array:24 [ "pii" => "S2387020616305393" "issn" => "23870206" "doi" => "10.1016/j.medcle.2016.03.034" "estado" => "S300" "fechaPublicacion" => "2016-09-02" "aid" => "3604" "copyright" => "Elsevier España, S.L.U.. All rights reserved" "copyrightAnyo" => "2016" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "crp" "cita" => "Med Clin. 2016;147:217-22" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "Traduccion" => array:1 [ "es" => array:19 [ "pii" => "S0025775316300665" "issn" => "00257753" "doi" => "10.1016/j.medcli.2016.03.034" "estado" => "S300" "fechaPublicacion" => "2016-09-02" "aid" => "3604" "copyright" => "Elsevier España, S.L.U." "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "crp" "cita" => "Med Clin. 2016;147:217-22" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 83 "formatos" => array:2 [ "HTML" => 55 "PDF" => 28 ] ] "es" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Diagnóstico y tratamiento</span>" "titulo" => "Enfermedad de Still del adulto" "tienePdf" => "es" "tieneTextoCompleto" => "es" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "217" "paginaFinal" => "222" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Adult-onset Still's disease" ] ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Santos Castañeda, Esther F. Vicente, Miguel A. González-Gay" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Santos" "apellidos" => "Castañeda" ] 1 => array:2 [ "nombre" => "Esther F." "apellidos" => "Vicente" ] 2 => array:2 [ "nombre" => "Miguel A." "apellidos" => "González-Gay" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2387020616305393" "doi" => "10.1016/j.medcle.2016.03.034" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020616305393?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775316300665?idApp=UINPBA00004N" "url" => "/00257753/0000014700000005/v2_201704290053/S0025775316300665/v2_201704290053/es/main.assets" ] ] "itemSiguiente" => array:19 [ "pii" => "S2387020616305472" "issn" => "23870206" "doi" => "10.1016/j.medcle.2016.05.052" "estado" => "S300" "fechaPublicacion" => "2016-09-02" "aid" => "3655" "copyright" => "Elsevier España, S.L.U." "documento" => "article" "crossmark" => 1 "subdocumento" => "pgl" "cita" => "Med Clin. 2016;147:223.e1-7" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Consensus statement</span>" "titulo" => "Mobilization of peripheral blood stem cells with plerixafor in poor mobilizer patients" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "223.e1" "paginaFinal" => "223.e7" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Movilización de progenitores hematopoyéticos a sangre periférica con plerixafor en pacientes malos movilizadores" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Juan-Manuel Sancho, Rafael Duarte, Laura Medina, Sergi Querol, Pedro Marín, Anna Sureda" "autores" => array:7 [ 0 => array:2 [ "nombre" => "Juan-Manuel" "apellidos" => "Sancho" ] 1 => array:2 [ "nombre" => "Rafael" "apellidos" => "Duarte" ] 2 => array:2 [ "nombre" => "Laura" "apellidos" => "Medina" ] 3 => array:2 [ "nombre" => "Sergi" "apellidos" => "Querol" ] 4 => array:2 [ "nombre" => "Pedro" "apellidos" => "Marín" ] 5 => array:2 [ "nombre" => "Anna" "apellidos" => "Sureda" ] 6 => array:1 [ "colaborador" => "on behalf of the Catalan Society of Haematology and Haemotherapy and Catalan-Balearic Society of Blood Transfusion Mobilisation Working" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0025775316301671" "doi" => "10.1016/j.medcli.2016.05.019" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775316301671?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020616305472?idApp=UINPBA00004N" "url" => "/23870206/0000014700000005/v1_201611300117/S2387020616305472/v1_201611300117/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S2387020616305423" "issn" => "23870206" "doi" => "10.1016/j.medcle.2016.04.066" "estado" => "S300" "fechaPublicacion" => "2016-09-02" "aid" => "3616" "copyright" => "Elsevier España, S.L.U." "documento" => "article" "crossmark" => 1 "subdocumento" => "sco" "cita" => "Med Clin. 2016;147:211-6" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Special article</span>" "titulo" => "Recommendations for the multidisciplinary management of tuberous sclerosis complex" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "211" "paginaFinal" => "216" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Recomendaciones para el abordaje multidisciplinar del complejo esclerosis tuberosa" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Alfons Macaya, Roser Torra" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Alfons" "apellidos" => "Macaya" ] 1 => array:2 [ "nombre" => "Roser" "apellidos" => "Torra" ] 2 => array:1 [ "colaborador" => "on behalf of the Spanish Multidisciplinary Group of Experts on Tuberous Sclerosis Complex (GEM-CET)" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0025775316300781" "doi" => "10.1016/j.medcli.2016.04.004" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775316300781?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020616305423?idApp=UINPBA00004N" "url" => "/23870206/0000014700000005/v1_201611300117/S2387020616305423/v1_201611300117/en/main.assets" ] "en" => array:16 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Diagnosis and treatment</span>" "titulo" => "Adult-onset Still's disease" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "217" "paginaFinal" => "222" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Santos Castañeda, Esther F. Vicente, Miguel A. González-Gay" "autores" => array:3 [ 0 => array:3 [ "nombre" => "Santos" "apellidos" => "Castañeda" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 1 => array:3 [ "nombre" => "Esther F." "apellidos" => "Vicente" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:4 [ "nombre" => "Miguel A." "apellidos" => "González-Gay" "email" => array:1 [ 0 => "miguelaggay@hotmail.com" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Servicio de Reumatología, Hospital de La Princesa, Instituto de Investigación Sanitaria de La Princesa (IIS-IP), Universidad Autónoma de Madrid (UAM), Madrid, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Reumatología, Hospital Universitario Marqués de Valdecilla, Santander, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, Universidad de Cantabria, Instituto de Investigación Sanitaria Valdecilla (IDIVAL), Santander, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Enfermedad de Still del adulto" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Adult-onset Still's disease (AOSD) is a systemic inflammatory disease of unknown aetiology characterised mainly by high fever, evanescent rash and joint affection. It was described in 1971 by Bywaters<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">1</span></a> in a series of 14 women who had presented with similar manifestations as those previously described by George Still in children in 1897.<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">2</span></a> It is now considered to be a disease located between autoinflammatory and autoimmune diseases.</p><p id="par0010" class="elsevierStylePara elsevierViewall">AOSD is a rare disease whose prevalence and incidence are not well known. It is estimated that the annual incidence rate is 0.16 to 0.4/100,000 people, regardless of race.<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">3,4</span></a> The prevalence ranges from 1 to 34 cases per million people.<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">4</span></a> It affects both sexes with a slight predominance in women. AOSD has a bimodal distribution peaking at ages between 15 and 25 and at 35 and 46, although cases have been reported in patients aged over 70.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Aetiology</span><p id="par0015" class="elsevierStylePara elsevierViewall">The precise aetiology of the disease is unknown. AOSD is a heterogeneous condition that falls halfway between autoinflammatory syndromes and autoimmune diseases, involving genetic and environmental factors which are not very well-known.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Some studies have associated AOSD with certain genes in the HLA system, as well as HLA-DR2 and DR4 in different populations, although these data have not been confirmed in other studies.<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">5</span></a> The association of cases in the family or of twins is exceptional. Recently, a Japanese study described its association with certain IL-18 polymorphisms, cytokine with an important role in the pathogenesis of the disease.<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">6</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">It also described cases related to certain viruses (mumps, EBV, CMV, measles, parainfluenza, adenovirus, etc.) and bacterial agents (yersinia, mycoplasma, chlamydia, borrelia), although these have occurred casually.<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">5</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Finally, there are also sporadic cases linking AOSD with solid tumours or of a haematologic lineage.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Immunopathogeny</span><p id="par0035" class="elsevierStylePara elsevierViewall">Either for reasons attributed to genetic factors, or environmental factors that are not well known, in AOSD there is an increased response of the innate immunity that causes a dysregulation of inflammasome. In addition, there is a participation of acquired immunity, predominantly Th1 type, with the overproduction of certain proinflammatory cytokines such as IL-1, IL-2, IL-6, IL-18, IFN-γ and TNF-α, cytokines that play a relevant role in the immunopathology of the disease.<a class="elsevierStyleCrossRefs" href="#bib0200"><span class="elsevierStyleSup">5,7,8</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Reflecting the innate immune response, the activation of neutrophils and macrophages is a characteristic feature of the disease. In this regard, factors such as M-CSF and IFN-γ, related to macrophage activation, are elevated in the serum of AOSD patients. Similarly, Toll-like receptors (TLR) play an important role in activating inflammasome, neutrophils selection and amplification of Th17 response. A recent study showed that the TLR7/MyD88 pathway was over-expressed in AOSD patients’ dendritic cells.<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">9</span></a> Furthermore, expression of TLR7 is elevated in patients with active disease, which decreases after treatment.</p><p id="par0045" class="elsevierStylePara elsevierViewall">In addition to Th1 cells, recent studies have shown the involvement of Th17 cells in the pathogenesis of the disease.<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">10</span></a> In this sense, elevated levels of circulating Th17 in patients with active disease that correlate well with ferritin activity and levels have been detected. In addition, regulatory T cells and the transforming growth factor β have been seen to be inversely associated with disease activity.<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">11</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">As a result of the above, the levels of the main proinflammatory cytokines, IL-1β, IL-6, IL-18, TNF-α and IFN-γ, are elevated in the serum of patients with active AOSD and decrease after effective treatment. These facts support the utility of treatments directed against these targets, especially IL-1 β and IL-6, which have shown to be very effective in this disease.</p><p id="par0055" class="elsevierStylePara elsevierViewall">Although the TNF-α levels are increased, they are lower than in other inflammatory diseases such rheumatoid arthritis (RA), and do not correlate with AOSD activity, which would explain that their effectiveness is less than that of IL-1 and IL-6 antagonists, especially in systemic forms. Other cytokines and chemokines involved in the pathogenesis of AOSD are IFN-γ and IL-8/CXXL8.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Clinical manifestations</span><p id="par0060" class="elsevierStylePara elsevierViewall">The characteristic triad of AOSD is characterised by high fever, evanescent rash and joint affectation. Fever occurs daily, often at ≥39<span class="elsevierStyleHsp" style=""></span>°C and typically with spiking temperatures. The rash is usually maculopapular, has a salmon colour, is sometimes itchy, and mostly affects the trunk and proximal limbs. It often coincides with spiking fevers and disappears when the fever subsides (resident evanescent rash). It can sometimes be caused by rubbing the skin or local microtrauma (Koebner phenomenon). Joint affectation is manifested by arthralgia or arthritis franca (70–100%), often symmetric and polyarticular. The most frequently affected joints are the knees, wrists, ankles and hands. AOSD typically affects carpi and tends to produce joint impingement and ankylosis. Affectation of the hips and shoulders at the onset of the disease is a sign of poor prognostic.</p><p id="par0065" class="elsevierStylePara elsevierViewall">Other common manifestations include: muscle pain, sore throat (non-exudative pharyngitis), painful lymphadenopathy, hepatosplenomegaly, pleurisy, pericarditis, abdominal pain and pulmonary infiltrates. Sometimes a fever of unknown origin (FUO) appear, to the point that about 10–15% of adult FUO are due to AOSD. The prevalence of AOSD main manifestations is shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">Less common manifestations of the disease include: myocardial involvement with myocarditis or necrosis, cardiac tamponade, meningoencephalitis, cerebral ischaemic attack, sensorineural deafness, orbital pseudotumor inflammatory, pure red cell marrow aplasia, tubulointerstitial nephritis, intestinal pseudo-obstruction, AA amyloidosis and Sjögren syndrome.<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">8</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">Among the most serious complications macrophage activation syndrome (MAS) must be noted, also called reactive hemophagocytic syndrome (RHS), which appears in 10–15% of cases. <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> shows the main symptoms that should alert the clinician to possible MAS/RHS. Other serious manifestations of AOSD are: fulminant acute hepatitis, thrombotic thrombocytopenic purpura, disseminated intravascular coagulopathy, diffuse alveolar haemorrhage and pulmonary arterial hypertension.<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">12</span></a></p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Laboratory</span><p id="par0080" class="elsevierStylePara elsevierViewall">Laboratory findings are not typical of AOSD and only reflect its systemic inflammatory nature. Elevated ESR and CRP is a consistent finding. A marked leukocytosis of between 10,000 and 30,000<span class="elsevierStyleHsp" style=""></span>leucocyte/mm<span class="elsevierStyleSup">3</span> with neutrophilia will also be observed in over 80% of patients, sometimes with figures of ≥30,000<span class="elsevierStyleHsp" style=""></span>cells/mm<span class="elsevierStyleSup">3</span>. Often, chronic anaemia and thrombocytosis disorder is observed. The existence of thrombocytopenia is rare and should alert the clinician to the possible emergence of a MAS. An increase of liver enzymes is a common finding (>75%<span class="elsevierStyleMonospace">)</span>and may present in a pattern of cytolysis, cholestasis, or mixed. A fairly characteristic finding that relates to the disease activity is elevated serum ferritin levels, which occurs in up to 70% of cases, with values of generally above 1000<span class="elsevierStyleHsp" style=""></span>μg/l or five times above the upper normal limit, with a fraction of decreased glycosylated ferritin.<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">8,13</span></a> In a healthy population, the percentage of glycosylated ferritin ranges between 50 and 80%.<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">14</span></a> In the presence of inflammatory diseases, this percentage decreases to 20–50%, but in AOSD, the proportion of glycosylated ferritin is <span class="elsevierStyleMonospace"><</span>20%. Interestingly, the presence of RF and ANA in AOSD is less than 10%, and when it appears it is usually at low titres, this being a point of special interest when establishing the differential diagnosis of autoimmune diseases.</p><p id="par0085" class="elsevierStylePara elsevierViewall">Importantly, many of the analytical findings that appear in AOSD are not exclusive and can also be seen in patients with MAS/RHS (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>). Recently, an increase in H-ferritin expression has been detected in the bone marrow and liver tissue of patients with MAS, which has been correlated with increased severity and mortality.<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">15</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Classification and diagnosis of adult Still's disease</span><p id="par0090" class="elsevierStylePara elsevierViewall">AOSD diagnosis in a patient with compatible clinical symptoms, is usually made by exclusion of other systemic processes, mainly infections, autoimmune diseases, autoinflammatory syndromes and tumour processes, usually of a haematologic lineage and some solid tumours.<a class="elsevierStyleCrossRefs" href="#bib0200"><span class="elsevierStyleSup">5,8</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">There are currently more than seven different criteria to classify patients with AOSD. The most well-known and used in clinical practice are those of Yamaguchi et al. (1992) and those of Fautrel et al. (2002) (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>). The Yamaguchi criteria are the most widespread, with sensitivity and specificity of 79.2 and 93.8%, respectively.<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">16</span></a> Its application requires the exclusion of other aforementioned systemic processes. Fautrel et al. criteria<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">17</span></a> rely heavily on the presence of serum ferritin levels that are five times above the upper normal limit levels of glycosylated ferritin <span class="elsevierStyleMonospace"><</span>20%. Its sensitivity and specificity are 80.6 and 98.5%, respectively.<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">17</span></a> The application of Fautrel criteria does not depend as much on the exclusion of other systemic processes as Yamaguchi criteria does, but has the disadvantage that they are not applicable in the early stages of the disease. <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> shows the two most widely used criteria.</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0100" class="elsevierStylePara elsevierViewall">The AOSD differential diagnosis is broad and often forces many other diagnostic tests for a definitive diagnosis (<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>).</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Evolution</span><p id="par0105" class="elsevierStylePara elsevierViewall">The evolution of AOSD is divided into three distinct categories: (1) single-phase, characterised by a self-limited outbreak, which usually resolves spontaneously within several weeks or months (∼30% of cases); (2) intermittent systemic, with episodes or recurrent outbreaks, with or without joint symptoms, symptoms disappear during the intercritical periods (∼30%), and (3) chronic joint, with usually destructive progressive polyarticular, which ultimately results in increased disability (∼40%). The main predictors of poor prognosis include early development of arthritis at the root of the limbs (shoulders and hips) and prolonged need for corticosteroids <span class="elsevierStyleMonospace">(></span>2 years). The strategy and duration of treatment differ for each of these patterns.<a class="elsevierStyleCrossRefs" href="#bib0200"><span class="elsevierStyleSup">5,8,18</span></a></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Treatment general considerations</span><p id="par0110" class="elsevierStylePara elsevierViewall">AOSD treatment is quite empirical and based on the results obtained in isolated cases and small series of patients. The main objectives of treatment are to control the inflammatory clinical profile, prevent organ or structural damage and reduce the iatrogenic and adverse effects of treatment.</p><p id="par0115" class="elsevierStylePara elsevierViewall">Non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids are the first line of treatment. NSAIDs are useful for 15–20% of patients, preferably in mild forms. The two most commonly used are indomethacin and aspirin in high doses. Their use in case of elevated transaminases is not recommended as they may precipitate fulminant hepatic failure.</p><p id="par0120" class="elsevierStylePara elsevierViewall">The effectiveness of corticosteroids may reach 60–70% of cases, being higher in cases of systemic involvement. The initial dose of corticosteroids is between 0.5 and 1<span class="elsevierStyleHsp" style=""></span>mg/kg, although doses of ≥0.8<span class="elsevierStyleHsp" style=""></span>mg/kg are usually recommended, which cause longer remissions and lower relapse rates. In the case of serious complications intravenous bolus can be used (500–1000<span class="elsevierStyleHsp" style=""></span>mg/day of methylprednisolone on three consecutive days). Unfortunately, a high percentage of patients (∼40–45%) develop a dependence or there are adverse effects. In these cases, the use of slow-acting disease-modifying agents (SADMA) is advised. Of these, the most widely used is methotrexate (MTX) at doses of 15–25<span class="elsevierStyleHsp" style=""></span>mg/week orally or parenterally, and the least commonly used is cyclosporin A (3–5<span class="elsevierStyleHsp" style=""></span>mg/kg/day orally). In case of refractoriness or adverse effects introducing biologics, both in systemic and articular forms, is advisable.</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Biological treatment of Still's disease</span><p id="par0125" class="elsevierStylePara elsevierViewall">There is increasing evidence of the utility of biological treatment for AOSD. They are currently reserved for refractory cases or those that are dependent on corticosteroids and SADMA, representing 20–25% of the total. In light of the above knowledge, the most effective biologics for treating AOSD are IL-1 and IL-6 antagonists and TNF-α inhibitors. We will review them all in chronological order of use.</p><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">TNF-α inhibitors</span><p id="par0130" class="elsevierStylePara elsevierViewall">TNF-α inhibitors were the first biological agents used in the AOSD. Of them, infliximab (IFX) was the first agent used at the doses and regimens used in RA. In particular, IFX showed, in the early 2000s, effectiveness and a marked corticosteroids sparing effect in isolated cases and small series of patients with both articular and systemic forms.<a class="elsevierStyleCrossRefs" href="#bib0270"><span class="elsevierStyleSup">19,20</span></a> In addition, its effect was fast and durable, persisting for between one and a half years<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">19</span></a> and 28 months depending on the series.<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">20</span></a> IFX has been used in monotherapy and in combination with MTX.</p><p id="par0135" class="elsevierStylePara elsevierViewall">Etanercept (ETA) was the second anti-TNF-α trialled. Its use is more limited and the results less satisfactory. ETA was the drug used in the first open prospective trial done with a biological agent in 12 patients with refractory AOSD and active polyarthritis.<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">21</span></a> Of these, three had systemic involvement. Two patients withdrew because of adverse effects. Of the 10 who completed only two reached an ACR of 70%. Of the three who had systemic involvement only one responded adequately.<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">21</span></a></p><p id="par0140" class="elsevierStylePara elsevierViewall">However, the results reported for these two anti-TNF-α have not been confirmed by other authors. In an observational study that included 20 patients (five systemic; 15 polyarticular) with AOSD that is refractory to corticosteroids and MTX, and in which 15 received IFX and 10 ETA (five received both drugs consecutively), only five achieved complete remission after 13 months: one from the ETA group and four from the IFX group. At follow-up on the last visit, 17 had stopped treatment: 11 because of loss or lack of efficacy, four because of side effects and two for other reasons.<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">22</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">Data with adalimumab (ADA) are scarce and results that do exist are contradictory. There have also been some cases of interaction between IFX, ETA and ADA, with positive results in 50% of the cases.<a class="elsevierStyleCrossRefs" href="#bib0290"><span class="elsevierStyleSup">23,24</span></a> There are no published data with golimumab nor with certolizumab, anti-TNF-α agents that have most recently appeared.</p><p id="par0150" class="elsevierStylePara elsevierViewall">As a summary of the above, we can conclude that patients with joint symptoms respond better to anti-TNF-α agents than those with systemic symptoms. Although there are no direct comparisons between medications, IFX seems more effective than ETA in these patients. In general, anti-TNF-α agents are well tolerated and their safety profile is similar to that described in other rheumatic diseases. Exceptionally, there have been isolated cases of MAS/RHS with ETA and ADA simulated an outbreak of the disease.</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">IL-1β antagonists</span><p id="par0155" class="elsevierStylePara elsevierViewall">IL-1β is one of the main cytokines involved in the immunopathology of AOSD. There are currently three IL-1β antagonists: anakinra (ANK), canakinumab (CNK) and rilonacept.</p><p id="par0160" class="elsevierStylePara elsevierViewall">ANK was approved in 2001 for the treatment of RA. Its use in AOSD is supported by the experience of an isolated, small series of cases in an open, prospective randomised clinical trial.<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">25</span></a> ANK has shown great efficacy in patients with AOSD refractory to corticosteroids and MTX – even in patients with severe manifestations and vital risk – as well as speed of action, with disappearance of symptoms only a few days after the first administration and an ability to reduce the dose of corticosteroids. The occurrence of relapse is frequent after discontinuation of the medication.<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">26</span></a></p><p id="par0165" class="elsevierStylePara elsevierViewall">Lequerré et al. conducted a retrospective study which included 15 patients with AOSD refractory to corticosteroids and MTX, whose average age was 38 and disease duration was 7.8 years. All had active and arthritis and 13 systemic involvement.<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">27</span></a> Eleven of the patients experienced a rapid and marked improvement: nine achieved complete remission and two partial remission. The corticosteroid dose was reduced significantly. However, four of the 15 had to stop treatment, either because of lack of efficacy or because of adverse effects.<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">27</span></a></p><p id="par0170" class="elsevierStylePara elsevierViewall">In 2015, Ortiz-Sanjuan et al. published the results of an open, multicentre, retrospective Spanish study that included 41 patients, the most extensive series seen today.<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">28</span></a> The mean age of patients was 34.4 and the median duration from initiation of treatment with ANK was 3.5 years. One year after treatment skin and joint manifestations decreased from 58.5 to 7.3% and 88 to 41.5%, respectively. Other clinical and laboratory parameters significantly improved quickly and were maintained. The dose of prednisone was reduced from 20 to 5<span class="elsevierStyleHsp" style=""></span>mg/day after a year of treatment. However, we should note that, in general, the systemic response was greater than the joint response.<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">28</span></a></p><p id="par0175" class="elsevierStylePara elsevierViewall">Although ANK is generally well tolerated, there have been some cases of serious effects such as acute respiratory distress or MAS. The ANK dose usually used is 100<span class="elsevierStyleHsp" style=""></span>mg/day subcutaneously associated with oral or parenteral MTX. If remission is sustained, the dose can be reduced to 50<span class="elsevierStyleHsp" style=""></span>mg/day or 100<span class="elsevierStyleHsp" style=""></span>mg every 48–72<span class="elsevierStyleHsp" style=""></span>h. The duration of treatment is not defined. The need for daily injections is an important limitation, which has resulted in the introduction of new IL-1β antagonists, among which CNK and rilonacept stand out, of a more sustained action.</p><p id="par0180" class="elsevierStylePara elsevierViewall">CNK is a human monoclonal antibody directed against IL-1β that is administered every eight weeks. CNK has been effective in JIA and autoinflammatory syndromes. Rilonacept is a soluble fusion protein also directed against IL-1 that is administered weekly and subcutaneously <span class="elsevierStyleMonospace">(</span>160<span class="elsevierStyleHsp" style=""></span>mg/week after a first dose of 220<span class="elsevierStyleHsp" style=""></span>mg).</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">IL-6 antagonists</span><p id="par0185" class="elsevierStylePara elsevierViewall">IL-6 is another key cytokine involved in the pathogenesis of AOSD. In addition, high levels of IL-6 have been detected in the serum of patients with active AOSD. For this reason, IL-6 has become a specific target in the treatment of this disease. Currently, the only IL-6 antagonist available is tocilizumab (TCZ).</p><p id="par0190" class="elsevierStylePara elsevierViewall">TCZ is a humanised monoclonal antibody that blocks both the membrane and soluble IL-6 receptor, specifically inhibiting the IL-6 actions. TCZ has shown efficacy in patients with AOSD refractory not only to MTX, but also ANK and anti-TNF-α.<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">29</span></a></p><p id="par0195" class="elsevierStylePara elsevierViewall">A Japanese study in 11 patients with AOSD refractory to anti-TNF-α and ANK showed efficacy for both systemic symptoms and joint pain, with a marked corticosteroids sparing effect.<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">30</span></a> The same was shown in a French study in 14 patients with AOSD, half with systemic symptoms, who had previously failed with other biological agents. At six months, the average DAS28 decreased from 5.6 to 2.9 in those patients with osteoarticular, while systemic symptoms disappeared in six out of seven patients. The corticosteroid dose was reduced by 56%.<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">31</span></a> Similar results have been obtained in another two studies with 11 and 15 patients with refractory AOSD, where equally rapid and durable responses were observed. In one of them, the beneficial effect of TCZ was maintained even six months after the treatment was discontinued.<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">32</span></a></p><p id="par0200" class="elsevierStylePara elsevierViewall">In 2014 the results were published of an open retrospective, multicentre Spanish study that included 34 patients with AOSD and inadequate response to corticosteroids, DMARDs and in many cases a biological agent.<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">33</span></a> The mean age of patients was 38.7 years and the duration of the disease until the start of TCZ was 4.2 years. After one year of treatment, joint symptoms were reduced from 97 to 32%, and fever and skin symptoms decreased from 59 to 6%.<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">33</span></a> Also, a marked reduction in markers of inflammation was observed. The mean dose of prednisone was reduced from 14 to 2.5<span class="elsevierStyleHsp" style=""></span>mg/day at 12 months of treatment.</p><p id="par0205" class="elsevierStylePara elsevierViewall">In a later study of 40 patients with refractory AOSD, the number of relapses of the disease in 10 of them treated with TCZ was more reduced than the others treated with other medications.<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">34</span></a></p><p id="par0210" class="elsevierStylePara elsevierViewall">The dose of TCZ in different studies varies between 4 and 8<span class="elsevierStyleHsp" style=""></span>mg/kg administered subcutaneously every 2–4 weeks. The overall safety profile is excellent, although two cases of MAS in patients treated with TCZ have been reported, one of them in regard to an infection associated with CMV.<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">35</span></a></p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Intravenous immunoglobulin</span><p id="par0215" class="elsevierStylePara elsevierViewall">The use of intravenous immunoglobulins has been shown to be effective in 8 out of 14 patients in two open studies, especially when used early. However, there are no controlled studies on its effectiveness, so its use is reserved for patients with serious and life-threatening events. The dose used is 2<span class="elsevierStyleHsp" style=""></span>g/kg administered over 2–5 days once a month.</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Other biological agents</span><p id="par0220" class="elsevierStylePara elsevierViewall">Experience with other biological agents is scarce. In this regard, treatment with rituximab, monoclonal antibody that induces depletion of B lymphocytes, has shown conflicting results in patients with AOSD refractory to other treatments. The same can be said of abatacept, fusion protein which interferes with the costimulation of T lymphocytes. Its use in AOSD has shown conflicting results.</p><p id="par0225" class="elsevierStylePara elsevierViewall">Advances in the understanding of AOSD molecular mechanisms facilitate establishing new targets in the near future. Of these, the most promising is the path of IL-18, although there are no current studies that allow us to confirm its therapeutic usefulness.</p></span></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Conclusion</span><p id="par0230" class="elsevierStylePara elsevierViewall">In summary, AOSD is an entity that shares features of autoimmune diseases and autoinflammatory syndromes. A definitive diagnosis is difficult and often requires exclusion of other systemic processes. The main cytokines involved in the immunopathology of the disease are: IL-1, IL-6, IL-18, TNF-α and IFN-γ. The first-line treatment includes NSAIDs, glucocorticoids and MTX. The use of biological agents has been effective for refractory patients or who those have adverse effects. IL-1 and IL-6 antagonists are effective for both systemic and articular forms. TNF-α inhibitors, however, are effective for rheumatic manifestations but less so for systemic manifestations. Research is needed to allow us to better differentiate between the phenotypes of the disease and find new biomarkers to monitor therapeutic response.</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Conflict of interest</span><p id="par0235" class="elsevierStylePara elsevierViewall">There are no conflicts of interest in this publication. Santos Castañeda has received education and research funding from Abbvie, MSD, Pfizer and Roche. Miguel A. Gonzalez-Gay has received education and research funding from <span class="elsevierStyleGrantSponsor" id="gs1">Abbvie</span>, <span class="elsevierStyleGrantSponsor" id="gs2">MSD</span>, <span class="elsevierStyleGrantSponsor" id="gs3">Pfizer</span> and <span class="elsevierStyleGrantSponsor" id="gs4">Roche</span>.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:12 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Aetiology" ] 2 => array:2 [ "identificador" => "sec0015" "titulo" => "Immunopathogeny" ] 3 => array:2 [ "identificador" => "sec0020" "titulo" => "Clinical manifestations" ] 4 => array:2 [ "identificador" => "sec0025" "titulo" => "Laboratory" ] 5 => array:2 [ "identificador" => "sec0030" "titulo" => "Classification and diagnosis of adult Still's disease" ] 6 => array:2 [ "identificador" => "sec0035" "titulo" => "Evolution" ] 7 => array:2 [ "identificador" => "sec0040" "titulo" => "Treatment general considerations" ] 8 => array:3 [ "identificador" => "sec0045" "titulo" => "Biological treatment of Still's disease" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0050" "titulo" => "TNF-α inhibitors" ] 1 => array:2 [ "identificador" => "sec0055" "titulo" => "IL-1β antagonists" ] 2 => array:2 [ "identificador" => "sec0060" "titulo" => "IL-6 antagonists" ] 3 => array:2 [ "identificador" => "sec0065" "titulo" => "Intravenous immunoglobulin" ] 4 => array:2 [ "identificador" => "sec0070" "titulo" => "Other biological agents" ] ] ] 9 => array:2 [ "identificador" => "sec0075" "titulo" => "Conclusion" ] 10 => array:2 [ "identificador" => "sec0080" "titulo" => "Conflict of interest" ] 11 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2016-03-14" "fechaAceptado" => "2016-03-21" "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Please cite this article as: Castañeda S, Vicente EF, González-Gay MA. Enfermedad de Still del adulto. Med Clin (Barc). 2016;147:217–222.</p>" ] ] "multimedia" => array:4 [ 0 => 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:3 [ "leyenda" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">ANA: antinuclear antibodies; RF: rheumatoid factor; Hb: haemoglobin; CRP: C-reactive protein; ESR: erythrocyte sedimentation rate.</p><p id="spar0905" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Source</span>: Modified from Castañeda et al.<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">8</span></a></p>" "tablatextoimagen" => array:2 [ 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">Clinical manifestations \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">Frequency (%)<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \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"><span class="elsevierStyleItalic">Fever</span><span class="elsevierStyleHsp" style=""></span>≥<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">39</span><span class="elsevierStyleHsp" style=""></span>°<span class="elsevierStyleItalic">C</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">90–100 \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"><span class="elsevierStyleItalic">Arthralgia/arthritis</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">70–100 \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"><span class="elsevierStyleItalic">Skin rash</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">70–90 \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"><span class="elsevierStyleItalic">Pharyngitis</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">50–90 \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"><span class="elsevierStyleItalic">Myalgia</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">50–80 \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"><span class="elsevierStyleItalic">Lymphadenopathy</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">40–75 \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"><span class="elsevierStyleItalic">Weight loss</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">30–70 \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"><span class="elsevierStyleItalic">Hepatomegaly</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">20–75 \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"><span class="elsevierStyleItalic">Splenomegaly</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">20–65 \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"><span class="elsevierStyleItalic">Pleurisy</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10–40 \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"><span class="elsevierStyleItalic">Pericarditis</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10–30 \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"><span class="elsevierStyleItalic">Myocarditis</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5–10 \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"><span class="elsevierStyleItalic">Pulmonary infiltrates</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10–20 \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"><span class="elsevierStyleItalic">Abdominal pain</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5–40 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1262282.png" ] ] 1 => 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">Laboratory \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">Frequency (%)<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \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"><span class="elsevierStyleItalic">Increased ESR</span> (><span class="elsevierStyleItalic">40</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">mm/h</span>) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">90–100 \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"><span class="elsevierStyleItalic">Elevated CRP</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">90–100 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Leucocyte</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Leukocytosis<span class="elsevierStyleHsp" style=""></span>≥<span class="elsevierStyleHsp" style=""></span>10,000/mm<span class="elsevierStyleSup">3</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">80–95 \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"><span class="elsevierStyleHsp" style=""></span>Leukocytosis<span class="elsevierStyleHsp" style=""></span>≥<span class="elsevierStyleHsp" style=""></span>15,000/mm<span class="elsevierStyleSup">3</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">50–80 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Neutrophils</span> (><span class="elsevierStyleItalic">80%</span>) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">80–90 \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"><span class="elsevierStyleItalic">Anaemia</span> (<span class="elsevierStyleItalic">Hb</span><span class="elsevierStyleHsp" style=""></span>≤<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">10</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">g/l</span>) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">65–70 \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"><span class="elsevierStyleItalic">Thrombocytosis</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">40–60 \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"><span class="elsevierStyleItalic">Low albumin</span> (≤<span class="elsevierStyleItalic">3</span>.<span class="elsevierStyleItalic">5</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">g/dl</span>) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">75–80 \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"><span class="elsevierStyleItalic">Elevated liver enzymes</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">50–75 \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"><span class="elsevierStyleItalic">Hyperferritinemia</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">45–60 \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"><span class="elsevierStyleItalic">Glycosylated ferritin</span><span class="elsevierStyleHsp" style=""></span>≤<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">20%</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">70–75 \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"><span class="elsevierStyleItalic">Negative ANA</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">>90 \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"><span class="elsevierStyleItalic">Negative RF</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">>90 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1262278.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0010">The reflected percentages depend on the series consulted.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Prevalence of the main clinical manifestations of adult-onset Still's disease.</p>" ] ] 1 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">BM: bone marrow; CNS: central nervous system; ESR: erythrocyte sedimentation rate.</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=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Clinical manifestations</span> \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"><span class="elsevierStyleHsp" style=""></span>High fever, not remittent \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"><span class="elsevierStyleHsp" style=""></span>Urticarial rash \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"><span class="elsevierStyleHsp" style=""></span>Lymphadenopathy \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"><span class="elsevierStyleHsp" style=""></span>Hepatosplenomegaly \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"><span class="elsevierStyleHsp" style=""></span>CNS alteration \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"><span class="elsevierStyleHsp" style=""></span>Haemorrhages \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"><span class="elsevierStyleVsp" style="height:0.5px"></span> \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"><span class="elsevierStyleItalic">Laboratory</span> \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"><span class="elsevierStyleHsp" style=""></span>Normal or low ESR \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"><span class="elsevierStyleHsp" style=""></span>Marked elevation of liver enzymes \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"><span class="elsevierStyleHsp" style=""></span>Pancytopenia \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"><span class="elsevierStyleHsp" style=""></span>Coagulopathy \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"><span class="elsevierStyleHsp" style=""></span>Hypofibrinogenemia \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"><span class="elsevierStyleHsp" style=""></span>Hypoalbuminemia \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"><span class="elsevierStyleHsp" style=""></span>Surprisingly high triglycerides \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"><span class="elsevierStyleHsp" style=""></span>Hyperferritinemia (usually<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>5000<span class="elsevierStyleHsp" style=""></span>μg/l) \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"><span class="elsevierStyleVsp" style="height:0.5px"></span> \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"><span class="elsevierStyleItalic">Histology (aspiration/BM biopsy; liver biopsy)</span> \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"><span class="elsevierStyleHsp" style=""></span>Hemophagocytosis of macrophages in BM \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"><span class="elsevierStyleHsp" style=""></span>Inflammatory infiltrate of CD68 expressing H-ferritin (BM or liver tissue) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1262279.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Symptoms and alarm signals for macrophage activation syndrome.</p>" ] ] 2 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">ANA: antinuclear antibodies; RF: rheumatoid factor.</p><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Source</span>: Yamaguchi et al.<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">16</span></a> and Fautrel et al.<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">17</span></a></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=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleBold">Yamaguchi et al., 1992 criteria</span> \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"><span class="elsevierStyleItalic">Major criteria</span><br><span class="elsevierStyleHsp" style=""></span>1. Fever ≥39<span class="elsevierStyleHsp" style=""></span>°C, lasting ≥1 week<br><span class="elsevierStyleHsp" style=""></span>2. Arthralgia or arthritis, lasting ≥2 weeks<br><span class="elsevierStyleHsp" style=""></span>3. Salmon-coloured rash, typically not itchy<br><span class="elsevierStyleHsp" style=""></span>4. Leukocytosis ≥10,000/mm<span class="elsevierStyleSup">3</span> with ≥80% polymorphonuclear cells \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"><span class="elsevierStyleItalic">Minor criteria</span><br><span class="elsevierStyleHsp" style=""></span>1. Sore throat<br><span class="elsevierStyleHsp" style=""></span>2. Lymphadenopathy<br><span class="elsevierStyleHsp" style=""></span>3. Hepatomegaly or splenomegaly<br><span class="elsevierStyleHsp" style=""></span>4. Abnormal liver function tests<br><span class="elsevierStyleHsp" style=""></span>5. Negative ANA and RF \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"><span class="elsevierStyleItalic">Exclusion criteria</span><br><span class="elsevierStyleHsp" style=""></span>1. Infections<br><span class="elsevierStyleHsp" style=""></span>2. Tumours (mainly lymphoma)<br><span class="elsevierStyleHsp" style=""></span>3. Other systemic diseases (mainly vasculitis) ≥five criteria are needed; of them, at least two major ones \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"><span class="elsevierStyleVsp" style="height:0.5px"></span> \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"><span class="elsevierStyleBold">Fautrel et al., 2002 criteria</span> \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"><span class="elsevierStyleItalic">Major criteria</span><br><span class="elsevierStyleHsp" style=""></span>1. Spiking fever ≥39<span class="elsevierStyleHsp" style=""></span>°C<br><span class="elsevierStyleHsp" style=""></span>2. Arthralgia<br><span class="elsevierStyleHsp" style=""></span>3. Transient erythema<br><span class="elsevierStyleHsp" style=""></span>4. Pharyngitis<br><span class="elsevierStyleHsp" style=""></span>5. Polymorphonuclear cells ≥80%<br><span class="elsevierStyleHsp" style=""></span>6. Glycosylated ferritin ≤20% \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"><span class="elsevierStyleItalic">Minor criteria</span><br><span class="elsevierStyleHsp" style=""></span>1. Maculopapular rash<br><span class="elsevierStyleHsp" style=""></span>2. Leukocytosis >10,000/mm<span class="elsevierStyleSup">3</span> ≥four major criteria or three major<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>two minor are required \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1262280.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Classification criteria of adult-onset Still's disease proposed by Yamaguchi and Fautrel.</p>" ] ] 3 => array:8 [ "identificador" => "tbl0020" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at4" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">ACPA: anticitrullinated protein antibody; ANCA: antineutrophil cytoplasmic antibodies; DRESS: drug reaction with eosinophilia and systemic symptoms; RF: rheumatoid factor; BM: bone marrow; PAN: polyarteritis nodosa; CRP: polymerase chain reaction; PET: positron emission tomography; CT: computed tomography; TNF: tumour necrosis factor; TRAPS: tumour necrosis factor receptor-associated periodic syndrome; HIV: human immunodeficiency virus.</p><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Source</span>: Adapted for <span class="elsevierStyleSmallCaps">Medicina Clínica</span> by Gerfaud-Valentin et al.<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">5</span></a></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="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Diseases \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">Diagnostic tests \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"><span class="elsevierStyleItalic">Infections (viruses, bacteria, parasites)</span><br><span class="elsevierStyleHsp" style=""></span>Viral: HIV, herpes, hepatitis, parvovirus…<br><span class="elsevierStyleHsp" style=""></span>Atypical: <span class="elsevierStyleItalic">Mycoplasma pneumoniae, Borrelia</span>…<br><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Endocarditis and sepsis</span><br><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Other: toxoplasmosis, yersiniosis</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><br>Serology, CRP<br>Serology, CRP<br>Blood cultures, ultrasound<br>Serology, CRP \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"><span class="elsevierStyleItalic">Neoplasms</span><br><span class="elsevierStyleHsp" style=""></span>Lymphomas (Hodgkin's and non-Hodgkin's)<br><span class="elsevierStyleHsp" style=""></span>Angioimmunoblastic T lymphoma<br><span class="elsevierStyleHsp" style=""></span>Castleman's disease<br><span class="elsevierStyleHsp" style=""></span>Myeloproliferative disorders<br><span class="elsevierStyleHsp" style=""></span>Certain solid tumours \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><br>CT, PET/CT, BM aspiration, biopsy<br><br>Specific or imaging tests \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"><span class="elsevierStyleItalic">Autoimmune diseases</span><br><span class="elsevierStyleHsp" style=""></span>Systemic lupus erythematosus<br><span class="elsevierStyleHsp" style=""></span>Rheumatoid arthritis<br><span class="elsevierStyleHsp" style=""></span>Dermatomyositis<br><span class="elsevierStyleHsp" style=""></span>Systemic vasculitis (PAN) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><br>Specific autoantibodies<br>RF, ACPA, X-rays<br>Muscle biopsy<br>ANCA, biopsy, arteriography \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"><span class="elsevierStyleItalic">Autoinflammatory syndromes</span><br><span class="elsevierStyleHsp" style=""></span>Familial mediterranean fever<br><span class="elsevierStyleHsp" style=""></span>Hyper-IgD syndrome<br><span class="elsevierStyleHsp" style=""></span>TNF receptor associated periodic syndrome (TRAPS) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><br>Family history, genetic analysis<br>Immunoglobulins count<br>Genetic analysis \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"><span class="elsevierStyleItalic">Drug reaction/DRESS syndrome</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Eosinophil count, skin biopsy \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"><span class="elsevierStyleItalic">Others</span><br><span class="elsevierStyleHsp" style=""></span>Sarcoidosis<br><span class="elsevierStyleHsp" style=""></span>Reactive arthritis<br><span class="elsevierStyleHsp" style=""></span>Schnitzler syndrome<br><span class="elsevierStyleHsp" style=""></span>Sweet's syndrome<br><span class="elsevierStyleHsp" style=""></span>Kikuchi disease \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><br><br>Imaging or diagnostic test based on clinical suspicion \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1262281.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Differential diagnosis of adult-onset Still's disease.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:35 [ 0 => array:3 [ "identificador" => "bib0180" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Still's disease in the adult" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "E.G. Bywaters" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Ann Rheum Dis" "fecha" => "1971" "volumen" => "30" "paginaInicial" => "121" "paginaFinal" => "133" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/5315135" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0185" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "On a form of chronic joint disease in children" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "G.F. Still" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Med Chir Trans" "fecha" => "1897" "volumen" => "80" "paginaInicial" => "47" "paginaFinal" => "60" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20896907" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0190" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Epidemiology of adult Still's disease: estimate of the incidence by a retrospective study in west France" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "G. Magadur-Joly" 1 => "E. Billaud" 2 => "J.H. Barrier" 3 => "Y.L. Pennec" 4 => "C. Masson" 5 => "P. Renou" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Ann Rheum Dis" "fecha" => "1995" "volumen" => "54" "paginaInicial" => "587" "paginaFinal" => "590" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7668903" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0195" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Epidemiology and outcome of adult-onset Still's disease in Northern Norway" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "K.J. Evensen" 1 => "H.C. Nossent" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1080/03009740510026616" "Revista" => array:6 [ "tituloSerie" => "Scand J Rheumatol" "fecha" => "2006" "volumen" => "35" "paginaInicial" => "48" "paginaFinal" => "51" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16467042" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0200" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Adult-onset Still's disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "M. Gerfaud-Valentin" 1 => "Y. Jamilloux" 2 => "J. Iwaz" 3 => "P. Sève" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.autrev.2014.01.058" "Revista" => array:6 [ "tituloSerie" => "Autoimmun Rev" "fecha" => "2014" "volumen" => "13" "paginaInicial" => "708" "paginaFinal" => "722" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24657513" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0205" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A promoter haplotype of the interleukin-18 gene is associated with juvenile idiopathic arthritis in the Japanese population" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "T. Sugiura" 1 => "N. Maeno" 2 => "Y. Kawaguchi" 3 => "S. Takei" 4 => "H. Imanaka" 5 => "Y. Kawano" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/ar1930" "Revista" => array:5 [ "tituloSerie" => "Arthritis Res Ther" "fecha" => "2006" "volumen" => "8" "paginaInicial" => "R60" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16563174" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0210" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:3 [ "comentario" => "[in French]" "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Pathophysiology, subtypes, and treatments of adult-onset Still's disease: an update" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "M. Gerfaud-Valentin" 1 => "P. Sève" 2 => "A. Hot" 3 => "C. Broussolle" 4 => "Y. Jamilloux" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Rev Med Intern" "fecha" => "2015" "volumen" => "36" "paginaInicial" => "319" "paginaFinal" => "327" ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0215" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:3 [ "comentario" => "[in press]" "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Adult-onset Still's disease: advances in the treatment" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "S. Castañeda" 1 => "R. Blanco" 2 => "M.A. González-Gay" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:2 [ "tituloSerie" => "Best Pract Res Clin Rheumatol" "fecha" => "2016" ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0220" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Involvement of TLR7 MyD88-dependent signaling pathway in the pathogenesis of adult-onset Still's disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D.Y. Chen" 1 => "C.C. Lin" 2 => "Y.M. Chen" 3 => "J.L. Lan" 4 => "W.T. Hung" 5 => "H.H. Chen" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/ar4193" "Revista" => array:5 [ "tituloSerie" => "Arthritis Res Ther" "fecha" => "2013" "volumen" => "15" "paginaInicial" => "R39" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23497717" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0225" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Predominance of Th1 cytokine in peripheral blood and pathological tissues of patients with active untreated adult onset Still's disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "D.Y. Chen" 1 => "J.L. Lan" 2 => "F.J. Lin" 3 => "T.Y. Hsieh" 4 => "M.C. Wen" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/ard.2003.013680" "Revista" => array:6 [ "tituloSerie" => "Ann Rheum Dis" "fecha" => "2004" "volumen" => "63" "paginaInicial" => "1300" "paginaFinal" => "1306" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15361391" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0230" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The associations of circulating CD4+CD25high regulatory T cells and TGF-β with disease activity and clinical course in patients with adult-onset Still's disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "D.Y. Chen" 1 => "Y.M. Chen" 2 => "H.H. Chen" 3 => "C.W. Hsieh" 4 => "C.C. Lin" 5 => "J.L. Lan" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3109/03008200903461462" "Revista" => array:6 [ "tituloSerie" => "Connect Tissue Res" "fecha" => "2010" "volumen" => "51" "paginaInicial" => "370" "paginaFinal" => "377" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20388015" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0235" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Life-threatening complications of adult-onset Still's disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "P. Efthimiou" 1 => "S. Kadavath" 2 => "B. Mehta" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s10067-014-2487-4" "Revista" => array:6 [ "tituloSerie" => "Clin Rheumatol" "fecha" => "2014" "volumen" => "33" "paginaInicial" => "305" "paginaFinal" => "314" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24435354" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0240" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Adult-onset Still's disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "J. Kádár" 1 => "E. Petrovicz" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.berh.2004.05.004" "Revista" => array:6 [ "tituloSerie" => "Best Pract Res Clin Rheumatol" "fecha" => "2004" "volumen" => "18" "paginaInicial" => "663" "paginaFinal" => "676" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15454125" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0245" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Diagnosis and management of adult onset Still's disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "P. Efthimiou" 1 => "P.K. Paik" 2 => "L. Bielory" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/ard.2005.042143" "Revista" => array:6 [ "tituloSerie" => "Ann Rheum Dis" "fecha" => "2006" "volumen" => "65" "paginaInicial" => "564" "paginaFinal" => "572" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16219707" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0250" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Increased level of H-ferritin and its imbalance with L-ferritin, in bone marrow and liver of patients with adult onset Still's disease, developing macrophage activation syndrome, correlate with the severity of the disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P. Ruscitti" 1 => "P. Cipriani" 2 => "P. di Benedetto" 3 => "F. Ciccia" 4 => "V. Liakouli" 5 => "F. Carubbi" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.autrev.2015.01.004" "Revista" => array:6 [ "tituloSerie" => "Autoimmun Rev" "fecha" => "2015" "volumen" => "14" "paginaInicial" => "429" "paginaFinal" => "437" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25599955" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0255" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Preliminary criteria for classification of adult Still's disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Yamaguchi" 1 => "A. Ohta" 2 => "T. Tsunematsu" 3 => "R. Kasukawa" 4 => "Y. Mizushima" 5 => "H. Kashiwagi" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Rheumatol" "fecha" => "1992" "volumen" => "19" "paginaInicial" => "424" "paginaFinal" => "430" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1578458" "web" => "Medline" ] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0260" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Proposal for a new set of classification criteria for adult-onset Still disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "B. Fautrel" 1 => "E. Zing" 2 => "J.L. Golmard" 3 => "G. Le Moel" 4 => "A. Bissery" 5 => "C. Rioux" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Medicine (Baltimore)" "fecha" => "2002" "volumen" => "81" "paginaInicial" => "194" "paginaFinal" => "200" ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0265" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Adult onset Still's disease (AOSD) in the era of biologic therapies: dichotomous view for cytokine and clinical expressions" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "A.T. Maria" 1 => "A. Le Quellec" 2 => "C. Jorgensen" 3 => "I. Touitou" 4 => "S. Rivière" 5 => "P. Guilpain" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.autrev.2014.08.032" "Revista" => array:6 [ "tituloSerie" => "Autoimmun Rev" "fecha" => "2014" "volumen" => "13" "paginaInicial" => "1149" "paginaFinal" => "1159" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25183244" "web" => "Medline" ] ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0270" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Successful treatment of refractory adult-onset Still's disease with infliximab. A prospective, non-comparative series of four patients" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "A. Kokkinos" 1 => "A. Iliopoulos" 2 => "P. Greka" 3 => "A. Efthymiou" 4 => "N. Katsilambros" 5 => "P.P. Sfikakis" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s10067-003-0775-5" "Revista" => array:6 [ "tituloSerie" => "Clin Rheumatol" "fecha" => "2004" "volumen" => "23" "paginaInicial" => "45" "paginaFinal" => "49" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14749983" "web" => "Medline" ] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0275" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Successful treatment of a small cohort of patients with adult onset of Still's disease with infliximab: first experiences" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "H.G. Kraetsch" 1 => "C. Antoni" 2 => "J.R. Kalden" 3 => "B. Manger" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Ann Rheum Dis" "fecha" => "2001" "volumen" => "60" "numero" => "Suppl. 3" "paginaInicial" => "iii55" "paginaFinal" => "iii57" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11890655" "web" => "Medline" ] ] ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0280" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Etanercept in the treatment of adult patients with Still's disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.E. Husni" 1 => "A.L. Maier" 2 => "P.J. Mease" 3 => "S.S. Overman" 4 => "P. Fraser" 5 => "E.M. Gravallese" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/art.10231" "Revista" => array:6 [ "tituloSerie" => "Arthritis Rheum" "fecha" => "2002" "volumen" => "46" "paginaInicial" => "1171" "paginaFinal" => "1176" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12115220" "web" => "Medline" ] ] ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0285" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Tumour necrosis factor alpha blocking agents in refractory adult Still's disease: an observational study of 20 cases" "autores" => array:1 [ 0 => array:3 [ "colaboracion" => "Club Rhumatismes et Inflammation" "etal" => false "autores" => array:4 [ 0 => "B. Fautrel" 1 => "J. Sibilia" 2 => "X. Mariette" 3 => "B. Combe" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/ard.2004.024026" "Revista" => array:6 [ "tituloSerie" => "Ann Rheum Dis" "fecha" => "2005" "volumen" => "64" "paginaInicial" => "262" "paginaFinal" => "266" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15184196" "web" => "Medline" ] ] ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib0290" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Adult-onset Still disease: manifestations, treatment, outcome, and prognostic factors in 57 patients" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Gerfaud-Valentin" 1 => "D. Maucort-Boulch" 2 => "A. Hot" 3 => "J. Iwaz" 4 => "J. Ninet" 5 => "I. Durieu" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Medicine (Baltimore)" "fecha" => "2014" "volumen" => "93" "paginaInicial" => "91" "paginaFinal" => "99" ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0295" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Is anti-TNF switching in refractory Still's disease safe and effective?" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "N.E. Aikawa" 1 => "A.C. Ribeiro" 2 => "C.G. Saad" 3 => "R.M. Pereira" 4 => "M. Levy" 5 => "C.A. Silva" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s10067-011-1735-0" "Revista" => array:6 [ "tituloSerie" => "Clin Rheumatol" "fecha" => "2011" "volumen" => "30" "paginaInicial" => "1129" "paginaFinal" => "1134" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21465126" "web" => "Medline" ] ] ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib0300" "etiqueta" => "25" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Beneficial effect of interleukin 1 inhibition with anakinra in adult-onset Still's disease. An open, randomized, multicenter study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D. Nordström" 1 => "A. Knight" 2 => "R. Luukkainen" 3 => "R. van Vollenhoven" 4 => "V. Rantalaiho" 5 => "A. Kajalainen" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3899/jrheum.111549" "Revista" => array:6 [ "tituloSerie" => "J Rheumatol" "fecha" => "2012" "volumen" => "39" "paginaInicial" => "2008" "paginaFinal" => "2011" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22859346" "web" => "Medline" ] ] ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib0305" "etiqueta" => "26" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Anakinra treatment in patients with adult-onset Still's disease is fast, effective, safe and steroid sparing: experience from an uncontrolled trial" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "G.D. Kalliolias" 1 => "P.E. Georgiou" 2 => "I.A. Antonopoulos" 3 => "A.P. Andonopoulos" 4 => "S.N. Liossis" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/ard.2006.066381" "Revista" => array:6 [ "tituloSerie" => "Ann Rheum Dis" "fecha" => "2007" "volumen" => "66" "paginaInicial" => "842" "paginaFinal" => "843" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17513574" "web" => "Medline" ] ] ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib0310" "etiqueta" => "27" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Interleukin-1 receptor antagonist (anakinra) treatment in patients with systemic-onset juvenile idiopathic arthritis or adult onset Still disease: preliminary experience in France" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "T. Lequerré" 1 => "P. Quartier" 2 => "D. Rosellini" 3 => "F. Alaoui" 4 => "M. de Bandt" 5 => "O. Mejjad" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/ard.2007.076034" "Revista" => array:6 [ "tituloSerie" => "Ann Rheum Dis" "fecha" => "2008" "volumen" => "67" "paginaInicial" => "302" "paginaFinal" => "308" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17947302" "web" => "Medline" ] ] ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib0315" "etiqueta" => "28" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Efficacy of anakinra in refractory adult-onset Still's disease: multicenter study of 41 patients and literature review" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "F. Ortiz-Sanjuán" 1 => "R. Blanco" 2 => "L. Riancho-Zarrabeitia" 3 => "S. Castañeda" 4 => "A. Olivé" 5 => "A. Riveros" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "Medicine (Baltimore)" "fecha" => "2015" "volumen" => "94" "paginaInicial" => "e1554" ] ] ] ] ] ] 28 => array:3 [ "identificador" => "bib0320" "etiqueta" => "29" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Successful treatment of adult-onset Still's disease refractory to TNF and IL-1 blockade by IL-6 receptor blockade" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Rech" 1 => "M. Ronneberger" 2 => "M. Englbrecht" 3 => "S. Finzel" 4 => "J. Katzenbeisser" 5 => "K. Manger" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/ard.2010.129403" "Revista" => array:6 [ "tituloSerie" => "Ann Rheum Dis" "fecha" => "2011" "volumen" => "70" "paginaInicial" => "390" "paginaFinal" => "392" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20650873" "web" => "Medline" ] ] ] ] ] ] ] ] 29 => array:3 [ "identificador" => "bib0325" "etiqueta" => "30" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Therapeutic response of patients with adult Still's disease to biologic agents: multicenter results in Japan" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R. Suematsu" 1 => "A. Ohta" 2 => "E. Matsuura" 3 => "H. Takahashi" 4 => "T. Fujii" 5 => "T. Horiuchi" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s10165-011-0569-6" "Revista" => array:6 [ "tituloSerie" => "Mod Rheumatol" "fecha" => "2012" "volumen" => "22" "paginaInicial" => "712" "paginaFinal" => "719" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22160845" "web" => "Medline" ] ] ] ] ] ] ] ] 30 => array:3 [ "identificador" => "bib0330" "etiqueta" => "31" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Tocilizumab in refractory adult Still's disease" "autores" => array:1 [ 0 => array:3 [ "colaboracion" => "Club Rhumatismes Et Inflammation" "etal" => true "autores" => array:6 [ 0 => "X. Puéchal" 1 => "M. DeBandt" 2 => "J.M. Berthelot" 3 => "M. Breban" 4 => "J.J. Dubost" 5 => "O. Fain" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Arthritis Care Res (Hoboken)" "fecha" => "2011" "volumen" => "63" "paginaInicial" => "155" "paginaFinal" => "159" ] ] ] ] ] ] 31 => array:3 [ "identificador" => "bib0335" "etiqueta" => "32" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Tocilizumab for the treatment of adult-onset Still's disease: results from a case series" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P. Cipriani" 1 => "P. Ruscitti" 2 => "F. Carubbi" 3 => "I. Pantano" 4 => "V. Liakouli" 5 => "O. Berardicurti" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s10067-013-2381-5" "Revista" => array:6 [ "tituloSerie" => "Clin Rheumatol" "fecha" => "2014" "volumen" => "33" "paginaInicial" => "49" "paginaFinal" => "55" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24005839" "web" => "Medline" ] ] ] ] ] ] ] ] 32 => array:3 [ "identificador" => "bib0340" "etiqueta" => "33" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Efficacy of tocilizumab in conventional treatment-refractory adult-onset Still's disease: multicenter retrospective open-label study of thirty-four patients" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "F. Ortiz-Sanjuán" 1 => "R. Blanco" 2 => "V. Calvo-Rio" 3 => "J. Narvaez" 4 => "E. Rubio Romero" 5 => "A. Olivé" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/art.38398" "Revista" => array:6 [ "tituloSerie" => "Arthritis Rheumatol" "fecha" => "2014" "volumen" => "66" "paginaInicial" => "1659" "paginaFinal" => "1665" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24515813" "web" => "Medline" ] ] ] ] ] ] ] ] 33 => array:3 [ "identificador" => "bib0345" "etiqueta" => "34" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The effect of tocilizumab on preventing relapses in adult-onset Still's disease: a retrospective, single-center study" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "N. Nishina" 1 => "Y. Kaneko" 2 => "H. Kameda" 3 => "T. Takeuchi" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3109/14397595.2014.973659" "Revista" => array:6 [ "tituloSerie" => "Mod Rheumatol" "fecha" => "2015" "volumen" => "25" "paginaInicial" => "401" "paginaFinal" => "404" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25401229" "web" => "Medline" ] ] ] ] ] ] ] ] 34 => array:3 [ "identificador" => "bib0350" "etiqueta" => "35" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Benefit and a possible risk of tocilizumab therapy for adult-onset Still's disease accompanied by macrophage-activation syndrome" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "M. Kobayashi" 1 => "Y. Takahashi" 2 => "H. Yamashita" 3 => "H. Kaneko" 4 => "A. Mimori" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s10165-010-0348-9" "Revista" => array:6 [ "tituloSerie" => "Mod Rheumatol" "fecha" => "2011" "volumen" => "21" "paginaInicial" => "92" "paginaFinal" => "96" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20737186" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/23870206/0000014700000005/v1_201611300117/S2387020616305393/v1_201611300117/en/main.assets" "Apartado" => array:4 [ "identificador" => "44144" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Diagnosis and treatment" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/23870206/0000014700000005/v1_201611300117/S2387020616305393/v1_201611300117/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020616305393?idApp=UINPBA00004N" ]
Journal Information
Vol. 147. Issue 5.
Pages 217-222 (September 2016)
Share
Download PDF
More article options
Vol. 147. Issue 5.
Pages 217-222 (September 2016)
Diagnosis and treatment
Adult-onset Still's disease
Enfermedad de Still del adulto
Visits
6
a Servicio de Reumatología, Hospital de La Princesa, Instituto de Investigación Sanitaria de La Princesa (IIS-IP), Universidad Autónoma de Madrid (UAM), Madrid, Spain
b Servicio de Reumatología, Hospital Universitario Marqués de Valdecilla, Santander, Spain
c Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, Universidad de Cantabria, Instituto de Investigación Sanitaria Valdecilla (IDIVAL), Santander, Spain
This item has received
Article information
These are the options to access the full texts of the publication Medicina Clínica (English Edition)
Subscriber
Subscribe
Purchase
Contact
Phone for subscriptions and reporting of errors
From Monday to Friday from 9 a.m. to 6 p.m. (GMT + 1) except for the months of July and August which will be from 9 a.m. to 3 p.m.
Calls from Spain
932 415 960
Calls from outside Spain
+34 932 415 960
E-mail