Fibrosis is characterized by a proliferation of fibroblasts and excessive extracellular matrix following chronic inflammation, and this replacement of organ tissue with fibrotic tissue causes a loss of function. Inflammatory bowel disease (IBD) is a chronic inflammation of the gastrointestinal tract, and intestinal fibrosis is common in IBD patients, resulting in several complications that require surgery, such as a stricture or penetration. This review describes the pathogenesis and various factors involved in intestinal fibrosis in IBD, including cytokines, growth factors, epithelial-mesenchymal and endothelial-mesenchymal transitions, and gut microbiota. Furthermore, histopathologic findings and scoring systems used for stenosis in IBD are discussed, and differences in the fibrosis patterns of ulcerative colitis and Crohn’s disease are compared. Biomarkers and therapeutic agents targeting intestinal fibrosis are briefly mentioned at the end.
Citations
Citations to this article as recorded by
Resistance to apoptosis in complicated Crohn's disease: Relevance in ileal fibrosis M. Seco-Cervera, D. Ortiz-Masiá, D.C. Macias-Ceja, S. Coll, L. Gisbert-Ferrándiz, J. Cosín-Roger, C. Bauset, M. Ortega, B. Heras-Morán, F. Navarro-Vicente, M. Millán, J.V. Esplugues, S. Calatayud, M.D. Barrachina Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease.2024; 1870(2): 166966. CrossRef
Food additives impair gut microbiota from healthy individuals and IBD patients in a colonic in vitro fermentation model Irma Gonza, Elizabeth Goya-Jorge, Caroline Douny, Samiha Boutaleb, Bernard Taminiau, Georges Daube, Marie–Louise Scippo, Edouard Louis, Véronique Delcenserie Food Research International.2024; 182: 114157. CrossRef
Epigenetic Regulation of EMP/EMT-Dependent Fibrosis Margherita Sisto, Sabrina Lisi International Journal of Molecular Sciences.2024; 25(5): 2775. CrossRef
Disease clearance in ulcerative colitis: A new therapeutic target for the future Syed Adeel Hassan, Neeraj Kapur, Fahad Sheikh, Anam Fahad, Somia Jamal World Journal of Gastroenterology.2024; 30(13): 1801. CrossRef
Pathways Affected by Falcarinol-Type Polyacetylenes and Implications for Their Anti-Inflammatory Function and Potential in Cancer Chemoprevention Ruyuf Alfurayhi, Lei Huang, Kirsten Brandt Foods.2023; 12(6): 1192. CrossRef
Time to eRAASe chronic inflammation: current advances and future perspectives on renin-angiotensin-aldosterone-system and chronic intestinal inflammation in dogs and humans Romy M. Heilmann, Georg Csukovich, Iwan A. Burgener, Franziska Dengler Frontiers in Veterinary Science.2023;[Epub] CrossRef
Role of the epithelial barrier in intestinal fibrosis associated with inflammatory bowel disease: relevance of the epithelial-to mesenchymal transition Dulce C. Macias-Ceja, M. Teresa Mendoza-Ballesteros, María Ortega-Albiach, M. Dolores Barrachina, Dolores Ortiz-Masià Frontiers in Cell and Developmental Biology.2023;[Epub] CrossRef
Chronic ulcerative colitis is a systemic inflammatory disease with uncertain etiology primarily involving the colonic mucosa. The mucosal biopsy interpretation is important for an evaluation of the disease state and further medical or surgical treatment. However, few clinical and pathological studies of the endoscopic diagnosis of this disease are available in Korea. Therefore, we evaluated the clinical and pathological characteristics of it diagnosed by endoscopic biopsy and analysed the reasons for the discrepancy between clinical and pathologic diagnosis for a more accurate endoscopic mucosal biopsy diagnosis in the future. A total of 702 cases of colonic mucosal biopsy specimens during Feb. 1994 and Jan. 1995 at Severance hospital, Yonsei University College of Medicine were reevaluated for the study. A clinical diagnosis of ulcerative colitis, after endoscopic examination, was made in 61(8.7%) cases. A pathological diagnosis was made when there is an increased inflammatory cell infiltration in the mucosa with evidences of a chronic crypt injury in the biopsy specimens. Using this criteria, a diagnosis was made in 32(52.3%) cases. In 29 cases the diagnosis was made in the first biopsy specimen and in the remaining 3 cases the diagnosis was made in the second or third biopsy specimens.
No pathologic diagnosis of ulcerative colitis was made in the cases that clinical diagnosis was not. In the 32 cases diagnosed as ulcerative colitis, 14 cases were involved the rectum and sigmoid colon, 9 cases were involved up to the descending colon, 1 case was involved up to the transverse colon and 8 cases showed pancolonic involvement. In 29 cases, which ulcerative colitis was suspected clinically but was not consistent with it pathologically, 8 cases were proved to be ischemic colitis, 5 cases were acute infectious colitis and one case was Crohn's disease by repeat examination and follow up. Ten cases were histologically within normal range and lesions subsided spontaneously with no recurrence. A conclusive diagnosis could not be made in 5 cases during this study period. From these results, we conclude that ulcerative colitis can be diagnosed accurately by endoscopic biopsy, and clinical follow up and repeat examination are valuable in the differential diagnosis of this disease.
Crohn's disease was originally described as a small bowel disorder and has been known to involve the large bowel in approximately 40% of all cases with or without concomitant ileal component. We describe two cases of Crohn's diseas of small intestine and colon with a summary of differential diagnosis with ulcerative colitis. Both cases were originally diagnosed and treated as ileal tuberculosis.
Grossly, there were skip lesions in both cases with prominent pseudopolyps and ulcerations in colon. Also noted were typical serpentine lesions in ileum as well as in colon. Microscopically, transmural inflammation was confirmed and one case showed scattered noncaseating granulomas in the wall. Submucosal edema and fibrosis with thickening of the wall was not prominent in colon.
Polymerase chain reaction performed on paraffin block for the demonstration of Mycobacterium tuberculosis in one case showed negative reaction.
Cytomegalovirus (CMV) infection is an uncommon association with idiopathic inflammatory bowel disease (IBD) often leading to a variety of serious complications. A total of 41 resected cases of IBD were examined to elucidate the pathologic features of intestinal CMV infection which was assessed by histologic examination and confirmed by immunohistochemistry with CMV antibody. Six cases were positve for CMV antibody; five cases in 19 ulcerative colitis (UC, 26.3%) and one case in 22 Crohn's disease (CD, 4.5%). Of 7 cases of the steroid-treated UC group, five cases were superinfected with CMV (71.4%) but none in 12 cases of the steroid-untreated UC group. All of the five CMV-positive cases in UC showed deep ulceration and transmural inflammation, while none of 10 UC cases without above features were CMV positive. Fibrinoid necrosis and thrombi were found in 83.3% of the CMV infected group, while none in the CMV-negative group of UC cases (p=0.01). We conclude that IBD, particularly UC, is susceptible to the CMV infection when steroid hormone is administered, and that deep colonic ulceration, transmural inflammation and fibrinoid necrosis of vasculature may suggest superinfection of CMV in UC patients. It seems that deep colonic ulceration may be the consequence of an ischemic change following vascular luminal occlusion or vasculitis by CMV infection.