Case Report
Visceral leishmaniasis in a patient with rheumatoid arthritis treated with methotrexate
Leishmaniasis visceral en un paciente con artritis reumatoide en tratamiento con metotrexato
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(B) Axial image of the first chest CT (window of pulmonary parenchyma) in which a nodular lesion of ground-glass attenuation is observed (arrow). (C) MIP (maximum intensity projection) axial image of the second chest CT (window of pulmonary parenchyma) in which a radiological progression is observed despite antituberculosis treatment and the galaxy sign: solid nodular opacities (arrows) surrounded by multiple solid 1–2<span class="elsevierStyleHsp" style=""></span>mm nodules. (D) Coronal imaging of SPECT/CT with gallium in which uptake by the pulmonary nodules (white arrows) is determined and by the right pulmonary hilar adenopathies and ipsilateral mediastinum (black arrows).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Luis Gorospe Sarasúa, Almudena Ureña-Vacas, Paola Arrieta, Astrid Lucía Santos-Carreño, Enrique Navas-Elorza, Carlos de la Puente-Bujidos" "autores" => array:6 [ 0 => array:2 [ "nombre" => "Luis" "apellidos" => "Gorospe Sarasúa" ] 1 => array:2 [ "nombre" => "Almudena" "apellidos" => "Ureña-Vacas" ] 2 => array:2 [ "nombre" => "Paola" "apellidos" => "Arrieta" ] 3 => array:2 [ "nombre" => "Astrid Lucía" "apellidos" => "Santos-Carreño" ] 4 => array:2 [ "nombre" => "Enrique" "apellidos" => "Navas-Elorza" ] 5 => array:2 [ "nombre" => "Carlos" "apellidos" => "de la Puente-Bujidos" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S1699258X17301985" "doi" => "10.1016/j.reuma.2017.07.022" "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/S1699258X17301985?idApp=UINPBA00004M" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173574318301588?idApp=UINPBA00004M" "url" => "/21735743/0000001500000006/v1_201911250632/S2173574318301588/v1_201911250632/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S2173574319301121" "issn" => "21735743" "doi" => "10.1016/j.reumae.2017.08.011" "estado" => "S300" "fechaPublicacion" => "2019-11-01" "aid" => "1122" "copyright" => "Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "crp" "cita" => "Reumatol Clin. 2019;15:e128-e129" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 1 "HTML" => 1 ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Case Report</span>" "titulo" => "Haemothorax in vascular Ehlers-Danlos syndrome" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "e128" "paginaFinal" => "e129" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Hemotórax en síndrome de Ehlers-Danlos tipo vascular" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "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" => 1216 "Ancho" => 1267 "Tamanyo" => 114300 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">CT image of the thorax, sagittal view. The internal mammary artery and the haematoma that originates from its rupture can be observed.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Kevin Álvarez, Jordi López, Jose Angel Hernández" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Kevin" "apellidos" => "Álvarez" ] 1 => array:2 [ "nombre" => "Jordi" "apellidos" => "López" ] 2 => array:2 [ "nombre" => "Jose Angel" "apellidos" => "Hernández" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S1699258X17302334" "doi" => "10.1016/j.reuma.2017.08.009" "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/S1699258X17302334?idApp=UINPBA00004M" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173574319301121?idApp=UINPBA00004M" "url" => "/21735743/0000001500000006/v1_201911250632/S2173574319301121/v1_201911250632/en/main.assets" ] "en" => array:21 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Case Report</span>" "titulo" => "Visceral leishmaniasis in a patient with rheumatoid arthritis treated with methotrexate" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "e130" "paginaFinal" => "e132" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Jesús Loarce-Martos, Sandra Garrote-Corral, Francesca Gioia, Javier Bachiller-Corral" "autores" => array:4 [ 0 => array:4 [ "nombre" => "Jesús" "apellidos" => "Loarce-Martos" "email" => array:1 [ 0 => "jesus.loarce@salud.madrid.org" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Sandra" "apellidos" => "Garrote-Corral" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "Francesca" "apellidos" => "Gioia" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "Javier" "apellidos" => "Bachiller-Corral" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Servicio de Reumatología, Hospital Universitario Ramón y Cajal, Madrid, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Enfermedades Infecciosas, Hospital Universitario Ramón y Cajal, Madrid, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Leishmaniasis visceral en un paciente con artritis reumatoide en tratamiento con metotrexato" ] ] "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" => 934 "Ancho" => 800 "Tamanyo" => 99063 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Bone marrow biopsy: several macrophages can be seen with <span class="elsevierStyleItalic">Leishmania</span> amastigotes in their interior (arrow).</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Leishmaniasis is a protozoal intracellular infection caused by the bite of a dipteral insect. The development of the disease depends on the virulence of the parasite and host risk factors, essentially the state of their immune system. Patients with rheumatoid arthritis (RA) are chronically treated with methotrexate and other immunosuppressants and are therefore at risk of developing infections.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">1</span></a> The spectrum of opportunistic infections is very broad in these patients, however, cases of leishmaniasis are rare, especially in patients treated only with methotrexate.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Clinical case</span><p id="par0010" class="elsevierStylePara elsevierViewall">We present the case of an 84-year-old male, resident of a southern area of Madrid (an area with a high rabbit population), with a personal history of hypertension, diabetes mellitus, dyslipidaemia, heart failure with atrial fibrillation, with pacemaker implantation due to a third degree atrioventricular heart block, diagnosed 6 years earlier with RA with positive rheumatoid factor, positive anti-cyclic citrullinated peptide antibodies, treated with weekly methotrexate 15<span class="elsevierStyleHsp" style=""></span>mg, with good clinical response. Admitted due to fever, shivering and chills over one week. On physical examination slight bibasalar crackles were observed. No adenopathies, visceromegaly or other data of infectious disease were observed. Analytical tests revealed pancytopenia (haemoglobin 10.9<span class="elsevierStyleHsp" style=""></span>g/dl, 2050 leukocytes with 1310<span class="elsevierStyleHsp" style=""></span>neutrophils/μl and 49,000 platelets/μl), C reactive protein (CPR) 104<span class="elsevierStyleHsp" style=""></span>mg/l and erythrocyte sedimentation rate 110<span class="elsevierStyleHsp" style=""></span>mm/h. Initially medullary toxicity by methotrexate was suspected, with probable bacterial superinfection.</p><p id="par0015" class="elsevierStylePara elsevierViewall">The methotrexate was suspended and several microbiological tests (blood cultures, urine culture, sputum culture, viral and bacterial serologies) and imaging tests (thoracic-abdominal computed tomography, transthoracic and transoesophageal echocardiography) were requested, all of which were not diagnostic of the patient's current condition. Treatment with folic acid and broad-spectrum empirical antibiotics was initiated. Given the persistence of fever and pancytopenia, a bone marrow biopsy was performed to diagnose visceral leishmaniasis (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). Serology for <span class="elsevierStyleItalic">Leishmania</span> was positive (titre 1/640) as was polymerase chain reaction (PCR) in the bone marrow biopsy and peripheral blood culture. By contrast, peripheral blood culture was negative. Treatment was started with liposomal amphotericin B 200<span class="elsevierStyleHsp" style=""></span>mg <span class="elsevierStyleSmallCaps">IV</span> initially every 4 days until reaching a cumulative dose of 2400<span class="elsevierStyleHsp" style=""></span>mg. When the treatment was completed, the patient had recovered from the pancytopenia, showed a decrease in antibody titres, and CPR in blood remained negative.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Discussion</span><p id="par0020" class="elsevierStylePara elsevierViewall">Leishmaniasis is a zoonosis caused by more than 20 species of intracellular protozoa of the genus <span class="elsevierStyleItalic">Leishmania</span>. It is transmitted through the bite of an infected female diptera (<span class="elsevierStyleItalic">Phlebotomus</span> and <span class="elsevierStyleItalic">Lutzomya</span> genuses). Mammals act as reservoirs, the most important in our environment being dogs and rodents.</p><p id="par0025" class="elsevierStylePara elsevierViewall">The infection may be asymptomatic, localised or disseminated (mucocutaneous or visceral). According to the World Health Organisation, there are between 900,000 and 1.3 million new cases each year worldwide; of these, between 200,000 and 400,000 have the visceral form. In the Mediterranean basin the infection is due to <span class="elsevierStyleItalic">Leishmania infantum</span> (<span class="elsevierStyleItalic">Leishmania donovani complex</span>), responsible for the visceral form. This is characterised by fever, weight loss, hepatosplenomegaly and pancytopenia. Progression of the disease depends on the aggressiveness of the parasite and on host risk factors such as immunosuppression. The activation of the cell-specific immune response of T helper 1 lymphocytes and the production of macrophage-activating cytokines, such as gamma interferon, interleukin 12 and tumour necrosis factor alpha TNF-α), play an essential role in defence against the disease. Methotrexate inhibits neutrophil chemotaxis and T lymphocyte proliferation, decreasing macrophage activation and response against the parasite.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Diagnosis can be made from tissue samples (skin, spleen, bone marrow or lymph nodes) by direct visualisation of the parasite, culture or quantification of DNA by CRP. CRP and antibody detection by ELISA or indirect immunofluorescence are performed from peripheral blood.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">1</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Conclusions</span><p id="par0035" class="elsevierStylePara elsevierViewall">RA affects .5%–1% of the world's population and most patients are treated with methotrexate.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">2</span></a> Multiple cases of visceral leishmaniasis have been described in patients with RA on biological therapy, especially in treatment with anti-TNF, but after a review of the literature we found only 9 cases published on patients treated with methotrexate alone, almost all of them in the Mediterranean area (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>) and, given the few cases, it is difficult to establish a subgroup of patients that is more susceptible to the infection.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall">Between 2009 and 2012 there was an outbreak of leishmaniasis in the Community of Madrid, affecting 446 people. Of the 160 patients with visceral leishmaniasis, 25 were on immunosuppressive therapy.<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">3,4</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">In conclusion, the presence of fever and pancytopenia in a patient with cell immunosuppression in an endemic area makes it necessary to rule out leishmaniasis. Exclusive therapy with methotrexate (without biological treatments) in RA may be sufficient to increase the risk of this infection. Bone marrow biopsy enables diagnosis of visceral leishmaniasis, as well as ruling out other causes of pancytopenia.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">1</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Ethical disclosures</span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Protection of human and animal subjects</span><p id="par0050" class="elsevierStylePara elsevierViewall">The authors declare that neither human nor animal testing has been carried out under this research.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Confidentiality of data</span><p id="par0055" class="elsevierStylePara elsevierViewall">The authors declare that they have complied with their work centre protocols for the publication of patient data.</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Right to privacy and informed consent</span><p id="par0060" class="elsevierStylePara elsevierViewall">The authors have obtained the informed consent of the patients and/or subjects referred to in the article. This document is held by the corresponding author.</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Conflict of interests</span><p id="par0065" class="elsevierStylePara elsevierViewall">The authors have no conflict of interests to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:12 [ 0 => array:3 [ "identificador" => "xres1268389" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1173990" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1268390" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1173989" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Clinical case" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Discussion" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Conclusions" ] 8 => array:3 [ "identificador" => "sec0025" "titulo" => "Ethical disclosures" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0030" "titulo" => "Protection of human and animal subjects" ] 1 => array:2 [ "identificador" => "sec0035" "titulo" => "Confidentiality of data" ] 2 => array:2 [ "identificador" => "sec0040" "titulo" => "Right to privacy and informed consent" ] ] ] 9 => array:2 [ "identificador" => "sec0045" "titulo" => "Conflict of interests" ] 10 => array:2 [ "identificador" => "xack435308" "titulo" => "Acknowledgements" ] 11 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2017-06-11" "fechaAceptado" => "2017-07-23" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1173990" "palabras" => array:3 [ 0 => "Visceral leishmaniasis" 1 => "Rheumatoid arthritis" 2 => "Methotrexate" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1173989" "palabras" => array:3 [ 0 => "Leishmaniasis visceral" 1 => "Artritis reumatoide" 2 => "Metotrexato" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">A large number of complications have been associated with rheumatoid arthritis (RA), those of infectious aetiology being of special relevance. Their high incidence is closely linked to the use of immunosuppressive medication.</p><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">The spectrum of agents causing opportunistic infections in patients with RA is very broad; however, there are relatively few cases of Leishmania infection, especially in patients not being treated with biological drugs.</p></span>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Los pacientes con artritis reumatoide (AR) pueden presentar un número amplio de complicaciones, siendo de especial importancia las de etiología infecciosa. Su elevada incidencia está muy ligada al uso de inmunosupresores.</p><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">El espectro de agentes causantes de infecciones oportunistas en pacientes con AR es muy amplio; sin embargo, son relativamente escasos los casos de infección por <span class="elsevierStyleItalic">Leishmania</span>, especialmente en pacientes sin tratamiento con fármacos biológicos.</p></span>" ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Loarce-Martos J, Garrote-Corral S, Gioia F, Bachiller-Corral J. Leishmaniasis visceral en un paciente con artritis reumatoide en tratamiento con metotrexato. Reumatol Clin. 2019;15:e130–e132.</p>" ] ] "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 934 "Ancho" => 800 "Tamanyo" => 99063 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Bone marrow biopsy: several macrophages can be seen with <span class="elsevierStyleItalic">Leishmania</span> amastigotes in their interior (arrow).</p>" ] ] 1 => 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:1 [ "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">Case \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">Author, year \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, sex, country \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">Comorbidity \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 (drug, dose, duration) \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" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" 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">Toqeer et al., 2012<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">5</span></a> \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">64 years, male, United Kingdom (trips to Spain) \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">18-Year history of RA \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">Methotrexate, unknown dose, 3 years \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" 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">Venizelos et al<span class="elsevierStyleSmallCaps">.</span>, 2009<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">6</span></a> \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">65 year, female, Greece \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">8-Year history of RA \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">Methotrexate, unknown dose, 8 years \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" 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">Harms et al., 2003<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">7</span></a> \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">67 years, male, Italy \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">Unspecified rheumatological disease \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">Methotrexate, unknown dose and duration \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" 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">Harmset al., 2003<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">7</span></a> \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">68 years, male, Italy \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">Unspecified rheumatological disease \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">Methotrexate and steroids, unknown dose and duration \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" 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">Garcia Olid et al., 2012<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">8</span></a> \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">67 years, male, Spain \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-Year history of RA \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">Methotrexate, 15<span class="elsevierStyleHsp" style=""></span>mg/week, unknown duration \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 \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">Garcia Olid et al., 2012<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">8</span></a> \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">51 years, male, Spain \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">16-Year history of RA \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">Methotrexate, 10<span class="elsevierStyleHsp" style=""></span>mg weekly, leflunomide 10<span class="elsevierStyleHsp" style=""></span>mg daily, unknown duration \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 \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">Karagiannidis et al., 2012<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">9</span></a> \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">79 years, female, Greece \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">3-Year history of RA \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">Methotrexate, 10<span class="elsevierStyleHsp" style=""></span>mg weekly, one year \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 \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">Reina et al., 2016<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">10</span></a> \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">64 years, female, Spain \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-Year history of RA \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">Methotrexate 15<span class="elsevierStyleHsp" style=""></span>mg weekly, prednisone, unknown duration \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 \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">Trigkidis et al., 2017<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">11</span></a> \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">71 years, female, Greece \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-Year history of RA \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">Methotrexate 2.5<span class="elsevierStyleHsp" style=""></span>mg weekly, 3 years, methylprednisolone 4<span class="elsevierStyleHsp" style=""></span>mg/day, 3 years \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2169556.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Cases of visceral leishmaniasis in patients treated with methotrexate described in the literature.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:11 [ 0 => array:3 [ "identificador" => "bib0060" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Leishmaniasis in rheumatology, haematology and oncology: Epidemiological, immunological and clinical aspects and caveats" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "C. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 October | 38 | 23 | 61 |
| 2024 September | 53 | 16 | 69 |
| 2024 August | 58 | 32 | 90 |
| 2024 July | 52 | 42 | 94 |
| 2024 June | 39 | 22 | 61 |
| 2024 May | 50 | 20 | 70 |
| 2024 April | 51 | 31 | 82 |
| 2024 March | 43 | 29 | 72 |
| 2024 February | 49 | 21 | 70 |
| 2024 January | 35 | 22 | 57 |
| 2023 December | 27 | 27 | 54 |
| 2023 November | 44 | 25 | 69 |
| 2023 October | 31 | 26 | 57 |
| 2023 September | 90 | 40 | 130 |
| 2023 August | 44 | 17 | 61 |
| 2023 July | 40 | 19 | 59 |
| 2023 June | 37 | 25 | 62 |
| 2023 May | 53 | 26 | 79 |
| 2023 April | 37 | 8 | 45 |
| 2023 March | 68 | 21 | 89 |
| 2023 February | 54 | 25 | 79 |
| 2023 January | 55 | 8 | 63 |
| 2022 December | 65 | 18 | 83 |
| 2022 November | 56 | 31 | 87 |
| 2022 October | 73 | 33 | 106 |
| 2022 September | 53 | 24 | 77 |
| 2022 August | 42 | 42 | 84 |
| 2022 July | 45 | 33 | 78 |
| 2022 June | 40 | 30 | 70 |
| 2022 May | 35 | 34 | 69 |
| 2022 April | 32 | 31 | 63 |
| 2022 March | 41 | 36 | 77 |
| 2022 February | 40 | 28 | 68 |
| 2022 January | 66 | 42 | 108 |
| 2021 December | 37 | 40 | 77 |
| 2021 November | 42 | 49 | 91 |
| 2021 October | 200 | 45 | 245 |
| 2021 September | 51 | 45 | 96 |
| 2021 August | 39 | 53 | 92 |
| 2021 July | 24 | 31 | 55 |
| 2021 June | 42 | 29 | 71 |
| 2021 May | 45 | 41 | 86 |
| 2021 April | 150 | 101 | 251 |
| 2021 March | 64 | 29 | 93 |
| 2021 February | 56 | 18 | 74 |
| 2021 January | 61 | 36 | 97 |
| 2020 December | 44 | 15 | 59 |
| 2020 November | 40 | 25 | 65 |
| 2020 October | 55 | 20 | 75 |
| 2020 September | 37 | 21 | 58 |
| 2020 August | 29 | 14 | 43 |
| 2020 July | 19 | 16 | 35 |
| 2020 June | 16 | 10 | 26 |
| 2020 May | 27 | 20 | 47 |
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