Pathogenesis of intestinal strictures in Crohn's disease—an update

Abstract

: Stricture formation in Crohn's disease is a complication of an important wound healing process in the intestine. The smooth muscle cells of the intestinal musculares bear a responsibility for the repair of injured intestine, and effect this wound healing process by proliferating and laying down collagen at the site of injury. Injury in the submucosa, and chronicity of injury, are important factors in the development of stricture. The resultant accumulation of collagenous scar, thickening of the muscle layers, and contracture, all play a role in producing the critical architectural changes in the intestinal wall that impede the aboral movement of chyme. Important putative facets of intestinal smooth muscle cell biology that are involved in stricture formation include: the synthesis and secretion of procollagen; the peculiar response of these cells to cytokines, ascorbate, and corticosteroids; and changes in cell phenotype that result from chronic inflammation. Therapeutic modalities designed to ameliorate the stricturing process will need to modulate these biological activities in resident intestinal smooth muscle cells.

Interleukin-4- and -13-induced hypercontractility of human intestinal muscle cells-implication for motility changes in Crohn's disease

“…The presence of T cells in the muscularis externa in Crohn's disease may also influence stricture formation, because it is known that muscle cell growth and proliferation, as well as collagen deposition, contribute to strictures (27), likely via the local production of transforming growth factor ␤ (TGF-␤) (25). In the present study, muscle cells from Crohn's disease patients were ϳ13% longer than control cells.…”

Phenotypic change and accumulation of smooth muscle cells in strictures in Crohn’s disease: relevance to local angiotensin II system

“…Surgical resection or endoscopic dilation is often required to relieve the obstruction, but recurrence is not rare after these treatments. Chronic inflammationrelated fibrosis has been considered to be a fundamental mechanism of the stricture formation [1][2][3]. Recently, the administration of infliximab, a monoclonal antibody against tumor necrosis factor, has appeared to be effective in inducing and maintaining remission in CD, but in some cases, it cannot prevent the stricture formation [3].…”

“…Fibromuscular accumulation in the submucosa, which is recognized as part of the wound-healing response, is a histological hallmark of strictures in CD [1][2][3][4]. Submucosal fibromuscular hyperplasia and obliterative muscularization are synonyms for this unique finding [5,6].…”

Predicting the need for surgery in obstructive Crohnʼs disease

“…In some patients stenosis is primarily due to fibrosis and muscle hypertrophy, whereas in other patients strictures are primarily related to active inflammation. 9,10 Differentiation of these types with imaging could facilitate appropriate management, with fibrotic strictures being treated surgically 11 and inflammatory stenoses being managed medically. 12 The authors attempt to address this challenging clinical problem.…”