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Concept: Malabsorption

384

Wheat gluten and related proteins can trigger an autoimmune enteropathy, known as coeliac disease, in people with genetic susceptibility. However, some individuals experience a range of symptoms in response to wheat ingestion, without the characteristic serological or histological evidence of coeliac disease. The aetiology and mechanism of these symptoms are unknown, and no biomarkers have been identified. We aimed to determine if sensitivity to wheat in the absence of coeliac disease is associated with systemic immune activation that may be linked to an enteropathy.

Concepts: Immune system, Wheat, Coeliac disease, Gluten, Gluten-free diet, Wheat allergy, Malabsorption, Gliadin

170

Celiac disease is a life-long autoimmune condition, affecting genetically susceptible individuals that may present with thromboembolic phenomena. This thrombophilia represents a puzzle with multiple constituents: hyperhomocysteinemia, B12 and\or folate deficiency, methylenetetrahydrofolate reductase mutations, and protein C and S deficiency due to vitamin K deficiency. However, the well known thrombogenic factors, antiphosphatidylserine/prothrombin and antiprothrombin have never been explored in celiac disease.

Concepts: Immune system, Coagulation, Escherichia coli, Folic acid, Coeliac disease, Vitamin K, Malabsorption, Methylenetetrahydrofolate reductase

169

BACKGROUND & AIMS: Little is known about the long-term outcomes of patients with Crohn’s disease (CD) who have a complete response to therapy with azathioprine. We assessed the long-term effects of azathioprine in responders. METHODS: We collected data from the MICISTA registry (a database from the Rothschild and Saint-Antoine Hospitals in Paris, France) on consecutive CD patients treated with azathioprine 1987-1999 who responded to therapy (steroid-free clinical remission at 1 year); they were followed until 2011 (n=220; 86 male; median age 32 years; median follow-up period, 12.6 years). Data were compared with those from 440 matched patients with CD who did not receive immunosuppressants during the same period of inclusion (controls). RESULTS: The cumulative rate of sustained remission 10 years after treatment with azathioprine was 3%. Among patients exposed to azathioprine during a prospective follow-up period (1995-2011, 1936 patient-years), the percent of patient-years with active disease (flare or complication during the calendar year) was 17.6%. Compared to the control group, at baseline, responders were more often active smokers with significantly more extensive disease, perianal lesions, and extra-digestive manifestations. During follow-up, responders had a significantly reduced risk of intestinal surgery (adjusted odds ratio [AOR], 0.69; 95% confidence interval [CI], 0.52-0.91) and of perianal surgery (AOR, 0.36; 95% CI, 0.27-0.46). A significantly higher percentage of responders developed cancers, including non-melanoma skin cancers, compared with controls (9.5% vs 4.1%;P <.01). Survival rates after 20 years were 92.8%±2.3% of responders vs 97.9%±0.8% of controls ( P =.01). CONCLUSION: Based on a study at a single center, patients with CD that responds to azathioprine have a smaller proportion of patient-years with active disease, and are less likely to be hospitalized or undergo intestinal surgery, than patients with CD who did not receive immunosuppressants. These benefits, however, could be offset by increased risk of malignancies.

Concepts: Epidemiology, Cancer, Hospital, Ulcerative colitis, Crohn's disease, Gastroenterology, Normal distribution, Malabsorption

33

IBS is a common gut disorder of uncertain pathogenesis. Among other factors, genetics and certain foods are proposed to contribute. Congenital sucrase-isomaltase deficiency (CSID) is a rare genetic form of disaccharide malabsorption characterised by diarrhoea, abdominal pain and bloating, which are features common to IBS. We tested sucrase-isomaltase (SI) gene variants for their potential relevance in IBS.

Concepts: Genetics, Bacteria, Abdominal pain, Gastroenterology, Irritable bowel syndrome, Coeliac disease, Malabsorption, Sucrose intolerance

28

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome (APECED) is an autosomal recessive disease due to mutations of the autoimmune regulator (AIRE) gene. Typical manifestations include candidiasis, Addison’s disease, and hypoparathyroidism. Type 1 diabetes, alopecia, vitiligo, ectodermal dystrophy, celiac disease and other intestinal dysfunctions, chronic atrophic gastritis, chronic active hepatitis, autoimmune thyroid disorders, pernicious anemia and premature ovarian failure are other rare associated diseases although other conditions have been associated with APECED.

Concepts: Immune system, Endocrinology, Autoimmune diseases, Autoimmunity, Malabsorption, Addison's disease, Pernicious anemia, Atrophic gastritis

28

Weight loss following esophagectomy is a management challenge for all patients. It is multifactorial with contributing factors including loss of gastric reservoir, rapid small bowel transit, malabsorption, and adjuvant chemotherapy. The development of a postoperative malabsorption syndrome, as a result of exocrine pancreatic insufficiency (EPI), is recognized in a subgroup of patients following gastrectomy. This has not previously been documented following esophageal resection. EPI can result in symptoms of flatulence, diarrhea, steatorrhea, vitamin deficiencies, and weight loss. It therefore has the potential to pose a significant level of morbidity in postoperative patients. There is some evidence that patients with proven EPI (fecal elastase-1 < 200 μg/g) may benefit from a trial of pancreatic enzyme replacement therapy (PERT). We observed symptoms compatible with EPI in a subgroup of patients following esophagectomy. We hypothesized that this was contributing to malabsorption and malnutrition in these patients. To investigate this, fecal elastase-1 was measured in postoperative patients, and in those with proven EPI, a trial of PERT was commenced in combination with specialist dietary education. At routine postoperative follow-up, which included assessment by a specialist dietitian, those patients with symptoms suggestive of malabsorption were given the opportunity to have their fecal elastase-1 measured. PERT was then offered to patients with fecal elastase-1 less than 200 μg/g (EPI) as well as those in the 200-500 μg/g range (mild EPI) with more severe symptoms. Fecal elastase-1 was measured in 63 patients between June 2009 and January 2011 at a median of 4 months (range 1-42) following surgery. Ten patients had fecal elastase-1 less than 200 μg/g, and all had failed to maintain preoperative weight. All accepted a trial of PERT. Nine (90%) had symptomatic improvement, and seven (70%) increased their weight. Thirty-nine patients had a fecal elastase-1 in the 200-500 μg/g range. Twelve were given a trial of PERT based on level of symptoms, five (42%) reported an improvement in symptoms, but only two (17%) gained weight. Our early results support the observation that EPI is a factor contributing to postoperative morbidity in patients recovering from esophagectomy and that these patients can benefit from a trial of PERT. Our study has limitations, and a formal trial is required to evaluate the impact of EPI and PERT following esophagectomy. Currently, our practice is to measure fecal elastase-1 in any patient with unexplained weight loss or symptoms of malabsorption. In patients with proven EPI or those who are symptomatic with mild EPI, a trial of PERT should be offered and symptoms reassessed.

Concepts: Nutrition, Pancreas, Crohn's disease, Intestine, Gastroenterology, Malabsorption, Chronic pancreatitis, Steatorrhea

27

Exclusive enteral nutrition is effective for inducing remission in active pediatric Crohn’s disease. Partial enteral nutrition (PEN) with free diet is ineffective for inducing remission, suggesting that the mechanism depends on exclusion of free diet. We developed an alternative diet based on PEN with exclusion of dietary components hypothesized to affect the microbiome or intestinal permeability.

Concepts: Protein, Nutrition, Death, Fat, Ulcerative colitis, Gastroenterology, Diet, Malabsorption

27

Video capsule endoscopy (VCE) is being increasingly used to investigate small bowel pathology. It is the gold standard for obscure gastrointestinal bleeding and iron deficiency anemia. VCE has been in use since 2001 and indications for its use are expanding. VCE is also a useful diagnostic tool in small bowel Crohn’s disease, celiac disease, surveillance of polyps, small bowel malignancy and drug-induced small bowel injury. Although VCE is considered a safe and easy procedure, there are a few limitations. These include cost, capsule retention and inability to take a biopsy and perform any therapeutic maneuvers. Contraindications for VCE include pregnancy, patients with a swallowing disorder, history of previous abdominal surgery or concurrent abdomino-pelvic irradiation. This is an overview of VCE, its role and indications in clinical practice, potential complications and contraindications, as well as the ongoing and expected advances in the field.

Concepts: Medical terms, Crohn's disease, Colonoscopy, Gastroenterology, Small intestine, Bowel obstruction, Iron deficiency anemia, Malabsorption

27

Intestinal tuberculosis (TB) and Crohn’s disease closely resemble each other clinically and morphologically. Little is known of cytokine regulation in intestinal TB.

Concepts: DNA, Gene, Gene expression, Bacteria, Transcription, Ulcerative colitis, Gastroenterology, Malabsorption

24

The inflammatory intestinal disorder Crohn’s disease (CD) has become a health challenge worldwide. The gut microbiota closely interacts with the host immune system, but its functional impact in CD is unclear. Except for studies on a small number of CD patients, analyses of the gut microbiota in CD have used 16S rDNA amplicon sequencing. Here we employed metagenomic shotgun sequencing to provide a detailed characterization of the compositional and functional features of the CD microbiota, comprising also unannotated bacteria, and investigated its modulation by exclusive enteral nutrition (EEN).

Concepts: Immune system, Antibody, Bacteria, Gut flora, Ulcerative colitis, Gastroenterology, Small intestine, Malabsorption