Bowel strictures are well recognized as one of the most severe complications in Crohn's disease, with variable impacts on the prognosis and often needing surgical or endoscopic treatment. Distinguishing inflammatory strictures from fibrotic ones is of primary importance due to the different therapeutic approaches required. Indeed, to better understand the pathogenesis of fibrosis, it is crucial to investigate molecular processes involving genetic factors, cytokines, alteration of the intestinal barrier, and epithelial and endothelial damage, leading to an increase in extracellular matrix synthesis, which ultimately ends in fibrosis. In such a complex mechanism, the gut microbiota also seems to play a role. A better comprehension of molecular processes underlying bowel fibrosis, in addition to radiological and histopathological findings, has led to the identification of high-risk patients for personalized follow-up and testing of new therapies, primarily in preclinical models, targeting specific pathways involving Transforming Growth Factor-β, interleukins, extracellular matrix balance, and gut microbiota. Our review aims to summarize current evidence about molecular factors involved in intestinal fibrosis' pathogenesis, paving the way for potential diagnostic biomarkers or anti-fibrotic treatments for stricturing Crohn's disease.

Crohn's disease (CD) is a chronic inflammatory disease of the digestive tract. The incidence of pediatric CD is increasing and is currently 2.5-11.4 per 100000 world-wide. Notably, approximately 25% of children with CD develop stricturing CD (SCD) that requires intervention. Symptomatic stricturing diseases refractory to pharmacological management frequently require non-pharmacological interventions. Non-pharmacological therapeutic strategies include endoscopic balloon dilatation, stricturoplasty, and surgical resection of the strictured segment. However, strictures tend to recur postoperatively regardless of treatment modality. The lifetime risk of surgery in patients with childhood SCD remains at 50%-90%. Thus, new and emerging strategies, advanced diagnostic tools, and minimally invasive approaches are under investigation to improve the outcomes and overall quality of life of pediatric patients with SCD.

Patients with Crohn's disease can present with a variety of clinical manifestations; treatment strategies should focus on long-term remission and improvement of quality of life. There is no standardized process of diagnosing, predicting prognosis, and treating the disease. This narrative review was based on a literature search using PubMed, Embase, and Science Direct. Data on unmet challenges in patients with Crohn's disease were extracted from identified manuscripts. The aim was to discuss present research on standardized processes in the management of patients with Crohn's disease and to identify the unmet needs in clinical evaluation and treatment approaches. There is no consensus on standardized diagnostic, treatment, and surveillance algorithms, particularly in assessing complications of Crohn's, such as stricturing disease, intestinal cancer risk, and cutaneous manifestations. Complications and treatment failure rates of conventional, interventional, and surgical therapy place emphasis on the need for standardized treatment algorithms, particularly in the case of acute complications of the disease. Research on standardized clinical approaches, reliable biomarkers for disease diagnosis and therapy monitoring, and new treatment agents is necessary to improve therapy and reduce complications in patients with Crohn's disease.

Background: TNFα inhibitors are regularly used to treat autoimmune diseases. Tuberculosis (TB) and viral hepatitis B are considered potential infectious complications, and screening and surveillance are therefore recommended. Current guidelines do not take into account regional differences in endemicity of these infections. Methods: A systematic literature review of TB and viral hepatitis in patients receiving TNFα-inhibitors was performed, searching in PubMed, Embase, MEDLINE and Web of Science databases. Studies were selected against predefined eligibility criteria and assessed using the Newcastle-Ottawa scale. The number of TB and viral hepatitis cases/1,000 TNFα-inhibitor patients were evaluated, and regional variation compared. Results: 105 observational studies involving over 140,000 patients were included. Overall, 1% of patients developed TB or viral hepatitis B. TB cases/1,000 TNFα-inhibitor patients were 4-fold higher in Asia, Africa, and South America than in Europe, North America, and Australasia where only 0%-0.4% of patients developed TB. Hepatitis B cases/1,000 patients were over 15-fold higher in countries with high prevalence (China, Taiwan, South Korea, Thailand) compared with low prevalence (p < 0.00001) where only 0.4% of patients developed hepatitis B. Only three of 143 patients developed viral hepatitis C, and there was insufficient data to allow regional sub-analysis. Conclusion: TB and viral hepatitis B infections in patients treated with TNFα inhibitors are largely confined to countries with high prevalence of these infections. As only 1/2,500 patients in low prevalence countries treated with TNFα inhibitors develop TB or viral hepatitis B, we suggest an individualized, risk-based approach, rather than universal screening for all patients.

Intestinal strictures remain one of the most intractable and common complications of Crohn's disease (CD). Approximately 70% of CD patients will develop fibrotic strictures after 10 years of CD diagnosis. Since specific antifibrotic therapies are unavailable, endoscopic balloon dilation and surgery remain the mainstay treatments despite a high recurrence rate. Besides, there are no reliable methods for accurately evaluating intestinal fibrosis. This is largely due to the fact that the mechanisms of initiation and propagation of intestinal fibrosis are poorly understood. There is growing evidence implying that the pathogenesis of stricturing CD involves the intricate interplay of factors including aberrant immune and nonimmune responses, host-microbiome dysbiosis, and genetic susceptibility. Currently, the progress on intestinal strictures has been fueled by the advent of novel techniques, such as single-cell sequencing, multi-omics, and artificial intelligence. Here, we perform a timely and comprehensive review of the substantial advances in intestinal strictures in 2021, aiming to provide prompt information regarding fibrosis and set the stage for the improvement of diagnosis, treatment, and prognosis of intestinal strictures.