Evolution After Anti-TNF Discontinuation in Patients With Inflammatory Bowel Disease: A Multicenter Long-Term Follow-Up Study.

OBJECTIVES: The aims of this study were to assess the risk of relapse after discontinuation of anti-tumor necrosis factor (anti-TNF) drugs in patients with inflammatory bowel disease (IBD), to identify the factors associated with relapse, and to evaluate the overcome after retreatment with the same anti-TNF in those who relapsed. METHODS: This was a retrospective, observational, multicenter study. IBD patients who had been treated with anti-TNFs and in whom these drugs were discontinued after clinical remission was achieved were included. RESULTS: A total of 1,055 patients were included. The incidence rate of relapse was 19% and 17% per patient-year in Crohn's disease and ulcerative colitis patients, respectively. In both Crohn's disease and ulcerative colitis patients in deep remission, the incidence rate of relapse was 19% per patient-year. The treatment with adalimumab vs. infliximab (hazard ratio (HR)=1.29; 95% confidence interval (CI)=1.01-1.66), elective discontinuation of anti-TNFs (HR=1.90; 95% CI=1.07-3.37) or discontinuation because of adverse events (HR=2.33; 95% CI=1.27-2.02) vs. a top-down strategy, colonic localization (HR=1.51; 95% CI=1.13-2.02) vs. ileal, and stricturing behavior (HR=1.5; 95% CI=1.09-2.05) vs. inflammatory were associated with a higher risk of relapse in Crohn's disease patients, whereas treatment with immunomodulators after discontinuation (HR=0.67; 95% CI=0.51-0.87) and age (HR=0.98; 95% CI=0.97-0.99) were protective factors. None of the factors were predictive in ulcerative colitis patients. Retreatment of relapse with the same anti-TNF was effective (80% responded) and safe. CONCLUSIONS: The incidence rate of inflammatory bowel disease relapse after anti-TNF discontinuation is relevant. Some predictive factors of relapse after anti-TNF withdrawal have been identified. Retreatment with the same anti-TNF drug was effective and safe.

Monitoring endoscopic postoperative recurrence in Crohn's disease after an ileocecal resection. Does capsule endoscopy have a role in the short and long term?

Background: Small bowel capsule endoscopy (SBCE) is a noninvasive method to detect endoscopic postoperative recurrence (POR) after an ileocolonic resection in Crohn's Disease (CD). Few studies have evaluated the role of SBCE in the early POR (= 12 months). Data for detection of late POR (>12 months) and evaluation of treatment response in previous POR is scarce. We aimed to assess the SBCE performance in the three scenarios (early-POR, late-POR, and previous-POR). Methods: Retrospective 11-year cohort study of SBCE procedures performed on CD patients with ileocolonic resection. Disease activity by Rutgeerts score (RS), correlation with biomarkers, and therapeutic changes were recorded. Results: We included 113 SBCE procedures (34 early-POR, 44 late-POR, and 35 previous-POR). 105 procedures (92.9%) were complete and 97 SBCE (85.5%) were conclusive with no differences between groups. Relevant POR (RS ≥i2) was more frequent in the early-POR group compared to late-POR (58.8% vs 27.3%, p=0.02). In the previous-POR, RS improved in 43.5% of procedures, worsened in 26%, and remained unchanged in 30.5%. Fecal calprotectin (FCP) value of 100µg/g displayed the best accuracy: sensitivity 53.8%, specificity 78.8%, positive predictive value 66.7% and negative predictive value 68.4%. SBCE guided therapeutic changes in 43 patients (38%). No adverse events occurred in our cohort. Conclusion: SBCE is a safe and effective method to assess POR in the early and late setting in clinical practice, and for the evaluation of treatment response to previous POR. FCP is an accurate surrogate marker of POR and 100µg/g value had the best overall accuracy.

[Genetic predisposition to bleeding during oral anticoagulants treatment]. / Predisposición genética al sangrado durante el tratamiento.

The degree of anticoagulation obtained during oral anticoagulation therapy with vitamin K antagonists (VKA) varies among patients due to individual and environmental factors. The rate of anticoagulation influences the hemorrhagic risk. Therefore, it is plausible that patients specially sensitive to oral anticoagulants are at higher hemorrhagic risk, specially during the first weeks. The role of a series of polymorphisms of the enzymes involved in the metabolism of VKA or in the vitamin K cycle are reviewed. Three polymorphisms, two in the cytochrome P450 2C9 and one in the VKORC1 enzyme, are responsible for a high portion of the variability observed in the sensitivity to AVK. Although the available literature suggests that these genetic variants could increase the risk of severe hemorrhage, larger, well designed studies are needed to confirm this notion.

Informed consent document in gastrointestinal endoscopy: understanding and acceptance by patients.

OBJECTIVE: We wanted to know if patients read and understand the informed consent (IC) document used for endoscopic procedures, and to evaluate the readability of IC. METHOD: During two months we gave patients studied in our endoscopy unit an anonymous questionnaire with different items concerning reading degree, knowledge of the technique, complications, sedation used, and information received. We evaluated IC readability using the Flesch index. RESULTS: 309 patients were included (mean age: 53 years, 55% males, 86% outpatients, 50% with basic education); 85% of patients read the IC, 96% considered they understood the exploration technique, 22% were not aware of severe complications, and 82% knew which kind of sedation would be used; 88% of patients received additional information from their doctors. Outpatients read the IC in a greater percentage versus inpatients (p < 0.05); patients with only basic education tended to ignore the possibility of complications (p < 0.05). Doctors gave more information to rural patients (p = 0.08), offered better information about complications to urban patients (p = 0.09), and offered more information on other diagnostic procedures to patients older than 50 years (p < 0.05). With the Flesch index we found that gastroscopy and colonoscopy ICs had a "standard" level of readability, while ERCP ICs were more complex. CONCLUSIONS: The majority of our patients read and understands the IC. Doctors adapt information to patient characteristics. Our IC documents have an acceptable level of readability, but given that 50% of our patients have only a basic educational status, we should attempt to provide an easier IC document.

[General malaise and diarrhea as the main manifestations of Giardia lamblia infection]. / Síndrome general y diarrea como manifestación de infección por Giardia lamblia.

Giardia lamblia is a ubiquitous intestinal protozoan. Transmission, which is fecal-oral, occurs after cyst ingestion, excystation and enterocyte adhesion. Symptoms include diarrhea, abdominal pain and other less frequent manifestations such as nausea, anorexia and weight loss. Enzyme immunoassay and direct fluorescent-antibody assay for antigen detection in stool samples, and small intestine biopsy provide the best diagnostic sensitivity. When an infection is suspected, duodenal biopsy should be carried out, even though endoscopic appearance may be normal. The most effective drugs in the treatment of this infection are metronidazole and tinidazole. We report a case of G. lamblia infection. The patient reported a clinical history of 4 months' duration with general malaise and diarrhea for the previous month. This form of presentation is rarely found in adults with this parasitosis. The diagnosis was based on the results of duodenal biopsy. The patient showed satisfactory response to treatment with metronidazole.

[Duodenal gangliocytic paraganglioma]. / Paraganglioma gangliocítico duodenal.

We present the case of an 85 year old male who was admitted to hospital with abdominal pain and jaundice. Different explorations were performed for this reason, with a mass observed in his 2nd duodenal portion. Histological study showed that it was a duodenal gangliocytic paraganglioma. The clinical characteristics of this infrequent tumour are described and we review the diagnosis and treatment.

[Isotretinoin and ulcerous colitis]. / Isotretinoína y colitis ulcerosa.

Isotretinoin is a drug obtained from retinoid acid, often used for the treatment of different types of acne. The way it acts on the dermo-epidermis has not been clearly described. Different studies reporting a relation, proportional or inverse, between isotretinoin and the occurrence or reactivation of an inflammatory bowel disease (IBD) have been found in the literature. Although there are several hypotheses about how this substance can affect the bowel mucous in the pathogenesis of the disease, none of them are definitive. We present a new case where the mentioned relation was evident. Therefore we suggest that when a patient treated with this isomer presents symptoms suggesting IBD, an endoscopic procedure should be performed in order to rule out inflammatory mucous changes.

[Recomendations of vaccination in patients with inflammatory bowel disease (IBD)]. / Recomendaciones de vacunación en pacientes con enfermedad inflamatoria intestinal (EII).

The concept of inflammatory bowel disease (IBD) covers three entities: ulcerative colitis (UC), Crohn's disease (CD) and indeterminate colitis (IC). These diseases have in common a chronic and relapsing course, alternating periods marked by inflammatory activity with other quiescent periods, in which the patient is asymptomatic. For many years treatment of the disease, especially in acute phases, was based on the use of corticoids. However, in recent decades we have witnessed significant advances from the therapeutic point of view. It is estimated that during the course of the disease's evolution 80% of patients will need corticoids, 40% immunomodulators (IMM), and as many as 20% will require a biological medicine to control their disease. While all of this is accompanied by an improvement in quality of life, less hospital admissions or surgical interventions, their use also involves an increase in the risk of suffering infections, either due to germs normally found in the community or opportunistic infections. Moreover, infections are a cause of morbidity and mortality associated with IBD and some of them can be prevented with vaccinations, hence the importance that vaccination programs are acquiring in this groups of patients. We present a review of the relevant literature and propose a vaccination protocol for patients diagnosed with IBD.

Recomendaciones de vacunación en pacientes con enfermedad inflamatoria intestinal (EII) / Recomendations of vaccination in patients with inflammatory bowel disease (IBD)

El concepto de enfermedad inflamatoria intestinal (EII) engloba tres entidades: la colitis ulcerosa (CU), la enfermedad de Crohn (EC) y la colitis inclasificable (CI). Estas enfermedades tienen en común el curso crónico y recidivante, alternando épocas de marcada actividad inflamatoria con otras quiescentes, en las que el paciente permanece asintomático. Durante muchos años la base del tratamiento, sobre todo en las fases agudas, se basó en el uso de corticoides. Sin embargo, a lo largo de las últimas décadas hemos asistido a avances importantes desde el punto de vista terapéutico. Así se estima que, a lo largo de la evolución de la enfermedad, el 80% de los pacientes van a precisar corticoides, el 40% inmunomoduladores (IMM) y hasta un 20% necesitará un fármaco biológico para el control de su enfermedad. Si bien todo ello se acompaña de una mejora en la calidad de vida, disminuyendo la necesidad de ingresos e intervenciones quirúrgicas, su uso implica también un incremento en el riesgo de sufrir infecciones, bien por gérmenes habituales en la comunidad o por gérmenes oportunistas. Las infecciones, además, son causa de morbimortalidad asociada a EII y algunas de ellas son prevenibles con vacunas, de ahí la importancia que los programas de vacunación están adquiriendo en este grupo de pacientes. Presentamos una revisión de la literatura al respecto y proponemos unas recomendaciones de vacunación para los pacientes diagnosticados de EII (AU)

The concept of inflammatory bowel disease (IBD) covers three entities: ulcerative colitis (UC), Crohn’s disease (CD) and indeterminate colitis (IC). These diseases have in common a chronic and relapsing course, alternating periods marked by inflammatory activity with other quiescent periods, in which the patient is asymptomatic. For many years treatment of the disease, especially in acute phases, was based on the use of corticoids. However, in recent decades we have witnessed significant advances from the therapeutic point of view. It is estimated that during the course of the disease’s evolution 80% of patients will need corticoids, 40% immunomodulators (IMM), and as many as 20% will require a biological medicine to control their disease. While all of this is accompanied by an improvement in quality of life, less hospital admissions or surgical interventions, their use also involves an increase in the risk of suffering infections, either due to germs normally found in the community or opportunistic infections. Moreover, infections are a cause of morbidity and mortality associated with IBD and some of them can be prevented with vaccinations, hence the importance that vaccination programs are acquiring in this groups of patients. We present a review of the relevant literature and propose a vaccination protocol for patients diagnosed with IBD (AU)

Incidencia y características de la esofagitis eosinofílica (EE) en adultos / Incidence and characteristics of eosinophilic esophagitis in adults

La esofagitis eosinofílica (EE) es una enfermedadcaracterizada por la infiltración de la mucosa del esófagopor eosinófilos, cuya incidencia en adultos pareceestar aumentando en los últimos años, de forma similara lo que ocurre en otras enfermedades de probable etiologíainmunoalérgica. Predomina en varones jóvenes yse manifiesta principalmente por disfagia e impactaciónalimentaria. Su tratamiento se basa en eliminar elalérgeno potencialmente implicado y la administraciónde corticoides.En el presente trabajo se revisan retrospectivamentelos casos de EE diagnosticados en el Hospital de Navarraentre enero de 2002 y agosto de 2008, encontrándose25 pacientes, lo que supone una incidencia de 2,13casos/105 habitantes/año. Un 72% de nuestros pacientespresentaban disfagia y un 52% historia de impactacióndel bolo alimentario, encontrándose alteracionesendoscópicas en 23 de los 25 casos. De 24 pacientesestudiados, un 76% manifestaban alergia alimentariao a neumoalérgenos, lo que apoya el fondo inmunoalérgicode la enfermedad y la necesidad de un estudioalergológico en todos las pacientes con EE. La mayoríade nuestros pacientes (22 de 24 valorados) presentaronbuena respuesta clínica al tratamiento, que se basó enevitar la exposición al alergeno potencialmente implicadoy/o la administración de corticoides (tópicos osistémicos) y/o la administración de inhibidores de la bomba de protones(AU)

Eosinophilic esophagitis (EE) is a disease characterisedby the infiltration of esophageal mucosa by eosinophils,whose incidence in adults seems to have beenincreasing in recent years, in a way that is similar towhat is occurring with other diseases of a probable immunoallergicaetiology. It predominates in young adultsand is mainly expressed by dysphagia and esophagealfood impactation. Treatment is based on eliminatingthe allergen that is potentially involved and the administrationof corticoids.This article offers a retrospective review of EEcases diagnosed in the Hospital de Navarra betweenJanuary 2002 and August 2008, with 25 patients found,which represents an incidence of 2.13 cases/105 inhabitants/year. Seventy-two percent of our patients showeddysphagia and 52% a history of food bolus impaction,with endoscopic alterations found in 23 of the 25 cases.Out of 24 patients studied, 76% showed an alimentaryallergy or to neumoallergens, which supports the immunoallergicbasis of the disease and the need for anallergy exam in all patients with EE. The majority of ourpatients (22 out of 24 evaluated) presented a good clinicalresponse to treatment, which was based on avoidingexposure to the potentially involved allergen and/or theadministration of corticoids (topical or systemic) and/or the administration of proton pump inhibitors(AU)

Predisposición genética al sangrado durante el tratamiento con anticoagulantes orales / Genetic predisposition to bleeding during treatment oral anticoagulants treatment

La anticoagulación conseguida durante el tratamiento con anticoagulantes orales antagonistas de la vitamina K (AVK) varía entre unos pacientes y otros debido a factores individuales y ambientales. La intensidad de la anticoagulación condiciona el riesgo hemorrágico. Por tanto, es probable que los pacientes especialmente sensibles a los AVK corran un riesgo hemorrágico mayor, especialmente durante las primeras semanas. En esta revisión se va a discutir el papel de una serie de polimorfismos de las enzimas involucradas en la metabolización de los AVK o en el ciclo de la vitamina K. Dos polimorfismos del citocromo P450 2C9 y uno de la enzima VKORC1 son responsables de un alto porcentaje de la variabilidad observada en la sensibilidad a los AVK. Aunque parece que dichas alteraciones genéticas se asocian con el riesgo de experimentar una hemorragia severa, confirmar este extremo requerirá estudios más amplios y mejor diseñados (AU)

The degree of anticoagulation obtained during oral anticoagulation therapy with vitamin K antagonists (VKA) varies among patients due to individual and environmental factors. The rate of anticoagulation influences the hemorrhagic risk. Therefore, it is plausible that patients specially sensitive to oral anticoagulants are at higher hemorrhagicc risk, specially during the first weeks. The role of a series of polymorphisms of the enzymes involved in the metabolism of VKA or in the vitamin K cycle are reviewed. Three polymorphisms, two in the cytochrome P450 2C9 and one in the VKORC1 enzyme, are responsible for a high portion of the variability observed in the sensitivity to AVK. Although the available literature suggests that these genetic variants could increase the risk of severe hemorrhage, larger, well designed studies are needed to confirm this notion (AU)

Estudio del grado de entendimiento y aceptación por nuestros pacientes de los consentimientos informados utilizados para endoscopia / Informed consent document in gastrointestinal endoscopy: understanding and acceptance by patients

Objetivo: conocer si los pacientes estudiados en nuestra unidad de endoscopia leen y comprenden el documento de consentimiento informado. Conocer la legibilidad de dichos consentimientos informados. Método: entregamos a los pacientes estudiados endoscopicamente en nuestra unidad un cuestionario acerca del grado de lectura del consentimiento informado, conocimiento de la técnica endoscópica, complicaciones, sedación utilizada e información recibida. Valoramos la legibilidad de nuestros consentimientos informados mediante el índice de Flesch. Resultados: 309 pacientes fueron incluidos (edad media: 53 años, 55% varones). El 85% de los pacientes se había leído el consentimiento informado, el 96% conocían la técnica endoscópica, 15,2% no conocían el riesgo de complicaciones graves durante la exploración. El 82% sabía qué tipo de sedación iba a recibir. El 88% recibieron información adicional por sus médicos. Los pacientes con estudios básicos tendieron a desconocer la posibilidad de complicaciones (p < 0,05). Los médicos aportaron más información a los pacientes de medio rural (p = 0,08), mejor información sobre las complicaciones a los pacientes de medio urbano (p = 0,09) y más información sobre exploraciones alternativas a los mayores de 50 años (p < 0,05). Los consentimientos informados de gastroscopia y colonoscopia tenían un nivel de legibilidad standard, mientras que el consentimiento informado de ERCP era más complejo. Conclusiones: la mayoría de nuestros pacientes leen y entienden el consentimiento informado. Los médicos tienden a adaptar la información que ofrecen a los pacientes a las características socioculturales de estos. Nuestros consentimientos informados tienen un nivel de legibilidad aceptable, pero esta debería ser mejorada para facilitar una mejor comprensión de los mismos

Objective: we wanted to know if patients read and understand the informed consent (IC) document used for endoscopic procedures, and to evaluate the readability of IC. Method: during two months we gave patients studied in our endoscopy unit an anonymous questionnaire with different items concerning reading degree, knowledge of the technique, complications, sedation used, and information received. We evaluated IC readability using the Flesch index. Results: 309 patients were included (mean age: 53 years, 55% males, 86% outpatients, 50% with basic education); 85% of patients read the IC, 96% considered they understood the exploration technique, 22% were not aware of severe complications, and 82% knew which kind of sedation would be used; 88% of patients received additional information from their doctors. Outpatients read the IC in a greater percentage versus inpatients (p < 0.05); patients with only basic education tended to ignore the possibility of complications (p < 0.05). Doctors gave more information to rural patients (p = 0.08), offered better information about complications to urban patients (p = 0.09), and offered more information on other diagnostic procedures to patients older than 50 years (p < 0.05). With the Flesch index we found that gastroscopy and colonoscopy ICs had a “standard” level of readability, while ERCP ICs were more complex. Conclusions: the majority of our patients read and understands the IC. Doctors adapt information to patient characteristics. Our IC documents have an acceptable level of readability, but given that 50% of our patients have only a basic educational status, we should attempt to provide an easier IC document

Paraganglioma gangliocítico duodenal / Duodenal gangliocytic paraganglioma

Se presenta el caso de un varón de 85 años queingresó por dolor abdominal e ictericia, por lo cual sele realizaron diversas exploraciones, apreciándose en2a porción duodenal una masa cuyo estudio histológicodemostró que se trataba de un paraganglioma gangliocíticoduodenal. Se describen las característicasclínicas de este infrecuente tumor y revisamos su diagnósticoy tratamiento

We present the case of an 85 year old male whowas admitted to hospital with abdominal pain andjaundice. Different explorations were performed forthis reason, with a mass observed in his 2nd duodenalportion. Histiological study showed that it was aduodenal gangliocytic paraganlioma. The clinicalcharacteristics of this infrequent tumour are describedand we review the diagnosis and treatment

Isotretinoína y colitis ulcerosa / Isotretinoin and ulcerous colitis

La isotretinoína (Roacután®), fármaco derivado del ácido retinoico, es utilizado en dermatología como tratamiento para diversos tipos de acné. Su mecanismo de acción a nivel dermo-epidérmico aún no ha sido completamente esclarecido. Existen en la literatura actual diversos estudios en los que se ha documentado una relación, proporcional o inversa, entre la toma de isotretinoína y el debut o reactivación de una enfermedad inflamatoria intestinal. Aunque se han propuesto diversas hipótesis por las cuales este fármaco podría actuar sobre la mucosa intestinal en la patogénesis de la enfermedad, ninguna de ellas ha sido concluyente. Presentamos aquí un nuevo caso en el que pudo evidenciarse la mencionada relación, por lo que creemos conveniente recordar que ante un paciente con síntomas sospechosos de enfermedad inflamatoria intestinal en tratamiento activo con este isómero, debe realizarse un procedimiento endoscópico para descartarla (AU)

Síndrome general y diarrea como manifestación de infección por Giardia lamblia / General malaise and diarrhea as the main manifestations of Giardia lamblia infection

La Giardia lamblia o Giardia duodenalis es un protozoo cosmopolita, cuya transmisión, fecal-oral, se produce por la ingestión de sus quistes, que se desenquistan y se adhieren a los enterocitos. La clínica se caracteriza por la aparición de diarrea, dolor abdominal y otros síntomas menos frecuentes, como náuseas, anorexia y pérdida de peso. Las pruebas de enzimoinmunoanálisis, la inmunofluorescencia directa para buscar antígenos en muestras fecales y la biopsia intestinal son las técnicas que ofrecen mejor sensibilidad diagnóstica. En los casos en que se sospeche esta infección debe realizarse una biopsia de duodeno, aunque el aspecto endoscópico sea normal. El metronidazol y el tinidazol son los fármacos con mayor eficacia en el tratamiento. Se presenta el caso de un paciente con infección por G. lamblia, que consultó por un cuadro de síndrome general de 4 meses de evolución, forma no usual de presentación en el adulto de esta parasitosis, al que se añadió un cuadro diarreico en el último mes, cuyo diagnóstico se estableció a partir de la biopsia duodenal. El paciente respondió satisfactoriamente al tratamiento con metronidazol

Giardia lamblia is a ubiquitous intestinal protozoan. Transmission, which is fecal-oral, occurs after cyst ingestion, excystation and enterocyte adhesion. Symptoms include diarrhea, abdominal pain and other less frequent manifestations such as nausea, anorexia and weight loss. Enzyme immunoassay and direct fluorescent-antibody assay for antigen detection in stool samples, and small intestine biopsy provide the best diagnostic sensitivity. When an infection is suspected, duodenal biopsy should be carried out, even though endoscopic appearance may be normal. The most effective drugs in the treatment of this infection are metronidazole and tinidazole. We report a case of G. lamblia infection. The patient reported a clinical history of 4 months' duration with general malaise and diarrhea for the previous month. This form of presentation is rarely found in adults with this parasitosis. The diagnosis was based on the results of duodenal biopsy. The patient showed satisfactory response to treatment with metronidazole