Case and Research Letters
Methotrexate-Induced Mucositis as a Sign of Bone Marrow Toxicity: A Retrospective Study of Clinical and Epidemiological Characteristics
La mucositis por metotrexato como marcador de toxicidad medular. Estudio retrospectivo de las características clínicas y epidemiológicas
D. Morgado-Carrasco
, C. Riquelme-Mc Loughlin, X. Fustà-Novell, P. Giavedoni
Autor para correspondencia
Servicio de Dermatología, Hospital Clínic de Barcelona, Universitat de Barcelona, Barcelona, Spain
Leído
7140
Vecesse ha leído el artículo
2100
Total PDF
5040
Total HTML
Compartir estadísticas
array:25 [ "pii" => "S1578219020301487" "issn" => "15782190" "doi" => "10.1016/j.adengl.2020.06.001" "estado" => "S300" "fechaPublicacion" => "2020-06-01" "aid" => "2319" "copyright" => "AEDV" "copyrightAnyo" => "2020" "documento" => "simple-article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "crp" "cita" => "Actas Dermosifiliogr. 2020;111:436-9" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "Traduccion" => array:1 [ "es" => array:20 [ "pii" => "S0001731020300740" "issn" => "00017310" "doi" => "10.1016/j.ad.2020.04.001" "estado" => "S300" "fechaPublicacion" => "2020-06-01" "aid" => "2319" "copyright" => "AEDV" "documento" => "simple-article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "crp" "cita" => "Actas Dermosifiliogr. 2020;111:436-9" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "es" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Carta científico-clínica</span>" "titulo" => "La mucositis por metotrexato como marcador de toxicidad medular. Estudio retrospectivo de las características clínicas y epidemiológicas" "tienePdf" => "es" "tieneTextoCompleto" => "es" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "436" "paginaFinal" => "439" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Methotrexate-Induced Mucositis as a Sign of Bone Marrow Toxicity: A Retrospective Study of Clinical and Epidemiological Characteristics" ] ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figura 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 970 "Ancho" => 1250 "Tamanyo" => 237964 ] ] "descripcion" => array:1 [ "es" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Úlceras cutáneas por metotrexato. A) Placas de psoriasis ulceradas en la espalda (caso 3). B) Carcinoma basocelular ulcerado en la pierna (caso 5).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "D. Morgado-Carrasco, C. Riquelme-Mc Loughlin, X. Fustà-Novell, P. Giavedoni" "autores" => array:4 [ 0 => array:2 [ "nombre" => "D." "apellidos" => "Morgado-Carrasco" ] 1 => array:2 [ "nombre" => "C." "apellidos" => "Riquelme-Mc Loughlin" ] 2 => array:2 [ "nombre" => "X." "apellidos" => "Fustà-Novell" ] 3 => array:2 [ "nombre" => "P." "apellidos" => "Giavedoni" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S1578219020301487" "doi" => "10.1016/j.adengl.2020.06.001" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1578219020301487?idApp=UINPBA000044" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0001731020300740?idApp=UINPBA000044" "url" => "/00017310/0000011100000005/v2_202008041611/S0001731020300740/v2_202008041611/es/main.assets" ] ] "itemSiguiente" => array:20 [ "pii" => "S1578219020301463" "issn" => "15782190" "doi" => "10.1016/j.adengl.2018.10.033" "estado" => "S300" "fechaPublicacion" => "2020-06-01" "aid" => "2313" "copyright" => "AEDV" "documento" => "simple-article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "crp" "cita" => "Actas Dermosifiliogr. 2020;111:439-41" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "en" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Case and Research Letters</span>" "titulo" => "Foreign-Body Reaction to Dermal Filler: Good Response to Treatment With Allopurinol" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "439" "paginaFinal" => "441" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Respuesta favorable al tratamiento con alopurinol de reacción granulomatosa a relleno" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 942 "Ancho" => 1255 "Tamanyo" => 424735 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Hematoxylin-eosin. A, Intense foreign-body granulomatous reaction (original magnification, ×20). B, Eosinophilic material (original magnification, ×40). C, Basophilic material (original magnification, ×40).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "V.A. González-Delgado, P. Cordero-Romero, L. Terrádez-Mas, J.M. Martín" "autores" => array:4 [ 0 => array:2 [ "nombre" => "V.A." "apellidos" => "González-Delgado" ] 1 => array:2 [ "nombre" => "P." "apellidos" => "Cordero-Romero" ] 2 => array:2 [ "nombre" => "L." "apellidos" => "Terrádez-Mas" ] 3 => array:2 [ "nombre" => "J.M." "apellidos" => "Martín" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0001731020300673" "doi" => "10.1016/j.ad.2018.10.029" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0001731020300673?idApp=UINPBA000044" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1578219020301463?idApp=UINPBA000044" "url" => "/15782190/0000011100000005/v3_202012020957/S1578219020301463/v3_202012020957/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S1578219020301451" "issn" => "15782190" "doi" => "10.1016/j.adengl.2018.11.025" "estado" => "S300" "fechaPublicacion" => "2020-06-01" "aid" => "2310" "documento" => "simple-article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "crp" "cita" => "Actas Dermosifiliogr. 2020;111:434-6" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "en" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Case and Research Letters</span>" "titulo" => "Solitary Glomus Tumor Presenting as a Telangiectatic Macule" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "434" "paginaFinal" => "436" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Mácula telangiectásica como forma de presentación de un tumor glómico solitario" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "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" => 755 "Ancho" => 755 "Tamanyo" => 75460 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Erythematous-pink macule surrounded by a pale halo.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "F. Allegue, D. González-Vilas, C. Fachal, A. Zulaica" "autores" => array:4 [ 0 => array:2 [ "nombre" => "F." "apellidos" => "Allegue" ] 1 => array:2 [ "nombre" => "D." "apellidos" => "González-Vilas" ] 2 => array:2 [ "nombre" => "C." "apellidos" => "Fachal" ] 3 => array:2 [ "nombre" => "A." "apellidos" => "Zulaica" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0001731020300648" "doi" => "10.1016/j.ad.2018.11.010" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0001731020300648?idApp=UINPBA000044" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1578219020301451?idApp=UINPBA000044" "url" => "/15782190/0000011100000005/v3_202012020957/S1578219020301451/v3_202012020957/en/main.assets" ] "en" => array:16 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Case and Research Letters</span>" "titulo" => "Methotrexate-Induced Mucositis as a Sign of Bone Marrow Toxicity: A Retrospective Study of Clinical and Epidemiological Characteristics" "tieneTextoCompleto" => true "saludo" => "To the Editor:" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "436" "paginaFinal" => "439" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "D. Morgado-Carrasco, C. Riquelme-Mc Loughlin, X. Fustà-Novell, P. Giavedoni" "autores" => array:4 [ 0 => array:4 [ "nombre" => "D." "apellidos" => "Morgado-Carrasco" "email" => array:1 [ 0 => "morgadodaniel8@gmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "C." "apellidos" => "Riquelme-Mc Loughlin" ] 2 => array:2 [ "nombre" => "X." "apellidos" => "Fustà-Novell" ] 3 => array:2 [ "nombre" => "P." "apellidos" => "Giavedoni" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Dermatología, Hospital Clínic de Barcelona, Universitat de Barcelona, Barcelona, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "La mucositis por metotrexato como marcador de toxicidad medular. Estudio retrospectivo de las características clínicas y epidemiológicas" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 970 "Ancho" => 1250 "Tamanyo" => 237964 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Cutaneous ulcers due to methotrexate. A, Ulcerated psoriasis plaques on the back (patient 3). B, Ulcerated basal cell carcinoma on the leg (patient 5).</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Methotrexate (MTX) is an antimetabolite that inhibits folic acid synthesis. It is widely used in dermatology, rheumatology, and oncology.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">1</span></a> Although MTX has a good safety profile, serious adverse effects such as pneumonitis, hepatic fibrosis, and bone marrow aplasia can occur.<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">1–3</span></a> Previous studies have suggested that MTX-induced mucositis may be a sign of bone marrow toxicity.<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">2,3</span></a> The aim of this study was to analyze clinical, laboratory, and epidemiological characteristics of patients with MTX-induced mucositis.</p><p id="par0010" class="elsevierStylePara elsevierViewall">We performed a retrospective study of patients with a diagnosis of MTX-induced mucositis or mouth ulcers evaluated by the dermatology department at our hospital between January 2013 and July 2018. The patients’ medical records were reviewed to collect epidemiological, clinical, and pictorial information. Five patients (1 man and 4 women) with a median age of 72 years (range, 50–90 years) were included. The epidemiological and clinical characteristics are summarized in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>. The median MTX dose was 15<span class="elsevierStyleHsp" style=""></span>mg/wk (range, 10–35<span class="elsevierStyleHsp" style=""></span>mg/wk). The route of administration was subcutaneous in 3/5 patients and oral in 2/5 patients. Two of the patients were taking MTX for psoriasis and 3 were taking it for rheumatoid arthritis. All the patients had erosions and necrotic crusts in the oral cavity (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A–D). Additional conditions included pancytopenia or bicytopenia in 4/4 patients, fever in 2/5, and skin ulcers in 2/5 (one had ulcerated psoriatic plaques and the other had an ulcerated basal cell carcinoma on the leg (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>A and B). Median peripheral blood leukocyte count was 2475<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">6</span> (range, 330–4200<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">6</span>). Additional laboratory values (median [range]) were hemoglobin 73.5<span class="elsevierStyleHsp" style=""></span>g/L (range, 53–92<span class="elsevierStyleHsp" style=""></span>g/L), mean corpuscular volume 98.5<span class="elsevierStyleHsp" style=""></span>fL (range, 93–105<span class="elsevierStyleHsp" style=""></span>fL), and platelets 92<span class="elsevierStyleHsp" style=""></span>500<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">6</span> (range, 37<span class="elsevierStyleHsp" style=""></span>000–128<span class="elsevierStyleHsp" style=""></span>000<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">6</span>). Serum creatinine levels were elevated in 2/4 patients (median, 2.42<span class="elsevierStyleHsp" style=""></span>mg/dL [range, 0.44–5<span class="elsevierStyleHsp" style=""></span>mg/dL]). Only 1 patient had impaired liver function reflected by elevated gamma-glutamyl transferase (156<span class="elsevierStyleHsp" style=""></span>mg/dL [reference value<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>40<span class="elsevierStyleHsp" style=""></span>mg/dL]) and prothrombin time (international normalized ratio, 1.4). Bone marrow aspiration was performed in 3/5 patients and showed marked hypocellularity, which is consistent with MTX toxicity. The most common trigger was use of a nonsteroidal anti-inflammatory drug (NSAID) (2/5), followed by an administration error (1/5), infection (1/5), and a lack of folic acid intake (1/5). Plasma MTX levels were normal (<0.3<span class="elsevierStyleHsp" style=""></span>mol/L) in 3/3 patients. Treatment included MTX withdrawal in 5/5 patients, intravenous folic acid in 4/5, and granulocyte colony stimulating factor in 1/5. All the patients achieved complete recovery and just 1 was restarted on MTX.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">The most common serious adverse effect of MTX is bone marrow toxicity, which has been observed in 2.5% to 10% of patients and is potentially fatal.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">4</span></a> Mucocutaneous ulceration is a characteristic finding in patients with acute MTX toxicity.<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">3,5</span></a> MTX inhibits cells with a fast turnover and therefore hematopoietic and skin cells are more likely to be affected by its antiproliferative action.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">6</span></a> MTX is mainly eliminated by glomerular filtration, and just a small fraction is metabolized in the liver. Decreased glomerular filtration rate due to dehydration, infection, and use of drugs such as NSAIDs can therefore lead to MTX accumulation and subsequent toxicity.<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">3,7</span></a> In our study, 3/4 patients had impaired kidney function and 3/5 were taking NSAIDs. These associations are consistent with previous reports describing dosing errors, kidney failure, drug-drug interactions (NSAIDs, antibiotics, or salicylates), and MTX reintroduction or dose increments as the main causes of MTX toxicity.<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">2,3,5,7</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">All the patients in our study with blood test results (4/4) had pancytopenia or bicytopenia, and 2 required empirical antibiotic therapy due to febrile neutropenia. These findings highlight the complex management of MTX-induced toxicity, the potential complications, and the need for a high index of clinical suspicion in patients who develop mucocutaneous ulcers while on MTX, particularly if they have risk factors for decreased glomerular filtration rate.<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">2,3</span></a> Elevated mean corpuscular volume (present in 2 of our patients) could be an early sign of bone marrow toxicity due to folic acid deficiency. Serum MTX levels were low in 3 of the 4 patients with mucositis and pancytopenia tested. These low levels can be explained by the cellular accumulation of the drug. Plasma concentrations are typically 0.01<span class="elsevierStyleHsp" style=""></span>M 24 hours after withdrawal of MTX, and serum levels do not correlate well with toxicity.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">7</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Skin ulcers due to MTX have mostly been described in association with psoriasis or previous injury.<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">2,5</span></a> In our series, ulcers were observed in psoriatic plaques in 1 patient and in a basal cell carcinoma in the other. Ulcers can, however, also affect healthy skin.</p><p id="par0030" class="elsevierStylePara elsevierViewall">MTX toxicity can cause high morbidity and mortality.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">3</span></a> Detection of mucocutaneous ulcers in a patient on MTX should raise suspicion of pancytopenia and kidney failure, even in patients on low MTX doses and with normal serum concentrations. These patients must be hospitalized and treated by a multidisciplinary team.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of Interest</span><p id="par0035" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflicts of Interest" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Morgado-Carrasco D, Riquelme-Mc Loughlin C, Fustà-Novell X, Giavedoni P. La mucositis por metotrexato como marcador de toxicidad medular. Estudio retrospectivo de las características clínicas y epidemiológicas. Actas Dermosifiliogr. 2020;111:436–439.</p>" ] ] "multimedia" => array:3 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1070 "Ancho" => 1255 "Tamanyo" => 228396 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Methotrexate-induced mucositis. Erosions and necrotic crusts. A, Patient 1. B, Patient 2. C, Patient 3. D, Patient 4.</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" => 970 "Ancho" => 1250 "Tamanyo" => 237964 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Cutaneous ulcers due to methotrexate. A, Ulcerated psoriasis plaques on the back (patient 3). B, Ulcerated basal cell carcinoma on the leg (patient 5).</p>" ] ] 2 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Abbreviations: CR, complete response; CRF, chronic renal failure; DM2, diabetes mellitus type 2; F, female; ID, insulin-dependent; M, male; MTX, methotrexate; NSAID, nonsteroidal anti-inflammatory drug.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Patient \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Age, y/Sex \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Comorbidities \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">MTX Dose \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Route of Administration \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Time on MTX \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Trigger \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Clinical Presentation \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Kidney Failure \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Clinical Course \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Treatment \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Reinitiation of MTX \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">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">90/F \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">Rheumatoid arthritisHypertensionBreast cancer \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<span class="elsevierStyleHsp" style=""></span>mg/wk \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">Oral \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 y \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">Administration error5<span class="elsevierStyleHsp" style=""></span>mg/d \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">Fever, mucositis, pancytopenia \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">No \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">CR \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">Withdrawal of MTXFolic acid 15<span class="elsevierStyleHsp" style=""></span>mg/d IV \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">No \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">61/F \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">Rheumatoid arthritisDM2HypertensionCRF (CrCl) \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<span class="elsevierStyleHsp" style=""></span>mg/wk \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">Subcutaneous \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 y \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">Folic acid not administered \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">Fever, mucositis, pancytopenia \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">YesClcr 25<span class="elsevierStyleHsp" style=""></span>mL/min \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">CR \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">Withdrawal of MTXFolic acid 15<span class="elsevierStyleHsp" style=""></span>mg/d IV \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">Yes10<span class="elsevierStyleHsp" style=""></span>mg/wk \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">50/F \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">PsoriasisID-DM2HypertensionCRF \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">25<span class="elsevierStyleHsp" style=""></span>mg/wk \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">Subcutaneous \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">25 y \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">Impaired renal function due to NSAID \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">Mucositis, skin ulcers, pancytopenia \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">YesClcr 9.8<span class="elsevierStyleHsp" style=""></span>mL/min \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">CR \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">Withdrawal of MTXFolic acid 140<span class="elsevierStyleHsp" style=""></span>mg IV followed by 50<span class="elsevierStyleHsp" style=""></span>mg IV every 6<span class="elsevierStyleHsp" style=""></span>h GCSF \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">No \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">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">72/F \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">PsoriasisDM2 \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">15<span class="elsevierStyleHsp" style=""></span>mg/wk \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">Subcutaneous \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 mo \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">Use of NSAIDs \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">Mucositis \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">Unknown \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">CR \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">Withdrawal of MTX \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">NoEtanercept \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">81/F \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">Rheumatoid arthritisChronic lung diseaseCRF \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<span class="elsevierStyleHsp" style=""></span>mg/wk \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">Oral \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">Unknown \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">Skin infection and NSAID \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">Mucositis, skin ulcers, bicytopenia \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">YesClcr 22<span class="elsevierStyleHsp" style=""></span>mL/min \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">CR \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">Withdrawal of MTXFolic acid IV (nonspecified dose) \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">Not known \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2443830.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Epidemiological and Clinical Characteristics of Patients With MTX-induced Toxicity and Mucocutaneous Lesions.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:7 [ 0 => array:3 [ "identificador" => "bib0040" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Metotrexato: guía de uso en psoriasis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "G. Carretero" 1 => "L. Puig" 2 => "L. Dehesa" 3 => "J.M. Carrascosa" 4 => "M. Ribera" 5 => "M. Sánchez-Regaña" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Actas Dermosifiliogr" "fecha" => "2010" "volumen" => "101" "paginaInicial" => "600" "paginaFinal" => "613" "itemHostRev" => array:3 [ "pii" => "S0140673617301885" "estado" => "S300" "issn" => "01406736" ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0045" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Toxicodermia por metotrexato con marcada dismaduración epidérmica" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.J. García de Villalta" 1 => "D. Ruiz-Genao" 2 => "S. Álvarez-Ruiz" 3 => "M. Aragüés" 4 => "J. Fraga" 5 => "J. Fernández Herrera" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Actas Dermosifiliogr" "fecha" => "2004" "volumen" => "95" "paginaInicial" => "567" "paginaFinal" => "570" ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0050" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cutaneous erosions: a herald for impending pancytopenia in methotrexate toxicity" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "M.B. Shiver" 1 => "L.A. Hall" 2 => "K.B. Conner" 3 => "G.E. Brown" 4 => "W.L. Cheung" 5 => "M.L. Wirges" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "Dermatol Online J" "fecha" => "2014" "volumen" => "20" "itemHostRev" => array:3 [ "pii" => "S0954611111002150" "estado" => "S300" "issn" => "09546111" ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0055" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Methotrexate in psoriasis: 26 years’ experience with low-dose long-term treatment" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "U.F. Haustein" 1 => "M. Rytter" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1046/j.1468-3083.2000.00058.x" "Revista" => array:6 [ "tituloSerie" => "J Eur Acad Dermatol Venereol" "fecha" => "2000" "volumen" => "14" "paginaInicial" => "382" "paginaFinal" => "388" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11305380" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0060" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Acute methotrexate toxicity seen as plaque psoriasis ulceration and necrosis: a diagnostic clue" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "J.L. Fridlington" 1 => "J.W. Tripple" 2 => "J.S. Reichenberg" 3 => "C.S.D.D. Hall" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Dermatol Online J" "fecha" => "2011" "volumen" => "17" "paginaInicial" => "2" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22233738" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0065" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Multiple toxic effects of low-dose methotrexate in a patient treated for psoriasis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "P.B. Bookstaver" 1 => "L. Norris" 2 => "C. Rudisill" 3 => "T. DeWitt" 4 => "S.F.J. Aziz" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2146/ajhp070676" "Revista" => array:6 [ "tituloSerie" => "Am J Health Syst Pharm" "fecha" => "2008" "volumen" => "65" "paginaInicial" => "2117" "paginaFinal" => "2121" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18997139" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0070" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Methotrexate-induced epidermal necrosis: a case series of 24 patients" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "T.J. Chen" 1 => "W.H. Chung" 2 => "C.B. Chen" 3 => "R.C.Y. Hui" 4 => "Y.H. Huang" 5 => "Y.T. Lu" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:3 [ "tituloSerie" => "J Am Acad Dermatol" "fecha" => "2017" "volumen" => "77" ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/15782190/0000011100000005/v3_202012020957/S1578219020301487/v3_202012020957/en/main.assets" "Apartado" => array:4 [ "identificador" => "6157" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Case and Research Letters" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/15782190/0000011100000005/v3_202012020957/S1578219020301487/v3_202012020957/en/main.pdf?idApp=UINPBA000044&text.app=https://actasdermo.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1578219020301487?idApp=UINPBA000044" ]
| año/Mes | Html | Total | |
|---|---|---|---|
| 2024 Noviembre | 8 | 7 | 15 |
| 2024 Octubre | 109 | 42 | 151 |
| 2024 Septiembre | 113 | 19 | 132 |
| 2024 Agosto | 149 | 52 | 201 |
| 2024 Julio | 101 | 26 | 127 |
| 2024 Junio | 95 | 29 | 124 |
| 2024 Mayo | 90 | 38 | 128 |
| 2024 Abril | 80 | 16 | 96 |
| 2024 Marzo | 93 | 25 | 118 |
| 2024 Febrero | 91 | 32 | 123 |
| 2024 Enero | 89 | 49 | 138 |
| 2023 Diciembre | 76 | 16 | 92 |
| 2023 Noviembre | 122 | 58 | 180 |
| 2023 Octubre | 123 | 44 | 167 |
| 2023 Septiembre | 110 | 45 | 155 |
| 2023 Agosto | 105 | 31 | 136 |
| 2023 Julio | 131 | 58 | 189 |
| 2023 Junio | 135 | 38 | 173 |
| 2023 Mayo | 204 | 45 | 249 |
| 2023 Abril | 99 | 52 | 151 |
| 2023 Marzo | 162 | 47 | 209 |
| 2023 Febrero | 134 | 32 | 166 |
| 2023 Enero | 154 | 30 | 184 |
| 2022 Diciembre | 89 | 45 | 134 |
| 2022 Noviembre | 83 | 38 | 121 |
| 2022 Octubre | 62 | 43 | 105 |
| 2022 Septiembre | 74 | 65 | 139 |
| 2022 Agosto | 52 | 62 | 114 |
| 2022 Julio | 66 | 60 | 126 |
| 2022 Junio | 48 | 41 | 89 |
| 2022 Mayo | 112 | 40 | 152 |
| 2022 Abril | 90 | 41 | 131 |
| 2022 Marzo | 96 | 66 | 162 |
| 2022 Febrero | 107 | 46 | 153 |
| 2022 Enero | 122 | 58 | 180 |
| 2021 Diciembre | 111 | 56 | 167 |
| 2021 Noviembre | 115 | 51 | 166 |
| 2021 Octubre | 119 | 71 | 190 |
| 2021 Septiembre | 76 | 45 | 121 |
| 2021 Agosto | 72 | 35 | 107 |
| 2021 Julio | 73 | 27 | 100 |
| 2021 Junio | 80 | 46 | 126 |
| 2021 Mayo | 80 | 52 | 132 |
| 2021 Abril | 261 | 81 | 342 |
| 2021 Marzo | 124 | 26 | 150 |
| 2021 Febrero | 69 | 28 | 97 |
| 2021 Enero | 39 | 21 | 60 |
| 2020 Diciembre | 27 | 17 | 44 |
| 2020 Noviembre | 28 | 20 | 48 |
| 2020 Octubre | 21 | 9 | 30 |
| 2020 Septiembre | 47 | 18 | 65 |
| 2020 Agosto | 47 | 23 | 70 |
| 2020 Julio | 58 | 25 | 83 |
| 2020 Junio | 19 | 13 | 32 |
Mostrar todo
