Scientific Letter
Co-existence of Crohn's disease and primary immune thrombocytopenia and its implications in treatment
Coexistencia de enfermedad de Crohn y trombocitopenia inmune primaria y sus implicaciones en el tratamiento
N. Crespo Madrid, C. Ruiz Hernández, L. Giraldo Escobar, G. Pujol Muncunill, J. Martín de Carpi
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Sección de Gastroenterología, Hepatología y Nutrición Pediátrica, Unidad para el Cuidado Integral de la Enfermedad Inflamatoria Intestinal Pediátrica, Hospital Sant Joan de Déu, Esplugues de Llobregat, Barcelona, Spain
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CT angiogram: (B) axial plane, arterial phase. (C) Sagittal plane, portal venous phase. Lesion in hepatic parenchyma anterior to the vena cava in segment I and part of segments <span class="elsevierStyleSmallCaps">VII</span>, <span class="elsevierStyleSmallCaps">IV</span> and <span class="elsevierStyleSmallCaps">II</span>, 43<span class="elsevierStyleHsp" style=""></span>mm<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>22<span class="elsevierStyleHsp" style=""></span>mm<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>34<span class="elsevierStyleHsp" style=""></span>mm, with peripheral nodular enhancement in the arterial phase and centripetal fill-in in the portal venous phase. Case 2: (D) abdominal ultrasound: right hepatic lobe replaced by a homogeneous 90<span class="elsevierStyleHsp" style=""></span>mm<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>50<span class="elsevierStyleHsp" style=""></span>mm mass with multiple intralesional vessels, with additional focal alterations of echogenicity in the left hepatic lobe. CT angiogram: (E) coronal plane in the arterial phase. (F) Axial plane in the portal venous phase: large liver mass, 90<span class="elsevierStyleHsp" style=""></span>mm<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>86<span class="elsevierStyleHsp" style=""></span>mm<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>70<span class="elsevierStyleHsp" style=""></span>mm, practically occupying the entire right hepatic lobe, sparing segments <span class="elsevierStyleSmallCaps">II</span>, <span class="elsevierStyleSmallCaps">III</span> and part of segment IV, showing marked peripheral nodular enhancement with centripetal progression during the portal venous phase. Several nodular foci with the same behaviour were also observed in the left hepatic lobe.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "M.A. Baena-Gómez, M.P. Priego Ruiz, E.M. González, M.J. Peña Rosa, R. 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Temporada 2013-14 en la Comunidad Valenciana" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1723 "Ancho" => 3229 "Tamanyo" => 267991 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Influenza vaccination coverage by disease, age group and sex. Autonomous Community of Valencia, 2013–2014 season.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "A.M. Alguacil-Ramos, R. Martín-Ivorra, J.A. Lluch-Rodrigo, E. Pastor-Villalba, A. Portero-Alonso" "autores" => array:5 [ 0 => array:2 [ "nombre" => "A.M." "apellidos" => "Alguacil-Ramos" ] 1 => array:2 [ "nombre" => "R." 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Crespo Madrid, C. Ruiz Hernández, L. Giraldo Escobar, G. Pujol Muncunill, J. Martín de Carpi" "autores" => array:5 [ 0 => array:2 [ "nombre" => "N." "apellidos" => "Crespo Madrid" ] 1 => array:2 [ "nombre" => "C." "apellidos" => "Ruiz Hernández" ] 2 => array:2 [ "nombre" => "L." "apellidos" => "Giraldo Escobar" ] 3 => array:2 [ "nombre" => "G." "apellidos" => "Pujol Muncunill" ] 4 => array:4 [ "nombre" => "J." "apellidos" => "Martín de Carpi" "email" => array:1 [ 0 => "Javiermartin@hsjdbcn.org" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Sección de Gastroenterología, Hepatología y Nutrición Pediátrica, Unidad para el Cuidado Integral de la Enfermedad Inflamatoria Intestinal Pediátrica, Hospital Sant Joan de Déu, Esplugues de Llobregat, Barcelona, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Coexistencia de enfermedad de Crohn y trombocitopenia inmune primaria y sus implicaciones en el tratamiento" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Inflammatory bowel disease (IBD) is a multisystemic disease in which 30% of affected patients develop some type of extraintestinal manifestation (EIM). Extraintestinal manifestations may emerge at different stages during the disease, and may or may not be associated to the level of activity.<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">1,2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Among the haematologic manifestations of IBD is primary immune thrombocytopenia (PIT), formerly known as idiopathic thrombocytopenic purpura. It is characterised by an isolated platelet count less than 100<span class="elsevierStyleHsp" style=""></span>000/mm<span class="elsevierStyleSup">3</span> in the absence of an initiating cause. It is diagnosed by the exclusion of other causes in patients with persistent thrombocytopenia (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">1,3,4</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">The association between IBD and PIT in children is rare, with prevalences estimated at 0.1–0.48%, and with a higher frequency of association with ulcerative colitis (UC) compared to Crohn's disease (CD).<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">3,5</span></a> We describe two cases of concurrent IBD and PIT, which are of interest considering the rarity of the association and the effects that the administered treatment may have on the course of disease.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Patient 1</span><p id="par0020" class="elsevierStylePara elsevierViewall">Female aged 11 years with a history of CD (Paris classification A1a L2 B1 G0) diagnosed based on the Oporto criteria at age 4 years and undergoing maintenance treatment with azathioprine (AZA) at 2.5<span class="elsevierStyleHsp" style=""></span>mg/kg/day. At 9 years of age, while in clinical remission, she presented with ecchymosis and petechiae of sudden onset. Blood testing found a platelet count of 2000/mm<span class="elsevierStyleSup">3</span>, and diagnostic tests were negative. The patient was given two doses of gammaglobulin (0.8<span class="elsevierStyleHsp" style=""></span>g/kg/dose) and intravenous corticosteroids (2<span class="elsevierStyleHsp" style=""></span>mg/kg/day) with no improvement, leading to diagnosis of PIT, and requiring maintenance therapy with gammaglobulin every three to four months (0.8<span class="elsevierStyleHsp" style=""></span>g/kg/dose) for persistent thrombocytopenia. Eighteen months after being diagnosed with PIT, the patient had a clinical and endoscopic relapse of CD (PCDAI 35; SES-CD, 6). Induction therapy was initiated with humanised anti-TNF factor alpha (adalimumab [ADA]) following the standard dosage with administration every two weeks (160, 80 and 40<span class="elsevierStyleHsp" style=""></span>mg by the subcutaneous route), after which the patient went into remission (PCDAI 0; faecal calprotectin [FC], 15<span class="elsevierStyleHsp" style=""></span>mg/kg). The patient responded favourably, with stabilisation of the platelet levels, and corticosteroid therapy was discontinued. At present, the patient is being treated with combined AZA-ADA, and has not required additional courses of gammaglobulin or corticosteroids 24 months after initiation of ADA. The patient is awaiting a control colonoscopy, based on which a switch to monotherapy will be considered.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Patient 2</span><p id="par0025" class="elsevierStylePara elsevierViewall">Male aged 15 years with a CD diagnosis (A1bL2B1G0) undergoing maintenance treatment with mercaptopurine (6-MP) (1.5<span class="elsevierStyleHsp" style=""></span>mg/kg/day). Seven months after the diagnosis, while in clinical remission (PCDAI 0), the patient developed isolated thrombocytopenia (85<span class="elsevierStyleHsp" style=""></span>000/mm<span class="elsevierStyleSup">3</span>). To rule out thiopurine-induced cytopenia (even though the rest of the cell counts and the thiopurine methyltransferase activity were normal), treatment was discontinued temporarily; the patient showed no improvement, with platelet levels reaching 9000/mm<span class="elsevierStyleSup">3</span>, so treatment was resumed. The PIT diagnosis was reached after diagnostic test results came up negative. The patient was treated with gammaglobulin (0.8<span class="elsevierStyleHsp" style=""></span>g/kg/dose) and showed an initial favourable response, although he subsequently needed corticosteroid therapy (0.4–1<span class="elsevierStyleHsp" style=""></span>mg/kg/day) for maintenance. At present, 19 months following the PIT diagnosis, the patient remains in clinical remission with stable laboratory results (PCDAI 0; FC, 20<span class="elsevierStyleHsp" style=""></span>mg/kg) under low-dose corticosteroid treatment (0.1<span class="elsevierStyleHsp" style=""></span>mg/kg/day) with concurrent administration of mercaptopurine.</p><p id="par0030" class="elsevierStylePara elsevierViewall">There are few descriptions of the association of CD and PIT in the literature (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>). The onset of PIT in association with IBD is variable, although based on the published cases it seems to occur more frequently after the diagnosis of IBD. Since the cases described in the literature involved UC more frequently than CD, we think it is worth noting that our patients with CD had exclusive colonic involvement, which supports the hypothesis that the inflammation of the colonic mucosa and/or the dysregulation of the local immune system may be associated with the development of PIT in these patients.<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">3,5</span></a></p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">Studies in adults have described cases of PIT refractory to conventional treatment that responded well to treatment with anti-TNF factor, and it has been hypothesised that the pathogenic mechanism involves the apoptosis of monocytes and macrophages (which produce TNF alpha, as do CD4 lymphocytes), with a decline in the anti-platelet antibodies produced by B lymphocytes.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">6</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">We believe that in the cases reviewed here, while conventional therapy was used when PIT first developed (gammaglobulin and corticosteroids), the adequate control of CD with anti-TNF factor agents in case 1 and thiopurines in case two allowed for the improved management and outcomes of PIT, without requiring further gammaglobulin doses. The additional option of discontinuing corticosteroid treatment in our patient treated with anti-TNF factor makes the possibility of escalating treatment in patient 2 attractive if his CD does not respond favourably.</p><p id="par0045" class="elsevierStylePara elsevierViewall">To conclude, it could be said that the association between PIT and CD is rare. The treatment used for maintaining CD in remission can also achieve adequate control of PIT. Thus, aggressive treatments can be avoided, improving quality of life in these patients.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Patient 1" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Patient 2" ] 2 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Crespo Madrid N, Ruiz Hernández C, Giraldo Escobar L, Pujol Muncunill G, Martín de Carpi J. Coexistencia de enfermedad de Crohn y trombocitopenia inmune primaria y sus implicaciones en el tratamiento. An Pediatr (Barc). 2015;83:433–435.</p>" ] ] "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "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="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Non-immune mechanism \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Immune mechanism \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Congenital thrombocytopenias, Bernard-Soulier syndrome, von Willebrand disease type IIb, MYH9-related disorders \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Post-transfusion purpura and alloimmune thrombocytopenia \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Bone marrow diseases: myelodysplastic syndromes, leukaemias, aplastic anaemia, bone marrow infiltration \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Drug-induced immune thrombocytopeniaRecent vaccinationInfection by HIV, HCV. Other infections \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Thrombotic thrombocytopenic purpura and other thrombotic microangiopathies \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Association with other autoimmune diseases: lupus erythematosus, antiphospholipid syndrome, inflammatory bowel disease and thyroid disorders, among others \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Chronic liver disease \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Association with common variable immunodeficiency and autoimmune lymphoproliferative syndrome \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Drug use (alcohol among others), natural medicine products and environmental toxins \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Thrombocytopenia following haematopoietic stem cell or solid organ transplant \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Drug-induced thrombocytopenia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Lymphoproliferative syndromes (CLL, NHL, HL, etc.) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab976895.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Causes of secondary PIT and thrombocytopenia.</p>" ] ] 1 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">CD, Crohn's disease; F, female; M, male; PIT, primary immune thrombocytopenia; AIT, autoimmune thrombocytopenia; 5-ASA, sulfasalazine.</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">Case \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Age at disease onset \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" 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="left" valign="top" scope="col" style="border-bottom: 2px solid black">Type of onset and time elapsed until first evidence of association \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Localisation of CD \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Platelets at onset of PIT \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Treatment of PIT \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Treatment of CD \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Surgery \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Remission of CD and PIT \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">1Higuchi et al.<a class="elsevierStyleCrossRef" href="#bib0045"><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="left" valign="top">11 years \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">CD 2.5 years before PIT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Colon \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><<span class="elsevierStyleHsp" style=""></span>10,000/mm<span class="elsevierStyleSup">3</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Gammaglobulin, corticosteroids \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Mercaptopurine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">2Higuchi et al.<a class="elsevierStyleCrossRef" href="#bib0045"><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="left" valign="top">2 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">CD 3 months before PIT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ileocolonic \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6000/mm<span class="elsevierStyleSup">3</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Corticosteroids \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5-ASA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">3Higuchi et al.<a class="elsevierStyleCrossRef" href="#bib0045"><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="left" valign="top">5 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">PIT 6 years before CD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ileocolonic \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><<span class="elsevierStyleHsp" style=""></span>10,000/mm<span class="elsevierStyleSup">3</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Gammaglobulin, corticosteroids \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5-ASA, cyclosporin, tacrolimus \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Splenectomy, colectomy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">4Manceñido et al.<a class="elsevierStyleCrossRef" href="#bib0055"><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="left" valign="top">17 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">CD 6 years before PIT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Colon \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><<span class="elsevierStyleHsp" style=""></span>10,000/mm<span class="elsevierStyleSup">3</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Gammaglobulin, corticosteroids \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5-ASA, corticosteroids \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">YesColectomy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">5Manceñido et al.<a class="elsevierStyleCrossRef" href="#bib0055"><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="left" valign="top">14 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">PIT 6 months before CD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Colon \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4000/mm<span class="elsevierStyleSup">3</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Gammaglobulin, corticosteroids \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5-ASA, azathioprine, corticosteroids, infliximab \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab976896.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Cases of Crohn's disease associated with primary immune thrombocytopenia described in the paediatric age group.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:6 [ 0 => array:3 [ "identificador" => "bib0035" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Extraintestinal manifestations of pediatric inflammatory bowel disease and their relation to disease type and severity" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "L. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 14 | 9 | 23 |
| 2024 October | 91 | 32 | 123 |
| 2024 September | 113 | 36 | 149 |
| 2024 August | 127 | 67 | 194 |
| 2024 July | 106 | 34 | 140 |
| 2024 June | 131 | 35 | 166 |
| 2024 May | 117 | 45 | 162 |
| 2024 April | 98 | 29 | 127 |
| 2024 March | 82 | 32 | 114 |
| 2024 February | 80 | 30 | 110 |
| 2024 January | 111 | 23 | 134 |
| 2023 December | 163 | 21 | 184 |
| 2023 November | 119 | 29 | 148 |
| 2023 October | 75 | 26 | 101 |
| 2023 September | 57 | 21 | 78 |
| 2023 August | 68 | 22 | 90 |
| 2023 July | 89 | 23 | 112 |
| 2023 June | 90 | 69 | 159 |
| 2023 May | 96 | 32 | 128 |
| 2023 April | 52 | 17 | 69 |
| 2023 March | 83 | 32 | 115 |
| 2023 February | 66 | 19 | 85 |
| 2023 January | 78 | 29 | 107 |
| 2022 December | 64 | 36 | 100 |
| 2022 November | 75 | 43 | 118 |
| 2022 October | 84 | 32 | 116 |
| 2022 September | 68 | 37 | 105 |
| 2022 August | 73 | 82 | 155 |
| 2022 July | 67 | 43 | 110 |
| 2022 June | 78 | 45 | 123 |
| 2022 May | 93 | 52 | 145 |
| 2022 April | 76 | 35 | 111 |
| 2022 March | 123 | 69 | 192 |
| 2022 February | 106 | 39 | 145 |
| 2022 January | 116 | 46 | 162 |
| 2021 December | 112 | 62 | 174 |
| 2021 November | 100 | 77 | 177 |
| 2021 October | 129 | 63 | 192 |
| 2021 September | 76 | 44 | 120 |
| 2021 August | 119 | 46 | 165 |
| 2021 July | 103 | 44 | 147 |
| 2021 June | 102 | 49 | 151 |
| 2021 May | 122 | 61 | 183 |
| 2021 April | 356 | 86 | 442 |
| 2021 March | 151 | 62 | 213 |
| 2021 February | 97 | 34 | 131 |
| 2021 January | 89 | 22 | 111 |
| 2020 December | 85 | 38 | 123 |
| 2020 November | 87 | 24 | 111 |
| 2020 October | 102 | 41 | 143 |
| 2020 September | 92 | 17 | 109 |
| 2020 August | 117 | 15 | 132 |
| 2020 July | 94 | 26 | 120 |
| 2020 June | 89 | 15 | 104 |
| 2020 May | 106 | 31 | 137 |
| 2020 April | 67 | 17 | 84 |
| 2020 March | 83 | 20 | 103 |
| 2020 February | 107 | 26 | 133 |
| 2020 January | 95 | 25 | 120 |
| 2019 December | 110 | 31 | 141 |
| 2019 November | 78 | 13 | 91 |
| 2019 October | 119 | 22 | 141 |
| 2019 September | 90 | 29 | 119 |
| 2019 August | 75 | 21 | 96 |
| 2019 July | 79 | 23 | 102 |
| 2019 June | 78 | 20 | 98 |
| 2019 May | 118 | 23 | 141 |
| 2019 April | 122 | 43 | 165 |
| 2019 March | 86 | 20 | 106 |
| 2019 February | 83 | 13 | 96 |
| 2019 January | 79 | 26 | 105 |
| 2018 December | 77 | 33 | 110 |
| 2018 November | 124 | 28 | 152 |
| 2018 October | 146 | 36 | 182 |
| 2018 September | 57 | 10 | 67 |
| 2018 August | 1 | 0 | 1 |
| 2018 July | 1 | 0 | 1 |
| 2018 June | 4 | 0 | 4 |
| 2018 May | 9 | 0 | 9 |
| 2018 April | 49 | 0 | 49 |
| 2018 March | 29 | 0 | 29 |
| 2018 February | 16 | 0 | 16 |
| 2018 January | 20 | 0 | 20 |
| 2017 December | 20 | 0 | 20 |
| 2017 November | 26 | 0 | 26 |
| 2017 October | 23 | 0 | 23 |
| 2017 September | 19 | 0 | 19 |
| 2017 August | 18 | 0 | 18 |
| 2017 July | 20 | 0 | 20 |
| 2017 June | 27 | 5 | 32 |
| 2017 May | 30 | 4 | 34 |
| 2017 April | 25 | 2 | 27 |
| 2017 March | 22 | 3 | 25 |
| 2017 February | 9 | 4 | 13 |
| 2017 January | 18 | 2 | 20 |
| 2016 December | 28 | 10 | 38 |
| 2016 November | 28 | 1 | 29 |
| 2016 October | 40 | 9 | 49 |
| 2016 September | 31 | 3 | 34 |
| 2016 August | 42 | 5 | 47 |
| 2016 July | 11 | 0 | 11 |
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