Crohn Disease

Crohn disease is a chronic, relapsing inflammatory bowel disease characterised by transmural (full-thickness) inflammation that can affect any portion of the gastrointestinal tract from mouth to anus. It most commonly involves the terminal ileum and proximal colon (ileocolonic pattern, 40% of cases), followed by small bowel only (30%) and colon only (30%). The pathogenesis involves a dysregulated immune response to intestinal microbiota in genetically susceptible individuals, triggered by environmental factors. The NOD2/CARD15 gene on chromosome 16 was the first identified susceptibility gene, involved in bacterial recognition by innate immune cells. Over 200 genetic loci have now been associated with Crohn disease. In the normal gut, the epithelial barrier separates luminal bacteria from the underlying immune cells. In Crohn disease, defects in barrier function allow bacterial translocation, which activates dendritic cells and macrophages in the lamina propria. These cells produce pro-inflammatory cytokines, particularly tumor necrosis factor-alpha (TNF-alpha), interleukin-12, and interleukin-23, which drive a Th1/Th17-mediated immune response. This creates a self-perpetuating cycle of inflammation, tissue injury, further barrier disruption, and increased bacterial translocation. Transmural inflammation is the hallmark of Crohn disease, distinguishing...