Psoriasis induced by antiTNF therapy in inflammatory bowel disease: Therapeutic management and evolution of both diseases in a nationwide cohort study.

BACKGROUND: some patients with inflammatory bowel disease (IBD) treated with antiTNF develop drug-induced psoriasis (antiTNF-IP). Several therapeutic strategies are possible. AIMS: to assess the management of antiTNF-IP in IBD, and its impact in both diseases. METHODS: patients with antiTNF-IP from ENEIDA registry were included. Therapeutic strategy was classified as continuing the same antiTNF, stopping antiTNF, switch to another antiTNF or swap to a non-antiTNF biologic. IP severity and IBD activity were assessed at baseline and 16, 32 and 54 weeks. RESULTS: 234 patients were included. At baseline, antiTNF-IP was moderate-severe in 60 % of them, and IBD was in remission in 80 %. Therapeutic strategy was associated to antiTNF-IP severity (p < 0.001). AntiTNF-IP improved at week 54 with all strategies, but continuing with the same antiTNF showed the worst results (p = 0.042). Among patients with IBD in remission, relapse was higher in those who stopped antiTNF (p = 0.025). In multivariate analysis, stopping antiTNF, trunk and palms and soles location were associated with antiTNF-IP remission; female sex and previous surgery in Crohn´s disease with IBD relapse. CONCLUSION: skin lesions severity and IBD activity seem to determine antiTNF-IP management. Continuing antiTNF in mild antiTNF-IP, and swap to ustekinumab or switch to another antiTNF in moderate-severe cases, are suitable strategies.

Indications and hemoglobin thresholds for red blood cell transfusion and iron replacement in adults with gastrointestinal bleeding: An algorithm proposed by gastroenterologists and patient blood management experts.

Gastrointestinal (GI) bleeding is associated with considerable morbidity and mortality. Red blood cell (RBC) transfusion has long been the cornerstone of treatment for anemia due to GI bleeding. However, blood is not devoid of potential adverse effects, and it is also a precious resource, with limited supplies in blood banks. Nowadays, all patients should benefit from a patient blood management (PBM) program that aims to minimize blood loss, optimize hematopoiesis (mainly by using iron replacement therapy), maximize tolerance of anemia, and avoid unnecessary transfusions. Integration of PBM into healthcare management reduces patient mortality and morbidity and supports a restrictive RBC transfusion approach by reducing transfusion rates. The European Commission has outlined strategies to support hospitals with the implementation of PBM, but it is vital that these initiatives are translated into clinical practice. To help optimize management of anemia and iron deficiency in adults with acute or chronic GI bleeding, we developed a protocol under the auspices of the Spanish Association of Gastroenterology, in collaboration with healthcare professionals from 16 hospitals across Spain, including expert advice from different specialties involved in PBM strategies, such as internal medicine physicians, intensive care specialists, and hematologists. Recommendations include how to identify patients who have anemia (or iron deficiency) requiring oral/intravenous iron replacement therapy and/or RBC transfusion (using a restrictive approach to transfusion), and transfusing RBC units 1 unit at a time, with assessment of patients after each given unit (i.e., "don't give two without review"). The advantages and limitations of oral versus intravenous iron and guidance on the safe and effective use of intravenous iron are also described. Implementation of a PBM strategy and clinical decision-making support, including early treatment of anemia with iron supplementation in patients with GI bleeding, may improve patient outcomes and lower hospital costs.

[ESPEN guideline: Clinical nutrition in inflammatory bowel disease]. / Guía ESPEN: Nutrición clínica en la enfermedad inflamatoria intestinal.

Introduction: Introduction: the ESPEN guideline offers a multidisciplinary focus on clinical nutrition in inflammatory bowel disease (IBD). Methodology: the guideline is based on a extensive systematic review of the literature, but relies on expert opinion when objective data are lacking or inconclusive. The conclusions and 64 recommendations have been subject to full peer review and a Delphi process, in which uniformly positive responses (agree or strongly agree) were required. Results: IBD is increasingly common and potential dietary factors in its etiology are briefly reviewed. Malnutrition is highly prevalent in IBD - especially in Crohn's disease. Increased energy and protein requirements are observed in some patients. The management of malnutrition in IBD is considered within the general context of support for malnourished patients. Treatment of iron deficiency (parenterally, if necessary) is strongly recommended. Routine provision of a special diet in IBD is not, however, supported. Parenteral nutrition is indicated only when enteral nutrition has failed or is impossible. The recommended perioperative management of patients with IBD undergoing surgery accords with general ESPEN guidance for patients having abdominal surgery. Probiotics may be helpful in UC but not in Crohn's disease. Primary therapy using nutrition to treat IBD is not supported in ulcerative colitis but is moderately well supported in Crohn's disease, especially in children, where the adverse consequences of steroid therapy are proportionally greater. However, exclusion diets are generally not recommended and there is little evidence to support any particular formula feed when nutritional regimens are constructed. Conclusions: available objective data to guide nutritional support and primary nutritional therapy in IBD are presented as 64 recommendations, of which 9 are very strong recommendations (grade A), 22 are strong recommendations (grade B), and 12 are based only on sparse evidence (grade 0); 21 recommendations are good practice points (GPP).

Introducción: Introducción: la guía ESPEN ofrece un enfoque multidisciplinar de la nutrición clínica en la enfermedad inflamatoria intestinal (EII). Metodología: la guía se basa en una extensa revisión sistemática de la literatura y en la opinión de expertos cuando faltan datos objetivos o estos no son concluyentes. Las conclusiones y las 64 recomendaciones han sido objeto de una revisión completa por pares y de un proceso Delphi en el que se requerían respuestas fuertemente positivas (de acuerdo o totalmente de acuerdo). Resultados: la EII es cada vez más común y se revisan brevemente los posibles factores dietéticos en su etiología. La desnutrición es muy prevalente en la EII, especialmente en la enfermedad de Crohn. En algunos pacientes se observan mayores requerimientos de energía y proteínas. El manejo de la desnutrición en la EII se considera dentro del contexto general de apoyo a los pacientes desnutridos. Se recomienda fuertemente el tratamiento de la deficiencia de hierro (por vía parenteral, si es necesario). Sin embargo, no se aconseja la prescripción de rutina de una dieta especial en la EII. La nutrición parenteral está indicada solo cuando la nutrición enteral ha fallado o es imposible. El manejo perioperatorio recomendado de los pacientes con EII sometidos a cirugía se hace de acuerdo con la guía general de la ESPEN para pacientes sometidos a cirugía abdominal. Los probióticos pueden ser útiles en la CU pero no en la enfermedad de Crohn. El tratamiento primario con nutrición para tratar la EII no está respaldado en la colitis ulcerosa, aunque está moderadamente bien soportado en la enfermedad de Crohn, especialmente en los niños, donde las consecuencias adversas de la terapia con esteroides son proporcionalmente mayores. Sin embargo, las dietas de exclusión generalmente no se recomiendan y hay poca evidencia que respalde cualquier fórmula de nutrición en particular cuando se realizan regímenes nutricionales. Conclusiones: los datos objetivos disponibles para guiar el apoyo nutricional y la terapia nutricional primaria en la EII se presentan como 64 recomendaciones, de las cuales 9 son recomendaciones muy fuertes (grado A), 22 son recomendaciones fuertes (grado B) y 12 se basan solo en evidencia escasa (grado 0); 21 recomendaciones son recomendaciones de buenas prácticas (GPP).

Prospective, study comparing the accuracy of two different stool antigen tests (Premier Platinum HpSA and novel ImmunoCard STAT! rapid test) for the diagnosis of Helicobacter pylori infection.

BACKGROUND: At present only monoclonal EIA (enzyme-immunoassay) stool antigen-tests have obtained optimal accuracy in the diagnosis of Helicobacter pylori. Our aim was to evaluate the accuracy of two stool antigen-tests, the validated Premier Platinum HpSA PLUS (EIA test) and the newly available ImmunoCard STAT! HpSA HD (rapid test) for the initial diagnosis and the confirmation of eradication of H. pylori infection. PATIENTS AND METHODS: Patients with indication of H. pylori diagnosis, or confirmation after treatment were included. Data were coded to protect personal data and ensure blindness between tests. Accuracy was considered as coincident diagnosis with the gold standard (13C-urea breath test, UBT). The EIA was used as a bench standard. All stool tests were performed in duplicate. RESULTS: 264 patients completed the protocol (100 naïve, 164 post-eradication). Average age was 52 years, 61% women, 11% ulcer. Positive diagnoses by UBT were 41% for naïve and 17% for post-eradication. Overall ImmunoCard and EIA accuracies were respectively 91% (95%C.I.=88-94%) and 89% (86-93%), sensitivities 72% (67-78%) and 72% (67-78%), and specificities 98% (96-100%), and 95% (92-97%). Concordance between ImmunoCard and EIA was 95% (93-98%). DISCUSSION: Our results indicate that the newly available ImmunoCard rapid stool antigen-test achieves 90% accuracy, with high specificity but suboptimal sensitivity. The ImmunoCard attained equivalent accuracies as the EIA bench standard, with 95% concordance.

Prevalence of Malnutrition and Nutritional Characteristics of Patients With Inflammatory Bowel Disease.

BACKGROUND AND AIMS: This study sought to determine the prevalence of malnutrition in patients with inflammatory bowel disease, to analyse the dietary beliefs and behaviours of these patients, to study their body composition, to evaluate their muscular strength and to identify the factors associated with malnutrition in these patients. METHODS: This was a prospective, multicentre study. Crohn's disease and ulcerative colitis patients from 30 Spanish centres, from the outpatient clinics, were included. A questionnaire of 11 items was applied to obtain data from patients' dietary behaviour and beliefs. Patients who accepted were evaluated to assess their nutritional status using Subjective Global Assessment and body mass index. Body composition was evaluated through bioelectrical impedance. RESULTS: A total of 1271 patients were included [51% women, median age 45 years, 60% Crohn's disease]. Of these, 333 patients underwent the nutritional evaluation. A total of 77% of patients declared that they avoided some foods to prevent disease relapse. Eighty-six per cent of patients avoided some foods when they had disease activity because of fear of worsening the flare. Sixty-seven per cent of patients modified their dietary habits after disease diagnosis. The prevalence of malnutrition was 16% [95% confidence interval = 12-20%]. In the multivariate analysis, history of abdominal surgery, active disease and avoidance of some foods during flares were associated with higher risk of malnutrition. CONCLUSIONS: The prevalence of malnutrition in inflammatory bowel disease patients was high. We identified some predictive factors of malnutrition. Most of the patients had self-imposed food restrictions, based on their beliefs.

Accuracy of the Ultra-Rapid Urease Test for diagnosis of Helicobacter pylori infection.

BACKGROUND: Rapid Urease Test (RUT) is a simple, cheap and relatively fast method for diagnosing Helicobacter pylori infection. It is therefore the preferred method used for patients undergoing gastroscopy. Most kits require 24h to give results. The new Ultra-Rapid Urease Test (URUT) kit by Biohit® requires less than 1h. OBJECTIVE: To determine URUT's diagnostic accuracy. METHOD: Prospective, blind, multi-centre study involving dyspeptic patients. One corpus biopsy and three antral biopsies were obtained during gastroscopy for standard histological analysis, RUT and URUT. The URUT result was checked after 1min, 5min, 30min and 60min and the RUT was checked over the course of 24h. Histology was used as the gold standard test. RESULTS: 144 patients were included, 68% female, with a mean age of 49 years old; 50% were H. pylori positive. RUT and URUT diagnoses were correct in 85.9% and 90% of the cases, respectively. The mean waiting time for a positive RUT result was 6h. The sensitivity, specificity, and positive and negative predictive values for RUT were, respectively, 82%, 90%, 89% and 84%. The URUT's results were similar (85%, 94%, 94% and 87%). These figures improved when patients taking PPIs were excluded (RUT: 86%, 91%, 93% and 83%; URUT: 91%, 94%, 96% and 89%). No statistically significant differences were found when comparing RUT and URUT distributions of correct diagnoses (McNemar's Test, p=0.3) but there was a tendency towards better results with the URUT. CONCLUSION: The URUT is equivalent to (or slightly better than) the traditional RUT in diagnosing H. pylori infection, and provides results in less than an hour.

IV Spanish Consensus Conference on Helicobacter pylori infection treatment. / IV Conferencia Española de Consenso sobre el tratamiento de la infección por Helicobacter pylori.

Helicobacter pylori approximately infect 50% of Spanish population and causes chronic gastritis, peptic ulcer and gastric cancer. Until now, three consensus meetings on H.pylori infection had been performed in Spain (the last in 2012). The changes in the treatment schemes, and the increasing available evidence, have justified organizing the IVSpanish Consensus Conference (March 2016), focused on the treatment of this infection. Nineteen experts participated, who performed a systematic review of the scientific evidence and developed a series of recommendation that were subjected to an anonymous Delphi process of iterative voting. Scientific evidence and the strength of the recommendation were classified using GRADE guidelines. As starting point, this consensus increased the minimum acceptable efficacy of recommended treatments that should reach, or preferably surpass, the 90% cure rate when prescribed empirically. Therefore, only quadruple therapies (with or without bismuth), and generally lasting 14 days, are recommended both for first and second line treatments. Non-bismuth quadruple concomitant regimen, including a proton pump inhibitor, clarithromycin, amoxicillin and metronidazole, is recommended as first line. In the present consensus, other first line alternatives and rescue treatments are also reviewed and recommended.

Phenotypic concordance in familial inflammatory bowel disease (IBD). Results of a nationwide IBD Spanish database.

BACKGROUND & AIMS: Disease outcome has been found to be poorer in familial inflammatory bowel disease (IBD) than in sporadic forms, but assessment of phenotypic concordance in familial IBD provided controversial results. We assessed the concordance for disease type and phenotypic features in IBD families. METHODS: Patients with familial IBD were identified from the IBD Spanish database ENEIDA. Families in whom at least two members were in the database were selected for concordance analysis (κ index). Concordance for type of IBD [Crohn's disease (CD) vs. ulcerative colitis (UC)], as well as for disease extent, localization and behaviour, perianal disease, extraintestinal manifestations, and indicators of severe disease (i.e., need for immunosuppressors, biological agents, and surgery) for those pairs concordant for IBD type, were analyzed. RESULTS: 798 out of 11,905 IBD patients (7%) in ENEIDA had familial history of IBD. Complete data of 107 families (231 patients and 144 consanguineous pairs) were available for concordance analyses. The youngest members of the pairs were diagnosed with IBD at a significantly younger age (p<0.001) than the oldest ones. Seventy-six percent of pairs matched up for the IBD type (κ=0.58; 95%CI: 0.42-0.73, moderate concordance). There was no relevant concordance for any of the phenotypic items assessed in both diseases. CONCLUSIONS: Familial IBD is associated with diagnostic anticipation in younger individuals. Familial history does not allow predicting any phenotypic feature other than IBD type.

Safety of thiopurine therapy in inflammatory bowel disease: long-term follow-up study of 3931 patients.

BACKGROUND: To evaluate the safety of thiopurines in patients with inflammatory bowel disease. To identify predictive factors associated with the development of thiopurine-induced adverse events. METHODS: Long-term incidence of adverse events was estimated in patients from a prospectively maintained Spanish nationwide database using Kaplan-Meier analysis. Cox regression analysis was performed to identify potential predictive factors of adverse events. RESULTS: Three thousand nine hundred and thirty-one patients were included. Ninety-five percent of patients were on azathioprine. The median follow-up with thiopurines was 44 months (range, 0-420). Adverse events occurred at a median of 1 month after starting treatment. The cumulative incidence of adverse events was 26%, with an annual risk of 7% per patient-year of treatment. Most frequent adverse events were nausea (8%), hepatotoxicity (4%), myelotoxicity (4%), and pancreatitis (4%). Four patients had lymphoma. Female and Crohn's disease increased the risk of having nausea. The risk of hepatotoxicity was lower in females and higher in Crohn's disease. The risk of myelotoxicity was significantly higher in patients treated with mercaptopurine and in females. The risk of pancreatitis was higher in Crohn's disease. Overall, 17% of patients discontinued thiopurine treatment due to adverse events. Thirty-seven percent of these patients started thiopurines again and 40% of them had adverse events again. CONCLUSIONS: As many as 1 of 4 patients on thiopurine therapy had adverse events during follow-up. A relatively high proportion of patients (17%) had to discontinue the treatment with thiopurines due to adverse events. However, more than half of patients that restarted thiopurine treatment after its discontinuation due to adverse events tolerated it. Several predictive factors for some adverse events have been identified.

Impact of current smoking on the clinical course of microscopic colitis.

BACKGROUND: Whether current smoking worsens the clinical course of microscopic colitis (MC) is unknown. The aim was to evaluate the impact of smoking on the clinical course of MC. METHODS: One hundred and eighty-four patients (72% women; age, 62.4 ± 1.1 years) with MC (118 collagenous colitis (CC) and 66 lymphocytic colitis (LC) were evaluated (39 of them were current smokers). In all the patients, smoking habits and clinical data at presentation, response to therapy, and clinical relapses during follow-up were prospectively recorded. Risk factors for clinical relapse were studied in 160 patients after a mean follow-up of 28 ± 1 months. Cox regression analysis was used to adjust for confounding variables. RESULTS: Age at diarrhea onset was 63.0 ± 1.4 years in nonsmokers and 50.4 ± 2.1 years in current smokers (P < 0.001). There was no significant influence of smoking habit on either clinical symptoms at diagnosis or clinical remission rate. Clinical relapse rate was 25.5% for CC and 29.6% for LC, with the mean relapse-free time 28.8 months (95% confidence interval, 26.3-31.4) for CC and 26.9 months (95% confidence interval, 26-30.3) for LC (P = 0.5). Multivariate analysis showed that age at diagnosis (<50 years versus others; adjusted hazard ratio, 2.8; 95% confidence interval, 1.3-6; P = 0.01) was associated with risk of relapse of CC but not LC. Current smoking was not an independent risk factor for either CC or LC relapse. CONCLUSIONS: Active smokers developed MC more than a decade before nonsmokers. Age at diagnosis, but not smoking, was an independent risk factor of relapse in patients with CC.

Epidemiological risk factors in microscopic colitis: a prospective case-control study.

BACKGROUND: The cause of collagenous colitis (CC) and lymphocytic colitis (LC) is unknown and epidemiological risk factors for CC and LC are not well studied. The aim was to evaluate in a case-control study epidemiological risk factors for CC and LC. METHODS: In all, 120 patients with CC, 70 with CL, and 128 controls were included. For all cases and controls information was prospectively recorded. A binary logistic regression analysis was performed separately for CC and LC. RESULTS: Independent associations observed with the diagnosis of CC were: current smoking (odds ratio [OR], 2.4), history of polyarthritis (OR, 20.8), and consumption of lansoprazole (OR, 6.4), low-dose aspirin (OR, 3.8), beta-blockers (OR, 3.6), and angiotensin II receptor antagonists (OR 0.20). In the case of LC they were: current smoking (OR, 3.8), associated autoimmune diseases (OR, 8), and consumption of sertraline (OR, 17.5), omeprazole (OR 2.7), low-dose aspirin (OR, 4.7), and oral antidiabetic drugs (OR, 0.14). CONCLUSIONS: The consumption of drugs, current smoking, and associated autoimmune diseases were independently associated with the risk of microscopic colitis.

Long-term durability of infliximab treatment in Crohn's disease and efficacy of dose "escalation" in patients losing response.

BACKGROUND: The efficacy of infliximab therapy in patients with Crohn's disease (CD) is unknown beyond 12 months. For patients who lose their initial response, consideration can be given to dose "escalation" to regain therapeutic benefit. AIM: Our primary goal was to evaluate the long-term durability of maintenance infliximab treatment. The secondary goals were to identify potential predictors of loss of infliximab efficacy, to evaluate the response to infliximab escalation, and the safety of the treatment with infliximab with and without escalation of dose. METHODS: CD patients treated with infliximab with response to an induction regimen were evaluated. Maintenance of long-term response was estimated using Kaplan-Meier analysis. The effect of specific variables was calculated using logistic regression analysis. Efficacy of dose escalation in patients who lose response to infliximab was analyzed. RESULTS: Three hundred and nine CD patients were included. The mean follow-up time with infliximab treatment was 41 months, and the majority (95%) were on concomitant immunosuppressive therapy. The annual risk of loss of response to infliximab was 12% per patient-year of treatment. After loss of response, 41% of patients were managed with infliximab therapy escalation. After the first intensified dose, 56% of patients achieved remission and 40% partial response. Concurrent immunomodulators enhanced and smoking decreased the proportion of patients who maintained response (P<0.05). CONCLUSIONS: A relevant proportion of CD patients on long-term infliximab treatment loss response. After loss of response, a high proportion of these patients initially respond to infliximab dose escalation. Concurrent immunomodulators may increase and smoking may decrease maintenance of response.

Clinical patterns and outcomes of ischaemic colitis: results of the Working Group for the Study of Ischaemic Colitis in Spain (CIE study).

BACKGROUND: There is a lack of prospective studies evaluating the natural history of colonic ischaemia (CI). We performed such a study to evaluate the clinical presentation, outcome, and mortality as well as clinical variables associated with poor prognosis. METHODS: An open, prospective, and multicentre study was conducted in 24 Spanish hospitals serving a population of 3.5 million people. The study included only patients who met criteria for definitive or probable CI. A website (www.colitisisquemica.org) provided logistical support. RESULTS: A total of 364 patients met criteria for inclusion. CI was suspected clinically in only 24.2% of cases. The distribution of clinical patterns was as follows: reversible colopathy (26.1%), transient colitis (43.7%), gangrenous colitis (9.9%), fulminant pancolitis (2.5%), and chronic segmental colitis (17.9%). A total of 47 patients (12.9%) had an unfavorable outcome as defined by mortality and/or the need for surgery. Multivariate analysis identified the following signs as independent risk factors for an unfavorable outcome: abdominal pain without rectal bleeding [odds ratio (OR) 3.9; 95% confidence interval (CI) = 1.6-9.3], non-bloody diarrhoea (OR 10; 95% CI = 3.7-27.4), and peritoneal signs (OR 7.3; 95% CI = 2.7-19.6). Unfavorable outcomes also were more frequent in isolated right colon ischaemia (IRCI) compared with non-IRCI (40.9 vs. 10.3%, respectively; p < 0.0001). The overall mortality rate was 7.7%. CONCLUSIONS: The clinical presentation of CI is very heterogeneous, perhaps explaining why clinical suspicion of this disease is so low. The presence of IRCI, and occurrence of peritoneal signs or onset of CI as severe abdominal pain without bleeding, should alert the physician to a potentially unfavorable course.

[Cholestasis of pregnancy]. / Colestasis gravídica.

Intrahepatic cholestasis of pregnancy (ICP) is a reversible cholestatic liver disease that may develop during the second or third trimester of pregnancy and resolves rapidly after delivery. The chief complaint is pruritus. Serum liver tests reveal moderate cholestasis with increased levels of bile salts (> or = 10 micromol/l) and aminotransferases. The pathogenesis of ICP is multifactorial. Potential contributors include a genetic predisposition interacting with the effects of estrogen and progesterone metabolites on bile secretory mechanisms, as well as environmental factors. ICP may cause fetal distress, with stillbirths or premature deliveries, leading to increased perinatal morbidity and mortality. Several drugs have been used for ICP treatment. The available evidence suggests that the most effective therapy is ursodeoxycholic acid, since this drug improves pruritus and liver function tests without maternal or fetal toxicity.