Carolina Figueroa

Enfermedad inflamatoria intestinal: Una mirada inmunológica

Inflammatory bowel diseases (IBD) are inflammatory diseases with a multifactorial component that involve the intestinal tract. The two relevant IBD syndromes are Crohns disease (CD) and ulcerative colitis (UC). One factor involved in IBD development is a genetic predisposition, associated to NOD2/CARD15 and Toll-like receptor 4 (TLR4) polymorphisms that might favor infectious enterocolitis that is possibly associated to the development of IBD. The identification of specific immunologic alterations in IBD and their relationship to the etiology of the disease is a relevant research topic. The role of intra and extracellular molecules, such as transcription factors and cytokines that are involved in the inflammatory response, needs to be understood. The relevance of immunologic molecules that might drive the immune response to a T helper (Th) 1, Th 2 or the recently described Th 17 phenotype, has been demonstrated in animal models and clinical studies with IBD patients. CD and UC predominantly behave with a Th 1 and Th 2 immune phenotype, respectively. Recently, an association between CD and Th 17 has been reported. The knowledge acquired from immunologic and molecular research will help to develop accurate diagnostic methods and efficient therapies (Rev Med Chile 2008; 136: 367-75). (Key words: Colitis, ulcerative; Crohn disease; T-Lymphocytes, Helper-Inducer; Inflammatory bowel diseases; Nod2 signaling adaptor protein)

Inflammatory bowel disease: A descriptive study of 716 local Chilean patients.

AIM To demographically and clinically characterize inflammatory bowel disease (IBD) from the local registry and update data previously published by our group. METHODS A descriptive study of a cohort based on a registry of patients aged 15 years or older who were diagnosed with IBD and attended the IBD program at Clínica Las Condes in Santiago, Chile. The registry was created in April 2012 and includes patients registered up to October 2015. The information was anonymously downloaded in a monthly report, and the information on patients with more than one visit was updated. The registry includes demographic, clinical and disease characteristics, including the Montreal Classification, medical treatment, surgeries and hospitalizations for crisis. Data regarding infection with Clostridium difficile (C. difficile) were incorporated in the registry in 2014. Data for patients who received consultations as second opinions and continued treatment at this institution were also analyzed. RESULTS The study included 716 patients with IBD: 508 patients (71%) were diagnosed with ulcerative colitis (UC), 196 patients (27%) were diagnosed with Crohns disease (CD) and 12 patients (2%) were diagnosed with unclassifiable IBD. The UC/CD ratio was 2.6/1. The median age was 36 years (range 16-88), and 58% of the patients were female, with a median age at diagnosis of 29 years (range 5-76). In the past 15 years, a sustained increase in the number of patients diagnosed with IBD was observed, where 87% of the patients were diagnosed between the years 2001 and 2015. In the cohort examined in the present study, extensive colitis (50%) and colonic involvement (44%) predominated in the patients with UC and CD, respectively. In CD patients, non-stricturing/non-penetrating behavior was more frequent (80%), and perianal disease was observed in 28% of the patients. There were significant differences in treatment between UC and CD, with a higher use of corticosteroids, and immunosuppressive and biological therapies was observed in the patients with CD (P < 0.05 and P < 0.01). Significant surgical differences were also observed: 5% of the UC patients underwent surgery, whereas 38% of the CD patients required at least one surgery (P < 0.01). The patients with CD were hospitalized more often during their disease course than the patients with UC (55% and 35% of the patients, respectively; P < 0.01). C. difficile infection was acquired by 5% of the patients in each group at some point during the disease course. Nearly half of the patients consulted at the institution for a second opinion, and 32% of these individuals continued treatment at the institution. CONCLUSION IBD has continued to increase in the study cohort, slowly approaching the level reported in developed countries.

Ionizing radiation exposure in patients with inflammatory bowel disease: are we overexposing our patients?

Imaging techniques are accurate and reliable in diagnosing inflammatory bowel disease (IBD). However, the main disadvantage of computed tomography (CT) compared with magnetic resonance imaging (MRI) is radiation exposure and the potential risk of cancer, especially since IBD patients are at increased risk of malignancies. This study aims to quantify and characterize effective radiation exposure of IBD patients.

Eventos adversos en la terapia farmacológica de la enfermedad inflamatoria intestinal

Background: The purpose of inflammatory bowel disease (IBD) treatment is to achieve resolution of symptoms and remission of disease with a minimum of adverse events (AE). Aim: To report AE of different prescriptions used for the treatment of IBD. Material and methods: Analysis of a registry of patients with IBD held at a private clinic from 1976 to 2013. All used medications, the occurrence and severity of AE were recorded. Results: The records of 346 patients aged 16 to 86 years, 74% with ulcerative colitis, were analyzed. The most commonly type of medications prescribed were 5-aminosalicylates (5-ASAs) in 329 patients (92%), followed by adrenal steroids in 218 (61%). Forty nine AE were recorded in the same number of patents (14%). These were more common in patients with Crohn disease (n=19, 21%). An univariate analysis, demonstrated that extra-intestinal manifestations, hospitalizations secondary to IBD crisis, requirement of surgery and treatment with steroids, immunosuppressants or biologic agents were significantly associated with the presence of AE. AEs were more common with immunosuppressants, followed by 5-ASAs and steroids. Discontinuation of therapy was required in 79, 100 and 43% of patients taking these medications, respectively. Twenty percent of AEs were severe. Leukopenia and pancytopenia along with alopecia were the most common AEs attributable to azathioprine. Conclusions: The occurrence of AEs in patients with IBD is uncommon. Even inmunosuppressants or biologic agents have a low rate of AE and most of them mild.

Enfermedad inflamatoria intestinal a partir de una experiencia local

BACKGROUND The incidence and prevalence of Inflammatory Bowel Disease (IBD) has increased. AIM To determine demographic and clinical characteristics of patients with IBD in a Chilean private hospital. PATIENTS AND METHODS Review of a prospective registry of patients with IBD, started on 2012. It includes clinical, imaging, endoscopical and pathological information of patients. RESULTS Data of 316 patients with IBD, aged 16 to 86 years (56% females), were analyzed. Ulcerative Colitis (UC), Crohn´s and non-classifiable IBD were diagnosed in 230, 77 and 9 patients, respectively. The disease was diagnosed in 82% of patients in the period between 2002 and 2012. There was a peak in the diagnosis of both UC and CD between 20 and 39 years of age, without gender differences. The disease switched from UC to CD in six patients. In four, there was a change in disease behavior. Thirty eight patients were treated with biological therapy. The median lapse between the diagnosis and the use of biological therapy was 1 year in patients diagnosed after 2007, compared with 5.5 years among those patients diagnosed before 2007 (p = 0.001). There was a trend towards a higher requirement of surgery until 2006. Subsequently there was a stabilization of the requirement, concomitant with the incorporation of biological therapy. CONCLUSIONS An adequate registry of IBD patients is necessary to improve demographic and clinical characteristics. A national registry is needed to assess the epidemiological changes of IBD in Chile.Background: The incidence and prevalence of Inflammatory Bowel Disease (IBD) has increased. Aim: To determine demographic and clinical characteristics of patients with IBD in a Chilean private hospital. Patients and methods: Review of a prospective registry of patients with IBD, started on 2012. It includes clinical, imaging, endoscopical and pathological information of patients. Results: Data of 316 patients with IBD, aged 16 to 86 years (56% females), were analyzed. Ulcerative Colitis (UC), Crohn´s and non-classifiable IBD were diagnosed in 230, 77 and 9 patients, respectively. The disease was diagnosed in 82% of patients in the period between 2002 and 2012. There was a peak in the diagnosis of both UC and CD between 20 and 39 years of age, without gender differences. The disease switched from UC to CD in six patients. In four, there was a change in disease behavior. Thirty eight patients were treated with biological therapy. The median lapse between the diagnosis and the use of biological therapy was 1 year in patients diagnosed after 2007, compared with 5.5 years among those patients diagnosed before 2007 (p=0.001). There was a trend towards a higher requirement of surgery until 2006. Posteriorly there was a stabilization of the requirement, concomitant with the incorporation of biological therapy. Conclusions: An adequate registry of IBD patients is necessary to improve demographic and clinical characteristics. A national registry is needed to assess the epidemiological changes of IBD in Chile.

Inflammatory bowel disease. Experience in 316 patients

BACKGROUND The incidence and prevalence of Inflammatory Bowel Disease (IBD) has increased. AIM To determine demographic and clinical characteristics of patients with IBD in a Chilean private hospital. PATIENTS AND METHODS Review of a prospective registry of patients with IBD, started on 2012. It includes clinical, imaging, endoscopical and pathological information of patients. RESULTS Data of 316 patients with IBD, aged 16 to 86 years (56% females), were analyzed. Ulcerative Colitis (UC), Crohn´s and non-classifiable IBD were diagnosed in 230, 77 and 9 patients, respectively. The disease was diagnosed in 82% of patients in the period between 2002 and 2012. There was a peak in the diagnosis of both UC and CD between 20 and 39 years of age, without gender differences. The disease switched from UC to CD in six patients. In four, there was a change in disease behavior. Thirty eight patients were treated with biological therapy. The median lapse between the diagnosis and the use of biological therapy was 1 year in patients diagnosed after 2007, compared with 5.5 years among those patients diagnosed before 2007 (p = 0.001). There was a trend towards a higher requirement of surgery until 2006. Subsequently there was a stabilization of the requirement, concomitant with the incorporation of biological therapy. CONCLUSIONS An adequate registry of IBD patients is necessary to improve demographic and clinical characteristics. A national registry is needed to assess the epidemiological changes of IBD in Chile.Background: The incidence and prevalence of Inflammatory Bowel Disease (IBD) has increased. Aim: To determine demographic and clinical characteristics of patients with IBD in a Chilean private hospital. Patients and methods: Review of a prospective registry of patients with IBD, started on 2012. It includes clinical, imaging, endoscopical and pathological information of patients. Results: Data of 316 patients with IBD, aged 16 to 86 years (56% females), were analyzed. Ulcerative Colitis (UC), Crohn´s and non-classifiable IBD were diagnosed in 230, 77 and 9 patients, respectively. The disease was diagnosed in 82% of patients in the period between 2002 and 2012. There was a peak in the diagnosis of both UC and CD between 20 and 39 years of age, without gender differences. The disease switched from UC to CD in six patients. In four, there was a change in disease behavior. Thirty eight patients were treated with biological therapy. The median lapse between the diagnosis and the use of biological therapy was 1 year in patients diagnosed after 2007, compared with 5.5 years among those patients diagnosed before 2007 (p=0.001). There was a trend towards a higher requirement of surgery until 2006. Posteriorly there was a stabilization of the requirement, concomitant with the incorporation of biological therapy. Conclusions: An adequate registry of IBD patients is necessary to improve demographic and clinical characteristics. A national registry is needed to assess the epidemiological changes of IBD in Chile.

Clinical, endoscopic and histological correlation and measures of association in ulcerative colitis

To determine the correlation between clinical, fecal, endoscopic and histological activity in patients with ulcerative colitis (UC).

O-025 Disease-Related Knowledge in Inflammatory Bowel Disease.

Background:Disease-related knowledge can positively influence in the acceptance of the disease, increase treatment compliance and improve quality of life in patients with Inflammatory Bowel Disease (IBD). It also allows the patients to become more involved in decisions regarding the treatment of their disease, achieving a better doctor-patient relationship. The aim of our study was to identify disease-related knowledge in patients with IBD and determine possible factors associated to the knowledge level. Methods:We conducted a prospective study including patients presenting to our outpatient IBD Program between October 2014 and July 2015. Adult patients (18 years or older) were invited to participate, answering a demographic and clinical questionnaire. A Spanish-translated version of the 24-item Crohns and Colitis Knowledge score (CCKNOW) was used to assess disease-related knowledge. Patients also completed a demographic and clinical questionnaire including age, gender, educational level, employment status, history of IBD surgery and current IBD treatment. The study was approved by our Institutional Review Board, and all patients signed an informed consent. For statistical analysis categorical variables were expressed as frequency and percentage, and compare using chi square test. For continuous variables medians and range were used, and compare with Mann Whitney Test (2 groups) or Kruskal-Wallis Test (more than 2 groups). A P value <0.05 was considered as statistically significant. Results:A total of 203 patients were included, 62% female, 66% with Ulcerative Colitis (UC), with a median of age of 34 years (range 18–79) and a median of disease duration of 4 years. More than half of the patients had university or postgraduate education (58%) and 68% were employed. Related to treatment, 41% were using 5-ASA and 30% immunomodulators. The median CCKNOW score was 9 (range 1–20). 71% of the patients answered more than 50% of the questions incorrectly or did not know the answer. A lower disease-related knowledge was observed in questions related to pregnancy/fertility and surgery/complications (less than 20% of the patients answered correctly). Patients >50 years (median CCKNOW score 8 versus 9.5; P = 0.033), with UC (9 versus 11 in Crohns Disease patients; P = 0.017), with less than 5 years of disease (9 versus 10; P = 0.045) and patients without IBD surgery (9 versus 11.5; P = 0.004) showed a lower disease-related knowledge. Interestingly, there was no association between CCKNOW scores and the educational level of the patients. Conclusions:Patients attending our IBD Program show a poor disease-related knowledge, which is similar to knowledge levels observed in developed countries. It is necessary to assess patients knowledge in order to develop educational strategies, and evaluate the impact of these in the compliance and quality of life of IBD patients.

Desarrollo de neoplasia en pacientes con enfermedad inflamatoria intestinal

BACKGROUND The chronic inflammation of the intestinal mucosa, the extra-intestinal manifestations of the disease and the immunosuppressive treatment of inflammatory bowel disease may increase cancer risk. AIM To report the demographic and clinical features of patients with IBD who developed a malignant tumor. MATERIAL AND METHODS Retrospective analysis of an IBD patient registry of a private clinic, diagnosed between 1976 and 2014. RESULTS 437 subjects were included, aged 15-88 years (58% women). Seventy two percent of patients had ulcerative colitis. The median time of follow up was 6 years. Ten patients (2.3%) developed a malignant tumor. In four, the tumor could be related to IBD (two colorectal cancers, one cholangiocarcinoma and one chronic myeloid leukemia (CML)). Two of 45 patients treated with biological therapy developed a tumor (CML and hypernephroma). Three of 170 patients on immunosuppressive treatment developed tumors. Only one had a tumor possibly related with the use of azathioprine (non-melanoma skin cancer). In only two patients, the treatment was changed at the time of their cancer diagnosis, from immunosuppressive medications to mesalamine. CONCLUSIONS Only a small proportion of these patients with IBD developed a malignant tumor. The treatment of IBD has to be determined by the severity of the disease and not by the fear of developing a neoplasia. Following recommendations is fundamental to decrease the possibility of developing this complication.Background: The chronic inflammation of the intestinal mucosa, the extra-intestinal manifestations of the disease and the immunosuppressive treatment of inflammatory bowel disease may increase cancer risk. Aim: To report the demographic and clinical features of patients with IBD who developed a malignant tumor. Material and methods: Retrospective analysis of an IBD patient registry of a private clinic, diagnosed between 1976 and 2014. Results: 437 subjects were included, aged 15–88 years (58% women). Seventy two percent of patients had ulcerative colitis. The median time of follow up was 6 years. Ten patients (2.3%) developed a malignant tumor. In four, the tumor could be related to IBD (two colorectal cancers, one cholangiocarcinoma and one chronic myeloid leukemia (CML)). Two of 45 patients treated with biological therapy developed a tumor (CML and hypernephroma). Three of 170 patients on immunosuppressive treatment developed tumors. Only one had a tumor possibly related with the use of azathioprine (non-melanoma skin cancer). In only two patients, the treatment was changed at the time of their cancer diagnosis, from immunosuppressive medications to mesalamine. Conclusions: Only a small proportion of these patients with IBD developed a malignant tumor. The treatment of IBD has to be determined by the severity of the disease and not by the fear of developing a neoplasia. Following recommendations is fundamental to decrease the possibility of developing this complication.

Glucocorticoids Impair Phagocytosis and Inflammatory Response Against Crohn’s Disease-Associated Adherent-Invasive Escherichia coli

Crohn’s disease (CD) is a chronic inflammatory bowel disorder characterized by deregulated inflammation triggered by environmental factors. Notably, adherent-invasive Escherichia coli (AIEC), a bacterium with the ability to survive within macrophages is believed to be one of such factors. Glucocorticoids are the first line treatment for CD and to date, it is unknown how they affect bactericidal and inflammatory properties of macrophages against AIEC. The aim of this study was to evaluate the impact of glucocorticoid treatment on AIEC infected macrophages. First, THP-1 cell-derived macrophages were infected with a CD2-a AIEC strain, in the presence or absence of the glucocorticoid dexamethasone (Dex) and mRNA microarray analysis was performed. Differentially expressed mRNAs were confirmed by TaqMan-qPCR. In addition, an amikacin protection assay was used to evaluate the phagocytic and bactericidal activity of Dex-treated macrophages infected with E. coli strains (CD2-a, HM605, NRG857c, and HB101). Finally, cytokine secretion and the inflammatory phenotype of macrophages were evaluated by ELISA and flow cytometry, respectively. The microarray analysis showed that CD2-a, Dex, and CD2-a + Dex-treated macrophages have differential inflammatory gene profiles. Also, canonical pathway analysis revealed decreased phagocytosis signaling by Dex and anti-inflammatory polarization on CD2-a + Dex macrophages. Moreover, amikacin protection assay showed reduced phagocytosis upon Dex treatment and TaqMan-qPCR confirmed Dex inhibition of three phagocytosis-associated genes. All bacteria strains induced TNF-α, IL-6, IL-23, CD40, and CD80, which was inhibited by Dex. Thus, our data demonstrate that glucocorticoids impair phagocytosis and induce anti-inflammatory polarization after AIEC infection, possibly contributing to the survival of AIEC in infected CD patients.