögren: estudio multicéntrico

Delia Reinaa,

Corresponding author

deliareinasanz@gmail.com

Corresponding author.

, Daniel Roig Vilasecaa, Vicenç Torrente-Segarraa, Dacia Cerdàa, Ivan Castellvíb, Cèsar Díaz Tornéb, Mireia Morenoc, Javier Narváezd, Vera Ortize, Rosana Blaviaf, Montserrat Martín-Baranerag, Hèctor Corominasa

a Servicio de Reumatología, Hospital Sant Joan Despí Moisès Broggi, Spain

b Servicio de Reumatología, Hospital de Sant Pau, Spain

c Servicio de Reumatología, Hospital Parc Taulí, Spain

d Servicio de Reumatología, Hospital de Bellvitge, Spain

e Servicio de Reumatología, Hospital de Granollers, Spain

f Servicio de Neumología, Hospital Sant Joan Despí Moisès Broggi, Spain

g Clinical Epidemiology Department, Consorci Sanitari Integral, Spain

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Primary Sj&#246;gren syndrome &#40;PSS&#41; is a chronic inflammatory autoimmune disease characterized typically by lymphocytic infiltration of the exocrine glands resulting in the sicca syndrome&#46; Although sicca features are the central clinical manifestations of the disease&#44; PSS can cause systemic extraglandular manifestations&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Pulmonary manifestations can be an extraglandular complication&#44; with reported prevalence varying widely &#40;9&#8211;75&#37;&#41;&#44; depending on the methods of detection and patient selection&#46; Lung involvement &#40;symptoms and either pulmonary function testing or radiographic abnormalities&#41; can occur in 10&#8211;20&#37; of patients&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">2</span></a> Image techniques&#44; such as chest radiographs and high resolution computerized tomography &#40;HRCT&#41;&#44; are the most useful tools to detect lung involvement&#46; A plain chest X-ray has a low sensitivity to detect early lung involvement&#46; Studies that systematically perform HRCTs&#44; even in asymptomatic patients&#44; report higher rates of pulmonary abnormalities compared with studies based on clinical symptoms&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">3</span></a> HRCT may identify ground-glass attenuation&#44; thin-walled cysts&#44; honeycombing&#44; reticular pattern&#44; small nodules and enlarged mediastinal lymph nodes&#46; Several histopathologic patterns have been described in PSS&#44; including nonspecific interstitial pneumonia &#40;NSIP&#41;&#44; usual interstitial pneumonia &#40;UIP&#41;&#44; organizing pneumonia &#40;OP&#41; and lymphocytic interstitial pneumonia &#40;LIP&#41;&#46; Most of these patterns are known as diffuse interstitial lung disease &#40;ILD&#41;&#46; LIP has a typical radiographic appearance in ground glass opacities with thin-walled cysts&#44; and the presence of these cysts on HRCT scan should raise clinical suspicion for PSS with ILD&#46;<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">4&#44;5</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">NSIP is the most commonly observed histopathological pattern in connective tissue diseases with ILD&#44; including PSS&#46; In patients with PSS and ILD&#44; HRCT and histopathological findings are well correlated<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">6</span></a> and a lung biopsy is usually not recommended&#46; However&#44; radiographic features suggestive of lymphoma &#40;consolidation&#44; large nodules or pleural effusions&#41; require thorough investigation<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">7</span></a> &#40;<a class="elsevierStyleCrossRefs" href="#fig0005">Figs&#46; 1&#8211;3</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">Bronchiolitis and bronchiectasis are the most common airway manifestations &#40;occasionally secondary to the fibrosis of the ILD&#41;&#46; Patients with PSS are also at an increased risk of lymphoma&#46; Other lung abnormalities have been described&#58; amyloidosis&#44; granulomatosis lung disease&#44; pseudolymphoma&#44; pulmonary hypertension and pleural disease&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">2</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Patients with ILD also show a restrictive functional defect that limits respiratory functionality in a variable range of severity&#46; Diffuse ILD is the most serious form of lung involvement due to its potentially progressive nature and simultaneously its risk of respiratory failure&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">8</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Pulmonary function test &#40;PFT&#41; are also necessary to demonstrate functional respiratory disability&#44; even in asymptomatic patients&#46; PFT might also be done very early after disease onset&#44; and the most reliable variable to detect functional defect related to an ILD is DLCO&#46; The presence of lower DLCO has been associated to higher mortality rates&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Recently&#44; an estimated prevalence of 22&#37; of diffuse ILD in PSS in a population-based hospital patient cohort has been described&#46; Pulmonary involvement is related to an increased mortality in PSS patients&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">9</span></a></p><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Objectives</span><p id="par0040" class="elsevierStylePara elsevierViewall">Considering the low prevalence of the lung involvement in PSS&#44; the heterogeneous pattern that can be found in the lung and the severity of the ILD&#44; the aim of this study was to evaluate the clinical characteristics of patients diagnosed with PSS with ILD at 5 Rheumatology clinics in the Barcelona area&#46;</p></span></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Materials and methods</span><p id="par0045" class="elsevierStylePara elsevierViewall">We performed a multicenter cohort in various Hospitals in Barcelona including 25 patients with PSS and ILD&#46; From a total of 743 patients with PSS&#44; 25 &#40;3&#46;4&#37;&#41; developed ILD&#46; The average of follow up of those patients with PSS was 15 years &#40;range 5&#8211;35&#41;&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">An identical database was used in the 5 clinics to collect the information&#46; The information of the study&#44; included in the database&#44; was collected retrospectively during 2013 from the 5 different clinics participating in the study&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">The PSS was diagnosed according to the American-European Consensus Group &#40;AECG&#41; criteria for PSS from 2002&#46; Registry data included&#58; age at evaluation&#44; gender&#44; date of diagnosis of PSS&#44; the type of criteria fulfilled for PSS&#44; immunology data &#40;anti-Ro 60&#44; anti-Ro 52&#44; anti-La&#44; RF&#44; ANA&#41;&#46; We also included the poor outcome prognostic factors of the illness&#44; such as hypergammaglobulinemia or b2-microglobulin and acute phase reactants&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Lung involvement disease variables included&#58; date of diagnosis of ILD&#44; results of bronchoalveolar lavage &#40;BAL&#41;&#44; HRCT&#44; pulmonary biopsy if needed&#44; PFTs with DLCO&#46; We recorded complementary tests that suggest poor further prognosis of the outcome of the disease&#58; echocardiography to measure pulmonary hypertension and a walking test to determine the functional respiratory capacity&#46; We also collected clinical information&#58; arthritis&#44; Raynaud phenomenon&#44; polyneuropathy&#44; parotid gland disease&#44; periodontal disease and purpura or cryoglobulinemia&#46; Treatment received before and during the process of the disease were collected&#44; such as the complications or associated processes&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Eular Sj&#246;gren&#39;s syndrome disease activity index &#40;ESSDAI&#41; was calculated&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">10</span></a> The ESSDAI is a clinical index designed to measure disease activity in patients with PSS&#46; There are 12 domains associated with disease activity &#40;scoring goes from 0 to 3&#41;&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">The data were analyzed descriptively&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Results</span><p id="par0075" class="elsevierStylePara elsevierViewall">In our cohort &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>25&#41;&#44; the mean age at evaluation was 70 years old &#40;&#177;8 years&#41;&#46; The majority were females&#46; In 15&#47;25 of the patients the diagnosis of ILD was done before the diagnosis of PSS&#46; The mean disease duration at evaluation was 7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10 years&#46; The wide variety of histopathological patterns from our cohort was&#58; 12 NSIP&#44; 5 UIP&#44; 4 OP&#44; 2 LIP&#46; Apart from those&#44; one patient was diagnosed of bronchoalveolitis and another one of lung fibrosis&#46; The majority of patients &#40;20&#47;25&#41; referred keratoconjunctivitis sicca&#44; and 20&#47;25 had xerosis&#46; The Schirmer test was pathological in 20 patients&#46; We did 15 salivary scintigraphies&#44; 11 were pathological&#44; and 15 lip biopsies were performed&#44; 10 with the specific focal lymphocytic sialoadenitis&#44; characterized by one or more tightly aggregated lymphocytes &#40;over 50&#41; adjacent to normal gland tissue&#46; These aggregates of lymphocytes are called foci and their total density is called a &#8220;focus score&#8221;&#44; highly specific of PSS pattern&#46; Anti-Ro 60 was positive in 16&#47;25 patients&#44; anti-Ro 52 was determined positive in 4&#47;9 patients&#46; Anti-La was positive in 10&#47;25 patients&#44; RF in 17&#47;25 and ANA in 22&#47;25 &#40;most of these determinations had a spotted pattern and a title &#8805;320&#41;&#46; Ten patients had hypergammaglobulinemia and the determination of b2microglobulin was normal almost in every patient&#46; The mean ESR when data was collected was 35<span class="elsevierStyleHsp" style=""></span>mm&#47;h and the PCR was 2&#46;3<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#46; BAL was performed in 11 patients&#44; 5 of them with &#62;10&#37; of lymphocytes &#40;5&#8211;70&#37;&#41;&#46; In 2 patients a lung biopsy was needed to confirm the diagnosis&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">The PFRs results are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#44; the majority had a clear restrictive pattern&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0085" class="elsevierStylePara elsevierViewall">Analytical findings and ESSDAI results&#44; as well as titers and patterns of ANA in the different pulmonary patterns are shown in <a class="elsevierStyleCrossRefs" href="#tbl0010">Tables 2 and 3</a>&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0090" class="elsevierStylePara elsevierViewall">Four patients had pulmonary hypertension and the walking test was performed in 20 patients&#44; showing pathological findings in half of them&#46; We collected 6 patients with arthritis&#44; 5 with Raynaud phenomenon&#44; 3 with polyneuropathy and 6 with parotid gland disease&#44; 1 with periodontal disease&#44; 4 with purpura or cryoglobulinemia&#46; As with other associated processes we collected&#58; 4 osteoporosis&#44; 2 respiratory infections&#44; 1 plaquetopenia&#44; 1 pernicious anemia&#44; 1 corneal ulcer and 1 primary biliary cirrhosis&#46; The majority of the patients received glucocorticoid therapy &#40;12 at a low dose and 16 at a high dose&#41;&#44; 7 needed antimalarial treatment and 10 immunosupressive treatment&#46; One patient needed a pulmonary transplant&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Mean ESSDAI was 4&#46;2 &#40;2&#8211;9&#41;&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Discussion</span><p id="par0100" class="elsevierStylePara elsevierViewall">Above the glandular manifestations&#44; present in almost all PSS patient&#44; a wide range of extraglandular clinical syndromes may appear in longstanding diseases with a heavy autoimmune background&#46; PSS can affect peripheral and central nervous system&#44; kidney&#44; skin&#44; musculoskeletal and the lungs&#46; Lung disease in the PSS patients can affect their superior and lower respiratory tract&#44; the diaphragm&#44; and the pulmonary vessels&#46; Furthermore&#44; lung lymphoproliferative disease can also be found&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Palm and collegues found a high population-based prevalence of clinical pulmonary involvement &#40;22&#37;&#41; among patients with PSS&#46; They also affirmed that patients with lung involvement had reduced quality of life and increased mortality&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">9</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">Patients with extraglandular manifestations frequently can have ILD&#46; Gardiner and collegues wrote that the prevalence of ILD in PSS patients is approximately 8&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">11</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">Recently&#44; Kreider wrote that 10&#8211;20&#37; of patients with PSS have lung involvement&#44; and subclinical lung disease is even more frequent and can include evidence of small airway disease and inflammation&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">2</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">ILD can be found in various connective tissue diseases&#46; In the PSS&#44; ILD is an extraglandular severe manifestation and it is particularly associated with patients that are positive with anti-Ro and anti-Ro52&#46; In a study done by Ito and collegues<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">6</span></a> they found that 61&#37; of 33 patients who had PSS had NSIP in the lung biopsy&#44; 4 had diffuse bronchiolitis&#44; 4 had non-Hodgkin&#39;s lymphomas of mucosal associated lymphoid tissue &#40;MALT&#41; and 5 patients had evidence of amyloidosis&#44; but none of these patients had evidence of LIP&#46; LIP was considered one of the most common pulmonary manifestations in PSS&#44; but recent studies have demonstrated a much lower prevalence &#40;0&#46;9&#8211;17&#37;&#41;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">4</span></a>&#46; The findings from our study show different results from the study done by Ito&#44; although we did not conduct biopsies in all the patients for the diagnosis&#46; We based our diagnosis basically on the HRCT due to findings in the HCRT are used to be well correlated to histopathologic finding&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">In patients with active extra-glandular manifestations and in those that are immunologically active it is mandatory to discard the presence of ILD by doing a HRCT and PFTs&#46; The symptoms of ILD are cough&#44; dyspnea&#44; bilateral infiltrates on radiograph and various patters of abnormalities on HRCT scan&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">8</span></a> These exams must be done in the primary stages due to the possible severity of the ILD&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">The lung disease can occur before the other more usual manifestations of the syndrome<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">12&#44;13</span></a> and also approximately 15&#37; to 20&#37; of patients presenting with chronic ILD can have an occult connective tissue disease&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">14</span></a> In our cohort&#44; in 60&#37; of the patients&#44; the ILD diagnosis was made before the PSS diagnosis&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">Although&#44; some factors have been proposed to be associated with a poor outcome in PSS&#44; specifically with a higher risk of lymphoma&#44; high levels of beta2-microglobulin&#44; presence of skin vasculitis&#44; decreased levels of C3&#44; C4 factors&#44; lower level of CD4 lymphocytes and a CD4&#47;CD8 beyond 0&#46;8&#44;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">15</span></a> the levels of b2microglobulin are not associated with the ILD&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">The pulmonary manifestation often shows a restrictive pattern and a low DLCO&#44; associated with a high morbidity and a high mortality&#46; In some patients the course of the illness could be benign with a stabilization in the lung disease&#46; Keeping in mind that the PSS with ILD associated to other connective tissue diseases can develop into a pulmonary fibrosis&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">It is mandatory a cross and a multi-disciplinary collaboration in the management of any of the connective tissue diseases with lung disease between rheumatologists and pulmonologists&#46; Rheumatologists help to detect an occult connective tissue disease in patients with &#8220;idiopathic ILD&#8221; by requiring careful attention to the historical clues&#44; the physical examination findings&#44; specific autoantibodies&#44; radiological and histopathological features&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">16</span></a> For pulmonologists it is important to recognize that PSS with ILD can result in severe disease and they can help in the lung disease management&#46; For a multidisciplinary approach pulmonologists need to learn clues to distinguish between idiopathic interstitial pneumonia from connective tissue disease associated with ILD&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">17</span></a></p><p id="par0150" class="elsevierStylePara elsevierViewall">Our study has an important limitation&#58; the information was collected retrospectively&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Conclusion</span><p id="par0155" class="elsevierStylePara elsevierViewall">To summarize&#44; we shall consider that lung involvement can occur in patients with PSS&#46; ILD is one of the extraglandulars manifestations in those patients&#46; In our cohort we observed the following histopathological patterns&#58; NSIP&#44; UIP&#44; OP and LIP &#40;in this order&#41;&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">Higher rates of mortality and morbidity in PSS are related to the ILD&#44; therefore&#44; patients affected with PSS must be screened to catch a precocious diagnosis doing all the complementary tests needed&#46; It is important to discard a connective tissue disease in patients with ILD&#46; In our cohort the majority of the patients were diagnosed of ILD before being diagnosed of PSS&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">Due to the low prevalence of the ILD in PSS&#44; multicentre cohorts are increasingly demanded to give information about the characteristics&#44; the management and treatment not only of the disease&#44; but also of the single organ complications&#46; A multidisciplinary management is needed&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Ethical disclosures</span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Protection of human and animal subjects</span><p id="par0175" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appear in this article&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Confidentiality of data</span><p id="par0180" class="elsevierStylePara elsevierViewall">The authors declare that they have followed the protocols of the workplace on the publication of patient data&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Right to privacy and informed consent</span><p id="par0185" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appear in this article&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Conflict of interest</span><p id="par0170" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interest&#46;</p></span></span>"
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          "identificador" => "sec0025"
          "titulo" => "Discussion"
        ]
        8 => array:2 [
          "identificador" => "sec0030"
          "titulo" => "Conclusion"
        ]
        9 => array:3 [
          "identificador" => "sec0040"
          "titulo" => "Ethical disclosures"
          "secciones" => array:3 [
            0 => array:2 [
              "identificador" => "sec0045"
              "titulo" => "Protection of human and animal subjects"
            ]
            1 => array:2 [
              "identificador" => "sec0050"
              "titulo" => "Confidentiality of data"
            ]
            2 => array:2 [
              "identificador" => "sec0055"
              "titulo" => "Right to privacy and informed consent"
            ]
          ]
        ]
        10 => array:2 [
          "identificador" => "sec0035"
          "titulo" => "Conflict of interest"
        ]
        11 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2015-07-31"
    "fechaAceptado" => "2015-09-24"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec821049"
          "palabras" => array:2 [
            0 => "Interstitial lung disease"
            1 => "Sj&#246;gren syndrome"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec821048"
          "palabras" => array:2 [
            0 => "Enfermedad pulmonar intersticial"
            1 => "S&#237;ndrome de Sj&#246;gren"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Primary Sj&#246;gren syndrome &#40;PSS&#41; is a chronic inflammatory autoimmune disease&#46; Interstitial lung disease &#40;ILD&#41; can be an extraglandular complication&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">To evaluate the clinical characteristics of patients diagnosed with PSS with ILD&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Multicentre cohort study with 25 patients diagnosed with PSS and ILD&#46; Data of PSS&#44; prognostic factors&#44; pulmonary involvement variables&#44; complementary tests that suggest a worse diagnosis and treatment given were collected&#46; EULAR index was measured for Sj&#246;gren&#39;s syndrome&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">We identified 25 patients&#46; In 15&#47;25 the diagnosis of ILD was done before the diagnosis of PSS&#46; The histopathological patterns found were&#58; 12 NSIP&#44; 5 UIP&#44; 4 OP&#44; 2 LIP&#46; PFRs showed restrictive pattern&#46; The majority of the patients received glucocorticoid therapy&#44; antimalarial or immunosuppressive treatment&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Patients affected with PSS must be screened to catch a precocious diagnosis of ILD&#46; The majority of the patients were diagnosed of ILD before being diagnosed of PSS&#46; Multicenter cohorts are increasingly demanded and a multidisciplinary management is needed&#46;</p></span>"
        "secciones" => array:5 [
          0 => array:1 [
            "identificador" => "abst0005"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Objective"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Methods"
          ]
          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Results"
          ]
          4 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Conclusions"
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        ]
      ]
      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0030" class="elsevierStyleSection elsevierViewall"><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">El s&#237;ndrome de Sj&#246;gren primario &#40;SSP&#41; es una enfermedad inflamatoria autoinmune&#46; La enfermedad pulmonar intersticial &#40;EPI&#41; puede ser una complicaci&#243;n extraglandular&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Evaluar las caracter&#237;sticas cl&#237;nicas de los pacientes diagnosticados de SSP con EPI&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Estudio de cohortes multic&#233;ntrico con 25 pacientes diagnosticados de SSP y EPI&#46; Se recopilaron datos propios del SSP&#44; factores pron&#243;stico&#44; variables de medida de la afectaci&#243;n pulmonar&#44; pruebas complementarias que sugieren un peor pron&#243;stico&#44; as&#237; como el tratamiento recibido&#46; Se calcul&#243; el &#237;ndice EULAR para el s&#237;ndrome de Sj&#246;gren&#46;</p></span> <span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Se identificaron 25 pacientes&#46; Quince de ellos fueron diagnosticados de EPI antes que de SSP&#46; Los patrones histopatol&#243;gicos encontrados fueron 12 con neumon&#237;a intersticial inespec&#237;fica&#44; 5 con neumon&#237;a intersticial com&#250;n&#44; 4 con neumon&#237;a organizada&#44; 2 con neumon&#237;a intersticial linfoc&#237;tica&#46; Las pruebas de funci&#243;n respiratoria mostraron un patr&#243;n restrictivo&#46; La mayor&#237;a de los pacientes recibi&#243; un tratamiento con glucocorticoides&#44; antipal&#250;dicos o inmunodepresores&#46;</p></span> <span id="abst0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Los pacientes afectados por SSP deben ser sometidos a pruebas para detectar un diagn&#243;stico precoz de EPI&#46; La mayor&#237;a de los pacientes fueron diagnosticados de EPI antes que de SSP&#46; Los estudios de cohortes multic&#233;ntricos son cada vez m&#225;s demandados y se precisa una gesti&#243;n multidisciplinar&#46;</p></span>"
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            "identificador" => "abst0040"
            "titulo" => "M&#233;todos"
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          3 => array:2 [
            "identificador" => "abst0045"
            "titulo" => "Resultados"
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            "identificador" => "abst0050"
            "titulo" => "Conclusiones"
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        "descripcion" => array:1 [
          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">HRCT&#46; Patchy involvement in ground glass opacity in right lung tending to fibrosis due to NSIP&#46;</p>"
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          "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">HRCT&#46; Peribronchial ground glass compatible with OP&#46;</p>"
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          "leyenda" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">TLC&#58; total lung capacity&#59; FEV1&#58; Force dexpiratory volume in 1<span class="elsevierStyleHsp" style=""></span>s&#59; FVC&#58; forced vital capacity&#59; DLCO&#58; carbonmonoxide diffusing capacity&#59; KCO&#58; CO transfer coefficient&#46;</p>"
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          "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Results of the PFRs&#46;</p>"
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          "leyenda" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">ESSDAI&#58; Eular Sj&#246;gren&#39;s syndrome disease index&#59; RF&#58; rheumatoid factor&#59; NSIP&#58; nonspecific interstitial pneumonia&#59; UIP&#58; usual interstitial pneumonia&#59; OP&#58; organizing pneumonia&#59; LIP&#58; lymphocytic interstitial pneumonia&#46;</p>"
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                0 => """
                  <table border="0" frame="\n
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                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">NSIP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">UIP&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ESSDAI&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2 &#40;2&#8211;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3 &#40;2&#8211;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6 &#40;5&#8211;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hypergammaglobulinemia&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Cryoglobulinemia&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">100&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Positive RF&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr></tbody></table>
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          "leyenda" => "<p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">NSIP&#58; nonspecific interstitial pneumonia&#59; UIP&#58; usual interstitial pneumonia&#59; OP&#58; organizing pneumonia&#59; LIP&#58; lymphocytic interstitial pneumonia&#46;</p>"
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">80&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">75&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">100&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">64&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">67&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Homogeneous pattern&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">67&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Spotted pattern&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">82&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">50&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">33&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Nucleolar pattern&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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        "descripcion" => array:1 [
          "en" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">Titers and patterns of ANA in the different pulmonary patterns&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:17 [
            0 => array:3 [
              "identificador" => "bib0090"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "New concepts in the pathogenesis of Sj&#246;gren&#39;s syndrome&#58; many questions&#44; fewer answers"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "A&#46; Hansen"
                            1 => "P&#46;E&#46; Lipsky"
                            2 => "T&#46; Dorner"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Curr Opin Rheumatol"
                        "fecha" => "2003"
                        "volumen" => "15"
                        "paginaInicial" => "563"
                        "paginaFinal" => "570"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12960481"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0095"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Pulmonary involvement in Sj&#246;gren syndrome"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "M&#46; Kreider"
                            1 => "K&#46; Highland"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1055/s-0034-1371529"
                      "Revista" => array:6 [
                        "tituloSerie" => "Semin Respir Crit Care Med"
                        "fecha" => "2014"
                        "volumen" => "35"
                        "paginaInicial" => "255"
                        "paginaFinal" => "264"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24668540"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0100"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Lung manifestation in asymptomatic patients with primary Sj&#246;gren syndrome&#58; assessment with high resolution CT and pulmonary function tests"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "M&#46; Uffmann"
                            1 => "H&#46;P&#46; Kiener"
                            2 => "A&#46;A&#46; Bankier"
                            3 => "M&#46;M&#46; Baldt"
                            4 => "T&#46; Zontsich"
                            5 => "C&#46;J&#46; Herold"
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Article information

ISSN: 21735743
Original language: English

DOI:10.1016/j.reumae.2015.09.009

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Year/Month	Html	Pdf	Total

2024 November	13	12	25
2024 October	69	36	105
2024 September	96	12	108
2024 August	84	32	116
2024 July	68	28	96
2024 June	55	29	84
2024 May	68	40	108
2024 April	74	16	90
2024 March	62	28	90
2024 February	78	22	100
2024 January	38	16	54
2023 December	53	28	81
2023 November	48	26	74
2023 October	67	26	93
2023 September	87	35	122
2023 August	59	32	91
2023 July	49	18	67
2023 June	47	17	64
2023 May	65	22	87
2023 April	44	21	65
2023 March	67	34	101
2023 February	55	24	79
2023 January	56	47	103
2022 December	124	34	158
2022 November	102	34	136
2022 October	88	39	127
2022 September	99	33	132
2022 August	102	46	148
2022 July	75	43	118
2022 June	64	37	101
2022 May	69	43	112
2022 April	72	47	119
2022 March	82	49	131
2022 February	59	17	76
2022 January	58	33	91
2021 December	52	34	86
2021 November	54	47	101
2021 October	49	48	97
2021 September	54	36	90
2021 August	49	37	86
2021 July	15	25	40
2021 June	47	44	91
2021 May	54	41	95
2021 April	344	79	423
2021 March	81	37	118
2021 February	36	23	59
2021 January	46	23	69
2020 December	69	29	98
2020 November	44	22	66
2020 October	37	20	57
2020 September	60	38	98
2020 August	39	23	62
2020 July	59	12	71
2020 June	43	20	63
2020 May	56	10	66
2020 April	26	14	40
2020 March	12	9	21
2020 February	1	0	1
2018 December	2	0	2
2018 May	2	0	2
2018 April	28	4	32
2018 March	41	8	49
2018 February	20	3	23
2018 January	14	5	19
2017 December	20	3	23
2017 November	20	7	27
2017 October	18	7	25
2017 September	25	11	36
2017 August	19	6	25
2017 July	18	7	25
2017 June	24	5	29
2017 May	25	17	42
2017 April	22	13	35
2017 March	22	9	31
2017 February	15	7	22
2017 January	15	8	23
2016 December	38	15	53
2016 November	30	15	45
2016 October	40	12	52
2016 September	41	10	51
2016 August	80	23	103
2016 July	50	16	66

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