The Clinical Spectrum of Gastroesophageal Reflux Disease: Facts and Fictions.

Background: This review addresses the intricate spectrum of gastroesophageal reflux disease (GERD), a condition affecting 10-30% of the Western population. GERD is characterized by the backflow of gastric contents into the esophagus, causing typical and atypical symptoms. Its pathophysiology involves various factors such as hiatal hernia, esophageal motor disorders, and dietary triggers. The review explores the complexities of GERD spectrum, including nonerosive reflux disease (NERD), reflux hypersensitivity (RH), and functional heartburn (FH). Summary: The diagnostic process for GERD, based on the Lyon Consensus 2.0 criteria, encompasses clinical evaluation, endoscopy, and functional tests, including pH-impedance and wireless-pH monitoring. NERD, a significant subset of GERD, is defined by reflux symptoms and abnormal reflux burden without mucosal damage. RH, classified under functional esophageal disorders by Rome IV criteria, presents with typical esophageal symptoms associated with reflux but lacks of structural, inflammatory, or motor causes. FH is identified by heartburn with normal endoscopy, reflux testing, and esophageal manometry results. The management of RH and FH, focusing on reducing esophageal hypersensitivity, varies from standard GERD treatments. Key Messages: The review emphasizes the necessity of personalized treatment strategies due to the complexity and overlap of GERD subtypes. It highlights the importance of a multidisciplinary approach, involving gastroenterologists, psychologists, and other specialists, to improve patient outcomes and quality of life. The article underscores that understanding the distinctions and overlaps among NERD, RH, and FH is crucial for effective management, and the need for innovative approaches in diagnosis and treatment to address the unique challenges of each subtype.

Pharmacological management of gastro-esophageal reflux disease: state of the art in 2024.

INTRODUCTION: Gastroesophageal reflux disease (GERD) is a chronic disease of the esophagus characterized by the regurgitation of stomach contents into the esophagus, causing troublesome symptoms and/or complications. Among patients with GERD, around 30% of patients have visible mucosal damage, while 70% have normal esophageal mucosa. Accordingly, the optimal pharmacological treatment of GERD should address different disease manifestations, including symptoms, the mucosal damage when present, and possible chronic complications, including strictures, Barrett's esophagus, and esophageal adenocarcinoma. AREAS COVERED: Available medical treatments for GERD include proton pump inhibitors (PPIs), potassium-competitive acid blockers (PCABs), histamine receptor antagonists (H2-RAs), prokinetics, and mucosal protectants, such as alginates, hyaluronic acid/chondroitin-sulfate, and poliprotect. Each compound has its own advantages and disadvantages, and knowledge of expected benefits and tips for their use is paramount for the success of treatment. In addition, the appropriateness of indications for initiating treatment is also crucial to achieve positive results when managing GERD patients. EXPERT OPINION: PPIs, PCABs, H2-RAs, prokinetics, and mucosal protectants can all be used in patients with GERD, but careful assessment of patients' characteristics as well as advantages and disadvantages of each therapeutic compound is essential to ensure successful treatment of GERD.

Comparing Point-of-Care Technology to ELISA Testing for Infliximab and Adalimumab Levels in Adult Inflammatory Bowel Disease Patients: A Prospective Pilot Study.

Introduction: Therapeutic drug monitoring (TDM) has proven to be a valuable strategy for optimizing biologic therapies, among which are anti-tumor necrosis factor (anti-TNF) treatments in inflammatory bowel disease (IBD). In particular, reactive TDM has been shown to manage treatment failures more cost-effectively than empirical dose adjustments for anti-TNF drugs. However, several challenges currently impede the widespread adoption of TDM in clinical practice, particularly addressing the delay between sample collection and result availability. To overcome this limitation, the use of point-of-care technology tests (POCTs) is a potential solution. Point-of-care technology tests are medical diagnostic tests performed at the site of patient care to provide immediate results, allowing for quicker decision-making and treatment. The current standard of care (SOC) for drug level measurement relies on the enzyme-linked immunosorbent assay (ELISA), a method that is time-consuming and requires specialized personnel. This study aims to evaluate a novel, user-friendly, and efficient POCT method (ProciseDx Inc.) and compare its performance with the SOC ELISA in assessing infliximab and adalimumab levels in blood samples from IBD patients. Methods: In this prospective, single-center study, we collected blood samples from IBD patients, both CD and UC, receiving infliximab (87 IBD patients; 50% UC and 50% CD) or adalimumab (60 patients; 14% UC and 48% CD) and we analyzed the blood's drugs levels using both the ProciseDx Analyzer POC and the SOC ELISA. We examined the correlation between the two methods using statistical analyses, including the Deming regression test. Additionally, we assessed the ease of use, turnaround time, and overall practicality of the POCT in a clinical setting. Results: The ProciseDx test demonstrated a strong correlation with the SOC ELISA for measuring both infliximab and adalimumab levels. In particular, the overall correlation between the ProciseDx POCT and the ELISA assessments showed an r coefficient of 0.83 with an R squared value of 0.691 (95% CI 0.717-0.902) for IFX measurements, and an r coefficient of 0.85 with an R squared value of 0.739 (95% CI 0.720-0.930). Conclusions: the ProciseDx POC test offers significantly faster turnaround times and is more straightforward to use, making it a viable alternative for routine clinical monitoring. Despite its promising potential, further refinement and validation of the ProciseDx test are necessary to ensure its effectiveness across diverse patient populations and clinical settings. Future research should focus on optimizing the POC tests' performance and evaluating its long-term impact on IBD management.

Refractory Crohn's Disease: Perspectives, Unmet Needs and Innovations.

Crohn's disease (CD) is a complex, chronic inflammatory bowel disease characterized by unpredictable flare-ups and periods of remission. Despite advances in treatment, CD remains a significant health burden, leading to substantial direct healthcare costs and out-of-pocket expenses for patients, especially in the first-year post-diagnosis. The impact of CD on patients' quality of life is profound, with significant reductions in physical, emotional, and social well-being. Despite advancements in therapeutic options, including biologics, immunomodulators, and small molecules, many patients struggle to achieve or maintain remission, leading to a considerable therapeutic ceiling. This has led to an increased focus on novel and emerging treatments. This context underscores the importance of exploring advanced and innovative treatment options for managing refractory CD. By examining the latest approaches, including immunomodulators, combination therapies, stem cell therapies, and emerging treatments like fecal microbiota transplantation and dietary interventions, there is an opportunity to gain a comprehensive understanding of how best to address and manage refractory cases of CD.

Emergent ecological patterns and modelling of gut microbiomes in health and in disease.

Recent advancements in next-generation sequencing have revolutionized our understanding of the human microbiome. Despite this progress, challenges persist in comprehending the microbiome's influence on disease, hindered by technical complexities in species classification, abundance estimation, and data compositionality. At the same time, the existence of macroecological laws describing the variation and diversity in microbial communities irrespective of their environment has been recently proposed using 16s data and explained by a simple phenomenological model of population dynamics. We here investigate the relationship between dysbiosis, i.e. in unhealthy individuals there are deviations from the "regular" composition of the gut microbial community, and the existence of macro-ecological emergent law in microbial communities. We first quantitatively reconstruct these patterns at the species level using shotgun data, and addressing the consequences of sampling effects and statistical errors on ecological patterns. We then ask if such patterns can discriminate between healthy and unhealthy cohorts. Concomitantly, we evaluate the efficacy of different statistical generative models, which incorporate sampling and population dynamics, to describe such patterns and distinguish which are expected by chance, versus those that are potentially informative about disease states or other biological drivers. A critical aspect of our analysis is understanding the relationship between model parameters, which have clear ecological interpretations, and the state of the gut microbiome, thereby enabling the generation of synthetic compositional data that distinctively represent healthy and unhealthy individuals. Our approach, grounded in theoretical ecology and statistical physics, allows for a robust comparison of these models with empirical data, enhancing our understanding of the strengths and limitations of simple microbial models of population dynamics.

From Pathogenesis to Treatment: Targeting Type-2 Inflammation in Eosinophilic Esophagitis.

Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder of the esophagus. EoE shares a common pathogenetic mechanism with other chronic disorders pertaining to the type 2 inflammatory spectrum, such as atopic dermatitis (AD), allergic rhinitis (AR), asthma, and chronic rhinosinusitis with nasal polyps (CRSwNP). The recent advancements in EoE pathogenesis understanding have unveiled new molecular targets implied within the "atopic march" picture as well as specific to EoE. These discoveries have led to the clinical evaluation of several novel drugs (monoclonal antibodies and immune modulators), specifically aimed at the modulation of Th2 inflammation. In this comprehensive review, we have focused on the subtle mechanisms of type 2 inflammatory disorders, highlighting the similarities and differences with EoE, taking a deeper look into the evolving field of biologic therapies, already approved or under current investigation.

Gemini-Assisted Deep Learning Classification Model for Automated Diagnosis of High-Resolution Esophageal Manometry Images.

Background/Objectives: To develop a deep learning model for esophageal motility disorder diagnosis using high-resolution manometry images with the aid of Gemini. Methods: Gemini assisted in developing this model by aiding in code writing, preprocessing, model optimization, and troubleshooting. Results: The model demonstrated an overall precision of 0.89 on the testing set, with an accuracy of 0.88, a recall of 0.88, and an F1-score of 0.885. It presented better results for multiple categories, particularly in the panesophageal pressurization category, with precision = 0.99 and recall = 0.99, yielding a balanced F1-score of 0.99. Conclusions: This study demonstrates the potential of artificial intelligence, particularly Gemini, in aiding the creation of robust deep learning models for medical image analysis, solving not just simple binary classification problems but more complex, multi-class image classification tasks.

Effect of hiatal hernia and esophagogastric junction morphology on esophageal motility: Evidence from high-resolution manometry studies.

BACKGROUND: High-resolution Manometry (HRM) is the most sensitive and specific test available for clinical assessment of hiatal hernia (HH), a common condition defined as the separation between the Lower Esophageal Sphincter (LES) and crural diaphragm (CD). While the link between HH and Gastroesophageal Reflux Disease (GERD) is established, the potential association of HH with esophageal dysmotility, independently from GERD, is uncertain. This study aimed to analyze if HH, with or without GERD, can associate with esophageal motility disorders. METHODS: Consecutive patients without previous esophageal surgery who underwent HRM between 2018 and 2022 were enrolled. All patients with symptoms suggestive of GERD underwent impedance-pH testing off-therapy. HH was defined as a separation >1 cm between LES and CD, and esophagogastric junction (EGJ) morphology was classified as: Type I, when there was no separation between LES and CD; Type II, in case of minimal separation (>1 and <3 cm); Type III, when ≥3 cm of separation was present. Demographic and clinical characteristics were collected at baseline, including Age, Gender, Alcohol-, Coffee- and Smoke-habits, GERD diagnosis and symptoms' duration. Two cohorts of patients, with and without HH, were retrospectively individuated, and their association with Ineffective Peristalsis, Hypercontractile Esophagus and Outflow Obstruction was analyzed with univariate and multivariate Logistic regressions using the statistical software R. KEY RESULTS: 848 consecutive patients were enrolled, and 295 cases of HH (34.8%), subdivided into 199 (23.5%) Type II- and 96 (11.3%) Type III-EGJ patients, were identified. Ineffective peristalsis was diagnosed in 162 (19.1%) subjects, Hypercontractile esophagus in 32 (3.8%), and Outflow Obstruction in 91 (10.7%), while GERD was present in 375 (44.2%) patients. HH was significantly associated with Ineffective Peristalsis (p < 0.001) and GERD (p < 0.001). Furthermore, HH resulted to be a risk factor for Ineffective peristalsis (OR 2.0, 95% CI 1.4-2.8, p < 0.001) both when the analysis was conducted in all the 848 subjects, independently from GERD, and when it was carried out in patients without GERD (OR 2.3, 95% CI 1.02-5.3, p = 0.04). The risk for Ineffective Peristalsis increased 1.3 times for every centimeter of HH. No statistically significant association was found between HH and Outflow obstruction or Hypercontractile Esophagus. CONCLUSIONS & INFERENCES: An increasing separation between the LES and CD may lead to a gradual and significant elevation in the risk of Ineffective Peristalsis. Interestingly, this association with HH is true in patients with and in those without GERD, suggesting that the anatomical alteration seems to play a major role in motility change.

Enhancing Oral 5-ASA Effectiveness in Mild-to-Moderate Ulcerative Colitis through an H. erinaceus-Based Nutraceutical Add-on Multi-Compound: The "HERICIUM-UC" Two-Arm Multicentre Retrospective Study.

Mild-to-moderate ulcerative colitis (UC) management is centred on 5-aminosalicylic acid (5-ASA) derivatives. Whether supplementing 5-ASA with nutraceuticals can provide real advantages in UC-relevant outcomes is unclear. This retrospective multicentre study compared clinical remission, response rates, and faecal calprotectin levels in a two-arm design, including patients treated with 5-ASA alone and those with additional H. erinaceus-based multi-compound supplementation. In the 5-ASA alone group, clinical response rates were 41% at three months (T1) and 60.2% at six months (T2), while corresponding clinical remission rates were 16.9% and 36.1%. In the nutraceutical supplementation group, clinical response rates were 49.6% (T1) and 70.4% (T2), with clinical remission rates of 30.4% (T1) and 50.9% (T2). No significant differences in clinical response rates between the groups at T1 (p = 0.231) and T2 (p = 0.143) emerged. Clinical remission rates differed significantly at both time points (p = 0.029 and p = 0.042, respectively). Faecal calprotectin levels decreased significantly in both groups during the retrospective follow-up (p < 0.05), and this was more pronounced in nutraceutical supplementation patients at both T1 (p = 0.005) and T2 (p = 0.01). No adverse events were reported. This multi-component nutraceutical supplementation offers real-world potential in controlling disease activity in patients with mild-to-moderate UC.

THE LYON SCORE: A NOVEL REFLUX SCORING SYSTEM BASED ON THE LYON CONSENSUS 2.0 THAT ASSOCIATES WITH TREATMENT OUTCOME FROM ANTI-REFLUX THERAPY.

BACKGROUND: We explored if a score derived from parameters from esophageal testing could increase confidence in diagnosing conclusive gastroesophageal reflux disease and in predicting outcome. METHODS: A prediction score was developed using metrics based on Lyon Consensus 2.0 thresholds extracted from endoscopy and pH-impedance monitoring. The Lyon score was the sum of weighted scores derived from a logistic regression model. The outcome was response to anti-reflux therapy, defined as 50% reduction in global symptoms on validated questionnaires. An existing database of endoscopy-negative patients with typical reflux symptoms undergoing esophageal testing from two centers (Europe and US) constituted the developmental cohort, while two separate cohorts (Europe and Asia) served as validation cohorts. Receiver operating characteristics (ROC) analysis determined performance of the Lyon score in predicting treatment response. RESULTS: In 281 developmental cohort patients (median age 53 years, 57.7% female), the Lyon score demonstrated an AUC of 0.819 in predicting 50% symptom improvement (p<0.001) on ROC, with an optimal threshold of 6.25 (sensitivity 81.2%, specificity 73.4%). Of the individual components, only acid exposure time (AUC 0.799, p<0.001), mean nocturnal baseline impedance (AUC 0.785, p<0.001) and reflux episodes (AUC 0.764, p<0.001) approached the Lyon score performance. The Lyon score segregated treatment response in both the European (AUC 0.908, p<0.001) and Asian validation cohorts (AUC 0.637, p<0.001), and outperformed the DeMeester score in sensitivity for predicting outcome in the developmental and Asian validation cohorts. CONCLUSION: The novel Lyon score segregates reflux phenotypes, and identifies likelihood of symptom response from antireflux therapy.

Distribution of esophageal inflammation in patients with eosinophilic esophagitis and its impact on diagnosis and outcome.

BACKGROUND: This study aimed to assess the distribution of esophageal inflammation in patients with eosinophilic esophagitis (EoE) and its impact on diagnosis and outcome. AIMS AND METHODS: Data from consecutive adult EoE patients who were followed-up at four Italian referral centers from October 2022 to October 2023 were retrospectively collected. RESULTS: One hundred forty-nine patients were included. Proximal EoE was observed in 8.1 % of patients; distal EoE in 27.5 %; and diffuse EoE in 64.4 %. Allergic rhinitis was more prevalent in distal and diffuse than proximal EoE (72.5 % vs. 61.5 % vs 33.3 %; P = 0.049). The prevalence of asthma, atopic dermatitis, oral allergy syndrome, and gastroesophageal reflux disease was not significantly different among the three EoE extent groups. Endoscopic inflammatory features at diagnosis were more prevalent in proximal EoE (91.7 % vs. 53.8 % distal [P = 0.01] vs. 66 % diffuse[P = 0.05]). No significant differences in fibrotic features and esophageal stenoses were observed. The clinical and histological remission rates after first-line therapy were comparable in all groups. CONCLUSION: Esophageal inflammation in EoE more frequently involves the entire esophagus, followed by isolated distal and proximal involvement. No clear correlation was observed between the histological extent of EoE at diagnosis and comorbidities or treatment response.

Suboptimal disease control and contributing factors in Italian IBD patients: The IBD-PODCAST Study.

BACKGROUND AND AIM: Suboptimal disease control (SDC) and its contributing factors in IBD according to STRIDE-II criteria is unclear. IBD-PODCAST was a non-interventional, international, multicenter real-world study to assess this. METHODS: Data from the Italian IBD cohort (N=220) are presented here. Participants aged ≥19 with confirmed IBD diagnosis of ≥1 year were consecutively enrolled. A retrospective chart review and cross-sectional assessment by physicians and patients within the past 12 months were performed. SDC or optimal disease control was assessed using adapted STRIDE-II criteria. RESULTS: At the index date, 53.4 % of 116 CD patients and 49.0 % of 104 UC patients had SDC, mainly attributed to a Short Inflammatory Bowel Disease Questionnaire score <50, failure to achieve endoscopic remission, and the presence of active extra-intestinal manifestations in both diseases. Disease monitoring with imaging and/or endoscopy during the previous year was conducted in ∼50 % of patients, with endoscopy performed in ∼40 %. Potential therapeutic adjustments were reported for half of the patients. CONCLUSIONS: This study highlights SDC in a significant portion of IBD Italian patients. These results emphasize the need for more proactive management strategies in both CD and UC patients.

Prevalence of Sexual Dysfunction In Inflammatory Bowel Disease: Systematic Review and Meta-Analysis.

BACKGROUND & AIM: Patients with inflammatory bowel disease (IBD) may experience symptoms of sexual dysfunction (SD). However, the magnitude of this problem remains uncertain. Therefore, we performed a systematic review and meta-analysis to assess the prevalence of SD in adult patients with IBD. METHODS: MEDLINE EMBASE, EMBASE Classic (from inception to 9th April 2024) were searched to identify observational studies reporting the prevalence of SD in adult patients with IBD based on validated screening instruments. Data were extracted, and pooled prevalence (PP), odds ratios (OR), and 95% confidence intervals (CIs) were calculated. RESULTS: Of 1017 citations evaluated, 18 articles fulfilled eligibility criteria, containing 2,694 patients with IBD recruited from 13 different countries. The PP of SD in IBD patients was 50.6% (95% CI=40.8%-60.5%; I2=96.3%) with an OR=2.94 (95% CI=1.99-4.35, I2=73.4) compared to healthy controls. When we considered UC or CD separately, the PP of SD was 64.8% (95% CI=45.1%-82.1%; I2=88.8%) in patients with UC, and 58.3% (95% CI=36.0%-79.0%; I2=95.3%) in patients with CD. In the subgroup analysis based on sex, the PP of SD was higher in females with IBD than in males (62.7% vs 34.0%; OR=3.99, 95% CI=2.80-5.68; I2=61.7%,). Furthermore, the PP of SD was higher in patients with active disease than patients with inactive disease (75.1% vs 34.2%; OR=9.65, 95% CI=1.02-91.33, I2=95.5%). CONCLUSION: We demonstrated high prevalence of SD in IBD patients, especially in women. Encouraging gastroenterologists to screen for, and treat, these disorders with a holistic approach might improve quality of life of patients with IBD.

Safety of potassium-competitive acid blockers in the treatment of gastroesophageal reflux disease.

INTRODUCTION: Proton pump inhibitors (PPIs) are the first-line treatment for gastroesophageal reflux disease (GERD). However, due to their intrinsic limitations, there are still unmet clinical needs that have fostered the development of potassium-competitive acid blockers (P-CABs). Currently, four different drugs (vonoprazan, tegoprazan, fexuprazan, and keverprazan) are marketed in some Asian countries, whereas only vonoprazan and tegoprazan are available in Western countries (USA and Brazil or Mexico, respectively). AREAS COVERED: This review summarizes the current knowledge on P-CABs acute and long-term safety in GERD treatment compared to that of PPIs. Full-text articles and abstracts were searched in PubMed. EXPERT OPINION: P-CABs proved to address some of the unmet clinical needs in GERD, with a favorable risk-benefit ratio compared to conventional PPIs. Preclinical and clinical findings have highlighted P-CAB safety to be superimposable, to that of PPIs, in short-term treatments, although further studies are warranted to monitor their effects in long-term therapy. From an epidemiological point of view, the paucity of rigorous data for many variables (e.g. age, ethnicity, drug interactions, comorbidities, genetic polymorphisms, interindividual susceptibility, and gut dysbiosis) deserves a worldwide framework of continuous pre/post-marketing pharmacovigilance programs to reduce potential confounding factors and accurately link acute and chronic P-CAB therapy to adverse outcomes.

Standard length of peroral endoscopic myotomy (POEM) for achalasia: a systematic review and meta-analysis.

Peroral endoscopic myotomy (POEM) is an established treatment for achalasia, yet there is still a lack of technical standardization. No clear definition of 'long', 'standard', or 'short' POEM exists to date. We conducted a systematic review with meta-analysis to analyze current POEM length standards. We included studies reporting technical details of POEM, in which no definite or comparative myotomy length was intentionally adopted (standard myotomy). The primary outcome was the pooled mean total myotomy length. Sub-group analyses were performed to explore heterogeneity across studies. From the initial 7172 records, 31 studies with 3023 patients were included. Pooled mean of total myotomy length was 10.39 cm (95% CI 10.06-10.71; I2 99.3%). Pooled mean of esophageal and gastric myotomy length, provided by 17 studies, was 7.11 cm (95% CI 6.51-7.71; I2 99.8%) and 2.81 cm (95% CI 2.41-3-22; I2 99.8%), respectively. On subgroup analysis for achalasia subtypes, pooled mean length in non-spastic achalasia (type I and II) was 10.17 cm (95% CI 9.91-10.43; I2 94.2%), while in type III it was 14.02 cm (95% CI 10.59-17.44; I2 98.9%). Pooled mean myotomy length for studies conducted between 2014-2020 was 10.53 cm (95% CI, 10.22-10.84; I2 99.1%) and 9.74 cm (95% CI, 7.95-11.54; I2 99.7%) in 2021-2022. Myotomy length during a 'standard' POEM is 10.4 cm, remaining over 10 cm in non-spastic achalasia. The high heterogeneity across studies confirms that the POEM technique needs further standardization. We found no significant time trend towards adopting short POEM, despite recent evidence supporting its use.

Clinical Characteristics, Endoscopic Findings, and Treatment Outcomes in Lymphocytic Esophagitis Compared to Eosinophilic Esophagitis.

INTRODUCTION: Lymphocytic and eosinophilic esophagitis (LyE and EoE) are immune-mediated esophageal diseases. Clinical characteristics, endoscopic findings, and treatment outcomes of LyE were compared to EoE. METHODS: This was an international retrospective study on adults enrolled at three centres in Europe. We recorded clinical characteristics and endoscopy findings at baseline, and symptoms, histology, and endoscopy outcomes following treatment of LyE and EoE patients. RESULTS: Demographics, clinical presentation, comorbidities, and endoscopy findings were largely different in 35 LyE compared to 59 EoE. Proton pump inhibitors (PPIs) response was generally lower in LyE. DISCUSSION: LyE is clinically different from EoE, but differences in treatment response need further investigation.

Eosinophils, Eosinophilic Gastrointestinal Diseases, and Inflammatory Bowel Disease: A Critical Review.

BACKGROUND/OBJECTIVES: Inflammatory bowel disease (IBD) and eosinophilic gastrointestinal diseases (EGIDs) are complex, multifactorial chronic inflammatory disorders affecting the gastrointestinal tract. Their epidemiology, particularly for eosinophilic esophagitis (EoE), is increasing worldwide, with a rise in the co-diagnosis of IBD and EGIDs. Both disorders share common risk factors, such as early exposure to antibiotics or specific dietary habits. Moreover, from a molecular perspective, eosinophilic infiltration is crucial in the diagnosis of eosinophilic disorders, and it also plays a pivotal role in IBD histological diagnosis. Indeed, recent evidence highlights the significant role of eosinophils in the health of the intestinal mucosal barrier and as mediators between innate and acquired immunity, even indicating a potential role in IBD pathogenesis. This narrative review aims to summarize the current evidence regarding the common clinical and molecular aspects of EGIDs and IBD and the current state of knowledge regarding overlap conditions and their pathogenesis. METHODS: Pubmed was searched until May 2023 to assess relevant studies describing the epidemiology, pathophysiology, and therapy of EGIDs in IBD. RESULTS: The immune pathways and mechanisms underlying both EGIDs and IBD remain partially known. An improved understanding of the role of eosinophils in overlapping conditions could lead to enhanced diagnostic precision, the development of more effective future therapeutic strategies, and a more accurate prediction of patient response. Consequently, the identification of red flags indicative of an eosinophilic disorder in IBD patients is of paramount importance and must be evaluated on a case-by-case basis.