Fibrosis IBD

Fibrosis-predominant strictures are less responsive than inflammation-predominant strictures to medical therapy. However, there is overlap between these types. Also, smooth muscle abnormalities and other connective tissue changes are important. Possibly, there is a “chronic inflammation–fibrosis–smooth muscle hyperplasia” sequence [1–4].

Fibrosis is probably a consequence of extracellular matrix deposition in excessive amounts. Cells responsible may include fibroblasts, myofibroblasts and smooth muscle cells (i.e. mesenchymal cells) and cells derived from a process of epithelial–mesenchymal transition. Other factors include abnormalities of matrix metalloproteinases, collagens, tenascin, tumour necrosis factor alpha and transforming growth factor beta. Derangement of intestinal flora, genetic abnormalities, DNA methylation and miRNAs may also contribute [5–9]. Fat wrapping, a feature typical of Crohn’s Disease, correlates with fibrosis, muscular changes and stricturing. Therefore, adipocyte cytokines could play a role in the process [2, 4, 10, 11]. Blood vessel degeneration, inflammation and proliferation may also occur in Crohn’s Disease, raising the possibility that ischaemia is a factor [1, 2]. Identification of suitable targets for anti-fibrotic drugs offers the possibility of future improvements in therapy [9].

Definitions of a stricture usually require narrowing of the lumen and variably include other items such as pre-stenotic dilatation and thickening of the wall. Histologically, connective tissue changes often affect all layers and include fibrosis, neural hyperplasia and vascular proliferation [2, 12–14]. The muscle layers can undergo demonstrate hypertrophy, hyperplasia, disorganisation and duplication. Muscle fibres may extend into other layers, particularly the submucosa, accompanied by vascular changes and leading to “obliterative muscularisation of the submucosa” [1].

Precise documentation of pathological changes in Crohn’s Disease strictures may be part of the assessment of the efficacy of new anti-stricture drugs and can be a reliable way to categorise response to therapy, also allowing comparison with imaging findings. Attempts to standardise scoring and to produce a scheme that is suitable for clinical trials are in progress [3, 15–18].

Clinically, there is a differential diagnosis for strictures in Crohn’s Disease that includes tumour, drugs, chronic ischaemia, chronic infection and diverticulosis. This is important because the possibility of neoplasia always requires consideration, especially when a stricture is persistent and difficult to manage.

References

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