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Mesalazine inhibits leucocyte chemotaxis and decreases the production of cytokines, leukotrienes and free radicals by a poorly known mechanism.</p><p id="par0010" class="elsevierStylePara elsevierViewall">It is generally a well-tolerated drug, with its most frequent adverse effects (≥1/100 to <1/10) being: gastrointestinal discomfort, headache, joint pain and rashes.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Severe haematological toxicity is very rare (<1/10,000), with the following entities being described: neutropenia, thrombocytopenia, aplastic anaemia, pancytopenia and leukopenia.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a> The toxic mechanism is unknown; it could be due to a harmful effect on stem cells or to the immune system-mediated destruction of peripheral blood cells.</p><p id="par0020" class="elsevierStylePara elsevierViewall">We describe the case of an 82-year-old woman with a recent diagnosis of UC, hypertension, hypothyroidism, polyarthritis and active chronic hepatitis B. She had naproxen and ibuprofen intolerance. She was on daily treatment with levothyroxine 75<span class="elsevierStyleHsp" style=""></span>μg, valsartan 80<span class="elsevierStyleHsp" style=""></span>mg, omeprazole 20<span class="elsevierStyleHsp" style=""></span>mg, acetylsalicylic acid 100<span class="elsevierStyleHsp" style=""></span>mg, tenofovir 245<span class="elsevierStyleHsp" style=""></span>mg, oral mesalazine 4<span class="elsevierStyleHsp" style=""></span>g and topical mesalazine 4<span class="elsevierStyleHsp" style=""></span>g.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Three months after being diagnosed with UC and starting treatment, the patient went to the emergency department with a 2-day history of fever, diffuse abdominal pain, nausea, increased bowel movements and hypotension, without dysuria or other infectious symptoms. Initially, she was diagnosed with a moderate flare-up of UC. A worsening of her disease was ruled out after performing an emergency colonoscopy.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Severe leukopenia and neutropenia (1.8<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span> cells/l; 0.03<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span> cells/l, 1.5%) (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>) were observed in the first lab tests. This, associated to hypotension and fever led to the diagnosis of a serious sepsis, starting empirical antibiotic therapy with piperacillin–tazobactam. She was admitted under the care of the geriatric department. Given the persistence of grade IV neutropenia, 300<span class="elsevierStyleHsp" style=""></span>μg of filgrastim were administered 48<span class="elsevierStyleHsp" style=""></span>h after admission. Likewise, vancomycin was added to the empirical antibiotic treatment.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">After other possible causes of neutropenia were ruled out (vitamin deficiencies, viral infections, immunological cause, among others), a possible iatrogenic origin was considered, suspecting that mesalazine was the main agent responsible for the adverse reaction. This drug was discontinued from treatment and an intensified filgrastim 480<span class="elsevierStyleHsp" style=""></span>μg daily regimen was established for 8 days. After this period, a significant leukocytosis with neutrophilia was observed, withdrawing the medication. Levels took 10 days to normalize since filgrastim discontinuation.</p><p id="par0040" class="elsevierStylePara elsevierViewall">During admission, the patient developed: (a) multifactorial non-oliguric acute renal failure, corrected with fluid therapy and water intake; (b) mild atypical right pleural effusion, probably related to renal failure, and (c) iron deficiency anaemia, corrected with a dose of intravenous iron.</p><p id="par0045" class="elsevierStylePara elsevierViewall">The patient was discharged afebrile, hemodynamically stable, with normal leucocyte (8.9<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleSup">9</span>/l) and neutrophil (60.1%) levels 23 days after admission and 10 doses of filgrastim.</p><p id="par0050" class="elsevierStylePara elsevierViewall">A score of 7 was obtained after applying the causality algorithm of the Spanish Pharmacovigilance System, classifying the causal relationship as “probable”.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">2</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">A literature search was carried out using the Pubmed, Micromedex and Martindale databases as data source. The keywords used were: “Neutropenia”, “agranulocytosis”, “mesalamine”, “mesalazine” and “sulfasalazine”. The search did not have a temporal limit.</p><p id="par0060" class="elsevierStylePara elsevierViewall">Individual cases of neutropenia associated with mesalazine are described in the literature. Publications were selected from the last 20 years where the underlying disease had a gastrointestinal origin. All patients received antibiotic prophylaxis during hospital admission.<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">3–5</span></a> In one of the cases the recovery of neutrophil levels occurred without the need to administer filgrastim.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">5</span></a> In the other two, it was necessary to administer filgrastim for 20 and 15 days, respectively.<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">3,4</span></a> Except in one case, neutropenia developed shortly after the start of treatment (2 weeks-3 months),<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">3–5</span></a> just as it happened with our patient.</p><p id="par0065" class="elsevierStylePara elsevierViewall">The haematological toxicity of mesalazine may be aggravated by the occurrence of severe infections. Therefore, mesalazine discontinuation should be accompanied by other additional measures such as antibiotic prophylaxis. As a precaution, patients on mesalazine treatment should undergo regular complete blood tests.</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: Freire González M, Moro-Agud M, Oviedo Briones M. Neutropenia febril grave inducida por mesalazina. Med Clin. 2018;151:e33–e34.</p>" ] ] "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1610 "Ancho" => 2167 "Tamanyo" => 173091 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Leucocyte and neutrophil count progression.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0030" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Agencia Española del Medicamento y Productos Sanitarios. Ficha técnica Pentasa<span class="elsevierStyleSup">®</span> 2<span class="elsevierStyleHsp" style=""></span>g granulado de liberación prolongada [Accessed 8 Mar 2018]. 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Vol. 151. Issue 6.
Pages e33-e34 (September 2018)
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Vol. 151. Issue 6.
Pages e33-e34 (September 2018)
Letter to the Editor
Severe febrile neutropenia induced by mesalazine
Neutropenia febril grave inducida por mesalazina
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