Bincy Abraham

Dietary Intake and Risk of Developing Inflammatory Bowel Disease: A Systematic Review of the Literature

OBJECTIVES:The incidence of inflammatory bowel disease (IBD) is increasing. Dietary factors such as the spread of the “Western” diet, high in fat and protein but low in fruits and vegetables, may be associated with the increase. Although many studies have evaluated the association between diet and IBD risk, there has been no systematic review.METHODS:We performed a systematic review using guideline-recommended methodology to evaluate the association between pre-illness intake of nutrients (fats, carbohydrates, protein) and food groups (fruits, vegetables, meats) and the risk of subsequent IBD diagnosis. Eligible studies were identified via structured keyword searches in PubMed and Google Scholar and manual searches.RESULTS:Nineteen studies were included, encompassing 2,609 IBD patients (1,269 Crohn’s disease (CD) and 1,340 ulcerative colitis (UC) patients) and over 4,000 controls. Studies reported a positive association between high intake of saturated fats, monounsaturated fatty acids, total polyunsaturated fatty acids (PUFAs), total omega-3 fatty acids, omega-6 fatty acids, mono- and disaccharides, and meat and increased subsequent CD risk. Studies reported a negative association between dietary fiber and fruits and subsequent CD risk. High intakes of total fats, total PUFAs, omega-6 fatty acids, and meat were associated with an increased risk of UC. High vegetable intake was associated with a decreased risk of UC.CONCLUSIONS:High dietary intakes of total fats, PUFAs, omega-6 fatty acids, and meat were associated with an increased risk of CD and UC. High fiber and fruit intakes were associated with decreased CD risk, and high vegetable intake was associated with decreased UC risk.

Review article: current treatment options and management of functional dyspepsia

Functional dyspepsia (FD), a common functional gastrointestinal disorder, is defined by the Rome III criteria as symptoms of epigastric pain or discomfort (prevalence in FD of 89–90%), postprandial fullness (75–88%), and early satiety (50–82%) within the last 3 months with symptom onset at least 6 months earlier. Patients cannot have any evidence of structural disease to explain symptoms and predominant symptoms of gastroesophageal reflux are exclusionary. Symptoms of FD are non‐specific and the pathophysiology is diverse, which explains in part why a universally effective treatment for FD remains elusive.

Effect of Amitriptyline and Escitalopram on Functional Dyspepsia: A Multicenter, Randomized Controlled Study.

BACKGROUND & AIMS Antidepressants are frequently prescribed to treat functional dyspepsia (FD), a common disorder characterized by upper abdominal symptoms, including discomfort or postprandial fullness. However, there is little evidence of the efficacy of these drugs in patients with FD. We performed a randomized, double-blind, placebo-controlled trial to evaluate the effects of antidepressant therapy on symptoms, gastric emptying (GE), and meal-induced satiety in patients with FD. METHODS We performed a study at 8 North American sites of patients who met the Rome II criteria for FD and did not have depression or use antidepressants. Patients (n = 292; 44 ± 15 years old, 75% were female, 70% with dysmotility-like FD, and 30% with ulcer-like FD) were randomly assigned to groups given placebo, 50 mg amitriptyline, or 10 mg escitalopram for 10 weeks. The primary end point was adequate relief of FD symptoms for ≥5 weeks of the last 10 weeks (of 12). Secondary end points included GE time, maximum tolerated volume in Nutrient Drink Test, and FD-related quality of life. RESULTS An adequate relief response was reported by 39 subjects given placebo (40%), 51 given amitriptyline (53%), and 37 given escitalopram (38%) (P = .05, after treatment, adjusted for baseline balancing factors including all subjects). Subjects with ulcer-like FD given amitriptyline were >3-fold more likely to report adequate relief than those given placebo (odds ratio = 3.1; 95% confidence interval: 1.1-9.0). Neither amitriptyline nor escitalopram appeared to affect GE or meal-induced satiety after the 10-week period in any group. Subjects with delayed GE were less likely to report adequate relief than subjects with normal GE (odds ratio = 0.4; 95% confidence interval: 0.2-0.8). Both antidepressants improved overall quality of life. CONCLUSIONS Amitriptyline, but not escitalopram, appears to benefit some patients with FD, particularly those with ulcer-like (painful) FD. Patients with delayed GE do not respond to these drugs. ClinicalTrials.gov ID: NCT00248651.

Natural History of Pediatric-onset Inflammatory Bowel Disease: A Systematic Review

Background/Aims: There has been no systematic review of natural history studies of pediatric-onset inflammatory bowel disease (IBD). We conducted a systematic review focused on understanding the long-term risks of growth failure, disease reclassification and extension, hospitalizations, cancer and death among patients with childhood IBD. Methods: PubMed searches and subsequent data abstraction were performed by 2 independent investigators. Studies published full in english with a 5-year minimum average follow-up in at least 30 patients with IBD onset before age 18 years. Results: We evaluated 41 total studies (only 2 population-based studies) with 3505 Crohn’s disease (CD) patients, 2071 ulcerative colitis (UC) patients, and 461 indeterminate colitis (IC). Growth failure was reported in CD (10% and 56%) more often than UC (0% to 10%) or non-IBD controls. Improvements in growth occurred after surgical resection in patients with CD. There was an increase in disease reclassification over time from UC and indeterminate colitis diagnosis to CD diagnosis. Patients with CD had higher number of hospitalizations and hospital days per year in comparison with UC patients in most studies. The reported surgery rates in CD ranged between 10% and 72%; the colectomy rates in UC ranged between 0% and 50%. Cancers were reported in 6 CD patients during a total 18,270 patient-years (PY) follow-up, and 8 UC patients in 18,115 PY. Deaths directly related to IBD were 63 during 39,719 PY. Conclusions: Childhood-onset IBD patients had growth failure reported in patients with CD more often than those with UC, had a reclassification of disease type to CD over time. Higher rates of surgery and hospitalizations were found with CD than with UC. The risk of cancer and death is low in this population.

Management of the pregnant IBD patient

Women with inflammatory bowel disease (IBD) and the physicians who care for them must make difficult decisions on issues of conception, pregnancy, and breastfeeding with very limited and often contradictory information. This review provides the most current information on the inheritance of IBD, fertility, pregnancy outcomes, the management of disease during pregnancy, and the safety of medications in pregnancy and breastfeeding. We would like to emphasize that the information presented here must be individualized to the specific situation of each patient, their acceptance of risk, and their degree of disease severity.

Fecal markers: calprotectin and lactoferrin.

Overall, fecal markers have been found to be more accurate than serum markers. However, fecal markers are not specific for IBD and may be elevated in a range of organic conditions. Fecal calprotectin and lactoferrin can still differentiate inflammatory disease from functional bowel disorders. Comparison studies have found an overall diagnostic accuracy in IBD of 80% to 100% for both calprotectin and lactoferrin. Elevated levels are found in both CD and UC making it difficult to distinguish between these 2 diagnoses from these biomarkers alone. Both markers correlated well to mucosal healing and histologic improvement. Hence, they may be useful in monitoring response to treatment and predicting endoscopic and clinical relapse. Overall, patients with elevated markers were at higher risk of postoperative recurrence than those with normal levels. Fecal markers are useful in predicting pouchitis as well. Fecal markers are helpful as an adjunctive tool in overall evaluation of patients with nonspecific symptoms and as a management tool in those with inflammatory disease to monitor disease activity and possibility of relapse. They are less invasive than colonoscopy and can help guide management in a more cost-effective manner.

MicroRNA signatures differentiate Crohn’s disease from ulcerative colitis

BackgroundExcessive and inappropriate immune responses are the hallmark of several autoimmune disorders, including the inflammatory bowel diseases (IBD): Crohn’s disease (CD) and ulcerative colitis (UC). A complex etiology involving both environmental and genetic factors influences IBD pathogenesis. The role of microRNAs (miRNAs), noncoding RNAs involved in regulating numerous biological processes, to IBD pathology, in terms of initiation and progression, remains ill-defined. In the present study, we evaluated the relationship between colon, peripheral blood, and saliva whole miRNome expression in IBD patients and non-inflammatory bowel disease (non-IBD) controls to identify miRNAs that could discriminate CD from UC. Quantitative real-time PCR (qRT-PCR) was used to validate and assess miRNA expression.ResultsMicroarray analysis demonstrated that upwards of twenty six miRNAs were changed in CD and UC colon biopsies relative to the non-IBD controls. CD was associated with the differential expression of 10 miRNAs while UC was associated with 6 miRNAs in matched colon tissues. CD was associated with altered expression of 6 miRNAs while UC was associated with 9 miRNAs in whole blood. Expression of miR-101 in CD patients and miR-21, miR-31, miR-142-3p, and miR-142-5p in UC patients were altered in saliva.ConclusionsOur results suggest that there is specific miRNA expression patterns associated with UC versus CD in three separate tissue/body fluids (colon, blood, and saliva). Further, the aberrant miRNA expression profiles indicate that miRNAs may be contributory to IBD pathogenesis, or at least reflect the underlying inflammation. Scrutinizing miRNA expression in saliva and blood samples may be beneficial in monitoring or diagnosing disease in IBD patients. A panel of miRNAs (miR-19a, miR-21, miR-31, miR-101, miR-146a, and miR-375) may be used as markers to identify and discriminate between CD and UC.

The natural history of ulcerative colitis in a pediatric population: a follow-up population-based cohort study

Background The natural history of ulcerative colitis (UC) has been poorly studied in children. Methods We performed a retrospective study in children diagnosed with UC with a follow-up. The diagnosis of UC was based on clinical, radiologic, endoscopic, and histologic examinations. We estimated the occurrence of colectomy, proctitis, and extraintestinal manifestations (EIMs) at the onset of the diagnosis and at the end of the study period. Results We identified 115 UC patients between 1986 and 2003 with a mean age at diagnosis of 10.6 ± 5.1 years. The cumulative rate of colectomy was 4.1% at 1 year, and 16% at 10 years. EIMs were experienced by 20% of the children; 48% had arthritis, 35% had sclerosing cholangitis, and 17% had aphthous stomatitis. Proctitis was noted in 29 patients and it was not associated with an increased risk of colectomy (relative risk = 1.4; 95% CI = 0.7–4.5), and girls were twice more likely to develop proctitis. The pathologic reading for disease extensions was recorded for all children at entry and only 62 children had pathological results at maximum follow-up. At entry, 25% of the children only had ulcerative proctitis (E1) localization, 40% had left-sided UC (E2), and 35% had extensive UC (E3). Among the patients with E1 localization, 20% had progressed to E2 and 80% had progressed to E3; among the patients with E2 localization, 40% had progressed to E3. Age, gender, and EIMs at time of diagnosis were not associated with extension of disease at maximal follow-up. The Z score of body mass index (BMI) of children was significantly higher at the end of the study. At diagnosis, 85% of patients received 5-aminosalicyclic acid, 60% received steroids, and 11% received an immunomodulator. The majority of patients were still using systemic steroids at and after 5 years from their entry date. Only 32 of the 91 children on steroids did not receive an immunomodulator. Conclusion Pediatric UC is associated with high rates of EIMs and colectomy that are not dependent on age, gender, or race, but is associated with a high rate of proctitis among girls. Understanding the clinical course of UC can optimize therapeutic interventions.

Transition from pediatric to adult care

One role of the pediatric gastroenterologist is to help adolescents become self-sufficient as they approach an age when they will shift care to adult medicine. From surveys of adult gastroenterologists, there is a need for significant improvement in transition of care. These surveys discovered that over half of the young patients moving from pediatric providers have deficits in their knowledge about their disease, and 69 % could not provide their medical regimen. Planning for successful transition should include starting early in adolescence, asking family and healthcare providers to foster independence, and confirming with the young adult that there is a desire to become self-sufficient. Education should begin by 12–14 years of age and laying a foundation for independence by 14–17 years. By age 17–18 years the focus should be on self-management and healthy life styles. Parents and the pediatric medical team all have to be encouraged to participate in this process if transition is to be successful. At the time of transfer of care it is important to provide all of the important history and prior treatment for the adult gastroenterologist to make sure adequate care continues. It is also useful to follow-up to be sure the young adult patient has transitioned successfully and is continuing to receive ongoing care.

Drug-induced, factitious, & idiopathic diarrhoea

The aetiology of diarrhoea can often be simple to identify, but in some cases may pose a challenge. The diagnosis of drug-induced diarrhoea can easily be sorted based on timing of the symptom with onset of a new drug. Treatment can vary from simply monitoring and eventual resolution with continuation of the drug, to discontinuation of the offending agent. In cases where a drug cannot always be stopped, additional medications can help control the symptom. Factitious diarrhoea can present a diagnostic challenge if the evaluating physician does not suspect its possibility. Typically a careful history, and in some cases, stool testing can provide clues. The diagnosis of idiopathic diarrhoea is often made when exhaustive testing provides no definite aetiology and the goal of management is supportive care and symptomatic treatment.