Case Report
Rituximab in the Treatment of Shrinking Lung Syndrome in Systemic Lupus Erythematosus
Rituximab en el tratamiento del síndrome del pulmón encogido del lupus eritematoso sistémico
Patricia Peñacoba Toribioa,
, María Emilia Córica Albanib, Mercedes Mayos Pérezc, Arturo Rodríguez de la Sernab
Corresponding author
a Servicio de Neumología, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
b Unidad de Reumatología, Servicio de Medicina Interna, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
c Unidad de Trastornos Respiratorios del Sueño, Servicio de Neumología, Hospital de la Santa Creu i Sant Pau, Centro de Investigación Biomédica en Red en Enfermedades Respiratorias (CibeRes), Universidad Autónoma de Barcelona, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
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"ppenacoba@santpau.cat" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "María Emilia" "apellidos" => "Córica Albani" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "Mercedes" "apellidos" => "Mayos Pérez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 3 => array:3 [ "nombre" => "Arturo" "apellidos" => "Rodríguez de la Serna" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Servicio de Neumología, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Unidad de Reumatología, Servicio de Medicina Interna, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Unidad de Trastornos Respiratorios del Sueño, Servicio de Neumología, Hospital de la Santa Creu i Sant Pau, Centro de Investigación Biomédica en Red en Enfermedades Respiratorias (CibeRes), Universidad Autónoma de Barcelona, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Rituximab en el tratamiento del síndrome del pulmón encogido del lupus eritematoso sistémico" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 348 "Ancho" => 1001 "Tamanyo" => 72171 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Posteroanterior chest X-ray and chest CT in which volume loss of both lungs and atelectasis in the bases is appreciated.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Shrunken lung syndrome (SLS) is a rare manifestation of some autoimmune diseases such as systemic lupus erythematosus (SLE). It is characterized by a restrictive type ventilatory defect and should be suspected in patients with SLE presenting unexplained dyspnea. Treatment is not well established. Although the use of systemic corticosteroids as first-line treatment has been proposed in refractory cases, other immunosuppressive drugs, such as rituximab, have been suggested.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Clinical Case</span><p id="par0010" class="elsevierStylePara elsevierViewall">The patient was a 57-year-old female followed by the Rheumatology Department since age 22, diagnosed with SLE in the context of fever, polyarticular pain, malar rash, and photosensitivity. She presented antinuclear antibodies 1/320 (normal <1/40), anti-native DNA 50.00<span class="elsevierStyleHsp" style=""></span>IU/ml (normal <15), IgG anticardiolipin 20.23<span class="elsevierStyleHsp" style=""></span>GPL/ml (normal 0.00–7.70), and positive anti-histone antibodies. She was initially treated with prednisone (15<span class="elsevierStyleHsp" style=""></span>g/day) and chloroquine (155<span class="elsevierStyleHsp" style=""></span>mg/day) with good response.</p><p id="par0015" class="elsevierStylePara elsevierViewall">At age 29, due to an episode of focal segmental glomerulonephritis, treatment with azathioprine was added 50<span class="elsevierStyleHsp" style=""></span>m g/12<span class="elsevierStyleHsp" style=""></span>h, with complete remission.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Years later, she presented moderate dyspnea accompanied by dry cough and pleuritic pain, and was evaluated by pneumology. She had crackling rales in the lung bases on auscultation. The chest X-ray showed elevation of both hemidiaphragms and bibasilar atelectasis (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). The pulmonary function tests (September 2008) showed an intense restrictive ventilatory defect, moderate decrease in the diffusion capacity of carbon monoxide, which fully corrected by alveolar volume, along with a slight decrease in peak inspiratory pressure (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). A chest computed tomography confirmed the loss of volume in both lungs and the presence of atelectasis in the bases (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">With these data, she was diagnosed with SLS associated with SLE. It was decided to increase the dose of prednisone to 30<span class="elsevierStyleHsp" style=""></span>mg/day, associated with an inhaled beta-2 adrenergic, with good initial clinical response.</p><p id="par0030" class="elsevierStylePara elsevierViewall">When trying to lower the dose of glucocorticoids (March 2009), the patient had a worsening of respiratory symptoms, with mild effort dyspnea and chest pain. Upon detection of lymphopenia and positivity of biomarkers (increased levels of anti-DNA antibodies and consumption of C4 complement), we decided to maintain the same previous dose of prednisone and azathioprine, adding mycophenolate mofetil at a dose of 720<span class="elsevierStyleHsp" style=""></span>mg/12<span class="elsevierStyleHsp" style=""></span>h. Six months later, she presented a new outbreak of arthritis, so the combined treatment was discontinued and rituximab was initiated (2 doses of 1<span class="elsevierStyleHsp" style=""></span>g separated by 15 days were administered; this pattern has been repeated every 6 months until publication).</p><p id="par0035" class="elsevierStylePara elsevierViewall">Under the established treatment, a progressive improvement in both the symptoms and the lung function tests (May 2011–April 2013) (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>) was seen, making it possible to reduce the dose of prednisone to 5<span class="elsevierStyleHsp" style=""></span>mg/24<span class="elsevierStyleHsp" style=""></span>h; she has remained clinically stable until this report.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Discussion</span><p id="par0040" class="elsevierStylePara elsevierViewall">We present the case of a patient who had SLS, who showed no significant clinical improvement with the classic treatment with corticosteroids and immunosuppressants, but which was achieved after initiation of rituximab.</p><p id="par0045" class="elsevierStylePara elsevierViewall">It is known that the pleuropulmonary involvement in SLE is present in 60%–80% of patients 1, wherein SLS is one of the less common manifestations.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Its prevalence is 7%,<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> higher in women with severe SLE refractory to treatment.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">The presenting symptoms are dyspnea and chest pain. Auscultation is usually normal.<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4,5</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">Respiratory function shows a restrictive type of ventilatory defect with reduced lung volumes. Imaging tests show no evidence of pleural, parenchymal or vascular disease.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">The cause of the SLS is not known.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1–3</span></a> There are several hypotheses including the presence of atelectasis by the loss of surfactant<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6,3,4</span></a> diaphragmatic myopathy, phrenic neuropathy, pleural adhesions, and inactivation of the diaphragm induced by pain.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> SLS has also been linked to anti-Ro antibody.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,3,7</span></a> None of these theories has been confirmed.</p><p id="par0065" class="elsevierStylePara elsevierViewall">The long-term prognosis is generally good, with clinical stabilization or improvement.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> Deterioration appears in only 2% of cases, requiring aggressive therapy<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8,9</span></a> or even mechanical ventilation.</p><p id="par0070" class="elsevierStylePara elsevierViewall">There is no definitive treatment of SLS, although glucocorticoids are considered the first line therapy, alone or in combination with other immunosuppressive agents.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> In addition, theophylline and beta-2 agonists are used with the intention to increase diaphragmatic strength.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,3</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">On the other hand, there has been much improvement both of pleuritic pain and of dyspnea in patients treated with rituximab. Rituximab is a chimeric mouse/human monoclonal antibody that specifically binds to the CD20 antigen expressed on pre-B and mature B lymphocytes. Although no prospective study of rituximab in SLS has been performed, isolated cases have been reported where refractory patients experience symptom improvement with increased exercise tolerance, and an improvement in respiratory function tests with increasing expiratory volume in the first second and forced vital capacity.<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3,10</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Conclusion</span><p id="par0080" class="elsevierStylePara elsevierViewall">So far, the treatment of choice for SLS is corticosteroids alone or in combination. Refractory cases may benefit from treatment with rituximab.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Ethical Responsibilities</span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Protection of persons and animals</span><p id="par0085" class="elsevierStylePara elsevierViewall">The authors state that no experiments were performed on persons or animals for this study.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Data confidentiality</span><p id="par0090" class="elsevierStylePara elsevierViewall">The authors state that they have followed their workplace protocols regarding the publication of patient data and all patients included in the study have received enough information and have given their written informed consent to participate in the study.</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Right to privacy and informed consent</span><p id="par0095" class="elsevierStylePara elsevierViewall">The authors state that they have obtained informed consent from patients and/or subjects referred to in this article. This document is in the possession of the corresponding author.</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Conflict of Interest</span><p id="par0100" class="elsevierStylePara elsevierViewall">The authors declare no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:2 [ "identificador" => "xres368262" "titulo" => "Abstract" ] 1 => array:2 [ "identificador" => "xpalclavsec347434" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xres368263" "titulo" => "Resumen" ] 3 => array:2 [ "identificador" => "xpalclavsec347435" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Clinical Case" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Discussion" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Conclusion" ] 8 => array:3 [ "identificador" => "sec0025" "titulo" => "Ethical Responsibilities" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0030" "titulo" => "Protection of persons and animals" ] 1 => array:2 [ "identificador" => "sec0035" "titulo" => "Data confidentiality" ] 2 => array:2 [ "identificador" => "sec0040" "titulo" => "Right to privacy and informed consent" ] ] ] 9 => array:2 [ "identificador" => "sec0045" "titulo" => "Conflict of Interest" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2013-07-11" "fechaAceptado" => "2013-09-26" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec347434" "palabras" => array:4 [ 0 => "Systemic lupus erythematosus" 1 => "Shrinking lung syndrome" 2 => "Glucocorticoids" 3 => "Rituximab" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec347435" "palabras" => array:4 [ 0 => "Lupus eritematoso sistémico" 1 => "Síndrome del pulmón encogido" 2 => "Glucocorticoides" 3 => "Rituximab" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Shrinking lung syndrome (SLS) is a rare manifestation of systemic lupus erythematosus. We report the case of a patient with non-responding SLS (neither to glucocorticoids nor immunosupresors), who showed remarkable improvement after the onset of treatment with rituximab. Although there is a little evidence, treatment with rituximab could be proposed in SLS when classical treatment fails.</p>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">El síndrome del pulmón encogido (SPE) es una manifestación poco frecuente del lupus eritematoso sistémico. Exponemos el caso de una paciente afectada de SPE, refractario al tratamiento con glucocorticoides e inmunosupresores, que tras el inicio de tratamiento con rituximab presentó marcada mejoría de los síntomas. Aunque la evidencia es escasa, el tratamiento con rituximab podría ser propuesto en el SPE cuando fracasa el tratamiento clásico.</p>" ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Peñacoba Toribio P, Córica Albani ME, Mayos Pérez M, Rodríguez de la Serna A. Rituximab en el tratamiento del síndrome del pulmón encogido del lupus eritematoso sistémico. Reumatol Clin. 2013;10:325–327.</p>" ] ] "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 348 "Ancho" => 1001 "Tamanyo" => 72171 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Posteroanterior chest X-ray and chest CT in which volume loss of both lungs and atelectasis in the bases is appreciated.</p>" ] ] 1 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "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"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">RFT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">September 08 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">February 09 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">May 11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Apr 13 \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">FVC, % \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">43 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">55 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">64 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">76 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">FEV1, % \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">46 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">52 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">61 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">61 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">FEV1/FVC, % \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">82 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">73 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">71 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">62 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">TLC, % \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">56 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">62 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">79 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DLCO, % \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">55 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">79 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">53 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DL/VA Adj, % \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">103 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">94 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">92 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">IP max, % \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">66 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">79 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">94 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab553685.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Evolution of Pulmonary Function Tests.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Presentation and prognosis of shrinking lung syndrome in systemic lupus erythematosus: report of four cases" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "D.C. 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Alves Pereira" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s10067-010-1427-1" "Revista" => array:6 [ "tituloSerie" => "Clin Rheumatol" "fecha" => "2010" "volumen" => "29" "paginaInicial" => "777" "paginaFinal" => "779" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20306212" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0040" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Shrinking lung syndrome: recognition, pathophysiology and therapeutic strategy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "D. Carmier" 1 => "E. Diot" 2 => "P. Diot" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1586/ers.10.84" "Revista" => array:6 [ "tituloSerie" => "Expert Rev Respir Med" "fecha" => "2011" "volumen" => "5" "paginaInicial" => "33" "paginaFinal" => "39" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21348584" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0045" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Shrinking lung syndrome: a rare manifestation of systemic lupus erythematosus" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "R. Vilaplana-Garcia" 1 => "A.J. Trujillo-Santos" 2 => "F.J. Vera-Mendez" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Arch Bronconeumol" "fecha" => "2008" "volumen" => "44" "paginaInicial" => "341" "paginaFinal" => "342" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18559226" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0050" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Successful treatment of shrinking lung syndrome with rituximab in a patient with systemic lupus erythematosus" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "H. Benham" 1 => "L. Garske" 2 => "P. Vecchio" 3 => "B.W. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 4 | 3 | 7 |
| 2024 October | 107 | 34 | 141 |
| 2024 September | 92 | 12 | 104 |
| 2024 August | 127 | 38 | 165 |
| 2024 July | 154 | 42 | 196 |
| 2024 June | 149 | 35 | 184 |
| 2024 May | 168 | 41 | 209 |
| 2024 April | 124 | 26 | 150 |
| 2024 March | 142 | 39 | 181 |
| 2024 February | 135 | 35 | 170 |
| 2024 January | 144 | 30 | 174 |
| 2023 December | 106 | 48 | 154 |
| 2023 November | 83 | 24 | 107 |
| 2023 October | 120 | 30 | 150 |
| 2023 September | 153 | 43 | 196 |
| 2023 August | 82 | 20 | 102 |
| 2023 July | 83 | 27 | 110 |
| 2023 June | 73 | 25 | 98 |
| 2023 May | 71 | 17 | 88 |
| 2023 April | 47 | 10 | 57 |
| 2023 March | 110 | 24 | 134 |
| 2023 February | 66 | 34 | 100 |
| 2023 January | 45 | 36 | 81 |
| 2022 December | 60 | 50 | 110 |
| 2022 November | 57 | 27 | 84 |
| 2022 October | 87 | 29 | 116 |
| 2022 September | 67 | 36 | 103 |
| 2022 August | 47 | 39 | 86 |
| 2022 July | 55 | 39 | 94 |
| 2022 June | 57 | 43 | 100 |
| 2022 May | 56 | 41 | 97 |
| 2022 April | 74 | 47 | 121 |
| 2022 March | 84 | 57 | 141 |
| 2022 February | 57 | 37 | 94 |
| 2022 January | 88 | 43 | 131 |
| 2021 December | 74 | 46 | 120 |
| 2021 November | 79 | 50 | 129 |
| 2021 October | 83 | 58 | 141 |
| 2021 September | 66 | 36 | 102 |
| 2021 August | 60 | 34 | 94 |
| 2021 July | 59 | 23 | 82 |
| 2021 June | 65 | 36 | 101 |
| 2021 May | 72 | 42 | 114 |
| 2021 April | 123 | 76 | 199 |
| 2021 March | 114 | 25 | 139 |
| 2021 February | 82 | 18 | 100 |
| 2021 January | 70 | 17 | 87 |
| 2020 December | 51 | 24 | 75 |
| 2020 November | 57 | 27 | 84 |
| 2020 October | 39 | 14 | 53 |
| 2020 September | 39 | 30 | 69 |
| 2020 August | 34 | 21 | 55 |
| 2020 July | 40 | 17 | 57 |
| 2020 June | 59 | 30 | 89 |
| 2020 May | 52 | 19 | 71 |
| 2020 April | 55 | 10 | 65 |
| 2020 March | 27 | 9 | 36 |
| 2020 February | 2 | 0 | 2 |
| 2019 December | 2 | 0 | 2 |
| 2019 November | 1 | 0 | 1 |
| 2019 October | 2 | 0 | 2 |
| 2019 June | 1 | 0 | 1 |
| 2019 May | 5 | 0 | 5 |
| 2019 April | 1 | 0 | 1 |
| 2019 March | 2 | 0 | 2 |
| 2018 December | 3 | 0 | 3 |
| 2018 May | 4 | 0 | 4 |
| 2018 April | 85 | 11 | 96 |
| 2018 March | 104 | 10 | 114 |
| 2018 February | 64 | 10 | 74 |
| 2018 January | 73 | 8 | 81 |
| 2017 December | 84 | 11 | 95 |
| 2017 November | 95 | 8 | 103 |
| 2017 October | 105 | 8 | 113 |
| 2017 September | 115 | 13 | 128 |
| 2017 August | 84 | 10 | 94 |
| 2017 July | 99 | 19 | 118 |
| 2017 June | 120 | 12 | 132 |
| 2017 May | 123 | 19 | 142 |
| 2017 April | 112 | 14 | 126 |
| 2017 March | 130 | 11 | 141 |
| 2017 February | 84 | 9 | 93 |
| 2017 January | 91 | 11 | 102 |
| 2016 December | 157 | 21 | 178 |
| 2016 November | 173 | 12 | 185 |
| 2016 October | 209 | 8 | 217 |
| 2016 September | 254 | 7 | 261 |
| 2016 August | 214 | 13 | 227 |
| 2016 July | 135 | 14 | 149 |
| 2016 April | 2 | 0 | 2 |
| 2016 March | 1 | 0 | 1 |
| 2015 December | 1 | 0 | 1 |
| 2015 September | 1 | 0 | 1 |
| 2015 August | 3 | 0 | 3 |
| 2015 July | 65 | 7 | 72 |
| 2015 June | 84 | 9 | 93 |
| 2015 May | 155 | 16 | 171 |
| 2015 April | 191 | 15 | 206 |
| 2015 March | 168 | 13 | 181 |
| 2015 February | 151 | 9 | 160 |
| 2015 January | 122 | 12 | 134 |
| 2014 December | 82 | 11 | 93 |
| 2014 November | 50 | 13 | 63 |
| 2014 October | 69 | 29 | 98 |
| 2014 September | 32 | 19 | 51 |
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