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Hospital Universitario Virgen de las Nieves, Granada, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Pancitopenia tras administración de metotrexato intralesional en un paciente en programa de hemodiálisis" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The use of intralesional methotrexate has been shown to be effective and safe in some types of skin tumours, especially keratoacanthoma.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> However, in patients with advanced renal failure, this treatment is not exempt from bone marrow toxicity.</p><p id="par0010" class="elsevierStylePara elsevierViewall">We report the case of a 75-year-old man, with a personal history of arterial hypertension and stage 5 chronic kidney disease, on haemodialysis. He had recently received two intralesional methotrexate injections of 15 and 25<span class="elsevierStyleHsp" style=""></span>mg for the treatment of two keratoacanthomas on the scalp.</p><p id="par0015" class="elsevierStylePara elsevierViewall">He came to the emergency department for a 48-h history of general malaise, asthenia, vomiting and constipation, accompanied by abdominal pain with abdominal guarding. An abdominal ultrasound was performed, reporting the presence of uncomplicated diverticulitis without hepatosplenomegaly. There was no fever or other infectious focality.</p><p id="par0020" class="elsevierStylePara elsevierViewall">The laboratory analysis showed pancytopenia, not present in recent previous analyses, with haemoglobin of 9.9<span class="elsevierStyleHsp" style=""></span>g/dL (mean corpuscular volume 93<span class="elsevierStyleHsp" style=""></span>fL), 760 leukocytes/L with a neutrophil count of 290<span class="elsevierStyleHsp" style=""></span>L<span class="elsevierStyleSup">–1</span> and 90,000 platelets/L. Biochemistry showed a creatinine value of 5.4<span class="elsevierStyleHsp" style=""></span>mg/dL, lactate dehydrogenase (LDH) of 201<span class="elsevierStyleHsp" style=""></span>U/L and C-reactive protein (CRP) of 190<span class="elsevierStyleHsp" style=""></span>mg/L. The microbiological study was negative and methotrexate concentrations were undetectable.</p><p id="par0025" class="elsevierStylePara elsevierViewall">In view of these findings, a peripheral blood smear was performed, showing leukopenia; few neutrophils and lymphocytes were observed without morphological abnormalities or signs of immaturity. Subsequently, a bone marrow aspirate was performed by sternal puncture, in the extension of which a bone marrow with decreased overall cellularity at the expense of the descent of the three series was observed, with no significant dysplastic features:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">•</span><p id="par0030" class="elsevierStylePara elsevierViewall">Leucocyte series: decreased granulocytic series, although present in all maturation stages. No signs of dysgranulopoiesis were observed. Plasmacytosis and lymphocytosis without morphological alterations, probably as filler cellularity.</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">•</span><p id="par0035" class="elsevierStylePara elsevierViewall">Erythroid series: few ortho and polychromatic erythroblasts showing some isolated binuclear erythroblasts.</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">•</span><p id="par0040" class="elsevierStylePara elsevierViewall">Platelet series: severely decreased megakaryocytes, some of them hypoploid.</p></li></ul></p><p id="par0045" class="elsevierStylePara elsevierViewall">The study was extended by fluorescent in situ hybridization (FISH) with a negative result for 5q31, 7q31, 20q and chromosome 8 trisomy. The karyotype results were normal (46XY).</p><p id="par0050" class="elsevierStylePara elsevierViewall">After the administration of broad-spectrum antibiotic therapy, intravenous calcium folinate, and granulocyte colony-stimulating factors, the patient's progression was favourable, with resolution of digestive symptoms, a decrease in acute phase reactants and remaining afebrile. In the following days there was a gradual recovery of the haematimetric parameters reaching normal values. The patient was discharged after ten days of hospitalization, with successive check-ups in the outpatient clinic, during which he remained free of cytopenia.</p><p id="par0055" class="elsevierStylePara elsevierViewall">Using the Naranjo<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> algorithm, a method for estimating the probability of adverse drug reactions, methotrexate is likely (7 points) to be responsible for this patient's laboratory/clinical findings.</p><p id="par0060" class="elsevierStylePara elsevierViewall">Methotrexate is a folic acid antagonist. Its mechanism of action consists of irreversibly inhibiting the enzyme dihydrofolate-reductase, causing a block in the synthesis of the nucleotide thymidine and some amino acids such as serine or methionine. It inhibits DNA and protein synthesis in dividing cells and, administered mainly orally or intravenously, is used as a treatment for various neoplasms and autoimmune diseases. Its toxicity is concentration- and exposure-dependent, with gastrointestinal, hepatic, renal and bone marrow toxicity being the most significant.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">The clinical case reported here is the fourth in the medical literature showing myelotoxicity due to intralesional methotrexate,<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4,5</span></a> with the presence of advanced renal failure on dialysis being a common feature in all of them. The systemic absorption of methotrexate after intralesional administration in patients with decreased excretion and subsequent accumulation seems to be the cause of toxicity in these patients.</p><p id="par0070" class="elsevierStylePara elsevierViewall">As a result of this case and the review of the literature, we must take into account that the intralesional methotrexate administration to treat localized dermatological lesions can lead to serious systemic complications in patients with advanced renal failure, even at low doses. For this reason, considering alternative treatments or, where appropriate, close monitoring of toxicity in these patients is recommended.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflict of interests</span><p id="par0075" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflict of interests.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflict of interests" ] 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: Gámez Jiménez EM, Muñoz Ballester J, Badiola J. Pancitopenia tras administración de metotrexato intralesional en un paciente en programa de hemodiálisis. Med Clin (Barc). 2021;156:527.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Intralesional agents in the management of cutaneous malignancy: a review" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "L.M. Good" 1 => "M.D. Miller" 2 => "W.A. High" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jaad.2009.12.013" "Revista" => array:6 [ "tituloSerie" => "J Am Acad Dermatol" "fecha" => "2011" "volumen" => "64" "paginaInicial" => "413" "paginaFinal" => "422" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20334952" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A method for estimating the probability of adverse drug reactions" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C.A. Naranjo" 1 => "U. Busto" 2 => "E.M. Sellers" 3 => "P. Sandor" 4 => "I. Ruiz" 5 => "E.A. Roberts" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/clpt.1981.154" "Revista" => array:6 [ "tituloSerie" => "Clin Pharmacol Ther" "fecha" => "1981" "volumen" => "30" "paginaInicial" => "239" "paginaFinal" => "245" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7249508" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "AHFS drug information" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "E.K. Snow" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:2 [ "fecha" => "2009" "editorial" => "Bethesda" ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Pancytopenia, mucositis, and hepatotoxicity after intralesional methotrexate injection in a patient treated with peritoneal dialysis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "K.N. Flynn" 1 => "M.S. Johnson" 2 => "W.C. Brink" 3 => "D.L. 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Vol. 156. Issue 10.
Pages 527 (May 2021)
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Vol. 156. Issue 10.
Pages 527 (May 2021)
Letter to the Editor
Pancytopenia after administration of intralesional methotrexate in a patient in hemodialysis program
Pancitopenia tras administración de metotrexato intralesional en un paciente en programa de hemodiálisis
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Elena María Gámez Jiménez, Julia Muñoz Ballester, Jon Badiola
Corresponding author
Unidad de Gestión Clínica de Hematología y Hemoterapia. Hospital Universitario Virgen de las Nieves, Granada, Spain
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