Case report
Mycophenolate mofetil-induced mouth ulcers in a kidney transplant patient: Case report and literature review
Úlceras orales secundarias a micofenolato mofetilo en un paciente trasplantado renal: caso clínico y revisión de la literatura
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Evolution and treatment of a difficult pathology" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "84" "paginaFinal" => "86" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Enfermedad de cambios mínimos compatible con nefropatía C1q en paciente pediátrico. Evolución y tratamiento de una enfermedad complicada" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 725 "Ancho" => 1255 "Tamanyo" => 158158 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">(A) Kidney biopsy. 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array:4 [ "nombre" => "Adrià" "apellidos" => "Plana-Pla" "email" => array:1 [ 0 => "adriplanapla@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Laura Cañas" "apellidos" => "Solé" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "Aram Boada" "apellidos" => "Garcia" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "Ricardo Lauzurica" "apellidos" => "Valdemoros" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Department of Dermatology, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Department of Nephrology, Hospital Universitari, Germans Trias i Pujol, Badalona, Barcelona, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "<span class="elsevierStyleItalic">Corresponding author</span>." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Úlceras orales secundarias a micofenolato mofetilo en un paciente trasplantado renal: caso clínico y revisión de la literatura" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 713 "Ancho" => 950 "Tamanyo" => 78617 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Clinical photograph shows 1 minor aphthous ulcer, on buccal mucosa.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Differential diagnosis of oral ulcers is often difficult, because it covers a large number of disorders. Some infections such as the herpes virus, bullous, autoimmune and hematologic diseases and some malignancies are just a few examples of what may ulcerate the oral mucosa.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">1</span></a> In immunocompromised patients, some unusual disorders, otherwise uncommon in immunocompetent individuals, should also be considered, such as fungal infections, cytomegalovirus (CMV) or drug-induced ulcers. The latter are normally produced by immunosuppressive drugs and are therefore usually seen in polymedicated patients who are susceptible to all kinds of infections, which makes correct diagnosis even more complex.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">2</span></a> Unlike some immunosuppressants, where a higher capacity for resulting in oral ulcers has been demonstrated (mTOR inhibitors are most commonly associated with this type of ulcers), as far as we know, mycophenolate mofetil (MMF) has been noted to rarely cause oral ulcers with only 9 patients reported.<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">1–6</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Here we report one new case of MMF-induced oral ulcerations. We also review all patients in the literature with this uncommon side effect.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Report</span><p id="par0015" class="elsevierStylePara elsevierViewall">A 67 year-old man with renal insufficiency due to polycystic kidney disease and arterial hypertension underwent a kidney transplant in 2015. He received immunosupressive treatment with metilprednisolone (5<span class="elsevierStyleHsp" style=""></span>mg/d), tacrolimus (16<span class="elsevierStyleHsp" style=""></span>mg/d) and MMF (2<span class="elsevierStyleHsp" style=""></span>g/d). Nine months after kidney transplantation 3 painful oral ulcers appeared on both sides of the tongue and on the oral mucosa. He also presented intense odynophagia, difficulty swallowing, decreased intake and weight loss without fever. On examination, 2 major aphthous ulcers, with surrounding edema and erythema were present on his tongue (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>) and 1 smaller erosion was observed in his buccal mucosa (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">Apart from the immunosupressive treatment, at this moment he was also taking oral valganciclovir because of a CMV infection reactivation. The blood sample test showed leukopenia, anemia and thrombocytopenia with a stable renal function (creatinine 2.2<span class="elsevierStyleHsp" style=""></span>mg/dl) and a normal hepatic profile. Levels of tacrolimus were correct in relation with the time after kidney transplantation.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Cultures of the oral lesions were negative for herpes simplex virus types 1 and 2, CMV, and fungus. Rapid plasma reagin (RPR) and HIV antibody testing results were nonreactive.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Oral biopsy showed nonspecific inflammatory changes on hematoxylin–eosin (H&E) staining. Finally MMF was subsequently discontinued. After 4 days, the patient's oral ulcers decreased considerably in size, with a significant reduction in his oral pain, improving the ability to eat and drink. After 9 days, complete healing of the patient's ulcers was observed. The patient has since remained off MMF with no recurrences of his ulcerations.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Discussion</span><p id="par0035" class="elsevierStylePara elsevierViewall">MMF is a powerful immunosuppressant that is often used to prevent acute rejection in hematopoietic stem cell or solid organ transplant patients as well as in some autoimmune diseases.<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">7,8</span></a> Its mechanism of action is based on inhibition of purine synthesis via inhibition of the inosine phosphate dehydrogenase enzyme. This results in a decrease in lymphocyte proliferation that is responsible for the immunosuppressive effects of the drug.<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">7,8</span></a> Its most common side effects are digestive in the form of diarrhea or vomiting with extremely varied other adverse effects. Among them, oral ulcers are one of the less frequent and therefore less known by dermatologists.</p><p id="par0040" class="elsevierStylePara elsevierViewall">We searched PubMed with the terms “mycophenolate mofetil” and “oral ulceration” and found 9 cases in the English-language literature. Characteristics of the patients are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">Since the first case reported in 2001, 9 additional cases of MMF-oral ulcerations have been described (including our patient) presenting as very painful ulcers<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">1</span></a> (2 or more ulcers per patient), located in the oral mucosa. One case had also anal ulcers and another, edema in gums. To date, all cases published, are in patients who have undergone a solid organ transplant and the dose of MMF that they were receiving, ranged from 1 to 2<span class="elsevierStyleHsp" style=""></span>g/d. In all the cases, the ulcers healed quickly once the drug was stopped. In every reported case improvement of the lesions is observed within the first 4–10 days and complete healing is seen in 6 weeks at most.<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">1–6</span></a> Our patient referred significant improvement only four days after stopping the drug. These lesions are usually not accompanied by other side effects and the interval time between starting the drug and the appearance of the ulcers varies greatly, with described cases ranging from 1 week to 3 years.</p><p id="par0050" class="elsevierStylePara elsevierViewall">From the microscopic point of view no specific findings are observed, usually showing nonspecific mixed inflammatory infiltrates with a negative immunofluorescence.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">1</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">Despite of this, in our opinion biopsy should always be performed in order to rule out other common diseases such as fungal infections or CMV.</p><p id="par0060" class="elsevierStylePara elsevierViewall">Regarding the pathogenesis of these lesions, most authors propose their appearance as the result of a direct cytotoxic effect of the drug on the mucosa although this point is not yet fully proven.</p><p id="par0065" class="elsevierStylePara elsevierViewall">In conclusion, oral ulcers caused by MMF are a rare cause of oral ulcers that dermatologists should be aware of.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Conflict of interests</span><p id="par0070" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interests.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:9 [ 0 => array:3 [ "identificador" => "xres1158891" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1085689" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1158892" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1085690" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Report" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Discussion" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Conflict of interests" ] 8 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2017-09-19" "fechaAceptado" => "2018-05-06" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1085689" "palabras" => array:4 [ 0 => "Kidney transplant" 1 => "Mycophenolate mofetil" 2 => "Mouth ulcers" 3 => "Cytomegalovirus" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1085690" "palabras" => array:4 [ 0 => "Trasplante renal" 1 => "Micofenolato mofetilo" 2 => "Úlceras orales" 3 => "Citomegalovirus" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Mouth ulcers are a cutaneous complication that can often affect kidney transplant patients, mostly due to the effect of immunosuppressive treatment.</p><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Even so, before asserting that said complication is indeed secondary to drugs, it is very important to establish a differential diagnosis with other mouth ulcer causes, such as systemic diseases or viral infections, which are also common in these patients.</p></span>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Las úlceras orales son una de las complicaciones cutáneas que pueden afectar con frecuencia a los pacientes trasplantados renales, debido muchas veces al efecto del tratamiento inmunosupresor.</p><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Aun así, es importante, antes de asegurar que dicha complicación es secundaria a los fármacos, establecer el diagnóstico diferencial con otras causas de úlceras orales como pueden ser enfermedades sistémicas o infecciones virales, también frecuentes en este tipo de pacientes.</p></span>" ] ] "multimedia" => array:3 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 713 "Ancho" => 950 "Tamanyo" => 112583 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Clinical photograph shows 2 major aphthous ulcers, with surrounding edema and erythema, on the tongue.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 713 "Ancho" => 950 "Tamanyo" => 78617 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Clinical photograph shows 1 minor aphthous ulcer, on buccal mucosa.</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="spar0040" class="elsevierStyleSimplePara elsevierViewall">MMF, mycophenolate mofetil.</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="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Study \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Year \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Age, years \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Sex \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Transplant type \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Time since transplant \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Clinical presentation \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Histopathology \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">MMF dose \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Concomitant drugs \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Outcome after MMF withdrawal \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Salik et al.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">1</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2015 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">68 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Renal \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8 months \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3 major oral ulcers, sever oral pain \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Nonspecific inflammatory changes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2<span class="elsevierStyleHsp" style=""></span>g/d \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Tacrolimus (16<span class="elsevierStyleHsp" style=""></span>mg/d) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Healing after 9 days \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Salik et al.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">1</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2015 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">59 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">W \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Liver \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5 months \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 major and 1 minor oral ulcers, sever oral pain \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Nonspecific inflammatory changes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2<span class="elsevierStyleHsp" style=""></span>g/d \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Tacrolimus (6<span class="elsevierStyleHsp" style=""></span>mg/d), prednisone (2.5<span class="elsevierStyleHsp" style=""></span>mg/d) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Healing after 4 days \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Salik et al.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">1</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2015 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">64 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">W \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Lung \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10 months \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 major and 4 minor oral ulcers and sever oral pain \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Nonspecific inflammatory changes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1<span class="elsevierStyleHsp" style=""></span>g/d \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ciclosporine (200<span class="elsevierStyleHsp" style=""></span>mg/d), prednisone (40<span class="elsevierStyleHsp" style=""></span>mg/d) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Healing after 7 days \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Philipone et al.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">2</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2014 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">54 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">W \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Renal \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5 months \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 major and several minor oral ulcers and sever oral pain \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Nonspecific inflammatory changes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2<span class="elsevierStyleHsp" style=""></span>g/d \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Tacrolimus (16<span class="elsevierStyleHsp" style=""></span>mg/d) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Healing 4 weeks \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Weng et al.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">3</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2011 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">23 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Renal \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5 months \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Several minor ulcers, gum swelling and sever oral pain \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No biopsy was done \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2<span class="elsevierStyleHsp" style=""></span>g/d \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ciclosporine (300<span class="elsevierStyleHsp" style=""></span>mg/d), prednisone (12.5<span class="elsevierStyleHsp" style=""></span>mg/d) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Great improvement after 1 week and complete healing after 6 weeks \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Naranjo et al.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">4</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2007 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">60 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">W \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Liver \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5 days \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 major oral ulcers \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No biopsy was done \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1<span class="elsevierStyleHsp" style=""></span>g/d \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Tacrolimus and prednisone (no doses specified) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Healing after 5 days \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Naranjo et al.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">4</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2007 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">31 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">W \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Liver \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No specified \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 major oral ulcers \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No biopsy was done \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.5<span class="elsevierStyleHsp" style=""></span>g/d \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ciclosporine and metilprednisolone (no doses specified) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Healing after 1 week \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Apostolou et al.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">5</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2004 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">62 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">W \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Renal \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 major and 3 minor oral ulcers and sever oral pain \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Nonspecific inflammatory changes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2<span class="elsevierStyleHsp" style=""></span>g/d \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Tacrolimus (4<span class="elsevierStyleHsp" style=""></span>mg/d), prednisone (7.5<span class="elsevierStyleHsp" style=""></span>mg/d) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Great improvement after 6 days and complete healing after 6 weeks \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Garrigue<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">6</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">52 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Renal \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6 months \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Several oral and anal ulcers and sever oral pain \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Nonspecific inflammatory changes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2<span class="elsevierStyleHsp" style=""></span>g/d \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ciclosporine (400<span class="elsevierStyleHsp" style=""></span>mg/d), prednisone (10<span class="elsevierStyleHsp" style=""></span>mg/d) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Complete healing after 3 weeks \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1978546.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Characteristics of the patients included in the study.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:8 [ 0 => array:3 [ "identificador" => "bib0045" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mycophenolate mofetil-induced oral ulcerations in solid organ transplant recipients: a report of 3 cases" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "J. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 17 | 9 | 26 |
| 2024 October | 91 | 56 | 147 |
| 2024 September | 117 | 58 | 175 |
| 2024 August | 104 | 88 | 192 |
| 2024 July | 125 | 55 | 180 |
| 2024 June | 115 | 56 | 171 |
| 2024 May | 78 | 42 | 120 |
| 2024 April | 77 | 42 | 119 |
| 2024 March | 120 | 40 | 160 |
| 2024 February | 106 | 42 | 148 |
| 2024 January | 101 | 51 | 152 |
| 2023 December | 192 | 25 | 217 |
| 2023 November | 374 | 73 | 447 |
| 2023 October | 593 | 59 | 652 |
| 2023 September | 511 | 71 | 582 |
| 2023 August | 467 | 41 | 508 |
| 2023 July | 402 | 54 | 456 |
| 2023 June | 368 | 28 | 396 |
| 2023 May | 297 | 61 | 358 |
| 2023 April | 267 | 37 | 304 |
| 2023 March | 394 | 40 | 434 |
| 2023 February | 280 | 42 | 322 |
| 2023 January | 313 | 37 | 350 |
| 2022 December | 400 | 46 | 446 |
| 2022 November | 324 | 61 | 385 |
| 2022 October | 306 | 71 | 377 |
| 2022 September | 248 | 45 | 293 |
| 2022 August | 260 | 66 | 326 |
| 2022 July | 271 | 67 | 338 |
| 2022 June | 312 | 52 | 364 |
| 2022 May | 320 | 31 | 351 |
| 2022 April | 359 | 70 | 429 |
| 2022 March | 328 | 66 | 394 |
| 2022 February | 389 | 66 | 455 |
| 2022 January | 383 | 57 | 440 |
| 2021 December | 310 | 41 | 351 |
| 2021 November | 219 | 36 | 255 |
| 2021 October | 369 | 74 | 443 |
| 2021 September | 361 | 53 | 414 |
| 2021 August | 368 | 68 | 436 |
| 2021 July | 325 | 64 | 389 |
| 2021 June | 371 | 31 | 402 |
| 2021 May | 387 | 48 | 435 |
| 2021 April | 758 | 79 | 837 |
| 2021 March | 465 | 33 | 498 |
| 2021 February | 382 | 38 | 420 |
| 2021 January | 275 | 26 | 301 |
| 2020 December | 277 | 26 | 303 |
| 2020 November | 234 | 23 | 257 |
| 2020 October | 183 | 19 | 202 |
| 2020 September | 220 | 21 | 241 |
| 2020 August | 210 | 22 | 232 |
| 2020 July | 224 | 13 | 237 |
| 2020 June | 177 | 21 | 198 |
| 2020 May | 187 | 13 | 200 |
| 2020 April | 310 | 34 | 344 |
| 2020 March | 262 | 15 | 277 |
| 2020 February | 273 | 21 | 294 |
| 2020 January | 329 | 44 | 373 |
| 2019 December | 192 | 29 | 221 |
| 2019 November | 134 | 27 | 161 |
| 2019 October | 140 | 28 | 168 |
| 2019 September | 121 | 22 | 143 |
| 2019 August | 74 | 18 | 92 |
| 2019 July | 74 | 27 | 101 |
| 2019 June | 52 | 29 | 81 |
| 2019 May | 50 | 27 | 77 |
| 2019 April | 97 | 78 | 175 |
| 2019 March | 22 | 29 | 51 |
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