Inflammatory Intestinal Diseases最新文献

Background: Chronic enteropathy associated with SLCO2A1 gene (CEAS) is a rare hereditary disorder characterized by multiple small intestinal ulcers, chronic anemia, and hypoproteinemia. Initially reported by Okabe et al. [J Jpn Soc Gastroenterol. 1968;65:1114-7] in 1968 as chronic nonspecific multiple ulcers of the small intestine, the condition was later identified as a genetic disorder caused by mutations in the SLCO2A1 gene, which encodes a prostaglandin (PG) transporter. Unlike typical autosomal recessive disorders, CEAS predominantly affects females and is frequently present with extraintestinal manifestations such as digital clubbing, pachydermia, and periostosis.

Summary: This review provides a comprehensive summary of the epidemiology, pathogenesis, clinical features, diagnostic criteria, and management of CEAS, with an emphasis on newly established diagnostic protocols in Japan. CEAS is characterized by multiple shallow circumferential or oblique ulcers in the small intestine, often resembling NSAID-induced enteropathy. Laboratory findings typically include iron deficiency anemia and hypoproteinemia, while urinary PG metabolite levels are significantly elevated. Genetic testing for SLCO2A1 mutations, particularly the c.940 + 1G>A splice site mutation, confirms the diagnosis. While symptomatic management with enteral nutrition, iron supplementation, blood transfusions, and albumin infusion is the mainstay of therapy, definitive treatments remain unavailable. Endoscopic balloon dilation may be useful in cases of intestinal strictures, but surgical intervention is frequently required.

Key messages: (i) CEAS should be considered in cases of chronic iron deficiency anemia and hypoproteinemia with unexplained small intestinal ulcers. (ii) Genetic testing for SLCO2A1 mutations, combined with assessment of small intestinal morphology, is essential for accurate diagnosis. (iii) Current treatment options are limited to symptomatic management and surgical intervention, highlighting the need for further research to develop effective therapies.

Introduction: It remains unclear whether Janus kinase (JAK) inhibitors differ in efficacy and safety between elderly and non-elderly patients with ulcerative colitis.

Methods: We retrospectively compared outcomes between patients who started a JAK inhibitor at ≥65 years (elderly group) and those <65 years (non-elderly group).

Results: Among 228, 215, and 159 patients treated with upadacitinib, filgotinib, and tofacitinib, we identified 14, 36, and 13 elderly patients, respectively. There were no significant differences in efficacy between elderly and non-elderly patients for any of the three JAK inhibitors. The elderly group had a 3-fold higher risk of herpes zoster infection with upadacitinib or tofacitinib compared to the non-elderly group, whereas the risk with filgotinib was less than 3% in both groups. The non-elderly group had a 3-fold higher risk of acne with upadacitinib.

Conclusion: Adverse event risks with JAK inhibitors should be considered by age. Given the limitations of this study, including its retrospective design and small sample size, further studies with larger sample sizes are needed to validate our findings.

Introduction: Crohn's disease (CD) is a chronic inflammatory condition of the digestive tract, characterized by a noncontinuous pattern of transmural inflammation, leading to a significant decline in quality of life and productivity. For biologic-naïve patients, anti-tumor necrosis factor (TNF)-α and anti-interleukin (IL)-12/23 therapies are commonly recommended. This study compares anti-IL-12/23 and anti-TNF-α for clinical remission, corticosteroid-free remission, endoscopic remission, and endoscopic response in biologic-naïve patients.

Methods: We searched PubMed, Google Scholar, VHL, Cochrane Library, Scopus, Web of Science, and ClinicalTrials.gov for randomized clinical trials and cohort studies. Data were analyzed using odds ratios (ORs) with 95% confidence intervals (CIs). A random-effects model was applied for meta-analysis.

Results: Only 6 out of 5,401 articles were included, involving a total of 1,103 patients. Of these, 636 (57.6%) received anti-TNF-α therapy (infliximab or adalimumab), while 467 (42.4%) received anti-IL-12/23 (ustekinumab) therapy. Within 52 weeks, there were no statistically significant differences found between Ustekinumab and anti-TNF-α in terms of clinical remission (OR: 0.92, 95% CI: 0.55-1.54, p = 0.75), endoscopic remission (OR = 0.583, 95% CI: 0.289-1.176; p = 0.13), corticosteroid-free remission (OR: 1.19, 95% CI: 0.87-1.64, p = 0.28), or endoscopic response (OR = 0.48, 95% CI: 0.147-1.578; p = 0.23).

Conclusion: This meta-analysis found no significant differences in clinical remission, corticosteroid-free remission, endoscopic remission, or endoscopic response within 52 weeks between ustekinumab and anti-TNF-α agents in biologic-naïve CD patients. However, due to study limitations, further high-quality, head-to-head trials are needed to refine treatment selection and optimize outcomes.

Background: Ciclosporin and infliximab have equal short-term efficacy in treating acute severe ulcerative colitis (ASUC). However, data about long-term outcome and switching to a second rescue therapy are limited.

Methods: Patients with steroid-refractory ASUC treated at a tertiary center in Switzerland were retrospectively analyzed regarding the outcome of different rescue therapies. Colectomy-free survival rates at 1, 3, and 5 years were estimated through Kaplan-Meier method. Furthermore, predictors of colectomy, the presence of adverse events at 1 year and mortality during the entire follow-up were assessed.

Results: We analyzed a total of 46 patients who were treated initially with either ciclosporin (n = 31) or infliximab (n = 15) due to steroid-refractory ASUC between January 2010 and July 2021. A total of 13% patients received a second rescue therapy. In sum, 78%, 67%, and 48% were colectomy-free at 1, 3, and 5 years, respectively. Although there was a significant difference between the three arms in colectomy-free survival (p = 0.026), a post hoc analysis could not demonstrate a difference between each individual therapy compared to another. The post hoc analysis indicated a nonsignificant benefit with sequential therapy in comparison to ciclosporin (CsA) regarding the colectomy-free survival (p = 0.087). The outcome between infliximab and CsA was not statistically different (p = 0.149). The number of previous advanced therapies was negatively associated with 1-year colectomy-free survival (p = 0.049). Other variables such as age at hospitalization, sex, dose of steroids, disease duration, and albumin did not correlate with a higher risk of 1-year colectomy.

Conclusions: This real-world single-center analysis confirms the equal efficacy and safety of infliximab and ciclosporin over a follow-up of 5 years. Patients not responding to the first may benefit of a second rescue therapy without increasing the risk of complication or mortality.

[This corrects the article DOI: 10.1159/000545081.].

Introduction: Patients with ulcerative colitis are prone to mental disorders and may be under psychological burden due to the development of ulcerative colitis-associated cancer. Therefore, evidence regarding awareness and concerns about cancer development is needed. We aimed to investigate the state of awareness regarding cancer in patients with ulcerative colitis, and their concerns about cancer, awareness of risk factors, and information-gathering methods.

Methods: Questionnaires were administered to patients with ulcerative colitis who regularly visited our hospital. The Cancer Worry Scale was used to quantitatively evaluate the anxiety of developing cancer and the psychological burden in daily life. The Inflammatory Bowel Disease Questionnaire and the Short Form-8 were used to evaluate quality of life. Factors associated with cancer risk were also investigated.

Results: A total of 112 patients were included; 78 patients have perceived a risk of developing colorectal cancer. Cancer Worry Scale for colorectal cancer was significantly higher than that for gastric cancer. Of the patients who answered that they perceived developing colorectal cancer with ulcerative colitis, 70% found more details about developing cancer by asking doctors; and 85.7% by using the internet and social networking services. The intestinal disease-specific self-administered questionnaire, Inflammatory Bowel Disease Questionnaire, score was associated with positive Cancer Worry Scale. In the Short Form-8, a lower Mental Component Summary was also associated with a positive Cancer Worry Scale.

Conclusion: Patients with ulcerative colitis can be affected by cancer worry. More scientific evidence, reliable information that patients can access, and accurate information conveyed by medical staff are required.

Introduction: Ileal pouch-vaginal fistula (PVF) is a severe complication that can occur following surgery for ulcerative colitis (UC). Most cases of PVF are managed surgically, and reports on successful closure through conservative treatment alone are limited. We report the first documented case of PVF closure without stoma formation, successfully treated with antibiotics and estriol vaginal tablets.

Case presentation: A 65-year-old woman was diagnosed in her 50s with total colitis-type UC. She developed steroid-dependent, refractory disease, prompting the indication of infliximab therapy. However, infliximab failed to maintain remission, necessitating restorative proctocolectomy with ileal pouch-anal anastomosis followed by loop ileostomy. The postoperative course was uneventful, and the ileostomy was closed 6 months later. Two years after surgery, she developed fever, diarrhea, and vaginal discharge containing fecal fluid. The endoscopic evaluation identified a PVF secondary to pouchitis. She was admitted to the hospital, placed on fasting, and treated with antibiotics and estriol vaginal tablets. Endoscopy 18 days after initiating of estriol therapy revealed vaginal wall thickening and PVF closure, and she was subsequently discharged. Estriol vaginal tablet administration continued for 3 months, and no recurrence has been observed 9 years following surgery.

Conclusion: Estriol vaginal tablets may be serve as an effective conservative treatment option for PVF following surgery for UC.

Background: Eosinophilic esophagitis (EoE) is a food- and aeroallergen-driven, type 2-mediated chronic inflammation that develops in genetically predisposed individuals with an impaired esophageal epithelial barrier. How pollutants, including detergents, the esophageal microbiome, immunity, and genetics trigger the multifaceted pathophysiology of EoE is not clear.

Summary: This review summarizes and discusses recent findings concerning the possible contribution of the environment/exposome, the esophageal microbiome, genetics, immunity, and epithelial barrier integrity to developing esophageal type 2 inflammation and fibrosis in EoE. After summarizing the current literature, we formulate research questions that we consider relevant to EoE.

Key messages: The anticipated progress in preclinical EoE animal models, primary cell culture technologies, sequencing technologies, and clinical trials, driven by academic research and the pharmaceutical industry, is poised to revolutionize our understanding of EoE. These advancements may uncover novel pathways that can be targeted for EoE treatment, inspiring hope for improved patient quality of life.

Background: Eosinophils and eosinophil infiltration are the hallmark for the diagnosis of eosinophilic esophagitis (EoE), which represents the most common cause of solid food dysphagia in young adults. However, the role of eosinophils in the pathogenesis of EoE has been increasingly questioned.

Summary: It is now well accepted that EoE is a Th2-mediated disorder with a myriad of inflammatory processes being involved rather than a single cell disease. In recent years, several nuances of EoE, so-called EoE variants, have been described, among which are EoE-like esophagitis, nonspecific esophagitis, lymphocytic esophagitis, and potentially also mast-cell esophagitis. These variants appear to have distinct molecular fingerprints sharing pronounced traits of EoE. Of note, there is a considerable flux between the variants (with frequent transitions) and eventual progression to EoE over time. Thus, EoE variants and EoE appear to be a spectrum disorder, where EoE only represents the most extreme phenotype.

Key messages: This review summarizes current knowledge about these different variants and discusses future directions and open questions.

Introduction: Fecal calprotectin is a validated biomarker for assessing disease activity in patients with inflammatory bowel disease (IBD). Blood calprotectin concentrations are correlated with disease activity in numerous immune-mediated inflammatory diseases. The aim of this study was to prospectively assess the diagnostic accuracy of plasma calprotectin as a potential biomarker of remission in IBD patients.

Methods: This prospective observational study enrolled 131 patients at the time of infliximab administration alongside clinical assessment and blood analyses on the same day. The primary endpoint was to assess the diagnostic accuracy of plasma calprotectin for predicting remission in patients with IBD.

Results: Plasma calprotectin concentration ≤10.5 ng/mL had a sensitivity of 98.6%, specificity of 100%, positive predictive value of 100%, negative predictive value of 96.3%, and an area under the receiver operating characteristic (AUROC) curve of 0.999 for diagnosing remission in patients with ulcerative colitis (UC). Plasma calprotectin had poor diagnostic accuracy for diagnosing remission in Crohn's disease. In UC, plasma calprotectin had significantly greater diagnostic accuracy than C-reactive protein for diagnosing remission (absolute difference between AUROCs, 0.06; 95% CI: 0.008 to 0.113; p = 0.03). Plasma calprotectin concentrations were not correlated with those measured in serum samples. The median serum-to-plasma calprotectin concentration ratio was 12-fold.

Conclusion: Plasma calprotectin is a promising biomarker for predicting remission in UC patients treated with infliximab.