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and had been diagnosed with RA in 2002 because of polyarthritis&#44; which was symmetrical&#44; erosive and seropositive &#40;positive for rheumatoid factor and anti-cyclic citrullinated peptide&#41;&#46; She progressively developed asymmetrical arthritis&#44; which affected large and small joints&#46; As background therapy for her disease she received 15<span class="elsevierStyleHsp" style=""></span>mg&#47;week of oral MTX&#44; 5<span class="elsevierStyleHsp" style=""></span>mg&#47;week of folic acid&#44; indomethacin at 25<span class="elsevierStyleHsp" style=""></span>mg&#47;8<span class="elsevierStyleHsp" style=""></span>h and low-dose prednisone&#46; She had no significant epidemiological history&#46; In 2012&#44; she had begun to note considerable weakness&#44; with episodes of spiking fever&#46; At the time of the present evaluation&#44; it had started 2 months earlier and was accompanied by pancytopenia &#40;leukocytes&#58; 3200 &#91;lymphocytes&#58; 1100&#93;&#44; hemoglobin&#58; 9<span class="elsevierStyleHsp" style=""></span>g&#47;L&#44; platelets&#58; 91&#44;000&#41;&#44; observed in a routine analysis&#46; She was admitted to the hospital to be studied&#46; The physical examination revealed mucocutaneous pallor and there were no signs of lymphadenopathy&#44; and the review of systems produced no new findings&#46; Treatment with MTX was discontinued due to the suspicion of hematotoxicity&#46; Abdominal ultrasound and computed tomography of abdomen and chest established the presence of splenomegaly&#46; Serology for human immunodeficiency virus and hepatitis B and C viruses was negative&#44; and a bone marrow aspirate &#40;BMA&#41; confirmed marrow cellularity preservation&#44; and diffuse intra- and extracellular involvement of leishmaniasis &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; Once the diagnosis of VL had been established&#44; treatment with liposomal amphotericin B was begun at a dose of 3<span class="elsevierStyleHsp" style=""></span>mg&#47;kg body weight until the patient had received 10 doses&#46; After 10 weeks&#44; she was afebrile and her blood count began to improve gradually until it was normal&#46; At the present time&#44; she is asymptomatic and is taking hydroxychloroquine&#44; and good clinical control has been achieved in the management of RA&#46;</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">Rheumatoid arthritis patients can develop a wide range of associated extra-articular comorbidities&#59; of these&#44; hematological disorders and infections account for a high percentage of cases&#44; and&#44; thus&#44; the differential diagnosis is very extensive&#46; Check-ups and follow-up visits of patients with RA are employed to monitor the analytical profile&#8212;hematological and biochemical&#8212;in accordance with recommended clinical practice guidelines&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> The study of a single cytopenia or of pancytopenia should include the complications of the disease itself&#44; the associated drug toxicity and possible nosocomial infections&#59; in addition&#44; hematological conditions should also be ruled out&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Leishmaniasis is understood to be a set of syndromes caused by infection of the protozoan of the genus <span class="elsevierStyleItalic">Leishmania</span>&#44; which is widely extended in tropical regions&#44; whereas <span class="elsevierStyleItalic">L&#46; infantum</span> causes a disease that is endemic in the Mediterranean&#46; It has three clinical profiles&#58; cutaneous&#44; mucosal and visceral&#46; The latter can be fatal in the absence of treatment&#46; It is transmitted by the bite of the phlebotomine sandfly&#46; Depending on the <span class="elsevierStyleItalic">Leishmania</span> species&#44; the genus of the transmitting insect and the geographic region&#44; the main reservoirs are dogs&#44; rodents and persons&#46; The onset of VL can be silent or&#44; in contrast&#44; full-blown &#40;kala-azar&#41;&#44; with its characteristic pentad&#58; prolonged fever&#44; weight loss&#44; hepatosplenomegaly&#44; pancytopenia and hypergammaglobulinemia&#46; At some point&#44; the subclinical disease can become symptomatic in patients who receive immunosuppressive agents like glucocorticoids&#44; MTX or BT&#46; There are three ways to establish the diagnosis of leishmaniasis&#58; clinical&#44; parasitic and immunological&#46; The parasitological diagnosis should be confirmed by the observation of the protozoan in a tissue or smear&#46; Should there be any doubt about the diagnosis&#44; the BMA provides satisfactory results&#46; The differential diagnosis of full-blown VL should include malignant hematological and lymphatic disorders&#44; as well as infectious diseases like malaria&#46; At the present time&#44; the treatment of choice of VL in developed countries is liposomal amphotericin B&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">In a review of the literature&#44; it is noteworthy that there are fewer cases of patients with RA being treated with MTX than those receiving anti-tumor necrosis factor &#40;TNF&#41; agents who develop <span class="elsevierStyleItalic">Leishmania</span> infection&#46; We have yet to know why&#46; These patients do not seem to have any common factor predisposing them to infection&#46; Methotrexate reduces the cell immune response&#44; inhibits neutrophil chemotaxis and T-cell proliferation&#44; and has been related to the development of infections by opportunistic pathogens&#44; among which we find <span class="elsevierStyleItalic">Leishmania</span>&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Patients with RA being treated with MTX have a greater predisposition to develop VL than the general population&#44; possibly due to immunological changes related to the underlying disease and the treatment they receive&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Tumor necrosis factor is a cytokine involved in the immune-mediated response to infection&#44; especially against intracellular pathogens&#46; The use of anti-TNF drugs in RA is growing&#44; and their utility is clearly related to an increase in the number of opportunistic infections in these patients&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">The diagnosis of VL should be considered in patients when there is a suspicion of infection if they are receiving MTX to treat an inflammatory rheumatic disease and live in regions in which leishmaniasis is endemic&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">The importance of the early diagnosis&#44; established during the follow-up visits in relation to the underlying disease&#44; made it possible for us to detect VL in our patient&#46; The prompt initiation of a specific treatment is fundamental in order to improve the prognosis of a potentially serious disease&#46; With this in mind&#44; we must not forget that&#44; although uncommon&#44; leishmaniasis is endemic in the Mediterranean&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Conclusion</span><p id="par0055" class="elsevierStylePara elsevierViewall">The current management of RA patients is very satisfactory&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> Improvements in monitoring and the identification of new therapeutic targets have resulted in high survival rates&#46; The prognosis is likewise more favorable&#59; however&#44; the same therapies that&#44; on occasion&#44; lead to remission&#44; also have certain additional risks&#46;<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">9&#44;10</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">The present report describes an infectious process that developed in the course of RA&#44; partially due to the associated susceptibility to chronic inflammatory disease&#44; together with the added risk conferred by immunosuppressive therapies like MTX&#46; The study of comorbidities of RA should emphasize infections by the usual pathogens&#44; without overlooking those produced by uncommon opportunistic microorganisms like <span class="elsevierStyleItalic">Leishmania</span>&#46;</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="par0065" class="elsevierStylePara elsevierViewall">The authors declare that no experiments were performed on humans or animals for this study&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Confidentiality of data</span><p id="par0070" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appear in this article&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Right to privacy and informed consent</span><p id="par0075" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appear in this article&#46;</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Conflicts of Interest</span><p id="par0080" class="elsevierStylePara elsevierViewall">The authors declare they have no conflicts of interest&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Patients with rheumatoid arthritis &#40;RA&#41; treated with disease-modifying antirheumatic drugs are susceptible to severe infections such as leishmaniasis&#46; As <span class="elsevierStyleItalic">L&#46; infantum</span> is endemic in the Mediterranean region&#44; it is necessary to rule this infectious process out in any RA patient presenting with fever and pancytopenia&#46; An early diagnosis based on a high suspicion can prevent a fatal outcome&#46;</p></span>"
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        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Los pacientes con artritis reumatoide &#40;AR&#41; tratados con f&#225;rmacos modificadores del curso de la enfermedad est&#225;n expuestos a desarrollar infecciones potencialmente graves como la leishmaniasis&#46; <span class="elsevierStyleItalic">L&#46; infantum</span> es end&#233;mica en el Mediterr&#225;neo&#44; hecho que obliga ante un paciente con AR que presenta fiebre y pancitopenia&#44; a descartar este proceso&#46; Un diagn&#243;stico de sospecha precoz&#44; puede evitar un curso y pron&#243;stico fatal&#46;</p></span>"
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Case Report
Visceral Leishmaniasis in a Rheumatoid Arthritis Patient Receiving Methotrexate
Kala-azar en un paciente con artritis reumatoide tratada con metotrexato
Delia Reinaa,
Corresponding author
deliareinasanz@gmail.com

Corresponding author.
, Dacia Cerdàa, Elena Güellb, Joaquín Martínez Montautib, Antonio Pinedac, Hèctor Corominasa
a Servicio de Reumatología, Hospital Moisès Broggi, Consorci Sanitari Integral, Sant Joan Despí, Barcelona, Spain
b Servicio de Medicina Interna, Hospital de Barcelona, Barcelona, Spain
c Servicio de Hematología, Hospital de Barcelona, Barcelona, Spain
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the scope of reported opportunistic infections is very wide&#44; ranging from primary infection by <span class="elsevierStyleItalic">Nocardia</span> or <span class="elsevierStyleItalic">Pneumocystis carinii</span> and fungal infections by <span class="elsevierStyleItalic">Candida</span>&#44; <span class="elsevierStyleItalic">Aspergillus</span>&#44; <span class="elsevierStyleItalic">Cryptococcus</span> or <span class="elsevierStyleItalic">Histoplasma</span>&#44; to viral infections&#44; mainly by herpes zoster&#46; Surprisingly&#44; although it is documented&#44; there are few cases of <span class="elsevierStyleItalic">Leishmania</span> infection&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">2&#8211;4</span></a> Given the low incidence of visceral leishmaniasis &#40;VL&#41; in the Mediterranean region&#44; there has been no recommendation for screening prior to initiating BT&#44; and periodical serological surveillance of these patients is proposed only if they live in areas in which the frequency is higher&#46;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">5&#44;6</span></a></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Case Report</span><p id="par0015" class="elsevierStylePara elsevierViewall">The patient was a 64-year-old woman who had undergone bilateral hip arthroplasty&#44; and had been diagnosed with RA in 2002 because of polyarthritis&#44; which was symmetrical&#44; erosive and seropositive &#40;positive for rheumatoid factor and anti-cyclic citrullinated peptide&#41;&#46; She progressively developed asymmetrical arthritis&#44; which affected large and small joints&#46; As background therapy for her disease she received 15<span class="elsevierStyleHsp" style=""></span>mg&#47;week of oral MTX&#44; 5<span class="elsevierStyleHsp" style=""></span>mg&#47;week of folic acid&#44; indomethacin at 25<span class="elsevierStyleHsp" style=""></span>mg&#47;8<span class="elsevierStyleHsp" style=""></span>h and low-dose prednisone&#46; She had no significant epidemiological history&#46; In 2012&#44; she had begun to note considerable weakness&#44; with episodes of spiking fever&#46; At the time of the present evaluation&#44; it had started 2 months earlier and was accompanied by pancytopenia &#40;leukocytes&#58; 3200 &#91;lymphocytes&#58; 1100&#93;&#44; hemoglobin&#58; 9<span class="elsevierStyleHsp" style=""></span>g&#47;L&#44; platelets&#58; 91&#44;000&#41;&#44; observed in a routine analysis&#46; She was admitted to the hospital to be studied&#46; The physical examination revealed mucocutaneous pallor and there were no signs of lymphadenopathy&#44; and the review of systems produced no new findings&#46; Treatment with MTX was discontinued due to the suspicion of hematotoxicity&#46; Abdominal ultrasound and computed tomography of abdomen and chest established the presence of splenomegaly&#46; Serology for human immunodeficiency virus and hepatitis B and C viruses was negative&#44; and a bone marrow aspirate &#40;BMA&#41; confirmed marrow cellularity preservation&#44; and diffuse intra- and extracellular involvement of leishmaniasis &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; Once the diagnosis of VL had been established&#44; treatment with liposomal amphotericin B was begun at a dose of 3<span class="elsevierStyleHsp" style=""></span>mg&#47;kg body weight until the patient had received 10 doses&#46; After 10 weeks&#44; she was afebrile and her blood count began to improve gradually until it was normal&#46; At the present time&#44; she is asymptomatic and is taking hydroxychloroquine&#44; and good clinical control has been achieved in the management of RA&#46;</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">Rheumatoid arthritis patients can develop a wide range of associated extra-articular comorbidities&#59; of these&#44; hematological disorders and infections account for a high percentage of cases&#44; and&#44; thus&#44; the differential diagnosis is very extensive&#46; Check-ups and follow-up visits of patients with RA are employed to monitor the analytical profile&#8212;hematological and biochemical&#8212;in accordance with recommended clinical practice guidelines&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> The study of a single cytopenia or of pancytopenia should include the complications of the disease itself&#44; the associated drug toxicity and possible nosocomial infections&#59; in addition&#44; hematological conditions should also be ruled out&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Leishmaniasis is understood to be a set of syndromes caused by infection of the protozoan of the genus <span class="elsevierStyleItalic">Leishmania</span>&#44; which is widely extended in tropical regions&#44; whereas <span class="elsevierStyleItalic">L&#46; infantum</span> causes a disease that is endemic in the Mediterranean&#46; It has three clinical profiles&#58; cutaneous&#44; mucosal and visceral&#46; The latter can be fatal in the absence of treatment&#46; It is transmitted by the bite of the phlebotomine sandfly&#46; Depending on the <span class="elsevierStyleItalic">Leishmania</span> species&#44; the genus of the transmitting insect and the geographic region&#44; the main reservoirs are dogs&#44; rodents and persons&#46; The onset of VL can be silent or&#44; in contrast&#44; full-blown &#40;kala-azar&#41;&#44; with its characteristic pentad&#58; prolonged fever&#44; weight loss&#44; hepatosplenomegaly&#44; pancytopenia and hypergammaglobulinemia&#46; At some point&#44; the subclinical disease can become symptomatic in patients who receive immunosuppressive agents like glucocorticoids&#44; MTX or BT&#46; There are three ways to establish the diagnosis of leishmaniasis&#58; clinical&#44; parasitic and immunological&#46; The parasitological diagnosis should be confirmed by the observation of the protozoan in a tissue or smear&#46; Should there be any doubt about the diagnosis&#44; the BMA provides satisfactory results&#46; The differential diagnosis of full-blown VL should include malignant hematological and lymphatic disorders&#44; as well as infectious diseases like malaria&#46; At the present time&#44; the treatment of choice of VL in developed countries is liposomal amphotericin B&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">In a review of the literature&#44; it is noteworthy that there are fewer cases of patients with RA being treated with MTX than those receiving anti-tumor necrosis factor &#40;TNF&#41; agents who develop <span class="elsevierStyleItalic">Leishmania</span> infection&#46; We have yet to know why&#46; These patients do not seem to have any common factor predisposing them to infection&#46; Methotrexate reduces the cell immune response&#44; inhibits neutrophil chemotaxis and T-cell proliferation&#44; and has been related to the development of infections by opportunistic pathogens&#44; among which we find <span class="elsevierStyleItalic">Leishmania</span>&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Patients with RA being treated with MTX have a greater predisposition to develop VL than the general population&#44; possibly due to immunological changes related to the underlying disease and the treatment they receive&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Tumor necrosis factor is a cytokine involved in the immune-mediated response to infection&#44; especially against intracellular pathogens&#46; The use of anti-TNF drugs in RA is growing&#44; and their utility is clearly related to an increase in the number of opportunistic infections in these patients&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">The diagnosis of VL should be considered in patients when there is a suspicion of infection if they are receiving MTX to treat an inflammatory rheumatic disease and live in regions in which leishmaniasis is endemic&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">The importance of the early diagnosis&#44; established during the follow-up visits in relation to the underlying disease&#44; made it possible for us to detect VL in our patient&#46; The prompt initiation of a specific treatment is fundamental in order to improve the prognosis of a potentially serious disease&#46; With this in mind&#44; we must not forget that&#44; although uncommon&#44; leishmaniasis is endemic in the Mediterranean&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Conclusion</span><p id="par0055" class="elsevierStylePara elsevierViewall">The current management of RA patients is very satisfactory&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> Improvements in monitoring and the identification of new therapeutic targets have resulted in high survival rates&#46; The prognosis is likewise more favorable&#59; however&#44; the same therapies that&#44; on occasion&#44; lead to remission&#44; also have certain additional risks&#46;<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">9&#44;10</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">The present report describes an infectious process that developed in the course of RA&#44; partially due to the associated susceptibility to chronic inflammatory disease&#44; together with the added risk conferred by immunosuppressive therapies like MTX&#46; The study of comorbidities of RA should emphasize infections by the usual pathogens&#44; without overlooking those produced by uncommon opportunistic microorganisms like <span class="elsevierStyleItalic">Leishmania</span>&#46;</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="par0065" class="elsevierStylePara elsevierViewall">The authors declare that no experiments were performed on humans or animals for this study&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Confidentiality of data</span><p id="par0070" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appear in this article&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Right to privacy and informed consent</span><p id="par0075" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appear in this article&#46;</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Conflicts of Interest</span><p id="par0080" class="elsevierStylePara elsevierViewall">The authors declare they have no conflicts of interest&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Patients with rheumatoid arthritis &#40;RA&#41; treated with disease-modifying antirheumatic drugs are susceptible to severe infections such as leishmaniasis&#46; As <span class="elsevierStyleItalic">L&#46; infantum</span> is endemic in the Mediterranean region&#44; it is necessary to rule this infectious process out in any RA patient presenting with fever and pancytopenia&#46; An early diagnosis based on a high suspicion can prevent a fatal outcome&#46;</p></span>"
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        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Los pacientes con artritis reumatoide &#40;AR&#41; tratados con f&#225;rmacos modificadores del curso de la enfermedad est&#225;n expuestos a desarrollar infecciones potencialmente graves como la leishmaniasis&#46; <span class="elsevierStyleItalic">L&#46; infantum</span> es end&#233;mica en el Mediterr&#225;neo&#44; hecho que obliga ante un paciente con AR que presenta fiebre y pancitopenia&#44; a descartar este proceso&#46; Un diagn&#243;stico de sospecha precoz&#44; puede evitar un curso y pron&#243;stico fatal&#46;</p></span>"
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Article information
ISSN: 21735743
Original language: English
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Idiomas
Reumatología Clínica (English Edition)
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