Review
Current diagnosis and treatment of Castleman's disease
Diagnóstico y tratamiento actual de la enfermedad de Castleman
A. González García, M.Á. Moreno Cobo, J.L. Patier de la Peña
Corresponding author
Servicio de Medicina Interna, Hospital Universitario Ramón y Cajal, Madrid, Spain
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Heart Failure</span>" "titulo" => "Organ protection possibilities in acute heart failure" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "157" "paginaFinal" => "164" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Posibilidades de organoprotección en la insuficiencia cardiaca aguda" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "fuente" => "Adapted from Metra et al.<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">20</span></a>" "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1807 "Ancho" => 2916 "Tamanyo" => 207276 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Mechanisms of renal function impairment in heart failure.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "M. 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Abbreviations: aPL: antiphospholipid antibodies; APS: antiphospholipid syndrome; OAPS: obstetric antiphospholipid syndrome.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "E. Esteve-Valverde, R. Ferrer-Oliveras, J. Alijotas-Reig" "autores" => array:3 [ 0 => array:2 [ "nombre" => "E." "apellidos" => "Esteve-Valverde" ] 1 => array:2 [ "nombre" => "R." "apellidos" => "Ferrer-Oliveras" ] 2 => array:2 [ "nombre" => "J." "apellidos" => "Alijotas-Reig" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0014256515002283" "doi" => "10.1016/j.rce.2015.09.003" "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/S0014256515002283?idApp=WRCEE" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2254887415001174?idApp=WRCEE" "url" => "/22548874/0000021600000003/v1_201604010056/S2254887415001174/v1_201604010056/en/main.assets" ] "en" => array:18 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Review</span>" "titulo" => "Current diagnosis and treatment of Castleman's disease" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "146" "paginaFinal" => "156" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "A. González García, M.Á. Moreno Cobo, J.L. Patier de la Peña" "autores" => array:3 [ 0 => array:2 [ "nombre" => "A." "apellidos" => "González García" ] 1 => array:2 [ "nombre" => "M.Á." "apellidos" => "Moreno Cobo" ] 2 => array:4 [ "nombre" => "J.L." "apellidos" => "Patier de la Peña" "email" => array:2 [ 0 => "joseluis.patier@salud.madrid.org" 1 => "patier43@hotmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Medicina Interna, Hospital Universitario Ramón y Cajal, Madrid, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Diagnóstico y tratamiento actual de la enfermedad de Castleman" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1330 "Ancho" => 2000 "Tamanyo" => 274150 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">(A) Large paracardiac mediastinal mass. (B) Prominent feeding arteries that are irrigating the mass can be identified (arrows). (C) Patient with CD in whom an anterior mediastinal mass can be observed in the CT scan. (D) There is uptake in the positron emission tomography.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Background</span><p id="par0005" class="elsevierStylePara elsevierViewall">Castleman's disease (CD), also known as angiofollicular lymph node hyperplasia, was reported between 1954 and 1956 by Castleman, a pathologist from the renowned Massachusetts General Hospital, based on a series of 13 patients with mediastinal masses that mimicked thymomas.<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">1</span></a> Over the last 60 years, the term Castleman's disease has remained a general label for the heterogeneous collection of reactive lymphoproliferative processes that share well-defined histological traits but that differ in their patterns of location, clinical expression and etiopathogenesis. The term includes at least 4 diseases with different diagnoses and treatments: (1) unicentric CD (UCD); (2) multicenter CD (MCD) associated with infection by the human herpes virus 8 (HHV-8) and by the human immunodeficiency virus (HIV) (MCD-HHV-8+/HIV+); (3) MCD with infection by HHV-8 but not by HIV (MCD-HHV-8+/HIV-); and (4) MCD not associated with any of these viruses, which has recently been called idiopathic MCD (iMCD). CD as a whole is considered a rare or minority disease. Despite the considerable interest the disease has generated since its initial description and the significant developments in research (more than 2700 entries in PubMed in September 2015), there is still no consensus on its treatment. Therefore, one of the objectives of this review is to facilitate an understanding of the current therapeutic options.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Epidemiology</span><p id="par0010" class="elsevierStylePara elsevierViewall">The incidence of CD is unknown. Based on patient cohort results extracted from databases, a number of authors have estimated an incidence of approximately 21 cases per million inhabitants in the United States.<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">2</span></a> The disease usually affects middle-aged people, although with a bimodal distribution with a peak in young patients (30–40 years) and another at approximately 60 years. The incidence is similar in both sexes. The incidence of MCD-HHV-8+/HIV+ has increased in recent years due to the AIDS epidemic.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Classification</span><p id="par0015" class="elsevierStylePara elsevierViewall">CD is classically divided into 2 types based on the onset of isolated adenomegaly (UCD) or polyadenopathies (MCD). These 2 conditions have very different clinical and histological characteristics.</p><p id="par0020" class="elsevierStylePara elsevierViewall">CD causes an architectural change in the structure of the lymph nodes, which affects all their compartments. Histologically, CD is classified into a hyaline-vascular (HV) form and a plasmocellular (PC) form, although mixed variants can occasionally be observed, especially in the MCD forms.<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">3</span></a> In the HV form, the follicles show atrophic germinal centers, invaded by dendritic follicular cells and hyalinized vessels, which form bridges and connections between them. These centers are surrounded by mantle lymphocytes arranged in concentric rings that mimic the typical “onion layer” presentation. Two subtypes have been reported in the HV form: the classical lymphoid subtype and the stroma-cell rich subtype. The latter subtype has been reported as a possible precursor of follicular dendritic cell sarcomas.<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">4</span></a> In the PC variant, the follicles show hyperplastic germinal centers, and the interfollicular regions characteristically contain polyclonal plasma cells; the characteristic vascular proliferation of the HV forms is not observed. A third histological variant, known as plasmablastic, has recently been reported,<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">5</span></a> which occurs in particularly aggressive cases of MCD associated with HHV-8<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">6</span></a> and in the forms associated with POEMS syndrome<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">7</span></a> (Crow-Fukase syndrome<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">8</span></a>).</p><p id="par0025" class="elsevierStylePara elsevierViewall">This morphological complexity carries over to clinical practice, because there are patients who show an overlap between UCD and MCD. In the early years, there was certain controversy in the literature when describing the cases. The limitations in disease staging and the limited experience with the histological analysis of samples fostered confusion among the clinical and histological variants. Despite the improvements in diagnostic techniques and the experience acquired with CD, there are still a number of issues concerning its classification. Isolated unicentric masses, which used to be identified with plain radiographs, can now be accompanied by adenopathies in other regions or by reactive splenomegaly. In a small number of cases, the use of techniques such as computed tomography, magnetic resonance and positron emission tomography blurs the unequivocal separation between UCD and MCD. Despite these difficulties, however, the majority of patients can be classified into one of the 2 variants (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Pathophysiology</span><p id="par0030" class="elsevierStylePara elsevierViewall">There have been major advances in understanding the pathophysiology of CD. There are various theories based on the repeated antigenic stimulus of nodal B lymphocytes in response to some etiological agent. The most accepted model is the one derived from an abnormal overproduction of interleukin-6 (IL-6) by B lymphocytes of the mantle zone. These cells are stimulated on most occasions by a viral antigen (HHV-8) and, less frequently, by endogenous or exogenous factors of still unknown origin.<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">9</span></a> The inflammatory mediators and co-infection by HHV-8 and HIV are important factors for explaining the symptoms and etiopathogenesis of CD. Below, we show the role of each of the compounds that are involved in the pathogenesis of the disease.</p><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Interleukin-6, interleukin-6 receptor and vascular endothelial growth factor</span><p id="par0035" class="elsevierStylePara elsevierViewall">IL-6 behaves as an inducer of B-cell proliferation. IL-6 is involved in the hepatic synthesis of acute-phase reactants and is responsible for the general symptoms, which are characteristic of numerous systemic inflammatory diseases.<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">10</span></a> IL-6 is also involved in hepcidin synthesis, which regulates serum iron levels and is the main cause of anemia in chronic diseases.<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">11</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Serum IL-6 concentrations are strikingly high in CD. IL-6 levels are even higher than in other diseases such as rheumatoid arthritis and multiple myeloma, where its pathogenic role is well-known.<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">10</span></a> Excess IL-6 induces a proinflammatory syndrome that explains the general symptoms typical of MCD and increased levels of acute phase reactants. High concentrations have also been reported in peripheral blood in cases of UCD that, after the single mass has been removed, experience a reduction, with symptom remission.<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">12</span></a> Differences in clinical expression in various populations have been identified. For example, very prominent skin manifestations have been reported in Asians, as well as pemphigus, renal damage and an increased frequency of interstitial pulmonary involvement.<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">13</span></a> Furthermore, differences have been reported in particular polymorphisms that affect IL-6R and that are associated with higher plasma IL-6R concentrations in patients with iMCD.<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">14</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">One of the functions of IL-6 is to induce vascular endothelial growth factor (VEGF) expression.<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">15</span></a> It is believed that this compound causes hypervascularization of the germinal regions of the lymph nodes in CD. Several researchers have found high serum VEGF levels in patients with CD, as well as its overexpression in plasma cells and interfollicular regions.<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">16</span></a> Although the involvement of VEGF in the pathogenesis of CD is indisputable, its mechanism of action is still unclear.</p><p id="par0050" class="elsevierStylePara elsevierViewall">These findings, along with the usefulness of blocking this inflammatory pathway as a possible therapy,<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">17</span></a> have established the fundamental role of IL-6 in the development of MCD and the perpetuation of its symptoms.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Human herpesvirus 8</span><p id="par0055" class="elsevierStylePara elsevierViewall">With the HIV epidemic in the 1980s, there was a reported increase in the incidence of Kaposi's sarcoma (KS), a previously uncommon skin cancer. In 1994, a new gamma virus belonging to the herpes virus family was sequenced in the biopsies of patients with KS: HHV-8.<a class="elsevierStyleCrossRef" href="#bib0445"><span class="elsevierStyleSup">18</span></a> In addition to KS, there are other diseases that are closely associated with this virus, such as body cavity lymphoma and MCD. The mechanism of action of HHV-8 consists of the secretion of viral particles homologs of human IL-6 (vIL-6) by B cells of the infected mantle. These particles hyperstimulate the production of B cells and the secretion of human IL-6, perpetuating the inflammatory cycle.<a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">19</span></a> This pathogenic mechanism has been confirmed due to the finding of a close correlation between disease activity and viral load.<a class="elsevierStyleCrossRef" href="#bib0455"><span class="elsevierStyleSup">20</span></a> It has been postulated that HHV-8 is a necessary but insufficient agent for causing the disease. HHV-8 has been reported in up to 40% of HIV- patients with MCD and in up to 100% of a series of patients with MCD and positive HIV serology.<a class="elsevierStyleCrossRef" href="#bib0460"><span class="elsevierStyleSup">21</span></a> This situation contrasts with the pathogenic mechanism of MCD and HHV-8, given that its initial stimulation is polyclonal. HHV-8 tends to perpetuate preferentially in plasmoblasts that express IgMλ light chains but not in those that express other types of Ig or k light-chain. Despite this monotypic expression, infected B cells do not show rearrangements of the heavy chains (IgH) and maintain their polyclonal character.<a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">22</span></a> The high-power replication of HHV-8 in monotypic B cells can over time cause IgH rearrangements, which lead to microlymphomas and even developed plasmablastic lymphomas.<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">5</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Human immunodeficiency virus</span><p id="par0060" class="elsevierStylePara elsevierViewall">MCD is considered a disease related to the complex of AIDS-associated lymphadenopathies, although its incidence is low within that spectrum (2%). A fundamental role in MCD has been attributed to HIV, given its high replicative capacity and persistent stimulation of B lymphocytes.<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">23</span></a> However, it is currently believed that immunosuppression and co-infection with HHV-8 are the main pathogenic factors of MCD.</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Unicentric Castleman's disease</span><p id="par0065" class="elsevierStylePara elsevierViewall">The paradigm of UCD corresponds to Castleman's original description in 1956.<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">1</span></a> Approximately 90% of cases correspond to the histological variant HV. Unlike the multicentric form, little is known about the etiopathogenesis of UCD. Excess IL-6 secretion has been found only in isolated cases with general symptoms. An association with either HHV-8 or HIV infection has not been reported. Although it can occur at any age, UCD tends to appear at younger ages and has a certain characteristic predilection for the female sex.<a class="elsevierStyleCrossRef" href="#bib0475"><span class="elsevierStyleSup">24</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">UCD is usually asymptomatic in most cases. The main characteristics of UCD are listed in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>. The most common symptoms are isolated swelling of a lymph node station. Symptoms can appear resulting from the local compression of neighboring anatomical structures. If systemic manifestations occur, they usually correspond to a PC histological pattern.</p><p id="par0075" class="elsevierStylePara elsevierViewall">Diverse local disorders have been reported, including mediastinal, cervical, abdominal and retroperitoneal disorders. Mediastinal masses can grow to a considerable size and present signs of hypervascularization, developing abnormal feeding vessels from the bronchial arteries (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1A and B</a>). Paraneoplastic pemphigus <a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">25</span></a> and bronchiolitis obliterans<a class="elsevierStyleCrossRef" href="#bib0485"><span class="elsevierStyleSup">26</span></a> have characteristically been reported as associated systemic manifestations. In these cases, the prognosis is poor due to the complications resulting from progressive respiratory failure and infections, which in many cases lead to death.<a class="elsevierStyleCrossRef" href="#bib0490"><span class="elsevierStyleSup">27</span></a></p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0080" class="elsevierStylePara elsevierViewall">Typically, there are no specific abnormal laboratory test results. Some patients can experience anemia with an iron deficiency profile, chronic or mixed disorders, hypoalbuminemia, hypergammaglobulinemia, increased erythrocyte sedimentation rates and higher C-reactive protein (CRP) levels.</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Multicentric Castleman's disease</span><p id="par0085" class="elsevierStylePara elsevierViewall">MCD has a very different profile from that of the unicentric variant. MCD can be more or less severe depending on whether it is associated with clonal conditions such as the syndrome characterized by polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes (POEMS syndrome) and HIV or HHV-8 infection.</p><p id="par0090" class="elsevierStylePara elsevierViewall">Prior to the AIDS epidemic, MCD presented in patients in the sixth decade of life. However, MCD associated with HIV usually affects younger populations.<a class="elsevierStyleCrossRefs" href="#bib0495"><span class="elsevierStyleSup">28,29</span></a> The evolution of MCD has been changed by the behavior of HIV infection in the last 2 decades. At the start of the 1990s, there was an increase in the incidence of MCD, which decreased by the end of the 2000s, thanks to the implementation of antiretroviral treatment.<a class="elsevierStyleCrossRef" href="#bib0505"><span class="elsevierStyleSup">30</span></a> However, there are subtypes of MCD depending on whether it is associated with HIV, HHV-8 or both. In HIV/HHV-8+ patients, the disease assumes a more aggressive and abrupt course. Given the frequent coexistence of HIV infection, KS and MCD, it was believed that HHV-8 was essential for developing the disease. In recent years, however, a number of cases of MCD associated with HIV with negative tests for HHV-8 have been published.<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">31</span></a> Moreover, there is a patient group with MCD that is not infected by HIV or HHV-8. In these cases, the etiology is unknown, although numerous theories have been proposed, including infectious causes by still unidentified agents, underlying autoimmune diseases, genetic mutations in the germinal line that affect the innate immunity and even malignancies, as promoters of this type of idiopathic MCD.<a class="elsevierStyleCrossRef" href="#bib0515"><span class="elsevierStyleSup">32</span></a> Current research efforts are focused on ascertaining the etiology in this subtype.</p><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Clinical presentation</span><p id="par0095" class="elsevierStylePara elsevierViewall">The clinical expression varies and depends on the extent of the disease, the blood cytokine concentration and positive/negative state of HIV and HHV-8 virus infection. Most patients have prominent general symptoms (fever, hyporexia, night-time sweats, asthenia), along with those resulting from lymph node and visceral involvement.<a class="elsevierStyleCrossRef" href="#bib0520"><span class="elsevierStyleSup">33</span></a> Patients with POEMS symptomatology present the clinical characteristics of that syndrome (skin changes and neurological and endocrine disorders),<a class="elsevierStyleCrossRef" href="#bib0525"><span class="elsevierStyleSup">34</span></a> sometimes accompanied by osteosclerotic bone involvement.<a class="elsevierStyleCrossRef" href="#bib0530"><span class="elsevierStyleSup">35</span></a><a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a> shows a case of idiopathic MCD, with a monoclonal peak and multiple osteosclerotic lesions, with osteoblastic activity in the scintigraphy.</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0100" class="elsevierStylePara elsevierViewall">From the neurological point of view, MCD can present as peripheral motor polyneuropathy in the context of POEMS or can affect the optic nerve in the form of papilledema.<a class="elsevierStyleCrossRef" href="#bib0535"><span class="elsevierStyleSup">36</span></a> There have been reports of other findings resulting from hypoalbuminemia in the context of TAFRO syndrome (a Japanese variant of MCD known as Castleman-Kojima disease, which combines thrombocytopenia, anasarca, reticulin fibrosis, renal dysfunction and organomegaly),<a class="elsevierStyleCrossRef" href="#bib0540"><span class="elsevierStyleSup">37</span></a> interstitial pulmonary involvement and even respiratory distress (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).<a class="elsevierStyleCrossRef" href="#bib0545"><span class="elsevierStyleSup">38</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">In iMCD, the clinical spectrum is broader than in the forms associated with HHV-8 and HIV. Symptom severity varies from flu-like conditions and generalized lymphadenopathy with intense constitutional symptoms to the development of multiple organ failure in the context of a macrophage-activation syndrome.<a class="elsevierStyleCrossRef" href="#bib0550"><span class="elsevierStyleSup">39</span></a> The disease course can be relapsing without treatment, gradually progressive or include severe exacerbations that lead to death.</p><p id="par0110" class="elsevierStylePara elsevierViewall">Occasionally, diseases need to be ruled out that can cause Castleman-like histological findings in the lymph nodes, such as systemic lupus erythematosus, Epstein–Barr virus infection, syphilis, a number of lymphomas and IgG4-related lymphadenopathy. Nevertheless, associations between MCD and the abovementioned conditions have been reported, which illustrates the diagnostic complexity.</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Abnormal laboratory test results</span><p id="par0115" class="elsevierStylePara elsevierViewall">Abnormal laboratory test results are common. Anemia of chronic disease is usually the most common. Hemolytic anemia, isolated or accompanied by thrombopenia, in the context of Evans syndrome can also be observed.<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">40</span></a> A multitude of immune-mediated pathogenic disorders have been documented (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>), as well as positivity for various autoantibodies, rheumatoid factor and cryoglobulins.<a class="elsevierStyleCrossRef" href="#bib0560"><span class="elsevierStyleSup">41</span></a> For cases in which an association with POEMS is suspected, the detection of monoclonal paraprotein through immunoelectrophoresis of blood and urine can be useful.</p></span></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Treatment</span><p id="par0120" class="elsevierStylePara elsevierViewall">UCD, MCD-HHV-8 (with or without HIV coinfection) and iMCD have different treatments. It is advisable to provide multidisciplinary care in reference centers that have a medical expert coordinator (hematologist or internist) and several medical and surgical specialties involved in the process. HIV units and the participation of a pathologist with experience in diagnosis are also instrumental.</p><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Unicentric Castleman's disease</span><p id="par0125" class="elsevierStylePara elsevierViewall">Complete surgical exeresis of the adenopathic cluster is the treatment of choice. Between 95% and 100% of cases remain cured in the long term.<a class="elsevierStyleCrossRef" href="#bib0475"><span class="elsevierStyleSup">24</span></a> When the surgical approach due to the location or close relationship with vital structures is complex, neoadjuvant treatment with steroids and rituximab can reduce the volume and margins of the cluster, facilitating complete exeresis.<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">42</span></a> In some cases, full remission has been reported with rituximab, without needing subsequent surgery.<a class="elsevierStyleCrossRef" href="#bib0570"><span class="elsevierStyleSup">43</span></a> Presurgical artery embolization techniques for large masses are acceptable in some cases.<a class="elsevierStyleCrossRef" href="#bib0575"><span class="elsevierStyleSup">44</span></a> Radiation therapy has been relegated to special conditions, despite the good remission rates obtained in historical series.<a class="elsevierStyleCrossRef" href="#bib0580"><span class="elsevierStyleSup">45</span></a></p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Multicentric Castleman's disease</span><p id="par0130" class="elsevierStylePara elsevierViewall">There is no unanimous consensus on the optimal treatment for the variants of MCD. The low prevalence and variable course (occasionally relapsing or rapidly progressive) makes it difficult to obtain a uniform collection of patients to conduct randomized prospective studies. There has been only one randomized, double-blind trial to test the efficacy of siltuximab versus placebo (a study that included 79 patients).<a class="elsevierStyleCrossRef" href="#bib0585"><span class="elsevierStyleSup">46</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall">A summary of the evidence from various therapies is provided below. The recommendations for each form of MCD are listed, showing a simple scheme that takes into account the etiologic agents involved and the severity of the clinical condition (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>).</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Chemotherapy</span><p id="par0140" class="elsevierStylePara elsevierViewall">Monotherapy with vinblastine, etoposide or doxorubicin has achieved symptom control and a partial unsustained response.<a class="elsevierStyleCrossRef" href="#bib0590"><span class="elsevierStyleSup">47</span></a> CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) or CVAD (cyclophosphamide, vincristine, doxorubicin and dexamethasone) combination chemotherapy is preferable to monotherapy because the former has achieved higher response rates and longer responses in 50% of cases in studies with 4-year follow-ups.<a class="elsevierStyleCrossRef" href="#bib0520"><span class="elsevierStyleSup">33</span></a> Polychemotherapy should be considered in clinical forms with multiple-organ damage.<a class="elsevierStyleCrossRef" href="#bib0595"><span class="elsevierStyleSup">48</span></a></p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Glucocorticoids</span><p id="par0145" class="elsevierStylePara elsevierViewall">Glucocorticoids have frequently been used in MCD. The response rate is usually high (60–70%) but the response is generally not sustained, and the treatment should not be considered long-term. In patients with MCD-HHV-8+/HIV+, Glucocorticoids increase mortality due to infections and the development of KS.<a class="elsevierStyleCrossRef" href="#bib0600"><span class="elsevierStyleSup">49</span></a> At present, the primary indication for glucocorticoids is limited to the initial control of symptoms, using them for short periods or as part of combined chemotherapy regimens, such as CHOP and CVAD with or without rituximab.</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Rituximab</span><p id="par0150" class="elsevierStylePara elsevierViewall">Rituximab, alone or combined with chemotherapy, has significant activity in all variants of ECM,<a class="elsevierStyleCrossRefs" href="#bib0595"><span class="elsevierStyleSup">48,50–52</span></a> even when used as rescue therapy.<a class="elsevierStyleCrossRefs" href="#bib0620"><span class="elsevierStyleSup">53,54</span></a> A percentage of patients with HIV infection can experience exacerbation of preexisting KS lesions following treatment with rituximab.<a class="elsevierStyleCrossRef" href="#bib0630"><span class="elsevierStyleSup">55</span></a> Caution is advised for these patients, especially in conditions of severe immunosuppression (detectable viral load, low CD4 or active prior KS). Immune-mediated phenomena can also occur after therapy with rituximab.<a class="elsevierStyleCrossRef" href="#bib0635"><span class="elsevierStyleSup">56</span></a> A prospective study with 24 patients with HIV+ MCD assessed rituximab as an adjuvant agent to chemotherapy to maintain remission.<a class="elsevierStyleCrossRef" href="#bib0640"><span class="elsevierStyleSup">57</span></a> With the strategy of one weekly dose of rituximab (375<span class="elsevierStyleHsp" style=""></span>mg/m<span class="elsevierStyleSup">2</span>) for 4 weeks, a response rate of 92% was observed, with full remission in 71% at 13 months. In a study of 49 patients with HIV+ MCD, 35 patients were treated with rituximab and 14 with rituximab and etoposide (a group considered at greater risk). Progression-free survival at 2 and 5 years for all treated patients was 85% and 61%, respectively. The 8 cases among both groups with histologically confirmed relapse responded to retreatment with rituximab.<a class="elsevierStyleCrossRef" href="#bib0605"><span class="elsevierStyleSup">50</span></a> The use of rituximab, however, decreased the transformation to lymphoproliferative neoplasia in a cohort of patients with MCD-HHV-8+/HIV+.<a class="elsevierStyleCrossRef" href="#bib0615"><span class="elsevierStyleSup">52</span></a></p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Anti-interleukin-6</span><p id="par0155" class="elsevierStylePara elsevierViewall">The use of monoclonal antibodies directed against IL-6 (siltuximab) or its receptor (tocilizumab) has shown clinical efficacy in iMCD.<a class="elsevierStyleCrossRefs" href="#bib0645"><span class="elsevierStyleSup">58–60</span></a> Tocilizumab has been approved for MCD in Japan since 2005, while siltuximab has been approved in the United States and Europe for treating iMCD since 2014. In Spain, the Ministry of Health is currently establishing the price, an indispensable condition for marketing the drug.</p><p id="par0160" class="elsevierStylePara elsevierViewall">In a phase II, randomized, double-blind multicenter study of siltuximab (11<span class="elsevierStyleHsp" style=""></span>mg/kg intravenously infused every 3 weeks) vs. placebo in 79 patients with moderately symptomatic iMCD, the overall response rate was higher in the treated group (34% vs. 0%), with improvement in the anemia, inflammation markers (CRP, erythrocyte sedimentation rate and fibrinogen) and the baseline clinical state. This study continues in a single open arm for the patients who responded, with the objective of understanding long-term safety and efficacy.<a class="elsevierStyleCrossRef" href="#bib0585"><span class="elsevierStyleSup">46</span></a></p><p id="par0165" class="elsevierStylePara elsevierViewall">The safety and efficacy of tocilizumab was assessed in a prospective, open multicenter trial that included 28 symptomatic patients with the PC variant of MCD<a class="elsevierStyleCrossRef" href="#bib0660"><span class="elsevierStyleSup">61</span></a> and with no HIV and 2 patients with HHV-8+. The patients were initially treated with an intravenous dosage of 8<span class="elsevierStyleHsp" style=""></span>mg/kg every 2 weeks for 16 weeks, with a subsequent extension phase that allowed for a varying dosage. After 16 weeks of treatment, improvement was observed in the clinical and laboratory parameters, with a reduction in the daily dose of glucocorticoids and without needing treatment with blood products.</p><p id="par0170" class="elsevierStylePara elsevierViewall">In short, therapy directed against IL-6 is a viable option and an important advance in iMCD. Nevertheless, long-term follow-up is needed to establish the optimal treatment duration and to determine whether the initial response rates translate into greater survival.</p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Antivirals</span><p id="par0175" class="elsevierStylePara elsevierViewall">The clinical manifestations of MCD are correlated with the viral load of serum HHV-8, which indicates that they could be directly related to the replication of the virus.<a class="elsevierStyleCrossRef" href="#bib0665"><span class="elsevierStyleSup">62</span></a> In a pilot study, 14 patients with MCD-HHV-8+/HIV+ were treated with high-dose zidovudine (600<span class="elsevierStyleHsp" style=""></span>mg orally every 6<span class="elsevierStyleHsp" style=""></span>h) and valganciclovir (900<span class="elsevierStyleHsp" style=""></span>mg orally every 12<span class="elsevierStyleHsp" style=""></span>h).<a class="elsevierStyleCrossRef" href="#bib0670"><span class="elsevierStyleSup">63</span></a> After a median follow-up of 43 months, overall survival at 12 months was 86%. Although there are no comparative studies on the addition of antivirals, experts recommend combining ganciclovir or valganciclovir with rituximab for patients with MCD-HHV-8+/HIV+.<a class="elsevierStyleCrossRef" href="#bib0610"><span class="elsevierStyleSup">51</span></a> The more symptomatic patients, those with preexisting KS or a greater degree of immunosuppression, are considered at high risk and should therefore undergo chemotherapy with etoposide and highly active antiretroviral therapy (HAART) without delay.<a class="elsevierStyleCrossRef" href="#bib0605"><span class="elsevierStyleSup">50</span></a></p></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Others</span><p id="par0180" class="elsevierStylePara elsevierViewall">For cases refractory to rituximab and several chemotherapy regimens, anakinra has been suggested as a possible therapeutic rescue regimen.<a class="elsevierStyleCrossRef" href="#bib0675"><span class="elsevierStyleSup">64</span></a> Bortezomib inhibits IL-6 secretion and decreases plasma IL-6 levels and those of CRP.<a class="elsevierStyleCrossRef" href="#bib0680"><span class="elsevierStyleSup">65</span></a> A response to the proteasome inhibitor has been reported in cases of MCD associated with myeloma<a class="elsevierStyleCrossRef" href="#bib0685"><span class="elsevierStyleSup">66</span></a> and POEMS.<a class="elsevierStyleCrossRefs" href="#bib0690"><span class="elsevierStyleSup">67,68</span></a> In another case, bortezomib was used with thalidomide.<a class="elsevierStyleCrossRef" href="#bib0700"><span class="elsevierStyleSup">69</span></a> Other individual cases have shown a response to lenalidomide<a class="elsevierStyleCrossRef" href="#bib0705"><span class="elsevierStyleSup">70</span></a> and thalidomide alone or in combination with rituximab.<a class="elsevierStyleCrossRef" href="#bib0710"><span class="elsevierStyleSup">71</span></a></p></span></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Future perspectives</span><p id="par0185" class="elsevierStylePara elsevierViewall">Despite recent developments, anti-IL-6 therapy is not effective for all patients. To date, this therapy has not been studied in combination with other immunomodulatory or antiangiogenic therapies or with chemotherapy. An initiative was created in 2012 by the global research network known as the Castleman Disease Collaborative Network (CDCN, <a id="intr0010" class="elsevierStyleInterRef" href="http://www.castlemannetwork.org/">www.castlemannetwork.org</a>) for research into the pathogenesis of this disease. The CDCN includes specialists from 13 countries and more than 200 member co-investigators in the United States, Europe and Asia. Based on this platform, an international registry of MCD will be created, which will help the study of this disease's natural history and its presentation forms and will help design multicenter clinical trials and consensus treatment protocols. The CDCN will also propose the discovery of new viruses involved in the disease, the identification of intracellular inflammatory pathways and studies on gene sequencing.</p></span><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Conflicts of interest</span><p id="par0190" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:14 [ 0 => array:3 [ "identificador" => "xres624514" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec637918" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres624515" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec637917" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Background" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Epidemiology" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Classification" ] 7 => array:3 [ "identificador" => "sec0020" "titulo" => "Pathophysiology" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0025" "titulo" => "Interleukin-6, interleukin-6 receptor and vascular endothelial growth factor" ] 1 => array:2 [ "identificador" => "sec0030" "titulo" => "Human herpesvirus 8" ] 2 => array:2 [ "identificador" => "sec0035" "titulo" => "Human immunodeficiency virus" ] ] ] 8 => array:2 [ "identificador" => "sec0040" "titulo" => "Unicentric Castleman's disease" ] 9 => array:3 [ "identificador" => "sec0045" "titulo" => "Multicentric Castleman's disease" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0050" "titulo" => "Clinical presentation" ] 1 => array:2 [ "identificador" => "sec0055" "titulo" => "Abnormal laboratory test results" ] ] ] 10 => array:3 [ "identificador" => "sec0060" "titulo" => "Treatment" "secciones" => array:8 [ 0 => array:2 [ "identificador" => "sec0065" "titulo" => "Unicentric Castleman's disease" ] 1 => array:2 [ "identificador" => "sec0070" "titulo" => "Multicentric Castleman's disease" ] 2 => array:2 [ "identificador" => "sec0075" "titulo" => "Chemotherapy" ] 3 => array:2 [ "identificador" => "sec0080" "titulo" => "Glucocorticoids" ] 4 => array:2 [ "identificador" => "sec0085" "titulo" => "Rituximab" ] 5 => array:2 [ "identificador" => "sec0090" "titulo" => "Anti-interleukin-6" ] 6 => array:2 [ "identificador" => "sec0095" "titulo" => "Antivirals" ] 7 => array:2 [ "identificador" => "sec0100" "titulo" => "Others" ] ] ] 11 => array:2 [ "identificador" => "sec0105" "titulo" => "Future perspectives" ] 12 => array:2 [ "identificador" => "sec0110" "titulo" => "Conflicts of interest" ] 13 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec637918" "palabras" => array:8 [ 0 => "Castleman's disease" 1 => "Multicentric Castleman's disease" 2 => "Angiofollicular lymph node hyperplasia" 3 => "Human immunodeficiency virus" 4 => "Human herpes virus 8" 5 => "Rituximab" 6 => "Tocilizumab" 7 => "Siltuximab" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec637917" "palabras" => array:8 [ 0 => "Enfermedad de Castleman" 1 => "Enfermedad de Castleman multicéntrica" 2 => "Hiperplasia linfoide angiofolicular" 3 => "Virus de la inmunodeficiencia humana" 4 => "Virus del herpes humano tipo 8" 5 => "Rituximab" 6 => "Tocilizumab" 7 => "Siltuximab" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Castleman's disease is not just a single disease but rather an uncommon, heterogeneous group of nonclonal lymphoproliferative disorders, which have a broad spectrum of clinical expression. Three histological types have been reported, along with several clinical forms according to clinical presentation, histological substrate and associated diseases. Interleukin-6, its receptor polymorphisms, the human immunodeficiency virus and the human herpes virus 8 are involved in the etiopathogenesis of Castleman's disease. The study of this disease has shed light on a syndrome whose incidence is unknown. Despite recent significant advances in our understanding of this disease and the increasing therapeutic experience with rituximab, tocilizumab and siltuximab, there are still difficult questions concerning its etiology, prognosis and optimal treatment.</p></span>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">La enfermedad de Castleman no es una única enfermedad. Bajo este epónimo se reúne un heterogéneo grupo de trastornos linfoproliferativos no clonales, muy infrecuentes, con un amplio espectro de expresión clínica. Se han descrito 3 tipos histológicos, junto con varias formas clínicas, según la forma de presentación, el sustrato histológico y las enfermedades asociadas. La interleucina 6, los polimorfismos del receptor de esta interleucina, el virus de la inmunodeficiencia humana y el virus herpes humano tipo 8 están implicados en la etiopatogenia y su estudio ha aportado luz al conocimiento de un síndrome cuya incidencia es desconocida. A pesar de avances recientes e importantes en su conocimiento y de la progresiva experiencia terapéutica con rituximab, tocilizumab y siltuximab, aún existen preguntas difíciles de contestar con los factores etiológicos, el abordaje terapéutico óptimo y el pronóstico.</p></span>" ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: González García A, Moreno Cobo MÁ, Patier de la Peña JL. Diagnóstico y tratamiento actual de la enfermedad de Castleman. Rev Clin Esp. 2016;216:146–156.</p>" ] ] "multimedia" => array:4 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1330 "Ancho" => 2000 "Tamanyo" => 274150 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">(A) Large paracardiac mediastinal mass. (B) Prominent feeding arteries that are irrigating the mass can be identified (arrows). (C) Patient with CD in whom an anterior mediastinal mass can be observed in the CT scan. (D) There is uptake in the positron emission tomography.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1569 "Ancho" => 2000 "Tamanyo" => 252674 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">(A and B) CT scan in sagittal and axial planes, with multiple osteosclerotic lesions in the sternum, thoracic spine and lumbar spine. (C) The scintigraphy shows the same lesions, which have significant tracer uptake due to its osteoblastic activity (arrows).</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 2218 "Ancho" => 3000 "Tamanyo" => 357642 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Treatment of Castleman's disease.</p>" ] ] 3 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">ANA, antinuclear antibodies; HHV-8, human herpes virus 8; HIV, human immunodeficiency virus; HV, hyaline vascular; PC, plasmocellular; POEMS, polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes; RA, rheumatoid arthritis; SLE, systemic lupus erythematosus; TTP, thrombotic thrombocytopenic purpura.</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="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Unicentric Castleman disease \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">Multicentric Castleman disease \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">Age \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">40 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Bimodal distribution (30–40 years and 60 years) \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">Symptoms \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Local compressive symptoms<br>Occasional autoimmune manifestations \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">General symptoms<br>Autoimmune manifestations<br>Association with POEMS \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">Organomegaly \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Uncommon \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Very common \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">Adenopathies \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Midline (cervical, mediastinal, abdominal) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Multiple concomitant cervical stations \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">Fever \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Uncommon \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Very common \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">Abnormal laboratory test results \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Occasionally anemia, hypergammaglobulinemia, acute-phase reactants \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Very common: anemia, thrombopenia (Evans syndrome), hypoalbuminemia (capillary leak), increased levels of acute-phase reactants, active urinary sediment \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">Associated systemic autoimmune manifestations \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Pemphigus<br>Bronchiolitis obliterans \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Evans syndrome<br>Cutaneous vasculitis (leucocytoclastic)<br>RA, SLE<br>Positive autoantibodies (ANA, antiphospholipid, Coombs)<br>Positive cryoglobulins<br>TTP<br>Acquired hemophilia<br>Glomerulonephritis<br>Behçet disease \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">Associated diseases \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">POEMS<br>Myasthenia gravis<br>Hodgkin's and non-Hodgkin's lymphoma<br>Kaposi sarcoma<br>Dendritic cell sarcoma<br>Systemic amyloidosis<br>Interstitial nephritis<br>Pulmonary arterial hypertension<br>Lymphocytic interstitial pneumonia, pulmonary fibrosis<br>Suprarenal failure \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">Histology \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Predominates in HV over Mixed-PC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Predominates in PC over mixed and less in HV \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">Association with HIV \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \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">Association with HHV-8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes<br>There are negative HHV-8 variants \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">Prognosis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Good, if the lesion is controlled \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Aggressive<br>Recurrent<br>Occasional high mortality \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">Treatment employed \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Local therapy<br>Surgical exeresis, radiation therapy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Systemic therapy<br>(corticosteroids, chemotherapy, rituximab, siltuximab, anakinra, tocilizumab, bortezomib, lenalidomide) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1024402.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Clinical, biological and evolutionary characteristics of Castleman's disease.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:71 [ 0 => array:3 [ "identificador" => "bib0360" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Localized mediastinal lymphnode hyperplasia resembling thymoma" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "B. Castleman" 1 => "L. Iverson" 2 => "V.P. Menendez" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Cancer" "fecha" => "1956" "volumen" => "9" "paginaInicial" => "822" "paginaFinal" => "830" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/13356266" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0365" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Use of a claims database to characterize and estimate the incidence of Castleman's disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "M.C.N. Mehra" 1 => "R.A. Stellhorn" 2 => "J. Vermeulen" 3 => "A. Desai" 4 => "N.C. Munshi" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "ASH Annual Meeting Abstracts" "fecha" => "2012" "volumen" => "120" "paginaInicial" => "4253" ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0370" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Multicentric angiofollicular lymph node hyperplasia: a clinicopathologic study of 16 cases" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "D.D. Weisenburger" 1 => "B.N. Nathwani" 2 => "C.D. Winberg" 3 => "H. Rappaport" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Hum Pathol" "fecha" => "1985" "volumen" => "16" "paginaInicial" => "162" "paginaFinal" => "172" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2579015" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0375" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Development of follicular dendritic cell sarcoma in hyaline-vascular Castleman's disease of the nasopharynx: tracing its evolution by sequential biopsies" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "A.C. Chan" 1 => "K.W. Chan" 2 => "J.K. Chan" 3 => "W.Y. Au" 4 => "W.K. Ho" 5 => "W.M. Ng" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Histopathology" "fecha" => "2001" "volumen" => "38" "paginaInicial" => "510" "paginaFinal" => "518" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11422494" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0380" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "HHV-8 is associated with a plasmablastic variant of Castleman disease that is linked to HHV-8-positive plasmablastic lymphoma" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "N. Dupin" 1 => "T.L. Diss" 2 => "P. Kellam" 3 => "M. Tulliez" 4 => "M.Q. Du" 5 => "D. Sicard" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Blood" "fecha" => "2000" "volumen" => "95" "paginaInicial" => "1406" "paginaFinal" => "1412" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10666218" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0385" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Plasmablastic microlymphoma arising in human herpesvirus-8-associated multicentric Castleman disease in a human immunodeficiency virus-seronegative patient with clinical response to anti-interleukin-6 therapy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "G. Koenig" 1 => "T.M. Stevens" 2 => "D. Peker" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/his.12718" "Revista" => array:2 [ "tituloSerie" => "Histopathology" "fecha" => "2015" ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0390" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Diagnosis of Castleman's disease by identification of an immunophenotypically aberrant population of mantle zone B lymphocytes in paraffin-embedded lymph node biopsies" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D.M. Menke" 1 => "M. Tiemann" 2 => "J.K. Camoriano" 3 => "S.F. Chang" 4 => "A. Madan" 5 => "M. Chow" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Am J Clin Pathol" "fecha" => "1996" "volumen" => "105" "paginaInicial" => "268" "paginaFinal" => "276" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8602606" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0395" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The Crow-Fukase syndrome: a study of 102 cases in Japan" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "T. Nakanishi" 1 => "I. Sobue" 2 => "Y. Toyokura" 3 => "H. Nishitani" 4 => "Y. Kuroiwa" 5 => "E. Satoyoshi" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Neurology" "fecha" => "1984" "volumen" => "34" "paginaInicial" => "712" "paginaFinal" => "720" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/6539431" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0400" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The aetiology and management of Castleman disease at 50 years: translating pathophysiology to patient care" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "C. Casper" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1365-2141.2004.05311.x" "Revista" => array:6 [ "tituloSerie" => "Br J Haematol" "fecha" => "2005" "volumen" => "129" "paginaInicial" => "3" "paginaFinal" => "17" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15801951" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0405" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Interleukin-6 as a key player in systemic inflammation and joint destruction" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "J.E. Fonseca" 1 => "M.J. Santos" 2 => "H. Canhao" 3 => "E. Choy" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.autrev.2009.01.012" "Revista" => array:6 [ "tituloSerie" => "Autoimmun Rev" "fecha" => "2009" "volumen" => "8" "paginaInicial" => "538" "paginaFinal" => "542" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19189867" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0410" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Iron-deficiency anemia in Castleman disease: implication of the interleukin 6/hepcidin pathway" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.B. Arlet" 1 => "O. Hermine" 2 => "L. Darnige" 3 => "V. Ostland" 4 => "M. Westerman" 5 => "C. Badoual" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1542/peds.2010-1123" "Revista" => array:6 [ "tituloSerie" => "Pediatrics" "fecha" => "2010" "volumen" => "126" "paginaInicial" => "e1608" "paginaFinal" => "e1612" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21041280" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0415" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Pathogenic significance of interleukin-6 (IL-6/BSF-2) in Castleman's disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "K. Yoshizaki" 1 => "T. Matsuda" 2 => "N. Nishimoto" 3 => "T. Kuritani" 4 => "L. Taeho" 5 => "K. Aozasa" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Blood" "fecha" => "1989" "volumen" => "74" "paginaInicial" => "1360" "paginaFinal" => "1367" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/2788466" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0420" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical and laboratory characterization of 114 cases of Castleman disease patients from a single centre: paraneoplastic pemphigus is an unfavourable prognostic factor" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "Y. Dong" 1 => "M. Wang" 2 => "L. Nong" 3 => "L. Wang" 4 => "X. Cen" 5 => "W. Liu" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/bjh.13378" "Revista" => array:6 [ "tituloSerie" => "Br J Haematol" "fecha" => "2015" "volumen" => "169" "paginaInicial" => "834" "paginaFinal" => "842" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25824806" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0425" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Interleukin-6 receptor polymorphism is prevalent in HIV-negative Castleman disease and is associated with increased soluble interleukin-6 receptor levels" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "K. Stone" 1 => "E. Woods" 2 => "S.M. Szmania" 3 => "O.W. Stephens" 4 => "T.K. Garg" 5 => "B. Barlogie" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1371/journal.pone.0054610" "Revista" => array:5 [ "tituloSerie" => "PLoS One" "fecha" => "2013" "volumen" => "8" "paginaInicial" => "e54610" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23372742" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0430" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Interleukin 6 induces the expression of vascular endothelial growth factor" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "T. Cohen" 1 => "D. Nahari" 2 => "L.W. Cerem" 3 => "G. Neufeld" 4 => "B.Z. Levi" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Biol Chem" "fecha" => "1996" "volumen" => "271" "paginaInicial" => "736" "paginaFinal" => "741" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8557680" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0435" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Expression of vascular endothelial growth factor in sera and lymph nodes of the plasma cell type of Castleman's disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Nishi" 1 => "K. Arimura" 2 => "A. Utsunomiya" 3 => "S. Yonezawa" 4 => "K. Kawakami" 5 => "N. Maeno" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Br J Haematol" "fecha" => "1999" "volumen" => "104" "paginaInicial" => "482" "paginaFinal" => "485" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10086783" "web" => "Medline" ] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0440" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Anti-interleukin 6 (IL-6) receptor antibody suppresses Castleman's disease like symptoms emerged in IL-6 transgenic mice" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Katsume" 1 => "H. Saito" 2 => "Y. Yamada" 3 => "K. Yorozu" 4 => "O. Ueda" 5 => "K. Akamatsu" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Cytokine" "fecha" => "2002" "volumen" => "20" "paginaInicial" => "304" "paginaFinal" => "311" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12633573" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0445" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi's sarcoma" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "Y. Chang" 1 => "E. Cesarman" 2 => "M.S. Pessin" 3 => "F. Lee" 4 => "J. Culpepper" 5 => "D.M. Knowles" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Science" "fecha" => "1994" "volumen" => "266" "paginaInicial" => "1865" "paginaFinal" => "1869" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7997879" "web" => "Medline" ] ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0450" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Highly selective escape from KSHV-mediated host mRNA shutoff and its implications for viral pathogenesis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "B. Glaunsinger" 1 => "D. Ganem" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1084/jem.20031881" "Revista" => array:6 [ "tituloSerie" => "J Exp Med" "fecha" => "2004" "volumen" => "200" "paginaInicial" => "391" "paginaFinal" => "398" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15289507" "web" => "Medline" ] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0455" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Plasma HHV8 DNA predicts relapse in individuals with HIV-associated multicentric Castleman disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Stebbing" 1 => "C. Adams" 2 => "A. Sanitt" 3 => "S. Mletzko" 4 => "M. Nelson" 5 => "B. Gazzard" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1182/blood-2011-02-335620" "Revista" => array:6 [ "tituloSerie" => "Blood" "fecha" => "2011" "volumen" => "118" "paginaInicial" => "271" "paginaFinal" => "275" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21511959" "web" => "Medline" ] ] ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0460" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Kaposi's sarcoma-associated herpesvirus-like DNA sequences in multicentric Castleman's disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Soulier" 1 => "L. Grollet" 2 => "E. Oksenhendler" 3 => "P. Cacoub" 4 => "D. Cazals-Hatem" 5 => "P. Babinet" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Blood" "fecha" => "1995" "volumen" => "86" "paginaInicial" => "1276" "paginaFinal" => "1280" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7632932" "web" => "Medline" ] ] ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0465" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Kaposi sarcoma-associated herpesvirus infects monotypic (IgM lambda) but polyclonal naive B cells in Castleman disease and associated lymphoproliferative disorders" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.Q. Du" 1 => "H. Liu" 2 => "T.C. Diss" 3 => "H. Ye" 4 => "R.A. Hamoudi" 5 => "N. Dupin" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Blood" "fecha" => "2001" "volumen" => "97" "paginaInicial" => "2130" "paginaFinal" => "2136" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11264181" "web" => "Medline" ] ] ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib0470" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "HIV infection is active and progressive in lymphoid tissue during the clinically latent stage of disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "G. Pantaleo" 1 => "C. Graziosi" 2 => "J.F. Demarest" 3 => "L. Butini" 4 => "M. Montroni" 5 => "C.H. Fox" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/362355a0" "Revista" => array:6 [ "tituloSerie" => "Nature" "fecha" => "1993" "volumen" => "362" "paginaInicial" => "355" "paginaFinal" => "358" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8455722" "web" => "Medline" ] ] ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0475" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Surgery in Castleman's disease: a systematic review of 404 published cases" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "N. Talat" 1 => "A.P. Belgaumkar" 2 => "K.M. Schulte" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/SLA.0b013e318249dcdc" "Revista" => array:6 [ "tituloSerie" => "Ann Surg" "fecha" => "2012" "volumen" => "255" "paginaInicial" => "677" "paginaFinal" => "684" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22367441" "web" => "Medline" ] ] ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib0480" "etiqueta" => "25" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Castleman's tumours and production of autoantibody in paraneoplastic pemphigus" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "L. Wang" 1 => "D. Bu" 2 => "Y. Yang" 3 => "X. Chen" 4 => "X. Zhu" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(04)15539-6" "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "2004" "volumen" => "363" "paginaInicial" => "525" "paginaFinal" => "531" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14975615" "web" => "Medline" ] ] ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib0485" "etiqueta" => "26" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "CD8+ T lymphocytes in bronchiolitis obliterans, paraneoplastic pemphigus, and solitary Castleman's disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "M.A. Hoffman" 1 => "X. Qiao" 2 => "G.J. Anhalt" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJM200307243490421" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2003" "volumen" => "349" "paginaInicial" => "407" "paginaFinal" => "408" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12878753" "web" => "Medline" ] ] ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib0490" "etiqueta" => "27" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Paraneoplastic pemphigus in association with Castleman's disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "O.V. Nikolskaia" 1 => "C.H. Nousari" 2 => "G.J. Anhalt" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Br J Dermatol" "fecha" => "2003" "volumen" => "149" "paginaInicial" => "1143" "paginaFinal" => "1151" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14674890" "web" => "Medline" ] ] ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib0495" "etiqueta" => "28" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Multicentric Castleman's disease in HIV infection: a clinical and pathological study of 20 patients" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "E. Oksenhendler" 1 => "M. Duarte" 2 => "J. Soulier" 3 => "P. Cacoub" 4 => "Y. Welker" 5 => "J. Cadranel" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "AIDS" "fecha" => "1996" "volumen" => "10" "paginaInicial" => "61" "paginaFinal" => "67" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8924253" "web" => "Medline" ] ] ] ] ] ] ] ] 28 => array:3 [ "identificador" => "bib0500" "etiqueta" => "29" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical epidemiology and treatment patterns of patients with multicentric Castleman disease: results from 2 US treatment centres" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D. Robinson Jr." 1 => "M. Reynolds" 2 => "C. Casper" 3 => "A. Dispenzieri" 4 => "J. Vermeulen" 5 => "K. Payne" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/bjh.12717" "Revista" => array:6 [ "tituloSerie" => "Br J Haematol" "fecha" => "2014" "volumen" => "165" "paginaInicial" => "39" "paginaFinal" => "48" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24387011" "web" => "Medline" ] ] ] ] ] ] ] ] 29 => array:3 [ "identificador" => "bib0505" "etiqueta" => "30" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The role of immune suppression and HHV-8 in the increasing incidence of HIV-associated multicentric Castleman's disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "T. Powles" 1 => "J. Stebbing" 2 => "A. Bazeos" 3 => "E. Hatzimichael" 4 => "S. Mandalia" 5 => "M. Nelson" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/annonc/mdn697" "Revista" => array:6 [ "tituloSerie" => "Ann Oncol" "fecha" => "2009" "volumen" => "20" "paginaInicial" => "775" "paginaFinal" => "779" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19179554" "web" => "Medline" ] ] ] ] ] ] ] ] 30 => array:3 [ "identificador" => "bib0510" "etiqueta" => "31" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "An unusual presentation of Castleman's disease: a case report" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "I.S. Izuchukwu" 1 => "K. Tourbaf" 2 => "M.C. Mahoney" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/1471-2334-3-20" "Revista" => array:5 [ "tituloSerie" => "BMC Infect Dis" "fecha" => "2003" "volumen" => "3" "paginaInicial" => "20" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12969507" "web" => "Medline" ] ] ] ] ] ] ] ] 31 => array:3 [ "identificador" => "bib0515" "etiqueta" => "32" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "HHV-8-negative, idiopathic multicentric Castleman disease: novel insights into biology, pathogenesis, and therapy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "D.C. Fajgenbaum" 1 => "F. van Rhee" 2 => "C.S. Nabel" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1182/blood-2013-12-545087" "Revista" => array:6 [ "tituloSerie" => "Blood" "fecha" => "2014" "volumen" => "123" "paginaInicial" => "2924" "paginaFinal" => "2933" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24622327" "web" => "Medline" ] ] ] ] ] ] ] ] 32 => array:3 [ "identificador" => "bib0520" "etiqueta" => "33" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The clinical behavior of localized and multicentric Castleman disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "J. Herrada" 1 => "F. Cabanillas" 2 => "L. Rice" 3 => "J. Manning" 4 => "W. Pugh" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Ann Intern Med" "fecha" => "1998" "volumen" => "128" "paginaInicial" => "657" "paginaFinal" => "662" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9537940" "web" => "Medline" ] ] ] ] ] ] ] ] 33 => array:3 [ "identificador" => "bib0525" "etiqueta" => "34" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "POEMS syndrome: update on diagnosis, risk-stratification, and management" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "A. Dispenzieri" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/ajh.24171" "Revista" => array:6 [ "tituloSerie" => "Am J Hematol" "fecha" => "2015" "volumen" => "90" "paginaInicial" => "951" "paginaFinal" => "962" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26331353" "web" => "Medline" ] ] ] ] ] ] ] ] 34 => array:3 [ "identificador" => "bib0530" "etiqueta" => "35" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The clinical spectrum of Castleman's disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Dispenzieri" 1 => "J.O. Armitage" 2 => "M.J. Loe" 3 => "S.M. Geyer" 4 => "J. Allred" 5 => "J.K. Camoriano" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/ajh.23291" "Revista" => array:6 [ "tituloSerie" => "Am J Hematol" "fecha" => "2012" "volumen" => "87" "paginaInicial" => "997" "paginaFinal" => "1002" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22791417" "web" => "Medline" ] ] ] ] ] ] ] ] 35 => array:3 [ "identificador" => "bib0535" "etiqueta" => "36" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Papilledema as the initial presentation of Castleman disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "G. Tian" 1 => "Y. Jing" 2 => "H. Jiang" 3 => "J. Wang" 4 => "X. Zhang" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/WNO.0000000000000096" "Revista" => array:6 [ "tituloSerie" => "J Neuroophthalmol" "fecha" => "2014" "volumen" => "34" "paginaInicial" => "169" "paginaFinal" => "172" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24423600" "web" => "Medline" ] ] ] ] ] ] ] ] 36 => array:3 [ "identificador" => "bib0540" "etiqueta" => "37" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Castleman-Kojima disease (TAFRO syndrome): a novel systemic inflammatory disease characterized by a constellation of symptoms, namely, thrombocytopenia, ascites (anasarca), microcytic anemia, myelofibrosis, renal dysfunction, and organomegaly: a status report and summary of Fukushima (6 June, 2012) and Nagoya meetings (22 September, 2012)" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "H. Kawabata" 1 => "K. Takai" 2 => "M. Kojima" 3 => "N. Nakamura" 4 => "S. Aoki" 5 => "S. Nakamura" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Clin Exp Hematop" "fecha" => "2013" "volumen" => "53" "paginaInicial" => "57" "paginaFinal" => "61" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23801135" "web" => "Medline" ] ] ] ] ] ] ] ] 37 => array:3 [ "identificador" => "bib0545" "etiqueta" => "38" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Pulmonary manifestations of multicentric Castleman's disease in HIV infection: a clinical, biological and radiological study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Guihot" 1 => "L.J. Couderc" 2 => "F. Agbalika" 3 => "L. Galicier" 4 => "P. Bossi" 5 => "E. Rivaud" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1183/09031936.05.00130304" "Revista" => array:6 [ "tituloSerie" => "Eur Respir J" "fecha" => "2005" "volumen" => "26" "paginaInicial" => "118" "paginaFinal" => "125" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15994398" "web" => "Medline" ] ] ] ] ] ] ] ] 38 => array:3 [ "identificador" => "bib0550" "etiqueta" => "39" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Human herpesvirus 8-related Castleman disease in the absence of HIV infection" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "A. Dossier" 1 => "V. Meignin" 2 => "C. Fieschi" 3 => "D. Boutboul" 4 => "E. Oksenhendler" 5 => "L. Galicier" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/cid/cis1009" "Revista" => array:6 [ "tituloSerie" => "Clin Infect Dis" "fecha" => "2013" "volumen" => "56" "paginaInicial" => "833" "paginaFinal" => "842" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23223599" "web" => "Medline" ] ] ] ] ] ] ] ] 39 => array:3 [ "identificador" => "bib0555" "etiqueta" => "40" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Evans syndrome as presentation of multicenter Castleman disease [en español]" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "A. Muela Molinero" 1 => "B. Ballesteros del Rio" 2 => "V. Sandoval Guerra" 3 => "J. Llor Banos" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Rev Clin Esp" "fecha" => "2003" "volumen" => "203" "paginaInicial" => "616" "paginaFinal" => "617" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14622519" "web" => "Medline" ] ] ] ] ] ] ] ] 40 => array:3 [ "identificador" => "bib0560" "etiqueta" => "41" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Castleman disease and associated autoimmune disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "T.W. Muskardin" 1 => "B.A. Peterson" 2 => "J.A. Molitor" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/BOR.0b013e32834db525" "Revista" => array:6 [ "tituloSerie" => "Curr Opin Rheumatol" "fecha" => "2012" "volumen" => "24" "paginaInicial" => "76" "paginaFinal" => "83" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22157415" "web" => "Medline" ] ] ] ] ] ] ] ] 41 => array:3 [ "identificador" => "bib0565" "etiqueta" => "42" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Treatment of unicentric Castleman disease with neoadjuvant rituximab" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "B. Bandera" 1 => "C. Ainsworth" 2 => "J. Shikle" 3 => "E. Rupard" 4 => "M. Roach" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1378/chest.09-2084" "Revista" => array:6 [ "tituloSerie" => "Chest" "fecha" => "2010" "volumen" => "138" "paginaInicial" => "1239" "paginaFinal" => "1241" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21051400" "web" => "Medline" ] ] ] ] ] ] ] ] 42 => array:3 [ "identificador" => "bib0570" "etiqueta" => "43" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Unicentric Castleman disease relapsed after rituximab-CHOP chemotherapy or radiation therapy in an adolescent" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "H.J. Baek" 1 => "H. Kook" 2 => "D.K. Han" 3 => "M.G. Shin" 4 => "H.S. Kim" 5 => "T.J. Hwang" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/MPH.0b013e3182352dc7" "Revista" => array:6 [ "tituloSerie" => "J Pediatr Hematol Oncol" "fecha" => "2012" "volumen" => "34" "paginaInicial" => "e206" "paginaFinal" => "e208" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22258344" "web" => "Medline" ] ] ] ] ] ] ] ] 43 => array:3 [ "identificador" => "bib0575" "etiqueta" => "44" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Successful treatment of mediastinal unicentric Castleman's disease using video-assisted thoracoscopic surgery with preoperative embolization" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "Y. Amano" 1 => "D. Takai" 2 => "N. Ohishi" 3 => "A. Shinozaki-Ushiku" 4 => "M. Fukayama" 5 => "M. Akahane" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1155/2013/354507" "Revista" => array:5 [ "tituloSerie" => "Case Rep Med" "fecha" => "2013" "volumen" => "2013" "paginaInicial" => "354507" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24198836" "web" => "Medline" ] ] ] ] ] ] ] ] 44 => array:3 [ "identificador" => "bib0580" "etiqueta" => "45" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cases report of unicentric Castleman's disease: revisit of radiotherapy role" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "O.K. Noh" 1 => "S.W. Lee" 2 => "J.W. Lee" 3 => "S.Y. Kim" 4 => "C.S. Kim" 5 => "E.K. Choi" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3857/roj.2013.31.1.48" "Revista" => array:6 [ "tituloSerie" => "Radiat Oncol J" "fecha" => "2013" "volumen" => "31" "paginaInicial" => "48" "paginaFinal" => "54" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23620869" "web" => "Medline" ] ] ] ] ] ] ] ] 45 => array:3 [ "identificador" => "bib0585" "etiqueta" => "46" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Siltuximab for multicentric Castleman's disease: a randomised, double-blind, placebo-controlled trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "F. Van Rhee" 1 => "R.S. Wong" 2 => "N. Munshi" 3 => "J.F. Rossi" 4 => "X.Y. Ke" 5 => "A. Fossa" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S1470-2045(14)70319-5" "Revista" => array:6 [ "tituloSerie" => "Lancet Oncol" "fecha" => "2014" "volumen" => "15" "paginaInicial" => "966" "paginaFinal" => "974" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25042199" "web" => "Medline" ] ] ] ] ] ] ] ] 46 => array:3 [ "identificador" => "bib0590" "etiqueta" => "47" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Treatment of HIV-associated multicentric Castleman's disease with oral etoposide" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "D. Scott" 1 => "L. Cabral" 2 => "W.J. Harrington Jr." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/1096-8652(200102)66:2<148::AID-AJH1034>3.0.CO;2-P" "Revista" => array:6 [ "tituloSerie" => "Am J Hematol" "fecha" => "2001" "volumen" => "66" "paginaInicial" => "148" "paginaFinal" => "150" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11421297" "web" => "Medline" ] ] ] ] ] ] ] ] 47 => array:3 [ "identificador" => "bib0595" "etiqueta" => "48" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Multicentric Castleman's disease treated with combination chemotherapy and rituximab in 4 HIV-positive men: a case series" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "A. Bestawros" 1 => "R. Michel" 2 => "C. Seguin" 3 => "J.P. Routy" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/ajh.21108" "Revista" => array:6 [ "tituloSerie" => "Am J Hematol" "fecha" => "2008" "volumen" => "83" "paginaInicial" => "508" "paginaFinal" => "511" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18027834" "web" => "Medline" ] ] ] ] ] ] ] ] 48 => array:3 [ "identificador" => "bib0600" "etiqueta" => "49" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A systemic lymphoproliferative disorder with morphologic features of Castleman's disease: clinical findings and clinicopathologic correlations in 15 patients" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "G. Frizzera" 1 => "B.A. Peterson" 2 => "E.D. Bayrd" 3 => "A. Goldman" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1200/jco.1985.3.9.1202" "Revista" => array:6 [ "tituloSerie" => "J Clin Oncol" "fecha" => "1985" "volumen" => "3" "paginaInicial" => "1202" "paginaFinal" => "1216" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/4031967" "web" => "Medline" ] ] ] ] ] ] ] ] 49 => array:3 [ "identificador" => "bib0605" "etiqueta" => "50" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical features and outcome in HIV-associated multicentric Castleman's disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Bower" 1 => "T. Newsom-Davis" 2 => "K. Naresh" 3 => "S. Merchant" 4 => "B. Lee" 5 => "B. Gazzard" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1200/JCO.2010.34.1909" "Revista" => array:6 [ "tituloSerie" => "J Clin Oncol" "fecha" => "2011" "volumen" => "29" "paginaInicial" => "2481" "paginaFinal" => "2486" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21555697" "web" => "Medline" ] ] ] ] ] ] ] ] 50 => array:3 [ "identificador" => "bib0610" "etiqueta" => "51" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "How I treat HIV-associated multicentric Castleman disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "M. Bower" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1182/blood-2010-07-290213" "Revista" => array:6 [ "tituloSerie" => "Blood" "fecha" => "2010" "volumen" => "116" "paginaInicial" => "4415" "paginaFinal" => "4421" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20688959" "web" => "Medline" ] ] ] ] ] ] ] ] 51 => array:3 [ "identificador" => "bib0615" "etiqueta" => "52" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Long-term remission in HIV-negative patients with multicentric Castleman's disease using rituximab" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "M. Ide" 1 => "Y. Kawachi" 2 => "Y. Izumi" 3 => "K. Kasagi" 4 => "T. Ogino" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1600-0609.2005.00570.x" "Revista" => array:6 [ "tituloSerie" => "Eur J Haematol" "fecha" => "2006" "volumen" => "76" "paginaInicial" => "119" "paginaFinal" => "123" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16405432" "web" => "Medline" ] ] ] ] ] ] ] ] 52 => array:3 [ "identificador" => "bib0620" "etiqueta" => "53" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Use of rituximab as a salvage therapy for HIV-associated multicentric Castleman disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "A. Casquero" 1 => "A. Barroso" 2 => "M.L. Fernandez Guerrero" 3 => "M. Gorgolas" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00277-005-0038-4" "Revista" => array:6 [ "tituloSerie" => "Ann Hematol" "fecha" => "2006" "volumen" => "85" "paginaInicial" => "185" "paginaFinal" => "187" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16341862" "web" => "Medline" ] ] ] ] ] ] ] ] 53 => array:3 [ "identificador" => "bib0625" "etiqueta" => "54" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Efficacy of rituximab in an aggressive form of multicentric Castleman disease associated with immune phenomena" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "E.M. Ocio" 1 => "F.M. Sanchez-Guijo" 2 => "M. Diez-Campelo" 3 => "C. Castilla" 4 => "O.J. Blanco" 5 => "D. Caballero" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/ajh.20283" "Revista" => array:6 [ "tituloSerie" => "Am J Hematol" "fecha" => "2005" "volumen" => "78" "paginaInicial" => "302" "paginaFinal" => "305" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15795923" "web" => "Medline" ] ] ] ] ] ] ] ] 54 => array:3 [ "identificador" => "bib0630" "etiqueta" => "55" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Rituximab decreases the risk of lymphoma in patients with HIV-associated multicentric Castleman disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "L. Gerard" 1 => "J.M. Michot" 2 => "S. Burcheri" …3 ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1182/blood-2011-08-376012" "Revista" => array:6 [ "tituloSerie" => "Blood" "fecha" => "2012" "volumen" => "119" "paginaInicial" => "2228" "paginaFinal" => "2233" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 55 => array:3 [ "identificador" => "bib0635" "etiqueta" => "56" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Parsonage-Turner syndrome during the treatment of HIV/HHV8-related multicentric Castleman disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.rce.2013.11.009" "Revista" => array:6 [ "tituloSerie" => "Rev Clin Esp" "fecha" => "2014" "volumen" => "214" "paginaInicial" => "e15" "paginaFinal" => "e17" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 56 => array:3 [ "identificador" => "bib0640" "etiqueta" => "57" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prospective study of rituximab in chemotherapy-dependent human immunodeficiency virus associated multicentric Castleman's disease: ANRS 117 CastlemaB Trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1200/JCO.2007.10.6732" "Revista" => array:6 [ "tituloSerie" => "J Clin Oncol" "fecha" => "2007" "volumen" => "25" "paginaInicial" => "3350" "paginaFinal" => "3356" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 57 => array:3 [ "identificador" => "bib0645" "etiqueta" => "58" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Brief report: alleviation of systemic manifestations of Castleman's disease by monoclonal anti-interleukin-6 antibody" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJM199403033300904" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "1994" "volumen" => "330" "paginaInicial" => "602" "paginaFinal" => "605" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 58 => array:3 [ "identificador" => "bib0650" "etiqueta" => "59" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Siltuximab, a novel anti-interleukin-6 monoclonal antibody, for Castleman's disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1200/JCO.2009.27.2377" "Revista" => array:6 [ "tituloSerie" => "J Clin Oncol" "fecha" => "2010" "volumen" => "28" "paginaInicial" => "3701" "paginaFinal" => "3708" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 59 => array:3 [ "identificador" => "bib0655" "etiqueta" => "60" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A phase I, open-label study of siltuximab, an anti-IL-6 monoclonal antibody, in patients with B-cell non-Hodgkin lymphoma, multiple myeloma, or Castleman disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1158/1078-0432.CCR-12-3349" "Revista" => array:6 [ "tituloSerie" => "Clin Cancer Res" "fecha" => "2013" "volumen" => "19" "paginaInicial" => "3659" "paginaFinal" => "3670" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 60 => array:3 [ "identificador" => "bib0660" "etiqueta" => "61" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Humanized anti-interleukin-6 receptor antibody treatment of multicentric Castleman disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1182/blood-2004-12-4602" "Revista" => array:6 [ "tituloSerie" => "Blood" "fecha" => "2005" "volumen" => "106" "paginaInicial" => "2627" "paginaFinal" => "2632" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 61 => array:3 [ "identificador" => "bib0665" "etiqueta" => "62" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "High levels of human herpesvirus 8 viral load, human interleukin-6, interleukin-10, and C reactive protein correlate with exacerbation of multicentric Castleman disease in HIV-infected patients" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Blood" "fecha" => "2000" "volumen" => "96" "paginaInicial" => "2069" "paginaFinal" => "2073" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 62 => array:3 [ "identificador" => "bib0670" "etiqueta" => "63" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "High-dose zidovudine plus valganciclovir for Kaposi sarcoma herpesvirus-associated multicentric Castleman disease: a pilot study of virus-activated cytotoxic therapy" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1182/blood-2010-11-317610" "Revista" => array:6 [ "tituloSerie" => "Blood" "fecha" => "2011" "volumen" => "117" "paginaInicial" => "6977" "paginaFinal" => "6986" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 63 => array:3 [ "identificador" => "bib0675" "etiqueta" => "64" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Successful treatment of Castleman's disease with interleukin-1 receptor antagonist (anakinra)" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ …3] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1158/1535-7163.MCT-10-0156" "Revista" => array:6 [ "tituloSerie" => "Mol Cancer Ther" "fecha" => "2010" "volumen" => "9" "paginaInicial" => "1485" "paginaFinal" => "1488" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 64 => array:3 [ "identificador" => "bib0680" "etiqueta" => "65" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Therapeutic benefit of bortezomib on acute graft-versus-host disease is tissue specific and is associated with interleukin-6 levels" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.bbmt.2014.07.022" "Revista" => array:6 [ "tituloSerie" => "Biol Blood Marrow Transplant" "fecha" => "2014" "volumen" => "20" "paginaInicial" => "1899" "paginaFinal" => "1904" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 65 => array:3 [ "identificador" => "bib0685" "etiqueta" => "66" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Successful treatment of multicentric Castleman's disease accompanying myeloma with bortezomib" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ …4] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:3 [ "tituloSerie" => "BMJ Case Rep" "fecha" => "2012" "paginaInicial" => "2012" ] ] ] ] ] ] 66 => array:3 [ "identificador" => "bib0690" "etiqueta" => "67" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Successful treatment with bortezomib and thalidomide for POEMS syndrome associated with multicentric mixed-type Castleman's disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/jjco/hyr120" "Revista" => array:6 [ "tituloSerie" => "Jpn J Clin Oncol" "fecha" => "2011" "volumen" => "41" "paginaInicial" => "1221" "paginaFinal" => "1224" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 67 => array:3 [ "identificador" => "bib0695" "etiqueta" => "68" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Efficacy of bortezomib in refractory form of multicentric Castleman disease associated to poems syndrome (MCD-POEMS variant)" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00277-009-0795-6" "Revista" => array:6 [ "tituloSerie" => "Ann Hematol" "fecha" => "2010" "volumen" => "89" "paginaInicial" => "217" "paginaFinal" => "219" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 68 => array:3 [ "identificador" => "bib0700" "etiqueta" => "69" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Rituximab and thalidomide combination therapy for Castleman disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1365-2141.2012.09157.x" "Revista" => array:6 [ "tituloSerie" => "Br J Haematol" "fecha" => "2012" "volumen" => "158" "paginaInicial" => "421" "paginaFinal" => "423" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 69 => array:3 [ "identificador" => "bib0705" "etiqueta" => "70" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Lenalidomide: a new treatment option for Castleman disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3109/10428194.2011.621564" "Revista" => array:6 [ "tituloSerie" => "Leuk Lymphoma" "fecha" => "2012" "volumen" => "53" "paginaInicial" => "2089" "paginaFinal" => "2091" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] 70 => array:3 [ "identificador" => "bib0710" "etiqueta" => "71" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Thalidomide for tocilizumab-resistant ascites with TAFRO syndrome" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ …6] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/ccr3.284" "Revista" => array:6 [ "tituloSerie" => "Clin Case Rep" "fecha" => "2015" "volumen" => "3" "paginaInicial" => "472" "paginaFinal" => "478" "link" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/22548874/0000021600000003/v1_201604010056/S2254887416000047/v1_201604010056/en/main.assets" "Apartado" => array:4 [ "identificador" => "48740" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Reviews" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/22548874/0000021600000003/v1_201604010056/S2254887416000047/v1_201604010056/en/main.pdf?idApp=WRCEE&text.app=https://revclinesp.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2254887416000047?idApp=WRCEE" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2023 March | 2 | 3 | 5 |
| 2019 October | 1 | 2 | 3 |
| 2018 April | 1 | 0 | 1 |
| 2016 April | 0 | 1 | 1 |
| 2016 February | 0 | 5 | 5 |
