Ulcerative colitis: moving beyond the mucosal dogma

Abstract

Ulcerative colitis has traditionally been regarded as a non-fibrotic, solely mucosal disease, whereas Crohn's disease is characterised by transmural inflammation and fibrosis. However, more recent evidence supports the existence of disease involvement beyond the mucosa in ulcerative colitis. Intestinal ultrasound has allowed for dynamic, in-vivo characterisation of the transmural alterations that occur in ulcerative colitis, such as increased bowel wall thickness, submucosal thickening, loss of bowel wall stratification, haustral loss, and mesenteric fibrofatty proliferation. There is a possibility that the thickened submucosa might even persist in patients with endoscopic remission, implying pathological processes that continue despite surface healing. Macroscopic and histological findings further support the existence of deeper disease processes, with studies showing colonic shortening, fibrotic strictures, muscularis mucosae thickening, submucosal fibrosis, and excess fat deposition, muscular remodelling, and fibrotic shifts. These transmural changes could possibly contribute to persistent functional bowel symptoms, such as diarrhoea, urgency, and incontinence. Despite these insights, major knowledge gaps remain, particularly regarding the clinical implications of these transmural changes, the development of reliable non-invasive tools to assess transmural alterations, and the potential role of transmural healing as a treatment target. This Viewpoint summarises the existing evidence of sonographic, macroscopic, and histopathological changes beyond the mucosa in ulcerative colitis. Although the transmural features of ulcerative colitis are not as extensive as in Crohn's disease, in which penetrating disease with fistulas, strictures, and abscesses are a major concern, recognising ulcerative colitis as a progressive disease that extends beyond the mucosa might have implications for future treatment strategies and targets.