Inflammatory bowel disease uncovered in fecal immunochemical test positive patients in a Canadian provincial colon cancer screening program.

Inflammatory Bowel Disease (IBD) is a chronic inflammatory condition that usually affects younger adults but has a second incidence peak in the older population. Although diagnosis of IBD is driven by symptoms, some patients are asymptomatic and incidentally discovered while participating in colon screening program (CSP). We aimed to identify the incidence and outcome of IBD in fecal immunochemical test (FIT) positive patients in the British Columbia CSP. We conducted a retrospective chart review of patients who had colonoscopies for positive FIT and were found to have colitis based on endoscopic and histological assessment. Of 93,994 patients who underwent screening colonoscopy for positive FIT between 2009 and 2017, 608 (0.6%) were found to have colitis. From 11 CSP sites, 191 patients met the inclusion criteria. 58 patients (30.4%) were diagnosed with ulcerative colitis, 109 (57.1%) with Crohn's disease (CD), and 24 (12.6%) with IBD unclassified. 124 patients (64.9%) received treatment, of which 34 (17.8%) received biologics and 4 (2.1%) required surgery. Our study demonstrated a clinically significant incidence of IBD, with novel finding of CD predominance, within a Canadian provincial CSP. Further research is needed to guide management of older patients with varying rates of IBD progression after incidental diagnosis.

Predicting mucosal inflammation in IBD patients using patient-reported symptom scores and a faecal calprotectin home test: protocol for a multicentre prospective validation study.

INTRODUCTION: Crohn's disease and ulcerative colitis are chronic inflammatory bowel diseases (IBD) with a relapsing-remitting nature. With adequate non-invasive prediction of mucosal inflammation, endoscopies can be prevented and treatment optimised earlier for better disease control. We aim to validate and recalibrate commonly used patient-reported symptom scores combined with a faecal calprotectin (FC) home test as non-invasive diagnostic tool for remote monitoring of IBD, both in daily practice and in a strict trial setting. Endoscopy will be used as the gold standard. METHODS AND ANALYSIS: In this multicentre prospective validation study, adult IBD patients are asked to fill out questionnaires regarding disease activity (Monitor IBD At Home, mobile Health Index, Manitoba IBD Index, IBD control and patient-HBI/patient-Simple Clinical Colitis Activity Index), perform a FC home test and collect a stool sample for routine laboratory FC measurement, before the start of the bowel preparation for the ileocolonoscopy. Endoscopic disease activity will be scored according to the simplified endoscopic score for Crohn's disease (CD) for CD patients or Ulcerative Colitis Endoscopic Index for Severity and Mayo Endoscopic Subscore for ulcerative colitis patients. The main study outcome is the diagnostic test accuracy of the various patient-reported scores to assess mucosal inflammation in combination with a FC home test. ETHICS AND DISSEMINATION: This study is approved by the Medical Research Ethics Committee of azM/UM in Maastricht dated 03 March 2021 (METC 20-085) and is monitored by the Clinical Trial Centre Maastricht according to Good Clinical Practice guidelines. Written informed consent will be obtained from all patients. Study results will be published in international peer-reviewed medical journals. TRIAL REGISTRATION NUMBER: NCT05886322.

Crohn's Disease Previously Mistreated as Intestinal Tuberculosis Complicated with Ileocecal Lump: A Case Report.

In Southeast Asia, the higher prevalence of Intestinal tuberculosis (TB) challenges the diagnosis of Crohn's disease (CD) due to their overlapping symptoms. This case involves a 25-year-old male misdiagnosed with Intestinal tuberculosis presenting with abdominal pain, weight loss, and bowel ulceration. Recurrence after anti-tubercular therapy led to further investigation paving to right hemicolectomy and histopathological analysis confirming Crohn's disease. This case highlights the complexity of the diagnosis of Crohn's disease in tuberculosis-prevalent areas, stressing the clinical importance, advanced diagnostics tools, and multidisciplinary approach for effective intervention.

Examining dietary interventions in Crohn's disease.

This editorial builds on the article by Shakhshir et al. We conducted an overview of evidence-based dietary interventions in adults with inflammatory bowel disease (IBD). In the IBD population, there may be a role for the Mediterranean diet due to its anti-inflammatory effects, long-term sustainability, and role in improving cardiovascular health. In active Crohn's disease, the use of exclusive enteral nutrition, the Crohn's disease exclusion diet, or the specific carbohydrate diet may be used as a short-term adjunct to medical therapy and may improve mucosal healing. The low-FODMAP diet can assist in reducing symptoms for patients without evidence of active bowel inflammation. As interest in nutritional therapy increases amongst clinicians and patients alike, it is integral that dietary therapies are understood and discussed in routine management of patients with IBD as part of holistic care, ideally through a multidisciplinary setting with involvement of experienced dietitians. This serves to improve clinician-patient engagement and reduce complications of IBD including micro and micronutrient deficiencies.

Delayed diagnosis in inflammatory bowel disease: Time to consider solutions.

In this editorial, we discuss a recently published manuscript by Blüthner et al in the World Journal of Gastroenterology, with a specific focus on the delayed diagnosis of inflammatory bowel disease (IBD). IBD, which includes Crohn's disease and ulcerative colitis, is a chronic intestinal disorder. A time lag may exist between the onset of inflammation and the appearance of signs and symptoms, potentially leading to an incorrect or delayed diagnosis, a situation referred to as the delayed diagnosis of IBD. Early diagnosis is crucial for effective patient treatment and prognosis, yet delayed diagnosis remains common. The reasons for delayed diagnosis of IBD are numerous and not yet fully understood. One key factor is the nonspecific nature of IBD symptoms, which can easily be mistaken for other conditions. Additionally, the lack of specific diagnostic methods for IBD contributes to these delays. Delayed diagnosis of IBD can result in numerous adverse consequences, including increased intestinal damage, fibrosis, a higher risk of colorectal cancer, and a decrease in the quality of life of the patient. Therefore, it is essential to diagnose IBD promptly by raising physician awareness, enhancing patient education, and developing new diagnostic methods.

Biochemical Modulators of Tight Junctions (TJs): Occludin, Claudin-2 and Zonulin as Biomarkers of Intestinal Barrier Leakage in the Diagnosis and Assessment of Inflammatory Bowel Disease Progression.

BACKGROUND: Considering the increasing worldwide prevalence of inflammatory bowel disease (IBD), the early diagnosis of this disease is extremely important. However, non-invasive diagnostic methods remain limited, while invasive techniques are the most commonly used in daily practice. Therefore, there is a serious need to find new non-invasive biomarkers of IBD. METHODS: The serum profiles of occludin, claudin-2, and zonulin were assessed in IBD patients using the ELISA method. The levels of the analyzed biomarkers were measured before and after a year of anti-inflammatory treatment, which was a tumor necrosis factor α (TNF-α) inhibitor (adalimumab) in patients with ulcerative colitis (UC) and conventional therapy in patients with Crohn's disease (CD). RESULTS: In IBD patients, the serum level of occludin (p < 0.001) decreased compared to healthy individuals, while the level of claudin-2 (p < 0.001) increased. Additionally, zonulin (p < 0.01) concentration increased in CD patients compared to the control group. The highest diagnostic ability was presented by occludin measurements with the area under the curve (AUC) of 0.959 (95% CI 0.907-1) in UC and 0.948 (95% CI 0.879-1) in CD. Claudin-2 also demonstrated very good ability in diagnosing UC and CD with AUC values of 0.864 (95% CI 0.776-0.952) and 0.896 (95% CI 0.792-0.999), respectively. The ability of zonulin to diagnose CD was estimated as good with an AUC of 0.74 (95% CI 0.598-0.881). Moreover, a significant correlation was identified between C-reactive protein (CRP), claudin-2 (r = -0.37; p < 0.05), and zonulin (r = -0.44; p < 0.05) in UC patients. Treatment with adalimumab improved the level of occludin, claudin-2, and zonulin in UC patients, while anti-inflammatory conventional therapy decreased the concentration of zonulin in CD. CONCLUSIONS: Occludin and claudin-2 measurements present significant utility in diagnosing both UC and CD, while zonulin assessments may be useful in CD diagnosis. Additionally, claudin-2 and zonulin measurements may be helpful in evaluating the intensity of the inflammatory process. Anti-TNF-α treatment improved the value of occludin, claudin-2, and zonulin, indicating its beneficial effect on the integrity of tight junctions in UC.

Is the identification of caseating granuloma in the intestine indicative of tuberculosis? a rare case of Crohn's disease.

BACKGROUND: Crohn's disease (CD) is a chronic intestinal inflammatory disorder, the etiology of which remains unknown, and is characterized by symptoms such as chronic abdominal pain, diarrhea, obstruction, and perianal lesions. Histopathology is widely regarded as the preferred method for diagnosing CD, although the histological diagnosis may lack specificity. The identification of granulomas is commonly believed to be the most reliable diagnostic indicator for CD, surpassing all other clinical features in significance. Nevertheless, research indicates that the detection rate of granulomas in CD exhibits considerable variability. Furthermore, granulomas can manifest in various specific infections including tuberculosis and Yersinia, as well as in a range of diseases characterized by macrophage reactions such as sarcoidosis and drug-induced enteritis. Granulomas associated with CD typically do not exhibit necrosis. However, the formation of caseous granulomas may occur as a result of secondary infections related to anti-CD drug treatment or perforation of the intestinal wall. CASE PRESENTATION: In this study, we present a case of a 28-year-old female patient diagnosed with CD exhibiting histologic granulomas, including both caseating and non-caseating forms, which demonstrated a positive response to medical treatment. CONCLUSION: In clinical practice, various forms of granulomas may indicate diverse underlying diseases, yet lack specificity. It is suggested that the presence of caseous granulomas should not be considered as a definitive exclusion criterion for the diagnosis when clinical, endoscopic, imaging and other histopathological features are consistent with CD. This study is the first report of caseous granulomas in CD without concomitant tuberculosis infection.

Review article: Measuring disease severity in inflammatory bowel disease - Beyond treat to target.

BACKGROUND: Inflammatory bowel disease (IBD) follows a heterogenous disease course and predicting a patient's prognosis is challenging. There is a wide burden of illness in IBD and existing tools measure disease activity at a snapshot in time. Comprehensive assessment of IBD severity should incorporate disease activity, prognosis, and the impacts of disease on a patient. This review investigates the concept of disease severity in adults with IBD to highlight key components contributing to this. METHODS: To perform this narrative review, a Medline search was conducted for full-text articles available at 1st March 2024 using search terms which encompassed disease activity assessment, disease severity, prognosis, natural history of Crohn's disease (CD) and ulcerative colitis (UC), and the burden of IBD. RESULTS: Current methods of disease assessment in IBD have evolved from a focus on the burden of symptoms to one that includes inflammatory targets, genetic, serological, and proteomic profiles, and assessments of quality-of-life (QoL), disability, and psychosocial health. Longitudinal studies of IBD suggest that the burden of illness is driven by disease phenotype, clinical markers of complicated disease course (previous intestinal resection, corticosteroid use, perianal disease in CD, recent hospitalisations in UC), gut inflammation, and the impact of IBD on the patient. CONCLUSIONS: Disease severity in IBD can be difficult to conceptualise due to the multitude of factors that contribute to IBD outcomes. Measurement of IBD severity may better encapsulate the full burden of illness rather than gut inflammation alone at a single timepoint and may be associated with longitudinal outcomes.

Dysbiotic signatures and diagnostic potential of gut microbial markers for inflammatory bowel disease in Korean population.

Fecal samples were collected from 640 individuals in Korea, including 523 patients with IBD (223 with Crohn's disease [CD] and 300 with ulcerative colitis [UC]) and 117 healthy controls. The samples were subjected to cross-sectional gut metagenomic analysis using 16 S rRNA sequencing and bioinformatics analysis. Patients with IBD, particularly those with CD, exhibited significantly lower alpha diversities than the healthy subjects. Differential abundance analysis revealed dysbiotic signatures, characterized by an expansion of the genus Escherichia-Shigella in patients with CD. Functional annotations showed that functional pathways related to bacterial pathogenesis and production of hydrogen sulfide (H2S) were strongly upregulated in patients with CD. A dysbiosis score, calculated based on functional characteristics, highly correlated with disease severity. Markers distinguishing between healthy subjects and patients with IBD showed accurate classification based on a small number of microbial taxa, which may be used to diagnose ambiguous cases. These findings confirm the taxonomic and functional dysbiosis of the gut microbiota in patients with IBD, especially those with CD. Taxa indicative of dysbiosis may have significant implications for future clinical research on the management and diagnosis of IBD.

Chylothorax in a Young Woman With Crohn Disease.

Chylothorax, which accounts for 1% to 3% of pleural effusions, typically results from either surgery (traumatic) or underlying malignancy (nontraumatic). Less common causes of nontraumatic chylothorax are numerous and include congenital lymphatic abnormalities, connective tissue diseases, cirrhosis, and infection, among others.1 We describe what appears to be the first reported case of chylothorax caused by chylous ascites in Crohn disease. This case highlights the importance of using diagnostic evidence to link new symptoms to preexisting diseases whenever possible, as well as the systemic nature of Crohn disease.

Inflammatory bowel diseases and spondyloarthritis: a focus on female patients.

OBJECTIVE: Ulcerative colitis and Crohn's disease are chronic inflammatory diseases and represent the two most important types of inflammatory bowel diseases (IBD), while spondyloarthritis (SpA) comprises a heterogeneous group of systemic inflammatory chronic rheumatic diseases, including peripheral SpA and axial SpA. Joint manifestations are the most commonly observed extraintestinal manifestations, and they can precede or not the diagnosis of IBD. Notably, in women, misdiagnoses of IBD as irritable bowel syndrome and SpA as fibromyalgia are common, leading to delayed diagnoses, increased disease burden, and poorer prognoses. This narrative review emphasizes the critical role of diagnostic tools in facilitating early referrals of IBD patients with suspected SpA and vice versa to rheumatologists and gastroenterologists, respectively. Special attention is given to the multidisciplinary approach for more effective management of these conditions, particularly in female patients. METHODS: In this narrative review, we critically evaluated the literature on this topic, focusing on papers written in English that address female issues in IBD and SpA. RESULTS: IBD and SpA are chronic inflammatory disorders often occurring in the same patients. Female patients are often misdiagnosed, and this delay in diagnosis is associated with a higher disease burden and a poorer prognosis. CONCLUSIONS: A multidisciplinary approach is needed to enable early referral between gastroenterologists and rheumatologists, as this means a better prognosis for patients with a reduction in the economic and social burden associated with IBD and SpA.

The Incidence and Risk Factors of Refeeding Syndrome-like Hypophosphatemia in Inflammatory Bowel Disease: A Preliminary Study.

BACKGROUND AND AIMS: Refeeding syndrome (RFS) is defined by the presence of acute electrolyte disturbances, including hypophosphatemia. Underlying disease(s), malnutrition and hospitalisation are known risk factors for RFS. It can occur in patients with inflammatory bowel disease (IBD). We aimed to determine the frequency of hypophosphatemia and the relationship between hypophosphatemia, disease severity and nutritional status in hospitalized patients with IBD. METHODS: This study was performed prospectively in hospitalized adult patients for the treatment of IBD in a tertiary-care hospital. Disease severity was assessed using Truelove and Witts score for ulcerative colitis (UC) and Crohn's Disease Activity Index for Crohn's disease (CD). Nutritional status was determined using Subjective Global Assessment (SGA). Serum phosphate concentration was recorded for first 7 days after hospitalization, and less than 0.65 mmol/l was defined as hypophosphatemia. RESULTS: Fifty participants (33 with UC and 17 with CD) were included in the study. The mean age of the study sample was 43.4±14.9 years, of which 64% were male. A total of 8.8% of patients with UC and 37.5% of patients with CD had severe (>moderate) disease upon study admission. Seventeen patients (34%) were malnourished. During the 7 study days, 23 participants (46%) had at least one episode of hypophosphatemia. Serum phosphate concentration was significantly and moderately correlated with serum potassium concentration in both the patients and the hypophosphatemia group on study day 3 (p<0.05). Multivariate logistic regression analysis showed that the presence of malnutrition [odds ratio (OR) = 3.64, 95% confidence interval (CI): 1.52-5.58, p=0.008), the administration of parenteral nutrition (OR=2.91, 95%Cl: 1.37-4.63, p=0.015), and severe IBD (OR=1.74, 95%CI: 1.03-3.42, p=0.020) were associated with hypophosphatemia. CONCLUSIONS: Approximately half of the participants exhibited at least one instance of hypophosphatemia during the study period. Hypophosphatemia was found to be associated with malnutrition, parenteral nutrition, and severe disease in patients with IBD requiring hospitalization.

Small bowel Crohn's disease neglected by gastroenterologists and anorectal surgeons with a 7-year delay in diagnosis: A case report.

RATIONAL: Small bowel Crohn's disease (SBCD) is a common site of Crohn's disease (CD). However, owing to the anatomical characteristics of the small bowel and the limitations of traditional examination methods, the detection and diagnosis of SBCD remain difficult. Gastroenterologists and anorectal surgeons should pay more attention to improving the early diagnosis rate, so as to improve the prognosis of patients and reduce the probability of surgery due to complications. PATIENT CONCERNS: Here, we presented a case of a young male with severe localized pain in the right kidney area and fever but no weight loss or diarrhea, who had a history of perianal abscess surgery 7 years ago and an elevated platelet count reviewing his previous medical examination report. DIAGNOSES: SBCD was not diagnosed until complications of intestinal fistula developed 7 years after perianal abscess surgery. INTERVENTIONS: Anti-infection treatment was administered due to elevated inflammatory markers and evidence of infection on computed tomography scan, and exclusive enteral nutrition (EEN) was then performed because of the diagnosis of SBCD. Although the infection was absorbed by the treatment with EEN, a laparoscopic modified partial enterectomy was finally performed due to the complication of intestinal fistula. OUTCOMES: The patient was discharged on the seventh postoperative day without postoperative complications and started biologic therapy 2 weeks after surgery because he had high-risk factors for postoperative recurrence. The pathological report revealed the involvement of the ileum in CD, and confirmed the existence of the intestinal fistula. LESSONS: Gastroenterologists and anorectal surgeons should be aware that perianal abscess could be the first manifestation of SBCD; even if typical CD manifestations are absent, proper further examinations are necessary based on the comprehensive analysis of clinical data of patients. In addition, the platelet count deserves attention in patients with potentially possible CD. More importantly, it is important to emphasize the importance of EEN in adult CD patients.

Serum amyloid A for predicting prognosis in patients with newly diagnosed Crohn's disease.

OBJECTIVE: Serum amyloid A (SAA) was found to be positively correlated with the activity of Crohn's disease (CD); however, its prognostic value remains uncertain. Here, we examined its predictive ability in newly diagnosed CD and explored genetic association. METHODS: This retrospective cohort study included patients newly diagnosed as CD at the First Affiliated Hospital of Sun Yat-sen University between June 2010 and March 2022. We employed receiver operating characteristic curve, Cox proportional hazard regression models and restricted cubic splines to investigate the prognostic performance of SAA for surgery and disease progression. To assess possible causality, a two-sample Mendelian randomisation (MR) of published genome-wide association study data was conducted. RESULTS: During 2187.6 person-years (median age, 28 years, 72.4% male), 87 surgery and 153 disease progression events were documented. A 100-unit increment in SAA level generated 14% higher risk for surgery (adjusted HR (95% CI): 1.14 (1.05-1.23), p=0.001) and 12% for disease progression (1.12 (1.05-1.19), p<0.001). Baseline SAA level ≥89.2 mg/L led to significantly elevated risks for surgery (2.08 (1.31-3.28), p=0.002) and disease progression (1.72 (1.22-2.41), p=0.002). Such associations were assessed as linear. Adding SAA into a scheduled model significantly improved its predictive performances for surgery and disease progression (p for net reclassification indexes and integrated discrimination indexes <0.001). Unfortunately, no genetic causality between SAA and CD was observed in MR analysis. Sensitivity analyses showed robust results. CONCLUSION: Although causality was not found, baseline SAA level was an independent predictor of surgery and disease progression in newly diagnosed CD, and had additive benefit to existing prediction models.

Perianal disease in inflammatory bowel disease: Broadening treatment and surveillance strategies for anal cancer.

The perianal disease affects up to one-third of individuals with Crohn's disease (CD), causing disabling symptoms and significant impairment in quality of life, particularly for those with perianal fistulising CD (PFCD). The collaborative effort between gastroenterologists and surgeons is essential for addressing PFCD to achieve fistula closure and promote luminal healing. Limited fistula healing rates with conventional therapies have prompted the emergence of new biological agents, endoscopic procedures and surgical techniques that show promising results. Among these, mesenchymal stem cells injection is a particularly hopeful therapy. In addition to the burden of fistulas, individuals with perianal CD may face an increased risk of developing anal cancer. This underscores the importance of surveillance programmes and timely interventions to prevent late diagnoses and poor outcomes. Currently, there is no established formal anal screening programme. In this review, we provide an overview of the current state of the art in managing PFCD, including novel medical, endoscopic and surgical approaches. The discussion also focuses on the relevance of establishing an anal cancer screening programme in CD, intending to propose a risk-based surveillance algorithm. The validation of this surveillance programme would be a significant step forward in improving patient care and outcomes.

New diagnostic strategies to distinguish Crohn's disease and gastrointestinal tuberculosis.

PURPOSE OF REVIEW: Despite advances in our radiological, histological and microbiological armamentarium, distinguishing between Crohn's disease (CD) and intestinal tuberculosis (ITB), especially in a TB endemic country, continues to be a challenging exercise in a significant number of patients. This review aims to summarize current available evidence on novel diagnostic techniques which have a potential to fill the gap in our knowledge of differentiating between ITB and CD. RECENT FINDINGS: Both ITB and CD are associated with altered host immune responses, and detection of these altered innate and adaptive immune cells has potential to distinguish ITB from CD. ITB and CD have different epigenetic, proteomic and metabolomic signatures, and recent research has focused on detecting these differences. In addition, the gut microbiome, which is involved in mucosal immunity and inflammatory responses, is considerably altered in both ITB and CD, and is another potential frontier, which can be tapped to discriminate between the two diseases. With technological advancements, we have newer radiological modalities including perfusion CT and dual-layer spectral detector CT enterography and evidence is emerging of their role in differentiating ITB from CD. Finally, time will tell whether the advent of artificial intelligence, with rapidly accumulating data in this field, will be the gamechanger in solving this puzzle of diagnostic dilemma between ITB and Crohn's disease. SUMMARY: Recent advances need to be clinically validated before they can be used as novel diagnostic measures to differentiate Intestinal TB from CD.