Case Report
Coexistence of anti-Jo1 and anti-signal recognition particle antibodies in a polymyositis patient
Coexistencia de anticuerpos anti-histidil-tRNA-sintetasa y anti-partícula de reconocimiento de la señal en un paciente con polimiositis
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(A) La TAC de tórax al diagnóstico reveló la presencia de discretos infiltrados intersticiales en vidrio deslustrado en las bases y la periferia de los pulmones y, en menor medida, en los campos medios, con ganglios linfáticos mediastínicos múltiples de menos de 17<span class="elsevierStyleHsp" style=""></span>mm y atelectasia segmentaria del lóbulo inferior derecho. (B) A los 3 meses la angioTAC no mostró imágenes de tromboembolismo pulmonar, pero sí se observaba una extensa afectación pulmonar bilateral con infiltrados intersticiales con opacidad en vidrio deslustrado y engrosamiento de los septos interlobulillares, así como áreas de fibrosis, estando más respetados los campos pulmonares anteriores.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Enrique Melguizo Madrid, Patricia Fernández Riejos, Francisco Javier Toyos Sáenz de Miera, Berta Fernández Pérez, Concepción González Rodríguez" "autores" => array:5 [ 0 => array:2 [ "nombre" => "Enrique" "apellidos" => "Melguizo Madrid" ] 1 => array:2 [ "nombre" => "Patricia" "apellidos" => "Fernández Riejos" ] 2 => array:2 [ "nombre" => "Francisco Javier" "apellidos" => "Toyos Sáenz de Miera" ] 3 => array:2 [ "nombre" => "Berta" "apellidos" => "Fernández Pérez" ] 4 => array:2 [ "nombre" => "Concepción" "apellidos" => "González Rodríguez" ] ] ] ] ] "idiomaDefecto" => "es" 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class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Patricia" "apellidos" => "Fernández Riejos" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "Francisco Javier" "apellidos" => "Toyos Sáenz de Miera" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "Berta" "apellidos" => "Fernández Pérez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 4 => array:3 [ "nombre" => "Concepción" "apellidos" => "González Rodríguez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Departamento de Bioquímica, Hospital Universitario Virgen Macarena, Sevilla, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Departamento de Reumatología, Hospital Universitario Virgen Macarena, Sevilla, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Coexistencia de anticuerpos anti-histidil-tRNA-sintetasa y anti-partícula de reconocimiento de la señal en un paciente con polimiositis" ] ] "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" => 1228 "Ancho" => 1500 "Tamanyo" => 250588 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Evolution of the pulmonary involvement shown by axial computed tomography (ACT). (A) ACT of the thorax at diagnosis revealed the presence of discrete interstitial infiltrates in ground glass opacity in the bases and periphery of the lungs, and to a lesser degree, in the mid-fields, with multiple mediastinal lymphatic ganglia of less than 17<span class="elsevierStyleHsp" style=""></span>mm and segmental atelectasis of the lower right lobe. (B) At 3 months the angio ACT showed no images of pulmonary thromboembolism, although extensive bilateral involvement of the lungs was observed, with interstitial infiltrates with ground glass opacity and interlobular septal thickening, as well as areas of fibrosis, while the anterior pulmonary fields were less involved.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Idiopathic inflammatory myopathies (IIM) are myopathies that are potentially treatable, and they are classified as: dermatomyositis, polymyositis (PM), necrotising autoimmune myositis and inclusion body myositis. Specific antibodies for myositis are frequent in patients with IIM, and they are useful in diagnosis and classification. The anti-Jo1 antibody is the most common, and together with the anti-signal recognition particle (anti-SRP) they are the most specific for PM. Anti-SRP is rare and appears isolated in myositis.</p><p id="par0010" class="elsevierStylePara elsevierViewall">We present an extremely rare clinical case in which anti-Jo-1 and anti-SRP coexist in the serum. We analyse the clinical evolution of the case to examine the effect of this coexistence and the possible interaction of both antibodies in the prognosis.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Clinical case</span><p id="par0015" class="elsevierStylePara elsevierViewall">A 60 year-old man, a smoker (40<span class="elsevierStyleHsp" style=""></span>packs/year), dyslipidemic hypertension and dyslipidemia, treated with 50<span class="elsevierStyleHsp" style=""></span>mg/24<span class="elsevierStyleHsp" style=""></span>h atenolol, 100<span class="elsevierStyleHsp" style=""></span>mg/24<span class="elsevierStyleHsp" style=""></span>h acetylsalicylic acid, 10<span class="elsevierStyleHsp" style=""></span>mg/24<span class="elsevierStyleHsp" style=""></span>h enalapril, 10<span class="elsevierStyleHsp" style=""></span>mg/24<span class="elsevierStyleHsp" style=""></span>h ezetimibe and 20<span class="elsevierStyleHsp" style=""></span>mg/24<span class="elsevierStyleHsp" style=""></span>h simvastatin (from September 2011 to February 2012; suspended due to the diagnosis of PM).</p><p id="par0020" class="elsevierStylePara elsevierViewall">When the patient was studied he had constitutional syndrome that had developed over 2 months, with evening fever (38<span class="elsevierStyleHsp" style=""></span>°<span class="elsevierStyleSmallCaps">C</span>) that went into remission with paracetamol; asthenia, hyporexia and weight loss (10<span class="elsevierStyleHsp" style=""></span>kg). He described proximal weakness, nocturnal dry non-productive cough and self-limiting transitory arthromyalgias, with no signs of the Raynaud phenomenon or skin disorders.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Pulmonary auscultation detected fine crackling rales in the bases and major axial muscle weakness and proximal weakness in the limbs.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Laboratory tests showed high serum levels of creatine kinase, dehydrogenase lactate, alanine aminotransferase, aspartate aminotransferase (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>), reactive C protein (79.2<span class="elsevierStyleHsp" style=""></span>mg/l), erythrocyte sedimentation rate (37<span class="elsevierStyleHsp" style=""></span>mm/h) and leukocytosis (13,200<span class="elsevierStyleHsp" style=""></span>U/mm<span class="elsevierStyleSup">3</span>; 76.5% neutrophils), with normal TSH (1.90<span class="elsevierStyleHsp" style=""></span>μUI/ml). Only the tumour markers Ca 15.3 (54.8<span class="elsevierStyleHsp" style=""></span>U/ml; normal: 2.0–37.0) and β2-microglobulin (4.63<span class="elsevierStyleHsp" style=""></span>mg/l; normal ≤3.0) were raised, although the absence of a tumour was checked by computed tomography of the thorax and abdomen. The PPD test was negative.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">Anticellular antibodies were detected in the serum. The immunoblot polymyositis profile (anti-Mi2, anti-Ku, anti Pm/SCL, anti-Jo1, anti-PL12, anti-PI7, anti-SSA 52<span class="elsevierStyleHsp" style=""></span>kDa, anti-EJ, anti-OJ and anti-SRP) was positive for anti-Jo-1 and anti-SRP.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Haplotypes for celiac disease were analysed; the patient was a heterozygote carrier of the DRB1*03:01-DQB1*02:01-DQA1*05:01 haplotype, although the anti-transglutaminase IgG and IgA antibody titrations were negative.</p><p id="par0045" class="elsevierStylePara elsevierViewall">The computed tomography results are shown in <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>, while the bronchoscopy study only showed supraglottal polypoidal lesions. Bronchial aspiration cytology was negative for neoplastic cells.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">The electromyogram showed a predominantly proximal myopathic process, with the presence of discrete signs of inflammatory activity that may appear in polymyositis.</p><p id="par0055" class="elsevierStylePara elsevierViewall">Quadriceps biopsy showed discrete distortion of the fascicular architecture with occasional atrophic perifascicular fibres. Occasional fibres were observed within the fascicules, with nuclear centralisation and signs of regeneration. The presence of perimysial and endomysial inflammatory lymphomonocytic infiltrates stood out.</p><p id="par0060" class="elsevierStylePara elsevierViewall">The diagnosis is based on raised levels of muscle enzymes, muscle biopsy, myositis-specific antibodies and anomalies in the electromyogram.</p><p id="par0065" class="elsevierStylePara elsevierViewall">Given these findings, treatment commenced with oral prednisone, 80<span class="elsevierStyleHsp" style=""></span>mg/24<span class="elsevierStyleHsp" style=""></span>h (1<span class="elsevierStyleHsp" style=""></span>mg/kg/24<span class="elsevierStyleHsp" style=""></span>h). The muscle pain and fever remitted quickly and muscle enzymes normalised after 3 months (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). However, the patient had an episode of deep vein thrombosis and progressive dyspnoea, even when resting, accompanied by a non-productive cough. Cyanosis was detected in the acral areas, with an O<span class="elsevierStyleInf">2</span> saturation of 92% with the oxygen therapy mask set to high flow.</p><p id="par0070" class="elsevierStylePara elsevierViewall">Venous Doppler ultrasound scan detected a superficial occlusive thrombus in the femoral vein, in the popliteal vein and in the origin of the tibial peroneal trunk. A clinical improvement was achieved using intravenous anticoagulant therapy in 3 pulses (1<span class="elsevierStyleHsp" style=""></span>g/24<span class="elsevierStyleHsp" style=""></span>h) of methylprednisolone and cyclophosphamide.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Discussion</span><p id="par0075" class="elsevierStylePara elsevierViewall">Anti-Jo-1 antibodies are the most common in IIM (20–30%).<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> They are associated with the anti-synthetase syndrome, which is characterised by polymyositis, diffuse interstitial pulmonary disease, polyarthritis, Raynaud phenomenon and hyperkeratosic skin lesions, with erythema over the metacarpophalangeal and interphalangeal joints.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> Patients with anti-Jo1 have myopathy (90%) and diffuse interstitial pulmonary disease (70%),<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> and the titration may be correlated with disease activity.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">Anti-SRP antibodies recognise the cytoplasmatic protein that binds to synthesised protein signal sequences for translocation to the endoplasmic reticule. They are found in 4% of adults with polymyositis and are not usually associated with other myositis autoantibodies.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a> They may trigger acute polymyositis, with severe muscle weakness, cardiac involvement, swift progression, a poor immunosuppressor response and increased mortality.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a> Muscle biopsies show abundant signs of cellular degeneration and regeneration, necrotic cells and a discrete inflammatory infiltrate. Nevertheless, the biopsy findings in our patient did not display this anti-SRP anatomo-pathological phenotype.</p><p id="par0085" class="elsevierStylePara elsevierViewall">Clinically, anti-Jo-1 antibodies are associated with diffuse interstitial pulmonary disease, and anti-SRP antibodies are associated with the acute onset of the disease, sustained increase of creatine kinase and severe weakness of the patient,<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> as was seen in this patient.</p><p id="par0090" class="elsevierStylePara elsevierViewall">Although the paraneoplastic form of inflammatory myopathies is known, the tumour has been clinically ruled out in our patient.</p><p id="par0095" class="elsevierStylePara elsevierViewall">Statin toxicity, which is present in 7–29% of cases, is associated with inflammatory myopathies,<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> as is the finding in serum of the anti-3-hydroxy-3-methylglutaril-enzime-reductase (anti-HMGCR) antibody, the pharmacological target of the statins. Myopathic symptoms usually disappear when the treatment is interrupted, and immunosuppressor therapy is needed.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a> In the case of statin-induced necrotising myopathy the symptoms have been found to persist, even when the treatment is interrupted, as occurred in our patient.</p><p id="par0100" class="elsevierStylePara elsevierViewall">However, no necrotic or regenerative fibres were found in the muscle biopsy, although foci of lymphocytes were found, strengthening the diagnosis of PM.</p><p id="par0105" class="elsevierStylePara elsevierViewall">The celiac disease haplotype of this patient confers the risk of autoimmune (odds ratio 3.6) and 15.5 times the risk of anti-Jo-1.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Conclusions</span><p id="par0110" class="elsevierStylePara elsevierViewall">The case presented here is unusual in clinical practice. PM is a rare disease in Spain (3.9/100,000). The coexistence of both autoantibodies is considered to be extremely rare, and in this case the antibodies were also useful in the diagnosis of autoimmune myopathy and the anti-synthetase syndrome. The association with anti-SRP antibodies caused severe muscle deterioration and a poor prognosis.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Conflict of interests</span><p id="par0115" class="elsevierStylePara elsevierViewall">The authors have no conflict of interests to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:3 [ "identificador" => "xres1268375" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1173976" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1268376" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1173975" "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" => "Conclusions" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Conflict of interests" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2017-06-08" "fechaAceptado" => "2017-12-21" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1173976" "palabras" => array:4 [ 0 => "Anti-Jo-1" 1 => "Anti-SRP" 2 => "Polymyositis" 3 => "Myopathies" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1173975" "palabras" => array:4 [ 0 => "Anti-histidil-tRNA-sintetasa" 1 => "Anti-partícula de reconocimiento de la señal" 2 => "Polimiositis" 3 => "Miopatías" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Idiopathic inflammatory myopathies are a heterogeneous group of potentially treatable myopathies. They are classified, on the basis of clinical and histopathological features, into four subtypes: dermatomyositis, polymyositis, necrotising autoimmune myositis and inclusion-body myositis. Myositis-associated antibodies and myositis-specific autoantibodies are frequently found in patients with idiopathic inflammatory myopathies, and are useful in the diagnosis and classification. Anti-histidyl transfer RNA synthetase antibody is the most widely prevalent and is highly specific for polymyositis. Signal recognition particle antibody is also a specific autoantibody for polymyositis, but it is infrequent and rarely found in patients having other myositis-specific autoantibodies.</p><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">We present a man with polymyositis who had both antibodies in serum, which is considered an extremely rare clinical situation. Here we analyse the clinical course and findings, and examine the effect of the coexistence and possible interaction on prognosis.</p></span>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Las miopatías inflamatorias idiopáticas son un grupo heterogéneo de miopatías potencialmente tratables. Se clasifican en 4 subtipos: dermatomiositis, polimiositis, miositis autoinmune necrosante y miositis por cuerpos de inclusión, en función de las características clínicas e histológicas. Los anticuerpos asociados a miositis y los autoanticuerpos específicos de miositis se encuentran frecuentemente en pacientes con miopatías inflamatorias, siendo útiles en el diagnóstico y clasificación. El anticuerpo anti-histidil tRNA sintetasa es el más prevalente y el más específico para polimiositis. El anticuerpo de partícula de reconocimiento de señal es también un autoanticuerpo especıfico para polimiositis, pero más infrecuente, y raramente se encuentra en pacientes que presentan otros autoanticuerpos específicos para miositis.</p><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">En este trabajo se presenta un paciente con polimiositis en el que coexisten los 2 autoanticuerpos en el suero, lo que se considera una situación clínica extremadamente rara. Aquí analizamos la evolución clínica y hallazgos para examinar el efecto de la coexistencia y la posible interacción sobre el pronóstico.</p></span>" ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Melguizo Madrid E, Fernández Riejos P, Toyos Sáenz de Miera FJ, Fernández Pérez B, González Rodríguez C. Coexistencia de anticuerpos anti-histidil-tRNA-sintetasa y anti-partícula de reconocimiento de la señal en un paciente con polimiositis. Reumatol Clin. 2019;15:e111–e113.</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" => 1228 "Ancho" => 1500 "Tamanyo" => 250588 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Evolution of the pulmonary involvement shown by axial computed tomography (ACT). (A) ACT of the thorax at diagnosis revealed the presence of discrete interstitial infiltrates in ground glass opacity in the bases and periphery of the lungs, and to a lesser degree, in the mid-fields, with multiple mediastinal lymphatic ganglia of less than 17<span class="elsevierStyleHsp" style=""></span>mm and segmental atelectasis of the lower right lobe. (B) At 3 months the angio ACT showed no images of pulmonary thromboembolism, although extensive bilateral involvement of the lungs was observed, with interstitial infiltrates with ground glass opacity and interlobular septal thickening, as well as areas of fibrosis, while the anterior pulmonary fields were less involved.</p>" ] ] 1 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">ALT: alanine aminotransferase; AST: aspartate aminotransferase; CK: creatine kinase; LDH: dehydrogenase lactate.</p>" "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="\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" scope="col" style="border-bottom: 2px solid black">Date \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">CK (UI/l) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">LDH (UI/l) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">AST (UI/l) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">ALT (UI/l) \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">09/03/2011 \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">120 \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="" 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">35 \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">35 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10/03/2011 \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">99 \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="" 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">48 \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">38 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; 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entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12/04/2012 \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">63 \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">612 \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">28 \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">32 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">04/05/2012 \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">697 \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">21 \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">39 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2169554.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Evolution of serum levels of CK, LDH, AST and ALT.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0055" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A comprehensive overview on myositis-specific antibodies: new and old biomarkers in idiopathic inflammatory myopathy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "M. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 8 | 3 | 11 |
| 2024 October | 43 | 29 | 72 |
| 2024 September | 55 | 28 | 83 |
| 2024 August | 78 | 44 | 122 |
| 2024 July | 59 | 29 | 88 |
| 2024 June | 68 | 35 | 103 |
| 2024 May | 66 | 22 | 88 |
| 2024 April | 77 | 35 | 112 |
| 2024 March | 59 | 41 | 100 |
| 2024 February | 57 | 27 | 84 |
| 2024 January | 59 | 23 | 82 |
| 2023 December | 50 | 18 | 68 |
| 2023 November | 75 | 24 | 99 |
| 2023 October | 43 | 27 | 70 |
| 2023 September | 120 | 40 | 160 |
| 2023 August | 59 | 12 | 71 |
| 2023 July | 59 | 21 | 80 |
| 2023 June | 50 | 24 | 74 |
| 2023 May | 55 | 22 | 77 |
| 2023 April | 57 | 4 | 61 |
| 2023 March | 90 | 23 | 113 |
| 2023 February | 63 | 22 | 85 |
| 2023 January | 47 | 15 | 62 |
| 2022 December | 71 | 24 | 95 |
| 2022 November | 55 | 19 | 74 |
| 2022 October | 74 | 31 | 105 |
| 2022 September | 47 | 38 | 85 |
| 2022 August | 42 | 42 | 84 |
| 2022 July | 45 | 28 | 73 |
| 2022 June | 38 | 30 | 68 |
| 2022 May | 59 | 40 | 99 |
| 2022 April | 52 | 30 | 82 |
| 2022 March | 50 | 47 | 97 |
| 2022 February | 60 | 26 | 86 |
| 2022 January | 69 | 34 | 103 |
| 2021 December | 35 | 44 | 79 |
| 2021 November | 43 | 36 | 79 |
| 2021 October | 47 | 33 | 80 |
| 2021 September | 42 | 42 | 84 |
| 2021 August | 36 | 23 | 59 |
| 2021 July | 45 | 32 | 77 |
| 2021 June | 54 | 31 | 85 |
| 2021 May | 44 | 55 | 99 |
| 2021 April | 121 | 87 | 208 |
| 2021 March | 67 | 25 | 92 |
| 2021 February | 41 | 11 | 52 |
| 2021 January | 42 | 13 | 55 |
| 2020 December | 39 | 16 | 55 |
| 2020 November | 49 | 13 | 62 |
| 2020 October | 41 | 20 | 61 |
| 2020 September | 52 | 29 | 81 |
| 2020 August | 94 | 25 | 119 |
| 2020 July | 64 | 7 | 71 |
| 2020 June | 34 | 13 | 47 |
| 2020 May | 45 | 22 | 67 |
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