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Neuro-ophthalmological manifestations of POEMS syndrome
Manifestaciones neurooftalmológicas del síndrome de POEMS
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"apellidos" => "Hermoso Fernández" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0365669119301856" "doi" => "10.1016/j.oftal.2019.05.015" "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/S0365669119301856?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173579419301380?idApp=UINPBA00004N" "url" => "/21735794/0000009400000010/v1_201910010751/S2173579419301380/v1_201910010751/en/main.assets" ] "en" => array:20 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Short communication</span>" "titulo" => "Neuro-ophthalmological manifestations of POEMS syndrome" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "495" "paginaFinal" => "499" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "A. Ortiz Zapata, P.L. Cárdenas, M.F. Acuña, M. Peralta Álvarez, J. Ortiz Zapata, B. Pizarro Imaicela" "autores" => array:6 [ 0 => array:4 [ "nombre" => "A." "apellidos" => "Ortiz Zapata" "email" => array:1 [ 0 => "docaortizoft@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "P.L." "apellidos" => "Cárdenas" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "M.F." "apellidos" => "Acuña" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "M." "apellidos" => "Peralta Álvarez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 4 => array:3 [ "nombre" => "J." "apellidos" => "Ortiz Zapata" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 5 => array:3 [ "nombre" => "B." "apellidos" => "Pizarro Imaicela" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Centro de Especialidades Oftalmológicas ALJAORZA (CEOA), Machala, Ecuador" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Fundación Oftalmológica de Santander, Clínica Carlos Ardila Lulle (FOSCAL), Bucaramanga, Colombia" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Clínica de Traumatología, Machala, Ecuador" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Escuela de Medicina, Universidad Técnica de Machala, Machala, Ecuador" "etiqueta" => "d" "identificador" => "aff0020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "<span class="elsevierStyleItalic">Corresponding author</span>." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Manifestaciones neurooftalmológicas del síndrome de POEMS" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1785 "Ancho" => 2511 "Tamanyo" => 424270 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Compostite image of right eye (RE) and left eye (LE) at baseline assessment. (A) Color photograph showing optic disc edema. (B) Fluorescing angiography in late times showing optic disc staining due to edema. (C) Macular thickness map taken with OCT HD macular SD, showing thicknesses of 441<span class="elsevierStyleHsp" style=""></span>μm in RE and 405<span class="elsevierStyleHsp" style=""></span>um in LE. (D) OCT HD macular SD evidencing bilateral serous detachment of neuroepithelium at the subfoveal level, in addition to follow-up with color photograph and OCT HD macular SD post-treatment months 1 and 3, showing diminished optic disc edema and significant improvement of bilateral serous detachments at the foveal level.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">The POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy, and Skin changes) is an infrequent and relatively unknown disease of plasmatic cells, with multisystemic compromise mainly in middle-aged males. It was first described by Scheinker in 1938. It has also been known as the Crow–Fukase syndrome, the Takatsuki syndrome or osteosclerotic myeloma.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Due to the heterogeneity of its expressions as illustrated by the POEMS acronym, its diagnostic could be complex and liable to be misinterpreted as chronic demyelinizing inflammatory neuropathy in up to 60%<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> of cases, or as other diseases. Even though the physiopathology of POEMS is not entirely clear, a chronic increase of proinflammatory cytokins has been evidenced, including IL-1, IL-6, IL-12, FNT-α and vascular endothelial growth factor (VEGF), inducing angiogenesis and increased vascular permeability, which could explain the diversity of clinic expressions of the disease.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The case of a patient with a POEMS syndrome diagnostic is presented. The disease debuted with ocular symptoms to subsequently develop multiple neuro-ophthalmological and systemic expressions, which receded with systemic chemotherapy based on dexamethasone and melphalan at 3 months follow-up.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Clinic case report</span><p id="par0015" class="elsevierStylePara elsevierViewall">Male, 38, who consulted due to a condition beginning 2 months earlier characterized by headache, bilateral blurry vision and myodesopsiae. In addition, the patient exhibited constitutional syndrome, fever and multiple adenopathies, for which reasons he was examined at the emergency department where liver and spleen megalia were documented, and tumoral lysis syndrome was indicated, with specific treatment being administered. Ophthalmological examination produced a corrected visual acuity of 20/50 and 20/200 in each eye, while the anterior segment did not exhibit alterations, with pupil reflexes remaining stable. Ocular fundus evidenced raised discs, blurred edges with flame hemorrhages and axoplasmatic deposits, absence of spontaneous venous pulsation, in addition to multiple retina pigment epithelium serous detachments, which were larger in the left eye (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). Complementary studies in both eyes revealed a neurological visual field with increased blind spot. Optical coherence tomography of the optic nerve showed an increased thickness of the nerve fiber layer reaching 464<span class="elsevierStyleHsp" style=""></span>μm in the right eye and 432<span class="elsevierStyleHsp" style=""></span>μm in the left eye, with diffuse reduction of the ganglion cell complex at the macular level and RPE multifocal detachment at the foveal level. Fluorescein angiography showed disc hyperfluorescence in late stages; standard electroretinogram evidenced significant compromise of cones and rods in addition to perception alteration and nerve stimuli conduction in visual evoked potential. Neuroimaging studies were essentially normal, with discrete distention of the bilateral perioptical sheath.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">During the hospital stay, the patient presented sensory-motor paraparesis with sphinter relaxation documented by means of electromyography, increased azoates in blood in addition to anasarca, polyserositis, subclinic hypothyroidism, diffuse skin alterations (sclerodactyly and acropachy) and generalized bone pain secondary to multiple osteoblastic lesions in long bones and spinal column, documented by means of bone gammagraphy, with negative biopsies. Causes such as multiple myeloma and selfimmune or infectious diseases were excluded. Tumor markers were negative. Lumbar puncture evidenced increased aperture pressure (38<span class="elsevierStyleHsp" style=""></span>cmH<span class="elsevierStyleInf">2</span>O), indicating idiopathic intracranial hypertension associated to hyper- proteinorachie. Treatment with oral acetazolamide was initiated. Monoclonal gammapathy was documented in blood with raised lambda chains in blood and urine. Axillary ganglion biopsy indicated Castleman’s disease, discarding malignity. Bone marrow aspiration with immunohistochemistry discarded tumor infiltration with plasmocytosis. VEGF levels in blood were increased, leading to consider the POEMS syndrome diagnostic and initiating systemic chemotherapy (dexamethasone/melphalan) with positive systemic response. The use of anti-VEGF or intravitreal steroids was not considered due to diagnostic difficulties and late diagnostic. Three months later motility and sensitivity in all 4 limbs partially improved, together with significant reduction in polyserositis and bone pain. At the neuro-opthalmological level, vision improved to reach 20/30 bilateral, with diminished thickness of the nerve fiber layer at the disc level and reduction of neuro-epithelium serous detachments (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). Electrophysiological studies demonstrated improvements in photoreceptors and nerve transmission in reference to the visual pathway.</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Discussion</span><p id="par0025" class="elsevierStylePara elsevierViewall">Even though the mechanisms leading to the development of the POEMS syndrome are not entirely elucidated, the increase of pro-inflammatory substances and cytokins, mainly VEGF, points to increased vascular permeability, hydro-electrolytic dysregulation and heterogeneous clinic expressions. The physiopathology of POEMS is shared by a number of entities including paraneoplastic syndromes and even some diseases with selfimmune characteristics such as those related to IgG4 and infectious processes, but above all with blood diseases such as the TAFRO syndrome, a variant of Castleman’s disease, the diagnostic criteria of which require the exclusion of the POEMS syndrome.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> The diagnostic criteria of POEMS was described by Dispenzieri in 2003 and modified with the passage of time. The latest update was released in 2018 by Suichi (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>), in which VEGF was catalogued as a major criteria for the disease, thus improving sensitivity and specificity. In contrast, the papiledema of the original description was removed.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">There are multiple neuro-opthalmological expressions associated to the POEMS syndrome, with papiledema being the most frequent with an incidence between 29 and 64%.<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6,7</span></a> It is characterized by being bilateral and chronic and the possibility of compromising vision in late stages but without reaching optic atrophy. Theories that endeavor to explain the physiopathology of POEMS range from angiogenesis phenomena and secondary to intracranial hypertension as in the present case. Other expressions include visual field loss which could be central and secondary to an increase in blind spots, or peripheral, as well as diplopia, macular edema, retinal serous detachments and neovascularization with increased choroidal thickness<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6,7</span></a> which has been confirmed by optical coherence tomography studies and directly correlated to VEGF levels.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> Some publications report vascular ischemic events at the level of the central retinal artery as a consequence of the POEMS syndrome,<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> although these episodes can occur in any visual pathway territory and produce significant campimetric defects.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Local ophthalmological management includes intravitreal application of anti-VEGF, vitrectomy with triamcinolone injection and even the use of acetazolamide to diminish vascular permeability. At the systemic level, treatment includes radiation, high doses of corticoids, alkylating drugs such as a cyclophosphamide or melphalan, and anti-TNF and anti-VEGF agents.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,5,10</span></a> Other treatments include interferon alpha, azathioprine, intravenous immunoglobulin or plasmapheresis and some authos even recommend autologous transplant of hematopoietic stem cells, with good response at 10 years.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">By way of conclusion, neuro-opthalmological expressions are frequent findings in patients with POEMS syndrome. Multidisciplinary management, together with local and systemic treatment, could help to improve visual and systemic symptomatology of said disease.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Conflict of interests</span><p id="par0045" class="elsevierStylePara elsevierViewall">No conflict of interests was declared by the authors.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:9 [ 0 => array:3 [ "identificador" => "xres1250890" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1159778" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1250891" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1159779" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Clinic case report" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Discussion" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Conflict of interests" ] 8 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2019-04-02" "fechaAceptado" => "2019-05-20" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1159778" "palabras" => array:4 [ 0 => "POEMS Syndrome" 1 => "Papilloedema" 2 => "Polyneuropathies" 3 => "Vision disorders" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1159779" "palabras" => array:4 [ 0 => "Síndrome POEMS" 1 => "Papiledema" 2 => "Polineuropatías" 3 => "Trastornos de la visión" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">The cases is presented of a 44 year-old male with a constitutional syndrome, fever, multiple swollen lymph nodes, and hepatosplenomegaly of two months onset. There was also mention of headache, bilateral blurred vision, and myiodesopsias. Best correct visual acuity was 20/50 and 20/200, respectively. The anterior segment was unremarkable. The fundus of both eyes (OU) showed raised and erased discs, accompanied by serous detachment, greater in the left eye. Complementary studies of OU showed a visual field with increased blind spot; fluorescein angiography indicated late disc hyperfluorescence. The electroretinogram showed compromise of cones and rods, and the visual evocated potential detected alteration in the perception and conduction of stimuli. The imaging studies were essentially normal. During his hospital admission he presented with paraparesis, renal failure, endocrinopathy, skin alterations, and osteoblastic lesions with negative biopsies. Monoclonal gammopathy was documented, and the diagnosis of POEMS (Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome was made. The chemotherapy started with Dexamethasone/Melphalan, with a good response at 3 months.</p></span>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Varón de 38 años acude por cuadro de 2 meses caracterizado por síndrome constitucional, alza térmica, poliadenopatías, hepatoesplenomegalia. Además indicó cefalea, visión borrosa bilateral y miodesopsias. Agudeza visual corregida fue 20/50 y 20/200 respectivamente. El segmento anterior sin alteración. El fondo de ojo evidenció discos sobreelevados y borrados, acompañado de desprendimiento seroso del neuroepitelio mayor en ojo izquierdo. Los estudios de ambos ojos mostraron un campo visual con aumento de la mancha ciega; la angiografía fluoresceínica indicó hiperfluorescencia tardía discal; el electrorretinograma evidenció compromiso de conos y bastones; el potencial visual detectó alteración en la percepción y conducción de estímulos. Los estudios de imagen fueron esencialmente normales. Durante su hospitalización presentó paraparesia, insuficiencia renal, endocrinopatía, alteraciones dérmicas y lesiones osteoblásticas con biopsias negativas. Se documentó gammapatía monoclonal planteándose el diagnóstico de Síndrome de POEMS iniciándose quimioterapia con Dexametasona/Melfalán con buena respuesta a los 3 meses.</p></span>" ] ] "NotaPie" => array:2 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0025">Please cite this article as: Ortiz Zapata A, Cárdenas PL, Acuña MF, Peralta Álvarez M, Ortiz Zapata J, Pizarro Imaicela B. Manifestaciones neurooftalmológicas del síndrome de POEMS. Arch Soc Esp Oftalmol. 2019. <span class="elsevierStyleInterRef" id="intr0005" href="https://doi.org/10.1016/j.oftal.2019.05.013">https://doi.org/10.1016/j.oftal.2019.05.013</span></p>" ] 1 => array:2 [ "etiqueta" => "☆☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0030">Paper submitted in full as a poster at the 32nd National and International Ophthalmology Congress of the Ophthalmology Society of Colombia, Cartagena (Colombia), August 2016.</p>" ] ] "multimedia" => array:3 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 999 "Ancho" => 1505 "Tamanyo" => 366852 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Findings in patient. (A) Axial section of orbital-cerebral nuclear magnetic resonance showing distention of the periocular sheath (blue arrow). (B,C) Panoramic reconstruction of the right and left eye fundus, respectively, evidencing optic discs with blurred and raised edges (yellow asterisk), associated to flame hemorrhages, axoplasmic deposits and serous detachments at the macular level. (D) Edema in the lower limbs (white arrow). (E) Skin alterations such as acropachia (yellow arrow) and sclerodactyly. (F). Vertebral biopsy showing signs of osteoblastic activity. (G) Axillary ganglion biopsy compatible with Castleman’s disease (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article).</p>" ] ] 1 => array:8 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1785 "Ancho" => 2511 "Tamanyo" => 424270 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Compostite image of right eye (RE) and left eye (LE) at baseline assessment. (A) Color photograph showing optic disc edema. (B) Fluorescing angiography in late times showing optic disc staining due to edema. (C) Macular thickness map taken with OCT HD macular SD, showing thicknesses of 441<span class="elsevierStyleHsp" style=""></span>μm in RE and 405<span class="elsevierStyleHsp" style=""></span>um in LE. (D) OCT HD macular SD evidencing bilateral serous detachment of neuroepithelium at the subfoveal level, in addition to follow-up with color photograph and OCT HD macular SD post-treatment months 1 and 3, showing diminished optic disc edema and significant improvement of bilateral serous detachments at the foveal level.</p>" ] ] 2 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0015" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">POEMS: Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammapathy and Skin alterations; VEGF: vascular endothelial growth factor.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Suichi<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a></th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Dispenzieri/Kuwabara<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a></th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Dispenzieri<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">c</span></a></th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " colspan="6" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Major criteria</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Polyneuropathy (typically demyelinizing) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Polyneuropathy (typically demyelinizing)<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">d</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Polyneuropathy \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Monoclonal plasma cell dyscrasia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Monoclonal plasma cell dyscrasia<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">d</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Monoclonal plasma cell dyscrasia \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">VEGF Elevation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Castleman disease \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Osteosclerotic lesions \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">VEGF elevation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " colspan="6" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Minor criteria</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Extravascular volume overload \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Organomegaly \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Osteosclerotic lesions \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Extravascular volume overload \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Castleman disease \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Changes in skin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Organomegaly \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Organomegaly \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Endocrinopathy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Edema \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Osteosclerotic lesions \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Changes in skin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Endocrinopathy \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Papiledema \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Changes in skin \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Thrombocytosis/polycythemia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Papiledema \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2139891.png" ] ] ] "notaPie" => array:4 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Three major criteria and at least 2 minor criteria are required.</p>" ] 1 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "b" "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Two mandatory criteria are required: one major and at least one minor criterion.</p>" ] 2 => array:3 [ "identificador" => "tblfn0015" "etiqueta" => "c" "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Two major criteria and at least one minor criterion are required.</p>" ] 3 => array:3 [ "identificador" => "tblfn0020" "etiqueta" => "d" "nota" => "<p class="elsevierStyleNotepara" id="npar0020">Mandatory criterion.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Existing diagnostic criteria for the POEMS syndrome.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Endocrine manifestations in POEMS syndrome: a case report and literature review" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "Y. 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Ortiz" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s10792-017-0636-x" "Revista" => array:6 [ "tituloSerie" => "Int Ophthalmol" "fecha" => "2018" "volumen" => "38" "paginaInicial" => "1641" "paginaFinal" => "1646" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28752346" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Proposal of new clinical diagnostic criteria for POEMS syndrome" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "T. Suichi" 1 => "S. Misawa" 2 => "Y. Sato" 3 => "M. Beppu" 4 => "E. Sakaida" 5 => "Y. 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Zhou" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/IAE.0000000000001409" "Revista" => array:6 [ "tituloSerie" => "Retina" "fecha" => "2017" "volumen" => "37" "paginaInicial" => "1784" "paginaFinal" => "1791" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27930460" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0040" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Changes in subfoveal choroidal thickness and reduction of serum levels of vascular endothelial growth factor in patients with POEMS syndrome" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "H. Yokouchi" 1 => "T. Baba" 2 => "S. Misawa" 3 => "M. Kitahashi" 4 => "T. Oshitari" 5 => "S. 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