Case And Research Letter
Acral Erosions and Ulcers: An Early Sign of Severe Acute Methotrexate Toxicity
Erosiones y úlceras acrales: manifestación precoz de toxicidad aguda grave por metrotexato
L. Maroñas-Jiménez
, M. Castellanos-González, J. Sanz Bueno, F. Vanaclocha Sebastián
Corresponding author
Servicio de Dermatología y Venereología, Hospital Universitario 12 de Octubre, Madrid, Spain
Read
8350
Timeswas read the article
2329
Total PDF
6021
Total HTML
Share statistics
array:23 [ "pii" => "S1578219014000456" "issn" => "15782190" "doi" => "10.1016/j.adengl.2013.05.007" "estado" => "S300" "fechaPublicacion" => "2014-04-01" "aid" => "865" "copyright" => "Elsevier España, S.L. and AEDV" "copyrightAnyo" => "2013" "documento" => "simple-article" "crossmark" => 0 "subdocumento" => "cor" "cita" => "Actas Dermosifiliogr. 2014;105:322-3" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 2699 "formatos" => array:3 [ "EPUB" => 37 "HTML" => 2042 "PDF" => 620 ] ] "Traduccion" => array:1 [ "es" => array:19 [ "pii" => "S0001731013002536" "issn" => "00017310" "doi" => "10.1016/j.ad.2013.05.006" "estado" => "S300" "fechaPublicacion" => "2014-04-01" "aid" => "865" "copyright" => "Elsevier España, S.L. y AEDV" "documento" => "simple-article" "crossmark" => 0 "subdocumento" => "cor" "cita" => "Actas Dermosifiliogr. 2014;105:322-3" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 2683 "formatos" => array:3 [ "EPUB" => 2 "HTML" => 1925 "PDF" => 756 ] ] "es" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Carta científico-clínica</span>" "titulo" => "Erosiones y úlceras acrales: manifestación precoz de toxicidad aguda grave por metrotexato" "tienePdf" => "es" "tieneTextoCompleto" => "es" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "322" "paginaFinal" => "323" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Acral Erosions and Ulcers: An Early Sign of Severe Acute Methotrexate Toxicity" ] ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figura 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1170 "Ancho" => 1667 "Tamanyo" => 244434 ] ] "descripcion" => array:1 [ "es" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A. Detalle clínico de las lesiones del segundo paciente: erosiones espiculadas profundas con halo violáceo periférico y costra hemorrágica en la superficie. B. Placa erosiva de superficie exudativo-costrosa en la aleta nasal derecha.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "L. Maroñas-Jiménez, M. Castellanos-González, J. Sanz Bueno, F. Vanaclocha Sebastián" "autores" => array:4 [ 0 => array:2 [ "nombre" => "L." "apellidos" => "Maroñas-Jiménez" ] 1 => array:2 [ "nombre" => "M." "apellidos" => "Castellanos-González" ] 2 => array:2 [ "nombre" => "J." "apellidos" => "Sanz Bueno" ] 3 => array:2 [ "nombre" => "F." "apellidos" => "Vanaclocha Sebastián" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S1578219014000456" "doi" => "10.1016/j.adengl.2013.05.007" "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/S1578219014000456?idApp=UINPBA000044" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0001731013002536?idApp=UINPBA000044" "url" => "/00017310/0000010500000003/v1_201404040105/S0001731013002536/v1_201404040105/es/main.assets" ] ] "itemAnterior" => array:19 [ "pii" => "S1578219014000420" "issn" => "15782190" "doi" => "10.1016/j.adengl.2013.04.024" "estado" => "S300" "fechaPublicacion" => "2014-04-01" "aid" => "856" "copyright" => "Elsevier España, S.L. and AEDV" "documento" => "simple-article" "crossmark" => 0 "subdocumento" => "cor" "cita" => "Actas Dermosifiliogr. 2014;105:319-21" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 3565 "formatos" => array:3 [ "EPUB" => 41 "HTML" => 2666 "PDF" => 858 ] ] "en" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Case and Research Letter</span>" "titulo" => "Pachydermodactyly Successfully Treated With Triamcinolone Injections" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "319" "paginaFinal" => "321" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Paquidermodactilia tratada con éxito con infiltraciones de triamcinolona" ] ] "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" => 1375 "Ancho" => 901 "Tamanyo" => 176488 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Pretreatment photograph showing the conspicuous, diffuse thickening around the proximal interphalangeal joints of all the fingers with the exception of the thumb and fifth finger.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "A. Plana Pla, J. Bassas Vila, M.A. Toro Montecinos, C. Ferrandiz Foraster" "autores" => array:4 [ 0 => array:2 [ "nombre" => "A." "apellidos" => "Plana Pla" ] 1 => array:2 [ "nombre" => "J." "apellidos" => "Bassas Vila" ] 2 => array:2 [ "nombre" => "M.A." "apellidos" => "Toro Montecinos" ] 3 => array:2 [ "nombre" => "C." "apellidos" => "Ferrandiz Foraster" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0001731013002329" "doi" => "10.1016/j.ad.2013.04.010" "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/S0001731013002329?idApp=UINPBA000044" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1578219014000420?idApp=UINPBA000044" "url" => "/15782190/0000010500000003/v1_201404030048/S1578219014000420/v1_201404030048/en/main.assets" ] "en" => array:15 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Case And Research Letter</span>" "titulo" => "Acral Erosions and Ulcers: An Early Sign of Severe Acute Methotrexate Toxicity" "tieneTextoCompleto" => true "saludo" => "<span class="elsevierStyleItalic">To the Editor</span>:" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "322" "paginaFinal" => "323" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "L. Maroñas-Jiménez, M. Castellanos-González, J. Sanz Bueno, F. Vanaclocha Sebastián" "autores" => array:4 [ 0 => array:4 [ "nombre" => "L." "apellidos" => "Maroñas-Jiménez" "email" => array:1 [ 0 => "lydia.maroasjimenez@gmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">¿</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "M." "apellidos" => "Castellanos-González" ] 2 => array:2 [ "nombre" => "J." "apellidos" => "Sanz Bueno" ] 3 => array:2 [ "nombre" => "F." "apellidos" => "Vanaclocha Sebastián" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Dermatología y Venereología, Hospital Universitario 12 de Octubre, Madrid, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding Author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Erosiones y úlceras acrales: manifestación precoz de toxicidad aguda grave por metrotexato" ] ] "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" => 662 "Ancho" => 1002 "Tamanyo" => 134953 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A and B, Bilateral, symmetrical, crusted erosive lesions with a retiform distribution on the dorsum of the feet and hands.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Methotrexate (MTX) is a drug with a good safety profile that is frequently used in dermatology. Although serious complications due to acute MTX toxicity typically occur in the context of antineoplastic doses (up to 1-3<span class="elsevierStyleHsp" style=""></span>g/m<span class="elsevierStyleSup">2</span> in some tumors), they occasionally occur in patients treated with considerably lower doses, and the early identification of these effects is essential. We present 3 patients who developed acute myelosuppression secondary to treatment with MTX. The initial signs in all the patients were similar forms of skin lesions; clinical observation of these lesions can be the key to the early diagnosis of this important condition.</p><p id="par0010" class="elsevierStylePara elsevierViewall">The first patient was a woman of 65 years of age with rheumatoid arthritis. She had been on treatment for 1 month with MTX, 20<span class="elsevierStyleHsp" style=""></span>mg/24<span class="elsevierStyleHsp" style=""></span>h, ibuprofen, 600<span class="elsevierStyleHsp" style=""></span>mg/8<span class="elsevierStyleHsp" style=""></span>h, and prednisone, 10<span class="elsevierStyleHsp" style=""></span>mg/24<span class="elsevierStyleHsp" style=""></span>h. She came to the emergency department with a 3-day history of fever and mucositis associated with painful edema of the hands of sudden onset and ulcers on both feet (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). After 48<span class="elsevierStyleHsp" style=""></span>hours of in-hospital observation, she developed severe pancytopenia with a neutrophil count of 400/μL (normal range, 1800-7600/μL), hemoglobin (Hb) of 9<span class="elsevierStyleHsp" style=""></span>g/dL (normal range, 11.4-15.1<span class="elsevierStyleHsp" style=""></span>g/dL), mean cell volume of 100<span class="elsevierStyleHsp" style=""></span>fL, and platelet count of 66 000/μL (normal range, 140 000-450 000/μL). Blood and urine cultures, microbiology study of the mucosas, and serology for human immunodeficiency virus, syphilis, hepatitis B and C viruses, parvovirus B19, cytomegalovirus, Epstein-Barr virus, and toxoplasma were negative.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">The second case was a 60-year-old man and the third case a 55-year-old woman; both patients had a history of mycosis fungoides for which they had been treated with MTX, the man for 4 months at a dose of 20 mg/wk and the woman for 6 months at a dose of 25<span class="elsevierStyleHsp" style=""></span>mg/wk. For the previous month they had also been treated with sulfamethoxazole/trimethoprim (SMX/TMP) 800/160<span class="elsevierStyleHsp" style=""></span>mg 3 times a week as prophylaxis for sepsis of cutaneous origin. They were seen for very painful acral erosions that had been present for a week (<a class="elsevierStyleCrossRefs" href="#fig0010">Figs. 2 and 3</a>). Blood tests in the man revealed a marked fall in the Hb to 7.9<span class="elsevierStyleHsp" style=""></span>g/dL from a value of 11.7<span class="elsevierStyleHsp" style=""></span>g/dL 2 weeks earlier, and in the woman revealed moderate bicytopenia that had not previously been detected (Hb of 10<span class="elsevierStyleHsp" style=""></span>g/dl and a white cell count of 2000/μL with 600 neutrophils/μL). Cultures of the skin lesions were negative for viruses and bacteria in both patients.</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">In all 3 patients, biopsy revealed reactive epidermal hyperplasia with areas of ulceration with a fibrin-covered base and dermal eosinophilia. The administration of MTX was interrupted and symptomatic treatment was started, leading to resolution of the skin lesions in less than 1 month in all cases. In the first patient it was necessary to add specific treatment (folinic acid and granulocyte colony stimulating factor) because of the severe pancytopenia, which showed a favorable response.</p><p id="par0025" class="elsevierStylePara elsevierViewall">MTX is an antimetabolite. It is a folic acid analog that competitively and reversibly inhibits the enzyme dihydrofolate reductase (DHFR), a key enzyme for cell DNA synthesis. This mechanism explains its antiproliferative activity and the profile of adverse effects at high doses; acute myelosuppression is the manifestation that carries the greatest threat to life.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> When used as at anti-inflammatory doses, the number of drug molecules bound to the enzyme is insufficient to achieve inhibition, and it is postulated that the effect a low doses may be related to the formation of intracellular polyglutamates.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> However, the marked inter- and intraindividual variability in its metabolism<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> and the possible coexistence of factors that increase its cellular availability means that, in practice, we must considered all patients on treatment with MTX to be susceptible to develop serious complications. Our 3 cases presented factors that could favor cytotoxicity: in the first patient, incorrect dosage (daily instead of weekly) leading to overdose, and treatment with ibuprofen, which interferes with the renal excretion of MTX and increases its free fraction in the plasma by displacing MTX from its protein binding sites; in the other patients, prophylaxis with SMX/TMP impeded the transformation of para-aminobenzoic acid into folic acid (SMX effect) and directly inhibited DHFR (TMP effect).</p><p id="par0030" class="elsevierStylePara elsevierViewall">Skin erosions and/or ulcers as the manifestation of acute cytotoxicity due to MTX is very rare. In the medical literature reviewed, we found only 5 cases in patients with no previous dermatosis.<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4–8</span></a> All were men on low-dose treatment for rheumatoid arthritis and only one of them presented general manifestations with fever, mucositis, and acute severe pancytopenia, similar to our first patient.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> Cell turnover is increased in patients with psoriasis and/or mycosis fungoides, and this increases the cutaneous tropism of MTX.<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9,10</span></a> Lawrence et al.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> describe 2 distinct clinical patterns with different prognoses in patients with psoriasis: type I, with erosions and/or ulcers that develop on plaques and heal within a few days after the withdrawal of MTX; and type II, with lesions on healthy skin that take weeks to resolve despite the withdrawal of treatment. The clinical recognition of this condition is important, as it must be differentiated from treatment inefficacy or a flare-up of the dermatosis; this typically occurs at the beginning or end of treatment, which could lead either to an increase in the dose or to the reintroduction of MTX. The common factor in all the cases described, both in individuals with lesions on underlying skin disease and in those with lesions on healthy skin, was the disproportionate pain of the lesions and their characteristic distribution on acral areas, as was observed in our patients.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Based on all we have described, we believe that the appearance of painful acral erosions and/or ulcers in patients receiving treatment with MTX must lead us to consider severe underlying cytotoxicity. Two fundamental factors in the prevention of potentially lethal adverse effects are detailed evaluation of all the concomitant medication and ensuring that patients understand the indicated MTX regimen.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Maroñas-Jiménez L, Castellanos-González M, Sanz Bueno J, Vanaclocha Sebastián F. Erosiones y úlceras acrales: manifestación precoz de toxicidad aguda grave por metrotexato. 2014 105:319–321.</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" => 361 "Ancho" => 1001 "Tamanyo" => 82172 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">A, Swelling of both hands with poorly defined areas of violaceous erythema on the bony prominences of the fingers. B, Round superficial ulcers with a clean base and hyperpigmented borders on the sole of the right foot and on the left heel.</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" => 662 "Ancho" => 1002 "Tamanyo" => 134953 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A and B, Bilateral, symmetrical, crusted erosive lesions with a retiform distribution on the dorsum of the feet and hands.</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" => 703 "Ancho" => 1001 "Tamanyo" => 127433 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A, Clinical image of the lesions in the second patient: deep spiculated erosions covered by a hemorrhagic scab and with a peripheral violaceous halo. B, Erosive plaque with a crusted exudative surface on the right ala nasi.</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" => "The remarkable spectrum of methotrexate toxicities" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "R.J. MacKendry" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Rheum Dis Clin North Am" "fecha" => "1997" "volumen" => "23" "paginaInicial" => "939" "paginaFinal" => "954" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9361162" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "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" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20858386" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Measurement of erythrocyte methotrexate polyglutamate levels: ready for clinical use in rheumatoid arthritis?" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.I. Danila" 1 => "L.B. Hughes" 2 => "E.E. Brown" 3 => "S.L. Morgan" 4 => "J.E. Baggott" 5 => "D.K. Arnett" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s11926-010-0120-3" "Revista" => array:6 [ "tituloSerie" => "Curr Rheumatol Rep" "fecha" => "2010" "volumen" => "12" "paginaInicial" => "342" "paginaFinal" => "347" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20665136" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cutaneous ulceration: An unusual sign of methotrexate toxicity---first report in a patient without psoriasis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "D. Ben-Amitai" 1 => "E. Hodak" 2 => "M. David" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Ann Pharmacother" "fecha" => "1998" "volumen" => "32" "paginaInicial" => "651" "paginaFinal" => "653" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9640483" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cutaneous ulcerations in a patient with rheumatoid arthritis receiving treatment with methotrexate" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "L.C. Montero" 1 => "R.S. Gómez" 2 => "J.F. de Quirós" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Rheumatol" "fecha" => "2000" "volumen" => "27" "paginaInicial" => "2290" "paginaFinal" => "2291" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10990260" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0030" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cutaneous ulceration as a sign of methotrexate toxicity" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "J. Del Pozo" 1 => "W. Martínez" 2 => "J. García-Silva" 3 => "M. Almagro" 4 => "C. Peña-Penabad" 5 => "E. Fonseca" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Eur J Dermatol" "fecha" => "2001" "volumen" => "11" "paginaInicial" => "450" "paginaFinal" => "452" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11525955" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0035" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Early-onset pancytopenia and skin ulcer following low-dose methotrexate therapy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "N. Hocaoglu" 1 => "R. Atilla" 2 => "F. Onen" 3 => "Y. Tuncok" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1177/0960327108094507" "Revista" => array:6 [ "tituloSerie" => "Hum Exp Toxicol" "fecha" => "2008" "volumen" => "27" "paginaInicial" => "585" "paginaFinal" => "589" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18829735" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0040" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Methotrexate-induced cutaneous ulcers in a nonpsoriatic patient: Case report and review of the literature" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "A. Kurian" 1 => "R. Haber" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Cutan Med Surg" "fecha" => "2011" "volumen" => "15" "paginaInicial" => "275" "paginaFinal" => "279" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21962187" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0045" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Two patterns of skin ulceration induced by methotrexate in patients with psoriasis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "C.M. Lawrence" 1 => "M.G. Dahl" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Am Acad Dermatol" "fecha" => "1984" "volumen" => "11" "paginaInicial" => "1059" "paginaFinal" => "1065" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/6512051" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0050" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:1 [ "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "D.L. Breneman" 1 => "T.J. Storer" 2 => "J.C. Breneman" 3 => "D.F. Mutasim" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "Methotrexate-induced cutaneous ulceration in patiens with erythrodermic mycosis fungoides" "fecha" => "2008" "volumen" => "4" "paginaInicial" => "1135" ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/15782190/0000010500000003/v1_201404030048/S1578219014000456/v1_201404030048/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/15782190/0000010500000003/v1_201404030048/S1578219014000456/v1_201404030048/en/main.pdf?idApp=UINPBA000044&text.app=https://actasdermo.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1578219014000456?idApp=UINPBA000044" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 17 | 6 | 23 |
| 2024 October | 114 | 55 | 169 |
| 2024 September | 115 | 26 | 141 |
| 2024 August | 167 | 80 | 247 |
| 2024 July | 116 | 61 | 177 |
| 2024 June | 154 | 53 | 207 |
| 2024 May | 110 | 43 | 153 |
| 2024 April | 108 | 32 | 140 |
| 2024 March | 110 | 44 | 154 |
| 2024 February | 81 | 31 | 112 |
| 2024 January | 108 | 36 | 144 |
| 2023 December | 76 | 17 | 93 |
| 2023 November | 87 | 24 | 111 |
| 2023 October | 113 | 36 | 149 |
| 2023 September | 80 | 37 | 117 |
| 2023 August | 80 | 18 | 98 |
| 2023 July | 114 | 28 | 142 |
| 2023 June | 89 | 21 | 110 |
| 2023 May | 107 | 17 | 124 |
| 2023 April | 98 | 26 | 124 |
| 2023 March | 78 | 17 | 95 |
| 2023 February | 85 | 25 | 110 |
| 2023 January | 58 | 35 | 93 |
| 2022 December | 60 | 35 | 95 |
| 2022 November | 36 | 22 | 58 |
| 2022 October | 38 | 19 | 57 |
| 2022 September | 38 | 33 | 71 |
| 2022 August | 33 | 30 | 63 |
| 2022 July | 35 | 33 | 68 |
| 2022 June | 38 | 22 | 60 |
| 2022 May | 60 | 34 | 94 |
| 2022 April | 74 | 32 | 106 |
| 2022 March | 70 | 48 | 118 |
| 2022 February | 71 | 28 | 99 |
| 2022 January | 62 | 26 | 88 |
| 2021 December | 52 | 36 | 88 |
| 2021 November | 64 | 37 | 101 |
| 2021 October | 71 | 48 | 119 |
| 2021 September | 59 | 37 | 96 |
| 2021 August | 55 | 31 | 86 |
| 2021 July | 88 | 33 | 121 |
| 2021 June | 62 | 28 | 90 |
| 2021 May | 64 | 26 | 90 |
| 2021 April | 112 | 69 | 181 |
| 2021 March | 84 | 28 | 112 |
| 2021 February | 40 | 36 | 76 |
| 2021 January | 41 | 17 | 58 |
| 2020 December | 42 | 14 | 56 |
| 2020 November | 18 | 14 | 32 |
| 2020 October | 31 | 16 | 47 |
| 2020 September | 29 | 16 | 45 |
| 2020 August | 33 | 17 | 50 |
| 2020 July | 33 | 13 | 46 |
| 2020 June | 24 | 25 | 49 |
| 2020 May | 28 | 15 | 43 |
| 2020 April | 34 | 11 | 45 |
| 2020 March | 34 | 11 | 45 |
| 2020 February | 5 | 1 | 6 |
| 2020 January | 4 | 0 | 4 |
| 2019 December | 8 | 2 | 10 |
| 2019 November | 4 | 1 | 5 |
| 2019 October | 0 | 3 | 3 |
| 2019 September | 4 | 0 | 4 |
| 2019 August | 4 | 2 | 6 |
| 2019 July | 4 | 3 | 7 |
| 2019 June | 6 | 12 | 18 |
| 2019 May | 4 | 17 | 21 |
| 2019 April | 2 | 13 | 15 |
| 2019 March | 4 | 10 | 14 |
| 2019 February | 2 | 1 | 3 |
| 2019 January | 2 | 6 | 8 |
| 2018 December | 4 | 0 | 4 |
| 2018 October | 6 | 0 | 6 |
| 2018 September | 4 | 2 | 6 |
| 2018 August | 0 | 2 | 2 |
| 2018 July | 0 | 1 | 1 |
| 2018 June | 0 | 5 | 5 |
| 2018 May | 0 | 8 | 8 |
| 2018 April | 0 | 2 | 2 |
| 2018 March | 0 | 1 | 1 |
| 2018 February | 49 | 7 | 56 |
| 2018 January | 53 | 5 | 58 |
| 2017 December | 61 | 9 | 70 |
| 2017 November | 52 | 5 | 57 |
| 2017 October | 44 | 17 | 61 |
| 2017 September | 53 | 19 | 72 |
| 2017 August | 73 | 23 | 96 |
| 2017 July | 62 | 41 | 103 |
| 2017 June | 61 | 35 | 96 |
| 2017 May | 72 | 36 | 108 |
| 2017 April | 53 | 49 | 102 |
| 2017 March | 64 | 26 | 90 |
| 2017 February | 40 | 16 | 56 |
| 2017 January | 36 | 23 | 59 |
| 2016 December | 56 | 13 | 69 |
| 2016 November | 72 | 11 | 83 |
| 2016 October | 91 | 17 | 108 |
| 2016 September | 152 | 15 | 167 |
| 2016 August | 67 | 16 | 83 |
| 2016 July | 41 | 10 | 51 |
| 2016 June | 11 | 12 | 23 |
| 2016 May | 6 | 9 | 15 |
| 2016 April | 14 | 1 | 15 |
| 2016 March | 7 | 1 | 8 |
| 2016 February | 4 | 3 | 7 |
| 2016 January | 9 | 3 | 12 |
| 2015 December | 6 | 1 | 7 |
| 2015 November | 11 | 2 | 13 |
| 2015 October | 9 | 4 | 13 |
| 2015 September | 8 | 0 | 8 |
| 2015 August | 10 | 2 | 12 |
| 2015 July | 70 | 11 | 81 |
| 2015 June | 74 | 9 | 83 |
| 2015 May | 54 | 2 | 56 |
| 2015 April | 43 | 5 | 48 |
| 2015 March | 25 | 2 | 27 |
| 2015 February | 45 | 3 | 48 |
| 2015 January | 44 | 1 | 45 |
| 2014 December | 53 | 5 | 58 |
| 2014 November | 28 | 3 | 31 |
| 2014 October | 37 | 5 | 42 |
| 2014 September | 28 | 3 | 31 |
| 2014 August | 16 | 2 | 18 |
| 2014 July | 25 | 7 | 32 |
| 2014 June | 26 | 9 | 35 |
| 2014 May | 35 | 22 | 57 |
| 2014 April | 26 | 9 | 35 |
Show all
