Eosinophilic Esophagitis Research Articles

The crucial role of allergists in the clinical management and treatment of eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus affecting mainly young individuals with a high burden of comorbid atopic diseases and is associated with increased morbidity. Proton pump inhibitors (PPIs) is often the first line of treatment by inducing clinical remission in 30-50% of patients. Recently new drugs, such as budesonide orodispersible tablets and a monoclonal antibody targeting interleukin-4 and 13, have been found to be effective in clinical trials and approved to treat this condition. A prompt diagnosis and correct management of these patients is of paramount importance to prevent fibrostenosis of the oesophagus and to improve the quality of life. The complex management of patients living with EoE requires the integrated cooperation of several specialists, including allergists, gastroenterologists, pathologists, dietitians, and psychologist.

Pediatric eosinophilic esophagitis: survey of gastroenterologists from Latin America and Spain

Pediatric eosinophilic esophagitis: survey of gastroenterologists from Latin America and Spain

Lymphocytic esophagitis and ringed esophagus.

Lymphocytic esophagitis is an uncommon condition characterized by the presence of intraepithelial lymphocytosis and lack of eosinophils in the esophageal biopsy samples. The main clinical manifestations include dysphagia, heartburn, and vomiting; endoscopic changes are absent in up to 30% of cases, and may mimic the common gross aspects of an eosinophilic esophagitis as rings, longitudinal furrows, and stenosis. The authors emphasize the role of this diagnosis confirmation as early as possible, with prompt and adequate management aiming to avoid eventual unfavorable outcomes. The objective of this manuscript is to emphasize the case study of an infrequent entity.

EoE pathogenesis: all clear?

Eosinophilic esophagitis (EoE) is a food—and aeroallergen-driven, Th2-mediated chronic inflammation that develops in genetically predisposed individuals. Exposure to pollutants, such as detergents, and the microbiome contribute further to EoE, characterized by an impaired epithelial barrier resulting in tissue remodeling, fibrosis, and strictures. Here, we discuss the pathophysiology of EoE and address open points that need to be resolved in the future.

Eosinophilic esophagitis patients report substantial disease burden comparable to more systemic immune-mediated diseases

BackgroundEosinophilic esophagitis (EoE) is a chronic Type 2 inflammation. One might assume that the disease-related impact on daily life is significantly smaller, given the relatively localized disease distribution, compared to more systemic immune-mediated diseases. This study aimed to evaluate the disease burden among various immune-mediated diseases, including EoE, inflammatory bowel disease (IBD), systemic sclerosis (SSC) and lupus erythematosus (SLE).MethodsA web-based questionnaire assessed baseline characteristics, general quality of life and disease-related impairment across several subdomains, including work, leisure and social life. The surveys were distributed by the respective Swiss patient organizations.ResultsOverall, 608 patients participated in the survey (EoE: 92; IBD: 407; SSC: 69; and SLE: 40). Although the overall perceived general impairment in everyday life, measured on a numeric rating scale (NRS), was higher in Crohn’s disease (CD), SSC, and SLE patients compared to EoE (median 3, IQR 2–6), there was no significant difference compared to ulcerative colitis (UC) (median 4, IQR 2–6, p = 0.31) or IBD patients overall (median 5, IQR 3–6; p = 0.05; Fig. 1a). Impairment in EoE was most pronounced and in the subdomain of leisure, consistent with other investigated diseases. Disease-related impairment was higher in women versus men and in patients with a longer diagnostic delay across all diseases.ConclusionsEoE patients’ perceived impairment in everyday life, particularly within subdomains such as leisure, is substantial and comparable to that experienced by patients with other immune-mediated disease states, including IBD. Notably, patient-perceived impairment was higher among female EoE patients and those with a longer diagnostic delay.

The index of severity for eosinophilic esophagitis reflects treatment response in children and associates with outcome variables

We aimed to categorize the severity of eosinophilic esophagitis using the recently developed Index of Severity of Eosinophilic Esophagitis (I-SEE), to assess the longitudinal response to treatment, and to correlate baseline severity with outcome variables. A retrospective analysis of a prospectively enrolled cohort of children at two centers was performed. I-SEE was calculated at diagnosis, at the second endoscopy after initial treatment, and at the last endoscopy over a mean of 35 months. We analyzed clinical, endoscopic, and histologic characteristics at baseline by disease severity, examined the change in severity at the second and last endoscopy, and evaluated the association of baseline disease severity with treatment variables. Of 95 children meeting inclusion criteria, 35%, 63%, and 2% had mild, moderate, and severe I-SEE scores, respectively, at baseline. Between baseline and the second endoscopy, the median I-SEE decreased from 7 (7–8) to 2 (0–5) (p < 0.001), and to 0 (0–3) at last endoscopy, with 53% of patients having inactive and 47% having mild scores (p < 0.001). Patients with histologic response at the second and final endoscopy had lower I-SEE scores than non-responders (p < 0.001). A higher baseline I-SEE score was associated with increased odds of receiving 2 or more treatments or combined therapy (OR 95% CI 1.28 (1.03–1.59) and (1.18 (1.04–1.39), respectively).Conclusions: The I-SEE score reflects longitudinal treatment response in children with EoE. Patients with higher baseline I-SEE may be at higher risk of requiring more than one treatment, sequentially or in combination.What is Known:• Eosinophilic esophagitis is a heterogenous disease with different degrees of severity.• The recently developed index of severity of eosinophilic esophagitis (I-SEE) incorporates frequency of symptoms, complications, and inflammatory and fibrostenotic findings and has shown to be a sensitive tool to change with treatment in a pediatric cohort.What is New:• We confirmed the sensitivity of the index, with a significant decrease in the score with treatment, with the decrease being more pronounced in children with histologic response.• A higher initial severity score was associated with the need for more treatments, sequentially or in combination.

Adverse events are lower in unsedated transnasal esophagoscopy versus sedated esophagogastroduodenoscopy.

Unsedated transnasal esophagoscopy (TNE) is an innovative and minimally invasive technique becoming more commonplace in pediatric gastroenterology. The advantages include no anesthesia, decreased cost, and less time away from work and school. There is no published data evaluating postprocedure adverse events (AE) with TNE. The aim of this study was to evaluate postprocedure AE associated with TNE compared to sedated esophagogastroduodenoscopy (EGD). AE data were prospectively collected for patients ages 5-22 years who underwent endoscopy at a tertiary children's hospital between January 2015 and June 2022. Demographic data and procedural factors were collected, and AE were categorized using a standardized scoring system. A total of 10,023 diagnostic EGD's on 7786 patients and 927 TNE's on 492 patients were performed. The total number of AE (Grade I-IV) observed were 196 after EGD and 1 after TNE. The total AE rate for EGD's was significantly higher than for TNE's (1.96% vs. 0.11%, p < 0.0001). The clinically significant AE (Grade II or higher) for EGD's was higher than TNE's (0.67% vs. 0%, p = 0.006). In controlling for eosinophilic esophagitis (EoE) as the indication, the total AE and the clinically significant AE for EGD's were higher than TNE's ([1.87% vs. 0.12% p < 0.001], [0.75% vs. 0% p = 0.01]). The postprocedure AE rate for TNE was lower than EGD both for overall and clinically significant AE. This suggests TNE is a safer approach for monitoring esophageal pathology than sedated EGD for patients who can undergo TNE.

Endoscopic response to topical steroids is associated with a need for fewer future esophageal dilations.

The eosinophilic esophagitis (EoE) Endoscopic Reference Score (EREFS) measures endoscopic severity. While a score of ≤2 has been proposed for endoscopic response, it is unknown whether achieving this threshold results in clinically important outcomes. We aimed to determine whether an EREFS response to topical steroids (tCS) is associated with a decreased need for future esophageal dilation. In this retrospective cohort study, we included patients with a new diagnosis of EoE who underwent esophageal dilation, were then treated with tCS, and had at least two follow-up endoscopies. Endoscopic response was defined as EREFS ≤2. Histological and global symptom responses were recorded. We compared patients with and without endoscopic response and calculated the number of subsequent dilations in each group. Of 113 EoE patients, 55 (49%) had endoscopic response post-tCS. Compared to endoscopic non-responders, responders were older (43.4 vs 34.4years; p = 0.001) and had lower EREFS (4.4 ± 1.6 vs. 6.3 ± 1.5; p < 0.001) at baseline. EREFS responders required fewer dilations on their initial post-treatment endoscopy (65% vs 90%; p = 0.002) and had greater symptom (92% vs 64%; p = 0.005) and histologic responses (82% vs 24% <15 eos/hpf; p < 0.001). Over the median follow-up time of 1106days, EREFS responders required fewer dilations than non-responders (4.5 ± 2.9 vs 6.2 ± 4.5; p = 0.03). Endoscopic responders to tCS required fewer esophageal dilations compared to non-responders. Responders also had better symptom and histologic responses. These results provide evidence that endoscopic response is associated with important clinical outcomes including a reduction in future esophageal dilations.

Eosinophilic esophagitis and allergic susceptibility: A systematic review and meta-analysis.

Eosinophilic esophagitis and allergic susceptibility: A systematic review and meta-analysis.

Eosinophilic Esophagitis (EoE): Allergy & Immunology Perspective on the Updated Guidelines.

Eosinophilic Esophagitis (EoE): Allergy & Immunology Perspective on the Updated Guidelines.

Histological Outcomes of Pharmacological Interventions in Eosinophilic Esophagitis for Adults and Children: A Network Meta-analysis of Randomized Controlled Trials.

Multiple pharmacological interventions have been studied for managing eosinophilic esophagitis (EoE). We performed a comprehensive systematic review and network meta-analysis of all available randomized controlled trials (RCT) to assess the efficacy and safety of these interventions in EoE in adults and children. We performed a comprehensive review of Embase, PubMed, MEDLINE OVID, Cochrane CENTRAL, and Web of Science through May 10, 2023. We performed frequentist approach network meta-analysis using random effects model. We calculated the odds ratio (OR) with 95% CI for dichotomous outcomes. Our search yielded 25 RCTs with 25 discrete interventions and 2067 patients. Compared with placebo, the following interventions improved histology (using study definitions) in decreasing order on ranking: orodispersible budesonide (ODB) low dose, ODB high dose, oral viscous budesonide (OVB) high dose, fluticasone tablet 1.5mg twice daily, fluticasone 3mg twice daily, esomeprazole, dupilumab every 2 weeks, dupilumab weekly, OVB medium dose, fluticasone 3mg daily, cendakimab 180mg, prednisone, swallowed fluticasone, fluticasone tablet 1.5mg daily, OVB low dose, reslizumab 3mg/kg, reslizumab 1mg/kg, and reslizumab 2mg/kg. Network meta-analysis demonstrates histological efficacy of multiple medications for EoE. Because of the heterogeneity and large effect size, we recommend more trials comparing pharmacotherapeutic interventions with each other and placebo. An important limitation of this study is absence of clinical efficacy data due to insufficient data. Other limitations include heterogeneity of operator, population, and outcome analysis.

Issue Information

On the Cover: “EndoFLIP distensibility index correlates with histologic findings in children with eosinophilic esophagitis” Almazan, et al., 824‐831

Dysphagia and Asthma: The Association of Eosinophilic Esophagitis, Asthma, and Its Effects on Outcomes

Dysphagia and Asthma: The Association of Eosinophilic Esophagitis, Asthma, and Its Effects on Outcomes

Economic Burden and Health Care Resource Utilization of Patients With Eosinophilic Esophagitis in the United States.

To estimate health care resource utilization (HCRU) and costs among patients with eosinophilic esophagitis (EoE) in the US. The EoE prevalence in the US has risen in recent years. Assessing HCRU and costs may assist in understanding the economic burden of EoE in the US. In IQVIA's PharMetrics Plus claims database, prevalent patients with EoE were identified and matched with non-EoE controls. The index date was a randomly selected EoE diagnosis date for the EoE cohort (January 2018 to June 2019) and a random date for non-EoE controls. Patients had 1-year of continuous enrollment before and after the index date, with ≥1 EoE diagnostic claim before the index. Descriptive and regression analyses adjusting for comorbidities unrelated to EoE were performed to compare HCRU and costs (EoE vs. non-EoE), 1-year after the index date. The analysis included 15,432 patients with EoE and matched non-EoE controls (mean age: 36.2y). The annual HCRU, including the mean outpatient visits, was higher in patients with EoE versus non-EoE controls [mean difference (MD): 9.2d; 95% CI: 8.8-9.6]; with consistent results across age groups. The mean total health care costs (annual) were ∼2.5 times higher in patients with EoE than in non-EoE controls. Patients with EoE who underwent esophageal dilation had higher HCRU (emergency room visit: MD: 0.9d; 95% CI: 0.8-1.0) and total health care costs (MD: $10,174; $8493-$11,855) than non-EoE controls. Patients with EoE had higher annual costs and HCRU than non-EoE controls, indicating a substantial economic burden, particularly among patients with EoE with prior esophageal dilation.

The changing epidemiology of paediatric childhood asthma and allergy in different regions of the world

Allergic disorders encompass a variety of conditions including asthma, atopic dermatitis, food allergy, allergic rhinitis, and eosinophilic esophagitis. These atopic disorders are connected via an abnormal host immune response to the environment. A series of longitudinal cross-sectional studies conducted over the past 3 decades have reported on the epidemiological trends that contribute towards the development of pediatric asthma and allergic disease. Infant birth cohort studies assessing the microbiome have offered clues as to the underlying biological mechanisms and basis for allergic disease. Why this abnormal immune response is occurring is the basis of decades of research and the reasons for this chapter. Our understanding of the biology of the immune system has increased exponentially with the advances in genomic testing, providing further opportunity for targeted treatments and more importantly, primary prevention of atopic disease.

Eosinophilic esophagitis without eosinophils – Do you want to mock me?

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. 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, non-specific 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. This review summarizes current knowledge about these different variants and discusses future directions and open questions.

Atopic condition of the esophagus - eosinophilic esophagitis - literature review

Introduction and purpose Eosinophilic esophagitis (EoE) is a chronic, immune-mediated disorder causing esophageal dysfunction in children and adults. Characterized by eosinophilic inflammation, EoE leads to dysphagia, food impaction, and esophageal remodeling. Since its classification in the 1990s, research has expanded, yet aspects of its pathogenesis, diagnosis, and management remain under investigation. This review compiles current knowledge on EoE, covering its pathophysiology, epidemiology, clinical presentation, diagnosis, treatment, and prognosis. By integrating recent findings and guidelines, it aims to enhance understanding and optimize care. Description of the state of knowledge EoE is defined by eosinophilic infiltration of the esophageal mucosa, leading to dysfunction. Diagnosis relies on histologic criteria, with ≥15 eosinophils per high-power field in biopsies. Endoscopic tools like the EoE Endoscopic Reference Score (EREFS) aid evaluation, though differentiation from GERD remains challenging. Treatment includes dietary modifications, pharmacologic therapy, and endoscopic interventions. First-line options are dietary elimination, proton pump inhibitors (PPIs), and topical corticosteroids, while emerging biologics target inflammatory pathways. Endoscopic dilation is reserved for fibrostenotic cases. Despite therapeutic advancements, EoE is a chronic condition requiring long-term management. Continued research is needed to refine treatment strategies and improve outcomes. Conclusions EoE requires lifelong management. While dietary, pharmacologic, and endoscopic treatments control symptoms, they do not halt disease progression. Biologic therapies offer promising advances, but further studies are needed to optimize long-term strategies and patient care.

Clinical description of adults with eosinophilic esophagitis treated at a Chilean university center.

Clinical description of adults with eosinophilic esophagitis treated at a Chilean university center.

EML4 Deficiency Causes Alveolar Macrophage Dysfunction and Interstitial Lung Disease

We report a novel inborn error of immunity in two siblings born to consanguineous parents who presented with short stature, failure to thrive, eosinophilic esophagitis, severe eczema, and early onset, progressive interstitial lung disease with lipoid pneumonia or pulmonary alveolar proteinosis (PAP)-like features. Genetic testing revealed both affected siblings harbored a homozygous deletion of a region of the EML4 gene, which encodes for echinoderm microtubule-associated protein-like 4 (EML4). Further analysis confirmed a lack of EML4 RNA or protein expression. EML4 deficiency has not been reported in the literature and very little is known about its physiological function. Thus, we generated EML4-deficient mice by CRISPR/Cas9 gene editing of EmL4 to examine the role of EML4 in immune function and lung disease. Consistent with the short stature of the patients, EML4-deficient mice were runted compared with wild-type (WT) mice. We also examined the lungs of EML4-deficient mice, particularly the alveolar macrophage (AMs) population, as defects in AM number or function are known to be associated with PAP. This revealed that EML4-deficient mice had significantly decreased alveolar macrophages (AMs) compared with WT mice, but no change in the frequencies of other immune cell populations. scRNA-seq demonstrated that among lung cells, EML4 deficiency had the greatest impact on the gene expression program of AMs. EML4-deficient AMs also showed increased lipid accumulation consistent with the foamy macrophages observed in the bronchioalveolar lavage of the patients. Under specific pathogen–free (SPF) conditions, EML4-deficient mice did not demonstrate lung pathology or fibrosis. However, colonization of EML4-deficient mice with more diverse microbiota by cohousing with “dirty” mice led to florid immune infiltration and fibrosis. Together, our results reveal that EML4 deficiency results in defects in AM which combined with microbial exposure may trigger inappropriate inflammatory responses and subsequent lung fibrosis.

When Manometry and Functional Lumen Imaging Probe Disagree: The Current Limitations of the Chicago Classification Version 4.0 and Probable Extended Indications of Functional Lumen Imaging Probe.

High-resolution manometry (HRM) has revolutionized evaluation of esophageal motility disorders, offering detailed pressure topography and refined diagnostic criteria codified through the Chicago classification (CC). However, patients with dysphagia may present with borderline or near-normal HRM findings, exhibiting clinically significant symptoms. CC version 4.0 (v4.0) addresses such scenarios by recommending provocative maneuvers and ancillary tests, notably functional lumen imaging probe (FLIP) and timed barium esophagography. However, growing evidence indicates that FLIP, which measures luminal distensibility under balloon distention, can detect structural or biomechanical abnormalities, such as hypertrophy or fibrosis, that remain inconspicuous on HRM. These discordant findings point to limitations in CC v4.0. FLIP complements HRM by assessing passive tissue properties and capturing balloon-induced contractility, thereby unmasking subtle esophageal wall stiffness not always reflected in integrated relaxation pressure or standard peristaltic metrics. Such discrepancies can arise in early or atypical achalasia, esophagogastric junction outflow obstruction, eosinophilic esophagitis, and even epiphrenic diverticula, where "normal" manometry may belie significant pathology. Present CC v4.0 guidelines do not specify how to incorporate FLIP-derived measures or reconcile disagreements with timed barium esophagography results, leaving certain phenotypes-including repetitive simultaneous contractions-under-recognized. These gaps underscore an overreliance on integrated relaxation pressure alone and insufficient integration of evolving FLIP technology. Thus, standardizing FLIP protocols, establishing normative distensibility data, and clarifying management pathways for manometry-FLIP discordance remain critical. Prospective, multicenter studies are needed to investigate long-term clinical outcomes and to refine how FLIP metrics can be formally integrated into future CC iterations. Ultimately, multimodal, symptom-driven approaches that leverage both HRM and FLIP are essential to fully characterize esophageal dysmotility and optimize therapy.