What is the Intestinal permeability in families with Crohn's?

"Intestinal permeability before and after ibuprofen in families of children with Crohn's Disease in Can J Gasteroenterol (1999)
Conclusions:  "Members of a subset of first-degree relatives of children with Crohn's disease have an exaggerated increase in intestinal permeability after ibuprofen ingestion. These findings are compatible with there being a genetic link between abnormalities of intestinal permeability and Crohn's disease."

"Increased Intestinal Permeability Precedes the Onset of Crohn’s Disease in a Subject With Familial Risk" in Gastroenterology (2000)
"In summary, increased intestinal permeability is com-mon among patients with Crohn’s disease, particularly when their disease is active, and in a subgroup of theirnondiseased relatives. Our case report describes a patientwith a strong family history of Crohn’s disease whose permeability to 51Cr-EDTA was increased 8 years beforethe diagnosis of Crohn’s disease. This contributes to the growing pool of evidence that a permeability defect and exposure of the lamina propria to luminal antigens are seminal events in the pathogenesis of inflammatory bowel disease. Longitudinal studies that stratify patients by their family history of inflammatory bowel disease areneeded to examine this mechanism further." [Italics mine.]

In summary, increased intestinal permeability is com-

"Increased intestinal permeability and NOD2 variants in familial and sporadic Crohn's disease" in Alim Pharmicol Ther (2006)
Conclusion:  "Intestinal permeability is raised in Crohn's disease patients and relatives, with higher rates in familial vs. sporadic healthy relatives. CARD15 mutations are associated with abnormal permeability in ileal Crohn's disease."

"Different intestinal permeability patterns in relatives and spouses of patients with Crohn's disease: an inherited defect in mucosal defence?" in Gut (1999)
Conclusions:  "The findings suggest that baseline permeability is determined by environmental factors, whereas permeability provoked by acetylsalicylic acid is a function of the genetically determined state of the mucosal barrier, and support the notion that environmental and hereditary factors interact in the pathogenesis of Crohn's disease."

"Genetic basis for increased intestinal permeability in families with Crohn's disease: role of CARD15 3020insC mutation?" in Gut (2006)
"In healthy first degree relatives, high mucosal permeability is associated with the presence of a CARD15 3020insC mutation. This indicates that genetic factors may be involved in impairment of intestinal barrier function in families with IBD."

"Subclinical Intestinal Inflammation in Siblings of Children with Crohn’s Disease" in Digestive Diseases and Sciences (2010)
"This study provides further evidence of subclinical intestinal inflammation amongst first-degree relatives of patients with Crohn’s disease. The presence of sub-clinical gut inflammation may be a risk factor for the subsequent development of Crohn’s disease."

How can subclinical Crohn's be diagnosed earlier?

"Prodromal Irritable Bowel Syndrome May Be Responsible for Delays in Diagnosis in Patients Presenting with Unrecognized Crohn’s Disease and Celiac Disease, but Not Ulcerative Colitis" in Digestive diseases and sciences (2011)
" This is the first study to make direct comparisons of prodrome periods between celiac disease and IBD. Prodrome duration in celiac disease is significantly longer and more often characterized by P-IBS than IBD. In celiac disease and CD, P-IBS increases prodrome duration. This may represent a failure to understand the overlap between IBS and celiac disease/IBD."

"The Manitoba Inflammatory Bowel Disease Cohort Study: Prolonged Symptoms Before Diagnosis—How Much Is Irritable Bowel Syndrome?" in Clinical Gastroenterology and Hepatology (2006)

"Background & Aims: The Manitoba Inflammatory Bowel Disease (IBD) Cohort Study is a population-based prospective cohort study of recently diagnosed IBD (n = 396). At enrollment, 162 (41%) indicated gastrointestinal symptom ≥3 years before diagnosis. We aimed to determine whether coexistence of irritable bowel syndrome (IBS) had a role in symptoms before IBD diagnosis.
Conclusions: These data suggest that older patients and those with likely and possible preexisting IBS are more likely to experience longer symptom duration before diagnosis of IBD. The prevalence rate of IBS was similar to estimated base rates in the general population."

"Isolated Ileal Erosions in Pts With Mildly Altered Bowel Habits: Discussion" from Medscape Today (2006)

"These cases raise the issue of the appropriate diagnostic approach in this situation. There are no formal guidelines about whether similar lesions should be classified by pathologists as nonspecific or as "suggestive of Crohn disease." One option is to use the diagnosis of "isolated ileal erosion" and add a comment stating "this lesion is idiopathic in most patients; however, in approximately one third, the disease will eventuate into typical Crohn disease, often after a prolonged interval."

"Identification of a prodromal period in Crohn's disease but not ulcerative colitis" in The American Journal of Gastroenterology (2000)

"There is a significant prodromal period before the time of diagnosis of Crohn's disease that is not found in ulcerative colitis even after exclusion of subjects with IBS."

"Family studies in Crohn's disease: new horizons in understanding disease pathogenesis, risk and prevention" in Gut (2011)
"Specific physiological abnormalities associated with CD, such as increased intestinal permeability and raised faecal calprotectin, are also abnormal in some relatives of patients with CD. The combination of genotypic factors and biomarkers of risk makes the development of models of disease prediction a realistic possibility. Furthermore, enhanced understanding of the genotype and phenotype of the at-risk state in relatives of patients with CD allows the earliest stages in the pathogenesis of CD to be investigated and may allow intervention to prevent disease onset."